Document MJaYxqbnbzXVnqKkK2X1wGm9j

HARARE - RAY. 406 MR226 _ 3224 -_ oDwuepwow94n17 TRADE SECRET Study Tide H-25134: Oral Approximate Lethal Dose (ALD) in Rats Laboratory Project ID: DuPont-9417 AUTHOR: Carol Finlay, BA STUDY COMPLETED ON: January 21, 2002 PERFORMING LABORATORY: E.L du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 ATSCACBL compte 9% cone! ww 121235113344:OOnrall AApppprrooxxiimmaattee LLeethaallDDoossee (ALDDJ)iinnRRaatss_ DDuurroomnotu94r1s7 CERTIFICATION We, the undersigned, declare that this report providesan accurate evaluation ofthe data obtained from this study. sentra, 5F1es k2Pa BS Associ Seems 21-Jaan-2002 Issued by Study Director: SulFSciiiemni3s4 f Uez aa400 a0 pain TSCACE! CompSao n Dees net ees ~m-------- F218 Ort AproLesthiDonsesALsD)nas Domo - STUDY INFORMATION nonceEY| . 1-25134 1 submiters Nobook Numb) [RNR) HaskellNumber: 25134 cas Regine umber[EID u(ri YN) oo LO) Physical Charctersies: Dark brown solid PEE Sponsor: EG.iImdiungPloonn,dtDeelNawe arem1a9o 8n9d8u Comr pas ny US.A. Study Initiated/Completed: November 28, 2001 / (see report cover page) In-Life Inited/Completed: December 7, 2001 / January 18, 2002 . SoncEl compan santized-poss sotoTM - nn = n LI25134:OOrnalAApppprroovxiimmaatteeLLeetthhaallDDoossee((ALLDDJ)iinnRRaatss STUDY PERSONNEL Study Director: Carol Finlay, B.A. Management: Judith C. Stadler, Ph.D., D.A.B.T. Primary Technician: Erica K. Pia, B.S. `Toxicology Report Preparation: Lisa G. Burchfield, A.A. Laboratory Veterinarian: William Singleton, D.V.M., A.C.LAM. DuDurpeonmt9417 Compe!sanniond-> gin TSCAa --_---------- --H=-251r34:oOrmaltAppporuoxmiamaetleeLehthaall DDoosee (MAULDDJ)iinaRRaatss_ bDuupPoonwts94d1n7y SUMMARY o6Fb7-0s2,e5r21v33e0d40,fwoa3rs4m0ao0dr,tmai5ln0ii0ts0yt,ear7ne5dd0c0al,sinaaincsadiln1gs1li,eg0no0sr0aolmfgdt/ooksxgiec.ibtyFyoiolnvtlroeawgarians1tgr4id-codsaiiynntgou,bbsatethireovnaatttisoonwmaeplreereirowadet.isgahteddosaensdof 3wNe0oi0g0dhemtagtoh/cskcguorcercxeuhdrirbbeiydtetddhuerdiidnaargyrtahhefeatestthudedoyds.ianyBgaofidtneytrhwdeeoirsaigtnhgtd.olsoBesrdsowoatnf.a3-p4sp0tra0oixmnigemd/akftgae.cle,yTph2ee%roirafntiedunmoi,steaadlndabtopderyianal wweeirgehotblsoesrsovefd auppprtoo3ximdaatyeslyaf7t%rodfoisniintgiailntwheeigrhatt dboysethdeadta7y5a0f0temrgd/oksgi.ng.ThTisheatraatldsoosheaddabt ody w1e1i,g0h0t0 lmogs/sokfg eaxphpirboixtiemdadtiealryrh8e%a aonfdinbirtoawlnw-esitgahitnetdhepedraiynaefutmerudpostiong2.days after dosing and body 5b`0oU0dn0ydewmegtih/gekhgct)o.nwdTihhteiinsonsasudobmfsittnhainiscsteesrtiesuddcyao,snstaihsedienorgrealdletAoorLablDefdvooesrreyHt-loo2mw5a1li3ne4trowaxtaiscsitgyre(atAeLrDthgarnea1t1er,0t0h0anmg/kg