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AR226-2802 DuPont-5206 TRADE SECRET Study Title H-24648 and H1-42-4D0a2y0:FeReedpinegatSedtu-Ddyosine MOriacleToxicity Study Laboratory Project ID: DuPont-5206 A uth o r: Susan A. MacKenzie, V.M.D., Ph.D., D.A.B.T. St u d y C o m p l e t e d o n : June 13,2001 Perform ing Laboratory: E.I. du Pont de Nemours and Company HElakstkoenllRLoaabdo,rPa.tOor.yBfooxr T50oxicology and Industrial Medicine Newark, Delaware 19714-0050 Page 1o f71 Company Sanitized. Does not contain TSCA C! H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 CERTIFICATION Wfroem, ththeisunstduedrys.igned, declare that this report provides an accurate evaluation of data obtained Approved by: Q k d M L .^ . '2& & Ahj< u //J u d ith C. Stadler, Ph.D., D.A.B.T. t / Director, General Toxicology Issued by Study Director: Susan A. MacKenzie, V.MD., PK.D., DA.B.T. Senior Research Scientist -200/ Date 1S-sTUAl-aol Date # Company Sanitized. Does not contain TSCA CBI 2 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 TABLE OF CONTENTS Page CERTIFICATION...........................................................................................................................2 STUDY INFORMATION................................................................................................................5 STUDY PERSONNEL.....................................................................................................................7 SUMMARY....................................................................................................................................... 8 INTRODUCTION.......................................................................................................................... 10 MABAT..ERTTeeIAssttLSGSuubiAdstNealDninceeMs.....E......T....H........O......D......S..........................................................................................................................................................................................................................................................................................................111000 CDEFHG...... ATAQDStesnuiuessiadttimrgyPaSannrDplmeteiHpenceaseniuiretsgaasbttn.noi.ao.d...nnG...P.d..r..arr..oen..y..utd...e..p....sA..s..t.....da..P....nm...e...d...r..i.i..n.S..o...i..t..ds..u..t.....dr......a..y.....t....i...S..o........nt....a...........r........t............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................111111123022 JI.. BFoooddy CWoenisguhmtsp.t..i.o..n..,..F..o..o..d...E...f.f.i..c.i.e..n..c..y..,..a..n..d...I.n..t..a.k..e...o..f...H..-..2..4..6..4..8...a..n..d...H...-..2..4..0..2...0...........................................1133 KL.. LCilvineircWal eOibgshetrsv..a..t.i.o..n..s..a:.n..d...M....o..r.t..a.l..i.t.y.........................................................................................................................................................................1133 M. Statistical Analyses...............................................................................................................14 RECORDS AND SAMPLE STORAGE..................................................................................... 14 RESABCU... LMMCTleeiSnaainnAcaBFNlooDOoddbyDsCWIeSorveCniasgUtuihomStnsSpsatIinaOondnNdB, .MFo..od.o.o.y.rd.tW.a.E.l.ei.f.tif.yg.i.c.h..i..t.e...n.G...c...a.y...i.,.n...a.....n......d.........I....n......t....a.....k......e.........o.......f......H.........-....2......4......6......4......8..........a.....n......d..........H.........-....2......4.......0.......2......0................................................11115556 D. Liver Weights....................................................................................................................... 16 CONCLUSIONS............................................................................................. REFERENCES............................................................................................................................... 19 18 Company Sanitized. Does not contain TSCA CBf 3 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 TABLE OF CONTENTS (Continued) Page TABLES.........................................................................................................................................20 TABLE 1 MEAN BODY WEIGHTS OF MALE MICE........................................................................................................21 TABLE 2 MEAN BODY WEIGHTS OF FEMALE MICE..................................................................................................22 TABLE 3 MEAN BODY WEIGHT GAINS OF MALE MICE.............................................................................................23 TABLE 4 MEAN BODY WEIGHT GAINS OF FEMALE MICE.......................................................................................24 TABLE 5 MEAN DAILY FOOD CONSUMPTION BY MALE MICE.............................................................................25 TABLE 6 MEAN DAILY FOOD CONSUMPTION BY FEMALE MICE........................................................................ 26 TABLE 7 MEAN DAILY FOOD EFFICIENCY OF MALE MICE.....................................................................................27 TABLE 8 MEAN DAILY FOOD EFFICIENCY OF FEMALE MICE................................................................................28 TABLE 9 MEAN DAILY INTAKE OF THE TEST SUBSTANCE BY MALE MICE...................................................29 TABLE 10 MEAN DAILY INTAKE OF THE TEST SUBSTANCE BY FEMALE MICE..........................................30 TABLE 11 SUMMARY OF CLINICAL OBSERVATIONS OF MALE MICE................................................................31 TABLE 12 SUMMARY OF CLINICAL OBSERVATIONS OF FEMALE MICE...........................................................32 TABLE 13 MEAN FINAL BODY AND LIVER WEIGHTS OF MALE MICE................................................................33 TABLE 14 MEAN FINAL BODY AND LIVER WEIGHTS OF FEMALE MICE.......................................................... 34 APPENDICES................................................. ............................................................................. 35 APPENDIX A INDIVIDUAL BODY WEIGHTS....................................................................................................................36 APPENDIX B INDIVIDUAL FOOD CONSUMPTION.........................................................................................................42 APPENDIX C INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY......................................................48 APPENDIX D INDIVIDUAL FINAL BODY AND LIVER WEIGHTS...........................................................................62 Company Sanitized. Does not contain TSCA CBI H-^4b48 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice STUDY INFORMATION Test Substance No. 1 9th Collective Nomenclature: Svnonvms/Codes: DuPont-5206 Haskell Number: 24648 CAS Registry Number: Composition: Known Impurities: Physical Characteristics: Colorless liquid Stability: ocTobhnseedrtivetiseotdns.subosftathnecestaupdpye;anroedevtoidbeencsetaoblfeinusntadbeirlitthyewas Company Sanitized. Does not contain TSCA CBI 5 -11---41-----D/-4-a0-y4--B-F--ea-en--da-i-nH--g--2-S4-t-Uu--2d-U-y-:-i-n-R-M-e--pi-ce-e-a-t-e--d----D--o-s--e--O--r--a-l--T--o--x-i-c-i-t-y---S--t-u-d--y----------------------- -------------------------------- DuPont-5206 STUDY INFORMATION (CONTINUED) Test Substance No. 2 H-24020 Known Impurities: Physical Characteristics: White solid Stability: The test substance appeared to be stable under the ocobsnedrivtieodn.s of the study; no evidence of instability was Sponsor: Daikin Industries, Ltd. O1-s1a,kNai5sh6i6--H8i5t8o5tsuJyaap,aSnettsu-shi Study Imtiated/Completed: 03-Nov-2000 / (see report cover page) In-Life Initiated/Completed: 06-Nov-2000 / 20-Nov-2000 Company Sanitized. Does not contain TSCA C8I 6 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice_______ STUDY PERSONNEL Study Director: Susan A. MacKenzie, V.M.D., Ph.D. Management: Judith C. Stadler, Ph.D. Primary Technician: Robert E. Walker, Jr. Report Preparation: Cecilia R. Kee, B.S. Laboratory Veterinarian: William Singleton, D.V.M., A.C.L.A.M. DWuaPnodnatLP.hWaremsat,cDeu.Vtic.Mals.,CAo.Cm.pLa.nAy.M. DuPont-5206 Company Sanitized. Does not contain TSCA CBJ 1 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice__________________________ DuPont-5206 SUMMARY pdTrahoyidssustoctuecdloyinvetervroaellnudlaiaetretgd(e0mthpeepnmrte)ilnaotmirvdiecipee.toctGeonnrcotyauiponsifnotghfeH5t-wm2o4al0tee2sa0tnosdur5bHsf-te2amn4c6ae4les8,.mHiD-c2eie4wt0a2ery0recaeonxndpcHoesn-e2trd4a6tfio4or8n,1st4ofor tahnedtcwlionitceaslt osubbssetravnactieosnws ewreer1e,e3v,a1l0u,at3e0d,1w0e0ek, loyr. 3A00ftperpmth.e B14o-ddyayweexigphotssu,rfeopoedricoodn,saulml npotinon, fasted mice were sacrificed and livers were removed and weighed. More3a0n0opvpemralwl (atses0t.2d0a,y00.