a1." g- UNITED STATES- 5 NATLDHALCENTEH FGFI 1.5 ENE-CI FEE EB 3315 HEEFJFIEH huxtiu IL I: Ilimulnr :?imcricim ancighl. EUSU 15 5.1er I'I'r'lithililiglull. RE: FrL-ullnm Iif Mt Request ND. Mr. Iirurt'n: 'l'ii'sh' letter is. in rusimnsu- In yuur l-?rccdum 111' .r'icl ruminant duiud 31. In I 5. mulcsling: I A mpg: ul?tiiu ducumuni untitlcd ?(Shim-951mm: chuctil ti'rr Carnelian" w: The diwilmcm is must tn hi: I'uuml in the U?iuc nt? All: 1i In lib: dwumcnl idcmiliud in part I I L?Il'ti'l'l? I'mm Suplumimr I. 1n the dutu the search is. mnduutcd. 1111: march I'm rusWIizaii'u should includu: :Iii inuulium 41ml indi'u'iduulh' iikcly Ln mnmin ruiiImnHi'L'I: rucurdj, including :11 learn the I?ullmi?ing: R3511 Hun: [ital-z. Richard "I?nmminJunnit'cr Unm?Im-ututu. iimu?n. Mil-u: Susan Burdcn. Huh-m Huriuuk. Elma: Hrir-i 'Hiu} ur. and lium?ui, Huimir Sh?ilu. 'I'hunma ['hriulnphur Hui-ha. lilizinu ?L?i'ung, Lind Siuumu Thu: rccunl ii; rcimsilii: in copy ul'1l'h: iil'luill'liuni untitlud Jim] unit ['umtlinri-" gum}.- uxfuui? mnnpiL-Ie its magnum-u: ruquuzal thruugh 11 milling ink-rim prmiuclinn. rcquc? is nnl: i251:ng uluwd thir: limc. ?L'r'iiun yin!" rqulL'hl iH L?lnwd. lulu will muniti- inlhmutiun cmwuming your 311-pqu rights For 1.1111." 1.'I.r1 [t?zrnu ilil'nuun'y queatiuns 1I1i.~: interim prndu?i?n ur jutrur Icq ucsl Erma?ally. picnic LL'biil.? Mcudmw :11 . il. at by pimnu Eli?-an-i-T-IH. Additiunully. }'Ull may suck Ihim Film E'uhli: Liaimn at uril?ll in [?rm Eh: lti?rrmuiinli Eunice-i "I'nu may mum-cl in [my will}: l'ulluu it?;I lambs: 115' mail. Ul?uc ul'?urumniunt Inihrmulinn Hun'iccra. Hnliunul LLHLI Records Admini?lmlinn. 25 EM [1 ?ducilphi Fin-4d. [Tullugu Park. ugih?u' 1437- WW5 l1l' I'm-g. 1 HTML: 43- Hincu rd}: 915?; Mary H1355 Hum"; Illircumr I'm Hulmgunmm Harm-nut ['cnicr l'qu Em'imn mcnm] .rihhuzmmunl UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, DC 20<60 Jonuruy 25, 20 18 Robcn Holden Lis.kow& Lewis One Shell Squ:,rc 701 Poydr:isS1rccc, Sui1c 5000 New Orlcnn.o;;. I.A 70 I J9 orr1ccor lpn•n.: (C.~SNo. I 26-99•8) In Support ofSummary /riformntion on th,• /1111..·Kratt.·, J Ri.d, /nfornullion .~,•.ffem (IRl.'i]. disseminoted by EPA ·s Oflicc of Rcscnreh nnd llcwlopmcnt (ORD) in 2010 (n:fcm,d 10 herein ns the " IRIS chloroprene o.PE' s con1oc1 infonna1ion: and Section VI sets forth 1hc rdicf1hat DPE is seeking." The F.PA R~~pon, c to OPE Rt'qucst for Cor tt clion lo the-Anochmcnts to lhis response. Ef'A addressc-sthe n.,.,.crtion..-.and topics raised in Section III of the in chc IRIS chloroprcnc assessment RFC:as thiS;scclion is relevant to the science cvaluntion reprcscn11:·d under EPA·s Guidelines far t:1twring and M,uimi:in,: tl1'• Quality, Ohju1friry. U1iliry and lnt,•griry of Jnformmion Di.u,•mlnat,·d by the Environmental Pro1,•rlfon Agenry (IQ(;). 