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## Bacillus tl mr iugie u sis 

## Pl a n t-i n co rp o r a t e d Protectants i n Corn: Bt Corn Le pidopteran ( Ca se 6501) an d Bt Corn Co l eo pt era n (C a se 6502 ) Co mbined Work Plan , S ummary Do c um e nt , nnd Propo se d Int e rim R eg i s tration Review D e ci s ion Se pt em b er 2015

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### Tab l e or Contents lntroduclion 

### J St:Uulory

**:~nd** Rf'f!ul:uor)' Authority 3 Un :and Usn,::r Information ., Sticnlific

**~St.'$3 Ritni**  **S** !\ A. Produce
**ha~ctcriz.:tlion** and Human lltllllh , \)Jt):5mtnl.." S 8. E; n, · ironmtntal A»cssmcnt 13 C. l nSC'C'I RnUtancr

**~llilln:a.:tmt'nt** 2.1 D . F.ndorrinC' Dbruptor

**&~tnint=** Prugnm 28 Co mbin ed \Vurk 

### rlan, S um m:ary Uocunt (' nt. and 

### l'ropma . -d 

### l n t uim Ht."'J.islrlllion Rt \ ' i tw Occbiun 29 Rati onale for l)ropo sc-d lnltrim RC"gbtration Rt\ ' frw D«Uion 30 NtXI Steps and Tim dine 38

••

21 1\ 'T I WDIJ<;T I ON The docket for /J udllus ll mringil:nsis P l ru H· i ncorporutcd Pro t ect ants in Corn: Bt Com Lcp idop lcmn (Cns c 6501) and Bl Com Co lcoplcrun (Cas e 6502i i s now open. inirim ing I he fl r.;l public commc nl period for rhis n:gi s lrulion r c,1cw ( docker number EPA -HQ ·OPP-20 1 5-0584). This docum ent is the l i nvironmcntal Protection ,. \ge:n cy's (EP A or the Agen cy) comb ined Wo rk 1'/tm, Sumnwry 

### DocJmJ,•nt, and 

### rropo sal lm erim Rc"gi.ftralion Rcrit .: w D.:cisio n for 

### Bt com ''hich i s bei ng iss ued pun;u;mt t o 40 CFR sect ions 1 55.50. 1 55.56. and 155.58. This document exp lains \\ hnt EPA 's Onicc of Pe s tic ide Progmms knows about B t com PlluH·i ncorporo kd Prorcctants (P IPs ) . h ighJig.l tting : u u ici p:uc:d data and assessment needs and provid ing an ant icipated t imd inc for completing t he Bt com PIP review. It a l so i nd u dcs the Agency's Propo sed l1li Crim Re g i strat ion Rev iew l) <."('ision fo r Bt com Plant· i n corpora t OO**prot~CttlntS.** H

cgis t crcd B t c om Plj)s incl ude vnrietics t O

r cont r

o l of lepid opteran (ens.: 6501) and coleopteran (case 6502) t nrg d pests . A r egis trot 

### ion review dec i sio n i s th e Agency's d ctcnnirnu ion wh ethe r n pcsticide meets . or d oes rtot mee t , the**~1andard** tbr regi str.n ion in the Fcdcrnl l nscctici de . Fungicide. an d Rodenticide i \ Ct (F IFRA). llw Agency may i ss ue. whe n i t dctcnn inc s it to be npproprintc. nn Interim Regi .s t r..uion Rc,;cw Decisio n**Ore** completi n b n re g . bir.ll io n review. Amon g o t her th ings . , the Interim Rc g i s tr"J.tion Review Decisi on may: 1 )**n.~uirc** new ris.k mitigmion mea sures: 2) impose interim ri s k mitigat ion measure s: 3) iden t i t

} · data or infonn:tt ion r eq u ired t o comp lete the rc\' iew: n nd 4) in cl ude schedules for s ubmin ing the r equ i red dat a. co nduc t ing the new ri.s.k nsscss mcnt and comp l e t

i ng the reg i s t ra t io n re v iew. For fun h cr int b nn:tti on on Dt com PIP s . additional docume nr s can be found in EPA's publ ic docker (E PA-HQ·OPP-2015-058 4) at \\

' WW . re gl d;H ion s. gov. STAT UTORY r\1' !0 RF.GULATORY A IJ TII!)R I TV FIFRA. as amended by th e Food Ql1ll li ry P r olccl io n .-\ co (FQP .-\ } of 1 996. mandarcd th e co ntinu ous r-.!Yicw of exi st ing pest ici des. All pest ic ides d i stributed o r sol d in t he Un ited S t a t

e.s sc n craJiy must be reg i s tered by the EPA b :tSC'd on scie ntific data s h owing that th ey will not**ca.u~e** un reasont'lblc risks t o hum:m health or t o the environment whe n used !'IS dinxu:d o n product la be l i ng. The n:gistr:llion 0:!\ ' icw progr:.lm is intended to make s ure t hat . 

### a.s th e ab i l ity t o assess ar\d red uce ri sk c , ·o lvcs n nd ns pol icies 3fl d prnctices change . a ll reg i s te red pesticides co nti nue to mcc t t h e s t atutory s tan dard of no w \ re.l.S(ln!tb lt: adverse e n· c:c ts. ChongL-'S in sc ience:. pub l ic pol ic y. and**J>C"~ticide** 

### use pr.tcticc:s 

## ,, ;u occur over time . Thro ugh the n. · gi s t rat ion r c,;cw rrogr.un. the Agency periodically r c· c . va.Juatc s pesticides to make s ure t h: u as th ese c han ges occur. p r

od uc t s i n th e**marke nc** **~** car\ contin ue to be u,_"Cd $!lfe l y. In fo rm at io n on thi s progrom is prtw idt"d 

### ns \\'WW.cpi-l.t:.QV/ QDp:imJI / rc.-g i s t r.ttio n**rC\~cw .**  111e Ag-.! n cy is impkrnt"ntin g t he regi s tratio n rc\'icw p r

ogmrn pu rsu.'l.nt 1 0 Sec ti on 3(g) o f t:IF R A. and wil l re view cnch registered pes t icide C\ ' Cf)' 15 year.; to d ctcnnine wheth er it cont inu es 

### w mt-ct the Fl FRA s tand ard fo r rcgistrntion. ' Inc rc g u l: uj ons so , ·cming r..:gistr.uion r e,

• icw begin a t 

## .;o CFR 1 55 . 40. The Ager 1 cy will consider bcndi t.S inl bmHH io n n nd d:tt a ns r e qu ired by FIFRA . Ti t t- pub l ic phase of r c:g i s tr.:tti on**TC\~Cw** beg ins when the in i tial dockcl is opent:d fOr e:tc h case. The d ocke t i s th e Agency's o pponunity to s ta.tc what 

### it know s 3bo ut t hepC'.)tiddc and wb:ll Dddition.:tl risk

**:m;al)~** and <bt3 or infonnntion it lxlic\CS t1J'C' m;-..--dcd 10 mnkc a rcgistntion rc'ic'' dcci.<ion The first lep idopteran Bt com PIP wn.c; rcgistcrtd i n 1996 and the

**fir.~t** coleopteran Bt com l'I P was registered in 2003. Neilhc r lcpk l opt cron n o r c olroptcrnn '' 'com PIP s lut\'c: undcrsonc n:n:gi s trotio n bcr:ausc pmduclS cont01in in g them were fi rs t

**rc~is tcred**  after No, ' cmbcr 1 9 84 . ll o wcvc r . EPA h M conducted n number of reas sess men ts of l h l'W s s in c e their

**rc~btnuion.** n.< de s cri bed i n s c. 'Ct io n IV of thi s document. Bt co m PIP

**n:g rJt**  **ons** 

### h.n"c h i s torically been issued w ith cxpim t ion dates and tcnns ofregi s t m ti o n th : at rcq ui re the generati on 

# or udditional d ata. lksc Steps have ensured th >t EPA can pc ri od ica ll ) ' rellSS<M the current scit·ncc und risk

**profit~** fo r the 

### rcsi s tcn..--d Bt com PIPs to cnsu..re the y continue to mcxt FIFRr\ 

### 's rc gistm tion sundnnls. 

### usr, M in l i SA <a : A Plant·i ncorpo nah."< l l 'rotc-ctnnt (PIP) i s defined ::ts a 

### ··pc.sticiUu l s ub stance t h01 t is i ntc nllc ll t o be produced nnd \I .S (.'\ l i

n o living p l n

nl. or in the produce th creoJ: nnd the genetic n

u

ucri al

**nc~ CS..."-'l**  **y** f o r it s produc t io n " (.JO CF R t 74. 3 ). ln co m , PIP s derived from flue ill us tlm ri n Mh •n

sis ( Bt ) h ll\' e bee n gc n ct i ca11y cn gi n c..:red i nto com h ybrit iS t o prov ide i n s ectidc.lll l JlrOtcc ti on agai nst ccrtn i n pc::.ut. One <:lass of Dt com PIP s ( c .asc 

### GSO I)

**~l.! ~**  lepi dopteran stn l k boring and l.!ar

**~cding** insect s

**(c.~** . • Huropc an co m bon:r. com carwom1. and so uth western com borer) : a sccond <lo ss (c:l.SC 6502) tara;cts colcoptcr.m r oot feeding inSC<ts (co m rootwo nn ) . A number of indhidual Dt toxins lu\ ' C been

**n:ghtc~** for control of lc-pidoptcr.Ln or rolroptcrnn l!ll};ct pests . which :uT dctnilcd in Table I below . M;my of the individualto.xins Bre combir'h."'<! 

### ,,;th other [h mxins to 

### crc:.ttc -pyramidc.'<l- (two or more loxins r.:uscting the 5.1I11C pest) o r ''Slacked"' (targeting multi pi\! re s t compl exes ) \'3rieties. Tab!< I . R<)li st en.-d Bt Com PIP s 

### ns or20 15. Ut I 'll' (tox in ) t- : \ ' (111 I'C Co d e Ca s e Tart:t · l

**·t'~ls** 

### Yt"ar Rtl!ist<rcd C r y lAb fit I I OQ6.l6 1 6501 Lep idop te ra 1 996 Cry 1A b MONSIO 006526 650 1 Lcpidop tc ro 1 996 Cry lf TCIS 07 006481 6501 

### Lcp ido piC'r.t 2001 Cry3Bbl MON 88017 006498 6502 Coloopc cr.1 2003 1 Cry34 f3 5 59122·7 006490 6502 Colcopccrn 2005 mCry3A 

### MIR (;G.I 006509 

### 6502 Cok-optcra 2006 Crylt\ . 1 05 MON 89034 006514 650 1 

### l .cpi4.loplcro 2008 Cry2Ab2 MON 89034 0065 15 6501 l.<pidoptcrn 2008 Vip3A:t20

**~1 R**  1 62 006599 6501 

### Lc piJortcm 2008 cCry3.1Ab 5307 016483 6502 Cokop1 cr.1 2 0 1 2 

## •• , • • • • I ' 

### ' ' 

## ' 

# . . 

# . . . • C.:I')JIJbl ":.s 1 M..a.l)

**gn lnrd**  ;b

**O~** S6l com Ul ... OOJ . MON $1017

**rc ~i**  **iC'ft'd** In .. OO.S) n:plxcd th as t'\C'Ot II.)

**~lit** )(M.Irt"C" of Cry3Bb 1 .Ot co m , 'afict i .:s an: predominantly fiel d com . thoug h severo I swee t co m nnd popco rn uses have a l so been**r~gi c:** **red .**  The r cs i st.:red 

### r, IP t ro it s (Tnb lc I) nrc b r e d in t o c om h ybrids \\i t h gcnct i .: b ock gr ou n ds that**h:l\'~ lx~1** **~ op** **ti ~.** **"d** f or d i tT crc nt c om· gr owi n g regions . O th er t rait'\. i nc l ud i ng he r bici d e t o l

eran ce, nmy :1lso be stac ked in th e conu n crci n ll y-::wu i l: l

blc: h ) ·

b ri ds . G r owers h :l \' e widely**:~dop cd**  Bt com 

### i n t he U.S .• bot h for control of lep ido pteran pest<; and com rOO t \ \ O rm . Fro m 20 11 to 2013 n n 

### annualavcmgc of94.6 mill ion acres of corn wen: g r

own in the 

### U . S. Of th ese. app r oxim; ucl y 

### 70.6 mill io n acres 

### ( 75 %) w ere plnn h :d to 

### Bt ' ' nrictic- s. St.ttckcd hy b rids . c on tai ni n g bo t h l cp idop t cr:m 

### ru 1 d roo t wom 1 t r..tits . were t h e mos t commo n an d 

### cov ere d 49 mill ion ncrcs (52 % of all com 

### ocre:sg c i n 20 1 2) . B t com 

### p r

od u cts with o n ly 

### lep idop t cr..\n tmit s 

### w er

e p lanted on 

### about 20 mi llio n a c res: 

### when co m bined \\oit h th e stm:kcd variet ies. a t o t

a l acf\!' o ge of obout 69 

### m illio n acres wa<; {: r o wn \\ i t

h lc p idop t c mn B t trait s . Roo t womt-o nl y t mi t.s wer e pl anted o n less t h:l n 1 .5 mill ion acres . gi , • i ng a total of abo ut 50 milli on r ootwomt-pro t cc t ed ncrcs . (Ac rc Jg .:**tig~s** are ru mual 

### a vcr. 1 gc s b ased on 201 1- 13 

### p

roprietary sur""Y dJUil). Ad op t io n of H t com hns steadi l y i n cre3Se d s ince th e 

### ti rs t n p

pro\'u l s were grun t ed in 1 996. In 2000 

### (prio r 10 t h e 

### r cs i str.ttion of rootworm - p r otecte d B t c om). 

### l cpidop t c r

rut-pro t ... "e t c

d co m was gro wn on a p proximat el y 200/o of U.S. cont ac-res. IJ)' 2006 . a l mo s t 40 % o f U.S. c om was B t 

### ( i

ncl u di n g room ·om1- pro t ccted \ • aricties ). Wi t h increased :wni l ::t bi li ty of reg i s t ered s t::tckcd lltld pyrrun idcd p r

od u clS. Bt com adopt ion r eached 60% in 2009 (USi l .'\ Econom ic Resear c h S t:r \' iccs data . sumrttllri?.e d 

### i n Womiak .: t n l.. 2013). SC IE N T I FI C ASS E SS \1 ENTS A . l, rodu c l**h~r:.tcl riz:nion**  a nd ltum:.ln H C': <h A ssess mtnl s The co mp lete product chamc teri 7..at ion and h w

n:tn hcnl t h**a..~s rncnts** **han~** been d oc um e nted in t he: Ag en cy's ·· B iopc-.s t ici d c R egistrat ion Ac ti on 

### Docume nt " (B R AD) f o r each rcg i s t cn.xt D t c om PIP. These I:J I{.. \ Os ha\'C bc.--cn peri od ically update d t o r c tl cc t n ew scien t ific info nn at io n an d d ata reviewed 

### os p.'ln of EPA's PIP r eassessme nt s (s.:c sec ti o n IV o f t h i s d oc u men t ). A ll of these docume n ts ore axail ablc on- li ne: Tab l e 2**cl d~**  t he ci tat ions n n d l i nk s t b r**~ch** 

### PIP ORAD u ndergo i ng**r~s r:uion** **~\ ic** **w.** EPA · s procluc t chamc tcri zatio n and hu m:m hl!a h h risk**n..~e ss** **me nt**  framework fOr Ot co m PIP s i s desc ri lx'<l i n Ko u gh & Edd s lc i n (2013) as wel l as in E P A's B RAD docu me n ts (Ta bl e 2). Si n ce each PI P \\ liS assesse d i n dh idually for rcgisuat ion. t his doc u ment wi ll con t a in on I)' n gc:ncral su mm :try of t he- st u dies 

### ty pi cally revie w ed fo r PIPs und 

### t he O \' trall ri sk assessment 

### con ci LLo; i on.o; .



### 5Tab!• 2. BRAD CitnliOII$ for RcgiSicmlUI Com 

### PIP s.

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### · II

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### · n1M.()()I0 .
Bt com PIPs :lie scncticnllr tron s fomu:d w i ng

**gc:n~'ti** dcri\ ·ed (rom the bacti!Tium &C'illus

**Ilw rlu~it·ruis**  ( 13t ) . n grnm·)X) S ith ·c boctt:riwn

**om mon!~**  **·** found in so il. Tr.msfonna ti on into the com plnnt sc n omc i s t ypicn ll ) ' nccomp l bht:O by ballist ic me ans (i.e .. n "sene gu n ") o r mcdi n t cd by lxu:terin

**(Agrobactt•ri~tm** /JIIIl t:{t l t'it•,s ! Rhi:obium r tu li obl t rh ·r). The t nms t bnucd genes cnc:oclc 

### for pro l cin s oxi tl .s . th:n spc cili colly nilCc t e ith e r lc:p idopterrut (ca.sc 6SO I ) 

### or co l eop t cr:m (case 6S02) target pests.

**os t**  of the rc t:;. b.tcrcd Ut 

# r•w s produce crysta l dcha·cndotosins (designa ted by 

### lh< ··Cry" " prefix ). Some 

### ol'1hcS<: Cry PIP s ore S)111hclically-<lcsi&'"'d (q; .. 

### mCry3,\) or 

### nre chimeric proteins cn.""alcd from poniOI\S of olh<'r Cry proteins (e.g . .. Cry

**\.105** and eCry3.1Ab) . 

### 6Such PIPs nrc typ icall y des igned to i m prove expn:ss ion in Ute com plant or increase in s.:cticida J ncti\' it y ngtdnst targe t pests. O ne rcgi.stt."n!'d PIP (V ip3Aa2 0) expresses a vegetative inse ctici dal protein (Yi p) . n group of Bt toxin_.. s tructu m ll y unrelated t o th.: Cr)' proteins. EPA's prod u ct dmr.tetcriz:ujon**nsscs.sm ~nt** **s** have exami n ed the nn tun: of the PIP (DNA com1ruction). how the PIP is incorponllL-d int o th e com plant, a nd how the PIP i s expressed in t he com plan1. Spccilicnlly.r hc Agen c y has evn l untL'C.I the follo,\ing types of dam t O

r Dt com PIP clt.ar.lctcri1.ation: • T ram:form alion sys t e m / proctss: S ubmiu cd data hl\'1! ' included u description of the p lasmid n!c t or con t u

i ni n g t h e Plfl. i n d u di11g r.:fercnccs to th e stra i ns of 

### Bacillus J!mrin Kh'llsis u.scd :15 the so urce of the DNA SC"qucnc c for the t oxin (l)r descriptions of the engineering process for chime r ic proteins). In addition. t he sour ces for marker proteins. promoters. tcm1inato rs and enhancers. as well as th e frngmc nt 

### si1..:, orienuulo n and mod i fic.ations t o the: orig i m

• l DNA scquc:nec have**tx~n** pro\'ldcd . The methods of inserti on (truns f o rm ation) into the com p lant genome have also bec: n documented i n t he char-Jctcri?.a t ion datu . • C h aracrc:riuti o n of the O!'liA l nscrltd i n th t Pl:mt: I nserted DNA ha s been characteri1.cd with res trictio n enz)111C digest" and Sout h ern blot datu of the DNA in the plant genome. The !Ulalys i s usoolly consists of D>-IA isolmion from the tran s l bnncd plant. digestion of thi s DNA wi th scw :nd Uiffercnt endonuckascs and**ybritl ~.u** **ion** of th ese re strict iOJl c:ndonuclcu.se frugmcnts \\ith J nbdcd·DN:\ which is comp l emcnt.ruy t o the introduced t rahs. This nnllys i s include.s not o n ly p

r

obes spccHic fo r the ent i re insert. bu t also probes n.<>cogni1.ingjus t the coding region s of tJ1c traits or DNA dement s outs ide**th~** codillJ; region. Po l ymcru . ·•c cha j n re - act ion (PCR) CLSS •) · s ut i l izi n g various sped lie and non·spcci l ic p r imers. genome wnlking. cosmid l i brories nnd DNA seq u encing have a l so been employed \\

i th sc nsith ·c Southern blott i ng techniqu es to more comp l etely describe t h e i nserted :U\d s urround i ng r eg ions . Tile infonnation nvai l nblc from the se blots can indic me the presence of al l the clements of the «::<pcctcd in s ert 

### ns well as iniOrrnation abo u t the possibility of delet ions and**he r**  e rr ors assoc iated with DNA introdu ction by trnnsfonn.:.tion. Comparison of Sou t hern b lots of ge1lt>mic DNA. digested us i ng a rnngc of restriction endonuclc::I.Scs . can nl s o rc ve i llthc: copy number of the ge ne s in t rod u ced nnd suspected linkage of t he t rai t s . A h crn:uive l y. the inten s ity of t he rnd io:tct iw labe l from b indjng the probe D>-lJ\ can n l so L"Stimatc t he numbe r of in s ert copies incorporJtt.-d i n t he plant**ge om** **.** When t he i nserted UNA con $ tnJct include s troi t s e xpressed only in b;Jctcrin and not expected to be eN pressed in the plant. da t a h ave been p r esented t o indic a te t hat there i s no transcrip t ion or trans lation ofth e bacterin] t rait. • lnhtril .a n cc and Srabilil y aflcr Tr :an5 form a li on : The: dntn gcnen'l t cd l O

r thi s endpo int hove c xrunin<d crosses lxtwc-cn sde<:lcd el i te l ines with the tran sfO rm e d Ot «::<pr essi n g linc. looki n g for the independent**segreg~ Hi** **01 1**  of the intmduct."d troito; i n the progeny . Trndi t ionnl bl\.-cding work done: during the dc\ ·c:Jopme nt of the plant l i ne by b:.ckc-ro ss ing cnn rc\' ca ( the li nkage of the introd u ced trahs as well as change- s in tra i t expression. The i nh critru 1 cc dntn is th e ratio of progcn> ' cxpf\!' s.sing the h emiz.ygous**tr o~i** **t** based on CXJX---ctcd**lcndc an**  inhcri tru1 ce. St3hilit> ' data hlve i nv o h ·cd e i ther an cxamin:uion**ft h~**  

### <'XJ11'\' SS ion of 1h c: 1ro it o r lr. tddng the ON ..- \ 7itself O\' tt SC\tr.ll pl311t gmcrotions. Ont ofthe m3in concC"ms with subility is spontlnrous lo ss ofthe inscncd

**D~A** o r loss of cOkacy due to gene s ilencing. None oft he Bt PIPs ha' e sho , \n i n dc:prnde:nt

**ns..~nm nt**  of t he introdu c ed t roitS ( the morkc r proldn Md t h e B t protei n w e n: cxam in .. -d) . This indittues t ltlt th e tr.ait s ll.n! o n t h

e snmc chro m oso me an d d os el y lin ked (cro SSO \ ' C

r cn:nts bc t w«n the tmi ts Jm v c n o t tx:c n dc tc cu:d ) . • PI"Oitl n C h llntclerb.n lion und Equh · a l cncc: Fo r llt Pll) s . dn1n hnvc been p resented • o Jcmo ns t ro tc th;at

**th~:** protdn exp ress ed fr o m th e in s erted DNA is s imil ar t o wh : at w a s prod u c

ed i n the

**so urc~**  U t bac t cri m n ' a n

d i s n ctivc as cspcc:ted :sg .:a. ins t tl lC i n

tcndrd tarset ins.."'tt . (Fo r PIP s.. i nc l ud i ng chime ric \ ' ori et.i cs . t he protei n

**u.~** for cOmJ'=Iri so n is m icro b i.:a. IJy·produccd b)' 

### E. coli . ) Som e pro t ei n

**ch;trxteri~tion** dat:. dcmOt\.\t.r.!.te th:u mierobi:ally-prodUC\.'<1 Bt prot e in i.s the cquh'Uirn11 0 dut cxprn.'<"CC in the plant This ;spp;t. rcnt scientific tautology ( when: plant produced protein is the .s.vnc: ns microbb.J protein i s the same 