-5174,)1.d8a4il,y5i.n7t6a,k2e4o.1f,Ho-r26420.240ming/mkga/ldeamy,icreesepxepcotisveedlyt;o m1,e3a,n10da, i3ly0,i1nt0a0k,e ii6nn.4tfa1ek,me2ao3l.fe8H,m-oi2rc4e863w4.80asmin0g.m2/k8ag,l/e0d.ma6yi8,c,er2e.es5xp2pe,co7tsi.ev2de8lty,o2;61m.,03e, a,o1nr0d1,a03i2l0ym,1ing0t/0ak,kgeo/drian3y0f,e0rmepsapplmeecmtwiviacesely0w..1aM9s,0e0a.2.n517d,,a0i1.l6.y863,, 2.37, 7.38, 25.6, or 98.8 mg/kg/day, respectively. Nreospcoonmsepotounedx-proeslautreedtodeeaitthhserotcecsutrsruebdsatanndcne.o clinical observations were considered to be a direct tHOwrleiev-sved2etieugr4srcha6uwtlti4bloea8si(ntngtasoedhnsritcbtn3eeod0.ffdaof0eyyBocpdw0otps-dcem1iyoi4ngnwo)hstfhbtueeHoimggsda-ehpiy2ntt4giwlo0rwoone2seui0sgwrpe.ehsse.taTrwellChsoeoooisrsbmseosswbpaeeslovrasevuesorernvoedodebbt-disonrseexeirnalrivacnvmetiyeedtdydagliprienrnoermmuedfvpueiae,cmclnetetiahtomfsleeenrmdisemcfee3(oiac0crfoneeepim,dnfpeepgm1fdfaf0ure0H1elc0dtio-sn02rtto4ooe36nrrc0p4o03b8rn0oe.pt0tdrpaNoypmtilopwo) monienfiogoebfhafotcdhy gain reflected effects on food efficiency in male and female mice exposed to both test substances. NBoothcotnessitsstuenbtstdainfcfeersepnrcoedsuicneadbcsoomlupteoounr dre-rlaetliavteedliivnecrrewaesiegshitnwlievreerowbeseigrvhetsdcboemtwpeaerendthtoe ctwonotrtoelsst. substances. Ionbsmeravleedmiincea,llstgartoisutpicsaflelydsdiigentsifcicoannttaiinnicnrgeaesietsheinr tbeostthsuabbsstoalnuctee.anWdirtehlabtoivthe tleivstersuwbesitgahntcsesw,eare mlivoenrowtoenigiehtdwoseer-ereosbpsoenrvseedwianseoibthseerrvmedalien3m00icpepemxpgorsoeudpu. pTthois10la0cpkpomf.fuNrtohefruirnthcereraisnecrweaasses in attributed to the body weight loss in these mice. otIenbssfteesrmuvbaesldetaimnncimecsei,c, eastfmaetdoisntdiociteaotlsnlyitehsadigtoncsioefn-ircteaasinpntoeidnnsc3erepwapsamessoaibnndsbeaorvbtheodvaebu,spwotloiutht3eb0a0ontdphprtmeels,attesixvucebeslptiavtnefcroerwst.ehieWghaibttsshowbleuortteeh tloivtehrewtweioghhtiginhefestmdaolseems.ice exposed to H-24020, where a plateau was observed in mice exposed Company Sanitized. Does not contain TSCA CBI 8 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 DEcfooxirmepitonapsrcayurreereeadxstpteoodoHsHlui--vr22ee44rt60ow428He0i.-pg2rhU4ot0dnw2ud0aceseradtlnheadsessHcmtoh-2naal4dnl6i,t14bio8upntppsmcrooondfinsuthicmsietseadnsletstulimymdygiic,lraeetrha(eet0ef.nrf2,eo0ce-otfasfbneosdcent0rovl.i1nev9dei-nrme-wflgfiefe/keicggtph/ladteravianyemlmfe(otNirecOres.EL) HH--2244002200 aanndd HH--2244664488,, rreessppeeccttiivveellyy)).anNdo1npoptambleindfieffmeraelencmesicien(t0h.e28maangdni0tu.2d1e mofgl/ikvge/rdwayeifgohrt tteohfeftehhceitgwihnee-lsrietfeeoxabpnsoedrsvluiervederlbewevteewligewheantsetfhsfieemctwtislaoortffeobsrot mtshuabtlesestsatnascnuedbss.fteamMncaaellsee;sshewoxweproeesvmeedro,trotehbeseomnthsaigtteinvsiettustduhebansotaffneemcffeeascl.etsat Company Sanitized. Does not contain TSCA CBI 9 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 INTRODUCTION The test substances, H-24648 and H-24020, are isomeric mixtures of ^ofifatssohotbporrelHspalmetorithgroeweveshxrmeititiincdmsscgoumhwambdatpiiesiixetetnlhratytuioanacdr7rcnieym5eedn.%cteiaboxxHrrtnptysaut-toanar2resaceix4unihmp6gcreeeo4ohddssn8tuictocniacrhhfeionHaans3niie-nntopd2gafpf4aiionmn10nrsdd2mpHoio0p2fsnr-fm.5p2elg%yr4rTroeo6etdnhrhb4auteertl8eeaca.ssrsnematsdcfrm.ooah(e,uirpe)glndleeheNtvitsctaohohcotfehaedfrHdiaansi1-ttnla2r4fiavo4faoiero0grmrrre2hm2ws0ta1.,eavtwinedaIgsndiahhltyaeibatslbsder.plaieirHnnNnect-vmooth2ihoe4aaiindsu0lsecss2scer0athsesuntaascuddsiodtynehfnyceefwt,ooma(p1arni)onamsttltasheesiebnnmooetiftdiahcle HbTlievh-c2eea4ruo0esb2nej0leai.ctr{t1gwi)veamesoetnhftethirniosmusttaeuldeoyfaewnxdapsfoetsmouraceloempmrpeiavcrieeo.uthsTlehy2euosiseroadmltroeorudsteefmooroftnhasedtirmratrienelilasittvirevaretieopnnolatwerngatesimasleeltneotcptweroditdhuce MATERIALS AND METHODS A. Test Guidelines None were applicable. B. Test Substance The following substances were tested: H-24648 (10% solution in water of active ingredient) H-24020 (white solid) NHSoo-2lue4tv6ioi4dn8esnwEcaenstoesfrupipnripsstleaie.bdiTlbihtyye,DtseausictkhsinuabsIsnatdacunhscaterniaegpse,piLenatdcre.odloHtro-2ob4re0p2sht0yasbwilceaasul snsutdapetperl,tihweedacsboyonbDdsieutirPovonendst.oCfhtheemsictuadly. C. Test Species Oi8n-S2e6p--O2c0t0-200, 0w0e,r7e1remceailveeadnfdro7m1 fCemhaarlleesCRrli:vCeDr -Llab(oICraRto)rBieRs,mInicce.,, Rwailtehiganh,aNssoirgtnheCdabriorltihnad.ate of bTspahececkiCgersrol:uuCsneDdd-ilpnrfeo(IvrCmioRaut)siBolyRntiosstreaavvianaliuwlaaabtesleclifhvrooesrmernethsbpeeoclniatsueesrsaettutohreeH,C-t2hr4le:0Cs2uD0p.-(pll)lieFmruaorntuhdseeprmwreaovsrioet,uhesexssttteurnadsiinievsaenatd 10 . Company Sanitized. Does not contain TSCA CBi H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 HhaarsdkinelelsLs,asbeonrsaittoirvyit.yTtohitshespteecstiessu/sbtsrtaainncael,saonids lcoownsiindceirdeednscueitoafbsleporneltaatnievoeutsodloisnegaesvesit.y, D. Animal Husbandry 1. Housing and Environmental Conditions All mice were housed in stainless steel, wire-mesh cages suspended above cage boards. Mice wraoseosrimgenshmowueesnreetdtmo3agpirneotruacpinasg.edeC,osanegxeaers1a2cs-ekhpsoawuraretlreie,ghpretr/lidooacrratkotecdayswcsliiegthn(imfnluetonhrteetsaocneginmrotaullipgrshotao)nmadneidnacdahitvawidteeuemakl.plyeAraafnttiuemrrealof 22 3C and a relative humidity of 50 20%. 2. Feed and Water Tap water was provided ad libitum. All mice were fed PMI Nutrition International, Inc. Certified RinocdoerpnotrLaatebdDiientto t5h0e0f2oaodd laitbcitounmc.enDtruartiinongsthsepetecisftie(edxbpyossutured)ypdeersiiogdn,.test substance was 3. Identification Paiaidnsbrecsisoinlegurtnnidtfceeoiecddaaottstohfisoeaiegnaucnnconmhulioqemmrunebetodetu6orts-awedgi.liregomrAieutapfHmrtseka,arsearakkanseecdsldhilcgomaannngmoiemtuehisndeaetletwntanoitualigfmsoirctobfeaueemtirpaopcsan,hon.trdmhaTertohihluleyeassieiitnnd.d3efoi-nv4rtmiidfdiauiegtadiilotbsindyooeefnnittthithfheieecriancttdhaiogievnepidnrlaueubsameelnlbsceer or 4. Health Monitoring Program tAfhosollssoepwetihcniagftiewpdrooiucnledtdhbueereHesaxasprkeeeclptleeLdrfaotboromirmaetdpoaprcyetraitnhoiedmiscacalilelhnyetatioflitcheniansnutdergeerntihtvyaitroocfnotmhneteansmttauilndaymn:otnleitvoerlisngarperboeglroawm, the Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional prseprqeesuceiirfneicemedeohnfetasthvaeynsedmcneotoantltstao,maefixnlacatenoetxdsinbs,teacltohewldomrthinaeaxmtiemdaxuhimmyducromonccacerobnnotcrneasnt,itoarnantsdiooonfrgkstaeanytoecdpohnbotyaspmthhieantmaensat.sn,uTifhnaeccltuudreinrg would not be expected to impact the integrity of the study. 11 Company Sanitized. Does not contain TSCA C H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 tTilhnahbecelovuraadanletiioddmriyitanylatnohhiefemathlfatiehlnvasatlenutrddeerypei.nonravtri.iraoEnn.vmaDleunaatttaailoamnreoomnfitathoienrsitnaeigdnpaetrdaosgderipadamnraoitstelianyddmfircoianmtiesstaetnureyddycboreyncdtohirteidosantastentndhdaaitnreagfnfeoctted E. Quarantine and Pretest Period Upeproiond.arrTivhaelmaticHeawskeerlel oLbasbeorrvaetdordya,itlhyefomricaenywcelrieniqcualalryanaptipnaerdenfot rsi6gndsayosfodfistehaese11ordainyjpurryeteanstd were weighed 3 times. On the bases of acceptable body weight gains and clinical observations, all mice were released from quarantine on test day -5 by the laboratory animal veterinarian designee. F. Study Design MaleGrouFpemale No./Group In 5 vmVn vIVVmI xDXmCI xxXrnv 555555 xXXvIVXn xXXxXXmVI XXVVIIII xXxXn XXXXIVVI 555 555 Dietary Cone. (ppm)a 0 ppm 1301 ppppppmmm 31030000 ppppppmmm 31 ppppmm 3103010000 ppppppppmmmm Test Substance Control HHHH----22224444000022220000 HH--2244002200 HHHH----22224444666644448888 HH--2244664488 aWeight/weight concentration of test substance (adjusted for purity). G. Assignment to Groups and Study Start Mice were selected for study use on the bases of adequate body weight gain, freedom from any cssetlailnetiicscttaeicldasmlilgyincsseigownfeidfriiesceadanisstterdioibfrfueitnreejdunrbcyey,scaaonmmdopanubgtoegrdiryzoeuwdpe, ibsgtohrdatytwifwiietehdiignrhatndm2o0em%anizsoawftitoihtnheismnoeatahsnaextw.thitehrienwaesreex.noThe 12 Company Sanitized. Does not contain tsoa obi H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 Dapipertaorxyimadamteilnyi4st2radtiaoyns ooffHag-e2.4648 and H-24020 began on test day 0 when the mice were H. Diet Preparation and Administration . H-24648 was received from the sponsor as a 10% solution in water. H-24020 was dissolved in dduIniseeteietod.rnniiTanztheitoedhneswaahlam,itgeIehnr,vcc.etoohCnitecchrleeetni,fstirdaeamedtiioeoRnncoiozddneieecdntetswn.LtaraHtaebt-rDi2,o4iwne0tao2sf0aa5adc0ntd0idev2deHati-non2dg4cr6toeh4ndo8tirreoownlutegdarhieseltyHasdm-ad2tie4xtd6he4etdo8sf,PaopmMrr3ieIovmNrotiuolntuurmmitteiieoxs.niansCgtohwnaitttrhol ddiieettsarwyeerxepmosiuxreed, afonrdthreefrsiagmereatpeedriuondtiolfutsiemde.. Diets were prepared once, prior to the first day of I. Body Weights All mice were weighed once per week. J. Food Consumption, Food Efficiency, and Intake of H-24648 and H-24020 The amount of food consumed by each mouse over each weighing interval was determined tcchoarlnocsuuulgmahtepodtui.tonth,emsetuadnyf.ooFdroemffitchieesnecyd,etaenrdmmineaatinodnasialyndinbtaokdeyowfeHig-h2t46d4at8a,amndeaHn-2d4a0il2y0fowoedre K. Clinical Observations and Mortality mACamanogioumens-egasliwmte1ai2cse4exi5naw7md9eiivrnieinadctuGiooarnnloldsyuupthcotaIednVdedtwlaeetcadltseamafnosodturoneibndxucadnemeddaindaoeirlodydneftohtaerdrsoatmubdgniachoyeormu1atnaatdlnhdbaeebdshntiausocvdramyior.darleAadbntedwehvaiatepvhrpioyoeuarwtraaepnniagdcthheaio.pnlpgoe,gaeircaaacnlhce evaluation. L. Liver Weights MSuircveivwinegre, neounth-afansatteidzemd ibcye cwaerbreonsadciroifxiicdeedafnoellsotwheisniga tahned1e4x-sdaanygeuxinpaotsiounre. pTehrieoodr(dteerstodfasyac1r4if)i.ce was random among all treatment groups within a sex. TwRheeleiaglthiivvedeer.lifTvroehmrewloievnieegrhsmtsfor(uopsmeeracinlelngotrtoohufeprfimXnaiXlcIebHosda(cymrwiaflieeci;egd1h0tb)0ywpdpeermseigcHna-l2wcu4el6ra4ete8rd)e,mwuoassvineigndafadinnvdaelrwtbeeonidgtlyhyewndeo.itghts determined just prior to necropsy. 