1ltc!intbm 1ation Md usscrtions in 1hc 0 1her ~-ctions a.reeit her not in dispute or a~ nol pc:rtinenllo 1hc cvaluution of science i.ssuc-sunder the RFC. 1/t~Nlt-l Addrtti R..c,ti...'111:...:,el • ~ ,,.fit,~-"" (URl) • llt:p i,'"'WM ~.l v~~ ()II ~ • 114llr,lu Ol'I 100')1,,.OltcO<'l•u- QO'o' . ""°'"'CllolOl'IIM''" RKJ «.d PfP,.I EPA-18-0077-A-000001 Conclu~ion The EP1\, after careful review of the RFC ~ubmittedby Oft£. has concluded 1h01th-e underlying infom1ation nnd conclusions presented in the. Toxicological Review o/<..Jrldrop rm t' (CAS No. I ]6-99-8) In Suppt, rt of Summary lnformatiou on the lntegrGtt, I Risk Informatio n Sy,1em (IRIS) ate consistent ,,.i lh the EPA's lnfonnation Qu:1lity Guidelines. Your Right to A11pu l If you arc dissa1is licd with 1hc re-sponsc.you may submit :1 Requestfor Rc:consi,.kro 1ion (It.FR) as described in EPA's lnfonnation Quality Guidelines. The EPA requests that :my such RFR be submitted If you choose to submit :1RFR. please .senda written ,vithin 90 days of the dllle of the EPA' s rc-sJX)nsc. request to the £PA Infommtion Qu:1lity Guidelines Processing Staff via mail (lnfonnution Quality Guidelines Processing Slaff. Mnil Code 2821T, USEPA. 1200 Pennsylvania Avenue. NW. Washington, DC 20460); or electronic mail (qu~1ljl~, ..•:p:1.::o, ). If you submit a RFR. please reference the case number assigned to this original Request for Corrcclion (RFC # 17002). Additional intbmt.ntionaboul how 10submit an RFR is listed on the EPA lnfonnation Quality Guidelines website at hJm; 1. :pa.g11.}qua!i1: j 1Jf~nn-:11i, •1~~uirtions ra ised by OPEin the RFC were ,ons idered by agency an d ext ernal peer reviewe rs duri ng assessment de velopment Jnd externa l pee r rev iew because DuPo nt (th e former own er of the la Place LouisiaM (Jcifit y tha t current ly producc-s c.h!o rop rene ) prov ided ext ensive comm ents d ur ing the pub !i< comm ent period . The EPA fully Jdd ressed the Issues ra lse-din the OPERFCregJ rd ing the ldent ifi i;.ati on. e~ lu atio n and inte rpre t atio n of epidemlo!oglca l eviden ce d urin g the dev elo pmen t Jnd publicat ion of th e IRIS chtoroprene assessment (see§ 4 .J), The process fo r d evelopment of th e IRIS ch!o rop rene ass-essment is desc ri bed In the Introd uctio n to t he assessment. Jnd the ev.aluJt lon of ep lde mi o!oglcJ I evidenc e Is des.c:ribed in Sectio n 4: HJzard lden tmcation . Appendh t A of the IRIS ch!oroprene Jssessmen t Includes the Summ,1ry of Externa l Peer Review .:ind Public Commen ts and Oisp0sition . The info rm ation presen ted in th e I RISchlo rop rene asscssml'.'nt m cct.s th e £PA IQC st an da,rds or ob je ctiv ity Jnd ut il ity . The c va,lu a,t ion of the cp idemlolog it al ev idence, and the co nJidl'.'r 3tion of mu lt ipl e !Ines o r eviden ce t o dr aw t he co nclusion th at chloroprene is J likely hum an ta rcinosen, w ere suppo rted by the numero us agency review groups ,1ndWJS un ,1nim ously suppo r1ed by th e c >rtcrna l pee r review pan el. Furth er, th e followi ng specifi c poin1s w ere evaluJt cd bJ sed o n Charge Questi o n 8 {App endi,c ;.