### :ss the pl3nt produ< < '<l proldn) hl\S been used 10 justify ' "" .... of the microbiolly - produced protein ns u

**t** s ub s ta.ncc i n t ox icit y t ests. Becau s e the:

**-: ~pression**  lc\'d of

**he.~** p ro teins i s so lo v. · i n pl w 1 ts. a.n d t he ma "(imum h37.:1 r d do.sc ocu t c o rol to xicity

**1** i s

**r~qu r~d**  as

**p:-~rt fth~**  h u

mnn h e alth ri s k o. sscs..c: m e nt f o r

**th e~**  p ro tein s: . the abi l ity to produc e the prote i n in an i ndustrial mi c ro be i s esse ntia l. Pr oper charn c tcri u ni on o f th e c qui\' a lcnc y between t h

ese mit:rob ia

J prot e in s and p l nnt e xpr..--ss cd p ro tei ns rmv idcs un a ltcm :. ti"c t o puri fy in g t he

**~1** mratcrinl as th e pl an t p roduced pro t ein from l:l rge \' O ium cs o f t i ss ue. 11u: lcslS d one to sup port t he cquh oslcnce ofmicrobial and p i lO t- produced B t protein hn, ·c

**incl d~**  **:** mo l ccuhlr sizing by

**SDS~P \G**  **E** and western blot :uuJrsis : immuno·n;ocognition using EliSA nnd wc: :st cm blot M.llysis: N · tmniool amino aci d sequencing; conlirm:uion of the lack of g l ycosyl:uion in the pla.nl·produced protein : and biooct h i 'l )' O:gnin$t 3

**mn~,;c** ofinscclS (often 

### p.--st species including the tn.rget pest). These c qu i\' : tlcncy dotn hnve b..""C n se ncrntC'd fo r n ll U t <:om PlPs n; g i s terttl tt) date . • l,rottin Exprt ss l o n : 

### · n1 c Bt protein c:;(pre ss io n leve l i n \ ' n rio us ti ss ue s throu ghout t he t:;row i n g seaso n has been dc:h:nni nc- d l b r e a ch rq !iS tc:n.'ti PIP . The se dDtn h B \' c . bC<" n d c t c

m1inC'd and pr csc nl cd. in t e nu s o f dr y wei ght. a s th e runo unt of p ro t e in prck nl i 11 h: a l : po llen. si lk. stun:. se .. ·d (kernel s) . r oot ti S) · t u: , and who le pbn1 . Data fo r p rotei n

**xpre..~ on**  Ju , ·c bee-n ob t a i

ned using qu:mlilali,·c ELISA onal)· scs. • Ansl y tial Mrth od:

**An:ll)lic~** methods and method \ ' :.llid:nions h;m : bl.ooen rtquired for eJch rcs;htnro Ut com PIP toxin . T'hous-h cxh rcg_istcrtd Ot com PIP h3s on c•cmpcion rrom tokrnncc . =!)tical m<lhod s are u.«d to dcl«t r or tho:

**pre~"'m:'c** of t he P IP in commerce. The

**nM ~1**  **cnl** me t hods dc\ ' eloped fo r Bt com PIP s h nve b..-cn EUS, \ -boscd t est k i\5 . ln depcn<knl l nbomt ory( l h ird pa n y) valid :. ti o n o f th e r. U S A k its ha s tx.-en rL"'qU i r c d . Pre, iou)ly , m e th od \ ' :t

lid : J.tion w a c; a.l s o ve ri l ie d b y E I' A 's OPI) MiCTObio logy l n bo mt ory n t F o n

**M~dc .**  !-. · 10. HOWI!\ ' Cr. EPA n o lo n ger condm:ts mcLhod

**vn lid**  **ui s**  pro, , idcd lhD t the Gra in Inspe c ti o n . l'n c k

c rs o ntl S t oc kyards Adminis tnni o n (( iii' S A ) o f the Uni h:c.l St3 t cs: Dcp:utm..:nt o f Agricu lt un: (U SDA) l w vcrifitd

**th~:** pc: r fo rm anc c 

### o f311 8appropria1c qualiLUi\C r.Jpid

**t~ t**  kit . The product c har.lctcri7.alion d:Ua re-quirements for all ofthe rcg.istc r ed U t co m PIP s h ; l\ ·e

**n** sa 1 is ti.. ."tt. Co mp lete descriplion s of 1. he s u bmi tt ed :;tOOics nnd

**r~ u**  a n! incl uded in th e llRA I> s f o r each PIP (Tobk 2) . There :u-c current l y n o o u iSUnd in s chomc l cri.a lli on d a la gap s f or n n y of t h e 

### B t cont I'W s . l l um: a n 

### health re views. i n d u di ns die t ary ass c:. -ss mcn lS t o s u ppo n 

### cxcmp t iOilS f ro rn fooJ toknanccs . were c onduc t ed for

**~cl\** Ot com PIP at t he t ime ofrcgistr r uion nnd 'LS part ofth e 200 I and 20 I 0 n=:3SSCSSmcnts.. l hc M"Clions below

**descri~** the

**~cncruJ** consitkrntions used 10 c\ alu.ate hUJIUI\ tk."3llh ri s lr.. for Bt I,IP s.. SJ'l'I."Citic conclusions and d.au sumnuric:s for indhidual PIP s c3l1 be found in the

**comspondin~** BRAD documcm (Tobi e 2). The blSic p rc mi st

**i~o. -d**  on fo r th e t oxicology asscssmcnb is I h.: fac t lh :: n all Bt PIP s arc 

### J HOtc in s. P ro te ins a rc co mmo nl y f O

u

nd i n th e diet an d ,

**.x c~**  **'I1** f or n fe w 

### we ll d es cribed pl

u

: n

omcn n. p r ese nt l itt l e ri s k us u m : mun a l il n h»,.."tn J. I n ;1dd it ion. f o r th e mnj o ri1 y o t' Ut pro tein s currc ml y rc,g is h :rcd . t he so urc e l ,. 11 .: t t:ri um ha s bee n a

**e~ d**  m ic rob iol

**pc id.:**  which has bee n ll f l p Rw cd f o r us c o n I O<k l crop s wi t h

om s pecifi c n:s tri c ti ons . O c

c

n u s c o f t heir 

### u.sc as mic r o bini pe sti c id es . 

### ; l fo n g h i s t ory of s.n l i:

**u...~** i s n.sso ci : llcd wi t h m.: my 

### Uc p rod u ces. Sc \ · cmJ t ypes of tlmu 

### :an: rc:quin'tl t br t he O t PIPs 10 dcmon.str.:nc 1h:u no unt{".lSOftlb l c ad\ crsc cO--..-cts \\ill

**~uh** from the asg. rc g:u c: exposure to these pro tein s. The: information is 

### intcndOO to :Jlow th.uthc Ot 

### protein bch.:wf:S ns w oul d lx

**c~J)\."'\,;h,.'\1** of a dicll.U) • protein. i s not s truclur.lll) • n:btcd to any knO\\ll food alle-rgen o r pro1cin toxin. and doc. not di s pl:ly 3tlY oral

**~icity** \\ hC'n ::tdmin isteC\.-d ot hill.h do ses. These

**da t:~.**  consis t of an 

### in vitro digestion il.SS3)'. amino acid >equcn c c h o moJOf!) ' compari so ns :Uld Mncu t e or.:a l toxici t y te:,t The 1.1cu t c ora l toxi cit y t est i s done m a nUl.\: im u m h li.Zllfd d ose usi n g r uril icd p ro tdn of th e 1;11• ns :tlcst sub stanc e . Due t o

**im ito**  **iom~** of 

### o blni nin g su nici c nt 

### q u ! uU ilic s o f pure prot ei n 

### t cs l s u b:.:tnncc fr om th e plant it se l f. m1 n ltcrn a t h ·c produ c ti on so un.: c; uflh c protei n i s o t l cn u sed suc h u s lht: l J a d llu .. f

**th ringh** 

**IJ s**  soun;c 

### o r gan is m o r an ind us trial fc nu cn t mio n mi c robe . The j u s tH icn t io n f or 

### e mplo y in g t h i

s a hc m ; at i \' c so urc " o f p ure pco h : i

n is t he cqu i \' nlcn c c d :lt::t

**di scu.~sc**  **d** ubow u nde r r rod u ct charnc t cri7 . .. :n(on . EPA be lim$ lh :u prolcin in>tJJbilily in discsti , ·c fluids 3l1d 11>c la d. of o d, ·cr.;e efT«:lS usins the rna. :<imum hxw.rd dose 3pproxh in gen ernl eliminate: the nc:cd for longcNc:nn

**t~1ing** of 01 PIPs . Dosing ofthese anim:sh. \\ilh the ma.ximwn ha.zard 

### dose:. along \\ i th the product

**ch:Jrncterb.~uion** d.at.:l should idcnlify potcnti:!l t oxins J.Od :tlle r

g:cns. and 

### rro"ide :tn 

### efrccth · e 11 11. .\Ul S l o detc nninc t he safety

**ofth~.-..c** 

### p rOlc:i n:,., The adequacy ofa h c cun-cn l lest in g r equireme n ts wu s disc u ssed otlhc JWlt: 7 . 2000 S cient ific , \d, ·isol)' Panel (S 1 \ Ij ) meeti ng. In thei r fin.:t. l r e

po rt , t h e S AP ag r e ed 

### in princiJ) Ic \\ 'ith d u: met h ods use d b y E P A to n:r;sc .:ts l ht: t oxici t y o f p ro tei n s csp r cs s " d i n Ill a nt s c s pccin ll y t he 

### I U

:L'!i m u

m h a1.n nl d ose npp ro: ad 1 . Dh•f fll')' Risk Cl m ruc t al:all t m 

### 9**eien ifi**  **c** d n t n und ot her r ele van t i n fonn:s t ion i n sup pO n o f B t co m PIP s n n

d consid cn.-d i L;; v

u li d i t y . c ompl c u ; nc ss ft n d rdi Bb i l it

y . omd t he rel a t io n s h i p of t h is i nfo m 1 n

t io n t o hum an ri s k. E l) i\ h us ; t lso co nsi d e red " ' ' oi l!lbl c i n f

onn n t io n c or l cc m i ng the vnriab i l it

y o f the s en s i t ivi t ie s o f majo r j d i." nt iti:tb l c s u bgro u ps o f

**eon~;umers .**  incl uding infants an d ch ildren . .\lum,wliwt T oxiC'ity mul Alltrgitliciry Asst . umml

**ut~** ornl tox icit y s t ud i c!' have bc: t n

**ub iu**  **~d** fo r

**~:a ch**  **r~: cd**  tlt co m PIP. These s t

u

die s h : we s h o wn n lack of m : u

mn ; t l ia n t oxici t y m h ig h l c\' e ls o f e x po s ure t o t h e PIP p ro t ein s o

nd dcm ons t rn tc sn fct y n t l

c \'cl s we ll : 1 b\w c th e max i mu m

**XlS..~; ib**  **c** expo sur e lc\' d s tha t ar c r easonab l y Unlicipa t cd in c.:om.

**:L.~ nlllhesc:**  co n clusion..s o n Dcu tc ornl tos:icity dnta w itll out requiring funhcr toxicity testing :lnd residue d:l1.0

**i~** similar to the: Agntey po s ition I"C'£. :.m! ing toxicity :snd the t\."quircmcnt o( R'Siduc da1a. forth< microbial £Jocil/rt : r lhuri11gfrnsis

**producL~** (rom which thc:.sc PlPs were dc r h ·

ctl (t h i!' microbial

**~iduc** nnd toxicity d.,la requirements

**a~** detai led i n 4 0 CF R §§ 158 . 21 30(d)( I )(i) : md 158. 2 1 40(<1)(7)) . When JU O t ci ns nrc t oxic. t h ey arc kno wn 1 0 oc t v l n a c u te mec h a ni s m s n nd a t very lo w dose lc \'c ls (Sjob l od et ::tl• • 1992). Ther e f

o r.. !. sinc e no

**cff "Cl~**  we re show n even a t reJ at

i \'d y h igh do_..:c le\ ·cls, the P J P

**pro ein.~**  are not con.side red 1oxic. Furtht-r . amino acid sequence comp3risons bJ,-c shown no

**similari~ ·**  bc:tw«n the n.-g.istrr\"d PIP rrotcins and known to.!\ it' proteins available in public protein datnb:lscs. S i

n

e -: 

## nt f'W s 

### a.rc p ro t e i

ns. oll crg cn ic potent i n

I h n.c; also be en

**Ci d~**  **r-.:d .**  C urn.:nl l y . n o defi ni tive t es t s fo r d ete n n ini ns t h e ollcr gc n ic po tc nt i n

l o r 11 0 \'C l p rotein s ex i s t . **nu~rdore.** E f' A h:1..10 t&. '<.l n

**wcigh -of**  **id ence**  oppro::.ch wh e re t he

**fo JI**  **\\ ~**  fac t ors 3r l! cO I \Sidc n-d ; so u rce of the

**tr.~it:** nmino acid seque nce C{)mparison 

### " ith known allc rs c ns: and bioche:mic::t l p r opc n ics of the protein. including in ·, itro

**di~C"Stibility** in

**simui:~IC'd ~~ric**  fluMi (SGF) Bnd

**~lycosyl:uion.** This

**app.rt>:~ch** is consisaent wi t h the appro3C'h outlined in lhc Annex to the

**Code ~**  Alimcntnriu."<

..

**uid elin~**  t Or the Condu ct o f Food Sai'C t y Assessment of foods D c ri, ·c:d f r

om Reco m b in an t DNA

**s.'"1 11~**  a llergc n ici t }'

**ss ~o**  **--ss t**  for B t c o m I ' ll ' s

**clud ~:S**  **:** • Sourc e o ft h e u a i t Bacillust hu ri n gh•n.ds is no t c ons idere d t o be 

### o. sou rce o f allcq;cnic protein.s . • Amino acid sequence . Amino add sequence comparisons of Ut com PIPs 

### ''ith known allergens has l!lhO\m no O\'C'rnll

**~Juence** simil'3rity or

**id~"nlit~ ·**  ot the (C', ·d of cig } U c o nt iguous nmino aci d residu \:'S . • Diges t ib i l i ty . PI I' pr ote ins have be<:n :.;ho wn t o

**c:s t**  **rorid ·**  u nder g as tri c c ond i t ions ( i .e .. s-i mu la t e d gas t ri c ll u id co n tai ni n g pep s i

n

). • G t rcosy l at i on . PIP r ro t ei J tS c x p rc .ssc-d i n cCim h :l\'e n o t bee n s h ow n t o be slyCOS) ' Ia t OO . • Conc;lusion. Considering all ofth4! tw::t.iiJblc infomution. EI)A has concluded tMt the potenti;:sl for the rt:gi.stcrt'd Ot com I' IPs to be: food allergens is minimo.l.

10In exam in i ng 3ggr cg.:ne exposure. EPA t:Ons idcrs ;.wai l ab l e i n t Onnatio n concern ing c: ;'\pos u r es from t h e pe s t icide r esidue in fOod und nil o t he r non·occupat ional**c~po r~** **.** includ in g drink ing w at er from 

### ground w ate r or su r fucc w :t

t c r 

### and expos ure t hrough pest ic ide us c 

### i n gurdc n s. la\\115, or bu i l

di n gs (r e-s ide nt ia l and other in door uses). The t \gcncy has cotL o; id cn :d uvai l nb l c infomuuton on lhc : 1 ggrc:gatc exposure Jcvcls of con s u mers (an d 

### majo r iden t ifiable s u bg ro u p s of consumers) to t he 

### P'o-'Sticidc chem ica l r es idue nod 

### to o t her rel:ucd subs t an c es. These co n s idcnu ions inc l ude die t ary 

### expo s ure um.Jcr 

### the t olerance exemp ti ons 

### i n e-OL--ct for t he**dues** of 

### the f- l l )s, and expOs ure from**on~occupa ti** **onal** sources . Expos ure via t h e s kin 

### o r i n haJatio n is 1 1 0 t 

### l i kely, .s in ce PIPs arc 

### conta i n'-

'C:I: wi t h i n 

### p l ont cell s. . which 

### ess ent ia l ly c l imin:ucs these e. xposu r c ro ute- s or 

### 1\.'C:I:uccs t h ese 

### expO s u r e r outes to 

### n eg li siblc. In ad d it ion , even if expo s u r e can occur t hro ugh i ntm l nt ion, the potential tO r a Bt con1 PIP s 

### to be 

### an alle r gen i s low . 

### ns dis c lt.'iSCd :.bow. Although the aJic r gc n ic i ty**a.~:;se:ssments** 

### h a ve fOc used on the po te nt i al t Or t bod ( IIJ ergcn i city. t he data ha\'e**~o** 

### i n

dk : ucd n l ow po te n t i a l fo r P IP pro t ei ns t o be i n h a l ation nllcrgens .**E:~Cposure** 

### to infantS nnd chi l dn: n 

### via res idential or 

### l mm usc is not 

### cxpech."\1 . lxcmLSC t he . use s i te s for 

### O t co m PIPs nrc 

### agri cuh ur aJ. Oral cxposufl:. a t \' cry low 

### le\'ci S . 

### ma y occ ur f r

om i n gest ion of**proces... ~cd**  

### com produc t s and. theo r etically. drink i ng wat e r . Expo sure i s nt low l eve ls due 

### «o t h e amount of PIP pro te i n 1ypically exp r essed in grain (a \'Cr)' s muJI per centage oflhc 

### to t al pro t dn) a n d steps taken during 

### c

o m p r

ocess i ng t h: u 

### l ike l y furthe r r ed u ce the amoum ofPlP protei n . 

### I n add i t ion. 

### oral t ox i c i

ty test i ng in 

### m n

mma ls s h owe-d no :.dvcrsc c tli:c t s. 

### Fu rthc n norc . lhc 

### cxpo..""Ctcd dietary expo s ure 

### from com is severn ! orders of m ag Jl itu dc lower t han t he**ou ~**  of PIP protein s h own to have no t oxici t y . l11e-reforc. cn:n if 

### ncgl i sib l c aggregatl!" 

### cxpO s un: s hou ld occur. 

### th e A ge n cy co ncl u d es that 

### s uc h e. xposu r c 

### w o u ld present n o h : mn 

### due t o 1 h e l uc k of m ammali an 

### tm:icitr nnd a llcrgcnic it y dcmo n $ t

ro t ed t O

r Bt com PIP p r

oteins . Cwuulmire £ffi·cu Se<lio n 40S(b) ( 2)(0 )(\') ofFFDCA n.-quire s I hal. w h en cons i de ri ng w h e l her 10 eslabl i sh. 

### mod i fy . or rc\ ·okc 

### a to l er.tn..:e. the Agency consider -ava i lable i n fom t a t io n ·· co n cerni n g t he 

### cumulmive**ciT~'\':ts:** o f a pan i c ul ar 

### P'o-""Sticidc " s res idues nnd "'o t he r substn ncc s t h:u 

### J uwc n common 

### mechan i sm of 

### toxicity:· Si n ce 

### Bt P I P p r o t

eins arc n ot considcr '- "'<1 toxic and do no t sh:ttC a commo n me-chanism of toxic ity \ \ith any other sub$l!lnccs . EPA ha.s concluded that t h en: urc no cumu l utivc: cOCC I $ 

### a.ssocime-d wi t h O t com 

### PIP s . FFDCA sect i on -l0S(b}(2)(C} pro\ · i dcs t ha t EPA s hall**a~scss** t he 3 \' :t i lahk i n tbnn : ni on abo u t cons u mpt ion pa tterns amo n g i n fa n tS und ch i l d ren. spec: in ! suscep ti bi l ity of infunts ; md chi ldren t o pesticide chcrni t: 1 l re si d u es nnd the c u mul n t i\

' C e ffe cts on infants and c h i ldren of t h e 

### rc s id u l."s and ot h e r s u bstJ.nccs \\ i t

h a comm on mechan i s m of t oxicity .l n :ldd iti on. FFDCA**~c on**  -lOS pnwidcs c h at EPA shall apply an addi t iorl.fi l h : n fold m a rg i n &.'1f 

### c:<po su n: ($0fc:ty) for IIinfants :mel children in the C3SC ofthn:shold dTc-cts to account (or pn:· o.nd post•n:u.al toxidty nnd the incompleteness of the datOb3sc unlt'M EPA determines thJt a difTercnt m3rgin of exposure

**(~.fcty)** " ;n be snfe for infants und chi l dren. For B t c o m P IP s .

**b.'t.~ d**  on n llt hc U\ ' ai lab l c in fo rm n t io n . t he Age n cy h od conc l u

d

ed th :a t th e r e i s n o t oxic ity. Thus. th en: llf\! no thr \. ""S h old cfl 't."(ts of co n c

ern nml . O.'i a r\:' s uh the provi sio n n;; q u i ri n g a n a d

di t io n u

l m arg in of s.a. f c t

)' d OC's n o t ap p l y .