13 Company Sanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 M. Statistical Analyses dSaigtaniffriocmanctheewteasstjgurdoguepdsatot pda<ta0.f0r5o.mTthhee cfoolnltorwolinggrosutpat.istical methods were used to compare Parameter BBooddyy WWeeiigghhtt Gain FFLooivooeddr ECWfofeniicsgiuhemnt cpytion Preliminary Test Test for lack of trend(2) hLSfoohermavnpeooinrgreome'-nsWaetleiiittslyykt1^'ft5oearsnt(d6) Method of Statistical Analysis nIfoptrseilginmifinicaarnyttest is Isfigpnriefliicmanintary test is JaSopenpqcluikceahntetiieoarnle*-3T5eorfptshtera trend test*45 pPareirlwimisienacroymtepsatrsisfoonr ORa wvOainrtieha-nwDceau*yn7n5aenftoat'llslyostewisste*od8f5 tKfeorslutl(os9wk) aeld-WwaitlhlisDtuesntn*8's5 IncOidbesnercveaotifoCnslinical None Cochran-Armitage test for trend*75c a Pairwise comparisons and associated preliminary tests were only conducted if the test for lack of trend was significant. b If the Shapiro-Wilk test was not significant but Levene's test was significant, a robust version of Dunnetfs test was used. c BIfotnhfeerinrocnidiecnocrerewcatisonnowtassigunsiefidc.ant, but a significant lack of fit occurred, then Fisher's exact test(l0) with a Absolute and relative (to body weight) liver weights were also compared between mice exposed to the two test substances using 2-way analysis of variance, followed by linear contrasts/25 RECORDS AND SAMPLE STORAGE Athlel sdpaotansaonrd. records for analytical characterizations conducted by the sponsor will be archived by RIraown MdaotuanatnadinthReecfionradlsreMpaonrtagweimllebnet,reWtaiilnmeidngattoHna, sDkeellalwLaarbeoratory, Newark, Delaware, or at Company Sanitized. Does not contain TSCA CBI 14 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice__________________________ DuPont-5206 RESULTS AND DISCUSSION A. (MTeaabnlesB1o-d4y, AWpepiegnhdtisxaBn)d Body Weight Gain In mice exposed to H-24020, exposure to 100 ppm (males only) or 300 ppm (males and females) pgraoindu(vceadriarebdleucsttaiotinsstic(caolmsipganriefidcatoncceo)n. trIonl)mianlems,emaneafinnaflinbaoldbyodwyeiwgehitgahntdinovtheera1ll0b0oadnydw3e0i0ghptpm geoinxrriopbtuioeapsllosubwrwoedawpsyeer8wrie4oe%dcig.ohamMtn.pdaaMl7rea2esb%aelnexobptofoocdscoeyondnwtttrrooeoillg,1.h0ret0Isnapanfneedcdmtbi3vao0lede0lysyp,.wpmBemeiogaHtnhht-f2ggin4raoa0inlu2bp0insoldolmoyssatwtl8ewe%igegriahogntuhdiptnso2tv3ehe%xerp,3tohr0see0esdp1pe4tpoc-mtdi3av0gyerlpoypu,mpof wpwtthheaeearseitsokw7ed8coa.o%sfnTecdoxhopefwmocfepsoeeuamnkrrtaeareobl(xell3ecag%etnreooddaucentpohddsnistt1ehrg%xoarplto.ooousfSfpeicodnlomoitntsoietatrlo3o10blf3,ot%ahrdneiyssoduwfil1nite0cnini0rigetgiphaaiptsln,embrdoeovhswdepayeredaiwcglmtlhieve(titgeagelhnsyatti)bn,odovbaodeuyvyrte0wtbr-ho1eteh4dige)y1h4bswt-eodlcedoaoiysgynshwdetoxewvgpieageoirhesntkuthorgoeevafefinirrst exposure represents increased liver weight (observed at necropsy). wI(otonfveeemm1igr0aiah0clltleeags(net)aexdipsnptr3oo(0dsvd0aeauydprci0pteao-mdb1lHr4ewe)-ds2ebtu4aroce6tdit4si8yot81inwc,%saeelx(iagcspnoihogdmtsnu7lipofr0aise%crsaetoindonc3ftebo0c)oo.cptnohpEtnmrsxtoerplxoa,oelnr)ssdeu.isnrapeMbemtoceoevtaiaev1nne0(flm0fiyinn.oaaalrleMl3sbb)0oao0ldaednypsydpwewtmxoeepiigpo1ghrs0hoet0tddiaonutnrcomde3d1a0o0l0vme0esperapeaanxmnldlpboosdedy wFw30eeem0iiggpahhlptte.msinIeonfxefmpmHoasa-le2leed4ss6teeo4xx8p1pol0oos0sesetdadn1tdto2o%331000a0np0pdpapmn2md2, %mo30,fe0aHrenp-s2ppo4mev6ce4trwia8vleellrloebyso,8tdo92yf%%iwnaaeintniigddahl71tb68go%%adiy,norwfwecseaopisgneh5ctrtt3o.i%vl,Melroyeef,sapconeofcfniittnnirviaotelilalby(lno.bodotydy bbstoiaodtliyosgtwiicceaailglllyhytssiiinggnntihiffiisiccaganrntot)u,dpduuewetaotsot9hb3eo%dmyoawgfnceioitgunhtdrteolloo.sfsTeofhfveeescert,tdhaielftfhseeorecunogcnhedsnwowteeearklel owalfelercxeopsnotsasitudirseetri.ecdaMllyean final significant. Males were more sensitive than females to the body weight effects of exposure to both wcoemrepgoeunnedrsa.llyExopfogsrueraetetromHa-g2n4i6tu48deptrhoadnuctheodseeffpercotdsuocnedbobdyyewxpeoigshutreantodHbo-2d4y0w20e.ight gain that B. M(TeaabnlesF5o-o1d0,CAopnpsuenmdpixtiCon), Food Efficiency, and Intake of H-24648 and H-24020 Nminoamleceooamnr pffeoomuondadlce-ormenlsiacuteemdopretifbofyencetoxsvpoeonrstufeorseotdtdoacyHosn-02su-47m64ap8ntidoinn0m-w1a4elrewemeprrieocedo.ubcsSeetrdavtbeisydtieicnxaplfleoymssuairgleentimofiicHcae-n2te4xi0np2co0rseeaindsetso 15 Company Sanitized. Does not contain TSCA CBt H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 H30-024p6p4m8 wHa-2s4c6o4m8.paFraobolde ctooncsounmtrpotl.ion in female mice exposed to 100 ppm and below of pHInr-o2md4ui6cc4ee8de,xrepexodpsuoecsdtuiotroensHtoi-n234o00vp2ep0ram,lleaxfnopdoodsauberofefvitecoiien1n0cm0ya,plcpeomsma(npmdarae1led0s0toopnpclmoyn)taornordl3s.3000I0npppmpmimc(emineaxflpeeosmsaaenldedstofemales) wpbroiotdhdyubwcoeeddiygrhwetdeguigacihtnitoegnfasfieinnctwsoevirneeraaalllllsgoforoooubdpseesf.rfviTceidheenwcgiyteh,ncdfooemor-dpaaenrfdefidccioteomnccpoyonutnrodl-sr.elFatoeoddpeaftfteicrinesnocybsreerfvleecdted Mo23o6r,f1e.H30a00,-n,02o3o4rp0v0p1,e2m0r10a20lwi0lmn,(agtfosee/rks0mt3g.2ad0/d0la0ea,yypm00,p.i-5mrc1e7e4s,wp)1eex.ad8cpsat4oii0lv,sy.ee15lid9.yn7,.tt6ao0,kM.251e,47eo3.a,11f,n,.H18do0-3ar2,i,6l43y6200..2i4,4n101tm0,ai0kn2g,e3/mko.o8graf,/l3dHea0an-my0d2,i4p8cr6pee34ms.e08pxewmipcnatogismsv/kee0adgl.ly2/etd.8oam,My10i,c,.er63eae8,nes1,px2d0ep.a,c5o3it2lsi0yve,,dei71ln.yt0t2o.a08k1,,e, M0.6e6a,n2d.3ai7l,y7in.3ta8k,2e5o.6f,Ho-r249684.88ming/fkegm/daaley,mriecsepeecxtpivoesleyd. to 1, 3,10, 30,100, or 300 ppm was 0.21, Otodahpifvaeptenthraroerainxyl2lticam(toketaenestsctebtesydanudatbtrhymsaett0iain3-on1i0ncs4.0ete)sprTiewnphdtmaeasdrkemoesfsioamoerl,feeial,sHasrer-ew2xbs4ppee6otlolw4snea8essdeebsnttyhowgemHresoara-uel2mep4csem0o2omdi0cifpee.ttahairHenreyodstahwcimeonenve3mce0geri0cn,eentpirndpaeemtxgiropeenngoxe.rsporeauodlps,teomwdteahtaosen3tshd3aea%misleayhmiignehtaekre C. (CTlainbilceasl1O1-b1s2e,rAvaptpieonndsixanDd)Mortality One female mouse exposed to 1ppm of H-24020 was found dead on test day 1. The cause of ddcoeeaamtthhpsowuinansdm-nrioectleadeteextdeprocmlsienidnicetadolbhouibgtshieterwrvacatosinoncnoestnoctrcoacntuisorirdneesdroeidfnHtmo-i2bc4ee0ce2ox0mp.opNsoeoudnotdothrHeerl-a2eta4er0dl2ya0ds.ethatehrse awnedrenono nbNaantoootdtdrieycb1aouwrnftleeesymdiidgdateheolrateeteedhmxfsfptoeooouccsbtscueeourbeearsrxtdeepodriorvHesience-dtd2m4citnoi6ocm4teh38p0ie.so0xugppnropodsum-eprde.HltaoN-t2eHo4d6-oe24tf4h8f6ee(4rcnt8co,.ltbinsuEittcnaamtoilpsasthyiictghhanaalsllvymwesuebisgreenweionfabisscseaoecnrbotvs)ne.eddrvaTtrehhydaisttionewft2ehferemecstaeilvseere D. (LTivabelreWs 1e1i-g1h2t,sAppendix E) Erexlaptoivsuer(elitvoeHr w-2e4ig0h2t0/fainnadlHbo-2d4y6w48eipgrhot)dulicveedr wstaetiigshtitcsailnlyaslligtrneiafitceadnmt ianlcergearosuespsi.n aEbxspoolusutereantod wHe-2ig4h0t2s0inanfedmHa-l2e4g6r4o8uppsroedxupcoesdedsttaoti3stipcpamllyasnidgnaibfoicvaen.t increases in absolute and relative liver 16 Company Sanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 Idwneemmigoahnltesstmwraeitcereedeaaxlsdpooosisnee-cdrreetsoapsHoend-2sie4n0ut2hp0et,o3th0the0eipn1pc0mr0eagpsrpeomuinpcao(bcnsocomelnupttarearetaidnodnto.recAloabntistvrooelull)tievbeuartnwtdhereeigmlahtatisgvneitluivdeerof the egfrfoeucptswraasngleesdsftrhoamn t1h1a7t%of-2th7e5%10o0fpcpomntrgorlo;ump.eaMn eaabnsoalbustoelluitveerliwveerigwhetiginhttshein3t0h0ep1p-m100grpopump w32a9s%22o9f%coonftrcooln; tmroela. nMreelaantivreelalitviveer wliveeigrhwteinigthhtes 3in00thpep1m-1g0r0opuppmwagsro3u1p9s%raonfgceodnftrrooml. 116%- Idnemmoanlestmraitceedeaxdpoossee-dretospHon-2se46u4p8t,oththeein1c0r0eapspemincaobnscoelnuttreatainodn.reAlabtisvoelultievearnwderieglahttisve liver twwTeg3of4rheafo4ceeisugo%rc2pehntf1sttwoors3rorfaa%welcsn,,eoglioerneneexfstdrpmscaooofltalsrhsn;loouaetmmrrniomeneltc1a.thiocrn3aeeM1tHar.%eose-le2afa-d2nt4thi70ivren92ee%l01talh0itaevoi0nve3fpder0cpwHlo0minve-pt2eigrpgr4ormh6wolt;4uegim8pnirg.oepthuahrMtonpesdea3i(unacb0cnos0teohmadplebpuptstah1moer-ele1lugdsi0tvar0etoemoprulieppcwvomeewenfriftaggwershocreottl3i)ugio0npbhn5sutt%slhtriaevtiohnne3fegrt0hcewm0odeenapfi1tgpgrr-onomh1milt0t.,u0grd1repoe2lpua4omtp%ifv-tehe Id3ne-3mf0eo0mnpaslptermamtegidcroeauedpxospsroea-snreegdseptdoofnHrso-em2i4n10m0280i%,cet-h2ee5xi4pn%ocsreeodafstceooin3nt-r3aob0ls.0opMluptemea.nanMrdeleraeatlniavtaeibvlsievoleliurvtewerelwiivgeehirgtswhitensigthhets3i-n30th0e p1ppmpmgrgoruopusprawnegreedcformompar1a1b4l%e t-o31c4o%ntroofl c(1o0n1tr%ol.anMde1a0n4a%bsoofluctoenatrnodl,rreelsaptievcetilviveleyr)w. eights in the Id33ne-03m0f0eop0mnppasmlptermagmtreogidcuroepausedpxrosapsnroeag-snreeegddsepftdoroofnHmrso-em21i42n615m24%38i-%c,3et5-h2e8e7x%i5pn%ocosrfeeocdafostcenootirn3not-lr3a.ob0lMs.0opMelupatemneaa.nabnMrsdeolerlauaetlnitavetaeiabvnlseidvolelriurevtlewearteliwiivvgeeehirlgtiswhviteensrigtwhheetsig3ihntsthe doi1nivpfetfphermleraep1ngcbpreoepsutmwpwsegeewrrnoeautnshponewtorsetatrncaetoginehstssiigicodhaefelrltreyhtdehsiab2gninogiilrfnooigcucaipocnsna.ttlrlfoTyrolhsm(ei1gr0encf6oiof%nirctera,aonntlthd,nebo1sur1mtf1rwa%olamlsoinpfecarcrocoehbnaatsorbeotlhlyi,necrrleliaosvnpsedeercttwohtieevtriehgelehywt)th.airnseTsthhheeosled fliovrelrivweeriwgheti,grhetlaetfifveecttso. cTohnutsr,ole,xipnofseumrealteomHi-c2e4.020 and H-24648 produced the same effect on aSsulitmbhsoitluaangrchgeemsn.aelMreasladltereesmnddoesnmsintornalistvetredartgewrdeeaiegtnehlratsrrgeenesdspiotlinivvsieetrysswtihnearanellfoeebmxspaeolrevsseeddtowgtrhiotehuplbisvo.ethrLeitvfefseetrcsetusnbolasftragbneocmtehset,netstwas nbdoeiobocstlreooerbgavsiseceedardvlilneaytdfsteihignmenfahielfiemigcshaaeenlxests.pt oceTsoxhenpdecoesmtoneadtr1gatnpotiipot1umndpieponmfomHfoat-hlf2eeH4s6,l-i42wv84eh0rbi2lwue0te.tithghSeehmetdfeaiffflelffceeitrnceitcnnrrcceereaaesscaehwsseeedidnreaolrnipvoldeatetrmecwaoounenisagsitdnhredtar/tweoedrderae plolassteoabusueprvteodthinethhiegsheemsticceo.ncTehnetramtiaognnitteusdteedoifnthfeempaelaeks.efTfehcist wwaass saitmtriiblaurteind mtoatlhees banoddyfewmeaiglehst. .Company Sanitized. Does not contain TSCA CBf 17 H-24648 and H-24020: Repeated-Dose Oral Toxicity Study 14-Day Feeding Study in Mice DuPont-5206 rcIisenaopnamonproetrtereidbcveifmooduriexsttthesuratrmutesdicntyuoe/dnd1y}t.a;initnchereedraeisfneodrHel-,i2vth4e0er2rw0ee.aisgTohnhtesfowmreetrhaeennddoiaftifloeybreisnnetcravekeeidnoitnfhtemhneaoltee-osmbt ssiceuerbvsfeteaddn-ec1fefpewpcmatsleonvfoettlhe Tssuehnbessritetainvwciateyss,.naoBndboittohhleodgesamicmoaelnlsyptlrsaaitgteenadiuftihcaeanndst/aodmrifedfeeacrperpenracosexeoiimbnsareteersvpNeodOniEsneLta,hteththleievseharmigreehsespseotxncdsoeinfcftoeerntehtnreactetiwoinno test in mH-a2le4s6.48Awt aasgiavlemnodsiteatlawryaycsonhcigehnetrratthioann athnadtfoofrtahegirveesnpognesnedteor,Hth-e24m0a2g0n, iwtuhdeenocformesppaornedsetoto pceHcoxoaontnptwstoeriersodnevled.etroret,Wdotthhthteoheeeyndbi2eotfhcfbteeceirusoaetrlbnorssceguoedibslcsus,atptaaleolnnyradcansedtidshgi,cenraaeimlflfliayecatwaig(vnonetsni.ttllauiytvdiaesettrioocwfaneldeliiygofhfrsetistrgwenwnoicfeiedrcesoaswnceotasmdspipsfefmarerrsaeeeldlnx.cs).teTashtTiweshrteeiecrrfeeaolrowleyb,asbsteherntevwoyeedcweo.ennrsmeisnitceoent t CONCLUSIONS Urenspdoenr stheeocfomnidcietiofends tohfethtwisostteusdtys,utbhsetraenwceass. no biologically significant difference in the liver wpTaainlnrhelcodeirtdgrreHueehaca-tsws2teeed4sawd6siae4nmnrs8eoaamblwoNeasbaloOglsslrebEuo1rutLvuepteppfacdsonmo.irdnn,TlsriaifhveseseletmaesrNttnaiwavtOltleeeiysEigg(tgLilrhcirovetafuealogpltrryaeswilrnsieveiexgiiefnpgnfreohimwfcsti/teacefodialinegnntahtomiltin3bnie-ccoflpeifrdfepeeeycamxtpswspeaaoesirnnisaigdemnfhdeaetamb)ttboeolasrivHolsveele-tu.mh2rt4eaEwin0cxaee2pnHig0doe-hxs2ortup4esrrol0Hewas2te-tei0o2dvr.4eeHt6ool-4ib2Hv8s4e,-e6r2ar44vs80ed20in Company Sanitized. Does not contain TSCA CBI 18 H14--2D4a6y48FeaenddinHg-2S4tu02d0y:inRMepiceeated-Dose Oral Toxicity Study DuPont-5206 REFERENCES 1 Kennedy G.L. (1987I)d. rIenlcarteeadsefluinormocohuesme ilcivaelsr.weight following feeding of| 2. WDrialepye,r,NNe.wR.Yaonrdk.Smith, H. (1981). Applied Regression Analysis, 2nd edition, pp 266-273. 