Da<kcl Number PA·HQ·OPP-2015-05~~ 

ww\\',rq;ubtions.so\' 

Bacillus tlmriugieusis Plant-incorporated Protectants in 

Corn: Bt Corn Lepidopteran (Case 6501) and Bt Corn 

Coleopteran (Case 6502) 

Combined Work Plan, Summary Document, nnd Proposed 

Interim Registration Review Decision 

September 2015 

o:uc: q Lnl ct?\5 I 
Table or Contents 

lntroduclion J 

St:Uulory :~nd Rf'f!ul:uor)' Authority 3 

Un :and Usn,::r Information ., 

Sticnlific ~St.'$3 RitniS !\ 

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 

Combined \Vurk rlan, S umm:ary Uocunt('nt. and l'ropma.-d lntuim Ht."'J.islrlllion 

Rt\'itw Occbiun 29 

Rationale for l)roposc-d lnltrim RC"gbtration Rt\'frw D«Uion 30 

NtXI Steps and Tim dine 38 

•• 

2 
11\'TIWDIJ<;TION 

The docket for /Judllus llmringil:nsis PlruH·incorporutcd Protect ants in Corn: Bt Com 

Lcpidoplcmn (Cnsc 6501) and Bl Com Colcoplcrun (Case 6502i is now open. iniriming I he flr.;l 

public commcnl period for rhis n:gislrulion rc,1cw (docker number EPA-HQ·OPP-2015-0584). 

This document is the linvironmcntal Protection ,.\ge:ncy's (EPA or the Agency) combined Work 

1'/tm, Sumnwry DocJmJ,•nt, and rroposallmerim Rc"gi.ftralion Rcrit.:w D.:cision for Bt com 

''hich is being issued pun;u;mt to 40 CFR sections 155.50. 155.56. and 155.58. This document 

explains \\ hnt EPA's Onicc of Pesticide Progmms knows about Bt com PlluH·incorporokd 

Prorcctants (PIPs). highJig.ltting :uuicip:uc:d data and assessment needs and providing an 

anticipated timdinc for completing the Bt com PIP review. It also ind udcs the Agency's 

Proposed l1liCrim Registration Review l)<."('ision for Bt com Plant·incorporatOO prot~CttlntS. 

Hcgistcrcd Bt com Plj)s include vnrietics tOr control of lepidopteran (ens.: 6501) and coleopteran 

(case 6502) tnrgd pests. 

A regis trot ion review decision is the Agency's dctcnnirnuion whether n pcsticide meets. 

or does rtot meet, the ~1andard tbr registr.nion in the Fcdcrnl lnsccticide. Fungicide. and 

Rodenticide i\ Ct (FIFRA). llw Agency may issue. when it dctcnnincs it to be npproprintc. nn 

Interim Regi.str..uion Rc,;cw Decision Ore completinb n reg.bir.llion review. Among other 

things., the Interim Rcgistr"J.tion Review Decision may: 1) n.~uirc new ris.k mitigmion measures: 

2) impose interim risk mitigation measures: 3) identit}· data or infonn:ttion required to complete 

the rc\'iew: nnd 4) include schedules for submining the required data. conducting the new ri.s.k 

nsscssmcnt and completing the registration review. For funhcr intbnn:ttion on Dt com PIPs. 

additional documenrs can be found in EPA's public docker (EPA-HQ·OPP-2015-0584) at 

\\'WW.regld;Hions.gov. 

STAT UTORY r\1'!0 RF.GULATORY A IJTII!)RITV 

FIFRA. as amended by the Food Ql1llliry Prolcclion .-\co (FQP.-\} of 1996. mandarcd the 

continuous r-.!Yicw of existing pesticides. All pesticides distributed or sold in the United State.s 

scncraJiy must be registered by the EPA b:tSC'd on scientific data showing that they will not ca.u~e 

unreasont'lblc risks to hum:m health or to the environment when used !'IS dinxu:d on product 

labeling. The n:gistr:llion 0:!\'icw progr:.lm is intended to make sure that. a.s the ability to assess 

ar\d reduce risk c,·olvcs nnd ns policies 3fld prnctices change. all registered pesticides continue to 

mcct the statutory standard of no w\re.l.S(ln!tblt: adverse en·c:cts. ChongL-'S in science:. public 

policy. and J>C"~ticide use pr.tcticc:s ,,;u occur over time. Through the n.·gistration rc,;cw 

rrogr.un. the Agency periodically rc·c.va.Juatcs pesticides to make sure th:u as these changes 

occur. products in the marke nc~ car\ continue to be u,_"Cd $!lfely. Information on this progrom is 

prtwidt"d ns \\'WW.cpi-l.t:.QV/QDp:imJI/rc.-gistr.ttion rC\~cw . 

111e Ag-.!ncy is impkrnt"nting the registration rc\'icw progmrn pursu.'l.nt 10 Section 3(g) of 

t:IFRA. and will review cnch registered pesticide C\'Cf)' 15 year.; to dctcnnine whether it 

continues w mt-ct the Fl FRA standard for rcgistrntion. 'Inc rcgul:ujons so,·cming r..:gistr.uion 

re,•icw begin at .;o CFR 155.40. The Ager1cy will consider bcndit.S inlbmHHion nnd d:tta ns 

required by FIFRA. Titt- public phase of rc:gistr.:ttion TC\~Cw begins when the initial dockcl is 

opent:d fOr e:tch case. The docket is the Agency's opponunity to sta.tc what it knows 3bout the 
pC'.)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 lepidopteran Bt com PIP wn.c; rcgistcrtd in 1996 and the fir.~t coleopteran Bt 

com l'IP was registered in 2003. Neilhcr lcpkloptcron nor colroptcrnn '''com PIPs lut\'c: 

undcrsonc n:n:gistrotion bcr:ausc pmduclS cont01ining them were first rc~istcred after No,'cmbcr 

1984. llowcvcr. EPA hM conducted n number of reassessments of lh l'Ws since their 

rc~btnuion. n.< described in sc.'Ction IV of this document. Bt com PIP n:g rJt ons h.n"c 

historically been issued with cxpimtion dates and tcnns of registmtion th:at rcquire the generation 

or udditional data. lksc Steps have ensured th>t EPA can pcriodicall)' rellSS<M the current 

scit·ncc und risk profit~ for the rcsistcn..--d Bt com PIPs to cnsu..re they continue to mcxt FIFRr\ 's 

rcgistmtion sundnnls. 

usr, M in liSA<a: 

A Plant·incorponah."<l l'rotc-ctnnt (PIP) is defined ::ts a ··pc.sticiUul substance th01t is 

intcnllcll to be produced nnd \I.S(.'\l in o living plnnl. or in the produce thcreoJ: nnd the genetic 

nuucrial nc~CS..."-'l y for its production" (.JO CFR t 74.3). ln com, PIPs derived from flue ill us 

tlmrinMh•nsis (Bt) hll\'e been gcnctica11y cnginc..:red into com hybritiS to provide insectidc.llll 

JlrOtcction against ccrtnin pc::.ut. One <:lass ofDt com PIPs (c.asc GSO I) ~l.! ~ lepidopteran stnlk 

boring and l.!ar ~cding insects (c.~ .• Huropcan com bon:r. com carwom1. and southwestern com 

borer): a sccond <loss (c:l.SC 6502) tara;cts colcoptcr.m root feeding inSC<ts (com rootwonn). 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) or 

''Slacked"' (targeting multi pi\! rest complexes) \'3rieties. 

Tab!< I. R<)listen.-d Bt Com PIPs ns or20 15. 

Ut I'll' (toxin) t-:\'(111 I'C Code Case Tart:t·l ·t'~ls Yt"ar 

Rtl!ist<rcd 

Cry lAb fit II OQ6.l61 6501 Lepidoptera 1996 

Cry1Ab MONSIO 006526 6501 Lcpidoptcro 1996 

Cry lf TCIS07 006481 6501 LcpidopiC'r.t 2001 

Cry3Bbl MON 88017 006498 6502 Coloopccr.1 20031 

Cry34f35 59122·7 006490 6502 Colcopccrn 2005 

mCry3A MIR (;G.I 006509 6502 Cok-optcra 2006 

Crylt\.105 MON 89034 006514 6501 l.cpi4.loplcro 2008 

Cry2Ab2 MON 89034 006515 6501 l.<pidoptcrn 2008 

Vip3A:t20 ~1 R 162 006599 6501 LcpiJortcm 2008 

cCry3.1Ab 5307 016483 6502 Cokop1cr.1 2012 

•• ,• • • • I ' ' ' ' . . . ..• C.:I')JIJbl ":.s 1M..a.l) gnlnrd ;b O~ S6l com Ul ... OOJ. MON $1017 rc~iiC'ft'd In .. OO.S) n:plxcd thas t'\C'Ot 

II.) ~lit )(M.Irt"C" of Cry3Bb 1. 
Ot com ,'aficti.:s an: predominantly field com. though severo I sweet com nnd popcorn 

uses have a lso been r~gi c: red . The rcsist.:red r,IP troits (Tnblc I) nrc bred into com hybrids 

\\ith gcncti.: bock grounds that h:l\'~ lx~1~ opti ~."d for ditTcrcnt com· growing regions. Other 

trait'\. including herbicide tolerance, nmy :1lso be stacked in the conuncrcinlly-::wuil:lblc: h)·brids. 

Growers h:l\'e widely :~dop cd Bt com in the U.S .• both for control of lepidopteran pest<; 

and com rOOt\\Orm. From 2011 to 2013 nn annualavcmgc of94.6 million acres of corn wen: 

grown in the U.S. Of these. approxim;ucly 70.6 million acres (75%) were plnnh:d to Bt ' 'nrictic-s. 

St.ttckcd hybrids. containing both lcpidoptcr:m ru1d rootwom1 tr..tits. were the most common and 

covered 49 million ncrcs (52% of all com ocre:sgc in 2012). Bt com products with only 

lepidoptcr..\n tmits were planted on about 20 million acres: when combined \\oith the stm:kcd 

varieties. a total acf\!'oge of obout 69 million acres wa<; {:rown \\i th lcpidoptcmn Bt traits. 

Rootwomt-only tmit.s were planted on less th:ln 1.5 million acres. gi,•ing a total of about 50 

million rootwomt-protccted ncrcs. (AcrcJg.: tig~s are rumual avcr.1gcs based on 201 1-13 

proprietary sur""Y dJUil). 

Adoption of Ht com hns steadily incre3Sed since the tirst nppro\'uls were grunted in 1996. 

In 2000 (prior 10 the rcsistr.ttion of root worm-protected Bt com). lcpidoptcrrut-prot ... "etcd com 

was grown on approximately 200/o of U.S. cont ac-res. IJ)' 2006. almost 40% of U.S. com was Bt 

(including room·om1-protccted \•aricties). With increased :wnil::tbility of registered st::tckcd lltld 

pyrrunidcd produclS. Bt com adoption reached 60% in 2009 (USil .'\ Economic Research 

St:r\'iccs data. sumrttllri?.ed in Womiak .:t nl.. 2013). 

SCIENT IFIC ASSESS\1ENTS 

A. l,roducl h~r:.tcl riz:nion and ltum:.ln HC':<h Assessmtnls 

The complete product chamcteri7..ation and hwn:tn hcnlth a..~s rncnts han~ been 

documented in the: Agency's ··Biopc-.sticidc Registration Action Document" (BRAD) for each 

rcgistcn.xt Dt com PIP. These I:JI{..\ Os ha\'C bc.--cn periodically updated to rctlcct new scientific 

infonnation and data reviewed os p.'ln of EPA's PIP reassessments (s.:c section IV of this 

document). All of these documents ore axailablc on-line: Table 2 cl d~ the citations nnd links 

tbr ~ch PIP ORAD undergoing r~s r:uion ~\ ic w. 

EPA· s procluct chamctcrization and hum:m hl!ahh risk n..~ess ment framework fOr Ot com 

PIPs is descrilx'<l in Kough & Eddslcin (2013) as well as in EPA's BRAD documents (Table 2). 

Since each PIP \\liS assessed indhidually for rcgisuation. this document will contain on I)' n 

gc:ncral summ:try of the- studies typically reviewed for PIPs und the O\'trall risk assessment 

conciLLo; ion.o;. 

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

~lr UK.AO Cil-.tlon ~utd or 

UP<101<d 

VipJAo20 

EftA, 1009. RiQ9tludJ<s Rt~istr.ation Actioo 0...."\Cumo:nt: R;,cllhu 

thuringiensii VipM.,20 ln}('C1ic:id.tl Protein itml the G~ne1k \t .:~tni:. l 

Ncce$.ury ror IL\ Produf:110fl (\'i.:l Elc:mc-nU of \'teh)r rNOV I J00) in ( \ tnl 

MIR162 ~biu (OI!CO Unique ldrntilirr: SY'N·IR 16:!-1), ;\\'llll3bk IU: 

hnn:t/www,Q'IJI. i:,(U:<'~,'!~nOOOO I 'chcm Gttb ti:X£ :tC'I oru.'r~hlllliJM dC'ci'io 

2009 

n PC~~?Q 1. (. 

£PA. :Oitb. Diopa.tlC'Mk Rcsis:ntion Actica J)o(wnC"n1: Cryll\b and 

C')•IAb. Cry IF Cry• If 8«/llt~• tJnul~t;:lnoiJ (6t)C«n Pllnt· loc-«pCQQN f'rc>t«Unl>. 2010 

AV2ibbk 21 ~P. (N,O\ 'N1.ticNol!~kidc-\ m~ m ·~ i lw>d.N!( 

EPA. 2010b. Riopc'UKkk RC't-i~ntion Action~~ (or Boriltu 

1bri"l:''""L• CrylUb I Pr\Xt!J\ and tbc Gcndic MJ.t«i.al N«es._\Oit)· (ot lu 

CryJDbl Produ<tion (\'«tot PV·Z~IIR IJL) in MO~ 86J Com (OECO Uniqut 1010 

ldcnt.ifkr. MQS.()0$6J.,) :u~d MOS &SOI1 Com (Of.CD Unique 

l<kntilkr: MON-IJ301 7·3) . 

h:tn;/,'\\WVI' • ' I '\llonM~i( <k~ trv3bbl·brnd n..l( 

E.PA. 2011k, Bl)tillu, t11urin sis CI)•J.4Abl and Cly3$Abl Procdns :~ d 

th~ G~netic !ltcri:al NtrtJ.\:ary for thc:ir Prod~~Cdon in F.\'tn1 I)AS·~9 22· 7 

Cry3 HAbl Com Biopt' ic d~ lh"ghlralion Action [)o..-umml ("RRAD), A\ ll.l ~blc ::.1 

hup::.'ww"',('NJ:_i'l\'lerrhroj J.'biopr)litidc;.r;n2Jrdi:roa.'lttb d«),bmd 006 

2010 

.QO.nd(. 

I:PA. 2010J. Rlopcshcidor R~).(f;)lion Anion Documrnt: MNtrl<'d Cl'yJA 

mC~3A Pro&C'WI Mid ~e Cmcu ~baf'NI ~~~ for thdr Product kin (Vb 2010 

Ekmm(.s off'l ... \1:!6) m J:., cnl MIR60.1 Com SYN-IR6o.t·S. A\ ~bbk x 

I hn~ \\~\\ tt\lL~ ~-:rkk:l h~~tc~~ mcnJ•wn:~r

EPA.2010r. O~JCidc Rq;lliWik»n Ad ion (}()cumtnt! ~ IA.JOj and 

Cry iA.IOS. Cry2t\b: n~ kl..W Prutttn\ 0111d thC' Gcn~ic M.lteri.ll N«nwr) for Th-eir 

CI)·ZAb:! Prod~ ion in Com (PC CoJn 006$ 1 S (Cr)!1Ab!). OOMI~ (C't)•IA. lOS)). 2010 

1\\'llil:tblc Ill: IU.!p:lLW\U't; n''iJ.¥(1\1 N'~iddp bjorotki~M msm=SQOJ:l· 

h<nd.nd(. 

EJ'A. 2012. On I\ Oio~, lc d(') R('gls,tr.ujoo Action Docu ~rtl : G:~cil us 

lhuringicn(i' eCryl. l1\b ins.«tkidJt ()(Ott in Md th~ .:mc:tic m:.tcri:.S 

c:Oyl.IAb n«tios.M)' ft.W iu produe1ion (\'i3 tkments of\·tctor PSYN ~7.&) in 5307 : 012 

C<'m (SYN· O.Sl07·1). ,\\-ailablc at: 

b!:! i!'.'o\4 ""' n:IJ:!ill nlc:m. ~ .'1• ~~umrnt Ocui!;Q- 1;,1' A ·II Cl:OPI'·~21 ~ · n1M.()()I0. 

Bt com PIPs :lie scncticnllr tronsfomu:d wing gc:n~'ti dcri\·ed (rom the bacti!Tium &C'illus 

Ilwrlu~it·ruis (13t). n grnm·)X)Sith·c boctt:riwn ommon!~· found in soil. Tr.msfonnation into the 

com plnnt scnomc is typicnll)' nccomplbht:O by ballistic means (i.e .. n "sene gun") or mcdintcd 

by lxu:terin (Agrobactt•ri~tm /JIIIlt:{tlt'it•,s! Rhi:obium rtuliobltrh·r). The tnmstbnucd genes cnc:oclc 

for prolcin soxitl.s. th:n spccilicolly nilCct either lc:pidopterrut (ca.sc 6SOI) or coleoptcr:m (case 

6S02) target pests. os t of the rct:;.b.tcrcd Ut r•ws produce crystal dcha·cndotosins (designated 

by lh< ··Cry"" prefix). Some ol'1hcS<: Cry PIPs 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). 

6 
Such PIPs nrc typically designed to improve expn:ssion in Ute com plant or increase ins.:cticidaJ 

ncti\'ity ngtdnst target pests. One rcgi.stt."n!'d PIP (Vip3Aa20) expresses a vegetative insecticidal 

protein (Yip). n group of Bt toxin_.. structumlly unrelated to th.: Cr)' proteins. 

EPA's product dmr.tetcriz:ujon nsscs.sm~nts have examined the nntun: of the PIP (DNA 

com1ruction). how the PIP is incorponllL-d into the com plant, and how the PIP is expressed in 

the com plan1. Spccilicnlly.rhc Agency has evnluntL'C.I the follo,\ing types of dam tOr Dt com 

PIP clt.ar.lctcri1.ation: 

• T ram:formalion system/proctss: Submiucd data hl\'1!' included u description of 

the plasmid n!ctor contuining the Plfl. ind udi11g r.:fercnccs to the strains of 

Bacillus J!mrinKh'llsis u.scd :15 the source of the DNA SC"qucncc for the toxin (l)r 

descriptions of the engineering process for chimeric proteins). In addition. the 

sources for marker proteins. promoters. tcm1inators and enhancers. as well as the 

frngmcnt si1..:, orienuulon and modific.ations to the: origim•l DNA scquc:nec have 

tx~n pro\'ldcd. The methods of insertion (trunsformation) into the com plant 

genome have also bec:n documented in the char-Jctcri?.ation datu. 