**un .**  th e JU O

\ ' is ions of C: (l n . w mp t io n I X'I IU ,· m s. $J>Cdn 1 susc ep t i b i

l ity. nnd cu mul: uive e O CctS d o not np p l y . E.xposun: 

### ,;:t the s kin or

**inh..1l:~otiun i~**  not likely sine<: PIP s un: conu.inc:d \\ithin pbn1 cells \\h.ich csscntia.lly climirutC'S the-se c. .. posure routes or mtuccs 1he:sc cxpo.sun: routes to

**nC'~1i~iblt .**  \Vorkcr txpoS\lrt' to lh f'IP protein ,.Ja seed dust is ttlso

**C'~p«trd** to be negligible bcc'3USC of the 1 0\\ ' a.mount of protdn C'Spn.":SSCd in trtlll5(orm<."<f pfanU . f f S\ I Ch exposure Should 0\:cur. t he Agenc y tondudcs th.'1t 

### it wou l d not be CXP'o- --ctC'd to present :tn) ' 

### risk due to th e lad:: of t o:< idty. If nny unre asonable udvt:rSc crrcc t s c.ausc d

**b~ ·**  expos ure t o O t com I ' IP s arc ide nti fied . t hese c ll' h t s mu.•:: t

**~re pone**  **d** to th -: 1 \ scncy ns re- qu i re d by

**~cc.** 6(nX2) oCFIFR A. J, llum a n lncid l!' nt s An init ial iiKidcn t searth wJ.s conducted was c onducted on ,\ugu s t 17. 2015 fo r this n:g,istr.llion r eview. One Dt com 1'11 1 im:idcnt (1021901) w:lS identified in the I nciden t Dau Sy >

l<m (IDS): chis iocidcnc in"oh ·C\lo fonncr in Minncsow "ho pl:uucd Yi<ldG:ud VT seed ( conuining Cry lAb nnd Cry3Bbl) in 2010 . The fnrmcr rcportcd fc.:ling lighlhcadcd. ,.,micing. o.nd passing out 3fter

**b~Lhing** dust from some 

## or

**~.he** seeds ( the incident

**\\~th** classified :1S modcrotc SC \ ' Crity) . HowC'\ ' <:r. these reported symptoms do not

**com.~pond** to

**tm~ ·**  knO\\ll e t ll'Cts rrom i n hu l n

t ion expos u re Bt com du .) t. S i nce mos t co m seed is tn:atl."<l with pest ici des other th:tn I h . it is m ore l i kely t lw.t th e re s pon s e \\otS t o an n ddOO. co n ventio nal

**chcrnic~ll** used t o trC'!t t th e see d . U n i

\!S$ th e tatn t c r wus sh0 \\ 1 1 t o h a ve i ngested th e co m

**sc ~.**  **"t. (h**  **gh y**  un l i kc:l y) . it d OI!S n ot 3Jl J >car t o be t l I

'Ood po i so n i n

g o r n ll c r.,; ic ti.!' Jic t io n t o B t p r o t

ein s . S in ce t h is: cas e w as no t l i k

e l

y r c lot .. -dto Bt. the r e i s no t n co n cern ot t h is t im e bosc d o n t h

e co nti n ued low frt.•q u enc y o f inc ident c:,:!>c.:S for U t com PIP s . Food colcr:mccs cxcmpcions f or

**~~:sidU<S** ofBc com Pll's lu• ·c b«:n .,ublish<.od in

**~0** CFR § 114 nnd on: sunuu:uizcd in Table 3 . A separ.ue excmpcion

**~0** CFR § 174 . 507) Ius b«:n estab l ished for n ucleic

**acid~** t h:u nrc patt ofthe PI P (i .e .. the encoding genetic

**m~ltc ri**  **al).** In

**:1d~ ition.**  no n lll.xim u

m res idue

**limit.~** (MRls) f or O t com Plf 's: h.wc been c!otab l ished by th e Code:<

**t\l imcnt**  **o.ritL~** Co m mi ssio n (Codex).

12Tablo 3. Food Tol<r:mcc E.wmpli ons EstJ>bli>ll«< for 131 Com PIP s. Ill rlr ( toxin) Toltnon« C ilotion

**0** CF R ) Crop• C r y lAb § 1 74.5 1I a ll crops Cry IF § 1 74.510 com Cry 313b1 § 1 74.518 con 1 Cry3 4Ab I / 35 Ab1

**~** I 74.506 com 

### mCr y.J,._ \ § 17 4 . 505 com CryiA . I OS § 114 .502 e o m . c: o uon. soylx.Jn

**C~ 2Ab2**  § 174.519 

### c o m. c o tton.

**soytk.~** Vip3A:ll0 

### § IH.SOI 

### c o m. con o n

**.C~ 3.1Ab**  § 174.532 com S. D11tn Ne ed s Th<:rc nrc: currently no idcr u i l k-d

**~1t~1** ga p s re gard ing produc t c hornc t cri 1!1 t i,)n o r hum ; m h

cahh for :my o f the r cgisrcrc d Bt com PIPs. EPA has ronduct . e-d cm i ronmc nul risk 

### 3.SSc$..Wents f or the Bt PIP s expressed 

### in com. G encr..J topics co , ·crcd in those

**D...\.<4,..,.~ rnc:n1s**  include e ffects on '' i ldlifc. gene tlow 10 rcl:ued ''ihJ pJ:mls nnd its poten1i:tl e ni."ClS. and fate of C r y pro tei ns in th e .:m ·ironmcnt The assess men ts arc b:J.sc d on d :ua sub mi ntd t o E PA during

**h~** de velo pment of I'l l >

com line s {i .e .. Expe rimental Usc P

en n it s) . n dditional dat a s ubmil h .'t

ll hr r<g i s t mtion. fede r al In sec ti c ide Fung i c ide ru1d

**l~l c:n**  **ici dc**  A ct (F IFRA ) S cic ruili c Adv i so ry Panel (S:\P)

**n:c n~wJ**  **ui on~.**  con s ul ta ti on s wi th sci cntilic cxpc n s . and rub l k co n u

nc:nt s on l l JP n:guJ3dons . Spcc ilic cm ·ironmc mal

**a~ ~mc:nts**  fo r i n di \i dual PIP s can be l b und in the BR.t\0 documents !' Or c;lch PIP ( Tnblc 2). This s«tion contains a general s ummary of the

**~nvir nmcntal**  

### risk assc:s.smcnt p.11"3di gm

**nd** conclusions 

### for 01 c o m

**PI~** u.s 

### a group . EPA uses o tiered ( Tiers I-IV)

**<c>~ing** S) 'SI <m ro 

### asso:ss lh< < o , i c i

l) of o PIP 10 rcprc.scntativc non - targe t organhm s th:lt could be

**c~;po scd**  to the toxin in the field cn\ironmcnL Tier I high dose s tuU ics r dlC't't u s creening app r o:Jc h to testi n g d-:signcd to n\3..\:imizc any t oxic

**~ffect s**  ofthe: t est sub s tan ce on the t e s t (no n-target) org.:tnism. 

### '11H . ' sc r c:cni n g h!'Sts eva l ua te s in 1;1<:· S

f "'·:cic:s inn laborat ory s ell i n g wit h mon olit y as t h

e end po i nt . Tier s II - IV

**~c ncrnlly**  encompas s d c: riniti\'c haz..1td l evel dc tcn n ina t itl n s .lc .lll gcr tcmt gre-enh ouse o r l ic:l d t e s t in g . and are imp le me nted when UI U.'lCCCJH ilb l c: c:llC.Ct.s nr c se e n a t the T i er I sc n .. "Cn i ng lc: \'C I .



## · n.c tic:rtd h3ZJJ'd asse ss ment

**~lppro"''-=h** was dc:vdopc;d for the: E I)A by the Americ.an

**n~titutc** of Bio l og.tc:s.l Science s ( AlOS) :md confirnted in l 996 as an acceptable method of 13cnvi r onmcnt:t l luv.,ard assessment by n FIFRA Scienti li c Ad\ ' i so r y P nnel (SAP) on m i crobi n l pes tici des o n d micro b ial tox i ns . The D« c m bc r 9. 1999 S A l ' ugrc .;.'<l th. at t he Tie r e

d

**nrp o.:~.ch**  wns sui tab l e for u Sc.• wi t h I}IP s : h oW1!\'Cr. t h is panel n. "Co m mtndcd thJL fo r

**I'U' ~**  wit h i nsect icid al rropcnics. i.lddi t ion:alti!S t ing ofbcndkinl in\ ·ertcbr.uc s

**clo~ly** re l ated to 11.1f!; ct species :md!or lik ely 10 be prescn1 in GM crop fields .should br: conducted . Tcsling of Ut Cry prolcin.s on !O pc.--cic-s: not closely «loh:d to the target irb4"C'l pest \\';15 not n:commendcd. although il is still pcrf onn<d 10 fulfill the publbh1:d ErA oon·t:trgcc

**~pee:** it s datn requireme-nts. ln October 2000. nnothcr SAP a lso
**~commended** dun lie l d te s tin g sho uh.l b.: used to C\ ' n lu

•. 'ltc popul:uion-lc\ ·cl dlC=cl;; on nonturg c:t o r gn n i s m s. The r \u gus t 

### 2002 SAP . and so m e p u

blic commen ts, gcncrolly ng r ccd w ith t hi s app r o a ch. \\i t h t hl! uddition.a l r cronu ncndat io n that i nd i ca t or org ani s m s should 

### be selected o n t he basis ofpotcmiJ.I for field expo s ure to tht subjec t pro t ein .

**lkln~cd** Ddn:rsc cff«ts :.nd!or occwnul:nion ofloxins through the food chain 3rc not CXJX"'-"'tcd to result rro m expo sure to 

### Bt PIPs.. o.nd these proteins o.re not roulintly tcSh .. -d for chronic efli.-ct s o n non - tnrgc:t orsnnisms . Howc:\ ' cr. the jO day test dur.uion requirement for most n o n - ta r get s t ud i1.o.s d01.--s a m oun t co s. ubc h ronic t es t i n

g \\ l ie n pcr i O

rmcd n t fi e l d \!Xpos urc t C)i dos e s . P ro tei ns :tlso do n ot b i o:tccum u lnt c . The b io l ob i cal nut u re o f p r

otei ns mnkcs th e m read il y suscep t ible to rnctnbolic . micro bin i . nnd obiotic dcwad : u io n once they nrc ingested or exc r eted into the cnvir onmcn1. Although 1hcrc arc rqx>rt.< th:lt some Cry p r otein." bind to soil pa n ic!!$. i1 kls also 

### lx"'Cn Sho\\n th:u 1he54: proteins arc dcgr.Kicd r.1pidly by soil microbial llor.1 upon elution from soil p. .

nicll.-s. 

### t. E m · iro nmenlal E spo su r r

**As,jt~~ mc-nt**  EPA's: risk

**ttSSCSSmcnl~** t Or Ut com PI Ps haw hccn center ed on

**nd\'t.:r~** c n i..--cts n t the field c.'<posun: rates. which \\"t'rc tyricatly based on protein expression lc\ ·cls \\ ithi n t he p lant for PIPs. Althou gh it 

### is recommcndc<l that non - "'S"

**tostin~** b< conductc<l >I>ICSI dose lOX the EEC v.hen e\ ·cr possible. I he: test dose margin can be

**~** llun lOX \\'he-re uncertainty in the system is low or where h i gh concc:ntnuions of te-st mntcri:t.l nrt not possible 10 ochic-\'C: due to tC'S t ors onism

**C:cdin~** h:t.bits . Fo r t he purposes ofth e no n · t mgct

**o~:..nism** (NTO)

**dics** submiucd i n s u p port of th e tcg i s tered ll t com PIP.s.lhe t est m :u cr i t

d dosc lc\ ' C

I S h ll \ ' C h c: c n base d o n the c

-S t i n

u:ued conccntrn t ion of t he JlJI ' inse-cti ci dal pro t dn expressed in t he t iss u r(s) tho t NTOs would most liL:dy be exposed to in the em · ironmcnt. Two scparntc SAP n:po ns (October 2000 :>nd Ausust 2002) rt<.'ommendc<l lh:!t nonUtrgcttesting of Bt Cry p r oteins s h oul d focus on in\'crtcbrate spcric-s expo.sal to the crop be

**in~**

**~s stcrcd**  **.** Fol l owing the SAP r ccommc n c.Lations. El)t \ dctcnninc-d thi.l t

**non·tm~ct** o r gan isms wi t h t h e

**gre:l cs**  **~.:sposu e**  po t c nt in lto C r y p ro tein i n t m i UJ;cn ic co m fi e l ds nrc be ne fi cia l i nsec t s. which feed on com poJi cn n n

d n.;.-ctn r. and so il i n v

c rtcbr.ucs. particul arl y Co lcoptcm n spcdcs. While EP.-\

**~** risk assessments of Ot com ha\' c focusc:tl prim:uily on these la'<n. the Agency r\."CC£1lizcs th.1t c . "posure to othcr non4orget ors:mism s can Ottur nnd 

### tw: required

**t~"'ing** on n."Presenuti\'c species (summ3rizcd in lhc 01: S:t section) . I n t he ''bsc n cc o f PIP· s pc:ci lie risk assessment guidance . EPA r cq u in: s tl J ' J

,I i c:mts for PIP

**~gistrntions** t o mc-ct the 40 CFR

**P~•n** l 58 dau r equir ements for

**nicrobi:llao~in s**  (§ l 58.2 1 50) .

**I~**" rhcsc

**rcquir~o."ffienL~** include testing on binK m:unmals. oon·tart;ct il\54-cts..

**bone~**

**·** lx"f:. p13nts. and

**~u:.tic** SJ)!o."'Cie:s • . As :tl:liC'd abo , ·c. much of1hc focus of BPPD"s ri s L

**G.'-'C~'mc:niS** has been on bc:nciicinl non - urgc1 im ·cncbratcs. sinc t: they arc most closely rel:ued to orgun isms susct"ptib!c 

### ao aha: insecticidal action of Uttosin.s . In uddition., carthwonn o.ntl Colkmbola (spri n gtail) studies h.I\ ' C' bee n submiucd t o t he t\gc n cy 10 t\$CCn(l i n t h e: po t c

n tiul

**~I S**  of O t i n scc t jcid:l l proteins 0 11 tx:ncficill decomposer s pe c i es. l1 1 c Oc t o ber 1000 SAl:; r ecommended th a t whi le m ; tu al pla nt mat c r i31 i s t he pref erred h ::, t nu:ucrinl. bllc t c.:ria l -<lc ri"cd protd n i s nl so o va li d tes t s u bstru 1 cc , particu lar l y in scenarios w her e

**1~1** a nima l s do n ot nonnall) • con. :mm c pl:tm tis...c;ue and " h eft' l:l rgc amoun t s of Cry protein (i.e .. Cry protein conccotrJtions lhat cxcc.:U lc:' ds prt"Scnt in pl ant tissue) 

### a n: n«dc.-d for mo..ximum h

r vnr\1 dose testins. Tes t

**sub!,t.at~ccs** used in NTO studies 

### h> :tuppon PIPs h:n · c included Bt containins pbnt mru.erical MK"h as gmin

**l~:t\ ~**  rootS. pollr:n. or purified. b.xtcrit\lly-produced Rt protein incorpOr.ucd int o lhc h.·st spt-ci .. 

### -s dir:t. For all ofthe r.:-si.st..:n:d Ut Plrs. cqui\"olc:ncy

**~tudies** h:a'·c br:cn submiucd to

**~.km ()(\)1r.nc**  t.h:st

**microbi311y~pnlfJuc:cJ** Ottoxins hJvc comparnb!c nct ivi t y TO those: derived from riBnt sources. A s:u mmnry o ft he-

**n:~** a

**h<~ t**  hl \ ' C bee n C\'a1U!lted f o r t he r q;i stc n:d ll t co m PIP s i s dcscrib!o.--d be l o w . Sped ti c resu lt s u n d c n d!X'i nt s for c -nc h NTO an: s u n

u

n:t r izc d i n BRAn s l b r C3C h rcgist<rc d PIP (Tob ie 2). A

**~·fan** Spt • dt•s A\ ' i:ln dir:t:U)· toxkity

**h.l.~** lx"'."ft

**~** 

### "ith Hcriugc broiler chicks

**(Gtlllt~s** dom.-stirru) th:u .t:1..n: n:.1.rcd cit.bC'r on Ut or non· At com groin. lhesc.- («.-ding !i•udic<ii: were' conductOO for -lO -+- cb)S lo c\'3.1uatc potenti3.1 

### eOl-clS of Ot rom grain on SW\ ' i\'31, body

**\\d~l.** f«d consumption. 

### fC't'd con, ·crs ion . :md

**c:trc3~5 ~icld** 

**.** Results from

**•h~** broiler Mudir:l!r> h:l\C shO \\n no trrotntcnt· rcl:ucd di t lerenccs. ind icaaing th:ll IJ1 nnd non- !11 com arc nulritioni'l l ly cqui\ ' :tlent. Relath ·ely long- t c n 11 \Jicuuy

**c:~posurc** to Bt f' ll ls i s n ot cxpcclcd t o result in ad\'l.'noe c11\.--ct'\ t o birds. A

\'o in oro l t oxici t y has been C\'O i u: u OO wit h th e No n hc m bobw hi te q ua i l (Co/inu s

**l'irf:hrlum~).** S tud ies ha, ·c ei t he r been d k l.nry (using Bt grJi n incoi}XIr r ucd ir u o di e t ) o r with n

**in lt**  or.t.l dose. No mono l i t i(.'.:, or ndn·111c dl'ccLS we re obscrocd in t ht;.

"SC :;;wdies


### "' ' ian i nhalation

**to~icity** 

### t \.':Stint has 

### not brxn n:quircd for Bt com fliPs. since exposure 

### to Ot proteins ' ' iD inhal:nion b nul

**cxp«H.~**

**.** JJ '

i/d .\/ammaliun Spetlc•,

**~1:tmmalian** wildlife

**c~po!ourc** 10 llt protdns i s con sidc n . -d l ikely: howeve r.

**nt..'Ullm;~linn** tc.lxico l ogy i n foml:l t ion

**g:uJu.•r~;.'\1** to Jo lc on Dt C r y p r o t

e i

ns docs no t

**~how** :1 h:ll.J.!d t o \ \ il d mamma ls. In nd d i t io n . ocu t c o r n ltox i city s t udies sub mi tted t o IW1\ in S UJlJ )() n

**of th**  **~** Bt c on1 PIP r csist r ot ions in d icate d t h ot n o

**.s gn**  **fica mt**  **os icit**  **·** wns se en when r odents w ere c . x

po s cd t o Bt I )CO t c i

ns n t ma.x imum h az.nr d Jo s l.! leve l :.. ' l1 1 crc fo rc. n o haznrd t o m; u nm: a l ia n \\ · iJ dl ifc is antici(XJ l cd n n

d dat3 o n wi l d mumma l te.s l ing hns no t been rl'<(Ui r ..:d for

**rl.!~i.s ro**  **ion.** 

### ISAqumfc S{Wch:s Fn: - shwntcr tish t oxicity ha s been c\'aJuatcd in tc:- , s t

s usi n gj u, ·cnik chnnnel ca tti s h (/cwlurtL f puncwuu) or rninbow trout

**(Oncho rl~•**  **·ncl s**  m,l ' ki

ss) . In 11 fi!w c nscs (Cry I A b. CrylA . IOS. Cry2A b2 ) ,,':J.i\'CN were: &r.ln tcd from conductins fn.""Shwatcr thh

**~udies** based on o presumed lack of c- .

\:posure of Bt com in ttqll.ltic- S}"Stnn s. In all but one of the:

**f~\\':llCf** fish Mudies conducted. n o mortal it) ' or sublcth31 cfl l.""CU \\ "ere obsc' n · ed

**in~** Bt lrt'atmcniS ( o Sludy conduct«! with mC ry 3A had n

**s:i l~**  mortality in the HHrcatcd group but no other adverse ctlCcto;) . Gh ·cnthc

**~suits** of th ese: s t u dies D.nd l ow nquntic expos ure . n o fre s hwater tish haz::ard i s cxpcch .. 

### -d from c:o mmcrtial cu hi\' O t ion o f

**~;urrl!ntly** re g i s tered Ot com I"' I P s . Toxichy to

**(~water ~u:t.tic**  i n\'c:rtc:bn:uc s h :u be-en to1ed \\ith Dnplmia magna. Studies \\t:fC conduc lcd as

**~8** hour) static mlt:W :tllimi tl n:ls \\ilh Bt poll en. sinc e this com tissue is expech."\1 to most like l y to be

**p~scnt** in

**r~h** \\ "'..ter. Though no signitican t effc:c lS w.:rc observed. the

**~lS** were tbund to be un:xccptablc bC'c.IUM! it Llkcs mon: th nn 42) hours for the target pests t o Sl i C.:CUtnb 

### co Bt protein s. In considcmtion ofthi s. and a

**publi h~,"\1**  rl.'pon (Rosi· Marshall ct a l.. 2007) oflld\'CI"SC cO"ccLs t o cmJd is tlic- .s exposed to Dt com liHc:r. EI)A mp,.1ircd n 7- 1 4 Daphni a

**tud y**  (or 311other fn :shw ater in\ ' Crtcbmtc

**r~;."prescnting** the

**(un~;tiona l**  sroup ofn leaf s.hr..'<ldcr in heodw : uer <1n-:uru ) for each resister«! PIP . Subsequent l y. other published litc:rature ro.iscd conccms with the

**osi-~ ;ush:tll**  s 1udy :md sugscSl4"<1 t:h=u the accuaJ risk to cOOdistlies w:1s much lower.

**~** a n.-suiL EPA n o longer n.-quiml additional oquatic in, · ertebratl.' s tudies to

**aM~es..~** ha7..ruds forC"xistin g Ut protein PIP

**n: ~htra**  **tions.** Before EP,\ wai\'ed lhc :tdditiona l m1u ; uic invcncbr:uc tc s tinM . two studies were

**ubmiHetL** lllc first. n 7- 14 day Daphnia study lor Cry I A. l 05 / Cry2Ab2. sho wed no t llliC t\So t mb lc adverse ci); • ..:ts (E PA. 20 I Oc). ThC' second

**ll..~** conducted 

### (or cCry3.1 Ab \\ith a k:1f s hrl"<iding

**fr~o·• hwnter**  iwpod. 

### Gommarus fusdo m s . :md also indicated th:.1t n o ud\ ·crsc d)'i.'Cts :.uc expected for

**fn-~m'Atcr** invcrtcbmtcs (EP A. 2 012). No sit:; niticant dirccr cxpost1n: s o( e.o;

twrinc t'lnd marine a.nimalo; t o Ut PIP s are nnticipo.tcd a...; a

**r~sult** of ngricu huro l production of Bt com. A s u ch. s tudies \\ith •: t aunrinl.' and/o r mnrine l i s h nml irwcrt ehrn h :s h a\'C not b<:cn required for Bt com

**1,. 11**  **~.** Bt kndotoxins produced by

**natural l~**  **<oQCcurring** IJuc'illus 1/Jurinxirnsls h:t \ ' e not sbo,\n roxicity to plnnt). n.e-reforc. cff« lS 10 non·tnrgct plan ts in the ttnestriill Md a qUI.ltic en\'ironments from Bt cum I'll' s nrc n ot exp<."CteJ nnd te s ting has not txcn r\--quircd. Tt·rrcMrla/

**lnwrubrm c·**  **.~** ..-\

s previously discussed . EPA ·s assessment on ntm--lM£: et in\ ' Crtcbrnt t"S htt ..; 1Br£,ely rocu....'C'd on hcndiciol ins«l sp.--ci cs for \\hich C .'IO'

po surc to Bt c o m PIP s c::m be c . "p«IC'd. Some Bt PIPs (CryJilb I. Cry34 / 35. mC ry3i\. <Cry3.1t\b ) S JK'Cificnlly tnrg<t c o m root worm spc:ci cs. \\ hich :u-c \\ilhin the order Colroptcnt (b..--c tl es). Sc\ ' cn:al of the 1'\.--q ui rOO te s t s indude s bt."'t'tlc

**~~ics.** 

### s ince it 

### is cxp«ted th : n th es e s pcdcs will be mo s t sw ccptib l c t o th e Ot t oxin. The toxicity of indi\'illual Bt PIP protdn s h as been c\ ' tt l untcd wi t h multip le S ['l.' cii.'S o fin"cncbmtc s includ i n

g: lady beetle

**(Coh•omt ~:llla**  maculato . 1/ippod.,miu com•trs,:Ms). c nru hid beetle 16(rwcilru cupuu.(), IU\"C' bc:ctJc (A/,•m•itciTCI

**bilitt~OJO)..** ph."'CbiOI) ' bu.: (Or ius

**/a~l'igaTU.J). gn.~** 

**13~\\ing** CL'hrysoptrla carm:t1), 

### pimt d flowcr bug (Orius insidioJif:),

**pJ~USilic** \\'3Sp (Nasonio \ '{

trfpt"tmis, lchnrumon promiJ .JO rho). colkmbola (Folsomlu c·tmdida ).