3. Selwyn, M.R. (1995). The use of trend tests to determine a no-observable-effect level in animal safety studies. Journal o fthe American College of Toxicology 14(2), 158-168. 4. BJoionmckehtreiekrae,4A1,.R1.3(31-915445.). A distribution-free K-sample test against ordered alternatives. 5. SLteavtiesnteic,sH(.J.(1O9l6k0in)., eRdo.)b,upspt 2te7s8t-f2o9r2e.quSatalintyfoordf vUarniiavnecressit.yCProenstsr,ibPuatlioonAslttoo.Probability and 6. sSahmappilreos,).S.BSi.oamnedtrWikialk5.,2M, 5.9B1.-(611916.5). An analysis of variance test for normality (complete 7. 3S4n9e-d3e5c2o.r,TGh.eWI.oawnadSCtaotcehUranni,vWers.Gity. (P1r9e6s7s,).IoSwtaa.tistical Methods, 6thedition, pp 246-248 and 8. wDiutnhnaetcto, nCt.rWol.. (J1.9A5m5)e.r.AStmatuisltti.pAlesscoocm. 5p0a,ri1so0n96p-r1o1c2e1d.ure for comparing several treatments 9. JK.rAumskearl., SWta.tHis.t.anAdssWoca.l4li7s,, W58.3A-6. 2(119. 52). Use of ranks in one-criterion analysis of variance. 10. NFieswheYr,oRrk.A. . (1985). Statistical Methodsfor Research Workers, 13thedition. Haffher' CompanySanHfeeU. Do no, TSCACB) 19 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ DuPont-5206 TABLES Company Sanitized. Does not contain TSCA CBI 20 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice ___________________________________________________________________ TABLE 1 MEAN BODY WEIGHTS OF MALE MICE DuPont-5206 Day 0 Day 7 Day 14 Mean Body Weights (g) of Mice Fed Diet Containing H-24020 Group I 0 ppm 29.3 1.8(5) 30.6 2.1(5) 32.3 2.4(5) Group III Group V 1 ppm 3 ppm 29.2 1.9(5) 29.4 2.6(5) 31.3 1.7(5) 31.0 2.9(5) 32.8 2.0(5) 32.5 3.3(5) Group VII Group IX 10 ppm 30 ppm 29.5 2.2(5) 29.5 1.7(5) 31.2 2.2 (5) 31.8 1-6(5) 32.8 2.4(5) 33.0 1.2(5) Group XI 100 ppm 29.3 1.2(5) 29.3 1.2(5) 27.0 1.3(5) Group XIII 300 ppm 30.1 1.8(5) 25.2# 0.9(5) 23.3# 1.1(5) Mean Body Weights (g) of Mice Fed Diet Containing H-24648 Company Sanitized. Does Group I 0 ppm Group XV 1 ppm Group XVII Group XIX Group XXI Group XXIII Group XXV 3 ppm 10 ppm 30 ppm 100 ppm 300 ppm Day 0 29.3 1.8(5) 30.0 1.4(5) 29.7 1.5(5) 28.0 1.8(5) 28.4 1.7(5) 29.7 3.0(5) 29.1 1.3(5) Day 7 30.6 2.1(5) 32.7 1.6(5) 31.6 2.0(5) 30.0 1.4(5) 30.3 2.0(5) 27.5# 2.3(5) 24.0# 2.2(5) Day 14 32.3 34.1 33.8 32.2 30.0 26.2# oOO3 2.4(5) Data summarized as: Mean 1.8(5) 1.8(5) 2.0(5) Standard Deviation (n) 3 Statistical Methods: Trend test (Jonckheere-Terpstra). 2.7(5) 1.2(5) # Statistically significant difference at p < 0.05. HI 8CO 8 21 22.7# 1.2(5) % H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_________________________ % TABLE 2 MEAN BODY WEIGHTS OF FEMALE MICE # DuPont-5206 Company Sanitized. Does not contain TSCA Day 0 Day 7 Day 14 Mean Body Weights (g) of Mice Fed Diet Containing H-24020 Group II 0 ppm 24.2 1-0(5) 25.0 1.7(5) 26.8 0.8(5) Group IV 1 ppm 23.7 0.6(5) 24.6 0.4(4) 25.7 0.2(4) Group VI 3 ppm 23.5 0.7(5) 24.8 0.7(5) 25.3 1.0(5) Group VIII Group X 10 ppm 30 ppm 23.5 1.4(5) 24.0 1.3(5) 25.4 2.0(5) 23.4 0.9(5) 26.5 2.0(5) 26.5 0.9(5) Group XII 100 ppm 23.9 1.2(5) 23.6 1.4(5) 26.1 2.6(5) Group XIV 300 ppm 24.0 1.3(5) 21.3# 0.6(5) 21.0# 0.8(5) Mean Body Weights (g) of Mice Fed Diet Containing H-24648 Group II Group XVI Group XVIII Group XX 0 ppm 1 ppm 3 ppm 10 ppm Day 0 24.2 1.0(5) 23.7 1.4(5) 24.0 1.2(5) 23.6 1.7(5) Day 7 25.0 1.7(5) 24.6 1.5(5) 25.3 1.4(5) 24.2 1.9(5) Day 14 Data summarized as: 26.8 0.8(5) Mean Standard Deviation 25.6 1.7(5) (n) 26.4 1.3(5) Statistical Methods: Trend test (Jonckheere-Terpstra). # Statistically significant difference at p < 0 .05 26.0 2.6(5) Group XXII Group XXIV Group XXVI 30 ppm 100 ppm 300 ppm 23.1 1.3(5) 24.4 1.8(5) 25.0 1.3(5) 24.5 0.9(5) 24.4 1.4(5) 21.3# 1.6(5) 26.5 1.1(5) 23.8 1.9(5) 20.5# 1.2(5) O 22 CD H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice________________________________________________ TABLE 3 MEAN BODY WEIGHT GAINS OF MALE MICE DuPont-5206 Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Mean Body Weight Gains (g) of Mice Fed Diet Containing H-24020 Group I 0 ppm 1.4 0.5(5) Group III Group V 1 ppm 3 ppm 2.1 0.6(5) 1.6 0.4(5) Group VII 10 ppm 1.6 0.5(5) Group IX 30 ppm 2.3 0.5(5) Group XI 100 ppm - 0.0 1.0(5) 1.7 0.4(5) 1.4 0.4(5) 1.5 0.5(5) 1.6 0.5(5) 1.2 0.5(5) -2.3# 1.1(5) 3.0 0.8(5) 3.5 0.8(5) 3.1 0.9(5) 3.3 0.6(5) 3.5 0.9(5) -2.4 1.3(5) Group XIII 300 ppm -4.9# 1-7(5) -1.9# 1.1(5) -6.8# 2.1(5) Mean Body Weight Gains (g) of Mice Fed Diet Containing H-24648 Group I 0 ppm Group XV 1 ppm Group XVII Group XIX Group XXI Group XXIII Group XXV 3 ppm .10 ppm 30 ppm 100 ppm 300 ppm Day 0 - Day 7 1.4 0.5(5) 2.7 0.3(5) 1.8 0.9(5) 2.1 0.6(5) 1.9 1.0(5) -2.2 2.9(5) -5.1# 2.5(5) Day 7 - Day 14 1.7 0.4(5) 1.5 0.3(5) 2.3 0.4(5) 2.1 0.8(5) -0.3 2.0(5) -1.3# 1.4(5) -1.3# 1.4(5) Day 0 - Day 14 3.0 4.1 0.8(5) 0.6(5) Data summarized as: Mean Standard Deviation (n) 4.1 0.6(5) Statistical Methods: Trend test (Jonckheere-Terpstra). # Statistically significant difference at p < 0.05. 4.2 1-0(5) 1.6 1.7(5) -3.5# 3.0(5) -6.4# 1-5(5) Company Sanitized. Does not contain TSCA O 23 CO H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_________________________________________________________________________________________________ TABLE 4 MEAN BODY WEIGHT GAINS OF FEMALE MICE DuPont-5206 Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Mean Body Weight Gains (g) of Mice Fed Diet Containing H-24020 Group II 0 ppm 0.8 1.1(5) 1.8 1.1(5) 2.6 0.7(5) Group IV 1 ppm 0.7 0.6(4) 1.1 0.5(4) 1.9 0.4(4) Group VI 3 ppm 1.3 0.8(5) 0.5 0.5(5) 1.8 1.2(5) Group VIII Group X 10 ppm 30 ppm 1.9 1.3(5) -0.6 1.1(5) 1.1 0.6(5) 3.1 0.7(5) 3.0 1.2(5) 2.5 0.7(5) Group XII 100 ppm -0.3# 0.5(5) 2.5 1-8(5) 2.2 1.7(5) Group XIV 300 ppm -2.6# 1.7(5) -0.3@ 0.8(5) -2.9 1.6(5) Mean Body Weights Gains (g) of Mice Fed Diet Containing H-24648 Group II 0 ppm Group XVI 1 ppm Group XVIII Group XX 3 ppm 10 ppm Group XXII Group XXIV Group XXVI 30 ppm 100 ppm 300 ppm Day 0 - Day 7 0.8 1.1(5) 0.8 0.5(5) 1.2 0.5(5) 0.6 0.4(5) 1.4 0.7(5) 0.1 1.9(5) -3.7# 1.1(5) Day 7 - Day 14 1.8 1.1(5) 1.0 0.3(5) 1.1 0.6(5) 1.8 1.3(5) 1.9 0.3(5) -0.6 1.1(5) -0.8# 1.0(5) Day 0 - Day 14 2.6 0.7(5) 1.8 0.7(5) Data summarized as: Mean Standard Deviation (n) 2.3 0.9(5) 2.4 1.2(5) 3.3 0.4(5) Statistical Methods: Trend test (Jonckheere-Terpstra) and/or non-parametric test # Statistically significant difference at p < 0.05 using Jonckheere-Terpstra. @ Statistically significant difference at p < 0.05 using Dunn's test. -0.6 2.6(5) (Dunn 's). -4.5# 0.7(5) 24 Company Sanitized. Does not contain TSCA CB H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice___________________________________________________________________________________________________________DuPont-5206 TABLE 5 MEAN DAILY FOOD CONSUMPTION BY MALE MICE Company Sanitized. Does not contain TSCA C Mean Daily Food Consumption (g) by Mice Fed Diet Containing H-24020 Day 0 - Day 7 Day 7 - Day 14 Group I 0 ppm 5.9 0.7(5) 6.1 0.9(5) Group III 1 ppm 6.2 0.8(5) 6.3 0.5(5) Group V 3 ppm 5.6 0.3(5) 6.3 0.6(5) Group VII 10 ppm 5.9 0.3 (5) 5.9 0.3(5) Group IX 30 ppm 5.7 0.5(5) 6.7 1.4(5) Group XI 100 ppm 5.6 0.7(5) 7.8 1.1(5) Day 0 - Day 14 6.0 0.7(5) 6.3 0.6(5) 6.0 0.3(5) 5.9 0.2(5) 6.2 0.9(5) 6.7 0.8(5) Group XIII 300 ppm 5.0 0.9(5) 5.1 1.6(5) 5.0 1-2(5 ) Mean Daily Food Consumption (g) by Mice Fed Diet Containing H-24648 Day 0 - Day 7 Group I 0 ppm 5.9 0.7(5) Group XV 1 ppm 6.2 0.3(5) Group XVII Group XIX 3 ppm 10 ppm 6.3 0.4(5) 5.9 0.2(5) Group :XXI Group XXIII Group XXV 30 ppm 100 ppm 300 ppm 5.9 0.8(5) 6.6 1.6(5) 6.8 0.9(5) Day 7 - Day 14 6.1 0.9(5) 6.5 0.5(5) 6.1 0.5(5) 5.5 0.5(5) 6.8 0.8(5) 6.0 1.1(5) 6.1 0.9(5) Data Day 0 - Day 14 summarized as: 6.0 6.4 0.7(5) 0.4(5) Mean Standard Deviation (n) 6.2 0.4(5) Statistical Methods: Trend test (Jonckheere-Terpstra). # Statistically significant difference at p < 0. 05. 5.7 0.3(5) 6.4 0.6(5) 6.3 1.2(5) 6.4 0.7(5) 25 as H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_________________ TABLE MEAN DAILY FOOD CONSUMPTION BY FEMALE MICE DuPont-5206 Company Sanitized. Does not contain TSCA CBt Mean Daily Food Consumption (g) by Mice Fed Diet Containing H- 24020 Day 0 - Day 7 Group II 0 ppm 5.9 1.1(5) Group IV 1 ppm 7.2 2.6(4) Group VI 3 ppm 5.1 0.5(5) Group VIII 10 ppm 6.0 0.8(5) Group X 30 ppm 5.8 0.5(5) Group XII 100 ppm 6.0 1.0(5) Day 7 - Day 14 6.2 1.3(5) 7.0 0.9(4) 6.3 0.9(5) 6.9 1.4(5) 6.3 0.9(5) 7.0 1.6(5) Day 0 - Day 14 6.1 1.2(5) 7.1 1.6(4) 5.7 0.6(5) 6.5 1.0(5) 6.1 0.5(5) 6.5 1.0(5) Group XIV 300 ppm 7.0 1.6(5) 7.4 1.6(5) 7.2 1.5(5 ) Mean Daily Food Consumption (g) by Mice Fed Diet Containing H- 24648 Group II Group XVI Group XVIII Group XX 0 ppm 1 ppm 3 ppm 10 ppm Day 0 - Day 7 5.9 1.1(5) 5.5 0.5(5) 5.5 0.5(5) 6.1 1.5(5) Day 7 - Day 14 6.2 1.3(5) 5.1 0.2(5) 5.8 1.0(5) 5.8 0.8(5) Data Day 0 - Day 14 summarized as: 6.1 5.3 1.2(5) 0.4(5) Mean Standard Deviation (n) 5.7 0.6(5) Statistical Methods: Trend test (Jonckheere-Terpstra). # Statistically significant difference at p < 0.05. 