• Characrc:riution of the O!'liA lnscrltd in tht Pl:mt: Inserted DNA has been 

characteri1.cd with restriction enz)111C digest" and Southern blot datu of the DNA 

in the plant genome. The !Ulalysis usoolly consists of D>-IA isolmion from the 

translbnncd plant. digestion of this DNA with scw:nd Uiffercnt endonuckascs and 

ybritl ~.u ion of these restrictiOJl c:ndonuclcu.se frugmcnts \\ith Jnbdcd·DN:\ 

which is complemcnt.ruy to the introduced trahs. This nnllysis include.s not only 

probes spccHic for the entire insert. but also probes n.<>cogni1.ingjust the coding 

regions of tJ1c traits or DNA dements outside th~ codillJ; region. Polymcru.·•c 

chajn re-action (PCR) CLSS•)·s utilizing various sped lie and non·spccilic primers. 

genome wnlking. cosmid librories nnd DNA sequencing have also been employed 

\\i th scnsith·c Southern blotting techniques to more completely describe the 

inserted :U\d surrounding regions. Tile infonnation nvailnblc from these blots can 

indicme the presence of all the clements of the «::<pcctcd insert ns well as 

iniOrrnation about the possibility of deletions and her errors associated with 

DNA introduction by trnnsfonn.:.tion. Comparison of Southern blots of ge1lt>mic 

DNA. digested using a rnngc of restriction endonuclc::I.Scs. can nlso rcveillthc: 

copy number of the genes introduced nnd suspected linkage of the traits. 

Ahcrn:uively. the intensity of the rndio:tctiw label from bindjng the probe D>-lJ\ 

can nlso L"Stimatc the number of insert copies incorporJtt.-d in the plant ge om . 

When the inserted UNA con$tnJct includes troits expressed only in b;Jctcrin and 

not expected to be eN pressed in the plant. data have been presented to indicate that 

there is no transcription or translation of the bacterin] trait. 

• lnhtril.ancc and Srabilily aflcr Tr:an5formalion: The: dntn gcnen'ltcd lOr this 

endpoint hove cxrunin<d crosses lxtwc-cn sde<:lcd elite lines with the transfOrmed 

Ot «::<pressing linc. looking for the independent segreg~Hi 011 of the intmduct."d troito; 

in the progeny. Trnditionnl bl\.-cding work done: during the dc\·c:Jopment of the 

plant line by b:.ckc-rossing cnn rc\'ca( the linkage of the introduced trahs as well as 

change-s in trait expression. The inhcritru1cc dntn is the ratio of progcn>' cxpf\!'s.sing 

the hemiz.ygous tro~i t based on CXJX---ctcd lcndc an inhcritru1ce. St3hilit>' data hlve 

invoh·cd either an cxamin:uion fth~ <'XJ11'\'SSion of1hc: 1roit or lr.tddng the ON..-\ 

7 
itself O\'tt SC\tr.ll pl311t gmcrotions. Ont of the m3in concC"ms with subility is 

spontlnrous loss of the inscncd D~A or loss of cOkacy due to gene silencing. 

None of the Bt PIPs ha' e sho,\n indc:prnde:nt ns..~nm nt of the introduced troitS 

(the morkcr proldn Md the Bt protein wen: cxamin .. -d). This indittues tltlt the 

tr.aits ll.n! on the snmc chromosome and d osely linked (croSSO\'Cr cn:nts bctw«n 

the tmits Jmvc not tx:cn dctccu:d). 

• PI"Oitln Chllntclerb.nlion und Equh·alcncc: For llt Pll)s. dn1n hnvc been 

presented •o Jcmonstrotc th;at th~: protdn expressed from the inserted DNA is 

similar to wh:at was produced in the so urc~ Ut bactcrimn 'and is nctivc as cspcc:ted 

:sg.:a.inst tllC intcndrd tarset ins.."'tt. (For PIPs.. including chimeric \'oriet.ics. the 

protein u.~ for cOmJ'=Irison is microbi.:a.IJy·produccd b)' E. coli.) Some protein 

ch;trxteri~tion dat:. dcmOt\.\t.r.!.te th:u mierobi:ally-prodUC\.'<1 Bt protein i.s the 

cquh'Uirn110 dut cxprn.'<"CC in the plant This ;spp;t.rcnt scientific tautology (when: 

plant produced protein is the .s.vnc: ns microbb.J protein is the same :ss the pl3nt 

produ<<'<l proldn) hl\S been used 10 justify '"" .... of the microbiolly-produced 

protein ns u t substa.ncc in toxicity tests. Because the: -: ~pression lc\'d of he.~ 

proteins is so lov.· in plw1ts. a.nd the ma"(imum h37.:1rd do.sc ocutc orol toxicity 1 

is r~qu r~d as p:-~rt fth~ humnn health risk o.sscs..c:ment for th e~ proteins:. the 

ability to produce the protein in an industrial microbe is essential. Proper 

charnctcriunion of the cqui\'alcncy between these mit:robiaJ proteins and plnnt 

expr..--sscd proteins rmvidcs un altcm:.ti"c to purifying the ~1 mratcrinl as the 

plant produced protein from l:lrge \'Oiumcs of tissue. 11u: lcslS done to support the 

cquhoslcnce of microbial and pilOt-produced Bt protein hn,·c incl d~: molccuhlr 

sizing by SDS~P \GE and western blot :uuJrsis: immuno·n;ocognition using 

EliSA nnd wc::stcm blot M.llysis: N·tmniool amino acid sequencing; 

conlirm:uion of the lack of glycosyl:uion in the pla.nl·produced protein: and 

bioocthi'l)' O:gnin$t 3 mn~,;c of inscclS (often p.--st species including the tn.rget pest). 

These cqui\':tlcncy dotn hnve b..""Cn sencrntC'd for nll Ut <:om PlPs n;gisterttl tt) 

date. 

• l,rottin Exprtsslon : ·n1c Bt protein c:;(pression level in \'nrious tissues 

throughout the t:;rowing season has been dc:h:nninc-d lbr each rq!iStc:n.'ti PIP. 

These dDtn hB\'c. bC<"n dctcm1inC'd and prcscnlcd. in tenus of dry weight. as the 

runount of protein prcknl i 11 h:al: pollen. silk. stun:. se .. ·d (kernels). root tiS)·t u:, 

and whole pbn1. Data for protein xpre..~ on Ju,·c bee-n obtained using 

qu:mlilali,·c ELISA onal)·scs. 

• Anslytial Mrthod: 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<lhods are u.«d to dcl«t ror tho: 

pre~"'m:'c of the PIP in commerce. The nM ~1 cnl methods dc\'eloped for Bt com 

PIPs hnve b..-cn EUS,\ -boscd test ki\5. lndepcn<knl lnbomtory(lhird pany) 

valid:.tion of the r.USA kits has tx.-en rL"'qUircd. Pre,iou)ly, method \':tlid:J.tion 

wac; a.lso veri lied by EI'A 's OPI) MiCTObiology l nbomtory nt Fon M~dc. !-.·10. 

HOWI!\'Cr. EPA no longer condm:ts mcLhod vn lid ui s pro,,idcd lhDt the Grain 

Inspection. l'nckcrs ontl Stockyards Administnnion ((iii'SA) of the Unih:c.l St3tcs: 

Dcp:utm..:nt of Agricultun: (USDA) lw vcrifitd th~: pc:rformancc of311 

8 
appropria1c qualiLUi\C r.Jpid t~ t kit. 

The product char.lctcri7.alion d:Ua re-quirements for all of the rcg.istcred Ut com PIPs h;l\·e 

n sa1isti..."tt. Complete descriplions of1.he submitted :;tOOics nnd r~ u an! included in the 

llRAI>s for each PIP (Tobk 2). There :u-c currently no ouiSUndins chomclcri.allion dala gaps for 

nny of the Bt cont I'Ws. 

llum:an health reviews. ind udins dietary assc:.-ssmcnlS to suppon cxcmptiOilS frorn fooJ 

toknanccs. were conducted for ~cl\ Ot com PIP at the time of rcgistrruion nnd 'LS part of the 

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 rislr.. for Bt I,IPs.. SJ'l'I."Citic conclusions and d.au sumnuric:s for indhidual 

PIPs c3l1 be found in the comspondin~ BRAD documcm (Tobie 2). 

The blSic prcmist i~o.-d on for the toxicology asscssmcnb is I h.: fact lh::n all Bt PIPs arc 

JHOtcins. Proteins arc commonly fOund in the diet and, .xc~ 'I1 for n few well described 

plu:nomcnn. present little risk us u m:munaliln h»,.."tnJ. In ;1ddition. for the mnjori1y ot' Ut proteins 

currcmly rc,gish:rcd. the source l,.11.:tt:rium has been a e~d microbiol pc id.: which has 

been llflpRwcd for usc on IO<kl crops withom specific n:strictions. Occnusc of their u.sc as 

micro bini pesticides. ;l fong history of s.nli: u...~ is n.ssoci:llcd with m.:my Uc produces. 

Sc\·cmJ types of tlmu :an: rc:quin'tl tbr the Ot PIPs 10 dcmon.str.:nc 1h:u no unt{".lSOftlblc 

ad\ crsc cO--..-cts \\ill ~uh from the asg.rcg:uc: exposure to these proteins. The: information is 

intcndOO to :Jlow th.uthc Ot protein bch.:wf:S ns would lx c~J)\."'\,;h,.'\1 of a dicll.U)• protein. is not 

struclur.lll)• n:btcd to any knO\\ll food alle-rgen or pro1cin toxin. and doc. not displ:ly 3tlY oral 

~icity \\hC'n ::tdministeC\.-d ot hill.h doses. These dat:~. consist of an in vitro digestion il.SS3)'. amino 

acid >equcncc homoJOf!)' comparisons :Uld Mncute or.:al toxicity te:,t The 1.1cutc oral toxicity test 

is done m a nUl.\:imum hli.Zllfd dose using r urilicd protdn of the 1;11• ns :tlcst substance. Due to 

imito iom~ of oblnining sunicicnt qu!uUilics of pure protein tcsl sub:.:tnncc from the plant itself. 

m1 nltcrnath·c production soun.:c; uflhc protein is otl cn used such us lht: lJad llu .. f th ringh IJ s 

soun;c organism or an industrial fcnucntmion microbe. The justHicntion for employing this 

ahcm;ati\'c sourc" of pure pcoh:in is the cqui\'nlcncc d:lt::t discu.~scd ubow under r roduct 

charnctcri7 ... :n(on. 

EPA be lim$ lh:u prolcin in>tJJbilily in discsti,·c fluids 3l1d 11>c lad. of od,·cr.;e efT«:lS 

usins the rna.:<imum hxw.rd dose 3pproxh in genernl eliminate: the nc:cd for longcNc:nn t~1ing 

of 01 PIPs. Dosing of these anim:sh. \\ilh the ma.ximwn ha.zard dose:. along \\ith the product 

ch:Jrncterb.~uion d.at.:l should idcnlify potcnti:!l toxins J.Od :tllerg:cns. and rro"ide :tn efrccth·e 

1111..\UlS lo detcnninc the safety ofth~.-..c prOlc:in:,., The adequacy ofahc cun-cnl lesting requirements 

wus discussed otlhc JWlt: 7. 2000 Scientific ,\d,·isol)' Panel (S1\ Ij) meeting. In their fin.:t.l report, 

the SAP agreed in princiJ)Ic \\'ith du: methods used by EPA to n:r;sc.:ts lht: toxicity of proteins 

csprcss"d in Ill ants cspccinlly the IU:L'!imum ha1.nnl dose nppro:ad1. 

Dh•ffll')' Risk Clmructal:alltm 

9 
eien ifi c dntn und other relevant infonn:stion in suppOn of Bt com PIPs nnd considcn.-d iL;; 

vulidity. complcu;ncss ftnd rdiBbility. omd the relationship of this infom1ntion to human risk. 

El)i\ hus ;tlso considered "' 'oil!lblc infonnntion corlccming the vnriability of the sensitivities of 

major jdi."ntiti:tblc subgroups of eon~;umers . including infants and children . 

.\lum,wliwt T oxiC'ity mul Alltrgitliciry Asst.umml 

ut~ ornl toxicity studic!' have bc:t n ub iu~d for ~:ach r~: cd tlt com PIP. These 

studies h:we shown n lack of m:umn;tlian toxicity m high lc\'els of exposure to the PIP proteins 

ond dcmonstrntc snfcty nt lc\'cls well :1b\wc the maximum XlS..~; ib c exposure lc\'d s that arc 

reasonably Unlicipatcd in c.:om. :L.~ nlllhesc: conclusion..s on Dcutc ornl tos:icity dnta witllout 

requiring funhcr toxicity testing :lnd residue d:l1.0 i~ similar to the: Agntey position 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 dcrh ·ctl (thi!' microbial ~iduc nnd toxicity d.,la requirements a~ 

detailed in 40 CFR §§ 158.21 30(d)( I )(i) :md 158.2140(<1)(7)). 

When JUOtcins nrc toxic. they arc known 10 oct vln acute mechanisms nnd at very low 

dose lc\'cls (Sjoblod et ::tl •• 1992). Therefor..!. since no cff"Cl~ were shown even at reJati\'dy high 

do_..:c le\·cls, the PJP pro ein.~ are not con.sidered 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. 

Sine-: nt f'Ws a.rc proteins. ollcrgcnic potent in I hn.c; also been Ci d~r-.:d . Curn.:nlly. no 

definitive tests for detenninins the ollcrgcnic potcntinl or 110\'Cl proteins exist. nu~rdore. Ef' A 

h:1..10 t&.'<.l n wcigh -of idence oppro::.ch where the foJI \\ ~ factors 3rl! cOI\Sidcn-d; source of 

the tr.~it: nmino acid sequence C{)mparison " ith known allcrscns: and bioche:mic::tl propcnics 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 with the appro3C'h outlined in lhc Annex to the Code~ Alimcntnriu."< 

.. uidelin~ tOr the Conduct of Food Sai'Cty Assessment of foods Dcri,·c:d from Recombinant 

DNA s.'"111~ allergcnicit}' ss~o--ss t for Bt com I' ll's clud~:S : 

• Source oft he uait Bacillusthuringh•n.ds is not considered to be o. source of 

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 contiguous nmino acid residu\:'S. 

• Digestibility. PI I' proteins have be<:n :.;hown to c:s t rorid · under gastric 

conditions (i.e .. s-imulated gastric lluid containing pepsin). 

• Gtrcosylation. PIP rroteiJtS cxprc.ssc-d in cCim h:l\'e not been shown to be 

slyCOS)'IatOO. 

• 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. 

10 
In examining 3ggrcg.:ne exposure. EPA t:Onsidcrs ;.wail able intOnnation concerning 

c:;'\posures from the pesticide residue in fOod und nil other non·occupational c~po r~. including 

drinking water from ground water or surfucc w:ttcr and exposure through pesticide usc in 

gurdcns. la\\115, or buildings (re-sidential and other indoor uses). 

The t\gcncy has cotLo;idcn:d uvailnblc infomuuton on lhc :1ggrc:gatc exposure Jcvcls of 

consumers (and major identifiable subgroups of consumers) to the P'o-'Sticidc chemical residue nod 

to other rel:ucd substances. These considcnuions include dietary exposure um.Jcr the tolerance 

exemptions in e-OL--ct for the dues of the f-ll)s, and expOsure from on~occupati onal sources. 

Exposure via the s kin or inhaJation is 110t likely, .since PIPs arc contain'-'C:I: within plont cells.. 

which essentially climin:ucs these e.xposurc route-s or 1\.'C:I:uccs these expOsure routes to neglisiblc. 

In addition, even if exposure can occur through intmlntion, the potential tOr a Bt con1 PIPs to be 

an allergen is low. ns disclt.'iSCd :.bow. Although the aJicrgcnicity a.~:;se:ssments have fOcused on 

the potential tOr tbod (IIJergcnicity. the data ha\'e ~o indk:ucd n low potential for PIP proteins 

to be inhalation nllcrgens. E:~Cposure to infantS nnd childn:n via residential or lmm usc is not 

cxpech."\1. lxcmLSC the. use sites for Ot com PIPs nrc agricuhuraJ. 

Oral cxposufl:. at \'cry low le\'ciS. may occur from ingestion of proces...~cd com products 

and. theoretically. drinking water. Exposure is nt low levels due «o the amount of PIP protein 

1ypically expressed in grain (a \'Cr)' smuJI percentage oflhc total protdn) and steps taken during 

com processing th:u likely further reduce the amoum ofPlP protein. In addition. oral toxicity 

testing in mnmmals showe-d no :.dvcrsc ctli:cts. Furthcnnorc. lhc cxpo..""Ctcd dietary exposure from 

com is severn! orders of magJlitudc lower than the ou ~ of PIP protein shown to have no 

toxicity. l11e-reforc. cn:n if ncglisiblc aggregatl!" cxpOsun: should occur. the Agency concludes 

that such e.xposurc would present no h:mn due to 1he luck of mammalian tm:icitr nnd 

allcrgcnicity dcmon$troted tOr Bt com PIP proteins. 

Cwuulmire £ffi·cu 

Se<lion 40S(b)(2)(0)(\') ofFFDCA n.-quires I hal. when considering whelher 10 eslablish. 

modify. or rc\·okc a toler.tn..:e. the Agency consider -available infomtation·· concerning the 

cumulmive ciT~'\':ts: of a panicular P'o-""Sticidc"s residues nnd "'other substnnccs th:u Juwc n common 

mechanism of toxicity:· 

Since Bt PIP proteins arc not considcr'-"'<1 toxic and do not sh:ttC a common me-chanism of 

toxicity \\ith any other sub$l!lnccs. EPA ha.s concluded that then: urc no cumulutivc: cOCCI$ 

a.ssocime-d with Ot com PIPs. 

FFDCA section -l0S(b}(2)(C} pro\·idcs that EPA shall a~scss the 3\':tilahk intbnn:nion 

about consumption patterns among infantS und children. spec: in! susceptibility of infunts ;md 

children to pesticide chcrnit:1l resid ues nnd the cumulnti\'C effects on infants and children of the 

rcsidul."s and other substJ.nccs \\i th a common mechanism oftoxicity.ln :lddition. FFDCA 

~c on -lOS pnwidcs chat EPA shall apply an additiorl.fil h: nfold margin &.'1f c:<posun: ($0fc:ty) for 

II 
infants :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 children. 

For Bt com PIPs. b.'t.~d on nllthc U\'ailablc informntion. the Agency hod concluded th:at 

there is no toxicity. Thus. then: llf\! no thr\.""Shold cfl't."(ts of concern nml. O.'i a r\:'suh the provision 

n;;quiring an additionul margin of s.a.fct)' dOC's not apply. un . the JUO\'isions of C:(ln.wmption 

IX'IIU,·ms. $J>Cdn1 susceptibility. nnd cumul:uive eOCctS do not npply. 