**honey~** (Api.s mc·llifi·rll). and carthw om 1 (Eisenlnfi• t lda), , \ddi t io n a l

**esting**

**'' ~**  n l so done 1 0 ftSSi!'SS the toxicity of so me Bt com PIP s to no 1H n

r

gc t lepido pteran {mon;t.rc-h buucr ll ics}. No s ignifi cant c tl (!oc t s 1 0 lo t l r beetles h aw been obscn ·cd in l c s t s wi th B t corn PIP s . cx c cpl f o r Cry3 4 / 35. Submillcd dn t u s h owed thlll Cr y 3-1 / 35 protei n w n.s toxic t o C . nw culma larvnc ot

**do ~**  lev els th a t

**cxcc~o-d** li cl d t: , ..:po.s m c ( Tier I A ssay). lt owc \' t:r. s ince tox ic cti:Ccts

**wcr~** not Sl:<n ut the field dose l c\

' cl 

### in ' ' T ier II r\.s.s:Ly when C. mCicttlululurvn<." were fed n .: uu.t'3.l prl.!y and pollen. i t is h ighly l ike l y that CC) · J.aJJS com \\ill notnd , · crsc l y a.ffi!CC l'. mal.·ulutu. Funhcor. :»duh ra."'Cfing and tri - trophic intcr.action (with into:<ic:llcd

**aphid.~ )**  $ho\\'-"\J no

**oo~h'crsc** 

### cffC'CIS (r om CC) · J.a /3 5 (S« 

### discussion in EI,A 201 Oc). 

### Simib.rly. no 

### toxiciay or ad\ ·crsc 

### ctrccts b3.\ ' C' b...""Cn obscrnd \\ith C:lr.lbid :md ron:

**lx-cd~** exce('ll for .sublcth31 dTcclS (body \\eig.tu diO"erences) 

### nol,'d in one lcsl "ilh cCry3.1Ab (se< 

### E I'A 2012) . Tes tin g 

### ,,;th other n on•tut);CI in SC'Cl5 ( prcd : uory bu gs.

**r~en laccwi**  **ng.** 

### p.1.r::lSitic hymcnop t cm. and collembo l u} h as no t sho \\n s is,niticant

**dvc:r ~c**  c:l1 « ts nmong nny o( lh c re gis tered Ut com PIP s. (No t e: ll tL!<e d o n gu i Uun e c (rom t he 2002 SAP. t es t i ng with Ni.L\ ' Qn/u

**rip~·nnis** 

### and gree n ktccwi ng (CIIt)•.-:op t•r/a carn.:a) w:l.'\

**di continu~:.'tl**  )i n cc both wer e

**dctcm**
**1i n~d**  1 0 be

**in ppropriatc**  t en SJX"'(ics.

**(ir~;.oen** lo .;cwing has been rep la c

e d by the minute piratl! bug (Or; us in.siJiosi . f) o.;; a Nnclicial prl'd.:uory non·tnrget .spcde $. 1

**Hone~**

**· b.~**  **o; ~dcily**  has been

**:~..Uc.~'\('(1** in lon"31 or aduh 

### feeding s audics o.ndlor whole hiw

**(~mi-iidd)** 1ests.

**\c ceptablc**  sludics h:l\ ' e been submitted for all

**ofd~ recist~n**  . ..J Ot 

### com

**PIP~** \\hich h:t\'e shcmn no signific3111 Dchcr:sc: cff«1s ( rtl;sth ·e to coniiol

**group~)** in tern\$ of mortts1ity. hi, ·c hc:lllh. or brood dc:vcl opmcm. B3.SI.""'Ci on the

**re~ults** pn!)Cnlc:d in thC'SC' studi es . OPPO h.ns co ncluded th:Jt ho n ey bee de\ ·elopmcnt ;snd su r.tlval nrc nol aflC:-c tcd by exposure to Bt C(l rn Jl()llcn . In addition. si n ce co m is wi nd pollinated and com pollen i s not o m ajo r p.:ttt ofthe 

### hon ey bee diet. 

### expo s ure to Ut c om pollen i s 

### CXJX'Ctcd t o be i n ci dcntlll. Enn hw onn toxicity lc s ain g 

### l w.s been conducted using nrtilidnl so i l s t ud i es. These feed i ng s tud it:S h:'l\'c dcmonstr:ttcd th 11 t Cr')' J lrOicin..'l :a n: not toxic to c a rth\\ Om l S at worst-cnsc c:m• ironmcntnl concent TJ. ti ons "nd no ndvcrsc cflCcts

**:u-~ CX~X~tcd.**  

### Monor,;h Brmtrjli,•s In response to concerns about po1cn1ia:l 

### ad\ ' Crsc:: effects of some Bt 

### com pollen on

**mo~h** h unerll ies ({)umms p/rxfppus) (docume nted in EPA 

### 2010l), E I'A n..-quin.'<! n..,; istr:lnts to conduct rcscarch 10 address iivl! b:uic

**are:a.~** rel ating t o the pc.Hcnti n l

**c~po sun:**  o f non ·Hug ct kr i dCip tcr:m s. 

### pmic u larJy

**rn on.orch~.**  10 llt co m poHcn. Th ese i ncludC'd: th e 

### distribution o f 

### mona r c h buttertl i es . mi l kwt"Cd J ' l

unt s n nd com : com pol l en r densl! nnd di s trib utio n in th e crwironme m : toxici t y 

### of 01 co m Cry proteins and llt com 

### pollen 10 IC I 'Iidoph.·ro n s ; m onnr c h eg g l nying ond (e(.'tli ng behavi or; an d

**tt~ h**  popu latio n monit ori n .:. A 

### ..S: 11 n

**c:~ll·i n**  (DCI) nolicc was

**~o;; ue:d**  on December 1 5. J 999 t n the rcg i , t nl nts of(r) • lt\b com . 17

### EPA's rl.!vicw of the

**~ubmittcd** 

### data (described in E PA 201 0:1) s h ow ed th at Cf')· tAb hns rcllnivc l y l ow tox i ci t y t o monarc h h lr\ ·ne nod t h e Cry l F pro t ei n has n o

**dc ~,**  **~tn c**  

### toxicity w 

### monarc h lnrvnc. 0\'crall. the n vn ilnbl c infonnnt ion i n d

ica te s u ' ' cry l ow probabi l i t

y of r isk t o m o narchs in nrcas be yon d th e 

### nC"ar edge of com field s. 

### In si de com 

### fic:J ds a nd a t the nca r .;.-d ge or C'Orn lidds 

### there is low prob3bility 

### ofmorun:h IM\'3C encountering a t oxic le, · d 

### of pollen f or t he registered kpidoplcf'3Jl Bt com products . The \\eight 

### of cvidctlfX ofcbu g_.Jthcn-d 

### t o stud> ' the cO'ecL.; of Bt pollen on monarch lan'OC 

### in the field indicate lh:t.t 

### miU;wcxd s in com fields 

### to with i n 1 m eter ofcornfields nrc unlikely 

### t o be dlL 'i tcd 

### wit h honnful rcn:- ls 

# or O t ro ll cn from du : most ''iddy r l n

nh .-d 

### variet i es of 

### Cry I Ab 

### or Cry IF com. Cons ideri ng 

### r bctors lim i ti n g espo s urc, 

### s uch 

### ns re l n

t h ·c l y l ow roll 

### e n .s h ed nn d monarch br cr:d i n

g over t o p 

### i n mu c h of th e Co m Bdl . the distribution of mi l kwe-ed plo.nlS 

### \\ i thin com fields compo'f't'l.l 1 0 

### other

**mi kw~,**  **-cd** 

### h ab ilats. the:

**cg ~** 

**b~;ng** and

**r~..** ....

**-din~;** octh; ty of mon:rn;h ltU "\

':l. e. 

### toscthcr \\ith the Jow t oxicity 

### ot'the Ut c o m P IP s iodi c,:,tc nlow proOObility for ad\c:rsc ciTccls on mOIUtt'h 131"\"nt'. 

### D:t..;;.cd on the rc:'iew 

### of th e s ubmiueclDCJ doto, 

### in combination " i th other data gcnc:mtetl since 

### 200 I . th e 

### A ge n c

y h as

**on uJ~,_'(!**  

### th.at the: curn:nt i nl b n nat i on on rnon.:m:h

**to~** icily 

### and exposure . doc s not f:ivc su t1ici cn t ..: aus c for un du e conc e rn of ,,;dcspr c:td

**ri ~**  

### t o monnrc h buller llie .s 

### n tthis time . 

### Addition.:t l tc s tin g with 

### mo re recent l y regis t cn;d PH' 

### tnli L4; (C ry t t\.1 

### OS. C I)· 2Ab2. and Vip3,-\320)

**ha.~** 

### n o t lx-cn rcquin.""<J. Uowc\'er, E PA " ill 

### continue t o closely 

### monitor the results front furthe-r roon:s.rch butterfly resc:treh

**n.~** 

### a 

### JW1 ofits regubtory O\'tr.tiB}ll 

### of Ht com 

### PIP product> . 

### S i n ce the commerc-iali;,r..l t ion or 

### B t c-rop s. 1h c

**num~r** 

### oflic:ld studi es pub l ish ed i n sc ienti fic 

### li1c:r n1urc i n combinJtion with the poS1·n"};iStr.llion 

### ficJd stud i C'$ sub mil1l-d to the 

### A

seney has nccurnul::ttcd to alc\'d \\ht11! cmpirie.:t.l conclusions c.111 bC' 

### made . 1 \ s 

### o resuiL the 

### iSSll e oflong r.lnl;C 

### cff«u or cuhh"3tion

**oft~** Cry 

### proteins on the in, ·cncbmte community st

ruc tu re i n Ut 

### crop fields has 

### si ncl! be en odcqu : 'Ul!l)' addr\.'".s.scd. 

### Sp«ilicnlty. a mcta·analy sis c.f 

### the da t n 

### co ll cl.!h."\1 from 42 field s tudies indi cated th ; 1t 

### n on · t nq; c t i n, · c rtcbnuc: s nrc

**~,;c crnlly**  

### mon: abu n dan t i

n Ot co u o n n n d B t m a ize fi d ds 

### t h an i n no n · t n

m sg en i c ll c l ds mnmi Q '->t

l 

### wi t h inSt"Cticidc s ( M tuYic r ct al. , 2007) . In m l di t ion .. n comprehen si ve re, • icw of s hort ond I ons t cm t field

**lud ic~**  o n 

### tltc cffeca.s ofi n, ·encbrnte 

### populltion s in Ut com and 

### co u on fields jndic:Hcd 

### th ::n oo unrt'3.SOnJble .Jd,'Crsc: cfl(ocb on: ukins place 3S :t I'C'$uh 

### of, , idc: scale Ot crop 

### cuJti , -ation (S:uwido <I al .. 2007). Another "'' ·ic\\ of fte!d tests publi>h<'<llo date conc:hl<k-.lth:ltlhc l:ll!l<· sca le studies 

### in

**~;ommcr l**  

### Bt cotton h•wc not 

### r e\ ' c:tlcd :my unexpected n on·taq; ct

**c: O~cts**  

### other t han subt l e s hin s in 

### the arthropod co mmunity

**.auS~;.'(I** by 

### tlt c c tT tcth ' C' contro l of the targ\!'t pe sts (R <tm ris c t tt l .. 

### 20 06). S l igh t 

### r e

du ctio n s in so m e 

### i n

n rt cbnah! prc:dntor popu l ntio lt .'i arc an 

### in-c , ;u,bl e r es ult of a ll pc S l mrutn gcmcnt proc t ices, 

### w hi ch re su lt in re du ction s i1 1 

### t he abundance ot' the j.X."'St S as prey . 0\'emll.lhc Agency is in

**a~-ment** \dth t.hC' 

### conclusioru; ofthese

**~•udics** and 

### collectively. these resultS provide c:c1cn5i\ ' e daum support t.tut Bt crops h3\ ' t" not C3uscd 

### long tc nn cn, ' ironmc ntnl cntcts on :t 

### pop ul a ti on

**I<!\ ~**  

### I t o

**or~oni :s**  **ms** 

### n o t urgctcd by Ot proteins.
18Soli Fort • So i l org:misms may be exposed to nt PIP s throug h co n tn cl \\il h corn roots (by direct (Ceding ) . plant r oot exudates. i n corporotio n of ubo ve · ground p lant tissue s i nto soi l t bllO\\ ' ing han ·c s t, or by soif·dcposited pOllen. Some e'idc n cc s u sg.:st-. th:u so i ls th:.u o n: high in clays and h u m ic :1cid.s an:- mon!' likely t o bi nd C r y pro t e i

n. Howcn •r, neutru l pH so i ls t e n d 10**h~\'C** h igh microbial activity and microbe s contr i bute 10 Cry protei n 

### Uc:grudation . In nddi t ion. a 

### study on the rc l ..:-a.sc t)f Cry prote ins i n the roo t cxud:a t c.:; of Bt cotto n has sho\\n th:H no Cry pw t e in s were 

### d .: t '- "Cil:d immu n ologically o r 

### by l a r vicidal 

### assay i n any so i l o r hydropo n ic sol ution in wh ich B t cotton had bt.--cn gt0\\11 

### (Sa.xcna nnd S t ot7.ky. 200 1 ). The weight of e vi dence**nd c~ucs**  that Cry prote i ns 

### do no t 

### accumul n te i n so il to nrthropod· t oxic lc, • el .s. 

### lh:c.ausc Cry pro h:i ns 

### arc t oxins derived from soil· i nhabi t ing baeteria,/ktd//us tlwringien sis. lhc dcgrodation of t hese tox in s f rom Bt com P I Ps i s expec t ed to be simi lo r to that of t h ese protdns t hn.t 

### are pr()duc , x l n: 1tu mlly from so il bacte ri n. To fu n her confim1 these rc su l l$, EPA hl1s n-quircd the soil fate cvaJuat i ons t o support n:gistrm io n . These s tu d ies hnvc: mc i,sUrl -d the r.Hc of degradati on ( DT ) of Ot PIPs in Bt · i n fuscd so i ls \\ith**tl~rcnt** inc u ba t ion t i mes. e i ther 

### by assessing bio.:J.cthity t o scnsi t h ·c insect SfX""Cics or by 

### c.Ji r c:ct l y measuring 

### Bt**l~w s**  with 

### ELISA or**Wcsu~m** 

### Blot a...;:.mys. Resu l ts 

### from the s tudies have sho\\1\ l h

Jtl Ul PIPs rnpid l y dcgrodc in S<)i l, wi l h**dc~md111ion** half·l i fcs ( DT ro) of -< I 0 days. Soil ,\ /icroor;.:uni , wJS Numerous publisl1ed S tud i es i n

dicate th:Jt exposure to 

### Cry prote i ns product.-d in B t PIP 

### crop p lan t s d oes n Otlldvcrsdy 

### am.-ct soil m icroorgon i s rn s (S: mvido 

### ct nl .. 

### 2007) , Altho u gh 

### a minimal tran si ent incrc..'lSC and shift i n micmbi:t.lf,.)pu hu ions m11y result from the p r esence of**ron sg** **~nic** p lant t iss u e in so il. no od,·en; c: c:l1\:· cts hnve been a t trib u ted to the Cry pro t eins. In add i t io n . t h e 

### so i l d..:-grodation s tud ies d i scussed above 

### ha,·..:- s hO\\TI th at 81 com 

### f' l f's de grade quickly i n soil. Wi th**reg n.l**  to t he 

### impact of gc n ctic:ally cngincel\!'d crops on :\Oil, EPA**ha..~~>** noted (EPA 20Hb) thO! ngricuhurn l practices themselves cause large chungcs in so i l n.nd so il mkrobial compOsi t ion. Fonh cmtorc. f:1c t ors suc h \ ' oriotion s in 

### seasons and we ather . plant growth stage. tmd p i ::Jllt vari..:- t ics . independent of be i ng gcoc t icnlly ens inccrcd, arc also rcspo nsib l..:- for sig.nifk.nnt sh ills 

### i n :;o i l mic r obial commwtit ics. rvlost s tud ie s wi t h g.enc t ic:tlly 

### cng i n,"Crcd crop s tO 

### dntc 

### ha\'C shO V•1l minor ot no etl'CclS on soi l mic r obes beyond the vari:t.t ion caused by the factots listed aOO \'c:, J. ll orizo nt :.t l T r. an d<'r ofTr ansg tn rs fr o m B t Cro p s EPA has C\'nlu:.. t,'tl the: potent ia l for h orizonml gene tran sf e r (HGl) from Dt c rops t o soi l org:anisms :m d has cons ide r ed possib l e r i s k imp li c:1t ions if s u ch a tr.lllsf..:-r w..:-rc t o occur. Ge n es th : u h 1wc been cng i nccr '" 'il into Bt**cror~s** arc mo s t l y l l:lU n d, or h a w their origi n, i n so i l - i nh:ab iti ng b.1cterin. So i l is also the h:1bi t at of other t ox in · produc ing J.J..Ictc ri a . nnd tr.m s i "Cr of the s e genes and/or toxins to other mic r oo r ganbms o r pkuns has not bee n de t ected. Fu n h cm1ore . several publ ish<.'<.! e xperiments. 

### that we r e cond u cted to as;sc.s..o; t he l ike l ihood of ll (iT , h av e been u nab l e t o detect gene transfer under typ icaJ en v ironmenta l c ond ition s. Horizonta l g<:ne transl"i: r to :;o i l organ i s m s has only**b~n** de t ec t <.'"tl with very p r om i scuo u s microbes under l nborat or

y cond i t ions ( <)designed to f h\'o r tmns li::r. 1\ s n

**r~.: ult**  of these findin gs o..nd t he: f.'\Ct th a t t he 

### Bt t o:< in sc nginC'Crcd 

### into cant 

### PIP ha\' c been d eri\'ed from

**soi l-**  **nhob in~**  boc teria. EPA h asco n el uded 1ha 11h e ri s k of ii GT of lr.lnSgc:ncs found

**in~** rcg lsten..'CJ 

### 81 com Pli' s is l ow. 4. GC'nC' J'l ow and \\' C'C'dinC';SS PoiC'otial The 010\'Cntc: nt oft ransgcnc :; rrontthe h os t plunt into wccds h as been n

**~is fican1**  co ncern for EI 1 A due t o the po ss ibility o fn o\-el expo sure s to the pesticid.:t l s u bs- t(Lncc. This c oncern has

**~n** cons.idcrOO for ( - Hch ofthc Bt com PH' s c urrently re g i s tered. o.nd wa s cxten..;ively r«x-aminc:d in 2 010 ( S« EPA 201 03). and EI)A bclic,·c:s th:ll these concerns haw: bc'm Sltisfc.ctorily ;u;ldR"S..<ed. lbc Agency h:ts determined lh : u there is no

**~iJ:I'Iilicant** ris k of gene

**c:~ptun:** nntJ

**t::<p~ssion** of an)' :tpf'U'O\ cd Bt cndOtO . '< i

n b) ' ''ild or \\i."<.'<ly reloti\ C3 of com in the U.S .. its

**possc:~ion.~** or tcnitorics. In addition. the USO J V r \l)f.IIS Ms

**mL1d~** this same

**dctennin~t ion**  under 

### its

**~:llu DI')**  **'** :nu h ori t y under the Pl nn l re st Act (sec Ot c:on 1 r isk asscs s mtnt : md derc s ul :u io n decis ions po s t ctl on US D N APHIS web s ite : h 11 p : /1 \\'\\ '\\' . Q

p

bj :0 . **U~:l .**  govfbjO!«h n O!Cl !j!\' / [l( I

**ilion ~**  I Q bh; !X'nd ins.:: h IIli i ) . Under FIFR.t-\ . 1hc Agency 

### tw rc:' • icwed the potcnti:. l for gene

**~pture** and expt\."'S.Sion of Bt cndoto:<in.10 by "ild or

**"tXd~ ·**  rdttti"cs of com. con on. and potatOC'S in the U. S .. ils possess ions. :'"Ufo r its tcrritorics . 

## nt PIP s that ha, ·e been rl!gistccro to <btc: hia\ ' C

**bt.~n** cxpr cs.scd ir1 agronom i c pl : mt .S pc!'cic s that. for the: m ost p.m. do n o t h: a\ c n rt.""a. <;On:tblc po:..s ibility of p.usi n t; their tr n il o;; to wil d m lli \'c pl: : mts. Fcrul s pccie:s rci : U\.-J t o Lhc.sc crops. OS t bund withi n the U ni ted States. cu n n01 be pollina t ed by th ese crops ( com. pouu o. t md co tton ) due t o t.Jifferenccs in chromosome nutt\bcr. phenology (i. t" . , pcriodjcit)' or t imint; ofl'\ ' ents \\ i thi n an organism ' s l ife

**c~clc!** as rdGtcd 

### co elim:llc!, e.g .• flowering lime) :1nd h:Jbi1:11. A F l F RJ\ Ef'A Scientific Ad•isory Pnncl mc:.:ti ng. held on O.:t ob<r 18-20. 2000 . fu1'111er

**tJiscu..~~cd** th e iss ue of gene flow . The panel agn.">Cd d u

n the potential tOr ge n e tr.:t ruf c:r between c

o m

**~l!)** a nd any rcccpli\' C plnnts \\ ithi n th e U.S .. its possessions u nd t erritories 

## ''':U of limited p r ob.lbil il y an d nearl y ri sk

**rr~c.** B:IS('d on t hese cx tcn s i\'C :m:t l yscs.. the po tential for sene tl ow and de\'d oprnc:nt o f weediness i s e xpec ted t o be low for the CWT'Cntly

**rq;i~lc:n."d** Bt con\ PIPs. S

. Ecolos:ic-a l Incident! Accordin g to a so:arch conductl'tl for Bt c om 1 1 11' !' on Ausw t 1 7. 20 1 S. u s ing th e Eco lo g ical Inci dent ln fomunion

**Sy~tcm** (EllS ) . one incident ( 1027769 ) wa .s re cor ded for :t Bt c

o m pr oduct . A honey bee d ie o f r \\015 rt"poncd b) ' D comm erci:tl

**~keeper** in Sout h Olk ota whose fann w as proximate: to r«c:ntly·pbntcd com tickls . The com h)hrid p l anted in l h e neisJtborins fields w::ts 3

**comm~UJ** '':lricty ofSnwtStn.x. 3 81 PIP prod uct containing Cry I F. C r y l A.1 05 . Cry2, \b2. Cry3bb I . nnd C ry34 13 5 . The>«.-.! w as also 1rrnted "ith clothi:midin (Poncho ). n con\'c nti onul pe s ticide . with

**be~** t ox icit y ( t he incident repon wu s m :.. dc by th e reg istran t of c l ot

h ia nidin. Bnye r t' r opS cicnee ) . 1c i s hi g hl y unlikely th at the bee die 

## on· was du e to t he Bt I)IP s in the SnunStn.x SC: l"tt .
**ch** of th e B1 p ro t e ins in

**SmartSt n~**  h:LS bcc:n C \' ; a h.uucd for 1xc

**o~ici y**  " ilh

**noobscn. ~tion**  ol' s igni tic3Jlt :1 dw rsc c11'e-cts i n tcnn s of mortal ity . hi"t :: 

### 2 0h ealth, or brood dc\ · cl opmcnt. In ad di t io n. lx"C cxpo sun: t o Bt PIP s in the planted com U tlht.* time of th e i ncident ( 1 - 2 days atier th e lh co m w as planted) would be lo w to non-exi s tent Bt PIPs**would~** co nt ai n ed**\\~thin** tht: see d s until genninnt io n a nd no po ll en ( t he likelie s t so urce of bc:c e xpos ure to Bt PIP s) w ou ld be p rese nt a t th3t t i me . 6.**[nvironm~nlal** Ri .sk t\ssts sm en l Concl u $ ion .s (No n·Li.sltd**Sp~its)** lllc: E P A uses a Maximum H azar d Do s e T ict\.'<1 sys t em fo r bi opc .s t

icide n on· targe t wi ld l ife h :v.ar d nss:essmc nt. Wh en n o ::td\ ·erse ellct tS : tt th e ma.ximum hazard s creenin g d ose nrc obs er\'cd on n:p rc.sc ntat ivc n on- targ et spec ie s. t h

e Agency concl ud es that there : a n: no unn: nson ::tblc ::Jd\ ·e rse**cll~ets** on n on-t a r get popul: uj ons: from the**u.._~** o f the pes t icide. At pre se nt. the Agen cy i s aw : 1tc of no identified s ignilicant nd\ ·c rsc ctTects of Cry protein on th e**:1bu d~** **mcc** of non·t:ltget orgnn i s ms i n an y popu la t ion in the aqum ic o r tcrrcs triu l ticld cn\'ironment. wheth er t hey nrc an i mal s . pl ants . pe s t p.llr n

.s itcs . pes t p r e-dators . o r po llin ato rs . Funhcr . E PA bclic\ ·cs that cult ivat ion of Ot com PIP s may have**few~r** adverse impactS on n on· t arget organ i s m $ t han u s c of c hemical pesticides for com produ c ti on. bec a u s e under n om1al cireum s tnncc s. Ot com requ i re s subs t an tially fc\\'cr app lic ation s: of chemica l i n se cticides. co mpared to producti o n o fn on·Bt com (sec E P A 2010a) . Fewe r chem ic al in sec tic id e ap p l i

c:-n ions generally resu lt in inc n:uscd popula t ions of bencli cia J o r g an is ms that co ntrol seco nd a ry pe-sts. such ns u phid s and l eafhoppers. Funher .**l' .r\**  h :.s detcnninc.."d th at there i s n o s ig nifi cant ri s k 

## or g ene ca pture and expression ofllt PI I' prote ins by wil d o r weedy rc l ::Jth ·es of co m i n th e U. S .. it s p<.l &.">C$-S ions. o r terri t ories (sec .. Gen e Fh ) w u nd Weedi n ess Polentinl .. abo \'c). available data do not indicntc that Cry**pr otei** **n. ~**  h a ve llJl Y mcasurnb lc :adverse c ll Cc t on mi c robi al po pu la t ions 

### in the: soi l 

### (se c ··S oi l 1'vtic roo r g ani s m s ·· obo\'e ) . n or has 

### ho ri :r.onta l tr.msfcr o f gene s f ro m transgen ic plants to so i l 

### bac t erin been 

### dcmomirntcd (se e ··Ho ri zo m al Trans t'Cr of**Trnn.~genes** f r

om Dt Cro p s " abo \·c). tn co n cl usion. th e ri s k a"-"essme n ts t b r Jlt com PIP s h ll \ ' C l b und n o hazard t o the cn\'ironmcnt t fom cultiv a ti on o r Bt co m in th e U.S. lntlir,• r; t Effa t s