5.9 1.1(5) Group XXII Group XXIV Group XXVI 30 ppm 100 ppm 300 ppm 5.7 0.8(5) 6.4 0.4(5) 8.0# 1.5(5) 6.8 1.9(5) 5.9 0.7(5) 5.7 0.6(5) 6.3 1-3(5) 6.1 0.4(5) 6.8# 1.0(5) 26 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice________________________ TABLE 7 MEAN DAILY FOOD EFFICIENCY OF MALE MICE DuPont-5206 Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Mean Daily Food Efficiency of Mice Fed Diet Containing H-24020 (g body weight gain/g food consumption) Group I 0 ppm 0.032 0.009(5) 0.039 0.009 (5) 0.036 0.007(5) Group III 1 ppm 0.049 0.017(5) 0.033 0.009(5) 0.041 0.009(5) Group V 3 ppm 0.040 0.010(5) 0.034 0.009(5) 0.037 0.008(5) Group VII 10 ppm 0.040 0.011(5) 0.040 0.012(5) 0.040 0.007(5) Group IX 30 ppm 0.059 0.011(5) 0.024 0.008(5) 0.040 . 0.006(5) Group XI 100 ppm Group XIII 300 ppm -0.002 0.029(5) -0.149# 0.070(5) -0.043# 0.021(5) -0.059# 0.038(5) -0.025 0.014(5) -0.105# 0.049(5) Mean Daily Food Efficiency of Mice Fed Diet Containing H-24648 (g body weight gain/g food consumption) Group I 0 ppm Group XV 1 ppm Group XVII 3 ppm Group XIX 10 ppm Group XXI 30 ppm Group XXIII Group XXV 100 ppm 300 ppm Day 0 - Day 7 0.032 0.061 0.009(5) 0.007(5) 0.042 0.019(5) Day 7 - Day 14 0.039 0.032 0.009(5) 0.006(5) 0.054 0.012(5) Data Day 0 - Day 14 summarized as: 0.036 0.046 0.007(5) 0.005(5) Mean Standard Deviation (n) 0.048 0.008(5) Statistical Methods: Trend test (Jonckheere- Terpstra). # Statistically :significant difference at p < 0.05. 0.051 0.017(5) 0.056 0.020(5) 0.053 0.013(5) 0.046 0.022(5) -0.005 0.044(5) 0.019 0.022(5) -0.058 0.076(5) -0.036# 0.036(5) -0.046 0.046(5) -0.111# 0.065(5) -0.033# 0.038(5) -0.072# 0.019(5) Company Sanitized. Does not contain TSCA cm 27 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice TABLE 8 MEAN DAILY FOOD EFFICIENCY OF FEMALE MICE DuPont-5206 Company Sanitized. Doee not contain tsca CBI Mean Daily Food Efficiency of Mice Fed Diet Containing H-24020 _____________ (g body weight gain/g food consumption) Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Group II 0 ppm Group XVI Group XVIII Group XX 1 ppm 3 ppm 10 ppm Group XXII Group XXIV Group XXVI 30 ppm 100 ppm 300 ppm 0.017 0.026(5) 0.018 0.020(4) 0.038 0.024(5) 0.049 0.038(5) -0.014 0.026(5) -0.007 -0.055# 0.011 (5) 0.030(5) 0.044 0.029(5) 0.023 0.010 (4) 0.010 0.008(5) 0.024 0.013(5) 0.070 0.009 (5) 0.051 -0.007 0.037(5) 0.015(5) 0.031 0.010(5) 0.020 0.008 (4) 0.022 0.013 (5) 0.036 0.018(5) 0.030 0.011(5) 0.025 -0.030 0.020(5) 0.015(5) Mean _D_a__i_l_y___F(ogodboEdfyfiwceiiegnhcty of Mice Fed gain/g food Diet Containing consumption) H-24648 Group II 0 ppm Group XVI 1 ppm Group XVIII 3 ppm Day 0 - Day 7 0.017 0.026(5) 0.022 0.011(5) 0.032 0.014(5) Day 7 - Day 14 0.044 0.029(5) 0.028 0.010(5) 0.029 0.021(5) Day 0 - Day 14 0.031 0.010(5) Data summarized as: Mean 0.025 0.009(5) 0.031 0.016(5) Standard Deviation (n) Statistical Methods: Trend test (Jonckheere-Terpstra) # Statistically significant difference at p < 0.05. Group XX 10 ppm 0.015 0.011(5) 0.044 0.028(5) 0.029 0.011(5) Group XXII Group XXIV Group XXVI 30 ppm 100 ppm 300 ppm 0.036 0.020(5) 0.002 0.043(5) -0.066# 0.016(5) 0.042 0.009(5) -0.014 0.023(5) - 0 .021# 0.026(5) 0.039 -0.006 -0.048# 0.010(5) 0.031(5) 0.010(5) -- "*------------------ 28 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_______ __________________________________ TABLE 9 MEAN DAILY INTAKE OF THE TEST SUBSTANCE BY MALE MICE DuPont-5206 Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Mean Daily Intake of H-24020 (mg/kg/day) Group I 0 ppm Group III 1 ppm Group V 3 ppm Group VII 10 ppm Group IX 30 ppm 0.00 0.00(5) 0.20 0.02(5) 0.55 0.06(5) 1.89 0.11(5) 5.38 0.67(5) 0.00 0.00(5) 0.19 0.02(5) 0.58 0.03(5) 1.80 0.08(5) 6.14 1.35(5) 0.00 0.00(5) 0.20 0.01(5) 0.57 0.03 (5) 1.84 0.08(5) 5.76 0.97(5) Group XI 100 ppm 19.09 1.87(5) 29.07 4.72(5) 24.08 2.83(5) Group XIII 300 ppm 59.87 11.72(5) 64.98 19.17(5) 62.43 14.81(5) Mean Daily Intake of H- 24648 (mg/kg/day) Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Group I 0 ppm 0.00 0.00(5) 0.00 0.00(5) 0.00 0.00(5) Group XV 1 ppm 0.19 0.01(5) 0.19 0.01(5) 0.19 0.01(5) Group XVII 3 ppm 0.60 0.07(5) 0.54 0.07(5) 0.57 0.07(5) Group XIX 10 ppm 1.97 0.11(5) 1.70 0.10(5) 1.83 0.07(5) Group XXI 30 ppm 5.88 0.68(5) 6.94 1.38(5) 6.41 0.94(5) Data summarized as: Mean Standard Deviation (n) Group XXIII Group XXV 100 ppm 300 ppm 24.44 6.76(5) 85.72 16.42(5) 23.08 4.88(5) 80.35 12.02(5) 23.76 5.52(5) 83.04 12.39(5) Company Sanitized. Does not contain TSCA CB> 29 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice __________________________________________________________________ TABLE 10 MEAN DAILY INTAKE OF THE TEST SUBSTANCE BY FEMALE MICE DuPont-5206 Day 0 - Day 7 Day 7 - Day 14 Day 0 - Day 14 Mean Daily Intake of H-24020 (mg/kg/day) Group II 0 ppm 0.00 0.00(5) 0.00 0.00(5) 0.00 ' 0.00(5) Group XVI 1 ppm 0.29 0.11(4) 0.27 0.03(4) 0.28 0.07(4) Group XVIII Group XX 3 ppm 10 ppm 0.62 0.06(5) 2.38 0.44(5) 0.75 0.08(5) 2.66 0.76(5) 0.68 0.05(5) 2.52 0.58(5) Group XXII Group XXIV Group XXVI 30 ppm 100 ppm 300 ppm 7.41 0.64(5) 25.33 4.13 (5) 98.49 24.27(5) 7.16 0.86(5) 26.70 5.43(5) 105.79 21.31(5) 7.28 0.53(5) 26.01 3.82(5) 102.14 21.72 (5) Mean Daily Intake of H-2464SI (mg/kg/day) - Group II Group XVI 0 ppm 1 ppm Day 0 - Day 7 0.00 0.00(5) 0.29 0.11 (4) Day 7 - Day 14 0.00 0.00(5) 0.27 0.03(4) Day 0 - Day 14 0.00 0.00(5) 0.21 0.02(5) Data summarized as: Mean Standard Deviation (n) Group XVIII Group XX 3 ppm 10 ppm 0.62 0.06(5) 2.38 0.44(5) 0.75 0.08(5) 2.66 0.76(5) 0.66 0.08(5) 2.37 0.35(5) Group XXII Group XXIV Group XXVI 30 ppm 100 ppm 300 ppm 7.41 0.64(5) 25.33 4.13(5) 98.49 24.27(5) 7.16 0.86(5) 26.70 5.43(5) 105.79 21.31(5) 7.38 1.49(5) 25.55 2.48(5) 98.84 18.75 (5) .Company Sanitized. Does not contain TSCA CBI 30 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice _____________________________________________________________________ TABLE 11 SUMMARY OF CLINICAL OBSERVATIONS OF MALE MICE Group Concentration (ppm) Animals in Group Clinical Observations of Mice Fed Diet Containing H-24020 I Ill V 01 3 55 5 VII IX XI 10 30 100 5 55 There were no abnormalities detected. DuPont-5206 XIII 300 5 Clinical Observations of Mice Fed Diet Containing H-24648 Group Concentration (ppm) Animals in Group Eye Observations Enophthalmus I XV XVII XIX XXI XXIII 01 3 10 30 100 55 5 5 55 Incidence Mean onset (Days) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) Incidence - The number of animals (percent of group) for which an observation was recorded. Mean onset (Days) - The mean of the first test day an observation was recorded for that group. Statistical Methods: Trend test (Cochran-Armitage). There were no statistically significant differences at p < 0.05. XXV 300 5 2 (40%) 7 Company Sanitized. Does not contain TSCA CBI 31 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_______________ DuPont-5206 TABLE 12 SUMMARY OF CLINICAL OBSERVATIONS OF FEMALE MICE Group Concentration (ppm) Animals in Group Wound Superficial Incidence Mean onset (Days) Misshapen Tail Incidence Mean onset (Days) Clinical Observations of Mice Fed Diet Containing H-24020 II IV 01 55 VI 3 5 VIII X XII 10 30 100 5 55 0 (0%) 0 (0%) 1 (20%) 7 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) XIV 300 5 0 (0%) 1 (20%) 7 Clinical Observations of Mice Fed Diet Containing H-24648 Group Concentration (ppm) Animals in Group Eye Observations Enophthalmus II XVI XVIII XX 01 3 10 55 5 5 XXII 30 5 XXIV 100 5 Incidence Mean onset (Days) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) Incidence - The number of animals (percent of group) for which an observation was recorded. Mean onset (Days) - The mean of the first test day an observation was recorded for that group. Statistical Methods: Trend test (Cochran-Armitage). There were n o :statistically significant differences at p < 0.05. XXVI 300 5 1 (20%) 7 Company Sanitized. Does not confoh i Sanitized. Does no! eonfsi. 32 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_________________________________________________________________________ DuPont-5206 TABLE 13 MEAN FINAL BODY AND LIVER WEIGHTS OF MALE MICE WEIGHT LIVER FINAL BODY LIVER/ FINAL BODY * 100 M e a n F i n a l B o d y W e i g h t s , A b s o l u t e L i v e r W e i g h t s , a n d R e l a t i v e L i v e r W e i g h t s (g) of Mice Fed Diet Containing H-24020 Group I 0 ppm 1.72 0.20(5) 32.30 2.39(5) 5.32 0.44(5) Group III 1 ppm 2.02# 0.11(5) 32.78 2.02(5) 6.17# 0.32(5) Group V 3 ppm 2.22# 0.16(5) 32.50 3.34(5) 6.85# 0.21(5) Group VII 10 pp m 2.79# 0.27(5) 32.80 2.40(5) 8.50# 0.38(5) Group IX 30 ppm 4.01# 0.22(5) 32.98 1.20(5) 12.18# 0.88(5) Group XI 100 ppm 4.72# 0.46(5) 26.98 1.29(5) 17.48#* 0.91(5) Group XIII 300 ppm 3.95# 0.19(5) 23.28# 1.07(5) 16.98# 1.09(5) M e a n F i n a l B o d y W e i g h t s , A b s o l u t e L i v e r W e i g h t s , a n d R e l a t i v e L i v e r W e i g h t s (g) of Mice Fed Diet Containing H-24648 WEIGHT LIVER FINAL BODY LIVER/ FINAL BODY * 100 Group I 0 ppm 1.72 0.20(5) 32.30 2.39(5) 5.32 0.44(5) Group XV 1 ppm 2.26# 0.11(5) 34.12 1.81(5) 6.62# 0.18(5) Group XVII 3 ppm 2.56# 0.31(5) 33.84 1.84(5) 7.56# 0.67(5) Group XIX 10 pp m 2.96# 0.30(5) 32.18 2.03(5) 9.20# 0.53(5) Group XXI 30 p p m 4.10# 0.44(5) 29.98 2.69(5) 13.69# 0.88(5) Group XXIII 100 ppm Group XXV 300 ppm 4.79# 0.41(4) 3.67# 0.35(5) 26.20# 1.16(5) 22.68# 1.25(5) 18.30#* 1.79(4) 16.22# 1.87(5) Data summarized as : Mean Standard Deviation (n) # Statistically significant difference from control at p < 0.05 by Jonckheere-Terpstra trend test. * Statistically significant difference between test substances at p < 0.05 by linear contrasts test. Company Sanitized. Does hol confaln TSCA CB! 33 %% H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________________________________________________________________ DuPont-5206 TABLE 14 MEAN FINAL BODY AND LIVER WEIGHTS OF FEMALE MICE Company Sanitized. Does not contain WEIGHT LIVER FINAL BODY LIVER/ FINAL BODY * 100 M e a n F i n a l B o d y W e i g h t s , A