E.xposun: ,;:t the skin or inh..1l:~otiun i~ not likely sine<: PIPs 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 10\\' a.mount of protdn C'Spn.":SSCd in trtlll5(orm<."<f pfanU. ff S\ICh exposure Should 

0\:cur. the Agency tondudcs th.'1t it would not be CXP'o---ctC'd to present :tn)' risk due to the lad:: of 

to:<idty. If nny unreasonable udvt:rSc crrccts c.auscd b~· exposure to Ot com I' IPs arc identified. 

these cll'h ts mu.•::t ~reponed to th-: 1\ scncy ns re-quired by ~cc. 6(nX2) oCFIFRA. 

J, lluma n lncidl!'nts 

An initial iiKidcnt searth wJ.s conducted was conducted on ,\ugust 17. 2015 for this 

n:g,istr.llion review. One Dt com 1'111 im:idcnt (1021901) w:lS identified in the Incident 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 etll'Cts 

rrom inhulntion exposure Bt com du.)t. Since most com seed is tn:atl."<l with pesticides other th:tn 

I h. it is more likely tlw.t the response \\otS to an nddOO. conventional chcrnic~ll used to trC'!tt the 

seed. Uni\!S$ the tatntcr wus sh0\\11 to have ingested the com sc~."t. (h gh y unlikc:ly). it dOI!S not 

3JlJ>car to be tl I'Ood poisoning or nllcr.,;ic ti.!'Jiction to Bt proteins. Since this: case was not likely 

rclot .. -dto Bt. there is not n concern ot this time boscd on the continued low frt.•q uency of incident 

c:,:!>c.:S for Ut com PIPs. 

Food colcr:mccs cxcmpcions for ~~: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 

established for nucleic acid~ th:u nrc patt oft he PI P (i.e .. the encoding genetic m~ltcri al). In 

:1d~ ition. no nlll.ximum residue limit.~ (MRls) for Ot com Plf's: h.wc been c!otablished by the 

Code:< t\l imcnto.ritL~ Commission (Codex). 

12 
Tablo 3. Food Tol<r:mcc E.wmplions EstJ>bli>ll«< for 131 Com PIPs. 

Ill rlr (toxin) Toltnon« Cilotion 0 CFR) Crop• 

Cry lAb § 174.51 I all crops 

Cry IF § 174.510 com 

Cry313b1 § 174.518 con1 

Cry34Ab I/35Ab1 ~ I 74.506 com 

mCry.J,._\ § 174.505 com 

CryiA.IOS § 114.502 eom. c:ouon. soylx.Jn 

C~2Ab2 § 174.519 com. cotton. soytk.~ 

Vip3A:ll0 § IH.SOI com. conon 

.C~ 3.1Ab § 174.532 com 

S. D11tn Needs 

Th<:rc nrc: currently no idcruilk-d ~1t~1 gaps regarding product chornctcri1!1ti,)n or hum;m 

hcahh for :my of the rcgisrcrcd Bt com PIPs. 

EPA has ronduct.e-d cmironmcnul risk 3.SSc$..Wents for the Bt PIPs expressed in com. 

Gencr..J topics co,·crcd in those D...\.<4,..,.~rnc:n1s include effects on ''ildlifc. gene tlow 10 rcl:ued ''ihJ 

pJ:mls nnd its poten1i:tl eni."ClS. and fate of Cry proteins in the .:m·ironmcnt The assessments arc 

b:J.scd on d:ua submintd to EPA during h~ development of I'l l> com lines {i.e .. Experimental Usc 

Penn its). ndditional data submilh.'tllhr r<gistmtion. federal Insecticide Fungicide ru1d 

l~l c:n icidc Act (FIFRA) Scicruilic Advisory Panel (S:\P) n:c n~wJ ui on~. consultations with 

scicntilic cxpcns. and rublk conunc:nts on llJP n:guJ3dons. 

Spccilic cm·ironmcmal a~ ~mc:nts for indi\idual PIPs can be lbund in the BR.t\0 

documents !'Or c;lch PIP (Tnblc 2). This s«tion contains a general summary of the 

~nvir nmcntal risk assc:s.smcnt p.11"3digm nd conclusions for 01 com PI~ u.s a group. 

EPA uses o tiered (Tiers I-IV) <c>~ing S)'SI<m ro asso:ss lh< <o, icil) of o PIP 10 

rcprc.scntativc non-target organhms th:lt could be c~;poscd to the toxin in the field cn\ironmcnL 

Tier I high dose stuUics rdlC't't u screening appro:Jch to testing d-:signcd to n\3..\:imizc any toxic 

~ffects of the: test substance on the test (non-target) org.:tnism. '11H.' scrc:cning h!'Sts evaluate sin1;1<:· 

Sf"'·:cic:s inn laboratory selling with monolity as the end point. Tiers II - IV ~c ncrnlly encompass 

dc:riniti\'c haz..1td level dctcnninatitlns.lc.lllgcr tcmt gre-enhouse or lic:ld testing. and are 

implemented when UIU.'lCCCJHilblc: c:llC.Ct.s nrc seen at the Tier I scn .. "Cning lc:\'CI. 

·n.c tic:rtd h3ZJJ'd assessment ~lppro"''-=h was dc:vdopc;d for the: EI)A by the Americ.an 

n~titutc of Biolog.tc:s.l Sciences (AlOS) :md confirnted in l996 as an acceptable method of 

13 
cnvironmcnt:tl luv.,ard assessment by n FIFRA Scientilic Ad\'isory Pnnel (SAP) on microbinl 

pesticides ond microbial toxins. The D«cmbcr 9. 1999 SAl' ugrc.;.'<l th.at the Tiered nrp o.:~.ch wns 

suitable for uSc.• with I}IPs: hoW1!\'Cr. this panel n."Commtndcd thJL for I'U'~ with insecticidal 

rropcnics. i.lddition:alti!Sting ofbcndkinl in\·ertcbr.ucs clo~ly related to 11.1f!;ct species :md!or 

likely 10 be prescn1 in GM crop fields .should br: conducted. Tcsling of Ut Cry prolcin.s on !Opc.--cic-s: 

not closely «loh:d to the target irb4"C'l pest \\';15 not n:commendcd. although il is still pcrfonn<d 10 

fulfill the publbh1:d ErA oon·t:trgcc ~pee: its datn requireme-nts. ln October 2000. nnothcr SAP 

also ~commended dun lield testing shouh.l b.: used to C\'nlu •. 'ltc popul:uion-lc\·cl dlC=cl;; on nonturgc:t orgnnisms. The r\ugust 2002 SAP. and some public comments, gcncrolly ngrccd with this 

approach. \\ith thl! uddition.al rcronuncndation that indicator organisms should be selected on the 

basis of potcmiJ.I for field exposure to tht subject protein. 

lkln~cd Ddn:rsc cff«ts :.nd!or occwnul:nion ofloxins through the food chain 3rc not 

CXJX"'-"'tcd to result rrom exposure to Bt PIPs.. o.nd these proteins o.re not roulintly tcSh .. -d for 

chronic efli.-cts on non-tnrgc:t orsnnisms. Howc:\'cr. the jO day test dur.uion requirement for most 

non-target studi1.o.s d01.--s a mount co s.ubchronic testing \\lien pcriOrmcd nt field \!Xposurc tC)i 

doses. Proteins :tlso do not bio:tccumulntc. The biolobical nuture of proteins mnkcs them readily 

susceptible to rnctnbolic. micro bini. nnd obiotic dcwad:uion once they nrc ingested or excreted 

into the cnvironmcn1. Although 1hcrc arc rqx>rt.< th:lt some Cry protein." bind to soil panic!!$. 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. Em·ironmenlal Esposurr As,jt~~ mc-nt 

EPA's: risk ttSSCSSmcnl~ tOr Ut com PIPs haw hccn centered on nd\'t.:r~ cni..--cts nt the 

field c.'<posun: rates. which \\"t'rc tyricatly based on protein expression lc\·cls \\ithin the plant for 

PIPs. Although it is recommcndc<l that non-"'S" tostin~ b< conductc<l >I>ICSI dose lOX the 

EEC v.hene\·cr possible. I he: test dose margin can be ~ llun lOX \\'he-re uncertainty in the 

system is low or where high concc:ntnuions of te-st mntcri:t.l nrt not possible 10 ochic-\'C: due to tC'St 

orsonism C:cdin~ h:t.bits. For the purposes of the non·tmgct o~:..nism (NTO) dics submiucd 

in support of the tcgistered llt com PIP.s.lhe test m:ucritd dosc lc\'CIS hll\'C hc:cn based on the 

c-Stinu:ued conccntrntion of the JlJI' inse-cticidal protdn expressed in the tissur(s) thot NTOs 

would most liL:dy be exposed to in the em·ironmcnt. 

Two scparntc SAP n:pons (October 2000 :>nd Ausust 2002) rt<.'ommendc<l lh:!t nonUtrgcttesting of Bt Cry proteins should focus on in\'crtcbrate spcric-s expo.sal to the crop be in~ 

~s stcrcd . Following the SAP rccommcnc.Lations. El)t\ dctcnninc-d thi.lt non·tm~ct organisms 

with the gre:l cs ~.:sposu e potcntinlto Cry protein in tmiUJ;cnic com fields nrc beneficial insects. 

which feed on com poJicn nnd n.;.-ctnr. and soil invcrtcbr.ucs. particularly Colcoptcmn 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:misms can Ottur nnd tw: required t~"'ing on 

n."Presenuti\'c species (summ3rizcd in lhc 01:S:t section). 

In the ''bscncc of PIP·spc:ci lie risk assessment guidance. EPA rcquin:s tlJ'J,Iic:mts for PIP 

~gistrntions to mc-ct the 40 CFR P~•n l 58 dau requirements for nicrobi:llao~ins (§ l 58.2150). 

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 risL G.'-'C~'mc:niS has been on 

bc:nciicinl non-urgc1 im·cncbratcs. sinct: they arc most closely rel:ued to orgunisms susct"ptib!c 

ao aha: insecticidal action of Uttosin.s. In uddition., carthwonn o.ntl Colkmbola (springtail) studies 

h.I\'C' been submiucd to the t\gcncy 10 t\$CCn(lin the: potcntiul ~IS of Ot inscctjcid:ll proteins 0 11 

tx:ncficill decomposer species. 

l11c October 1000 SAl:; recommended that while m;tual plant matcri31 is the preferred h::,t 

nu:ucrinl. bllctc.:rial-<lcri"cd protdn is nlso o valid test substru1cc, particularly in scenarios where 

1~1 animals do not nonnall)• con.:mmc pl:tm tis...c;ue and " heft' l:lrgc amounts of Cry protein (i.e .. 

Cry protein conccotrJtions lhat cxcc.:U lc:' ds prt"Scnt in plant tissue) an: n«dc.-d for mo..ximum 

hrvnr\1 dose testins. Test 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 into lhc h.·st spt-ci .. -s dir:t. For all of the 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 nctivity TO those: derived from riBnt sources. 

A s:ummnry o ft he- n:~ a h<~ t hl\'C been C\'a1U!lted for the rq;istcn:d llt com PIPs is 

dcscrib!o.--d below. Sped tic results und cnd!X'ints for c-nch NTO an: sunun:trizcd in BRAns lbr 

C3Ch rcgist<rcd PIP (Tobie 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,·crsion. :md c:trc3~5 ~icld . Results from •h~ broiler Mudir:l!r> h:l\C shO\\n no trrotntcnt· 

rcl:ucd ditlerenccs. indicaaing th:ll IJ1 nnd non-!11 com arc nulritioni'llly cqui\':tlent. Relath·ely 

long-tcn11 \Jicuuy c:~posurc to Bt f'llls is not cxpcclcd to result in ad\'l.'noe c11\.--ct'\ to birds. 

A\'oin orol toxicity has been C\'Oiu:uOO with the Nonhcm bobwhite quail (Co/inus 

l'irf:hrlum~). Studies ha,·c either been dk l.nry (using Bt grJin incoi}XIrrucd iruo diet) or with n 

in lt or.t.l dose. No monoliti(.'.:, or ndn·111c dl'ccLS were obscrocd in tht;."SC :;;wdies 

"''ian inhalation 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 is considcn.-d likely: however. nt..'Ullm;~linn 

tc.lxicology infoml:ltion g:uJu.•r~;.'\1 to Jolc on Dt Cry proteins docs not ~how :1 h:ll.J.!d to \\ild 

mammals. In nddition. ocutc ornltoxicity studies submitted to IW1\ in SUJlJ)()n ofth ~ Bt con1 PIP 

rcsistrotions indicated thot no .s gn ficamtos icit · wns seen when rodents were c.xposcd to Bt 

I)COtcins nt ma.ximum haz.nrd Josl.! level:.. 'l11crcforc. no haznrd to m;unm:alian \\·iJdlifc is 

antici(XJlcd nnd dat3 on wild mummal te.sling hns not been rl'<(Uir..:d for rl.!~i.s ro ion. 

IS 
Aqumfc S{Wch:s 

Fn:-shwntcr tish toxicity has been c\'aJuatcd in tc:-,sts usingju,·cnik chnnnel cattish 

(/cwlurtLf puncwuu) or rninbow trout (Onchorl~•·ncl s m,l'kiss). In 11 fi!w cnscs (Cry I A b. 

CrylA.IOS. Cry2Ab2) ,,':J.i\'CN were: &r.lntcd from conductins fn.""Shwatcr thh ~udies based on o 

presumed lack of c-.\:posure of Bt com in ttqll.ltic- S}"Stnns. In all but one of the: f~\\':llCf fish 

Mudies conducted. no mortal it)' or sublcth31 cfll.""CU \\"ere obsc'n ·ed in~ Bt lrt'atmcniS (o Sludy 

conduct«! with mCry3A had n s:i l~ mortality in the HHrcatcd group but no other adverse 

ctlCcto;). Gh·cnthc ~suits of these: studies D.nd low nquntic exposure. no freshwater tish haz::ard is 

cxpcch .. -d from c:ommcrtial cuhi\'Otion of ~;urrl!ntly registered Ot com I"' IPs. 

Toxichy to (~water ~u:t.tic in\'c:rtc:bn:ucs h:u be-en to1ed \\ith Dnplmia magna. 

Studies \\t:fC conduclcd as ~8 hour) static mlt:W:tllimitln:ls \\ilh Bt pollen. since this com 

tissue is expech."\1 to most likely to be p~scnt in r~h \\"'..ter. Though no signiticant effc:clS w.:rc 

observed. the ~lS were tbund to be un:xccptablc bC'c.IUM! it Llkcs mon: thnn 42) hours for the 

target pests to SliC.:CUtnb co Bt proteins. In considcmtion of this. and a publi h~,"\1 rl.'pon (Rosi· 

Marshall ct al .. 2007) of lld\'CI"SC cO"ccLs to cmJdistlic-.s exposed to Dt com liHc:r. EI)A mp,.1ircd n 

7-14 Daphnia tud y (or 311other fn:shwater in\'Crtcbmtc r~;."prescnting the (un~;tional sroup of n 

leaf s.hr..'<ldcr in heodw:uer <1n-:uru) for each resister«! PIP. Subsequently. other published 

litc:rature ro.iscd conccms with the osi-~ ;ush:tll s1udy :md sugscSl4"<1 t:h=u the accuaJ risk to 

cOOdistlies w:1s much lower. ~ a n.-suiL EPA no longer n.-quiml additional oquatic in,·ertebratl.' 

studies to aM~es..~ ha7..ruds forC"xisting Ut protein PIP n:~htrations. Before EP,\ wai\'ed lhc 

:tdditional m1u;uic invcncbr:uc tcstinM. two studies were ubmiHetL lllc first. n 7-14 day 

Daphnia study lor Cry I A. l 05/Cry2Ab2. showed no tllliCt\Sotmblc adverse ci); • ..:ts (EPA. 20 I Oc). 

ThC' second ll..~ conducted (or cCry3.1 Ab \\ith a k:1f shrl"<iding fr~o·• hwnter iwpod. Gommarus 

fusdoms. :md also indicated th:.1t no ud\·crsc d)'i.'Cts :.uc expected for fn-~m'Atcr invcrtcbmtcs 

(EPA. 2012). 

No sit:;niticant dirccr cxpost1n:s o( e.o;twrinc t'lnd marine a.nimalo; to Ut PIPs are nnticipo.tcd 

a...; a r~sult of ngricuhurol production of Bt com. A such. studies \\ith •:taunrinl.' and/or mnrine lish 

nml irwcrtehrnh:s ha\'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 plants in the ttnestriill Md aqUI.ltic 

en\'ironments from Bt cum I'll's nrc not exp<."CteJ nnd testing has not txcn r\--quircd. 

Tt·rrcMrla/ lnwrubrmc·.~ 

..-\s previously discussed. EPA ·s assessment on ntm--lM£:et in\'Crtcbrntt"S htt..; 1Br£,ely 

rocu....'C'd on hcndiciol ins«l sp.--cics for \\hich C.'IO'posurc to Bt com PIPs c::m be c."p«IC'd. Some 

Bt PIPs (CryJilb I. Cry34/35. mCry3i\. <Cry3.1t\b) SJK'Cificnlly tnrg<t com root worm spc:cics. 

\\ hich :u-c \\ilhin the order Colroptcnt (b..--ctles). Sc\'cn:al of the 1'\.--quirOO tests indudes bt."'t'tlc 

~~ics. since it is cxp«ted th:n these spcdcs will be most swccptiblc to the Ot toxin. The 

toxicity of indi\'illual Bt PIP protdns has been c\'ttluntcd with multiple S['l.'cii.'S ofin"cncbmtcs 

including: lady beetle (Coh•omt ~:llla maculato. 1/ippod.,miu com•trs,:Ms). cnruhid 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), pimtd flowcr bug (Orius insidioJif:), pJ~USilic \\'3Sp (Nasonio 

\'{trfpt"tmis, lchnrumon promiJ.JOrho). colkmbola (Folsomlu c·tmdida). honey~ (Api.s 

mc·llifi·rll). and carthwom1 (Eisenlnfi•tlda), ,\dditional esting ''~ nlso done 10 ftSSi!'SS the 

toxicity of some Bt com PIPs to no1Hnrgct lepidopteran {mon;t.rc-h buucrllics}. 

No significant ctl(!oc ts 10 lotlr beetles haw been obscn·cd in lcsts with Bt corn PIPs. 

cxccpl for Cry34/35. Submillcd dntu showed thlll Cry 3-1/35 protein wn.s toxic to C. nwculma 

larvnc ot do~ levels that cxcc~o-d licld t:,..:po.smc (Tier I Assay). ltowc\'t:r. since toxic cti:Ccts wcr~ 

not Sl:<n ut the field dose lc\'cl in '' Tier II r\.s.s:Ly when C. mCicttlululurvn<." were fed n.:uu.t'3.l prl.!y 

and pollen. it is highly likely that CC)·J.aJJS com \\ill notnd,·crscly 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 (rom 

CC)·J.a/35 (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< EI'A 2012). 