of -Y CompanySantzed.Dossnotcontain TSCACBI 125134: Oral Approximate Lethal Dose (ALD) in Rats DuPont9417 INTRODUCTION aaTddhmmeiinnpiiussrttpeeorrseeeddoawfshtihacisshintcgeasluteswoeardasldetdoaotsdheetttehormemairlnoeenarantthsae.pdpTarhyooexfiAmdaLotDseilwnegatshoadrlewfdiiotnsheeidn(aA1s4LtDh)e olfowHe-s2t5d1o3s4ewhen days post exposure. MATERIALS AND METHODS A. Test Substance ssTuuhbceshttaaessntcasecuabhspatnpagenecaiern,tceHood-l2ob5er13sotr4a,pbhlweyasusincdsaleuprspttlahiteee,dcwobnaydsitthoiebossnepsrovoneftds.ohreasstauddya.rkNboreovwindesnolcied.ofTihnsetatbeisltity, B. Animal Husbandry cNMaoagrletehbCoCeaarCrdosDl.i(nSaE.aDc)RhaItrGastSwweaBrsReahrsoastuissgenwededrseainrugenlcyieqiiunveesdtiadfiernnolteimsfsCichsaatterielolen,snwRiuirmvebe-ermreLswahbhoicrcaahtgoewrsaiesssu,rsepIcenoncrd.deRdalaebiogvhe, _ 3afdfiigxietdsotfo tthheecaangei.malThneumrbaetsr.wePreMItaNiult-rmiatrikoend,Inutserinnaatgiownaatle,r-Inicn.soCleurtbilfeimedarRkoedre,nwtitLhabteDhdieeo1tansta50ca0r2d and water were availableadlibitun. AtfhosolslseopewtcihinaftgipwerdoouiclnedtdhubereeHesaxsapkreeecltpleedLraftbooorrimametpdoarpcyetraitnohideimscacalilelhnyetaitlfoitcheniasnnutdergeeritnthvyaoitfroctnohmneetnastmtaiulndsam:notniltevoerlisnagrperboeglroawm, the + Water samples are analyzed and other contaminants. for total bacterial counts, and the presenceof coliforms, lead, + Feed samples are analyzedfor total bacterial, spore, and fungal counts. bSyamtphleecsagferwoamshferress.hly washed cages and cage racks are analyzed to ensure adequate sanitation rsCpeeerqctuiiiffriieeemddeahnnetiasmvaaynldmefnteoaetldsoi,s auefsxlecadte,oexdgiunsa,tracathneltdoermeiadnaxbtiyemdtuhhemydmcraoonncucaferanbctotrnuasrt,eioranntsdoomfoerkgeeatnyoscppoehcnoitsfapihmeaidtnneausnt.rii,tTiihonencalluding pwroeusledncneootfbetheexspeeccotnetdatmoiniamnptasctbethleowinttheegrmitayoxfitmhuemsctoundyc.enration stated by the manufacturer Company Sanhized. Dossnotcontain TSCA CBI -Y HE:251e34; oOrnalliApopprooxiimmasteelLeetbhailDDoossee(MADLD))nRinaRttss DDuuppoonm9sa1a7y - lTahbeoraatnoirymanheiamlatlh vaentderiennavriiraon.nmeEnvtaalluamtoinoinotfortihnegsperdoagtraadmidisnaodtmiinndiisctaetreeadnbyyctohnediattitoennsditnhgat affected the validityofthe study `Rmaatisntwaeirneedquoanraanttiimneerd-,cownetirgohlelded,,a1n2d-ohbosuerrlviegdhtf/o1r2g-ehnoeurradlarhekaclytchlef.orE6ndvaiyrs.onmAennitmaallcornodoimtisownesroef