### · n 1c p urpo s e 

### o r us i n

g PIP p lan ts i s the - same as for an y ot h er pest**man.:~.gcmcnt** t a cti c . i.e . . to reduce pest pop u lati ons below eco n omic injury l c\'eiS. As o re s ult t he nb un dancc of pes t i nsec t s s hould be s ig nitic:uu l y n.'ti uccd : md t h is w ill h u vc co rrespo n di n g imp l icotions for th ose o r g ani s m s th.lt e x p lo it th ese pests as prey a nd hos t s. Thus. t he po!cnt ial fo r these i n di r ec t**c~: olo** **gi cal**  cOCc t s on b io lo g ical control o r g anis:nt. '> s h o u ld n ot be n!gardcd as a 

### w1iqu c ecolog ic .n.l ri sk assoc iate-d wi th**h~** PIP c r op . So me n.-du ct io n s. h o wc\'c r . shou ld be e x pected if th e pes t manfigcmcnt stra te gy i s eJTccth ·c. Since PIP crop s a.r c ot1en gr0\\11 in \' icinity wi th co n\'enti o nal c- r

ops to prc\ ·cnt r esis tan c e build· up by the tlliget pc st(s) . s pe c ial is t**~: mtug** **on s**  ca n pers i st in t h('S c "refu ge s ." a._..; well as in other cro p s :m d n o n-c r o p**h::~bitats.** thu.s r etai nin g the potcntia l for reco lonization o f 

### the PIP c r op area . B ase d o n the se consi d crnt ions . regul ato ry te s tin g of the**p...~i t**  prcd : ators a nd parasitoid s of targ e t pests: may C\ ' Cntually b.! con. ..;;i dcr ... '<l 

### u nn ece'SS31)' .
217.

**End llnJ:4.'**  **n~d** Spec i ts A! , '(«.'.); n1tnt Endnngcrcd 

### S JX-c-ies USSC$S mcnt s (ESA) h a\'c been 

### complc1ed and arc docume nted in the 

### BRAD documtniS for oath ro gis 1<re d I'll' (T able 2). 1110 l o

S A fo r
**Lcpi~op1cran** 

### B1 com (CllSc 6501) \\ ':IS 

### la.u upda1ro 3S prut 

### ofo 2010 rt3SS<S$mtn1 ofB1 <om I'll's (scr 

### dhcussion in lht ··Rntion:t!c For Proposed lntc:rim Registration R eview 

### l>t."Cisioo- secti on below). Colroptcr.m Bt to m (case 6502) was ulso updn1ro in 20 1 0 . 1hou£h a sub><quen1 ESA wasconduc1cd in 20 1 2 for

**~Cry3.1Ab.** Si n c

e 

### the 2010 / 20 1 2 endangered S]JC'C i CS 

### dl.!h: -nninations.. Ef'A is .:murc 

### that t1dditional

**pidopt~:r.m** 

### and Co1eoptcmn s pec i e s have been l ist ed by 

### t he U.S. fish 

### nnd Wild l ife: Sc l"\ ·icc. 

### EI'A docs not 

### CX)X"1:1th csc add iti onu l 

### spec i es t o uffcct p r eviou s 

### "no cm.-ct" lindin gs th :u

**wen~** made: for both Lcpidopternn a n

d Co lcoptcr.m 131 com. largely bec uusc 

### exposure to Dt 

### Pll' s isli mitC'd 

### to inl:)cstion or contnc ; t ''ilJt 

### pollen . Noncthl:lt:». EVA wiiJ :J:t;nin 

### update the Bt com 

### t:s:As 10 include these additiorul spa:ies. 1'hc 

### updated

**ll..'-....C ~.nX"nts**  

## ,, ;u be

**dc.~rilk.--d** in the 

### lntc: rim RebistrJtion R e, · icw

**lA~i.sion** 

### ror both 

### cases (SC'c .. 

### Nc.M

**Su~ps** nnd 

### Timc1inc - :.u the 

### end of thi s document) . 

### For the

**ur po**  **s~** of the Propo s ed I nterim Rcgi.S trmion Review 

### Deci s i on. the di s cuss io n 

### th o t t

b ll ows 

### summ nritr.cs t l 1e ESAs that wt:n: 

### updated i n 2010 12

012 .



## · n,e p r im:lr) · route ofex:pnsurc to Bt PIP Jlr O

t cins in com is throug h i n t;cst i o n ofcon1 tissue. 

### Since llt 

### com PIP

**rotein~** 41\: 

### not exp«tc:d to ha\'c ad, ·crsc c:fl'cct s on nwnma1s . bird s. 

### plants . fra.hwo.ter and 

### cstuarincfm:arine iis.h 3Jld 

### in, · crtcbrotes. oon·t.argcl insect,. (Si.!'C 

### discuss ion bdow) :1tld other inn:rtebr:.ue spccia at the: Es1 . im:ucd Environmc:nl!ll Conccntnnion (EEC) . "No 

### EITect'· decennino.tions 

### ha , · .: been made for all Ot com £'IPs " ilh res· pcxt to dir ...

**~t** 

### and indin:ct etl'ccl5 t o fcdcr:llly li st ed t hn! .atcneti nnd cnd:m ge n.'d ("' l ish:· .J ") 

### s pecie s. In ml dition. EPA d ocs n ot cxp...--<:1 

### that nny 

### thrcmcned o r 

### c n dllllKCI\.-d plant 

### specie .;." wi ll lx: nl)' ected by 

### ou t cross in g t o wi ld rcl : tti\'c s or by 

### com petiti on with suc h entities. JJ y b rid co m docs 

### n o t exis t i n the '' i l d. 

### nor n r...- lhcn: '' ild pl cuu s 

### tOOt C3Jl intcrbrc...od 

### with com in the Un ilcd Sutcs. 

### Because oflhc $Cicctivi•y ofB1 com PIP s for some lcpidop1eran (co.<e 6SOI PIPs. see Table 1 ) ""d Co l rop 1 crnn (<OS< 

### 6S021'1Ps) SPC<i«.1hcr.cxists some concern for l is1c d SPeCie s \\

ithin 

### t hese

**rder ~.**  1llcrc l 0 rc. E I'A hns 

### cond u cted nssc.ss mcnts lbr l isted l cp idop teron 

### n.nd coleopteran spec ie s to 

### c:!\'a l u

: ne potcnti:al 

### expo s ure 1.111d cnCcLS 

### from llt cont Pll) s. For Lcpidopter.:t. cx:unin :llion of county distribut ions of cod:lllgcT'C'd / th rc.l hmOO Lcpidop!cr.m >l'<"i<S (lis!cd by 

### 1hc U .S. Fi<h and 

### Wildlife Service) rela1i, ·c 10 com produc1ion counties in the 

### Unitt'd Sutes clr3rly indicated th:u

**an~ ·**  

### pcucntial concern regording runge owrllp


### ,, ;th com production w ns m:1inly f\. "Stricccd co

**th~** 

### K nmcr b l ue buuerny (l.JV.'aeiJ.:s mfliss<l sa mm •li

s). 

### Kt: s..:arch dc:mon s tr mcs d ust some Bt PIP r ro 1 cins 

### rue sc lecch ·d y t ox i c t o lcpido ptcmn larv:u: 

### n t lidd c oncentrat ions 

### and t h at 

### th e Kamer b l ut:

**ull t:t**  **ll ·**  is 

### the only endangered lep i dopteran speci es th:tt mny be 

### cxposetl t o Jl t 

### com {via pollen). llowc\' cr , 

### the Knmcr blue h os t p lant. the wild 

### lupine. d ocs 

### not occur in 

### com field s. ·n,crcforc it 

### ;sppcars hi g hl y unlikely th ;t t sig.nific:1111 numbers of lupine would oce:ur \\ ithin n few ( t\\0 )

**tnet~rs** 

### of com 

### field edge. where the cox · ic 

### le,·cls of com 

### pollen mny be pn:scnt. 

### f.\tn wing lhc:

**c()(lSCrvatin~** 

### assumption th.3t 

### Kamer blue 

### lan · ae 

### an: rcl:ui, ·cty sens itive t o all 

### Be ftr \"'ICins 

### in all Bt com .:\' t:nts. 

### the lik t" Jihood that the lan -: 1e 

### would encounu:r

**~u tlici**  **cn t**  g rain s 

### of Ot 

### corn pollen co exert t oxicity i s 

### cxtrcm c: l y n:mo1c . Al so ,

**c\ l~n**  **t** data 

### and i n formm i o n indi ca te t hn t l h t: likelihood 

### of w i l

d l upines

**occurrin~;** 

### n

djuccnt t o co m 11dlls 

### i s l ow. Morc o\'cr . I 

### he

**~werlop** 

### of t he lime 

### ofthe

**co r**  

### when t:om poJicn is shed wilh 

### t he times o f 

### the year \\hen 

### K ame r blu e l an · :u: n rc likely 1 0 be 

### present is li mited . 

# , 

# --Atler cnrcful rc\;cw of a\ · aHabll! d : ua, EPA**l.l~ ten** **ncc.l** th at exposure o f the Karner blue btmer ny to h:mnfu l l evd s of Dt com plnnt ti ss ue is n ot exp...--ctcd. like,\isc. a rt:\'icw of the prcfcm . "d hab i tats of othe r lepidopteran species l isted 3.'i endangert."<< 

### by th e U.S. Fish and**Wi lil~**  Servic e i nd ica ted that expos ure to h:mnfulle\'els of Ot com inse<:tici dal proteins would n(lt**t~1kc** pl nce. The main reason s t b r t he Ind. of cxpo:>"Ur c a rc gcog.rnp h kal and habitat l imit ntions. These SJX"C ie s**ar~** located in non · mai7.c productio n arc:ts and/or t heir habitat docs not encompass o.grkuhuro l area s . A comp let e di scussion of t he Lt.")lidoptcran ESA can be fOund in 

### EPA 2010:1. For Co l eoptera . 18 speci es were l i sted as threatened o r endangered 3.'i of20 1 2 . Of th ose . 16 occur in count ies in wh ich co m is grmm. E ight of these spcc ii. "S : m:**ubterranean ~**  and exposure to Cry proteins expre$$Cd in piMt tissues is not expected 

### i n th ese environments (none of these spec ies feed o n corn roo t s) . ' ll1e n:mnining spec it s existing abo\'C gr ou nd. in**tcrr~ trial**  o r nquatic habitats. are hab itat**SJK"Cial :;**  duu nr c la r

g dy ex cl uded from o.gricuJturol areas due to thdr spcci ii c h:.tbit:lt re·<Ju ircmcnt s . Whi l e habitot 'i t)f some of t hese**Sp<.·cic:~** may occu r nearby to :.tgricuhun)l nn:.as where Bt com PU• s may be cu hivull.. -d , expos ure ,;n cons umpti on of Bt com tissue i s not anticipated due to t heir s pecilic 1000 r eq uirement s that would exclude consump ti on of com p lant material (i.e .. t hey nrc prcdators .' s ca,·cngers or consume srx-cilic I 'Cxxl p l nnts) . EPA also h. a.c: previou s ly dctc m1incd that expo s un: 1 0 Cry prote ins i n pollen ou t si d e of arc.a.s where Bt com i s cuhivotcd is l imi ted (EPA 2010a). The Arncric . nn burying bt.--et l c (Nicrop ltoru s american us) is the only species t hat may potentially util ize :1r.ms where co m i s grown. EPA ha.sdetenni n ed t h:lt thi s s pecies is not**exp...~ted** t o be expo se d because it l:.trgcty fe .:_-d. ;. on carri o n (s ec di scussio n in EPA 2010 c). Based on t he :.tvail!tblc: int O

rm ation . exposure of li st c:d colc:op tc: r.m s pc:dcs to Bt com PIP proteins is not CXJX.-ctcd . Thcrctb r c . a "N o EOi:-ct"" dctc:nnin.:.uion has been made t O

r direct cfli:-cts t o these spc:cics . Since et1t.--ct.;; on o t he r insec t s or ot her anim:tl or plan t Ul:<:t arc n ot**an ici** **pated ~**  as discussed nbo\'C, n .. No Effec t" dctcm1in.ation has nJs.o**bt.~n** mode t O

r indirec t etl'l.-cts t(l l iS tt"tl colcoptcmns and tOr e ffects to the ir critical h !lb ill'lt. The rc\ • iewcd t oxicologica l dnul shows the rclati\'c inscnsiti,;ty of n range of insects in non - Lepidoptcr.m or Co k optcran order s to Bt com l•IP pro tein s . ind ic ati ng thot Bt com h ybrids arc n ot l ikel y t o h n\'e deltimenm l**tf cct~**  on n on -Lepidopteran or Coleop ter an in sccts i n c l

uded on the:**endi.ln~c:rcdlthrcatened sp..~** **ics** 

### li st In add i tion, o t her ins"""Ct species i n th e orders Diptcra. Hem i ptera . Odonal3 nnd Orthopter.t that arc li s ted as cndnngcn."C.lfthre me ncd s peci es are t'Ound in dune. mendow t prairic or open forest habitats and arc not clo s ely assoc - i31cd ''i th row crop productjon. ot1cn tjmcs due 

### w the S P'o"<:itici t y ofth e h:.tbitru of their h ost pl a nK C . l nsNt ll.t si.s lllnrt J\lana g.tmtnl Ot com PIPs arc l i kely at g n:::ttcr ris.k tbr n!sistanee th::tn conwn t io n : tJ pe s tici des. This is been usc PIPs arc cxpn:s.s.ed at re l tu i \'dy hi g h k\ ·cl s throughout the**ii~** of the plant. compared to com ·c nti on31 pe s ticides whic h typ ically ha\'C sho rter pc:riod s of c nic acy . Prolonged exposure to Ot PIP .s in com. ofte n O\'Cr multip le - ge n erat ions per sc:t.o;on, cxcrL' s ign ilicant se l ect io n pres s ure t O

r resistance t o dc\ • e lop (f; f 1 A 1 998 . Matten ct n l . 2013) .Gi\ ' C:n thl.! cm • iro nm entalnnd economic bt:uc: l itS or Bt c:om PIP s (EP1\ 20 1 Oa) . susc ep tib ilit y to Ill has been

**con si**  **d~·l\.-d** o ··public good .. (I' I' OC 1996) t 1 nd l! I'A has i ndicntc:d th at re $ iSt:mcc to Bt PIPs would CO I Ut itutc on unre-asonable a dverse c fl'ect under FIFRA (Mn.t t cn ctnl. 20 1 3). ' l l1crcforc. as 1cnns o.nd conditionsofrcgistr.nion.the ..-\sent)' Jus n."'qui r cd in sec t n:sist:mcc monoscmcnt (JR.\ I) pions for oi l commcrciolly-rq;istcml Bt Pll' s. 

### lksc pl>nS addn.'SS potcntiol m.istnnc<

**=on~** th<: nujor tnrgct pes15 : Europ.:on com bc>Nr (ECB). southwo:stom com bon-r (SWCII). ond com c:uwom> (CE.W) fo r Lcpidopccmn Bt com (cnsc 6501) ond c- om root worm (C RW ) for Colcoptcr:m Bt com(<= 6502) . lllc primary rcsistnncc: miti g.o tion s trnte gy l ms

**b~~n** t he usc 

# or rdu sc in c-on jun c ti on with Jlt com. RcfuJ::CS sc r\'e as so ur ce-s uf Ut·stLo;ceptib!c in s ects nnd arc typicall y a portion oft he com cnlp thlt is devoted to 3 non·Ot '"'riety . For Ut com I,IPs.. tw o refus;e configurations ha\'e bc'm cmp!O) ' cd: I ) -structured- n:ru,c. romiSting of non · Bt c;om pllnted in bhX"ks or s trips proximate 10 llt fields. ond 2) S«d blends. in which !It lllld non -Be <om S«.'ds tm: cominglcd \\

i thin t he some SC\.'\1 bags. l denlly. refuse i s deployed i n combin:a ti on with I) Ill s th:at

**cxp rc$..~**  l llrgc a mounts of llt toxins agai n st the t:lfgct pes15. Thi s so coiled

**-hi ~:**  **h** uO,.,·rcfusc Slr:ltcgy·· (SAl ' 1 998. EPA 2010a) cn,!tun: ..

**~** th=u only resistant homoZ)' SOtc ( RR ) scnotypcs "ill 

### suni,·e c.xposurc to Bt PIP s.. Since

**~""Sistnncc** genes

**:~re** 3SSU.rncd to 

### be r:1re in the popul:uion. there is 310'' likelihood of rcsismnt :;u" hors ln Bt field s. 

### lltc few rcsist..'lnl indi, · idu::tls th:at 

### sur.i, · c

**a~** likely to encounter susc eptible:

**in~~"Cts** from refuses "hkh. n.\Sumi n g mndom mating. \\ill dilute the numbt!r of resis tanc e scncs in the overall population. High dose h as

**~n** de lined by t h e 1998 SAP ns ·· 2s tim<:S the protein co n c cntr.ui on n 1:1:c s.s ary t o kill susc crtih l !! I I.U'\'3c." Five \ ' crilico t io n meth ods were p r ovided by th e panel. t wo of\\hich would be sunici cnt todeiinc n f ' IP us high do se. For Bt com. the rrgi!lh:n.-d Bl PIPs ha\'C gcncr.tlly

**tx~n** dctcnnint'd to be high dose for ECB and SWCO. buc nc>t for CEW or CRW. The: BR.-\0 documents for each rcgistcml PIP (Table 2) contnin a summary ofthe dose t.lctCmlin.:nions for each pol Thoug h high dose

**~.xprc .ss**  **un** is it.le aJ , IRM can 

### 1x: pm ct iccd l O

r non- h igh dose insects with refuge s and ciTcc ti \'e r ej;iSHlnc..: mo ni toring. Thl.! co n c

ern. howeve r . is th n t heterozygo t e genotypes ( KS) may s tU"\ ' i \'c exposure. u ltim ately

**incfX"n ~**  th e amount of

**rc- .s**  **i~t :mcc**  ger l cs i n o population . To funhcr reduce the lil:clihood of resistance . rcsbtrants h3\'C oombincd Ot PIP troits in pyramids lllnt express two or mon: toxin.' against the S..'lmc pest complex. Rc-SC'arch hos shown 

### ch:n p)Ttlmids or two troits \\ith

**indc~mlen t**  **mod~ s**  of oc t ion ( i.e . • no cross

**~si.stnncc** polcutin l) nnd h ig h ncth • it y (dos e )

**ct~ n**  d!! lay th e C\'o l ution of rcsisumcc r dath ·c t o si n gle troh ' ·a rictic .s ( Roush 1 99K. Zhao ct al. 2003. Gould 2006: mode l ing s ununari7.cd i n Mottc n <1 ol. 2013) . Given the impr oved durability offered by pymmid.s. EPA h:LS upprtwed smaller rdu gQ for pyr.:unids comp:tt<d to sinj;lc PIP produces (SC'< Tabk

**~below ).**  1. C ur rtn t I RM

**K~quinm tnb**  ror Bt Com IRM S1 rt11cgics lOr 11t com h n v c bc:cn SUJlfiO rtcd 

### by extensive dnll.t On JX:S l b io l ogy . J>J F 1 expre ssio n (l.!osc). bas eli ne pest SU $

CCpt ib i l it

y. mode of action. 3fld polentin l cross r e-s i stance between B l 1oxins. !)imul:ition

**model~** ha, ·c b...--cn frequent!)' usOO to C\':tlu : t.tC" n:fu£-c op-tions nndu.":->e .ss t he durab i l i t

y of fit com PIP s under di t )Cn:nt cond i t ions . Pe-s t b iology infonn at ion fo r l .cphfoptcran pests ha..- been summarized inEPt \ 2010a and for CRW in EPA 2010b. EPA's**a.~css mcnts**  of dt) S C, ('ross**csistru1c~.** n nd s i mul a t io n modeling for c m; h regis t ered PW 

### nrc contai n ed i n the rcspccti\ ' C ORAD document-; (Tnb l e 2). Gc n c:rally. the Lep id optcr:tn -: l cth ·c tox i ns arc h igh do s e ngu ill!>1 ECB and SWCI), but n ot CEW. None oft he fou r r egistered Co l eoptemn - :activc tox i ns is con s idc:rt"d h igh dose lhr C:.:R W. Spcci lie refuge req u irement s fo r s i ng l e tra.it and pyramided Dt co m PIPs arc dc. scr i bcd in Table ..J . Other rcq u irenl cnLS. including insect icide usc l i mi t:at ions in r cf

u s.:s and wid t h re q u i

rements (fo r refu ges \\ith s t r i

p conligumtio n s). aJso app l y to s truc t ured r efuges in so me ca..se ..s (E PA 

### 20 I Of). Cotton-growing n:gions have a larger n: I Ugc n:qui r cmc n t due t o greater ri!'

.S i sumcc co ncerns wit h com c; a rwom 1. wh ich**~~d .;**  on both com nnd cotton . Suc cess ive generations ofCEW cou ld be cxpo s OO t oU t PIP s i n b01h crops. he ighten ing the s e l t."Ciion**prc s$** **r~** for**c~ tancc.**  The 

### 1 cnns nnd cond it ions of registrotion s pecify a numbe r of post-reg i s t.rJt ion IRtvt IX'quin:mcnts . inc l uding.**grow~.:r ~;.-ducat**  ion programs. a refUge compliance s tra t egy. a nd r es i s tance mo n itorin g for the: key target pests (EI'A 

### 20 1 0f). These stewards h ip pro grams Ill'\! carried out 

### by re g i s trant s . 

### ' 'i t h annual r..:-ponin g to the A seney. To dat..:- . all J)t com rc gistmnts ha \·c been i n comp li ance with t he**R~1** n.-qu i r cmcnts .**ab e~** **.** Refu ge**n:qui :mc** **~** tO r s in g le toxi n nnd pymmidcd O t com PIP s 8 1 C'OI'n**I~ X'**  Tnrj,!tt pt.$- I .S StntC" turC'd**tfu~c:** Pro)lmlt) ' 10 Ot Oc- l ds S«d bk nd S i ngtc: to . xin LtpidoJ'I{CI':l C'om Ue l t:**2~•** < 1 /2 mi le- N t ,\ C'-'C lon re gio ns:**~•** Sin gl e- 10xin Co l eOCI(Cr3 1\ ll re-gions :**~•** Adj:tetnt or w i lhi n**~-** Com Uc:lt : combined <:>r Combi.nc:d n=fu s c: :**(S.Cp.'ll!l-1~** S i

n

g l e tO:\ in lC'pidoptern +**~~lc-** 20'! '. re f u

ges 3d j lcc:-nt Of w i thin refu s e' f iX**(suc k~J** **)** Colcc p iC'r.l Co i1 0 r \ rctlcru.:**~C'p31<1\ C"**  Sc:p.mltC' rcfu:;e .s: lcpid o ptc:-nm peru 10 ' :. (C R\V ) :IJKt**$~·** ad}:l c:c:n t (C R W

) an d < nOO rcq u imJ) (I.C" r ) refu ge-s**mile** ( Lc:p } Com**el ~~**  S !i (sep:untc 1)

· r.u nid lcp i d

optc:-r.J CO!tOO r\·g.ioru :**20 0.**  < 1 / 2 mile re fug t'**rcqu ~d**  i n couon re gi oru) f') ' r..mi d Cokop tcrn All rc & i oo.s: S !;. t \Jj >Kc ot o r "ith i n 5•. 