Testing ,,;th other non•tut);CI inSC'Cl5 (prcd:uory bugs. r~en laccwi ng. p.1.r::lSitic 

hymcnoptcm. and collembolu} has not sho\\n sis,niticant dvc:r~c c:l1« ts nmong nny o( lhc 

registered Ut com PIPs. (Note: lltL!<ed on guiUunec (rom the 2002 SAP. testing with Ni.L\'Qn/u 

rip~·nnis and green ktccwing (CIIt)•.-:opt•r/a carn.:a) w:l.'\ di continu~:.'tl )incc both were 

dctcm1in~d 10 be in ppropriatc ten SJX"'(ics. (ir~;.oen lo.;cwing has been replaced 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 saudics o.ndlor whole hiw 

(~mi-iidd) 1ests. \cceptablc 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:vclopmcm. B3.SI.""'Ci on the re~ults pn!)Cnlc:d in thC'SC' studies. 

OPPO h.ns concluded th:Jt honey bee de\·elopmcnt ;snd sur.tlval nrc nol aflC:-ctcd by exposure to Bt 

C(lrn Jl()llcn. In addition. since com is wind pollinated and com pollen is not o major p.:ttt of the 

honey bee diet. exposure to Ut com pollen is CXJX'Ctcd to be incidcntlll. 

Ennhwonn toxicity lcsaing lw.s been conducted using nrtilidnl soil studies. These feeding 

studit:S h:'l\'c dcmonstr:ttcd th11t Cr')' JlrOicin..'l :an: not toxic to carth\\OmlS at worst-cnsc 

c:m•ironmcntnl concentTJ.tions "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 hunerllies ({)umms p/rxfppus) (documented in EPA 2010l), EI'A n..-quin.'<! n..,;istr:lnts to 

conduct rcscarch 10 address iivl! b:uic are:a.~ relating to the pc.Hcntinl c~posun: of non·Hugct 

kridCiptcr:ms. pmicularJy rn on.orch~. 10 llt com poHcn. These includC'd: the distribution of 

monarch buttertlies. milkwt"Cd J'lunts nnd com: com pollen rdensl! nnd distribution in the 

crwironmem: toxicity of 01 com Cry proteins and llt com pollen 10 ICI'Iidoph.·rons; monnrch egg 

lnying ond (e(.'tling behavior; and tt~ h population monitorin.:. A ..S:11 n c:~ll·i n (DCI) nolicc 

was ~o;; ue:d on December 15. J999 tn the rcgi, tnlnts of(r)•lt\b com. 

17 
EPA's rl.!vicw of the ~ubmittcd data (described in EPA 201 0:1) showed that Cf')·tAb hns 

rcllnivcly low toxicity to monarch hlr\·ne nod the Cryl F protein has no dc ~,~tn c toxicity w 

monarch lnrvnc. 0\'crall. the nvnilnblc infonnntion indicates u ''cry low probability of risk to 

monarchs in nrcas beyond the nC"ar edge of com fields. Inside com fic:Jds and at the ncar .;.-dge or 

C'Orn lidds there is low prob3bility of morun:h IM\'3C encountering a toxic le,·d of pollen for the 

registered kpidoplcf'3Jl Bt com products. The \\eight of cvidctlfX of cbu g_.Jthcn-d to stud>' the 

cO'ecL.; of Bt pollen on monarch lan'OC in the field indicate lh:t.t miU;wcxds in com fields to 

within 1 meter of cornfields nrc unlikely to be dlL'itcd with honnful rcn:-ls or Ot rollcn from du: 

most ''iddy r lnnh.-d varieties of Cry I Ab or Cry IF com. Considering rbctors limiting esposurc, 

such ns relnth·cly low roll en .shed nnd monarch brcr:ding overtop in much of the Com Bdl. the 

distribution of milkwe-ed plo.nlS \\i thin com fields compo'f't'l.l 10 other mi kw~,-cd habilats. the: cg~ 

b~;ng and r~.. .... -din~; octh;ty of mon:rn;h ltU"\':l.e. toscthcr \\ith the Jow toxicity ot'the Ut com PIPs 

iodic,:,tc nlow proOObility for ad\c:rsc ciTccls on mOIUtt'h 131"\"nt'. 

D:t..;;.cd on the rc:'iew of the submiueclDCJ doto, in combination " ith other data gcnc:mtetl 

since 200 I. the Agency has on uJ~,_'(! th.at the: curn:nt inlbnnation on rnon.:m:h to~ icily and 

exposure. docs not f:ivc sut1icicnt ..:ausc for undue concern of ,,;dcsprc:td ri ~ to monnrch 

bullerllie.s ntthis time. Addition.:tl tcsting with more recently registcn;d PH' tnliL4; (Cry t t\.1 OS. 

CI)·2Ab2. and Vip3,-\320) ha.~ not lx-cn rcquin.""<J. Uowc\'er, EPA "ill continue to closely monitor 

the results front furthe-r roon:s.rch butterfly resc:treh n.~ a JW1 of its regubtory O\'tr.tiB}ll of Ht com 

PIP product>. 

Since the commerc-iali;,r..ltion or Bt c-rops. 1hc num~r oflic:ld studies published in 

scientific li1c:rn1urc in combinJtion with the poS1·n"};iStr.llion ficJd studiC'$ submil1l-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 

iSSlle oflong r.lnl;C cff«u or cuhh"3tion oft~ Cry proteins on the in,·cncbmte community 

structure in Ut crop fields has sincl! been odcqu:'Ul!l)' addr\.'".s.scd. Sp«ilicnlty. a mcta·analysis c.f 

the datn collcl.!h."\1 from 42 field studies indicated th;1t non·tnq;ct in,·crtcbnuc:s nrc ~,;c crnlly mon: 

abundant in Ot couon nnd Bt maize fid ds than in non·tnmsgenic llclds mnmiQ'->tl with 

inSt"Cticidcs (MtuYicr ct al., 2007). In mldition .. n comprehensive re,•icw of short ond Ions tcmt 

field ludic~ on tltc cffeca.s ofin,·encbrnte populltions in Ut com and couon 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<· 

scale studies in ~;ommcr l Bt cotton h•wc not re\'c:tlcd :my unexpected non·taq;ct c: O~cts other 

than subtle shins in the arthropod community .auS~;.'(I by tltc ctTtcth'C' control of the targ\!'t pests 

(R<tmris ct ttl .. 2006). Slight reductions in some inn rtcbnah! prc:dntor populntiolt.'i arc an 

in-c,;u,ble result of all pcSl mrutngcmcnt proctices, which result in reductions i11 the abundance ot' 

the j.X."'StS as prey. 

0\'emll.lhc Agency is in a~-ment \dth t.hC' conclusioru; of these ~•udics and 

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

tcnn cn,'ironmcntnl cntcts on :t population I<!\ ~ I to or~oni :sms not urgctcd by Ot proteins. 

18 
Soli Fort• 

Soil org:misms may be exposed to nt PIPs through contncl \\ilh corn roots (by direct 

(Ceding). plant root exudates. incorporotion of ubove·ground plant tissues into soil tbllO\\'ing 

han·cst, or by soif·dcposited pOllen. Some e'idcncc susg.:st-. th:u soils th:.u on: high in clays and 

humic :1cid.s an:- mon!' likely to bind Cry protein. Howcn•r, neutrul pH soils tend 10 h~\'C high 

microbial activity and microbes contribute 10 Cry protein Uc:grudation. In nddition. a study on the 

rcl..:-a.sc t)f Cry proteins in the root cxud:atc.:; of Bt cotton has sho\\n th:H no Cry pwteins were 

d.:t'-"Cil:d immunologically or by larvicidal assay in any soil or hydroponic solution in which Bt 

cotton had bt.--cn gt0\\11 (Sa.xcna nnd Stot7.ky. 2001). The weight of evidence nd c~ucs that Cry 

proteins do not accumulnte in soil to nrthropod·toxic lc,•el.s. lh:c.ausc Cry proh:ins arc toxins 

derived from soil·inhabiting baeteria,/ktd//us tlwringiensis. lhc dcgrodation of these toxins from 

Bt com PIPs is expected to be similor to that of these protdns thn.t are pr()duc,xl n:1tumlly from 

soil bacterin. 

To fun her confim1 these rcsull$, EPA hl1s n-quircd the soil fate cvaJuations to support 

n:gistrmion. These studies hnvc: mci,sUrl-d the r.Hc of degradation (DT) of Ot PIPs in Bt·infuscd 

soils \\ith tl~rcnt incubation times. either by assessing bio.:J.cthity to scnsith·c insect SfX""Cics or 

by c.Jirc:ctly measuring Bt l~w s with ELISA or Wcsu~m Blot a...;:.mys. Results from the studies 

have sho\\1\ lhJtl Ul PIPs rnpidly dcgrodc in S<)il, wilh dc~md111ion half·lifcs (DTro) of-< I 0 days. 

Soil ,\/icroor;.:uni,wJS 

Numerous publisl1ed Studies indicate th:Jt exposure to Cry proteins product.-d in Bt PIP 

crop plants does nOtlldvcrsdy am.-ct soil microorgonisrns (S:mvido ct nl .. 2007), Although a 

minimal transient incrc..'lSC and shift in micmbi:t.lf,.)puhuions m11y result from the presence of 

ronsg~nic plant tissue in soil. no od,·en;c: c:l1\:·cts hnve been attributed to the Cry proteins. In 

addition. the soil d..:-grodation studies discussed above ha,·..:-shO\\TI that 81 com f'lf's degrade 

quickly in soil. With reg n.l to the impact of gcnctic:ally cngincel\!'d crops on :\Oil, EPA ha..~~> noted 

(EPA 20Hb) thO! ngricuhurnl practices themselves cause large chungcs in soil n.nd soil mkrobial 

compOsition. Fonhcmtorc. f:1c tors such \'oriotions in seasons and weather. plant growth stage. 

tmd pi::Jllt vari..:-tics. independent of being gcocticnlly ensinccrcd, arc also rcsponsibl..:- for 

sig.nifk.nnt shills in :;oil microbial commwtitics. rvlost studies with g.enctic:tlly cngin,"Crcd crops 

tO dntc ha\'C shOV•1l minor ot no etl'CclS on soil microbes beyond the vari:t.tion caused by the 

factots listed aOO\'c:, 

J. llorizont:.tl T r.and<'r ofTransgtnrs from Bt Crops 

EPA has C\'nlu:..t,'tl the: potential for horizonml gene transfer (HGl) from Dt crops to soil 

org:anisms :md has considered possible risk implic:1tions if such a tr.lllsf..:-r w..:-rc to occur. Genes 

th:u h1wc been cnginccr'"'il into Bt cror~s arc mostly ll:lUnd, or haw their origin, in soil-inh:abiting 

b.1cterin. Soil is also the h:1bitat of other toxin·producing J.J..Ictcria. nnd tr.msi"Cr of these genes 

and/or toxins to other microorganbms or pkuns has not been detected. Funhcm1ore. several 

publish<.'<.! experiments. that were conducted to as;sc.s..o; the likelihood of ll(iT, have been unable to 

detect gene transfer under typicaJ environmental conditions. Horizontal g<:ne transl"i:r to :;oil 

organisms has only b~n detect<.'"tl with very promiscuous microbes under lnboratory conditions 

( <) 
designed to fh\'or tmnsli::r. 

1\ s n r~.: ult of these findings o..nd the: f.'\Ct that the Bt to:<inscnginC'Crcd into cant PIP ha\'c 

been deri\'ed from soi l- nhob in~ bocteria. EPA hasconeluded 1ha11he risk ofiiGT of 

lr.lnSgc:ncs found in~ rcglsten..'CJ 81 com Pli's is low. 

4. GC'nC' J'low and \\'C'C'dinC';SS PoiC'otial 

The 010\'Cntc:nt oftransgcnc:; rrontthe host plunt into wccds has been n ~is fican1 

concern for EI1A due to the possibility ofno\-el exposures to the pesticid.:tl subs-t(Lncc. This 

concern has ~n cons.idcrOO for (-Hch ofthc Bt com PH's currently registered. o.nd was 

cxten..;ively r«x-aminc:d in 2010 (S« EPA 20103). 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 risk of gene 

c:~ptun: nntJ t::<p~ssion of an)' :tpf'U'O\ cd Bt cndOtO.'<in b)' ''ild or \\i."<.'<ly reloti\ C3 of com in the 

U.S .. its possc:~ion.~ or tcnitorics. In addition. the USOJVr\l)f.IIS Ms mL1d~ this same 

dctennin~t ion under its ~:llu DI')' :nuhority under the Plnnl rest Act (sec Ot c:on1 risk asscssmtnt 

:md dercs ul:uion decisions postctl on USDN APHIS web site: 

h 11 p:/1\\'\\ '\\' .Q pbj :0. U~:l. gov fbjO!«hnO!Cl!j!\'/[l( I ilion~ IQ bh; !X'nd ins.:: h IIlii ). 

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. conon. and potatOC'S in the U.S .. ils 

possessions. :'"Ufor its tcrritorics. nt PIPs that ha,·e been rl!gistccro to <btc: hia\'C bt.~n cxprcs.scd 

ir1 agronomic pl:mt .Spc!'cics that. for the: most p.m. do not h:a\ c n rt.""a.<;On:tblc po:..sibility of p.usint; 

their trnilo;; to wild mlli\'c pl::mts. Fcrul spccie:s rci:U\.-J to Lhc.sc crops. OS tbund within the United 

States. cunn01 be pollinated by these crops (com. pouuo. tmd cotton) due to t.Jifferenccs in 

chromosome nutt\bcr. phenology (i.t"., pcriodjcit)' or timint; of l'\'ents \\ithin an organism's life 

c~clc! as rdGtcd co elim:llc!, e.g .• flowering lime) :1nd h:Jbi1:11. 

A FlFRJ\ Ef'A Scientific Ad•isory Pnncl mc:.:ting. held on O.:tob<r 18-20. 2000. fu1'111er 

tJiscu..~~cd the issue of gene flow. The panel agn.">Cd dun the potential tOr gene tr.:trufc:r between 

com ~l!) and any rcccpli\'C plnnts \\ithin the U.S .. its possessions und territories ''':U of 

limited prob.lbilily and nearly risk rr~c. B:IS('d on these cxtcnsi\'C :m:tlyscs.. the potential for sene 

tlow and de\'doprnc:nt o f weediness is expected to be low for the CWT'Cntly rq;i~lc:n."d Bt con\ 

PIPs. 

S. Ecolos:ic-al Incident! 

According to a so:arch conductl'tl for Bt com 1

1

11'!' on Auswt 17. 201 S. using the 

Ecological Incident lnfomunion Sy~tcm (EllS). one incident (1027769) wa.s recorded for :t Bt 

com product. A honey bee die ofr \\015 rt"poncd b)' D commerci:tl ~keeper in South Olkota 

whose fann was proximate: to r«c:ntly·pbntcd com tickls. The com h)hrid planted in lhe 

neisJtborins fields w::ts 3 comm~UJ '':lricty ofSnwtStn.x. 3 81 PIP product containing Cry I F. 

Cryl A.1 05. Cry2,\b2. Cry3bb I. nnd Cry34135. The>«.-.! was also 1rrnted "ith clothi:midin 

(Poncho). n con\'cntionul pesticide. with be~ toxicity (the incident repon wus m:..dc by the 

registrant of clothianidin. Bnyer t'ropScicnee). 1c is highly unlikely that the bee die on· was due 

to the Bt I)IPs in the SnunStn.x SC:l"tt. ch of the B1 proteins in SmartStn~ h:LS bcc:n C\';ah.uucd 

for 1xc o~ici y " ilh noobscn. ~tion ol'signitic3Jlt :1dwrsc c11'e-cts in tcnns of mortality. hi"t:: 

20 
health, or brood dc\·clopmcnt. In addition. lx"C cxposun: to Bt PIPs in the planted com Utlht.* 

time of the incident (1-2 days atier the lh com was planted) would be low to non-existent Bt 

PIPs would~ contained \\~thin tht: seeds until genninntion and no pollen (the likeliest source of 

bc:c exposure to Bt PIPs) would be present at th3t time. 

6. [nvironm~nlal Ri.sk t\sstssmenl Conclu$ion.s (Non·Li.sltd Sp~its) 

lllc: EPA uses a Maximum Hazard Dose Tict\.'<1 system for biopc.sticide non· target 

wildlife h:v.ard nss:essmcnt. When no ::td\·erse ellcttS :tt the ma.ximum hazard screening dose nrc 

obser\'cd on n:prc.scntativc non-target species. the Agency concludes that there :an: no 

unn:nson::tblc ::Jd\·erse cll~ets on non-target popul:ujons: from the u.._~ of the pesticide. 

At present. the Agency is aw:1tc of no identified signilicant nd\·crsc ctTects of Cry protein 

on the :1bu d~mcc of non·t:ltget orgnnisms in any population in the aqumic or tcrrcstriul ticld 

cn\'ironment. whether they nrc animals. plants. pest p.llrn.sitcs. pest pre-dators. or pollinators. 

Funhcr. EPA bclic\·cs that cultivation of Ot com PIPs may have few~r adverse impactS on non· 

target organism$ than usc of chemical pesticides for com production. because under nom1al 

cireumstnnccs. Ot com requires substantially fc\\'cr applications: of chemical insecticides. 

compared to production ofnon·Bt com (sec EPA 2010a). Fewer chemical insecticide 

applic:-nions generally result in incn:uscd populations of bencliciaJ organisms that control 

secondary pe-sts. such ns uphids and leafhoppers. Funher. l'.r\ h:.s detcnninc.."d that there is no 

significant risk or gene capture and expression ofllt PI I' proteins by wild or weedy rcl::Jth·es of 

com in the U.S .. its p<.l&.">C$-Sions. or territories (sec .. Gene Fh)w und Weediness Polentinl .. abo\'c). 

available data do not indicntc that Cry protei n.~ have llJlY mcasurnblc :adverse cllCct on microbial 

populations in the: soil (sec ··Soil 1'vticroorganisms·· obo\'e). nor has hori:r.ontal tr.msfcr of genes 

from transgenic plants to soil bacterin been dcmomirntcd (see ··Horizomal Transt'Cr of 

Trnn.~genes from Dt Crops" abo\·c). tn conclusion. the risk a"-"essments tbr Jlt com PIPs hll\'C 

lbund no hazard to the cn\'ironmcnt tfom cultivation or Bt com in the U.S. 

lntlir,•r;t Effats 

·n1c purpose or using PIP plants is the-same as for any other pest man.:~.gcmcnt tactic. i.e .. 

to reduce pest populations below economic injury lc\'eiS. As o result the nbundancc of pest 

insects should be signitic:uuly n.'tiuccd :md this will huvc corresponding implicotions for those 

organisms th.lt exploit these pests as prey and hosts. Thus. the po!cntial for these indirect 

c~:ologi cal cOCcts on biological control organis:nt.'> should not be n!gardcd as a w1iquc ecologic.n.l 

risk associate-d with h~ PIP crop. Some n.-ductions. howc\'cr. should be expected if the pest 

manfigcmcnt strategy is eJTccth·c. Since PIP crops a.rc ot1en gr0\\11 in \'icinity with con\'entional 

c-rops to prc\·cnt resistance build· up by the tlliget pcst(s). specialist ~:mtugon s can persist in 

th('Sc "refuges." a._..; well as in other crops :md non-crop h::~bitats. thu.s retaining the potcntial for 

recolonization of the PIP crop area. Based on these considcrntions. regulatory testing of the 

p...~i t prcd:ators and parasitoids of target pests: may C\'Cntually b.! con...;;idcr ... '<l unnece'SS31)'. 