atEdhxveceurrrossoeilmoysnsawfofeeurctetsittdaheregtvehatelesidedifrtoayanrogftetshemewpeesrrteauotdyuf.rseomfal2l3ma+gn1itCudaendanrdel/aotrbivreiheufmdiudriattyioonfa5n0d+di1d0n%o.t C. Protocol lTihqeuecfioendt.aiTnehreoftetsetsstusbusbtsatnacnecweawsasthheenastteidrreidn.aT6h5eCtewsattseurbsbtaatnhcuentwialsthseustepsetnsduebdstiannccoerwnaosfl and caadlmciunliastteedrebdasteod1ornatthpeersudsopseenrsaitoenbcyonicnetnratgraasttiroicn ainntdubbatoidoyn.weTihghetsvocloullmeecsteaddmoinntihsetedraeydowfere pdaoopsspitrneogxx.piomsDauotreseleysda5ay0d%m1.i4niwAsadtdseirtteeidsotnradalanlygye,1d5|.frraFotomwlla2os3w0di0onsgtoeadd1m1ait,n06i07s00trmmaggt/i/koknggo.fotfThbheoedtydeoswtseisinuggbhdsttaaiynnwciean,scrratetemssetwndetarsyeof|; observed for clinical signsof toxicity. ~~ o3Tfhiiemllernaestsssa,wweienrjeeukrwyet,ihorgrohuaegbdhnoaounrtdmtaohlbesbe1er4hv-aedvdaiyodraoibwlseyerruevntamitlaidosniegpndesaroiilfoydt.tohxriOcobiustgeyhrovsuauttbistoihndesedsft,oudraynm.dorttPhaaeltnihtoaytloalgneyadstsigns `examinationsoftest animals were not performed. -YY `CompanySanized.Dorotecontsain TSCA CBI ot 0pp RESULTS AND DISCUSSION A. Dosing and Mortality Data No deaths occurred during the study. The dose regimen is detailed below. --_ Coo[it ansa ove] Volume Concentration| Initial Body g/kg (mL) (mg/mL) Weight (g Mortalit Coo a0 30 [vo] er errab * Administered in 3 portions approximately 15 minutes apart, B. Clinical Signs and Body Weights Body weight the rat dosed lossof approximately 2%ofinital body weight occurred by the at 3400 mg/kg. Theratdosed at 5000 mg/kg exhibited diarrhea day after dosing the day after in dosing. Brown-stained face, perineum, and perianal were observed up to 3 days after dosing in the rat weight dboysethdeadta7y5a0f0temrgd/oksgi.ng.ThiTsherartaatldsoosheaddabt o1d1y,0`0w0eimghgt/lkogsseoxfhiabpitperdoxdiimaartrheelay a7n%d obfroiwnint.ial stained perineum up to 2 days after dosing and body weight lossofapproximately 8% of initial weight the day after dosing. CONCLUSIONS bUonddyerwetihgehcto.ndTihtiisonssuobfstthainscestisudcyo,nstihedeorreadl ALD to be vfeorryH-lo2w51i3n4towxaiscitgyre(atAeLrDthgarnea1t1er,0t0h0anmg/kg of 5000 mg/kg) when administered as asingle oral dose to male rats. CompanySaniirod. DowsnotcontainTSCA Ca 325134: Oral Approsimate Lethal Dose (ALD) in Rats. DuPon9417 RECORDS AND SAMPLE STORAGE kNSenpweoacwrinkm,easnDstehlGeafawE.paIpr.leid,cuaobrPloaent)t,IrdaoenwNMeodmauotnaut,raasinndanRtdehceCoofridmnsaplaMrnaenypaoRrgteecmwoierlnldtsb,eMWarienltamagiinenemgdteoantnt,HCaDesenktleealrlw.a)Lraebo(rfaotromreyr,ly -YY `Company Samtzed. Domotscontsain TSCA CBI