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ST-351 Final Report ToxDoes 11-340 Final Report 28-Day Oral Study in Rats (ToxDocs Study Number 11-340, MTDID 8391) Study Director: Jill Hart, AAS, LATg 3M Toxicology Assessment& Compliance Assurance, 270-2A-08 Saint Paul, MN 55144 Phone: 651-733-8586 Principle Investigator: John Butenhoff, Ph.D., CIH, DABT 3M Medical Department, 220-6W-08 Saint Paul, MN 55144 Phone: 651-733-1962 `Testing Facility: 3M Strategic Toxicology Laboratory, 3M Center, 270-35-06 St. Paul, MN 55144 Experiment In-Life Start Date: ~~ 9-1-2011 Experiment In-Life End Date: 10-12-2011 "ONFIDENTIALITY STATEMENT `This report contains the unpublished results of research sponsored by 3M. These results may not be published, either wholly or in part, or reviewed or quoted in any other publication without the prior authorizationof 3M. 1. ST-351 Final Report "ToxDocs 11-340 Study Summary `The objective of this study (ToxDocs Study Number 11-340) was to investigate the bilateral pupillary reflex responses in male Sprague Dawley rats (n=12/dose group) during 28 daily oral NdoHsye'sPwFiBthA,ei3t0heranvdeh1i5cl0emcgo/nktgr/odla(yD)I. water) or MTDID 8391 (ammonium perfluorobutyrate, All rats survived until scheduled necropsy. Twenty-four hours after the last treatment, ocular tissues (n=12/dose group) were removed and processed accordingly for Western blot and retina `whole-mount evaluation performed in the laboratory ofDr. Don Fox at University of Houston, SancahloyoslisoffoOrptthoemeotcrulya.r sNaompoltehseratriespsueendsianmgplaetsthweertiemceoolflepcrteepda.ra tWieosntoefrnthbilsotrse and port histology and will be appended to this report when they become available. Study Objective "The objectiveofthis study was to investigate the bilateral pupillary reflex responses in male Sprague Dawley rats during a 28-day oral dose study with either vehicle control (DI water) or 'MTDID 8391 (ammonium perfluorobutyrate). Rats received 28 consecutive daily dosesofeither pvuephiilcllaercyornetfrloelxowreMreTDevIaDlua8t3e9d1d(uNrHin,g'tPhFeBtAr,ea1tm5e0nmtgp/ekrdi/odd.ayT)wveinatyor-afloguarvhaoguer.s Paefrtierodtihce blialsatteral treatment, ocular tissues from all rats were removedandprocessed accordingly for Western blot aOpntdormeettirnay.whole-mount histology evaluation by Dr. Don Fox, Universityof Houston, School of Experimental Procedures & Observation `Test Material: [emi |momssor Other Identifiers `Ammonium perfluorobutyrate, E-19895, NHyPFBA Lot/Batch Number 3M NB# 140499-10/11 CFC CF-CONH, 98.8% pure, 28.9% in water [swt foam Species Selection: a. ST-351 Final Report ToxDocs 11-340 `rTohdeenAtnispmeaclieUsstaogoepAtpipmliizceautsieoonfptreosttocmoalte(riAaUl.A 2Sp0r1a1g-u0e00D1a)wrleeqyuirraetsswtheereusseeloecfatesdmaalsl theyare commonly assessment. used in oral toxicitytestingto generate data for human health risk Animal Husbandry: Hbootutsoimngca--gReastesxcferpotmdtuhreimnagidnossitnugdywhgircohuprewqeurieriinngditvheiidruarlelmyohvoaulsferdoimncsatgaensd.ard solidD10ieatll/Waantiemral--scaodmmleibrictiuamltlhyraovuagihloaubtlethceersttiufideyd. rodent chow and tap water were provided tEenmvpierraotnumreeno--tf 7E2nv&ir3onFm,ehnutmaildicotnytorfol3s0f-o7r0t%h,e aanmiimnalimruomomofwe1r0eesxecthtaongmeasiontfairnooam air