21 
7. EndllnJ:4.' n~d Specits A!,'(«.'.);n1tnt 

Endnngcrcd SJX-c-ies USSC$Smcnts (ESA) ha\'c been complc1ed and arc documented in the 

BRAD documtniS for oath rogis1<red I'll' (Table 2). 1110 loSA for 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 Review l>t."Cisioo-section below). Colroptcr.m Bt 

tom (case 6502) was ulso updn1ro in 2010. 1hou£h a sub><quen1 ESA wasconduc1cd in 2012 for 

~Cry3.1Ab. Since the 2010/2012 endangered S]JC'CiCS dl.!h:-nninations.. Ef'A is .:murc that 

t1dditional pidopt~:r.m and Co1eoptcmn species have been listed by the U.S. fish nnd Wildlife: 

Scl"\·icc. EI'A docs not CX)X"1:1thcsc additionul species to uffcct previous "no cm.-ct" lindings th:u 

wen~ made: for both Lcpidopternn and Colcoptcr.m 131 com. largely becuusc exposure to Dt Pll's 

islimitC'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 Re,·icw lA~i.sion ror both cases (SC'c .. Nc.M Su~ps nnd Timc1inc- :.u the end 

of this document). For the urpos~ of the Proposed Interim Rcgi.Strmion Review Decision. the 

discussion thot tbllows summnritr.cs tl1e ESAs that wt:n: updated in 201012012. 

·n,e prim:lr)· route of ex:pnsurc to Bt PIP JlrOtcins in com is through int;cstion of con1 

tissue. Since llt com PIP rotein~ 41\: not exp«tc:d to ha\'c ad,·crsc c:fl'ccts on nwnma1s. birds. 

plants. fra.hwo.ter and cstuarincfm:arine iis.h 3Jld in,·crtcbrotes. oon·t.argcl insect,. (Si.!'C discussion 

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 to fcdcr:llly listed thn!.atcneti nnd cnd:mgen.'d ("'lish:·.J") species. In mldition. EPA docs not 

cxp...--<:1 that nny thrcmcned or cndllllKCI\.-d plant specie.;." will lx: nl)'ected by outcrossing to wild 

rcl:tti\'cs or by competition with such entities. J Jybrid com docs not exist in the ''i ld. nor nr...-

lhcn: ''ild plcuus tOOt C3Jl intcrbrc...od with com in the Unilcd Sutcs. 

Because oflhc $Cicctivi•y ofB1 com PIPs for some lcpidop1eran (co.<e 6SOI PIPs. see 

Table 1) ""d Colrop1crnn (<OS< 6S021'1Ps) SPC<i«.1hcr.cxists some concern for lis1cd SPeCies 

\\ithin these rder~. 1llcrcl0 rc. EI'A hns conducted nssc.ssmcnts lbr listed lcpidopteron n.nd 

coleopteran species to c:!\'alu:ne potcnti:al exposure 1.111d cnCcLS from llt cont Pll)s. 

For Lcpidopter.:t. cx:unin:llion of county distributions of cod:lllgcT'C'd/thrc.lhmOO 

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 wns m:1inly f\."Stricccd co th~ Knmcr blue buuerny (l.JV.'aeiJ.:s mfliss<l 

samm•lis). Kt:s..:arch dc:monstrmcs dust some Bt PIP r ro1cins rue sclecch·d y toxic to lcpidoptcmn 

larv:u: nt lidd concentrations and that the Kamer blut: ull t:t ll · is the only endangered 

lepidopteran species th:tt mny be cxposetl to Jlt com {via pollen). llowc\'cr, the Knmcr blue host 

plant. the wild lupine. docs not occur in com fields. ·n,crcforc it ;sppcars highly unlikely th;tt 

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 sensitive to all Be ftr\"'ICins in all Bt com .:\'t:nts. the likt" Jihood 

that the lan-:1e would encounu:r ~u tlici cn t grains of Ot corn pollen co exert toxicity is cxtrcmc:ly 

n:mo1c. Also, c\ l~n t data and informmion indicate thnt lht: likelihood of wild lupines occurrin~; 

ndjuccnt to com 11dlls is low. Morco\'cr. I he ~werlop of the lime of the cor when t:om poJicn is 

shed wilh the times of the year \\hen Kamer blue lan·:u: nrc likely 10 be present is limited. 

, 

--
Atler cnrcful rc\;cw of a\·aHabll! d:ua, EPA l.l~ ten ncc.l that exposure of the Karner blue 

btmerny to h:mnful levds of Dt com plnnt tissue is not exp...--ctcd. like,\isc. a rt:\'icw of the 

prcfcm."d habitats of other lepidopteran species listed 3.'i endangert."<< by the U.S. Fish and 

Wi lil~ Service indicated that exposure to h:mnfulle\'els of Ot com inse<:ticidal proteins would 

n(lt t~1kc plnce. The main reasons tbr the Ind. of cxpo:>"Urc arc gcog.rnphkal and habitat 

limitntions. These SJX"Cies ar~ located in non·mai7.c production arc:ts and/or their habitat docs not 

encompass o.grkuhurol areas. A complete discussion of the Lt.")lidoptcran ESA can be fOund in 

EPA 2010:1. 

For Coleoptera. 18 species were listed as threatened or endangered 3.'i of2012. Of those. 

16 occur in counties in which com is grmm. Eight of these spccii."S :m: ubterranean~ and 

exposure to Cry proteins expre$$Cd in piMt tissues is not expected in these environments (none 

of these species feed on corn roots). 'll1e n:mnining spec its existing abo\'C ground. in tcrr~ trial 

or nquatic habitats. are habitat SJK"Cial :; duu nrc largdy excluded from o.gricuJturol areas due to 

thdr spcciiic h:.tbit:lt re·<Juircmcnts. While habitot'i t)f some of these Sp<.·cic:~ may occur nearby to 

:.tgricuhun)l nn:.as where Bt com PU•s may be cuhivull..-d, exposure ,;n consumption of Bt com 

tissue is not anticipated due to their specilic 1000 requirements that would exclude consumption 

of com plant material (i.e .. they nrc prcdators.'sca,·cngers or consume srx-cilic I'Cxxl plnnts). EPA 

also h.a.c: previously dctcm1incd that exposun: 10 Cry proteins in pollen outside of arc.a.s where Bt 

com is cuhivotcd is limited (EPA 2010a). 

The Arncric.nn burying bt.--etlc (Nicropltorus american us) is the only species that may 

potentially utilize :1r.ms where com is grown. EPA ha.sdetennined th:lt this species is not 

exp...~ted to be exposed because it l:.trgcty fe.:_-d.;. on carrion (sec discussion in EPA 2010c). Based 

on the :.tvail!tblc: intOrmation. exposure of listc:d colc:optc:r.m spc:dcs to Bt com PIP proteins is not 

CXJX.-ctcd. Thcrctbrc. a "No EOi:-ct"" dctc:nnin.:.uion has been made tOr direct cfli:-cts to these 

spc:cics. Since et1t.--ct.;; on other insects or other anim:tl or plant Ul:<:t arc not an ici pated~ as 

discussed nbo\'C, n .. No Effect" dctcm1in.ation has nJs.o bt.~n mode tOr indirect etl'l.-cts t(l liStt"tl 

colcoptcmns and tOr effects to their critical h!lbill'lt. 

The rc\•iewcd toxicological dnul shows the rclati\'c inscnsiti,;ty of n range of insects in 

non-Lepidoptcr.m or Cokoptcran orders to Bt com l•IP proteins. indicating thot Bt com hybrids 

arc not likely to hn\'e deltimenml tfcct~ on non-Lepidopteran or Coleopteran insccts included on 

the: endi.ln~c:rcdlthrcatened sp..~ ics list In addition, other ins"""Ct species in the orders Diptcra. 

Hemiptera. Odonal3 nnd Orthopter.t that arc listed as cndnngcn."C.lfthremencd species are t'Ound in 

dune. mendowtprairic or open forest habitats and arc not closely assoc-i31cd ''ith row crop 

productjon. ot1cn tjmcs due w the SP'o"<:iticity of the h:.tbitru of their host planK 

C. l nsNt ll.tsi.slllnrt J\lanag.tmtnl 

Ot com PIPs arc likely at gn:::ttcr ris.k tbr n!sistanee th::tn conwntion:tJ pesticides. This is 

been usc PIPs arc cxpn:s.s.ed at reltui\'dy high k\·cls throughout the ii~ of the plant. compared to 

com·cntion31 pesticides which typically ha\'C shorter pc:riods of cnicacy. Prolonged exposure to 

Ot PIP.s in com. often O\'Cr multiple-generations per sc:t.o;on, cxcrL' signilicant selection pressure 

tOr resistance to dc\•elop (f;f

1

A 1998. Matten ct nl. 2013). 
Gi\'C:n thl.! cm•ironmentalnnd economic bt:uc:litS or Bt c:om PIPs (EP1\ 201 Oa). 

susceptibility to Ill has been consid~·l\.-d o ··public good .. (I'I'OC 1996) t1nd l!I'A has indicntc:d 

that re$iSt:mcc to Bt PIPs would COIUtitutc on unre-asonable adverse cfl'ect under FIFRA (Mn.ttcn 

ctnl. 2013). 'll1crcforc. as 1cnns o.nd conditionsofrcgistr.nion.the ..-\sent)' Jus n."'quircd insect 

n:sist:mcc monoscmcnt (JR.\ I) pions for oil 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) for Lcpidopccmn Bt com (cnsc 

6501) ond c-om root worm (CRW) for Colcoptcr:m Bt com(<= 6502). 

lllc primary rcsistnncc: mitig.otion strntegy lms b~~n the usc or rdusc in c-onjunction with 

Jlt com. RcfuJ::CS scr\'e as source-s uf Ut·stLo;ceptib!c insects nnd arc typically a portion of the 

com cnlp thlt is devoted to 3 non·Ot '"'riety. For Ut com I,IPs.. two 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 strips 

proximate 10 llt fields. ond 2) S«d blends. in which !It lllld non-Be <om S«.'ds tm: cominglcd 

\\ithin the some SC\.'\1 bags. 

ldenlly. refuse is deployed in combin:ation with I) Ills th:at cxprc$..~ lllrgc amounts of llt 

toxins against the t:lfgct pes15. This so coiled -hi~:h uO,.,·rcfusc Slr:ltcgy·· (SAl' 1998. EPA 

2010a) cn,!tun: .. ~ th=u only resistant homoZ)'SOtc (RR) scnotypcs "ill suni,·e c.xposurc to Bt PIPs.. 

Since ~""Sistnncc genes :~re 3SSU.rncd to be r:1re in the popul:uion. there is 310'' likelihood of 

rcsismnt :;u" hors ln Bt fields. lltc few rcsist..'lnl indi,·idu::tls th:at sur.i,·c a~ likely to encounter 

susceptible: in~~"Cts from refuses "hkh. n.\Suming mndom mating. \\ill dilute the numbt!r of 

resistance scncs in the overall population. High dose has ~n de lined by the 1998 SAP ns ··2s 

tim<:S the protein conccntr.uion n1:1:cs.sary to kill susccrtihl!! II.U'\'3c." Five \'crilicotion methods 

were provided by the panel. two of\\hich would be sunicicnt todeiinc n f'IP us high dose. 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 of the dose t.lctCmlin.:nions for each pol 

Though high dose ~.xprc.ss un is it.leaJ, IRM can 1x: pmcticcd lOr non-high dose insects 

with refuges and ciTccti\'e rej;iSHlnc..: monitoring. Thl.! concern. however. is thnt heterozygote 

genotypes (KS) may stU"\'i \'c exposure. ultimately incfX"n ~ the amount of rc-.si~t:mcc gerlcs in 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~mlent mod~s of oct ion (i.e .• no cross ~si.stnncc polcutinl) 

nnd high ncth•ity (dose) ct~n d!!lay the C\'olution of rcsisumcc rdath·c to single troh '·arictic.s 

(Roush 199K. Zhao ct al. 2003. Gould 2006: modeling sununari7.cd in Mottcn <1 ol. 2013). Given 

the improved durability offered by pymmid.s. EPA h:LS upprtwed smaller rdugQ for pyr.:unids 

comp:tt<d to sinj;lc PIP produces (SC'< Tabk ~below). 

1. Currtnt IRM K~quinmtnb ror Bt Com 

IRM S1rt11cgics lOr 11t com hnvc bc:cn SUJlfiOrtcd by extensive dnll.t On JX:Sl biology. J>J F1 

expression (l.!osc). baseline pest SU$CCptibility. mode of action. 3fld polentinl cross re-sistance 

between Bl 1oxins. !)imul:ition model~ ha,·c b...--cn frequent!)' usOO to C\':tlu:t.tC" n:fu£-c op-tions nnd 
u.":->e.ss the durability of fit com PIPs under dit)Cn:nt conditions. Pe-st biology infonnation for 

l.cphfoptcran pests ha..- been summarized inEPt\ 2010a and for CRW in EPA 2010b. EPA's 

a.~cssmcnts of dt)SC, ('ross csistru1c~. nnd simulation modeling for cm;h registered PW nrc 

contained in the rcspccti\'C ORAD document-; (Tnble 2). Gcnc:rally. the Lepidoptcr:tn-:lcth·c 

toxins arc high dose nguill!>1 ECB and SWCI), but not CEW. None oft he four registered 

Coleoptemn-:activc toxins is considc:rt"d high dose lhr C:.:R W. 

Spcci lie refuge requirements for single tra.it and pyramided Dt com PIPs arc dc.scribcd in 

Table ..J. Other rcquirenlcnLS. including insecticide usc limit:ations in rcfus.:s and width 

requirements (for refuges \\ith strip conligumtions). aJso apply to structured refuges in some 

ca..se..s (EPA 20 I Of). Cotton-growing n:gions have a larger n:IUgc n:quircmcnt due to greater 

ri!'.Sisumcc concerns with com c;arwom1. which ~~d.; on both com nnd cotton. Successive 

generations ofCEW could be cxposOO toUt PIPs in b01h crops. heightening the selt."Ciion 

prcs$ r~ for c~ tancc. 

The 1cnns nnd conditions of registrotion specify a number of post-regist.rJtion IRtvt 

IX'quin:mcnts. including. grow~.:r ~;.-ducat ion programs. a refUge compliance strategy. and resistance 

monitoring for the: key target pests (EI'A 2010f). These stewardship programs Ill'\! carried out by 

registrants. ' 'ith annual r..:-poning to the A seney. To dat..:-. all J)t com rcgistmnts ha\·c been in 

compliance with the R~1 n.-quircmcnts. 

ab e~. Refuge n:qui :mc ~ tOr single toxin nnd pymmidcd Ot com PIPs 

81 C'OI'n I~ X' Tnrj,!tt pt.$-I.S StntC"turC'd tfu~c: Pro)lmlt)' 10 Ot Oc-lds S«d bknd 

Singtc: to.xin LtpidoJ'I{CI':l C'om Uelt: 2~• <1/2 mile- Nt,\ C'-'Clon regions: ~• 

Single- 10xin ColeOCI(Cr3 1\ll re-gions: ~• Adj:tetnt or wilhin ~- Com Uc:lt: combined <:>r Combi.nc:d n=fus c:: (S.Cp.'ll!l-1~ Single tO:\ in lC'pidoptern + ~~lc- 20'!'. refuges 3djlcc:-nt Of within refuse' fiX (suck~J ) ColccpiC'r.l Coi10r\ rctlcru.: ~C'p31<1\C" Sc:p.mltC' rcfu:;e.s: lcpidoptc:-nm peru 10' :. (CR\V) :IJKt $~· ad}:lc:c:nt (CR W) and < nOO rcquimJ) (I.C"r) refuge-s mile (Lc:p} 

Com el ~~ S!i (sep:untc 

1)·r.unid lcpidoptc:-r.J CO!tOO r\·g.ioru: 20 0. <1/2 mile refugt' rcqu ~d in 

couon regioru) 

f')'r..mid Cokoptcrn All rc&ioo.s: S!;. t\Jj>Kcot or "ithin 5 •. ,. COrn lklt: combined 5% Arc:u wilh lcps: <1/1 5,. (.ioep.mtl(' 1-'yr.:~mid lcpidop<c:-m - rtfugc mile n:-fugc n:qui.m.J in (>tO<k«l) Co optcr.~ Conon regions: combine-!,! A~:t.J. ,\ilh CRW ooly: 

conoo r~to ) 0. rd ugc :.tJj3C<-nl or "'ithin 

Refuge complinncc prognuns for Bt com PIPs cnta.ila Jti.fac~ cd approach that 

includes the demcnls listed below. All of these aspecL..; arc required by the wrms and conditions 

25 
of rcgisutnion (sped lie n.""quircmcnts urc c:onuincd in EPA 201 Ot): 

• IRM Educotion ~ .. rogrnm: Companies arc rcttuin:d to implement nn .;.'ducJtioruJl progmn' 

designed to COO\'C:)' 10 users the im~rtancc orc:omp1ying \\ith the IRM progr:mt. The 

educational progr:un in,·oht"S the usc of muhip1c media (e.g •. focc-to-facc rn«tings.. 

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. 

• Grower \~n.-ement : Companies arc required to ~ntcr into :1 contra..:tual arrangcmc:nt 

bct\\'Ccn the re-gistront n.nd grower to obligntc :lt.lhcr.:ncc to IRM n:quir\!mcnts. 

• Annuai iRM su.r"cy: RegistmnlS must coordinate a S\lr\'cy (conduct.:d ononymously by 

:m indrpcndcnt research finn) to pro, ide :1 suuisticaJiy r~presenuti\'c s.:smpk of growers 

from ,'UJious rom·giO\\ing n:-gions in tht U.S. RcsuJts from lhc :~ouncy nrc used to ~~s 

le\·cls of i7Q\\Cf complian« with refuges 35 well ns grower moli\'ntions. :miludc:s. and 

R'a50r\S for non-tompli3ncc. 

• Qn .. fhnn U$.SCssmcnts: Rl."gi tronts :m: rcquin.'\llo dc\'dop nn on-site a.SSC'ssment progrom 

in which troincd personnel from each company m:Lkc \'isits to f:tnn.s srowing Bl c:om. 