# ,. COrn lklt : comb ined 5 % A r c :u wilh lc ps: < 1 /1 

# 5 ,. (.ioep.mtl('**1-'yr.:~mid** lcp idop<c:-m - rt fu gc m ile n:-fugc n:q u i.m.J in (>tO<k«l)**Co optcr.~**  Conon re gi on s: comb in e- !,!**A~:t. J.** **,\ilh** CR W oo l y : conoo**r~to )** **0.** r d ug c :. tJj 3C<- nl o r "' it h

i n Refu ge compl inncc prognun s for Bt com PIPs cn t a.ila**Jti.fac~ cd**  approach t hat i n

clude s the demc nls li sted bel o w. All of these aspecL..; arc requ i red by the wrms and conditio n s 

### 25of rc gisutnion (sped lie n.""quircmcnts u rc c:onuincd in EPA 20 1 O

t ): • IRM Educo t io n

**~** ..ro grnm : Co mpanies arc rcttuin:d t o imp lement nn .;.'ducJt ioruJl pro g mn' designed to COO\ ' C:)' 10 users the

**im~rtancc** orc:omp1ying \\ i th the IRM p r

ogr:mt. The educational progr:un in,·oht"S the usc ofmuhip1c media ( e .g •. focc-to-facc rn« ti ngs.. m:t.ilins \\titlcn mnteril11S. growcr guides. bag l3g.S-. ond electronic 

### communications such 

### 'LS by 

### intcrrn:L rn<lio. or tclc\ ' ision

**c:ommcn:i~ls.** • Growe r

**\~n.-ement :**  Co m pa n ies arc required t o

**~ntcr** into :1 c ontra..:tual arrang cmc:nt bct\\'Ccn the 

### re- gistront n .n d gro wer t o o b l i

gn tc :lt.lh cr.:ncc to IRM n:quir\! mcnts . • Annu ai iRM s u.r"cy : Re g istm n

lS mu s t 

### coordinate a S\l r\ ' cy ( conduct.:d on o nymou sly by :m i ndrpcndcnt r esearch f inn ) to pro , ide 

### : 1 suuisticaJ iy

**r~presenuti\'c** s.:s mpk of growers from ,'UJious rom · giO\ \ ing n:-gions in tht U.S. RcsuJts from lhc

**:~ouncy** nrc used t o

**~~s** le\ ·cls of i7Q\\Cf complian« with refuges 35 well ns growe r moli\'ntions. :miludc:s. and R' a50r\S for n on -tompli 3ncc. • Qn .. f hnn 

### U$.SCss mcnts:

**Rl."gi tronts**  :m: r cquin.'\llo dc\'dop nn o n- site a.SSC'ss ment progrom 

### in wh ich 

### t roi n cd personnel from each c omp any 

### m : Lkc \ ' isits to 

### f:tn n.s s rowin g Bl c: o m . Ourin 1; t he s e vis it '\. c ompli un ce wi th refu ge re q ui r ements is assessed nnd gro wers out o f comp 1 i:t.ncc

**;~ n:**  idcntitied for com:t ti\'e crct j on under the Phased Comp li nncc App r o:1ch. • TipS and 

### complaints:

**Rc gi~r:llllS**  must

**~blish** :t means for the reponing and im ·C'-Stigation ofincidcn«) of

**~ruse** OOlX'ompliuncc. • P h3.5Cd Compli3nc e Appro..-,ch ( PCJ-\): Resi str.lnts

**m~** "-mp!oy a conshlent set of procedurt: s (for n il Ot com rct;,istrdntS) t O nddrcss non-complinncc Mlo n g

**~ro \\**  **CtS** 

### nnd see d dt::t1cr.;. R

efuge 

### complinn ce ac t i \

• iti cs nrc 

### coordin:tho.'\1 by t he n:gistr.mts.

**~me** of whil;h (grower sur ve ys) on: coordiJUt<d through th< Agricultur.d Biotechnology Stcwardshir Technical Commill« (ADSTC 1 ). An annual 

### complil.nce report is n:quin."d to be submiltcd in xootd:lncc " i th 1he temt.' and conditions of F\:gistmtion th:u includes <bra from a he gN\\c r sUI'\ · cys. on-f11nn 

### asSC"SSmr:nts. antl i' C, \ ac ti ons . El,;\ 

### "s 1\!\icws ofth<)C

**~poru** :1.re 

### summ:tri'IL"'<i in the BRAD documents for Lcpidopt crnn (E PA 20 1 0n) n nd Colcoptcnlfl (EPA 20 1 0b) Bt co rn . These 

### t.Jocumenu were upduiL-d i n 20 1 0:

**ub cquenl**  EPA review s of lhe nnn u:1l B 1com comp l ianc e n:pon s haw bee n posted t o the Agency's IR]II docket (El' A· BQ-OPP- 20 11 -0922). 3. R Hls lanc:<' Monilorin:

**Throu~h** t he terms of

**K~i strotio**  **n.** Bt com Kgbtrunts are rcq1a in:d co imp lement a n: sis tnncc moni t o ring progmm f o r the major targe t pes t s (l:C n. SWCB. CflW.n nll CRW). A prim a r y go:al of 

### r es is tance monitorin g i s 

### t O

d etce t s h i ll s in the f requenc y of rc: sis tnn c c gene s (i.e .. susc eptib i lit y dumgcs) befon: th..: onse t

**ofrc~isunc..:** lead s to 

### ,,;dc:spre :td Ut c r op fai lure (S t 'C E I'A 201 0a). Monitorins for n:si.suncc 

### has

**consi~tcd** oftwo main components: I) iR\C)tigmion of 

### unexpected licl d 

### dan1.:tsc 

### rc pons from gro wers. cxten. 41 ion ascn1.S. consullM tS. o r company ugronomisu, n nd 2) m o nitori ng for chnng es 

### in susceptibility through tn q;,ctc:..J 

### fl'Opu l.:ttio n I The A gnculturall)i0¢C'thnolog) '

**t":Ud~h p**  Trthnk:a J Cc-mmiltC'C b <111 indU)lr) t'On\Onium o r U l ccm rt f' rrgi.s1r.mb.. incllldint; MOOSlll:o. Oo",

**ri~r. ~d**  S)ngC'fiU . 

### 26-.umrling :md testing.. U ncxp«lt"d d.."lm.:Jge reportS nuy n:' cost the occurrence oftoc:.Uized n->isunce (o r ho t Spots ) bc:focc the cll"e<:tS <>n spr<:td. R<>istancc m oni toring through llllj;<t<d field );lunrling 

### c::m rc, · rol ctuno cs in susc eptibility o( seos.mphie.ally rcpr'C'SC'nunh ·c popul:u.ions . In th-.: c'cn t that rcs isumcc is con linncd. a r cmC'dit \J octjon plan i s tri gscrcd 115 define-d by the l <rnt S ofrc g istr:uion (:«. -c EPA 20 1 Of). S i mi l ur to r e-fuge compl ian c e, much of t hc r esistance monilorin g work i s coord in ated th roug h ABSTC. includi n g in.scc t SJmpling nnd biOO.."'SilY S to determine S U

$

Ccptib i l i

ty. Re ports covering cnch monitorin g pe s t and t o .

xin nr<: sub mincd annually to th..: Agene)' · EPA ' s rc viC\\ ' $ of th e monitoring re ports arc s uHun o rit,'\1 i n the BRAD d ocumc n L"' l b rt ach PIP ( Tubk 2. upJ4ltc.*d in 20 1 0) . Subst.""qucnt rc: )bt:lnc c monitoring review s hn\ ' c been po.stcd to the Agcncy"s IRM dockct(EPA - IIQ-OPP- 2011-0922). To cbtc. the Rlljor Lep idopteran urgot pc>!S (ECB. S\\ ' CB. :>nd CI!W) r<Rilin .su$ccp 1 ib lc to the re gistered Ut com 1 oxins. H owe ver. i b

ll 3m1 )'\\ 0m1. a scco nd:tr) • com pesL w as

**wn** to h:lvc de\ ' Clopc:U

**n:si~1J.nCC** to C ryl Fin Puerto Rico . Rc s i suncc h:& $ n lso been dctcr t c'd in C RW 10 the Co lcop tcr:m Bt to xins. Cry3Bbl and mCry3A. FA IV - Cry / F Rcs is WIIf'' FA W is a

**~"'Condor)**

**'** com tx .S t in mo s t of the U.S .. t hough i t is :1 m ajor pest in tropical

**nr~lS** where it 0\ " etwintc:r.; (includin g l ' ucrto Rico ). (n the U.S .. O \ '

tl"'\i ntcring is limited 10 the c;;t;crcmc southern portions of Florida :md T

**~x us.**  However. infc slnt ions in th< U.S.. can occur nnnu:11 1 y from FA W migrotin g nonhw:.ud from O\ " Cr'\\ i ntering )it(:) in the:

**Cruibb..~.** Durins 2 006.

**cbnl3~<** to SC\Cr:ll contrn <'fOi>l ;md r=<h Cry I I' (TCI507) lields "" " obscn · ... "d in Puerto Riro.

**Bioa ssa**  **~** off i\ W collec ted from these licfd s s hO\\cd th nt the FA W p

o pul ; uions had high 1olero.ncc 10 C r y l F. including no

**moru~lity** 10 u diaJ:,OO s tic conccntnttion ( 10.000 ns Cry l F / cm:) and an C !l 1illl : llcd n.· s iSUlnc.:c: rat io > 1 67. Re s i s tance l ikely C\'Oh ' t.."d

**du~.:** to climntic cond iti ons a Jio,,in g for y&: : lr-ro un d maize produ ct i on and cont in ual insec t pn:ssurc:. limit et

l F 1 \ W migmt io n (is ltlJld t:nviro n mcnl). and h igh adop t ion ofC:ryl F com. 1l1ough n remedial action 

### p l an i s not n.-quired by the tcmlS of rc g , i s u n tion for fA W. t he r.:gi s t nant.s ( Dow AsroScknc\!' S and

**Pion~r**

**)** impkmcntC'd a plan d..:.sig ned to reduce the s ckcti on pn:ssure for FA\\' resistance: t o Cry I F com. This pl30 wa.s

**ru'i~IObOU:.** to that requiml by EPA for the prim>ry lllrg<t p<5IS of Bt corn (f:C II . S\\'CB. ond CEW) , The companies ins!IOCtcd gro\\cts to usc :thcm3tc c ontrols {insecticides) for Ft\ W :md disc ontinu..-d !.O.Id ofC r y l f com o n the: isl:>nd. Subsequent :malysis has sh0 \\11th : u the n: s iS l!lnt tmit i s .. li:<t"U - in the popul:ation {i.e . • th e re \\ ' Crc no n.ssoc:iatcd fitne ss

**co st~**  with the Imi l ) . c\ ·c:n with ou t t he con t inued p r ese nc e of the

**.:k '('**  **ting** ngc nt (Cry I F). Bt'C:au s ..: of th i s. Cry IF co m has no t been cu hi \"n t cd on t he . is lan d since

**n.: ~t~mc**  **c** wa s d etec ted . R isks t o mninl : md com production co u l d n: s uh if re s i stant FA \V migrJtl! nM t hw:ard into cast coast s lnt \.".S , pro\'idcd tho se sta tes haw s ig nil ko nt C r y l F com use. Alon g the s e line- s. academic

**~~: an:**  he rs h:t\'C idcntiliro Cl) • l F-rcsistrull FA W col l cct<.-d from local ion s in Florid>. G<'Orti>. and Nonh C3to lin o( llunng et nl.. 2014) . It 

### is probable t. hc5c popul>lions also

**ori~,;inatcd** in the

**Cnrib~a.n mO\**  **in~** north :15 pan of an annual mi gro tinn p : mcm. To dote. 

### 27howc\ ' Cr. r eports Ql" unexpected d r un:tgt: t o Cry I F com in t he U.S. have b.."'C n limitc:J. In

**r~spoJl.S.C** t o th e r isks. Dow nnd r•i onccr h:&vc i ncren.'iC'd

**n.~is once**  **monit ori**  **~** l O

r FA Win an: ns where the jX "S t mo y be. p resent 

### nml wi ll work \\ith

**l1 ~ctcd**  g. r owc:rs 10 imp l eme nt ''best m:..n:tgemcnt 

### pr.tctices .. in the C\'cn l 

### oC FA W dam3gc . lktoits of the FA W

**~httlnCC** c3SC' and n:-l.lt"'\1

**~h** a rc summ:ui7A"d in E P .,.- \ 101 0(3) nnd in t he public litcrotur c ( Stor<r 

### ct ol.

**20 12**  **~** CR W llt• , , · is tcm a- C ry ) liM . m C r:dA R c .. 

### :ri.

"tam · .. • C K W

**prc~nt s**  sis niticant chall c ngi!S t br IRM . Rc.-gi s tcn.--d PJP tmit s ure no t consider ed ''high dose: ·· ror the insect. 35 CRW is Jess susc ept ible t o Bt

**toxin.~** t.h3.n

**Ol~r** turset insects. The insect h:Js :thc mn t o bi: highly odnptBblc t o control s tr:uc gics. inclu din g chcmicotl peSiic:ides 31\d cultutJ.l c o ntrol s. I n addition. CRW can bcdiflicultto te s t in laboratol') ' bi035:..'\ays. Sc\'cnl l :'Otudics by n. "Scttrch s c ient ists huvc documented cUSi.-"S of ficld·cvol\ ' cd com rootwonn (C RW ) re s i s tance t o Ill co m . The

**li ~t**  o fti 1.: S .: s t udies. Ga...;s mann c t n l . (20 11 ). demonstrn1cd thut CR W eo ll ccted from damaged (1) • 31Jb l llclds i n lowll

**durin~** 2009 were

**~ignifican tlr**  Je ss

**~m.ccp tib**  **c** t o the t ox i n d un CRW rrom 

### ui'Klrun:lgOO or n o n · Ut Sield.s.
, \ddition::tl C3SC'S

**fC~ 3Bbl**  drun.:tt;c chJ.ractt:ri1..ed n.< fidd n:sisumce lu\ ' C' sinc e b«n documcnlcd from other locnti ons in Iowa nnd Illinoi s (0DSS illJJlll cl ol . 2012. Gru y 2012). E PA 's r.:vicw ofthese tt"ports (EP , \ 20 1 3) c o ncluded t hat current rcsistnnce moni1oring str:llegic:s and rcfugc - bttsed 

### IRM a pp roac he s nrc likdy

**in dcqunte**  f o r C RW. Subseque ntl y. cro ss n: s ist nnce h

as al s o been d e t ected between th e Cry3 Bbl and m CrylA t ox in s. su gges t i n

g n co mmon JUL"Chanism ofrcsi s tuncc for t ox i ns s tructumll y similar t o Cry3

**(Gtl..~~num n**  ct u l. :!01 4). In re sponse: to these con«m.' lll-'1'0 re\ ric ,,cd CR W t'ltSi.st:1.DC'C monitoring nnd remcdiotion

**ros. r.un.**  **~** identified sci ent ifi c unceruinti cs nssoci:utd 

### ,, ; th C RW n:sistrulC'c. nnd proposed impro \ • cmentS

**ba.._~""ti** on t wa.ilablc i n form :: ui on (EPA 20 13 ). ,\Scientific t \ d,i.sory Panel w us con\'cncd in 20 1 3 t o fH \Widc gu idance on r cs i s umcc monitoring for tRW (SAP webs ite :

**b.un: /{**  **www ~p**  **q;o\' /scipQ**  **I)' /St**  **m\.'C1in gsJ20**  **3/ 041**  **mc-ct nc.**  **Jllml).** " lllc p311 c l wn.. -. t as ked with C\ ' !lhiA1 itl g E PA' s rc s:b t:'"cc moni t oring ( s nmplitl g. bioas.s3y s. nnd dclini11S

**resiru~ncc)** and rcmcdiDlnclion

**tmtc ics**  **.** Key

**~1 ecommenda**  **tion. ~**  (S AP 20 1 ..$ ) included utilizing 

### on ln1egr :ucd Pest

**~l onogcme**  **nt** ( I PM ) u p

proach " i th CRW to mlucc S< lcction pr<SSun: ror

**1'\.~istnnce. i~ins**  tbC' scope of sampling. impmvins re si suncc dctccti on

**n...'-~ s..**  i111d usina: cn'C:cti\'e t ool.s (e.g .. mp rotation ) in rc:sponse CO C3.'iC S of con tinned resistnncc . 

### Ba SC"d o n thl' SAP' s re commendatio ns. E PA dr.an(."t.l o 

### propos..1l to

**~:nl uJ**  **cl!** IRC\ · 1 for C R\V. ·rh c propo s.: a l wa s s ubmitted t o

**ndu.s tr~**  **·** (A B STC) o n A u

glt;;t 27,2014 . Sub sequent ly. EPA ost nb li s hcd o public comment period forth< pr Op<>S.ll. A public

**doc~ct** wa s established ( ErA·HQ·OPP ·20 I.j..()S05 ) " ith on FR notice of "' "'ilobil ity (SO FR

**~56.1 ).**  The comment peri od ron from Jonu:uy 28.2 0 1 5 through April15. 2015. G <n<mtins 87 toul commcnL<. E f'A ha s held se \ ·cral

**cc ti**  **n~ s**  with A B STC t o

**di~ us..."**  the pr opo s n lthroug h

**lay** 201 S. Ncg otinti on o n 1hc propo sn 1 i s

**soi ~:.**  and a dditi ona l nl< ."t lin!;S with 1 \BS TC will be planned i n order to come t o n n agree ment on : 1 ppmpriatc miti g.: ui on n nd imp lcmcnlllt io n mech anis m . 28:iwmn:;sries of C3t . h

**n~lin~.** u n:5po05e to comment$ dol;umc-nt.

**WKith~ tiruJi;,.~,...,j**  I fU-1 cntuncemcnts "ill be i ocludcd 

### i n lhc public docke t :md dt'SC'ribcd in EJl; \ 

### ·s Interim Rcg.i . stro.tion

**Jte, i~w**  Decision for thb case (5«

**"N~~~** Stc=JlS a:nd Timcline- 31 the end ofthis document). U. t- : ndocrin" Disruptor Scrf'('nin)::

**Jlru~r11m** As

**r~quircd** by the Admini s t nl t or u n

der FFDCA s ection 408(p). t he EP A h:1..o;; dt: \ ' e l opcd th e

**ndocrinc** Disruptor Screen i n g r•rogr: un (I.H)S P ) nnd has be g un to imp lement the screening pro g mm th : u i s robe used to l e-$ t n i l pc ) ticidcs in order t o 

### detenni nc whether 

### ccnain subsunccs (includ i ng pesticide 

### nctl\ ' C nnd o ther in g n:odicnLS) m:Ly 

### ha\ ·c an tfl"l:ct in human .s o r \\ildlifc s imi 1 M to :1n eilC.-c:t produced by n

**'"n:uurall~**

**·** occurring estrogen. or o ther s uch endocrine ctlCcts 

### as the ; \ dministr.nor nuy

**d~ i~llt**  **"** FFDCA section 408(p)(4) outhori tcslhc: AdminiSir.lto r. by on kr. t o exempl from the n.-quirem.:nt s ofthe Estro s enic

**Su~t:ancC"s** Scrccnins P rogram a biolo..:.ic subst:tncc or other

**~ut't)t:ancc** 

### if a detennin.m ion 

### i s m:1dc tJunthe 

### s ubsuncc is not anticipated I n produce a.ny 

### el)'ect in hum:ms similar 10 on effect produced hy o nat umlly occurrins c s trogl!nic suhSU'Incc. llctwe<n Octobe r 2009 and Fchn o n

ry 2010.1 h c EPA issued t <

S

t ordc rs/dnr :o c:oll - ins for the llr s t RrOup of 67 

### chemical s . which contains 

### 58 pesticide octivc ingred ient s and 9 i n e n in 1; rcdicnts. 

### A second 

### list of

**chcmic;~.l**

**s** identilicd for 

### EDSP

**scrccnin~** wo.. ; publi s hed on June

**1~.** 20 1 3:: ond includes some pestlcidc:s sc: hcrluled l O

r re g i s trot ion rc\ • icw and chcmic.a ls found in w

: 1tcr . BacilltLf t lw.rlnJ:lf!n..<ris ( mi c r obia l) or l•lP s dcri\'cd from Bt W\: 

### noc n mnn g 1he group of pe- sticide ncti\"e ingn:odiC'nts on the li<ts to be sc- rcrocd under the F.DSI' .

·n,e E P A believe-s that

**I'll' ~**  d.:ri,. ·td (rom 

### Bacillad th llringlt•nd" tlr(' 5ubs t3.nces tOOt would n

o t 

### likdy produce any cfH.-c1 i n hun1nn s si milar to an eilCct product"d by l t na1Ura1Jy 

### OC"cuning c :o, tto j:; cnic subsuncc . A s

**~uch.** pursuamto Sec1ion -40S(p X4). the EJ • , , will deu.-nninc- in the future \\ hc:thcr it can exempt I'll' s \kri\ ' l"tt fr om Bacillus llturin glt•tuh · l'mmthc

**rl"<}oi ~mcn**  **iS** of lhc Scclio n 408(p) EI>SJ.'. In the C\ ' COI I hc E I 'A docs dCit:nninc IO cscmrtthis subs t rutcc from th e 

### E

I)SP. an ordi: r will be: i ssued. For funJ1cr infonuution on th.: stn ll1. -.: of the EDSP. th<." polidt.. 'S nn d procedures. the l ist of chemicals. futun: lists. the test g uideline s n.nd the Tkr I scn:c:n i ng Nttcry. p le3SC visit our

**\\C~ tc:**  **31/11/p :/A**  **t'lt l'OO**  

### &,.,W ' wdo •

**~IR NF.**  **O** WORK PLAN, SUMMARY

**OOCU~IF.NT,ANO** ! 'ROt•OSF. Il ll\TF.R IM REG I STRAT I ON RF.V I F,W IIF,CJ S IOl' In uccord.ancc 

### ,,;th 40 CFR

**Sco ion.~**  1 55.50 , 155.56. m1d 1 SS.S 8,1hc , \gcncy i s issuing 1hi s combincd Work PJan. Summnr y I)Qcumcnl. and Pro)Xl std Interim Rcgislr::Hion Re\ • icw Deci s ion. 