pdearyhoofurp,upainlldaray1r2e-fhloexurexlaigmhitn/adtairoknc,ycilne.whTichhet1h2e-hroouormlwigahst/kdeaprtk dcayrckleiwnathseamltoerrneidnognutnhteil the pupillary reflex examination was completed. Exposure: Daily Dose | Dose gags[oom| @isCilolnetdrowlater) 150 make/day | me[7324 hourdsospeost last 24 hours post last * Dose refers to the sat form ofthe main componentofthe test atc. dMoTsiDnIgDso8l3u9ti1onwawsasproerpaallryedgiivnevnehtiocrlaets(dpiesrtikllgedbowadtyerw)eiasgh3s0 fmogr/2m8L.conFsievceutmiLveodfaytsh.e Observation: Each animal was observed daily for morbidity/mortalty. Body Weights: dAalillyradtsoswienrgevwoeliugmheesdfwoeretkhley.subTsheequbeondty7wdeaiygshtunitniflonremxattisocnhewdausleudsewdeitgohicnalgc.ulaAtlel tahtes were also weighed prior to necropsy. a ST-351 Final Report ToxDocs 11-340 Pupillary Reflex Evaluation (PRE): Pre-dosing and interim pupillary reflex evaluations were performed on all rats throughout the study based on methods provided by Dr. Don Fox. Necropsy and Specimen Collection: All the rats were euthanized by decapitation 24 hours after last dose. Immediately after decapitation, ocular tissues were removed and processed accordingly for either Western bolts or retina whole-mount histology. Results & Discussion All rats survived until scheduled necropsy. Data for body weights are summarizedin Table 1. All MTDID 8391-dosed rats gain weight similar to control rats. Bilateral pupillary reflex evaluation results are presented in Table 2. The corresponding ocular Wester blots and histology data are pending, and they will be appended to this report when they become available. 4. ST-351 Final Report Signatures ReportPreparedBy: 7 easo t Jill Hart Study Director Reviewed By: A lots John Butenhoff, Ph.D., DABT, CIH Principle Investigator ToxDocs 11-340 27 NAR. 26/3 Date 24 war 20/2. Date 5. ST-351 Final Report ToxDocs 11-340 Table 1: Data for body weights and liver weights iy Pre-Doso| Week2| Wee3k| Weeks|Po Gaoew | oDoese | Anima#l|Tail Mark BWoediygh| SWeoigyht| SWooiygt| WSeaigyht| B(oBd0y.9 9) (9) 9 9) a [[ooroaors||uT|| o2e6s0|| 2086|| os2w0 || osaart|| s3e6r5 || [[RrsatooTTww|| 605 ||2201 || 2s0o6r||santa||oas0|| [[RCaiRtotz1T | vvi |225003||2s0008 ||s30r2|| 33820|| seas || [[oCirRsottsa||vwwn||226667||220060|| 332256|| 3s0a2s|| ssse0 || [[rroottss||xx || oooo ||ooop||a ot8||ooso|| saesso|| [[oorrsstter|| ax||ap0e4|| oo1r3||ootatr||soeos|| aorss|| [[rosreto|Iw1 || 2o0o4r [|2a0rr||aa86||ast20||ssars|| [[RoraazzztT| w || 20665 ||a2024||a15|| ss5626|| osrais || [[CCioRRaazzeo| [vv i [22604 ||20151 || s3s0s0|| s1s8||sourss || FC I T TN T 0 3 7 [[iarRseazre||xx ||oooets|| oootp||ssa6|| ssaass|| s3e50s || [[oCirraesoo[Taxr|| o0ee|| sstt0||ssor|| ssosrs||sssmii|] "6. ST-351 Final Report ToxDoes 11-340 Table 2: Bilateral pupillary reflex evaluation (PRE) data fr pre s1.201 [pre psz0nt|_siwsrooert|| sazwonei || asgeezroen sDoosne|| Oo wTaari Rooeh Reonet RBoet | [IiC MeTosoro TmI [+ [TsoE rTssToTTS e S S ES | mar ve > + I~ BE[im= stslw[| +[+e [H oT%e W] TT EaT : CITTT ITT ES ES ESS C E ECS C ES S S ES S C 0 S ES || [frssato T1 =Tewe T Te eTT [Fmre7 saztzlw Cw 0TEw S E TsE TeTCuS SPBP | MIEi7 saelT vi[S E +T E EST STE oTEESS1SY PS PPsy1 BBeP || [MIrTeo2as7r3o w [T +[ow eTTweTTS oeTSV P ] y | Dessol a|+[+To +[w+[TT T+] "4 ==PPuuppssreessppoonnddoeddtFo kttssitmruuantdicohnsstoriwctsedcnoonrsmracliyon =n