Ourin1; these visit'\. compliunce with refuge requirements is assessed nnd growers out of 

comp1i:t.ncc ;~n: idcntitied for com:tti\'e crctjon under the Phased Complinncc Appro:1ch. 

• TipS and complaints: Rcgi~r:llllS must ~blish :t means for the reponing and 

im·C'-Stigation ofincidcn«) of ~ruse OOlX'ompliuncc. 

• Ph3.5Cd Compli3nce Appro..-,ch (PCJ-\): Resistr.lnts m~ "-mp!oy a conshlent set of 

procedurt:s (for nil Ot com rct;,istrdntS) tO nddrcss non-complinncc Mlong ~ro\\ CtS nnd 

seed dt::t1cr.;. 

Refuge complinnce acti\•itics nrc coordin:tho.'\1 by the n:gistr.mts. ~me of whil;h (grower 

surveys) on: coordiJUt<d through th< Agricultur.d Biotechnology Stcwardshir Technical 

Commill« (ADSTC1

). 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\\cr sUI'\·cys. on-f11nn 

asSC"SSmr:nts. antl i'C,\ actions. El,;\ "s 1\!\icws ofth<)C ~poru :1.re summ:tri'IL"'<i in the BRAD 

documents for Lcpidoptcrnn (EPA 2010n) nnd Colcoptcnlfl (EPA 2010b) Bt corn. These 

t.Jocumenu were upduiL-d in 2010: ub cquenl EPA reviews oflhe nnnu:1l B1 com compliance 

n:pons haw been posted to the Agency's IR]II docket (El'A·BQ-OPP-2011 -0922). 

3. RHlslanc:<' Monilorin: 

Throu~h the terms of K~istrotio n. Bt com Kgbtrunts are rcq1ain:d co implement a 

n:sistnncc monitoring progmm for the major target pests (l:Cn. SWCB. CflW.nnll CRW). A 

primary go:al of resistance monitoring is tO detcet shills in the frequency of rc:sistnncc genes (i.e .. 

susceptibility dumgcs) befon: th..: onset ofrc~isunc..: leads to ,,;dc:spre:td Ut crop failure (St'C 

EI'A 201 0a). 

Monitorins for n:si.suncc has consi~tcd of two main components: I) iR\C)tigmion of 

unexpected licld dan1.:tsc rcpons from growers. cxten.41 ion ascn1.S. consullMtS. or company 

ugronomisu, nnd 2) monitoring for chnnges in susceptibility through tnq;,ctc:..J fl'Opul.:ttion 

I The Agnculturall)i0¢C'thnolog)' t":Ud~h p Trthnk:aJ Cc-mmiltC'C b <111 indU)lr) t'On\Onium or Ul ccm rtf' 

rrgi.s1r.mb.. incllldint; MOOSlll:o. Oo", ri~r. ~d S)ngC'fiU. 

26 
-.umrling :md testing.. Uncxp«lt"d d.."lm.:Jge reportS nuy n:' cost the occurrence oftoc:.Uized 

n->isunce (or hot Spots) bc:focc the cll"e<:tS <>n spr<:td. R<>istancc monitoring through llllj;<t<d 

field );lunrling c::m rc,·rol ctunocs in susceptibility o( seos.mphie.ally rcpr'C'SC'nunh·c popul:u.ions. 

In th-.: c'cnt that rcsisumcc is conlinncd. a rcmC'dit\J octjon plan is trigscrcd 115 define-d by the 

l<rntS of rcgistr:uion (:«.-c EPA 201 Of). 

Similur to re-fuge compliance, much ofthc resistance moniloring work is coordinated 

through ABSTC. including in.scct SJmpling nnd biOO.."'SilYS to determine SU$Ccptibility. Reports 

covering cnch monitoring pest and to.xin nr<: submincd annually to th..: A gene)'· EPA's rcviC\\'$ 

of the monitoring reports arc suHunorit,'\1 in the BRAD documcnL"' lbrtach PIP (Tubk 2. 

upJ4ltc.*d in 201 0). Subst.""qucnt rc:)bt:lncc monitoring reviews hn\'c been po.stcd to the Agcncy"s 

IRM dockct(EPA-IIQ-OPP-2011-0922). 

To cbtc. the Rlljor Lepidopteran urgot pc>!S (ECB. S\\'CB. :>nd CI!W) r<Rilin 

.su$ccp1iblc to the registered Ut com 1oxins. However. ibll 3m1)'\\0m1. a sccond:tr)• com pesL was 

wn to h:lvc de\'Clopc:U n:si~1J.nCC to Cryl Fin Puerto Rico. Rcsisuncc h:&$ nlso been dctcrtc'd 

in CRW 10 the Colcoptcr:m Bt toxins. Cry3Bbl and mCry3A. 

FA IV - Cry/ F RcsisWIIf'' 

FA W is a ~"'Condor)' com tx.St in most of the U.S .. though it is :1 major pest in tropical 

nr~lS where it 0\"etwintc:r.; (including l'ucrto Rico). (n the U.S .. O\'tl"'\intcring is limited 10 the 

c;;t;crcmc southern portions of Florida :md T ~xus. However. infcslntions in th< U.S.. can occur 

nnnu:111y from FA W migroting nonhw:.ud from O\"Cr'\\i ntering )it(:) in the: Cruibb..~. 

Durins 2006. cbnl3~< to SC\Cr:ll contrn<'fOi>l ;md r=<h Cry I I' (TCI507) lields """ 

obscn· ... "d in Puerto Riro. Bioassa ~ off i\ W collected from these licfds shO\\cd thnt the FA W 

popul;uions had high 1olero.ncc 10 Cryl F. including no moru~lity 10 u diaJ:,OOstic conccntnttion 

(10.000 ns Cryl F/cm:) and an C!l1illl:llcd n.·siSUlnc.:c: ratio > 167. Resistance l ikely C\'Oh't.."d du~.: to 

climntic conditions aJio,,ing for y&::lr-round maize production and continual insect pn:ssurc:. 

limitetl F1\ W migmtion (isltlJld t:nvironmcnl). and high adoption ofC:ryl F com. 

1l1ough n remedial action plan is not n.-quired by the tcmlS of rcg,isuntion for fA W. the 

r.:gistnant.s (Dow AsroScknc\!'S and Pion~r) impkmcntC'd a plan d..:.signed to reduce the sckction 

pn:ssure for FA\\' resistance: to Cry IF 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:CII. S\\'CB. ond CEW), The companies ins!IOCtcd gro\\cts 

to usc :thcm3tc controls {insecticides) for Ft\ W :md discontinu..-d !.O.Id ofCry l f com on the: 

isl:>nd. 

Subsequent :malysis has sh0\\11th:u the n:siSl!lnt tmit is .. li:<t"U- in the popul:ation {i.e .• 

there \\'Crc no n.ssoc:iatcd fitness cost~ with the I mil). c\·c:n without the continued presence of the 

.:k'(' ting ngcnt (Cry I F). Bt'C:aus..: of this. Cry IF com has not been cuhi\"ntcd on the. island since 

n.: ~t~mcc was detected. Risks to mninl:md com production could n:suh if resistant FA \V migrJtl! 

nMthw:ard into cast coast slnt\.".S, pro\'idcd those states haw signilkont Cry l F com use. Along 

these line-s. academic ~~: an: hers h:t\'C idcntiliro Cl)•l F-rcsistrull FA W collcct<.-d from local ions 

in Florid>. G<'Orti>. and Nonh C3tolino(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 migrotinn p:mcm. To dote. 

27 
howc\'Cr. reports Ql" unexpected drun:tgt: to Cry IF com in the U.S. have b.."'Cn limitc:J. In 

r~spoJl.S.C to the risks. Dow nnd r•ionccr h:&vc incren.'iC'd n.~is once monit ori ~ lOr FA Win an:ns 

where the jX"St moy be. present nml will work \\ith l1~ctcd g.rowc:rs 10 implement ''best 

m:..n:tgemcnt pr.tctices .. in the C\'cnl oC FA W dam3gc. 

lktoits of the FA W ~httlnCC c3SC' and n:-l.lt"'\1 ~h arc summ:ui7A"d in EP.,.-\ 1010(3) 

nnd in the public litcroturc (Stor<r ct ol. 20 12 ~ 

CR W llt•,,·istcma-Cry) liM. mCr:dA Rc .. :ri"tam . · .. • 

CK W prc~nts sisniticant challcngi!S tbr IRM. Rc.-gistcn.--d PJP tmits ure not considered 

''high dose:·· ror the insect. 35 CRW is Jess susceptible to Bt toxin.~ t.h3.n Ol~r turset insects. The 

insect h:Js :thcmn to bi: highly odnptBblc to control str:ucgics. including chcmicotl peSiic:ides 31\d 

cultutJ.l controls. In addition. CRW can bcdiflicultto test in laboratol')' bi035:..'\ays. 

Sc\'cnll :'Otudics by n."Scttrch scientists huvc documented cUSi.-"S of ficld·cvol\'cd com 

rootwonn (CRW) resistance to Ill com. The li ~t ofti1.:S.: studies. Ga...;smann ct nl. (2011 ). 

demonstrn1cd thut CRW eollccted from damaged (1)•31Jb l llclds in lowll durin~ 2009 were 

~ignificantlr Jess ~m.ccptib c to the toxin dun CRW rrom ui'Klrun:lgOO or non·Ut Sield.s. 

,\ddition::tl C3SC'S fC~3Bbl drun.:tt;c chJ.ractt:ri1..ed n.< fidd n:sisumce lu\'C' since b«n 

documcnlcd from other locntions in Iowa nnd Illinois (0DSSillJJlll cl ol. 2012. Gruy 2012). EPA's 

r.:vicw of these tt"ports (EP,\ 20 13) concluded that current rcsistnnce moni1oring str:llegic:s and 

rcfugc-bttsed IRM approaches nrc likdy in dcqunte for CRW. Subsequently. cross n:sistnnce 

has also been detected between the Cry3Bbl and mCrylA toxins. suggesting n common 

JUL"Chanism ofrcsistuncc for toxins structumlly similar to Cry3 (Gtl..~~num n ct ul. :!01 4). 

In response: to these con«m.' lll-'1'0 re\ric,,cd CRW t'ltSi.st:1.DC'C monitoring nnd 

remcdiotion ros.r.un.~ identified scientific unceruintics nssoci:utd ,,; th CRW n:sistrulC'c. nnd 

proposed impro\•cmentS ba.._~""ti on twa.ilablc inform::uion (EPA 2013). ,\Scientific t\ d,i.sory 

Panel wus con\'cncd in 2013 to fH\Widc guidance on rcsisumcc monitoring for tRW (SAP 

website: b.un: /{www ~p q;o\'/scipQI)'/St m\.'C1in gsJ20 3/ 041 mc-ct nc.Jllml). "lllc p311cl wn..-. 

tasked with C\'!lhiA1itlg EPA's rcs:bt:'"cc monitoring (snmplitlg. bioas.s3ys. nnd dclini11S 

resiru~ncc) and rcmcdiDlnclion tmtc ics. Key ~1 ecommendation.~ (SAP 201 ..$) included 

utilizing on ln1egr:ucd Pest ~l onogcment (I PM) upproach " ith CRW to mlucc S<lcction pr<SSun: 

ror 1'\.~istnnce. i~ins tbC' scope of sampling. impmvins resisuncc dctcction n...'-~ s.. i111d usina: 

cn'C:cti\'e tool.s (e.g .. mp rotation) in rc:sponse CO C3.'iCS of con tinned resistnncc. 

BaSC"d on thl' SAP's recommendations. EPA dr.an(."t.l o propos..1l to ~:nl uJ cl! IRC\·1 for 

CR\V. ·rhc propos.:al was submitted to ndu.s tr~· (ABSTC) on Auglt;;t 27,2014. Subsequently. 

EPA ostnblishcd o public comment period forth< prOp<>S.ll. A public doc~ct was established 

(ErA·HQ·OPP·20I.j..()S05) " ith on FR notice of "'"'ilobility (SO FR ~56.1 ). The comment 

period ron from Jonu:uy 28.2015 through April15. 2015. G<n<mtins 87 toul commcnL<. 

Ef'A has held se\·cral ccti n~s with ABSTC to di~us..." the proposnlthrough lay 201 S. 

Ncgotintion on 1hc proposn1 is soi ~:. and additional nl<."tlin!;S with 1\BSTC will be planned in 

order to come to nn agreement on :1ppmpriatc mitig.:uion nnd implcmcnllltion mechanism. 

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 iocludcd in lhc public docket :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 of this document). 

U. t-:ndocrin" Disruptor Scrf'('nin):: Jlru~r11m 

As r~quircd by the Administnltor under FFDCA section 408(p). the EPA h:1..o;; dt:\'elopcd 

the ndocrinc Disruptor Screening r•rogr:un (I.H)SP) nnd has begun to implement the screening 

progmm th:u is robe used to le-$t nil pc)ticidcs in order to detenninc whether ccnain subsunccs 

(including pesticide nctl\'C nnd other ingn:odicnLS) m:Ly ha\·c an tfl"l:ct in human.s or \\ildlifc 

simi 1M to :1n eilC.-c:t produced by n '"n:uurall~· occurring estrogen. or other such endocrine ctlCcts 

as the ;\ dministr.nor nuy d~i~llt " 

FFDCA section 408(p)(4) outhoritcslhc: AdminiSir.ltor. by onkr. to exempl from the 

n.-quirem.:nts of the Estrosenic Su~t:ancC"s Scrccnins Program a biolo..:.ic subst:tncc or other 

~ut't)t:ancc if a detennin.mion is m:1dc tJunthe subsuncc is not anticipated In produce a.ny el)'ect in 

hum:ms similar 10 on effect produced hy o natumlly occurrins cstrogl!nic suhSU'Incc. 

llctwe<n October 2009 and Fchnonry 2010.1hc EPA issued t<St ordcrs/dnr:o c:oll-ins for 

the llrst RrOup of 67 chemicals. which contains 58 pesticide octivc ingredients and 9 inen 

in1;rcdicnts. A second list of chcmic;~.l s identilicd for EDSP scrccnin~ wo..; published on June 1~. 

2013:: ond includes some pestlcidc:s sc:hcrluled lOr registrotion rc\•icw and chcmic.als found in 

w:1tcr. BacilltLf tlw.rlnJ:lf!n..<ris (microbial) or l•lPs dcri\'cd from Bt W\: noc nmnng 1he group of 

pe-sticide ncti\"e ingn:odiC'nts on the li<ts to be sc-rcrocd under the F.DSI'. 

·n,e EPA believe-s that I'll'~ d.:ri,.·td (rom Bacillad thllringlt•nd" tlr(' 5ubst3.nces tOOt would 

not likdy produce any cfH.-c1 in hun1nns similar to an eilCct product"d by lt na1Ura1Jy OC"cuning 

c:o,ttoj:;cnic subsuncc. As ~uch. pursuamto Sec1ion -40S(pX4). the EJ•,, will deu.-nninc- in the 

future \\ hc:thcr it can exempt I'll's \kri\'l"tt from Bacillus llturinglt•tuh· l'mmthc rl"<}oi ~mcniS of 

lhc Scclion 408(p) EI>SJ.'. In the C\'COI Ihc EI'A docs dCit:nninc IO cscmrtthis substrutcc from the 

EI)SP. an ordi:r will be: issued. 

For funJ1cr infonuution on th.: stnll1.-.: of the EDSP. th<." polidt..'S nnd procedures. the list of 

chemicals. futun: lists. the test guidelines n.nd the Tkr I scn:c:ning Nttcry. ple3SC visit our 

\\C~ tc: 31/11/p:/At'lt l'OO &,.,W'wdo • 

~IR NF. O WORK PLAN, SUMMARY OOCU~IF.NT,ANO !'ROt•OSF.Il ll\TF.RIM 

REG ISTRATION RF.VI F,W IIF,CJSIOl' 

In uccord.ancc ,,;th 40 CFR Sco ion.~ 155.50, 155.56. m1d 1SS.S8,1hc ,\gcncy is issuing 

1his combincd Work PJan. Summnry I)Qcumcnl. and Pro)Xlstd Interim Rcgislr::Hion Re\•icw 

Decision. l.:xccpl for the: EDSI

1 and ESA components oftht' Bt con1 I'll' n:gi:-;tnuion review 

C:lSC, the ,\ gcncy has made th\.· following interim decision; (I) no nddition:al data arc required ut 

this timc; :and (2) no changes to the nO"ectcd n:sistrntions or their ab~: ling nrc n"cdcd m this time. 

: ~ hnp:/. \\...,w «gut:uioru.gO\' .' !d\l('wncnlO..t&ii,()-EPA· Q..QPPT ·1009.().177..0074 for the SC\.--ond l~t of 

chemiC'.l.ll.. 

29 
EPA has not idt.:ntiiicd any ri ~ of concern to human hc.:t:Jth or the cnvironm<:nt. Rr:sist.nnce risks 

to Bt com nrc mitigntcd by an Insect Rcsistttncc an gt.:m~.: nt plan {required by the ccnns nnd 

conditions of rcJ;istmtion). which mnndiJtcs the usc of refuges. resistance monitoring. and grower 

complinnec progrwns. Cum:ntly rcgistcn-d uses of Bt com I'll's ure not cxpc.."Cted 10 result in 

ad,·crsc cff«IS for listed and non-list1..-d SJX""Cics (including poUirotors). or critical h.lbimt. 

However. since the c:ndangcn.-d species dC'Icnnin:uions \\CIT made for Rt com PIPs in 2010 :md 

2012. EPA ;, nwnre !hot addition.> I l.cpidopt<rnn ond Cok'Opl<rnn sp«ic::l have !>:en iS~cd h)' th< 

U.S. ~i h nnd \\'ildlili: Servi.,.,. EM doc::s not cxpc..:t thes< odditionnl species to ul1i:ct prcvio"' 

"no cn~cct .. linding..~ that were mode for both Lcpidoph:run and Coleopteran Ht com. fargdy 

l.x--c.ausc exposure toUt I'JI's is limited to ingestion or contuct with JXtllcn. Nonetheless. EPA 

\\ill again update the Dt com l:.SAs to iJK')ud&: these additional SJ"."'Cics as pan fth~: fin.a1 

ision for these rC'giSiration review cases. 