### l.:xccp l for th e: EDS I 1 and ES A components oftht' Bt con1 I'll' 

### n:g i :-;tnu ion rev iew C:l S C, th e , \ gcncy has made t h\.· followi n g i nterim decision ; (I) no ndd iti on:a l data arc required u t thi s timc; :and (2) no change s to the nO"ectcd n:sistrnt ions or t heir

**ab~:**lin g nrc n"cdcd m th i s time.
:

**~** hnp :/.

**\\...,w «gut:uioru**  **.gO\'**

**.' !d\l('wncnlO..t&ii,()-EPA·**  **Q..QPPT** ·1009.().177..0074 fo r the SC\.--ond

**l~ t**  of chemiC'.l.ll.. 

### 29EPA ha s not idt.:ntiiicd any

**ri ~**  of conce rn to hum an hc.:t:Jth o r the cnviro nm<:nt. R r:sist.n n ce ri sks to B t com nrc mitigntcd by an I nsec t Rc s i s tttncc

**an gt.:m~.:**  **nt** p lan {requ ired by the ccnns nnd condition s of rcJ; is tmtion). which mn n diJtcs the usc ofrefug es . resistance monitoring. and g rower complinnec progrwns . Cum:ntl y rc gistc n-d use s of Bt co m I 'll's ure not cxpc.."C t ed 10 result in ad, ·crsc cff«I S for listed and non- li s t1..-d SJX""Cics (including poUirotors) . or critical h.lbimt. H

o we ver. si nce the c:ndangcn.-d s pecies dC'Icnnin:uions \\CIT made for Rt com PIP s in 2010 :md 2012. EPA ;, n w nre !hot a ddition.> I l.cpidopt<rnn ond Cok'Opl<rnn sp« ic::l have !>:en

**iS~cd** h) ' th< U. S.

**~i h**  nnd \\'ild l ili: Servi.,.,. E M doc::s not cxpc..:t t hes< odditionnl species to ul1i:c t prc vio"' "no

**cn~cct** .. **lindin g..~**  t hat were mode f o r both Lcpidoph:run and Coleopteran Ht co m. fargdy l.x--c.ausc exposure toUt I'JI' s i s lim ited to ingestion or con tu c t with JXtllcn . Nonethele s s. EPA \\ill 

### again update 

### the Dt 

### com l :.S A s to iJK')ud&: th ese add iti ona l SJ"."'Cics as pan

**fth~:** fin.a1

**ision** for these rC' g iSirati o n review cases. RAT IO NAl.. 

### F. FOR PROPO SF.O

**IIHF.RI~ I**  RF.GISTRATIOS RE V IEW m :CJSION E PA i s propos ing lhi s combined Work Pl a n. Summary Document. n nd l>ropOsed Int erim Rc s i s trJtion Re vie w Decis ion for Ill com PIPs(<" ' "' " 6SO I nnd 6502) . E I'A hdicvcs thi s combined Work Pllln. Summary 0 Q(u mL"nt. :lJld

**Pr opoS«~**  Interi m Re g i !.1rn ti on Review Deci sio n is appropri3 t c fo r the Bt c om l ' ll ,s bcc.a.usc: t he y ht!\ ' C

**~~n** continu:tlly re ass....'SSC<I sinc e the fi rs t rcgistr.nions wt:n: issued in the 1990's. Scv-crnl sr>«ilic

**t.~ts. conduct~.'CI**  in 200 I and 2010 . **w~rc** trit::Sf.."f\.'\1 by rcsistmt ion cxpit:ltion d . :ucs . For insect n.":S isumcc m:w'lg ... -ment. EPA

**perfomt.~ on~oin~**  re\ • iew s by

**rcquirin~** (\'i3 the tl!'m u ;md condi ti ons of

**gis: tr.uion**  **)** an n un l repOrtS 

### thnt provide 

### d11tn on dac 

### efi\.'Cli\'c nc ss ofthe pr ogrnm . In addit ion. the 

### ; \ gc ncy has c

on \'cnc.·d 19 Scicruilic Advi so r y Jl a nd s si n ce 1995thnt hove addre-ssed se icntit ic i s..c; ucs

**a..~ iot**  **cd** " i th E PA' s re g ul : u ory O \'CI'$ight o fBt PIP s. These reassessment u c: t i\'itks

**t\ c**  been pub lic prooc sscs with docket comment periods. op:n

**m~ting.s.** and the posting of risk 3SSCSSmen t and n: gul3to ry documents to EP t\ · s website . t\ sumnury ofC" ach 

# or these rcasscssmrol ne t

**ion.~** is

**de:scri~-d** in 1his section. A. [Jplring Rt-gistrati o n ; Ot cont J1Jil n:gi s trnt io n .'\ ha\' c been hi s tori c:t lly issu ed " i th exp ira ti on

**~tcs.** These cxp ir.uion d:l t c .s haxc allowed E PA to 1'\!\'icw and updn tc scie ntific a.ssc:ssmcnts ( o r tlte PIP s and make cb:lnge-s t o lhe aem\S 3tld conditions ofre g.istr:uion 10 irnplement risk

**mi i~tion**  me:LSUCCS. E t• A ·s scientific

**~""<:S.-.ments** ofOt C'O m PIPs nre detailed in .. Oiopesticidc

**Rc~istr.uion** Action Doc ument s .. (BR.t \D s) tklt :ue pub l lc.lHy a"n. i lab(e on BI 1 PD ' s wc bsitl!

**www s:o**  **a.gsw/rs;~ ticidcs**  **bj P<'**  **Hicidc!t+' ip**  **s).** The se URADs were upd a h:d ns part of th e 200 1 and 2010 rc:a :iS<Ss mcnts that wcr.: co ntlucted t o support

**cstcn ions**  of exp iri n g Ot com PIP regi s trati ons .

**E~ 1c**  **h** time :1 r cgi s tr:ni o n h l tS bt.-cn extend ed , it lms been

**a.~ed** o n a lind i n

g th at th e product met th e FIFR.t\ n:gi s: tr.ui on S tMdard . The first Bt com l'l £' producb. containing C r y I Ab 3nd Cry I F . WC'rC' ft"ii)lert-d 31 d iflCrent time s bclwC'Cn 1996 t o 200 l . All of th<!S4! product.s la.rgcte!d ll! pidoplcr.m pest$ ( c .uc 6501) :md wt:r..: "i vc n variou s .: :< pinuio n d::ltcs in 200 1 . O n Cktolxr 15. 2001. the s e Bt c om

**smnion s**  were ex1cndcd to Ot:t Ohi.! r I S . 2008 . Concurren tly . EPA i s.s uct!" UI V

\0 document 

### 30for C Q · IAb 3Zld Cry IF Bt com <kscribing chi: regulatory and scienc e r'C\ ' i cw actions th:lt were conduc ted ns p3n ofthe n. '3S.Si!':SSmcn1 co suppo n tM n:g. i.s trac ion

**\;tcnsion.~~;** (E: I•A 2001 ). In 2008. 1hc rcgi s tmtio n s \\ Cr -.: ag:sin extended to exp i re on Sc;ptcmbc r 30. 20 10 . · fhjs

**ll cm~d**  EPt \ ad dition:tl time to n:vicw dat:111nd conduct ::tn Oihcr

**cicntific** rc:tS scss mcnt to s uppon l onge r exte- n sion period s. Thi s s« ond

**rL~St."S..'ii;mC"nt** olso i n cluded colooptcr.tn U1 com Pill s

**(c~asc** 6502) . which hnd not been

**n:o istc~d**  01 du: time of th e 2001

**rc:~. sscss**  **ntcnt.** Ear li er Bt c om BRA I) documt:nts were updnlt.'< l o ni.l

**rn adc**  a\'ail ab lc t b r conuucn t \'ill OPP" s public p.:tnicip. ·uion program . Both the 200 1 und 2010

**rcas:se ~th.'nts**  ore de sc ribed in more dcuil in JX•ns D nnd E

**~><!low**

**.** A s n result ofthe 20 I 0 n: asscs.smcnl . E PA :tg3in c xt cndC'd lhc f'C'gisuntions of Bt com PIPs on Scp«mh<!r JO . 2010 . The J \gcncy cJ<, · elopcd a risk· boscd appro:><h IOdetennine !he cxtcn$iOn lime fo r indhidl.L31 1U com rct;.istr.nioos.. Rq; ismuions \\ilh lo"cr risk o f insect r'c:')htancc ( i.e .. pyr.unided \ rui ct ics) \\CI\! gh · tn longer cxtcrui on periods 1Mn those with h i ghc;r risk (i.e . . si ngle trail producl <). The s pecilic mclhodology. o. < d< -scrih<!d in I he 20 1 0 BRAD d oc ument s . is ns follow s:

··· n t c f cxtcns ion

**troh :~y)**  iuclullc s n:gistmtion period s of tin.·. ci gh l . and twelve year s : a liftccn

**y~ar** rl!gi stnlt ion peri od \\ i ll3lso be :l\'fli l obk. if adc< 1 un l e l

y S U

J >poncd by our sc ience ns.scssmcnt 

### In t h is s c h eme. ( i ) n product \\ith a si n gl e 1•11' t oxi n . 

### nml a 200 /o C'XIC"mal

**n:fug~.** qunliti cs (or 

### n fi\ ' C ycar

**r~gist.rolion:** ( ii ) U prod u c t \\ith 

### pyrn.midOO F•tP r oxi n.'i (i .e .. t\\ ' 0 o r m or4,; t ox i ns with di.stin.;:t. n o n-c . r

os.s n:::t cling modes of n c1i o n) . that a n:: non - high dose (the dclinition fo r 3 high dose product remain "' unch:angcd). 

### ";th either :1 SC'c:d blend Or "XtCm:tJ n:fugc, qualifies for :ln dghl )C.lf rc si,tr,Uion: (iii) Q produc-t \\ith py mmidcd PIP t oxim (i. e . , two o r more toxins with dhlinet. non<mss reJcting modes of

**t:~ction).** that :1rc high-dose, \\ilh ei ther o S«d blend or c x tcm :t.l rciugc. qml i fies: for a tweh · .: ycJ.t rcgistr:Uion : (iv) 3 rrocJuct \\ith pyramided J,JI, t oxi ns {i. e . • tW OO r m on: toxins \\ilh di st inct11 0n...:ro:..s re-ac- tin g m odes of nction s) . with d thcr u 

### seed blend or external refuge, t lmt h as been dctcmtined by EPA' s s cicm : c

**u~~ssmc nlto**  be 1 500 /o as durab le us the baseline s in g l e toxi n produc.:t with n 20 %

**c~ tcnt** 

**l** refu ge. wo u ld qual i fy for n t ili ccn yc:ll' r.:gi s trotio n . t• mJucts determined by El) t \ 's science

**assc~s m.:ntlo**  be

**lt: s.~**  th. :m 100 % a ·o; durobtc us the b:lscli n c si n gle toxin product with o 20% c . xtcrnnl refuge \\Oul\1 not qualify for a fh c )'cnr rc g i s tnnion and the

**~~ is**  **tr..at io**  **n** period for suc h produclS \\ill be dcccmt incd on n ('a$4: by-cnsc basis consistent \\ith the lc\ cl of risk

**h~y** pose . Similnrl) ' . **im'la~Ka ''her~**  other risk issu'l$ nuy nrisc . or 

### ''here OO \ d resi!)'UUX C' conc;cms may lx: prcscnL \\ Ould Dlso b: dct(nnincd on n c.lSC-by-ca.sc 

### b.l.sis. 3S "ill novel Kfu gc configur.ltions t1ut nuy

**p~nt** unique dur.lbility profiles."' FoliO\\ i ns this st.mtcgy. Ut co m p r odu,ts " i1h single:: toxin s were extended until

**cptcm~r** 30,2015. Olhcr pymmidcd producls were given

**c~tclu:ion**

**$** oiS-12 )'Cili'S ( no JS year exten si on s \\'en: app r o\'cd). l•ri o r t o f urth e r cxu• n di ng th ese: rcgis t n. l ions. J; Jlr\ \\ill C\";t)uatc whc th c:r t hey st ill meet FIFRA rcgi S t ruliC'l n .s t n

n

dnrds . For t he co l copt.:ron llt com \':trictics that

**~p rc**  in 20 1 5. E PA is cul't'c:Jll1y working to impro\ ' C the i nsec t r\! Sis tan cc

**m:tnng~mcnt** s trotcgics for cont roo t worm (sc:e the ln.sc.·ct Rc s i s tnnce MM.:tgcn-tent portion of the Scicnti lic A SSCS.. "ffilcnts S (.'Ciion). th ough the.."k' cHOrt s will extend p3Sl

**Sept.:m~r** 30. 20 

## Is . To ollow l b r completion 

## or these nc ti\ • itics. EPA will cxtcnd

**lh~** opira t io n lbte of these products t o Jnmury 31. 2016 . Other Jlsingle trait

**n;gistr.nion.~** tnfJ;eting only lepidopteran peSIS \\ill be cxtrndcd in accordan«: \\ith the parodil!l' t do=rib..-.1 ob<W< (i.e,, ror 3 

### fi'< year period to September )0. 2020). 

## n. l nnoc t Rnis t :ant('

**:\hn:a~('mcnt**

**~c t**  resistance .
**:mag~ mcnt**  (IRM). described in dc t nil in th-.: Scicntilic 1\SS(S.SmcnL 'i sec tion oft h is doc u ment.

**oddrc .ssc...~tn**  risk to B t com PIP s: the potcmin llbr t nrgct inse c t pests to ad:tr t h) the Bt t oxin (s) in PIP $..

**rcnd cri**  **n~** them inefTec t h ·c fo r cCi n trol. Since I) IPs h:t\'e bt.--cn registered in the 1 990's. I R.M ho.s been rm tmcrt; i ng science

**th:~t** hus r.:qu irx.-d

**EI ~A**  to P<riodically roasscss and odjust its

**rc~ulntol) ·**  approaches (Mottcn ct al. 20 13). E PA' s tus fn.--qurndy utili74"<1 the FIFR.t-\ Science Advisory Puncl (SAl') 

### as a mCJ.n s to C\'3luatc and n:>.<S<SS lfL\1 opproachc< (sc.: S«:tion C below ). SAPs conducted in 1998 and 2000 (SC ' cr.:ll years afie r the first Bt com 

### rrgic;;.trotions were appnwcd) helped establish core mitig3tion

**~tnllcgies** inc ludin g the usc ofrefu ge to delay the development 

### or n: Si<iiWICC. Subsequent SAPs ha\ 'c pro\'ided g uid3t1cc on com rootworm IRM (2002. 2013) nnd the

**u...~** of54.--cd blends as nn altcm;atc refuge stmtcsy (2009. 2010). Since IR.M is u s tew ardsh i p JJrognu n . sig n i fican t data rev i ew a nd u naly s i s fo r IR.M occurs nflcr the produc t a r c r cci stc:n!\1 (I.'.Q .. r.:sistrmcc mo n itorill £,). To i llu s tnttc.·. tWA has re qu ired \'arious tcnn s ofregistr:lli on to nddr .. -ss thes.: risks and assess th e cf'f'cctivcncss oCthc J R

f\ ·

1

**~tm t.:gics**  **.** Sc vcml of the temu ofrcj;i)tnstion require annual rC"port s to be s ubmiucd to EPA. \\hic:h include: • Refuge rompli!lnCC c.bta . Rcgi.s.tr.U\ts 3lC rc-quill:'d to conduc-t annual third

**p;~rty** SUI'\'C)'S CO dclemliOC lhc knJ Of C:Ompli:mcc \\ith Slruc:tui"C'\\ refuge O.""qUin:mC"nts (sec

**Table~ ).**  **Thi~** sur\'cy is coordinated throu gh t he t \t;ricuhur.a113iotC"Chnotogy Sti!Wardship Tcc hnicu l Comm ittee ( ABSTC ). u con!!oOrtium of the PIP rcgi str.mts.. such that o n e SUI"\'CY co vcD all kpidoptt!ran an d colt'optcr.m·prott.-ctcd Bt c om rcg i str:s t ion s. A S '-"CCi nd comp l iarn;c nsp«l in\'o l vc s the usc of on-fo n n 

### ac;;.scssntcn t s . in which L' ac h rc s istrant 

### visitS II AAmr l c O f their 

### CUStomers 10 1'\!\'iCW nd h en:nce t o rcfuJ;c rl!tluin:rncnL'i. Growers may ultim ately be denied access to the company's Bt com proc.lucu if found out of comp l inncc in two consccU1lvc ye-ars. Both the third party sur\'CY und on · farm nsscssmcnt d:. tn arc included in each :mnU31 report to

**l)A ~**  • Rcsisunce monitorin •. An

**:tnnU3ll\.~i.st:ulec** monitoring n:pon is rcquimf for each of the registered Bt com PIP toxins (fable 1). Resistance monitoring consists

**primaril~** of two clc-mrnt.s: I) responding to and in\ ' t:Stigntins repons 

### or une.SJ'I'-"""Cicd

**tar~ct ~~**  **Unm~~** to Bt com (a potcnti;s.l indicato r ofre$iSl3nCe). and 2) snmpling nnd te s tin g

**tar~ct** ir\St."Cts to dct«t nny s hills in

**susc cptibilit~**  **·** to Bt toxin (s). Dnu1 for -.:ach o f the maj or lepidopteran nnd cokop tcron tnrge t pe sts arc i 1

1Cl udcd i n t he nnnun l r-.:ports. Data f r om the s e rcpons allow the Agency to co n tinunlly rc, · icw th.: a d

t'quacy oft he IRM

**tr mcgi-.:s**  and make ndjwtnu:nts: as 

### nccdro . To illustrate. submi ttC'd d:.tn

**:"how ~.'((**  de-clining mtt"S of rcCugc compli:mcc during

**th~o::** 2007-10 growing $el.<;Ons (I! I' ' A 20103). 1 \ S n fi."Sult EPA impose'd n nwnber of additiorutl tc:nn s of n:sistr:nion I.W'Sered 31

**impro\in~ ~ompli:mcc**  rates 

# ., , _\\tk"n Ot com n:-gist.ratioro ncrc cxccndN in 2010 (EPA 20101) . **Similo.rl~.** conc e rns about the ck\dopmcnt ofresb.'t:l.nec ;unong com n»l\ \ O nn lriggcrcd a

**re-a_~(J11Cnt** of the IRM program for coleop teran O t com (SC'(' scclion F) below. EPA r c \

• i c ws

**ofth~.: rcfu~c**  compliance and res iSt:tncc monit oring data a r c- p ublically l Wnil:tb lc in a docke t

**est 1bli**  **hcd** l b r IRM : EJl A- J I Q - OPP-20 11 -09 22 (rc:g u b. t io n s. gov) . In nddilion, UI'Jll} s cicnt b'ts fr\.·qw n t l) '

**pr..:.. n1**  dn t u f r

om s u ch reports ot sc i c:n t if i c rn c cli ngs (e .g . • Cnto m o l

ogicn l Societ y ofAmcr i cn) u n

d o1 h cr fo rum s . A key <Ompon<nt of EP, \ ·s "'" '-«<> m<nts of Bt PIPs hos b..-.:n the I'll ' IV\ Scientific 1 \d\ i.sory P anel (SAP ). The SAP 

### scncs 3.S :m independent p:cr rc\ icw

**bod~**
**·** nnd

**consiSL~** of scien tific expertS in ::1 r.ms;c ofdi..sciplilll.$ n:l<Yant to hc.3Jth ;md em iron"'cnul h.sucs for

**~~~1icide:s. ~fc-cting.s**  are open to th(' public. 

### " ith opponunities t o rro\ · id(' \\rittcn :md ! o r or.d

**comm~ nts,**  nnd o .n

: c o nduct«t i n .1ccorcbncc with the Fcdernl t \d, isory Co mmittee Act (f ACA ). S i nce 1992. EPA

**a~** co n\'cnl-d n total of 19 SAr • mee t i n

gs r dllh:d t oUt PIPs . Th o u gh t hree o f th e-se m ee t i n

gs \\ ' t rc specific t o Bt co u on PIP s. m os t nddrcss cd s c i e nt ific iss u es t O r Bt com PI Ps . A l i s t oft h ese mcc t i n

J;.S i s

**dc:tn l<.**  **l** i n Ta ble 

### 5 bel ow . A t pre se nt . n o ndd iti onll m

cc: ting s 

### a n .- plann e d . St\P mc:clings ha\ ·c

**bc~n** hdd t o pm,idc guidance on 1'1 P 

### chattlctcrization :md risk

**3.)$C'S."\mcnt..~** 

### for hum3n health. non·"ugct organisms . and insect

**re<i~t** 

### m3n.1gcm cnl . Speci fic

**p.lne!'l~** hoYc :dso focus..."'ti on nmcl Ot PIP s (e .g . • first corn rooh\Onn PIP).

**ri~b** for existing uail s (c.s.. 

### resbtancc rnan:Jgcment for 

### C<'m rootwonn PIPs ) . :uxi

**propo~-d** chungcs to IRM 

### str:ttcgics

**.~** .• )C>Cd bknd.s). Since the: )Cicn<:'c of3gricultut:ll biou . -chno1ot;Y i) C'On t inu311y cmcrg . ing. lhc sc meetin gs Jmve

**prc.wid~d** a mc:m s for E .I'A 1 0 :u:fdn:s,s new sci cntific issues t hat h::t\ ' C arisen s in ce rc:gist r ntion. Ex:unplc s includ e

**n-t: ~.:t**  co n .e:em s (t'.g .. gene flow. t oxicit) ' t o moiUU"(h

**huttt:**

**ll ~).**  h um an heal t h

**co et:rn**  **~ (t:.~**  .. :- 11l crgcnici t y) . an d irucc t

**Tl mnct**  mn nageme n t (e . g . . i n sc:c t b io l ogy . se ed b l e nd

**t~: gc)** 
**,** 

### T ll bl c !li . Lis t 

### o f F I FR..o\ SAI • mct: t i n

gs r cl atc: d 

### to scienti fi c i ss uc: s n."lsoci: ucd \\i t h 

### B t 

### r •J Ps (Table udnp tod from :VIon <n n t u l . 2013) FJ FRA SAP Mtttiag\ D 21t(s) Topics

**Co rnJ**  Subp.md on Pbnt Pcsziddc:s ' IA...:nnbC'r 18 . 199.2 ()dining ris.J..s of PIP s S ub p.'llll' J o n Pl::mt Potiddcs

**~b rt**  **h** I. 1995 t-. t on,.lu ll o Comp.tny' s npplk:nio n f o r reg i s tnn ion or Bt

**ub x-.:**  **cs** ft • m•b r lonl s tldlu

**\.'n ~in**  J Pl oant·pnl kKies \\C'fe rM.l."nCJ rt;IJH· ii'IC'Orpor'.IIC' d pi"U(C"CtlllU (PI Ps) i.n 1001 (ollov.inJ; pubJic3 c ion or P I P ' " " ul.lltion i i n lbC' Ftderlll R q;iutr ( RC' i.UI.Ii l ions l.'nJC'r th<' f'tdC'r.lllm«tKkk.

**un~icJdC'.** ll.nd RodC'nl icidC' Ace ((W rbnc·lrKorpontC'd Proc.«Un.ts ( Focmnl)

**~t·** f"nlkidn. fe'd<r.IJ

**R~ Ut"**  66( I J9): J1711-l7SI7)- 33FIFRA SAP l\! C<' IinJ.:.!i llut r(•) TopiC's 

### Conn:d Subp: m d o n Dr P lr.nt • P.:st i cide s :.nd Fcbru :uy9·1 1. 199 8 /Jt 

### r'lll i n sec t r cs ist :mce Rcsisuncc: M :truscm c nt m:uusnnc nt Out::u:tniLDtton and Non - T3J];d OrpnMl O«nnh<T 8-9. 1999 ProdiKt cturxtcriT .: llion. non· Requimnn'lt (or ProtC' in Pbnt Pot iC'iJci l41b-et

**Of~nisms** Food

**Aller ~enichy**  ofC I)9C

**Endoco~in** 11 nd Febru:ll'}' 29 - Ma..:h 3. lium : m hc:a hh Other N'on-d it:\."Stib l c r•r (lt

ein s !000 l\

· 13mm.:'l lirm To . \ic it y As ses!iment GuiddillC's Jun e 6·9. 