b s o l u t e L i v e r W e i g h t s , a n d R e l a t i v e L i v e r W e i g h t s (g) of Mice Fed Diet Containing H-24020 G r o u p II 0 ppm 1.44 0.15(5) 26.78 0.81(5) 5.40 0.61(5) Group IV 1 ppm 1.45 0.04(4) 25.73 0.22(4) 5.64 0.19(4) Group VI 3 ppm 1.56# 0.07(5) 25.32 1.01(5) 6.16# 0.26(5) Group VIII 10 p pm 2.12# 0.18(5) 26.54 2.02(5) 8.01#* 0.80(5) Group X 30 p p m 2.95# 0.16(5) 26.50 0.91(5) 11.14# 0.35(5) Group XII 100 ppm 3.67# 0.48(5) 26.12 2.65(5) 14.08# 1.56(5) Group XIV 300 ppm 3.56#* 0.36(5) 21.02# 0.79(5) 16.96# 1.63(5) WEIGHT LIVER FINAL BODY LIVER/ FINAL BODY * 100 M e a n F i n a l B o d y W e i g h t s , A b s o l u t e L i v e r W e i g h t s , a n d R e l a t i v e L i v e r W e i g h t s (g) of Mice Fed Diet Containing H-24648 Group I 0 ppm 1.44 0.15(5) 26.78 0.81(5) 5.40 0.61(5) Group XV 1 ppm 1.53 0.07(5) 25.56 1.73(5) 5.99 0.27(5) Group XVII 3 ppm 1.78# 0.19(5) 26.36 1.25(5) 6.75# 0.53(5) Group XIX 10 pp m 2.38# 0.34(5) 25.98 2.59(5) 9.14#* 0.38(5) Group XXI 30 p p m 3.15# 0.19(5) 26.48 1.07(5) 11.89# 0.42(5) Group XXIII 100 ppm Group XXV 300 ppm 3.71# 0.52(5) 3.97#* 0.58(5) 23.78 1.85(5) 20.48# 1.22(5) 15.59# 1.42(5) 19.33# 2.03(5) Data summarized as: Mean Standard Deviation (n) # Statistically significant difference from control at p < 0.05 by Jonckheere-Terpstra trend test. * Statistically significant difference between test substances at p < 0.05 by linear contrasts test. 0>01 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice________ DuPont-5206 APPENDICES CompanySanitized. Does not contain re^n 35 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 APPENDIX A INDIVIDUAL BODY WEIGHTS CmP8"1' D o e , nol 36 tsca ce| H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ Individual Body Weights (g) of Control Mice Day 0 Male, I Control 124503 124504 124505 124506 124507 31.9 28.0 27.8 30.3 28.4 Day 7 33.2 29.0 28.8 32.6 29.6 Day 14 35.3 30.7 30.4 34.5 30.6 Female, II Control 124574 124575 124576 124577 124578 24.1 24.1 24.8 22.7 25.2 24.7 23.3 26.7 23.3 26.8 26.1 26.1 27.8 26.4 27.5 DuPont-5206 m Company Sanitized. Does not contain TSCA CBI 37 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Body Weights (g) of Mice Fed Diet Containing H-24020 Day 0 Male, III 1 ppm H-24020 124508 124509 124510 124511 124512 30.4 27.1 27.6 31.8 29.3 Day 7 32.7 30.2 29.2 33.4 31.2 Day 14 34.7 31.4 30.2 34.8 32.8 Male, V 3 ppm H-24020 124513 124514 124515 124516 124517 29.9 29.5 25.7 29.0 32.9 31.4 30.6 26.9 30.9 35.0 32.7 32.0 28.0 32.4 37.4 Male, VII 10 ppm H-24020 124518 124519 124520 124521 124522 29.4 26.8 28.2 30.9 32.3 31.8 28.1 30.0 32.2 33.7 33.1 29.5 31.9 33.4 36.1 Male, IX 30 ppm H-24020 124523 124524 124525 124526 124527 32.1 30.3 28.5 27.8 28.7 34.0 32.6 31.1 29.7 31.7 34.4 33.5 32.3 31.3 33.4 Male, XI 100 ppm H-24020 124528 124529 124530 124531 124532 30.5 27.7 30.2 28.6 29.7 30.9 28.6 30.2 28.9 28.0 27.2 26.9 29.0 25.6 26.2 Male, XIII 300 ppm H-24020 124533 124534 124535 124536 124537 30.3 29.2 32.4 27.7 30.7 24.4 24.4 25.4 25.0 26.6 23.8 21.5 23.1 24.2 23.8 Company Sanitized. Does not contain TSCA CBI 38 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ DuPont-5206 Individual Body Weights (g) of Mice Fed Diet Containing H-24020 Day 0 Day 7 Female, IV 1 ppm H-24020 124579 124580 124582 124583 124640 23.0 24.2 23.1 24.3 23.8 24.4 24.7 25.1 24.1 Day 14 25.8 25.4 25.8 25.9 Female, VI 3 ppm H-24020 124584 124585 124586 124587 124588 22.9 23.3 23.3 23.3 24.7 25.6 24.1 24.2 24.9 25.4 26.8 24.7 24.2 25.1 25.8 Female, VIII 10 ppm H-24020 124589 124590 124591 124592 124593 22.4 23.8 21.9 23.9 25.5 23.1 26.2 23.6 27.7 26.4 23.7 27.0 25.3 28.4 28.3 Female, X 30 ppm H-24020 124594 124596 124597 124598 124641 23.8 22.1 23.7 24.8 25.7 23.3 22.0 24.5 23.4 23.7 26.0 25.4 26.9 26.4 27.8 Female, XII 100 ppm H-24020 124599 124600 124601 124602 124603 23.2 24.9 22.2 24.1 25.2 23.0 25.1 21.5 24.2 24.4 22.4 28.2 24.4 27.0 28.6 Female, XIV 300 ppm H-24020 124604 124605 124606 124607 124608 23.5 23.9 22.8 23.5 26.1 21.3 21.9 21.8 21.1 20.5 20.2 21.2 22.2 20.4 21.1 Company Sanitized. Does not contain TSCA CBi 39 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Body Weights (g) of Mice Fed Diet Containing H-24648 Day 0 Male, XV 1 ppm H-24648 124538 124539 124540 124541 124542 30.6 30.9 28.0 31.3 29.2 Day 7 33.4 33.6 30.5 34.3 31.5 Day 14 34.9 35.2 32.0 36.1 32.4 Male, XVII 3 ppm H-24648 124543 124544 124545 124546 124547 28.5 28.1 31.8 30.7 29.6 30.0 29.2 33.0 33.9 31.8 32.8 31.4 35.6 35.7 33.7 Male, XIX 10 ppm H-24648 124548 124549 124550 124552 124569 30.5 26.5 26.8 29.2 26.8 31.8 29.1 29.6 31.1 28.6 34.7 31.5 31.8 33.5 29.4 Male, XXI 30 ppm H-24648 124553 124554 124555 124556 124557 29.9 27.7 25.9 28.3 30.1 30.4 32.5 30.4 29.2 27.2 25.9 30.9 32.3 32.6 30.0 Male, XXIII 100 ppm H-2468 124558 124559 124560 124561 124562 29.4 27.6 26.8 34.6 30.2 27.7 23.4 28.8 29.0 28.6 26.6 24.3 27.3 26.8 26.0 Male, XXV 300 ppm H-24648 124563 124564 124566 124567 124570 30.6 28.2 28.7 30.2 27.6 22.7 27.0 23.9 25.1 21.2 22.9 23.9 23.3 22.7 20.6 Company Sanitized. Does not contain TSCA CBt 40 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Body Weights (g) of Mice Fed Diet Containing H-24648 Day 0 Day 7 Female, XVI 1 ppm H-24648 124609 124610 124611 124612 124613 23.4 24.6 22.4 22.5 25.7 23.6 25.9 23.1 23.8 26.4 Day 14 24.3 27.4 24.1 24.5 27.5 Female, XVIII 3 ppm H-24648 124614 124615 124616 124617 124618 25.5 23.8 22.5 23.6 24.8 27.1 24.2 24.0 24.8 26.3 27.7 24.9 26.1 25.5 27.6 Female, XX 10 ppm H-24648 124619 124620 124621 124622 124623 22.5 24.4 21.7 23.1 26.1 22.6 25.5 22.2 23.9 26.6 24.1 26.2 24.6 24.6 30.4 Female, XXII 30 ppm H-24648 124624 124625 124626 124627 124628 21.6 23.3 22.3 23.5 25.0 23.1 24.8 24.7 24.7 25.4 24.9 26.6 26.3 26.7 27.9 Female, XXIV 100 ppm H-24648 124629 124630 124632 124633 124639 23.0 24.7 24.4 27.2 22.5 22.1 24.7 24.4 25.2 25.7 21.8 24.4 22.1 24.3 26.3 Female, XXVI 300 ppm H-24648 124634 124635 124636 124637 124638 25.0 23.8 24.1 24.8 27.2 23.1 19.5 20.6 20.3 22.8 21.2 20.2 19.2 19.6 22.2 Company Sanitized. Does not contain TqriA CBI 41 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ DuPont-5206 APPENDIX B INDIVIDUAL FOOD CONSUMPTION Company Sanitized. Does not enn3u * <?** 42 ^smpany Sanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Food Consumption (g/day) by Control Mice Day 7 Male, I Control 124503 124504 124505 124506 124507 6.3 5.1 5.7 6.9 5.6 Day 14 7.3 5.0 5.9 6.4 5.9 Female, II Control 124574 124575 124576 124577 124578 6.3 4.9 7.7 5.3 5.2 6.6 5.2 8.3 5.9 5.3 DuPont-5206 Company Sanitized. Does nof contain TSCA CBI 43 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ DuPont-5206 Individual Food Consumption (g/day) by Mice Fed Diet Containing H-24020 Day 7 Day 14 Male, III 1 ppm H-24020 124508 124509 124510 124511 124512 7.4 5.8 5.7 6.6 5.5 6.8 6.3 6.3 6.7 5.5 Male, V 3 ppm H-24020 124513 124514 124515 124516 124517 5.1 5.8 5.7 5.7 5.9 6.6 5.8 5.6 6.8 6.9 Male, VII 10 ppm H-24020 124518 124519 124520 124521 124522 5.9 5.4 6.2 5.8 6.1 6.0 5.5 5.8 6.2 6.0 Male, IX 30 ppm H-24020 124523 124524 124525 124526 124527 5.3 5.2 5.6 6.2 6.2 5.4 5.8 6.3 7.2 9.0 Male, XI 100 ppm H-24020 124528 124529 124530 124531 124532 5.7 5.3 6.4 6.0 4.7 6.9 6.5 8.4 9.2 8.1 Male, XIII 300 ppm H-24020 124533 124534 124535 124536 124537 5.3 4.8 3.9 6.4 4.7 4.2 5.0 3.7 7.8 4.6 44 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Food Consumption (g/day) by Mice Fed Diet Containing H-24020 Day 7 Day 14 Female, IV 1 ppm H-24020 124580 124582 124583 124640 5.3 4.8 8.0 10.5 7.3 5.7 7.6 7.5 Female, VI 3 ppm H-24020 124584 124585 124586 124587 124588 5.1 5.7 4.7 4.6 5.4 7.8 6.1 5.5 5.9 6.2 Female, VIII 10 ppm H-24020 124589 124590 124591 124592 124593 6.9 6.3 5.4 4.9 6.4 9.1 6.4 7.4 5.3 6.6 Female, X 30 ppm H-24020 124594 124596 124597 124598 124641 5.7 5.2 5.4 6.5 6.0 6.0 6.0 6.0 5.6 8.0 Female, XII 100 ppm H-24020 124599 124600 124601 124602 124603 6.4 7.4 5.9 4.8 5.4 6.4 6.7 7.1 5.1 9.4 Female, XIV 300 ppm H-24020 124604 124605 124606 124607 124608 8.9 4.9 7.4 5.8 8.0 8.4 6.5 8.9 5.1 8.2 Company Sanitized. Does no! contain TSCA CBJ 45 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Food Consumption (g/day) by Mice Fed Diet Containing H-24648 Day 7 Male, XV 1 ppm H-24648 124538 124539 124540 124541 124542 6.1 6.8 6.3 6.1 6.0 Day 14 6.5 7.1 6.3 6.8 5.8 Male, XVII 3 ppm H-24648 124543 124544 124545 124546 124547 6.6 6.7 5.7 6.5 6.0 6.0 6.8 5.6 5.7 6.2 Male, XIX 10 ppm H-24648 124548 124549 124550 124552 124569 5.9 5.8 5.6 6.0 6.2 5.7 4.9 5.6 6.0 5.0 Male, XXI 30 ppm H-24648 124553 124554 124555 124556 124557 '5.6 7.2 5.3 5.5 6.1 6.7 7.7 7.6 6.0 6.2 M a l e , X X I I I 100 ppm H-2468 124558 124559 124560 124561 124562 5.2 7.6 8.0 4.7 7.8 6.2 7.4 6.4 4.5 5.6 Male, XXV 300 ppm H-24648 124563 124564 124566 124567 124570 5.5 6.6 7.6 6.5 7.8 5.8 5.0 7.3 6.6 5.6 Company Sanitized. Does not contain TSCA CBI 46 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice___________ DuPont-5206 Individual Food Consumption (g/day) by Mice Fed Diet Containing H-24648 Day 7 Day 14 Female, XVI 1 ppm H-24648 124609 124610 124611 124612 124613 5.6 5.8 5.4 6.0 4.6 5.3 5.1 4.9 5.4 4.8 Female, XVIII 3 ppm H-24648 124614 124615 124616 124617 124618 5.8 5.6 4.7 5.6 5.9 5.4 7.4 4.7 5.7 5.8 Female, XX 10 ppm H-24648 124619 124620 124621 124622 124623 6.5 5.2 4.8 5.5 8.6 6.1 4.8 5.2 5.9 6.8 Female, XXII 30 ppm H-24648 124624 124625 124626 124627 124628 5.5 5.0 5.5 7.1 5.6 6.7 4.8 5.6 9.6 7.4 Female, XXIV 100 ppm H-24648 124629 124630 124632 124633 124639 6.4 5.8 6.4 6.9 6.4 5.2 5.7 6.9 6.1 5.4 Female, XXVI 300 ppm H-24648 124634 124635 124636 124637 124638 5.9 10.1 8.5 7.8 7.5 5.1 6.4 5.4 5.4 6.2 Company Sanitized. Does not contain TSCA CBI 47 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 APPENDIX C INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY *) Company Sanitized. Does not contain TSCA CB! 48 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Male, I Control Individual Clinical Observations and Animal 124503 124504 124505 124506 