\ , pages A-10 to A-12) t o the review panel wh ii;h asked "Unde r th e EPA' s 200S Guidelines fo r Carcinogen Risk Anes.sment t200S, 08623 7) th e Agency con du ded th at i;hlorop rene is likely to be carc.i nogenlc to humans by ;.'Ill ro utes of exposur e. PICJsc comment o n the cancer weight of evidence ch arac1erization . Is th e can,cer weight of cviden,c i;ha racter ization s-clen tifl canv j ustified " ? Sf,ctout o f si,c tot al) pe-er reviewers com ment ed th at the ch.Jracterizat lon of chlo roprene JS · Iil(ety to be carcin ogenic to h umans" was appropria t e and clCJrl v just ified based on the anlmal and genoto)( lcity datJ. Thre e reviewers commente-d thJ t the .Jnlmal d Jta prov ided .1mple evidence of cJrclnogenesls In both se)(es of two roden t species (mo use and ra,t) at multip le o rgan sites, m any of which were di stal to t he pol nt ,of • cont act , In fJc t. tw o review ers furth er suggcs tt' d th at the strength of th e epld t'm iologica l eviden ce wJs sufficient to change th<' de scri ptor to "cardn ogenic to hum .-in s." No Mw stlt"nti fk evidenc e w as pr ovi ded In t he OPER~Ctha t wou ld Jlt e, th is concl usion , 8. The tV R Oo<'sNot Reflect the Best AvJIIJ b!e Sc.Jen ee or Sound an d Objective Sc.lentlfic Pract ices This topic l.sreki ted to po int n1 of the OPEreque st t hat the IRIS chtorop rene .1ssessmcnt be corrected, i.e •• th;,t " th e EPA derived inhalatio n un it ri~k UUR} or S x 10 " per ug/m 1 be replaced wit h 3 valu e derived by Rambo11environ o f 3.2 x 10 ' per ug/n,l, or wit hd rawn ." Or.)ftso f the £PA assessment 2 EPA-18-0077-A-000005 document wetc reviewed by lntcrnJ I ~ lcncc ci .pcrts w ithin EPA.by science rcvicwNs from other fcder.11Jecnclcs., .1ndby the White HOU!,(',Jnd it wJs cxternJlly peer reviewed bv independent expcn s including opportunit y for publi c comment. EPA notes thJt mJny of the topics Jnd JsscrtHlns ralscd by OPEin the RFCwe re considered by agency and ~tcrna l peer rc.-vlewe r s during .u~essmc.nt deve,,!opment and external peer review because DuPont (the former owner or the La Place Loulsi.in;, facility thJt currently produces chloroprcne) provided extensive comments during the publlc comment period. The follow ing S subtopics arc addrcssC{Iin turn . 1. The JUR rs Prlmorily 8osed on Doto from the Female .t..ro use, Which is Uniquely Sensitive to Chforoprene Exposure t he EPAfull y .1ddresscdthe Issues rJlsepme nt of the IRIS chlorop rene ,1ssessm ent is de scribed in t he Int roduction to the .1sseismcn1, and the evJfuJt ion of evidence is d eKribed in var ious subsc-ctions of the assessment. Append ix A of t he IRIS chlo rop rene auc-ssment includes t he SummJry o f Externa l Peer Revie w and Public Comments and Disposit ion . The info rma t ion pr esente d In the IRIS chtoroprene assessment mee t s the EPA !QC st:indards of ob je ctivity and ut ilit y. N. lnd fc.lte-d in th e assessment, th e identifteatio n, cv:i lua tion and interpretat ion of the eviden cl' , incl uding dose-·r esponsc mod eli ng of mu lti ple tu mors consis t