RATIONAl.. F. FOR PROPOSF.O IIHF.RI~I RF.GISTRATIOS REVIEW m :CJSION 

EPA is proposing lhis combined Work Plan. Summary Document. nnd l>ropOsed Interim 

RcsistrJtion Review Decision for Ill com PIPs(<"'"'" 6SOI nnd 6502). EI'A hdicvcs this 

combined Work Pllln. Summary 0Q(umL"nt. :lJld PropoS«~ Interim Regi!.1rntion Review Decision 

is appropri3tc for the Bt com l'll,s bcc.a.usc: they ht!\'C ~~n continu:tlly reass....'SSC<I since the first 

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 rcsistmtion cxpit:ltion d:ucs . . For insect n.":Sisumcc m:w'lg ... -ment. EPA 

perfomt.~ on~oin~ re\•iews by rcquirin~ (\'i3 the tl!'mu ;md conditions of gis:tr.uion) annunl 

repOrtS thnt provide d11tn on dac efi\.'Cli\'cncss of the progrnm. In addition. the ;\ gcncy has 

con\'cnc.·d 19 Scicruilic Advisory Jlands since 1995thnt hove addre-ssed seicntitic is..c;ucs 

a..~iotcd " i th EPA's regul:uory O\'CI'$ight ofBt PIPs. These reassessment uc:ti\'itks t\ c been 

public proocsscs with docket comment periods. op:n m~ting.s. and the posting of risk 

3SSCSSment and n:gul3tory documents to EP t\ · s website. t\ sumnury of C"ach or these 

rcasscssmrol net ion.~ is de:scri~-d in 1his section. 

A. [Jplring Rt-gistration; 

Ot cont J1Jil n:gistrntion.'\ ha\'c been historic:tlly issued " i th expiration ~tcs. These 

cxpir.uion d:ltc.s haxc allowed EPA to 1'\!\'icw and updntc scientific a.ssc:ssmcnts (or tlte PIPs and 

make cb:lnge-s to lhe aem\S 3tld conditions ofreg.istr:uion 10 irnplement risk mi i~tion me:LSUCCS. 

Et•A ·s scientific ~""<:S.-.ments ofOt C'Om PIPs nre detailed in .. Oiopesticidc Rc~istr.uion Action 

Documents .. (BR.t\Ds) tklt :ue publlc.lHy a"n.ilab(e on BI1

PD's wcbsitl! 

www s:oa.gsw/rs;~ticidcs bj P<'Hicidc!t+' ips). These URADs were updah:d ns part of the 2001 

and 2010 rc:a:iS<Ssmcnts that wcr.: contlucted to support cstcn ions of expiring Ot com PIP 

registrations. E~1c h time :1 rcgistr:nion hltS bt.-cn extended, it lms been a.~ed on a linding that the 

product met the FIFR.t\ n:gis:tr.uion StMdard. 

The first Bt com l'l£' producb. containing Cry I Ab 3nd Cry I F. WC'rC' ft"ii)lert-d 31 

diflCrent times bclwC'Cn 1996 to 200 l. All of th<!S4! product.s la.rgcte!d ll!pidoplcr.m pest$ (c.uc 

6501) :md wt:r..: "ivcn various .::<pinuion d::ltcs in 2001. On Cktolxr 15. 2001. these Bt com 

smnions were ex1cndcd to Ot:tOhi.!r IS. 2008. Concurrently. EPA is.suct!" UIV\0 document 

30 
for CQ·IAb 3Zld Cry IF Bt com <kscribing chi: regulatory and science r'C\'icw actions th:lt were 

conducted ns p3n of the n.'3S.Si!':SSmcn1 co suppon tM n:g.i.stracion \;tcnsion.~~; (E:I•A 2001). 

In 2008. 1hc rcgistmtions \\Cr-.: ag:sin extended to expire on Sc;ptcmbcr 30. 2010. ·fhjs 

llcm~d EPt\ addition:tl time to n:vicw dat:111nd conduct ::tnOihcr cicntific rc:tSscssmcnt to 

suppon longer exte-nsion periods. This s«ond rL~St."S..'ii;mC"nt olso included colooptcr.tn U1 com 

Pills (c~asc 6502). which hnd not been n:o istc~d 01 du: time of the 2001 rc:~.sscss ntcnt. Earlier Bt 

com BRA I) documt:nts were updnlt.'<l oni.l rn adc a\'ailablc tbr conuucnt \'ill OPP"s public 

p.:tnicip.·uion program. Both the 2001 und 2010 rcas:se~th.'nts ore described in more dcuil in 

JX•ns D nnd E ~><!low. 

As n result of the 20 I 0 n:asscs.smcnl. EPA :tg3in cxtcndC'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 for indhidl.L31 1U com rct;.istr.nioos.. Rq;ismuions \\ilh lo"cr risk of insect 

r'c:')htancc (i.e .. pyr.unided \ ruictics) \\CI\! gh·tn longer cxtcruion periods 1Mn those with highc;r 

risk (i.e .. single trail producl<). The specilic mclhodology. o.< d<-scrih<!d in I he 2010 BRAD 

documents. is ns follows: 

···n tc fcxtcnsion troh:~y) iuclullcs n:gistmtion periods of tin.·. cighl. and twelve years: a 

liftccn y~ar rl!gistnltion period \\i ll3lso be :l\'flilobk. if adc<1unlely SUJ>poncd by our 

science ns.scssmcnt In this scheme. (i) n product \\ith a single 1•11' toxin. nml a 200/o 

C'XIC"mal n:fug~. qunlitics (or n fi\'C ycar r~gist.rolion: (ii) U product \\ith pyrn.midOO F•tP 

roxin.'i (i.e .. t\\'0 or mor4,; toxins with di.stin.;:t. non-c.ros.s n:::tcling modes of nc1ion). that an:: 

non-high dose (the dclinition for 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 rcsi,tr,Uion: (iii) Q produc-t \\ith 

pymmidcd PIP toxim (i.e., two or more toxins with dhlinet. non<mss reJcting modes of 

t:~ction). that :1rc high-dose, \\ilh either o S«d blend or cxtcm:t.l rciugc. qmlifies: for a 

tweh·.: ycJ.t rcgistr:Uion: (iv) 3 rrocJuct \\ith pyramided J,JI, toxins {i.e .• tWO Or mon: 

toxins \\ilh distinct110n...:ro:..s re-ac-ting modes of nctions). with d thcr u seed blend or 

external refuge, tlmt has been dctcmtined by EPA's scicm:c u~~ssmcnlto be 1 500/o as 

durable us the baseline single toxin produc.:t with n 20% c~ tcnt l refuge. would qualify for 

n tiliccn yc:ll' r.:gistrotion. t•mJucts determined by El)t\ 's science assc~sm.:ntlo be lt:s.~ 

th.:m 100% a·o; durobtc us the b:lsclinc single toxin product with o 20% c.xtcrnnl refuge 

\\Oul\1 not qualify for a fh c )'cnr rcgistnnion and the ~~is tr..atio n period for such produclS 

\\ill be dcccmtincd 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!)'UUXC' conc;cms 

may lx: prcscnL \\Ould Dlso b: dct(nnincd on n c.lSC-by-ca.sc b.l.sis. 3S "ill novel Kfugc 

configur.ltions t1ut nuy p~nt unique dur.lbility profiles."' 

FoliO\\i ns this st.mtcgy. Ut com produ,ts " i1h single:: toxins were extended until 

cptcm~r 30,2015. Olhcr pymmidcd producls were given c~tclu:ion$ oiS-12 )'Cili'S (no JS year 

extensions \\'en: appro\'cd). l•rior to further cxu•nding these: rcgistn.lions. J;Jlr\ \\ill C\";t)uatc 

whcthc:r they still meet FIFRA rcgiStruliC'ln .stnndnrds. For the colcopt.:ron llt com \':trictics that 

~p rc in 2015. EPA is cul't'c:Jll1y working to impro\'C the insect r\!Sistancc m:tnng~mcnt strotcgics 

for cont root worm (sc:e the ln.sc.·ct Rcsistnnce MM.:tgcn-tent portion of the Scicnti lic ASSCS.."ffilcnts 

S(.'Ciion). though the.."k' cHOrts will extend p3Sl Sept.:m~r 30. 20 Is. To ollow lbr completion or 

these ncti\•itics. EPA will cxtcnd lh~ opiration lbte of these products to Jnmury 31. 2016. Other 

Jl 
single 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. lnnoct Rnist:ant(' :\hn:a~('mcnt 

~ct resistance. :mag~ mcnt (IRM). described in dctnil in th-.: Scicntilic 1\SS(S.SmcnL'i 

section of this document. oddrc.ssc...~tn risk to Bt com PIPs: the potcminllbr tnrgct insect pests to 

ad:trt h) the Bt toxin(s) in PIP$.. rcnd cri n~ them inefTecth·c for cCintrol. Since I) IPs h:t\'e bt.--cn 

registered in the 1990's. IR.M ho.s been rm tmcrt;ing science th:~t hus r.:quirx.-d EI~A to 

P<riodically roasscss and odjust its rc~ulntol)· approaches (Mottcn ct al. 20 13). 

EPA's tus fn.--qurndy utili74"<1 the FIFR.t-\ Science Advisory Puncl (SAl') as a mCJ.ns 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 afier the first Bt com rrgic;;.trotions were appnwcd) helped establish core mitig3tion 

~tnllcgies including the usc of refuge to delay the development or n:Si<iiWICC. Subsequent SAPs 

ha\'c pro\'ided guid3t1cc 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 stewardship JJrognun. significant data review and unalysis for IR.M occurs 

nflcr the product arc rccistc:n!\1 (I.'.Q .. r.:sistrmcc monitorill£,). To illustnttc.·. tWA has required 

\'arious tcnns of registr:llion to nddr .. -ss thes.: risks and assess the cf'f'cctivcncss oCthc JRf\1 ·

~tm t.:gics. Scvcml of the temu ofrcj;i)tnstion require annual rC"ports to be submiucd 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 through the t\t;ricuhur.a113iotC"Chnotogy 

Sti!Wardship Tcchnicul Committee (ABSTC). u con!!oOrtium of the PIP rcgistr.mts.. 

such that one SUI"\'CY covcD all kpidoptt!ran and colt'optcr.m·prott.-ctcd Bt com 

rcgistr:stions. A S'-"CCind compliarn;c nsp«l in\'olvcs the usc of on-fonn 

ac;;.scssntcnts. in which L'ach rcsistrant visitS II AAmrlc Of their CUStomers 10 1'\!\'iCW 

ndhen:nce to rcfuJ;c rl!tluin:rncnL'i. Growers may ultimately be denied access to 

the company's Bt com proc.lucu if found out of complinncc 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 indicator of re$iSl3nCe). and 

2) snmpling nnd testing tar~ct ir\St."Cts to dct«t nny shills in susccptibilit~· to Bt 

toxin(s). Dnu1 for -.:ach of the major lepidopteran nnd cokoptcron tnrget pests arc 

i11Cludcd in the nnnunl r-.:ports. 

Data from these rcpons allow the Agency to continunlly rc,·icw th.: adt'quacy of the IRM 

trmcgi-.:s and make ndjwtnu:nts: as nccdro. To illustrate. submittC'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:nns 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~. concerns about the 

ck\dopmcnt ofresb.'t:l.nec ;unong com n»l\\Onn lriggcrcd a re-a_~(J11Cnt of the IRM program 

for coleopteran Ot com (SC'(' scclion F) below. 

EPA rc\•icws ofth~.: rcfu~c compliance and resiSt:tncc monitoring data arc- publically 

lWnil:tblc in a docket est 1bli hcd lbr IRM: EJlA-JIQ-OPP-2011 -0922 (rc:gub.tions.gov). In 

nddilion, UI'Jll} scicntb'ts fr\.·qwntl)' pr..:.. n1 dntu from such reports ot scic:ntific rncclings (e.g .• 

Cntomologicnl Society of Amcricn) und o1hcr forums. 

A key <Ompon<nt of EP,\ ·s "'"'-«<>m<nts ofBt PIPs hos b..-.:n the I'll' IV\ Scientific 

1\d\ i.sory Panel (SAP). The SAP scncs 3.S :m independent p:cr rc\ icw bod~· nnd consiSL~ of 

scientific expertS in ::1 r.ms;c of di..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 to rro\·id(' \\rittcn :md!or or.d 

comm~nts, nnd o.n: conduct«t in .1ccorcbncc with the Fcdernl t\d,isory Committee Act (f ACA). 

Since 1992. EPA a~ con\'cnl-d n total of 19 SAr• meetings rdllh:d toUt PIPs. Though 

three of the-se meetings \\'t rc specific to Bt couon PIPs. most nddrcsscd scientific issues tOr Bt 

com PIPs. A list of these mcctinJ;.S is dc:tn l<. l in Table 5 below. At present. no ndditionll 

mcc:tings an.- planned. 

St\P mc:clings ha\·c bc~n hdd to 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.1gcmcnl. Specific 

p.lne!'l~ hoYc :dso focus..."'ti on nmcl Ot PIPs (e.g .• first corn rooh\Onn PIP). ri~b for existing uails 

(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'Ontinu311y cmcrg.ing. 

lhcsc meetings Jmve prc.wid~d a mc:ms for E.I'A 10 :u:fdn:s,s new scicntific issues that h::t\'C arisen 

since rc:gistrntion. Ex:unplcs include n-t: ~.:t con.e:ems (t'.g .. gene flow. toxicit)' to moiUU"(h 

huttt: ll ~). human health co et:rn~ (t:.~ .. :-11lcrgcnicity). and irucct Tl mnct mnnagement (e.g .. 

insc:ct biology. seed blend t~: gc), 

Tllblc !li. List of FIFR..o\ SAI•mct:tings rclatc:d to scientific issuc:s n."lsoci:ucd \\ith Bt r•J Ps (Table 

udnptod from :VIon<n nt ul. 2013) 

FJFRA SAP Mtttiag\ D21t(s) Topics Co rnJ 

Subp.md on Pbnt Pcsziddc:s' IA...:nnbC'r 18. 199.2 ()dining ris.J..s of PIPs 

Subp.'llll'J on Pl::mt Potiddcs ~brth I. 1995 t-.ton,.lullo Comp.tny' s 

npplk:nion for registnnion or 

Bt ub x-.: cs ft•m•brlonls tldlu 

\.'n ~in 

J Ploant·pnlkKies \\C'fe rM.l."nCJ rt;IJH·ii'IC'Orpor'.IIC'd pi"U(C"CtlllU (PIPs) i.n 1001 (ollov.inJ; pubJic3cion or PIP 

' ""ul.lltioni in lbC' Ftderlll Rq;iutr (RC'i.UI.Iilions l.'nJC'r th<' f'tdC'r.lllm«tKkk. un~icJdC'. ll.nd RodC'nlicidC' Ace ((W 

rbnc·lrKorpontC'd Proc.«Un.ts (Focmnl) ~t· f"nlkidn. fe'd<r.IJ R~Ut" 66( IJ9): J1711-l7SI7)-

33 
FIFRA SAP l\!C<'IinJ.:.!i llutr(•) TopiC's Conn:d 

Subp:md on Dr Plr.nt•P.:sticides :.nd Fcbru:uy9·1 1. 1998 /Jt r'lll insect rcsist:mce 

Rcsisuncc: M:truscmcnt m:uusnncnt 

Out::u:tniLDtton and Non-T3J];d OrpnMl O«nnh<T 8-9. 1999 ProdiKt cturxtcriT.:llion. non· 

Requimnn'lt (or ProtC'in Pbnt PotiC'iJci l41b-et Of~nisms 

Food Aller~enichy ofCI)9C Endoco~in 11nd Febru:ll'}' 29 - Ma..:h 3. lium:m hc:ahh 

Other N'on-dit:\."Stiblc r•r(lteins !000 

l\·13mm.:'llirm To.\icity Asses!iment GuiddillC's June 6·9. :woo Product ch:nactcrirntion, 

for Protein Pl:tnt l)oticidcs hum:m he 31th 

l!i$ues Peruining to the Bs Pl:.:mt·Pc)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~\"111Cill 

Ao;;sc.ssment of Scientific lnfommtion S'o\·c:mber 23. 2000 II unum heahh 

Conu ming StRrLink® Com 

ASSC'iSrncm flf ,\dditional Scientific July 11·18, :001 flum n hc::thh 

lnfonnation Concerning Swlinl Com 

Com ROOI\\l'fln Plant·l~orpor.uN August 27-:!9. 2002 Non•t.trlrt in.'C:'Cts. iru«t 

ProtC'C'tanc lnS«t R~isbnce ~l:l.n.l,Crtlcnt ~i:.un;;~ mJn~gement 

and on· g~c I meet Issues 

Product Clutrnctc:ri7Aiion. llumtln l ll•Bhh Ju n~: 8-1 0. =oo-l \Vitk SLrikc-1\ cotton hum:m 

Ri.">k. Ecologic:.1l kisk. t\nd s~t R\.'stsumcc he:.hM:colo,t;ic-al risk 11nd 

M:ma ml!'nt F'or Bt CoHcm Producl) insect r~:.,i~oL:mce m:sn:tgcmmt; 

llollprdlb ;md llollt;.1JillP II 

inS«t r'C"i~e m3ll.l£nnmt 

Sticntirte Issues A"'SSCi:stc:d \\'ith.th" llumttn Mnrch 1·2. 2005 Hum:t.n fK"Ilhh 

I k ah.h .s.scss ~:nt of The Cryl-lAb I t'rotcin 

E\'cnt MIR(tQ.I Modilie;:l CryJA l'l\"'tt:in llt Mo.:h 14·1S, 2006 llumnn hcahh. 

Com··PI:.m lncC"trpor.atcd Prot~t:. m em·ironnl.:lllalft\:ologic31 rh k 

issue~ 

Arut~ sis of :1 N~tur.aJ Refuse: of~on.Conon June Il-lS. ::006 lns«t rtSiSW1« m~n~gC"mcnt 

Hosts for MonS3nto'.s Bollprd II Conoo 

E\ 41\IO'Ition of the:- Roi:)(:lncc Risks from <Xcob.."f 2J-2S, ::006 lllX'.:I r;;sisc.-.ncc m3n3gc:mc:nt 

Using 100~~ 0C'IIIc:..rdt: and Bollg;,rd" II 

Conon as r•nn ofn l,ink Bollwonn 

Er.:ldieation Progmm in the Stat\: of 1\ '1.. 

Rcsistttnce Ki,b from Using A SC'C'd Mi.x 

Refuge \\ith Pion«f's Op1imum ,\crcM:il.'l 1 

f<bf\ury !3~25. 2009 InS« I tc"i'1An« mtt.tUI£,C:nu,,il 

Com RootY.onn·Protttlcd Com 

Scic:-ntirte IS5UC'$ As.~i:lred "ith f)Jta fc:bruuy 25·:!6. 2009 Prodm <h.:trnc ltri7:~1ian. 