124507 Observation General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design Female, II Control . Animal Observation 124574 General observation, No Abnormality Detected Sacrificed by design 124575 General observation. No Abnormality Detected Sacrificed by design 124576 General observation, No Abnormality Detected Sacrificed by design 124577 General observation, No Abnormality Detected Sacrificed by design 124578 General observation, No Abnormality Detected Sacrificed by design Company Sanitized. Does not contain TSCA CBI 49 Mortality of Control Mice Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Days 0-14 14 0-14 14 0-14 14 0-14 14 104-1 4 # DuPont-5206 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ Individual Clinical Observations and Mortality Male, III 1 ppm H-24020 Animal Observation 124508 General observation, No Abnormality Detected Sacrificed by design 124509 General observation. No Abnormality Detected Sacrificed by design 124510 General observation, No Abnormality Detected Sacrificed by design 124511 General observation, No Abnormality Detected Sacrificed by design 124512 General observation, No Abnormality Detected Sacrificed by design Male, V 3 ppm H-24020 Animal Observation 124513 General observation. No Abnormality Detected Sacrificed by design 124514 General observation, No Abnormality Detected Sacrificed by design 124515 General observation, No Abnormality Detected Sacrificed by design 124516 General observation. No Abnormality Detected Sacrificed by design 124517 General observation, No Abnormality Detected Sacrificed by design Company Sanitized. Does not contain TSCA CBi 50 of Mice Fed Diet Containing H-24020 DuPont-5206 Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice________________ Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24020 Male, VII 10 ppm H-24020 Animal Observation Days 124518 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124519 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124520 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124521 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124522 General observation, No Abnormality Detected Sacrificed by design 0-14 14 Male, IX 30 ppm H-24020 Animal Observation 124523 General observation, No Abnormality Detected Sacrificed by design 124524 General observation, No Abnormality Detected Sacrificed by design 124525 General observation. No Abnormality Detected Sacrificed by design 124526 General observation, No Abnormality Detected Sacrificed by design 124527 General observation. No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 i DuPont-5206 Company Sanitized. Does not contain o>cn 51 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________ ' ____________________ vj Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24020 Male, XI 100 ppm H-24020 Animal 124528 124529 Observation General observation, No Abnorma1ity Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 124530 124531 124532 General observation. No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0-14 14 Male, XIII 300 ppm H-24020 Animal Observation 124533 General observation. No Abnormality Detected Sacrificed by design 124534 General observation. No Abnormality Detected Sacrificed by design 124535 General observation, No Abnormality Detected Sacrificed by design 124536 General observation, No Abnormality Detected Sacrificed by design 124537 General observation, No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 i DuPont-5206 .Company Sanitized. Does not contain TSCA CBI 52 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ Individual Clinical Observations and Mortality Female, IV 1 ppm H-24020 Animal Observation . 124579 General observation. No Abnormality Detected Found dead in cage. 124580 General observation. No Abnormality Detected Sacrificed by design 124582 General observation, No Abnormality Detected Sacrificed by design 124583 General observation. No Abnormality Detected Sacrificed by design 124640 General observation, No Abnormality Detected Sacrificed by design Female, VI 3 ppm H-24020 Animal Observation 124584 General observation, No Abnormality Detected Sacrificed by design 124585 General observation, No Abnormality Detected Wound, Superficial, Neck Sacrificed by design 124586 General observation, No Abnormality Detected Sacrificed by design 124587 General observation, No Abnormality Detected Sacrificed by design 124588 General observation, No Abnormality Detected Sacrificed by design Company Sanitized. Does not contain TSCA CBI 53 of Mice Fed Diet Containing H-24020 DuPont-5206 Days 10-1 0-14 14 0-14 14 0-14 14 0-14 14 Days 0-14 14 0,14 7 14 0-14 14 0-14 14 0-14 14 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality Female, VIII 10 ppm H-24020 Animal Observation . 124589 General observation. No Abnormality Detected Sacrificed by design 124590 General observation, No Abnormality Detected Sacrificed by design 124591 General observation. No Abnormality Detected Sacrificed by design 124592 General observation, No Abnormality Detected Sacrificed by design 124593 General observation, No Abnormality Detected Sacrificed by design Female, X 30 ppm H-24020 Animal Observation 124594 General observation, No Abnormality Detected Sacrificed by design 124596 General observation, No Abnormality Detected Sacrificed by design 124597 General observation, No Abnormality Detected Sacrificed by design 124598 General observation, No Abnormality Detected Sacrificed by design 124641 General observation, No Abnormality Detected Sacrificed by design Company Sanitized. Does not contain tsoa m i 54 of Mice Fed Diet Containing H-24020 DuPont-5206 Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_________ ___________________________________________ individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24020 Female, XII 100 ppm H-24020 Animal 124599 124600 124601 124602 124603 Observation General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation. No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design General observation, No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Female, XIV 300 ppm H-24020 Animal Observation 124604 General observation. No Abnormality Detected Misshapen Observations, Tail Sacrificed by design 124605 General observation. No Abnormality Detected Sacrificed by design 124606 General observation, No Abnormality Detected Sacrificed by design 124607 General observation, No Abnormality Detected Sacrificed by design 124608 General observation, No Abnormality Detected Sacrificed by design Days 0-7 14 14 0-14 14 0-14 14 0-14 14 0-14 14 DuPont-5206 Company Sanitized. Does not contain TSCA C2E 55 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24648 Male, XV 1 ppm H-24648 Animal Observation . Days 124538 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124539 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124540 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124541 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124542 General observation. No Abnormality Detected Sacrificed by design 0-14 14 # DuPont-5206 Male, XVII 3 ppm H-24648 Animal Observation 124543 General observation. No Abnormality Detected Sacrificed by design 124544 General observation, NO Abnormality Detected Sacrificed by design 124545 General observation, NO Abnormality Detected Sacrificed by design 124546 General observation, No Abnormality Detected Sacrificed by design 124547 General observation, No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Company Sanitized. Does not contain >otiono 56 % H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________ Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24648 Male, XIX 10 ppm H-24648 Animal Observation Days 124548 General observation, No Abnormality Detected . Sacrificed by design 0-14 14 124549 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124550 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124552 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124569 General observation. No Abnormality Detected Sacrificed by design 0-14 14 Male, XXI 30 ppm H-24648 Animal Observation 124553 General observation, No Abnormality Detected Sacrificed by design 124554 General observation, No Abnormality Detected Sacrificed by design 124555 General observation. NO Abnormality Detected Sacrificed by design 124556 General observation, No Abnormality Detected Sacrificed by design 124557 General observation. No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 DuPont-5206 Company Sanitized. Does not contain TSCA CBI 57 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice__________________ Individual Clinical Observations and Mortality Male, XXIII 100 ppm H-2468 Animal Observation 124558 General observation, No Abnormality Detected Sacrificed by design 124559 General observation, No Abnormality Detected Sacrificed by design 124560 General observation, No Abnormality Detected Sacrificed by design 124561 General observation, No Abnormality Detected Sacrificed by design 124562 General observation. No Abnormality Detected Sacrificed by design Male, XXV 300 ppm H-24648 Animal Observation 124563 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Left Sacrificed by design 124564 General observation, No Abnormality Detected Sacrificed by design 124566 General observation, No Abnormality Detected Sacrificed by design 124567 General observation, No Abnormality Detected Sacrificed by design 124570 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Sacrificed by design Company Sanitized. Does not contain TSCA CBI 58 of Mice Fed Diet Containing H-24648 <# DuPont-5206 Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Days 0 7-14 14 0-14 14 0-14 14 0-14 14 0 7-14 14 % H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality- Female, XVI 1 ppm H-24648 Animal Observation . 