ent with recommend.itions o f th e NRC (§ S.4 o f the IRIS chlorop rene assessment ). w ere-consldc-rc-d in t he derivJt ion of th e IUR. The de rl vation of the IUR and the documenta tion describi ng this de rivat ion were suppo rt ed by th e nume rous rev iew groups and the ma jorit y of the externa l peer tcvlew pane l bee Charge Quest ions 9 and 11, PJces A· 14 10 A · 16). The OPE RFCinclu ded an un published .analysis develope d by Ram boll Environ th.at dctivc-d J we d the con clu sions and rC'Commendatlons of both th e ext ern al peer rev iew pane l fo r the ch1orop renc ;nsessme nt and the NRC (1994) in pursuing a mu ftit um or mode ling app roach . or part iculJr no te is the conc lu sion of the NRC th at b.ts!ng cancer an alyses o n simpl y the mos t poten t tumor (In this CJSClung tumor s in fema1c m ice) o r the number of tumor bea ring ani mals wou ld bias the estima te of J chcm iCJl's tru e carcinoge nic potency . As for EPA's conclus ion of a gc no toxic mode of action ;:ind OPE's J lt ernJ tf'o•ecytotoxic.itv/ regenerat r.'c prohfcr:it ion mode of act io n, the cMoropr c ne cx t c-rnal pc,e, reviewers we re una nimous in t heir supp ort o f a gcno toxlc mode of act ion. Furthe r, even if J cytotoxlc ity/tcgene rative pro li feratio n mod e of action w as Jct Ive in addi t ion to a genotoxic mode of action, the cenotoxlc mocfe o1act ion woul d st ill drive EPA's OnA.1.2,2 of the IRIS chlorop rene Jssessment pro vide s det Jiled respo nses of the externa l peer review l)Jne l o n issues re late-cl to the sultJbllity of th e 2-yeJr NTP study for RfCderivation (Charge Question 4, page A-4), cho ice of endpo ints on which t o basis the dcrlvJtlon of the RfC(ChJrge Question S, pJge A·S}, the use of Benchma rk Dose mode ling fo r RfC derivatio n (Charse Questio n 6, page A-7) , and th e rat ionale for th e S<'lection of the unc('tt aint y facto rs for th-ederivation of the Rrc {Charge Que1tion 7, page A ·9). The ln fo rmJtion presen ted in the IRISchloroprcne Jss.es.s m ent meet,- the £PA IQC standa rd s or object ivity Jnd util ity. As incll cJted In the assessm ent, the ident ification, evalu atio n and inte rpret .'ltion of evidence of non ~c.anceref fect s result ing f rom ch1oropr ene exposur e wa s fully considered in the deriv.:,tion of the RfC. The derivJ tion of th e RfC and t he documentat ion describing this,derivatio n w ere supported by the numerous review groups Jncf the extern al pee r review panel. No n ew sde ntific cvlden-ce wJs prov ided in t he OPERFCthat would alter the developme nt and deri~t ion of the RfC fo r chloroprene. Conclusion The EPA, a he r careful review of th e RFC submitted by OPE,has concluded tha t the unde rl ying informat ion and concl usions presented in the Toxi'cologicol Revie w of Chloroprc nc (CAS No. 126 •99 ·8) In Support of Summary lnformoti on on rhe Integrat ed Risk lnfarmorion System (IRIS) arc consi1tc nt wit h the EPA's lnform.:, tion QuJlit y Guidelines. 9 EPA-18-0077-A-000012