Requin-d 10 R~gislcr Pl.:mt-lncorpOr:Uc<l humttn h<ohh. non·l:trgc« 

Prolectnnli on:a hm~. '\:1\C flow 

JJ 
flfRA SAP )fotl;nt:,> O.t<(•) Topits Co\ rt'd 

lnscc• Resil.t.mcc M:uugcmcnt for 

Sm3rtSL1.~n.t RC'fug~:-l Hhc·Il:llt-ll tJI:uU· 

De<<mb<r S-9. :010 lnS«I ASistMcc mruug.cmmt 

lntC'ItpOr:tl4'd Prolcc-tant (I'll') Corn S«J 

Blend 

Scientific Uncertnintie;<; As..'"Oei:Ucd with December J-5. 2013 ln:.cct rc-s- rmcc m~n:tgcnu.•fU 

Corn ROOI\\Orrn Rcsistn.ncc footo nitorin.: fl)( 

llt C('IOl rt~uu lncorpornted Prot ~UU I.S (P P~) 

ll. 2001 Bt PIPs 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,ish:rc:d PIPs in Bt com :u the 1irnc (c:ouon :md pouto PIPs "m; also included in the 

rt' .. lSscssmcnt). This rc,ic-w was trisscn.-d by registrations that w.:rc aimed to t:Xpirc on various 

dote" in 2001. As a rl!sult of1hc reassessment. the A gene\' decided 10 cKtcnd the Bt com 1',111 

- . n:sislmtions 10 2008 (sec se<:tion A abo,<). 

EI)A 's 200 I rc,·icw was "conducted :~. J on open nnd trnnsparcm public process that 

incO rJ){)nll~ d sound and cumnt ~icncc. :and substantial public in\'ol\'t.:lllt.:nt .. (CPr\ 2001). EPt\ 

rcvit.:\\cd upd.1tcd scientitic intbnn:uion for product chn..ractcri,...ttion. humt1n health. ecological 

c:llC.cts. insect raisuncc- m;U\OJ{;Cn1Cnt. ru'!d bctlclits. Guidan~ from the multiple SAP 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) was crc::~tcd during I he r~rntlo 

document the Agency's scimtilic C'\11IU.1tions ~PIP regulatory hhtory (EPA 2001). 

EPA concluded tktt Cry lAb and Cry l F Bt com do not pose risks to huml.n htahh or 

to non-target species. although risk concerns were idcntitiOO. tbr illscct resi~trmcc man:tgcmcnt. 

'OU:' ~VieW a).SO identifiel.f Clc~lf bC'ncfiiS in ICm\S of OCOn(lmiCS, hliiT)!IO henhh (cOO\'CntiOil::tl 

pesticide reduction). ;md the c•wironmcnt. To adllrcs.s thc-IRM concc.·ms. the Agency imposed 

t..:rms of rcgistrJtion (included us J':trt of the llt com rct;istrJtjon t: cnsiC'I l.lil) 10 estnblish rl)'fuge 

n:quiremcnts. ri'sistnnce monitorin.:. t;mwcr education. and compliM<:c las~urnncc . In nddilion. 

tcnns m:re included requiring 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 levels in soil 

• Non ur~ct cbta: non-target i~"Cts. morun:h buuerOy c .-y1Ah long tcnn cx·posurc. 

chronic 3\i:m test 

• Insect R"sisunce M!!..nOf.1:111C'nl: potential for nonh·.south 1110\'Cmcm of corn ca.rwom1. 

impact of insecticide usc in r..:fugc.s., dc\'clopmcnt of o discriminating test dose for 

south\\'('Stem com bon:r 

TI1c tfnln described obow '' re subsequ<:ntly submitted. n.:\'icwcd. ond incorpor.ncd into 

EP,\ ·s 2010 Bt com reassessment ()(:c the folfo,,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..'imcnt wns condu,tcd OS 3 public proc~. with multiple 

opponunitics tOr stakeholder in\'Ol\'\.'11\\.'nl. EPA considered all public commc-nlS in lin:1li1jng the 

reassessment and regulatory posilion (El'A 2001). Public input \\1tS oblnint..-d from the followins 

ncaivilics: 

• SAP pcc:r ft'\'iew of El)A 's rc:lsses.smcnt (October I -20. 2000: Report issued 

March 12. 2001 ), Open J>ublic JUL~ting \\ith opportunity for public comment 

CPA's drnJ\ reassessment (BRAD) \\':15 m::tdc :l\'ailnblc in the public mc:cting 

docl<ct. (SAP website: 

hnp:b\ "'"'" . .;(Sl ~O\·/ i ooJ 'ISJ(! m'-'~ i ngsi200Q! I 0 I &00 mtg .htm) 

• T""hniC31 briclin& for the Bt PIPs 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 period for the Bt Pll's re3SscssmcntlllRAD (July 17-,\ugust 31, 

2001). Or<n public camment rcriod on the drnfi risk mitigation and regulatory 

options dcscrilx:d in EI1A 's BR.t\0 document (nnnOIIIlCt.."tl in 66 FR 37227). 

t:. 2010 81 Corn RrnsstssmC'nl 

Similar to the 2001 rcassc~)1t cnL EI'A 's 2010 review of Bt com was uigscn.'d by 

expiring registrations. In 2008.all B1 com rcgisuations were extended to September 30. 2010 

(S<'C section A ot>o,·e). To suppon funh<r extending th= n:gisu:uions beyond 2010. EPA 

n.-e\·nluah.-<1 current sdmtilic infonn.1tion. n:\icwcd Studies h."quin."'C!M h:rms and conditions of 

reghu-.nion. nnd updated BR.t\ 0 documcnl~ for cxh Bt PIP toxin. The 2010 QS.SCMmcnt 

included the CryiAb and Cryl F I'll's that"""' the focus of the 2001 n:usscssmcnt os w<:ll t\S 

other Ot PIPs registered between 2002 nnd 2009. These n~wer PH•s: included com·rootworm 

\"nrictics {co,;c 6502). 

The fl)llowing Bt PIP to in~ wei'\! included in chc: 2010 re3ssessmcnt: 

• CrylAb 

• Cry IF 

• CryiA.IOS 

• Cry2Ab2 

• CryJ[Ibl 

• Cry3~Abi CI') 3Si\bl 

• mCry3A 

A major pan of the 2010 rcnsscssmc:nt wa.o; IR..\·t. r•ast reviews of complianc.c dutn hnd 

indlcutcd thut adherence to rc i. ~1: f\."quircmcnts \\1tncd in the yc!lr$ pn:ccding the reassessment 

(UPJ\ 2010a). To ;uJdress this issue. EP,\ imposed terms of rc r:Hi n f\!quiring that registronts 

implement additional mC".tM,lO:$ to imprm·c rdu1;.c compliance (EPA 20101), 

36 
EP,\ ;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 caddistlies were not cnu.scd by llttosicity. but were due to other ditli:rcne.:s bs:t\\CCn 

the nttc: t substnnccs. In reg,1rJs to non·tnrsctlnscct testing.u JH'C\'ious SAP (2002) had 

rc:commcndcd tcstjng Oriu.s inJidio~ s (minute pi rotc bug). Thou~h EPA ~qui red OritLf test in£. 

1\:'glstrants t;.'S(X:'ricnccd logistic:1l dillicuhic:s in testing the in.S'-"CI. liP A rc:c\'uhmtcd current 

scic:millc iniOnnruion and concludi.-d dun toxicity to Orius(a Hcmipt\!ron insect) is not c.xpc<:tcd 

since the toxicity of the ~si.stcrell Ot PIP tr::tits is restrich."<< h) Lcpidopu:r.m nnd Coleopteran 

inS«l~. Both of these issues wen: rl!\'iC\\Cd in EPA (201 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 indirect effects) for nlllis:ted 1hreatcncd or 

cnd:mt;er"d species. llu:rcforc. no CCliUllhations \\ith the U.S. Fish and Wildlife Service were 

n:quirc-d under the EndaJlgcR.·ll Stx"Cics 1\ct. 111e upd!ued :l~SCSS Tlcnts nrc dctnilcd in h~ BRAJ) 

document lOr c:1ch PJI>, 

No ch;u1£.eS were needed for EI•A 's hum!ln health J,Sscssmcn&.s (compleh."<i lOr the initial 

rl!gistr.-uion of 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 solicit public input on the n:3sscssmc-nt EPA utiliu---d the public p;uticipation process 

dc\'dopcd by the Oilice of l't'!iticidc l)rogr.uns in 2009. l11is proC't').S W:\S estnblished to increase 

opponunities for the public to ~;onuncm on pesticide risk nsscssmcnlS nnd proposed registration 

oct ions Gill p;//www 2. CJxt. t;o\' nc~t idd !J·Icg is 1 mtio nlpu bl ic·p~l n ic j nat jo II· p[S)(!.'"-o\· rc l:ist tJtl.Uw.: 

ncairm•). For the Ot com n:as.sc:ssment. I!PA CSlfiblishcd n c.lockct in rc~; ln ons go\' (EPA4 HQ· 

OJlJl-201 0-0607) \\i lh 3 30 doy .. ·nmmc:nt period. The r\gcncy poSit..'illhc following documents 

for comment: 

• 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 ror Cry3Bb1. Cry3.Sf3SAb1. and mCry3A 

• Rc\iew of aquatic in\'Cnebr:ue and Oriw' tCloting ;~,ucs 

• Proposed tcnns ::tnd condition.;; for the Ot COI'n rt:gbtmtion ex. tensions 

EPA rt:'Cci\'ed ra totul of 10 comments in response to the public p:trticip:ttion process. 

SC\'CII conunc:nts were n.-cdved rrom Ut corn registrantS on~into. S) gcnt~l. Dow. PionC't'r. 

and J\ llSTC). one from the :-4atioool Com Growers Association. one from 1he Center for Sd~ncc 

37 
in the Public lntetl-st. nnd orK" Crom I he J\ssodation of J\merican S«d Control Oflkials. r\ 

n:sp<> ~c to commc:nts was posted to the docket after the t:ommcnt period concluded. 

ll!t..~ on the rtasscssmcm. EPA ex-tended the Il l com n:gisrr.nions to d:JtCS between 

September 30. 201 S and September 30. 2021. in acroRb.nce \\ith the str.ucgy dclailcd in section 

A abo\"<. The firulizcd lonn.< :>nd condilions (EPA 20101) :>nd updnlcd BRADdo<umeniS (EPA 

2010a·<) ho'< bl-cn posted 10 lh< ,\~•'fl<y"s PIP web Jl-1&< 

(ht [!j wwW \'p: ,.:o\·/rei'ticidc bin!"X.':-Ii~t:jlh:s sli ndcx hlrll). 

NEXT STEPS ANil TIMEI.INE 

,-\ Fcderul Register Notice \\ill3llll0uncx the a\·:lii:Jbility of this: combii'K'd Work l,lan :md 

Swnnury Documc:nt and PropoS«! Interim Rcgistr.nion Review Decision fur lh com PIP.s Md 

I low n 60-dny comment period. If there are no sisnificn.nt comments or additiorY.ll inforrn:Jtion 

submined to dtc docket during the comment period dun kads the Agency to ch•anbc iL..; proposed 

dr:cision. EI'A may issue M Interim Rcgis'lr.'llion ltcvicw IX-.:ision for Ht com PIPs (cases 6501 

:md 6502). However. 3 final dc-ci:,.ion for Bt Com PIPs may be issue-d without h.:wing previously 

issued a.n interim dl"Cision. A fin31 d«bion on the Bt conti'IPs rcgistr.uion tc\'icw c-ases \\ill 

ocour 30<r on EDSP FFDC,\ S..'<:lion ~OS p) <k«rmin:uion 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 comrletcd. 

EPA hi\$ created the following ~o-stimatcd timelinc for the completion ofUt com PIPs 

registration review. 

Rc-;:i,lnallon Rt\;('1\' ror Ill Corn PIPs- Projrcrrd ktgistr.ation Rt\'itw Timrlinr 

Acth"ilirs I F..itim::~~tt'd Oat'" 

Opening lhc: Docket :>nd Combined Work Pl:m. Summ:lf)' Do<umcn~ :md lnlcrim Rq;istmrion 

Review Decision 

Open Public Docket nnd ,-.ublic Comment Period for Combined Work 2015 - September 

l'bn. Summ1~' Dotument, and J)roposc:U lnterim Rcgistnuion Review 

Decision 

Close l'ubli< Commrnl Period 201 S- Now:mber 

Interim Rcs:islr.Jtion Re\•iew lkdsion 2016 June 

fin:tl Rccistr.uion Re\•icw IA"Cision ond Begin ost-~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 ~llmg~mcnt. niopcsticid~ and Pollution ~\ cn1ion Oi\ision, \Va)hington. DC. 

EPN73?1S-98/00I. 

1 i\ fin:t.l deci.~o n on the 8ur-Jllw thurif!J:,Itmb Nlm·incorporntN f'Mc-cttnu in Com ""Shtrntion ~vi(".v c.ues, in 

a.ccord.mce with .SOC FR S«tionl55.1 ~8. Y.iU occur :~ftc-r :m [ I)SP Fl'I>CA S('(lion .:OS(p) dclennin3lion h:tS bfC'n 

m3de .:tnd thr l.'ftdtVI!~C1\-d s:p«ic=s :b.WiSIIlC'nts lu\C' been trpd3.1C'J 

38 
EP:\. 2001. Biopcsticidcs Rcgistr.ll.ion Action Document · Bacillus thuringicnsis PlantIncorporated ProtcctanL~ . Dated October 15, 200 I. t\\'rtilablc ot: 

http://\\'' w. cp.:l.gov lt,)tJChmx! llbjNxs:t i c i dc§.i je:o/b~ bmd .ht1n. 

EI'A. 2009. 13iop<:stidJ.:s RcgistrtlliOn t\ction Document: Dncillu.~ thuringicnsis Vip3Aa20 

Insecticidal Protein and the Genetic Material Necessary for Its Production (via Elements of 

Ve<tor p:-<OVI300) in !;vent MIRI62 Maize (O!;Cll Unique ldcntiticr: SYN-IR162-4). 

A \'ailablc at: hup://www.cpa.gov/oppOQOO llchcm search/reg :~oc tio s/rcgis tration. dcci ()n PC006599 3·t\pr-09.!'9f. 

EPA. 201 Oa. Biopesticidc Rcgistmtion Action Document: Cry lAb and Cry! F Ba,·il/us 

thuringh·nsls (Ut) Cont l'l:lllt·lncorpomh!d Proh."'\:t.anLii. Updated September. 2010. Available ut 

hllp://\, ww. c Qf!.!.!!.W I rc.-1' ticldcstbi QI?C§t kidcs/p i rsfc a· I f:.c;o·l :'tb-bpd.pd f. 

EPA. 2010b. Biopcsticidc Registration Action Document for Bacillus tlmringifnsis Cry3Bbl 

Protein nnd the (jenctic Molc:rial Ncccss:lry lbr Its ProcJuction (Vector I

1V-ZMIR 131.) in MOX 

863 Com (OECD Unique ldentiticr: MON-00863-5). 

Ill! p j/ /www .c p:l.J.!lW /oppbppd 1/b i opcsticidcs.fpi psfcrv 3 bb I · bmd. pd r 

EPA. 2010e. Boeillus thuringicnsis Cry34Ab l :utd Cry35Abl Proteins ond the Genetic Mmerinl 

Neces.snry tbr their Production in E\'cnti):\S-59122-7 Com Biopcsticide Registr::nion Action 

Document (BRAD). Revised September. 2010. Available ttl 

h 11 p:/1" ww. c p;1. gov /oppbppd 1/b owsticldc~ i n grcd i c ntslu:c h docs.lb rnd 006--' ?Q. rxU: 

EPA. 2010d. Biopcsticidc Registration .. \ ction Document: Modified Cry3.-\ l)rotein and the 

Genetic Matcri:ll Necessary for their Production (Via Elements of pZ~ 26) in Event 11R6~ 

Cont SYN-IR604-S. Revised September. 2010. Availabk at 

tp:l/w'''"·coo gm·/JX--slicidcs.l opc-~ilici :s ps mcrv3 ms;LndJ: 

EPA. 201 Oc. Biopcstiddc Rcgistmtion t\ction Document: Cry I A.l 05 and Cry2Ab2 lll5Ccticidal 

l'roldn...;. nnd the Genetic f\·laterial Necessary for Their Production in Com {PC Codes 006515 

(Cry2Ab2). 0065 14 (Cry I A. l 05)]. Upd;ttc<l September. 2010. A voilablc at: 

http://\\'\\'\\', C t)J. go\' /JX""51icidC'$..'bj CIIX'st ic dS' pj :m · $4}0 34 • hnul. (XI f. 

EPA. 20!0f. Tenns and Conditions for Dt Com Regi:amtions. :\vu.ilabfc at 

h tt p:/1\\ W\\'. cpa. gov lop pbppd lib i opcs ici c~pi ~!bJ:5C'l DJ ·tc nns.cond i 1 ions. pel f. 

El'A. 2010g. BPPD Response to t\ BSTC CommentS (In l'roposcd Tcnns nnd Conditions for 

2010 Expiring Bt Com Registrations. Data Required to Register Pl:mt-lncorpor.ncd Protcctants: 

Aqu.:uic lnwrtc-brntes and Orius Testing Issues. Memorandum from Z. VuiurLis coM. 

Mendelsohn, d::th!d September 17. 2010. 

EI•A. 2013. White l .. upcron Com Rootworm Rcsistonct' l\·fonitoring tOr llt l .. llnt·lncorpomtcd 

ProK..:Illnts. September 27. 2013. Availnbk in OI'P docket" EPA·HQ·OPP-2013·0490 (sec 

ht t p://w'' -w .cpa.govt S<; iool v snvtms£.l.illb O 1311 2o.4 I 3m«t i ng .Juntl ). 

39 
(io..~.sm:mn A.J., J.L. Pel7.old·tvfa.xwdl. R.S. Kewcshnn. and t\•I.W. Dunbar. 2011. Fidd--c,·oh·cd 

resistance to lltmai1.e by western com rootwonn. PLOS om: 6 (7): e22629. 

hup:lfdx.doi.or£1 I 0. 13 71/joumal.woc.0022629. 

Gassmann AJ., J.L Pctzold·Ma.xwcll. R.S. Kewcshrul. and M.IV. Dunbar. 2012. Western com 

root worm and Bt maize challenges of P'-">:S t resistance in the field. GM Crops ami Food 3(3): 235· 

2-14. hup:/ldx.doi.org/1 0.4 161/gmcr.20744. 

Gassmann A.L JL Pct wld axwcll .li.ll. Clitlon. ~1.\V. Dunbar. A.~t HolTmann. D.A. 

lns,bcr. and R.S. Kcwcshan. 201~. Fidd·<.:\'Ol\'cd resistance by western com rootworm to 

muhipk Bacillus thuringiensis toxins in mn ~n c mfl .c. Proc. Nat. Acd. Sci. Il l ( 14 ): 5141· 

5146. hup:l/\nnv.pnas.orglccildoi/1 0.1 073/pnns.l3!71 7? 1 I I. 

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tields by Western com roon.vorm. The Bullrtin No. 20. August 24.2012. 

ht 1 p:/1bu I let in. i V'". iII i no i cdulo.rt clc. php?ld- 1 704. 

Huang. F .. J.A. Qureshi. R.L Meagher. D.O. Rci>ig. G.P. He:•d. D.A. A ndow, X. Ni. 0. Kent<. 

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41