124609 General observation, No Abnormality Detected Sacrificed by design 124610 General observation. No Abnormality Detected Sacrificed by design 124611 General observation, No Abnormality Detected Sacrificed by design 124612 General observation, No Abnormality Detected Sacrificed by design 124613 General observation. No Abnormality Detected Sacrificed by design Female, XVIII 3 ppm H-24648 Animal Observation 124614 General observation. No Abnormality Detected Sacrificed by design 124615 General observation, No Abnormality Detected Sacrificed by design 124616 General observation, No Abnormality Detected Sacrificed by design 124617 General observation, No Abnormality Detected Sacrificed by design 124618 General observation. No Abnormality Detected Sacrificed by design Company Sanitized. Does not contain TSCA C 59 of Mice Fed Diet Containing H-24648 # DuPont-5206 Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 Company Sanitized. Does not contain TSCA CBf % H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24648 Female, XX 10 ppm H-24648 Animal 124619 Observation General observation, No Abnorma1ity Detected Sacrificed by design Days 0-14 14 124620 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124621 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124622 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124623 General observation, No Abnormality D etected Sacrificed by design 0-14 14 Female, XXII 30 ppm H-24648 Animal Observation 124624 General observation, No Abnormality Detected Sacrificed by design 124625 General observation. No Abnormality Detected Sacrificed by design 124626 General observation, No Abnormality Detected Sacrificed by design 124627 General observation, No Abnormality Detected Sacrificed by design 124628 General observation, No Abnormality Detected Sacrificed by design Days 0-14 14 0-14 14 0-14 14 0-14 14 0-14 14 DuPont-5206 60 i Company Sanitized. Does not contain TSCA CBI H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice Individual Clinical Observations and Mortality of Mice Fed Diet Containing H-24648 Female, XXIV 100 ppm H-24648 Animal Observation Days 124609 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124610 General observation. No Abnormality Detected Sacrificed by design 0-14 14 124611 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124612 General observation, No Abnormality Detected Sacrificed by design 0-14 14 124613 General observation. No Abnormality Detected Sacrificed by design 0-14 14 DuPont-5206 male, XXVI 300 ppm H-24648 124634 General observation, No Abnormality Detected Sacrificed by design 124635 General observation, No Abnormality Detected Sacrificed by design 124636 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Sacrificed by design 124637 General observation, No Abnormality Detected Sacrificed by design 124638 General observation, No Abnormality Detected Sacrificed by design 0-14 14 0-14 14 0 7-14 14 0-14 14 0-14 14 61 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 APPENDIX D INDIVIDUAL FINAL BODY AND LIVER WEIGHTS Company Sanitized. Does not contain TSCA CBI 62 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 INDIVIDUAL FINAL BODY (FBW) AND LIVER WEIGHTS OF CONTROL MICE Group : I 0 ppm Control Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124503 124504 124505 124506 124507 35.30 30.70 30.40 34.50 30.60 2.044 5.7904 1.501 4.8893 1.753 5.7664 1.695 4.9130 1.608 5.2549 Group : II 0 ppm Control Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124574 124575 124576 124577 124578 26.10 26.10 27.80 26.40 27.50 1.294 4.9579 1.487 5.6973 1.375 4.9460 1.674 6.3409 1.385 5.0364 Company Sanitized. Does not contain TSCA CBI 63 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice________ DuPont-5206 Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24020 Group : III 1 ppm H-24020 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124508 124509 124510 124511 124512 34.70 31.40 30.20 34.80 32.80 2.097 6.0432 2.076 6.6115 1.827 6.0497 2.018 5.7989 2.088 6.3659 Group : V 3 ppm H--24020 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124513 124514 124515 124516 124517 32.70 32.00 28.00 32.40 37.40 2.244 6.8624 2.206 6.8938 1.975 7.0536 2.248 6.9383 2.432 6.5027 Group : VII 10 ppm H-24020 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124518 124519 124520 124521 124522 33.10 29.50 31.90 33.40 36.10 2.947 8.9033 2.344 7.9458 2.722 8.5329 2.934 8.7844 3.009 8.3352 Group : IX 30 ppm H-24020 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124523 124524 124525 124526 124527 34.40 33.50 32.30 31.30 33.40 4.175 12.137 3.676 10.973 4.195 12.988 4.095 13.083 3.922 11.743 ' Company Sanitized. Does not contain TSCA C8I 64 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Final Body (FBW) and Liver Weights of Mice Fed.Diet Containing H-24020 Group : XI 100 ppm H-24020 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124528 124529 124530 124531 124532 27.20 26.90 29.00 25.60 26.20 4.866 17.890 4.672 17.368 5.392 18.593 4.121 16.098 4.572 17.450 Group : XIII 300 ppm H-24020 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124533 124534 124535 124536 124537 23.80 21.50 23.10 24.20 23.80 3.887 16.332 3.839 17.856 4.239 18.351 4.028 16.645 3.741 15.718 Company Sanitized. Does not contain TSCA C~ 65 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice_____________________ DuPont-5206 Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24020 Group : IV 1 ppm H-24020 Sex : FEMALES ANIMAL 124579 124580 124582 124583 124640 FBW (Gms) _a 25.80 25.40 25.80 25.90 LIVER (Gms) %FBW 1.449 5.6163 1.487 5.8543 1.391 5.3915 1.473 5.6873 Group : VI 3 ppm H-24020 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124584 124585 124586 124587 124588 26.80 24.70 24.20 25.10 25.80 1.654 6.1716 1.611 6.5223 1.519 6.2769 1.496 5.9602 1.512 5.8605 Group : VIII 10 ppm H-24020 Sex : FEMALES | ANIMAL 1 124589 124590 124591 124592 124593 FBW LIVER (Gms) (Gms) %FBW 23.70 27.00 25.30 28.40 28.30 2.013 8.4937 2.314 8.5704 2.102 8.3083 1.881 6.6232 2.285 8.0742 Group : X 30 ppm H-24020 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124594 124596 124597 124598 124641 26.00 25.40 26.90 26.40 27.80 2.906 11.177 2.789 10.980 3.141 11.677 2.834 10.735 3.094 11.129 aMouse was found dead on test day 1. Company Sanitized. Does not contain TSCA C2 66 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24020 Group : XII 100 ppm H-24020 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124599 124600 124601 124602 124603 22.40 28.20 24.40 27.00 28.60 3.610 16.116 3.872 13.730 3.123 12.799 3.374 12.496 4.358 15.238 Group : XIV 300 ppm H-24020 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124604 124605 124606 124607 124608 20.20 21.20 22.20 20.40 21.10 3.753 18.579 3.604 17.000 3.998 18.009 3.443 16.877 3.025 14.336 Company SaniHzad. Ooas nol conlaln TSCA C8I 67 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24648 Group : XV 1 ppm H-24648 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124538 124539 124540 124541 124542 34.90 35.20 32.00 36.10 32.40 2.312 6.6246 2.396 6.8068 2.123 6.6344 2.285 6.3296 2.165 6.6821 Group : XVII 3 ppm H-24648 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124543 124544 124545 124546 124547 32.80 31.40 35.60 35.70 33.70 2.299 7.0091 2.453 7.8121 2.669 7.4972 3.055 8.5574 2.329 6.9110 Group : XIX 10 ppm H-24648 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124548 124549 124550 124552 124569 34.70 31.50 31.80 33.50 29.40 3.387 9.7608 2.629 8.3460 3.014 9.4780 3.077 9.1851 2.714 9.2313 Group : XXI 30 ppm H-24648 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124553 124554 124555 124556 124557 32.50 29.20 25.90 32.30 30.00 3.988 12.271 4.117 14.099 3.481 13.440 4.696 14.539 4.222 14.073 ' Company Sanitized. Does not contain TSCA CBI 68 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24648 Group : XXIII 100 ppm H-24648 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124558 124559 124560 124561 124562 26.60 24.30 27.30 26.80 26.00 5.084 19.113 4.806 19.778 5.075 18.590 4.214 15.724 _a _ Group : XXV 300 ppm H-24648 Sex : MALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124563 124564 124566 124567 124570 22.90 23.90 23.30 22.70 20.60 3.736 16.314 3.313 13.862 3.538 15.185 4.225 18.612 3.530 17.136 9 Due to error, the liver was not weighed. Company Sanitized- Does not contain TSCA CBi 69 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Final Body (FBW) and Liver Weights of Mice Fed. Diet Containing H-24648 Group : XVI 1 ppm H-24648 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124609 124610 124611 124612 124613 24.30 27.40 24.10 24.50 27.50 1.480 6.0905 1.611 5.8796 1.547 6.4191 1.429 5.8327 1.580 5.7455 Group : XVIII 3 ppm H-24648 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124614 124615 124616 124617 124618 27.70 24.90 26.10 25.50 27.60 1.742 6.2888 1.605 6.4458 1.828 7.0038 1.644 6.4471 2.091 7.5761 Group : XX 10 ppm H-24648 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124619 124620 124621 124622 124623 24.10 26.20 24.60 24.60 30.40 2.095 8.6929 2.449 9.3473 2.196 8.9268 2.232 9.0732 2.942 9.6776 Mean S.D. 25.98 2.59 2.383 9.1436 0.338 0.3814 Group : XXII 30 ppm H-24648 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124624 124625 124626 124627 124628 24.90 26.60 26.30 26.70 27.90 2.857 11.474 3.248 12.211 3.050 11.597 3.325 12.453 3.264 11.699 ' Company Sanitized. Does no confaH TSCA CSf 70 H-24648 and H-24020: Repeated-Dose Oral Toxicity 14-Day Feeding Study in Mice DuPont-5206 Individual Final Body (FBW) and Liver Weights of Mice Fed Diet Containing H-24648 Group : XXIV 100 ppm H-24648 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124629 124630 124632 124633 124639 21.80 24.40 22.10 24.30 26.30 3.307 15.170 3.299 13.520 3.421 15.480 4.185 17.222 4.360 16.578 Group : XXVI 300 ppm H-24648 Sex : FEMALES ANIMAL FBW LIVER (Gms) (Gms) %FBW 124634 124635 124636 124637 124638 21.20 20.20 19.20 19.60 22.20 4.741 22.363 4.019 19.896 3.246 16.906 3.588 18.306 4.258 19.180 Company Sanitized. Does not contain TSCA CB1 71
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CUNY - The Graduate CenterColumbia University Mailman School of Public Health - Sociomedical Sciences