## :woo Prod u c t ch:nactc rirn t io n , for P rote in P l:tnt l) otic idcs hum :m he 31th l!i$ues Peruining to the Bs Pl:.:mt ·P c)ticides Octobtr 1!·::!0.2000 J lum:sn ha.llh .md Ri.o;k :md lknc:lit Assessments em ironmC'ntal rid.:

**~nu:nt** ttnd in_i«t f\"Sistanc"C

**ttnll~\"111C ill**  A o;;sc.ss ment of Sc ient ifi c ln f o mmti o n S'o\ · c:mber 23. 2000 I I u num h eahh Co n u min g S t R

rLink ® Com ASSC'iSrncm flf , \dditi o nal Scientific Jul y 11·18, :001

**flum n**  hc::t hh lnfonnation Concerning Swlinl Com Com ROOI\\l'fln

**Plant ·l**  **~orpor.uN** August 27-:!9. 2002 Non•t.trlrt in.'C:'Cts. iru«t Prot C'C'tanc l nS«t

**R~isbnce ~l:l.n**  **.l,Crtlc nt**  **~i:.un;;~ mJn~g**  **ement** a nd

**on· g~**  **c** I mee t Iss ue s Prod u ct Clutrnctc: ri7Aiio n. ll u mtl n l ll •Bhh

**Ju n~:**  8 -1 0. 

### = oo-l \Vi t k S L rik c-1\ cotton hu m :m R i

.">k. Ecolog ic:.1l ki sk. t\nd

**s~ t**  R\.' sts umcc h e:. h M:co l o,t; ic-a l ri sk 11n d

**M:ma ml!'nt**  F'or Bt Co H c m Producl) insect

**r~:.,i~oL:mc e**  m:sn:tg c mmt ; llollprdlb ;md llollt;.1Jil lP II inS«t

**r'C"i~ e**  m3ll.l£nnmt St icnt irte I ss u es A"'SSCi:stc:d \\'ith.th" ll umttn Mnrch 1·2 . 2005 Hum:t.n fK"Ilhh I k a h.h

**.s.scss ~:nt**  o f The Cryl-lAb I t'rotc i n E\'c nt M IR (tQ. I Modi li e;:l CryJA l 'l\"' tt: i n llt Mo.: h 1 4·1S, 2006 llum n n hca hh. Com··P I :. m l n cC"trpor.atcd

**Prot~t:. m**  em · ironn l.: lllalft\:o l ogic3 1 r h k

**issue~**

**Arut~ sis**  of :1

**N~tur.aJ** Re fuse:

**of~on.Conon** June Il - lS. ::006 lns«t rtSiSW1«

**m~n~gC"mcnt** Hosts for MonS3nto'.s Bollprd II Conoo E

\ 4 1 \IO'Ition of the:- R oi:)(:lncc R isks fro m <Xcob.."f 2J-2S, ::006 lllX'.:I r;; sisc.-.nc c m3n3gc:mc:nt Using

**100 ~~**  0 C'I II c :..rd t: and Bollg;,rd" II Co n on as r• n n o fn l , ink Boll wo nn Er.:ld i ea t ion Prog mm in the S tat \: o f 1 \ '1.. R

csis t ttnce K i,b from Using A SC'C'd Mi .x R

efuge \\ith Pion«f's Op1imum , \crcM:il.'l 1 f< bf\ury

**!3~25 .**  2009 I nS« I t c"i'1An« mtt.tUI£,C: nu ,,il Com RootY.onn·Protttlcd Com Scic:-ntirte I S5UC'$

**As.~i:lred** "ith f)Jta fc:b ruuy 25·:!6. 2009 Prodm

**<h.:trnc ltri7:~1ian.**  Requin-d 1 0

**R~ gis**  **lcr** Pl .: m t -ln corpOr: U

c<l h u mttn h<o hh . no n·l :trgc« Pro l ectnn li

**on:a hm~.**  '\:1\C fl ow


### JJflfRA SAP )fotl;nt:,> O.t<(•) T opits

**Co\ rt'd**  lnscc• Resil.t.mcc M:uugcmcnt for

**Sm3rtSL1.~n.t RC'fu**  **g~:-l Hhc·Il:llt-ll**  tJI:uU· De<<mb<r S-9. :010 lnS«I ASistMc c mruug.cmmt lntC'ItpOr:t l4'd Prolcc-tant (I'll') 

### Corn S« J B lend Scie ntifi c U n certnint i e;<; As..'"Oe i :Ucd with D ece mber J-5. 2013 l n:.cct

**rc-s- rmcc**  **m~ n:t**  **gcnu.•fU** Corn R OO I\\ O rrn Rcsistn. ncc footo nito rin .: fl)( llt C('IOl

**rt ~uu**  lnc orpornt ed

**Prot ~UU**  **I.S (P**  **P~)** ll. 200 1 Bt P I Ps R<U.S>< -"' mrnt In 2001. EPA condU<t<d a c:<>mpn:hcnsi• ·c r=mcnt ofCryl,\b and Cry IF. th<: two r-cs,i s h:rc:d PIPs in Bt com :u the 1irnc (c:ouon :md pouto PIP s "m; also included in the rt'

.. lSscssmcnt). This r c,ic-w was trisscn.-d by registrations that w.:rc aimed to t:Xpirc o n v a rious do t e" in 2001. As a rl! sult of 1 hc rea ss essment. the A gene\' dec ided 1 0 cKtcnd t he Bt com 1',11 1 

# - . n:s is l mt ions 10 2008 (sec se<: tio n A abo ,< ).

E I

)A 's 200 I rc , · ic w wa s "conducted

**:~. J**  o n ope n nnd t rnnsparcm public process that

**in cO**  **rJ ){)nll~**  **d** so und an d cumnt

**~icncc.** :and substan t ia

l public in \'o l \'t.:lllt.:nt .. (C Pr\ 200 1 ). EPt \ rcvit.:\\cd upd.1tc d scientitic int bnn:uion for produc t chn..ractcri ,...t ti on . humt1 n health. ecological 

### c:llC.cts. in sect raisuncc- m;U\OJ{;Cn1Cnt. 

### ru'!d bctlclits.

**Guidan~** f r

om the multiple SA P meetings conduc1ed in 1998 - 2000 \\':IS a.lso incorpomlt:d into EPA ·s

**reviS~.'<I** s.cicntitic tlSSC'SSmcnts. A ''Uiopc:r.litidcs Rcgist.rn.tion Action Doc:umcm- (BRAD) wa s

**crc::~tcd** during I he

**r~rntlo** document the Agency's scimtilic C'\11IU.1tions

**~PIP** regulatory hhtory (E PA 2001). EPA concluded tktt Cry lAb and Cry l F Bt com d o not pose ri sks to huml.n htahh o r t o non - t a r

ge t speci e s. alth oug h ri s k concerns we r e idcntitiOO. tbr i l lscc t

**resi~trmcc** man:tgcmcnt . 'OU:'

**~VieW** a ) .SO ide ntifie l.f

**Clc~lf** bC'ncfiiS in ICm\S of OCOn(lmiC S, h liiT) ! IO hen hh (cOO\'Cn tiOil ::t l pesticide red uc t io n). ;md t he c•wironmcnt . To adllrcs.s thc-IRM concc. · m s. t he Agency i m posed t ..:rm s o f rcg i s trJ t io n (incl uded us J':trt of the llt co m r ct; i strJtj on

**t: cnsiC'I**  **l.lil)** 10 estnb l is h rl)'fuge n:q ui re mcn t s . ri'sistnnce m oni t orin.:. t;mwcr education. and c ompli M<:c

**las~urnn cc**  **.** In ndd i l ion. tcnns m:re in cluded requirin g conl1m1.ltllry dom for the

**h)\ \i**  **n~:** • £-'rodui'l Ch:trnclcrizntion ' Hutrultl l-lc:1hh :

**ruul~'lkal method.~.**  protein cs:prt"SSion. runino ocid !o<quc:ncing. heat smbilitr • Soil Accumub.tion: Cr) • lt\b . Crylf protein l e vels in soil •

**Non ur~c** 
**t** cbta: non-target

**i~"Cts.** morun:h buuerOy c .-y1Ah l ong tcnn cx · posurc. ch r onic 3 \ i:m test • In s ect R"s i sunce M !!..nOf.1: 111C'n l : potent ia l for n onh ·.south 1110\' C mcm of corn ca.rwom1 . impa ct of in sect ici de usc in r..:fugc.s., dc\'clopmcnt of o di sc riminat i n

g t es t dose for so uth\\'(' S tem co m bon:r TI 1 c tfnln described obow

**'' re**  s ub seq u<:ntly submitted. n.:\'icwcd. o n d i nc orpor.nc d into E

P , \ ·s 20 1 0 Bt com reas sessment ()(:c the f o lf o,,ing

**~"'\:t on)**  ..

**Th~** 1 \ gcncy funhi'r requjred 35

### 3nmni iR.\ · I

**n:port. ~**  

### to be 

### submintd for n."'Sisanncc monitoring and

**~fugc** 

### compliance (sec section 

### 0 000\e). 

### The 2001 Dt PIP re:l $ .. "iC"S..'im cnt wns condu,tcd OS 3 

### publ ic

**proc~.** 

### with multiple oppo nunitic s t Or stakeholder in\ ' Ol\ ' \.'11\\.'nl. 

### EPA considered all publi c commc- n lS i n li n:1 l i1j ng 

### the re assess men t an d regul atory po s ili on ( E l'A 200 1 ). Pub lic input \\ 1 t S 

### ob l nint..-d from t he followins nca ivili cs: • SAP pcc:r ft'\ ' iew of E l)A ' s rc : lsses.s mcnt (Oc t ober I

**-20.** 

### 2000 : Report i ss ued March 1 2. 200 1 ) , Ope n J>ub l ic

**JUL~ting** \\ith 

### opportu nity for public comment 

### CPA's drnJ\ reasses s ment (BRAD) \\':15 

### m::tdc :l\'ailnblc i n th e public mc:cting docl<ct . (SA P website: hnp: b

\ "'"'" .

**.;(Sl ~O\**  **·/ i** ooJ

**'I SJ(!**  **m'-'~** i ngsi200Q ! I 0 I &00 

### mtg . htm) 

### • T""hniC31 briclin& for the 

### Bt PIP s r<:t.<S<-ssn>rnt (July

**2~.** 

### 2001 ). Open pubic m«tins (:mnounccd in 

### 66 FR 37221) tO present EPA"s reJS-<cs.<mcnt conchuions and

**addres..~** 

### que-stioru , • Public ' ommcnt per i od for the Bt Pll's re3S scssmcntlllRAD (Jul y 17- , \u g ust 31, 2001 ) . Or<n publ ic camme nt rcriod 

### o n the drnfi ri s k m i ti gation and re g u lat ory opt ions dc s crilx:d in E I 1 

### A ' s 

### BR.t\0 document (n nn OI IIl C t.."t l 

### i n 66 FR 37227) . 

### t:. 20 1 0 81 Corn Rrn sstss mC'nl Si milar to the 

### 2001

**rc assc~)1t**  **cnL** 

### E I'A 's 20 10 review o f Bt com w as ui gs cn.'d by 

### expiring registrations . In 2008.all B1 com rcgisuations were extended to September 3 0. 2010 (S<'C 

### section A ot>o,·e). To suppon funh<r extending th= 

### n:gisu:uions beyond 2010 . E PA 

### n.-e\ ·nluah . -<1 current 

### sdmtilic infonn.1tion. n:\icwcd 

### Studies h."quin."'C!M h:rms and 

### conditions 

### of reghu-.nion. nnd updated B R.t \ 0

**documcnl~** 

### for cxh 

### Bt PIP toxin. The 2010 QS.SCMmcnt in cl u ded the 

### CryiAb and Cryl F 

### I' l l' s that"""' the focus of the 200 1 n:usscssmcnt 

### os w<:ll t\S 

### other Ot PIP s registered between 2002 nnd 2009. These

**n~wer** 

### PH• s: i n cluded com·rootworm \" n rict i cs {co,;c 6502).

The 

### fl)llowing Bt PIP

**to in**  **~** 

### wei'\! i n cl ude d in chc: 

### 2010 r e3ssess mcnt : • CrylAb • C ry IF • CryiA . IOS • Cry2Ab2 • CryJ[Ibl •

**Cry3~Abi CI')**  **3Si\bl** 

### • mCry3A A majo r pan of th e 2010 rcnsscssmc:nt wa.o; IR..\ · t. r•ast review s of complianc . c dutn hnd ind lcu tcd th u t a d herence to

**rc i.**  **~1:** 

### f\."quircmcnt s \\ 1 tncd in 

### the yc!lr $ pn:ccdi n g the reassessment (UPJ\ 2010a). To ; uJdre ss thi s i ss u e. E P

, \ im posed terms of

**rc r:**  **Hi n**  

### f\!quiri n g that regi s tront s imp lement additional mC" .tM ,lO: $ 

### t o imprm ·c rdu1;.c 

### compliance (E PA 20 1 0 1 ), 36EP,\ ;dso rc\isited se\ct'31 «ological concerns for ::tqwtic in\ ' Crtcbnut:S and non · target

**in..~ts**

**,** In response to concerns a.boul pcucnti:t.l

**Uttoxicit~ to**  caddi.)Oic-s (Trichoptcr.t). El,A I'C\it:wed :1

**num~**
**r** O( peer n:'\ · it\\Cd ) tUdies thtll

**U..'l..~** the issue. Thi:SC (Up!f'S showed th=tt cO'C-cts to caddis tl ies were n ot cnu.scd by llttosici t y . but were due to other ditli:rcne.:s bs:t\\CCn the

**nttc:**

**t** subs tnn ccs. In 

### reg,1rJs to non·tnrsctlnscc t t est i ng.u JH ' C\' ious SAP (2002) had rc:commcndc d t cstjng Oriu. s

**inJidio~**
**s** ( mi nute pi rotc b u g).

**Th ou~**  **h** EPA

**~qui** red OritLf test in£. 1\:'g lst r a nt s t;.'S(X:'ricnccd l ogistic : 1l dilli cu h ic: s i n t es t i n

g t he i n .S '-"CI. l i P A rc:c \'u hmtcd c urrent 

### scic:m illc iniOnnruion 

### an d concludi.-d d un t ox i c it y 

### t o Oriu s(a 

### H c mi p t \!ro n i nsec t ) is not 

### c.xpc<:tcd s ince the 

### toxicity of th e

**~si.stcrell** Ot PIP tr::tits is 

### restric h. "<< h) Lcpidopu:r.m nn d Coleopteran

**inS«l~.** B o th ofthese issues wen: rl!\ ' iC\\Cd in EPA (20 1 Og) and in th.: upd:ued ORAD documents . In addition to the non·lJll&<l i»UCS olxw<. EPA 3lso ""'"""'ill<\lond updated the cndnnscrcd SJX"'Cies lindingS for the n:giStert.--..d Ht toxins. In all c;J.)C'S. EPA upheld the pre,· ious concha:;. ion 

### or-no effect·· (including 

### din.-ct and indirec t effects) for n llli s: ted 1hreatcncd or cnd:mt;er"d species. llu:rcforc. n o CCliU ll hations \\ ith the U.S. Fi s h and Wildl i fe Service were 

### n:q ui r c- d under 

### t h e Enda Jlgc R.·ll Stx"C i cs 1 \ct. 

### 111e upd!ued

**:l~SCSS Tlcnts**  nrc dc t ni l c

d 

### in

**h~** BRAJ) doc um ent l O

r c:1c h P JI > , No ch;u1£.eS were needed for E I•A 's h um!ln health J,Sscssmcn&.s (comp l eh."<i l O

r the initial rl!gi s tr.-uion o f the Bt com I'I

**!~-)** und 1hc existing 1oleronce exemptions 

### ns pan of the 2010 n:MSCssment. All prod\K't

**d:~arach:rilntion'human** hc:alth conclusions MC demiled in the

**'"~pcxti\**
**c** BRADs for e:ach rq:isu:rcd Ot com I)IP. To so lic it public input on the n:3sscssmc-nt EPA utiliu---d the publ ic p;uticipatio n process dc\'dopcd by the Oilice ofl't'!iticidc l)ro gr.uns in 2009 . l1 1i s proC't').S W:\S estnblis hed t o incre ase oppo nunities for the public to

**~;onuncm** on pe st i c ide ri sk nsscss mcnlS nnd proposed reg i stration oct io n s 

### Gill p ;// www 2. CJxt .

**t;o\' nc~t**  idd !J·Icg i s 1 mt io n l p ubl

**ic·p~**

**l** n ic j nat jo I I· p[S)(!.'"-o\· rc l:ist tJtl.Uw.: 

## ncair m •). For th e Ot 

### com n :as.sc: ssme nt. I! P A CSlfib l is hcd n c.l ockct in

**rc~; ln**  **ons go**  **\'** (E PA4 HQ· O J l J

l -20 1 0-0607) \\ i l

h 3 30 doy .. ·n mmc:nt period. The r\g cncy poS it.. 'illh c fol l owing d oc umen ts for co mment : • Updated lll{;\1) uocumcnts for: 1 ) Cry I Ab!Cry I F. 2) Cry I A.I05 / Cry2Ab2. 3) Cry3Bbl. 4) Cry341351\b l. nnd 5 ) mCryJ , \ • A Btu\D for Optimum Acn:Ma.x ( nsccd blend containing Cry34135Abl 311d noo-Bt com) • IRM resi:..u.nec monitoring rc\kws 

### ro r Cry3Bb1. Cry3.Sf3SAb1. and mCry3A • Rc\iew of aqua t ic in\ ' Cnebr: ue and Oriw ' tCloting

**;~,ucs** • Proposed tcn ns ::tnd cond ition .;; for t h e O t COI'n rt:gb t mt ion ex. tensions E PA rt:'Cci\'ed ra t o t

u

l of 10 comme nt s i n r esponse t o t he publi c p:trticip:t ti on 

### proce ss. SC\'CII co nu nc:nts w ere n. -cdved 

### rrom U t corn regi strantS

**on~ int**  **o. S)**  **gcnt~l.** Dow. P ionC't'r . and J \ llSTC). o n e from th e :-4atiooo l Co m Growers Assoc iation. one from 1he Ce nter for

**Sd~ncc** 

### 37in the Publi c lntetl-st. nnd orK" Crom I he J \ssodation of J \merican S«d Contr o l Oflkials. r \

**n: sp<>**  **~c** t o commc:nts was posted to the docket after t h e t:ommcn t period c oncluded .

**ll !t..~**  on the rt asscssmcm. E PA ex-tended th e I l l co m n:gisrr.nion s t o d:JtCS between Septembe r 30. 201 S an d Septembe r 30 . 2021 . in acroRb.nce \\ ith the str.ucgy dclailcd in section A abo\"<. The firulizcd lonn.< :>nd condilions (E PA 20101) :>nd updnlcd BRADdo<umeniS (EPA 20 1 0a·<) ho'< bl-cn pos ted 10 lh<

**,\~• 'fl**  **<y"s** PIP web Jl-1&<

**(ht [!j**  **wwW \'p:**  **,.: o\**  **·/ re**  **i' ticidc**  **bin!"X.':-Ii~t:jlh:s sli**  **ndcx hlrll).**  NEXT STEPS ANil TIMEI.INE

, -\ Fcderul Register Notice \\ill3llll0uncx the a\ · :lii:Jbility ofthi s: combii'K'd W o rk l,lan :md Swnnury Documc:nt and PropoS«! Interim Rcg istr.nion Review Dec ision fur lh com PIP .s Md

**I** low n 60-dny comment period . If there are no sisnificn.nt comments or addit i orY.ll i nforrn:Jt io n s ubmined to dtc docket durin g th e comment period dun k a ds the Agency t o ch • anbc iL..; propo s ed dr:cision. E I 'A may iss ue M Int erim Rcg is'lr.'llion ltc vicw IX-.:i s ion for Ht com PIP s (case s 650 1 :md 6502) . H owever. 3 final dc-ci :,.io n for Bt Com PIP s may be i ss ue-d with o ut h .: w in g previou s ly i ssu ed 

### a.n interim dl"Ci s ion. A fin 31 d«bion on the Bt conti'IPs rcgistr.ui on tc\'icw c-ases \\ill ocour 30<r on E DSP FFDC , \ S..'<:lion

**~OS p)**  <k«rmin:ui on has bccn m:ldc ond EPA upcbl«lhc Bt 

### com cnda.ngcf\.'"d 

### sp...--cics

**~1cnts** 

### to include 

### additional species li)IC\ISincc the last

**n.r..~ssmenl"i** were co mrletcd. EPA h i\$ created the followi n g

**~o -st**  **imatcd** timelinc for the c omplet ion ofUt com PIP s registra t ion review . Rc-;:i,lnall o n Rt\;('1\ ' ror Ill Corn P I Ps- Pro jrc rrd ktgistr.ation Rt\ ' i tw Timrlinr Acth " ilirs I

**F..itim::~~tt'd** Oat'" Opening lhc: Docket :>nd Combined Work Pl:m. Summ:lf)'

**Do<umcn~** :md lnlcrim Rq;istmr ion Re v iew Deci sio n Open Public Docket nnd ,-.ublic Comment Period for Co mbined Work 2015 - Sep tem ber l'bn.

**Summ 1~'**  Dotument, and J)ropos c:U lnterim R cgis tnuion Revie w Deci sion Close l'ubli< Commrnl Period 201 

### S- Now :mber I nterim Rcs:i slr.J tion Re\ • iew 

### lkd sion 2016 June fin:tl Rc c i s tr.u ion Re\ • icw IA"C ision ond B egin

**os t-~**  **bio n**  followup' TtlD Rf.FF.ItF. NCES EPA. 1998. 

### The En\'ironmcnul Proc«tion

**Agcnc~ ·s**  \ V'hite

**~p.--r** on Bt Pltmt·l,c:sticide

**Rcslsum~e ~ll**  **mg~mc nt.**  **niopcsticid~** and P ollution

**~\ cn1ion**  O i\ision, \V a)hington . DC. EPN73?1S-98 / 00I.
1 i\ fin:t. l

**deci .~o**  **n** on t h e 8ur-Jllw thur i f!J:, Itmb Nlm · i ncorporntN f' Mc-cttnu in Com "" Sht rnt i on

**~vi(".v** c.ue s, in a.c cord.mce wi th .SOC FR S«tionl55 . 1

**~8.** Y.iU occur

**:~ftc-r** :m [ I) S P Fl ' I>CA S('(lion .: OS(p) dcle nn i n3 li o n h :tS bfC' n m3de .:tnd thr

**l.'ftdtVI!~C1\-d** s:p«ic=s :b.WiSIIlC'nts lu\C' been trpd3.1C'J 38EP:\. 200 1. B iopcst i c idcs Rcgistr.ll.ion Action Doc ument · Baci ll us th uring icns i s PlantIn corporated**Pro tc** **ctanL~ .**  Date d Oc t ober 15 , 200 I . t\\ ' rti labl c ot : h tt p :// \\'' 

### w. c p.:l.gov l t,)tJChmx! l lbjNxs:t i c 

### i**dc §.i** **je :o/** **b~** bmd . ht 1n. EI'A . 2009. 13iop<: s tid J.:s Rcgi s trtll iOn t \ction Doc u m

ent:**Dncillu. ~**  t huri ng icnsis Vip3Aa20 Inse ctic idal Protein and the Gene t ic Mate ri a l Ne c essary for I ts Produc ti o n (v ia E lements of Ve<tor p:-<OVI300) in !;vent MIR I 62 Maize (O!;Cl l Uni que ldc ntiticr: SYN-IR162-4). A \' a il a bl c at: hup :/ / www .cpa.gov/ oppOQOO l l chc m searc h / reg**:~oc tio** **s/rcgis trati** **on. dcci** **()n** PC 006599 3·t\pr - 09.!'9f. EPA . 20 1 

### Oa. Biopesticidc Rcgis t mt io n Action Documen t : Cry l Ab and Cry! F 

### Ba, · il/us thurin gh· n sls (Ut) Cont l' l:lllt ·ln corpom h

!d Proh."'\: t.anLii . Updated September . 20 1 0. Avai lab l e u t hllp :/ / \, ww. c Qf! . !.!!.W I rc.-1' t icldcstb i QI?C§t kidc s/ pi r sf c 

## a ·I f:. c;o · l :'tb-bpd .pd f. EPA. 2010b . Biopc st icidc Reg is t ra t io n A ct

i on Document for Bacillus tlmringifnsi s C ry3Bbl Protein nnd t he (jenctic Molc: ri a l Nccc ss:l r y lbr It s Pr ocJuction (Vector I 1 V-ZMIR 1 31.) in MOX 863 Co m (OECD Unique ldentitic r : MON - 00863 - 5). 

### Ill! p j/ / www. c p:l.J.!lW / oppbppd 1/b i opcs t ici d cs .f p i

p sf c

r v 3

bb I · bmd .pd 

### r EPA. 20 1 0e. Boe ill us thu ri ngicnsis Cry34Ab l :utd Cry 3 5Ab l Protein s ond t he Gen etic Mm erin l Neces. s n r y tb r the ir P roduction i n E\'cnti):\S-59 1 22 - 7 Com Biopc s tici de Registr: :n ion Ac t ion Document (BRAD). Revi sed Sep tember . 20 1 0 . Avai la

ble tt l h 11 p : /1 " ww. c p;1 . gov/ oppbppd 1/b**owsticldc~ i**  n grcd i c nt s l u: c h docs .lb rnd 006--' ?Q . 

### rxU : E PA. 20 1 0d . Biopcstici d c Re gis tratio n .. \ ct ion Document: Modi fied Cry3.-\ l )rote in and t he Gene t ic Matcri:ll Necessary for the i r P rod uct ion (V ia Ele men ts of**pZ~ 26)**  in Event**11R6~** Cont SY N-I R604-S . R ev i sed September . 20 1 0. Avai labk at**tp: l/** **w'''"·coo gm** **·/ JX--slicidcs** **.l opc-** **~ilici :s** **ps mcrv3** **ms;LndJ:** EPA. 20 1 

### Oc . Biopcs t id dc Rc g i s tmtion t \ction Documen t: Cry I A.l 

### 05 and Cr y2A b 2 lll5Cct ici dal l' ro l dn...;. nnd t h e Gene ti c f\ · laterial Necessary for The ir Pr oduc ti on in Com {PC Codes 006515 (C r y2Ab2). 0065 1 4 (Cry I A. l 05) ] . Upd ; ttc<l Septembe r . 2010 . A vo i lablc at: http : //

\ \'\\'\\' , C t )J . g o\' / JX""5 1 ici dC'$ ..'b j CIIX'st ic**dS' pj** **:m ·**  $4}0 34 • hnul. (XI f. EPA. 20 ! 0f . Tenns and Cond i t ions fo r Dt Com R egi : amtions . :\ vu .il abfc a t h

tt p :/1 \ \ W\\ ' . cpa . gov l op pbppd lib i**opcs ici** **c~pi ~!bJ:5C'l** **DJ** · tc n n s .cond i 1 ions . pel f . E l' A. 20 1 0g. B PPD Response to t \ BSTC Co mmen tS (In l'roposcd Tcnns nnd Co n d iti ons for 2010 Exp i ri n g Bt Com Re g i s t rations . D ata R equ ired t o Re g i s t e

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