Document nk52Y3rOdyL6d5kQdKpYeqdjG

AR QAG _ 0653 PFOS Pharmacokinetic - 2 000169 _ . Ce _ 4980 28 Day Percutaneous Absorption Study wien Fc-98 in Albino Rabbits cec'd Maw tq 151 IM Foxe Lig Experiment No: conducted Ac: Dates Conducted: Conducted By: 097980630 SRiakfeertyLaEbvoarlautaotriioens,LabIoncr.atory St. Paul, Minnesota October 25, 1979 to December 17, 1979 O & x e Sule ASdtvuadnyceDdirTeocxtiocrologist Reviewed m7: HL mr, Y 3 h KSipLervibseonr,s,Acu8te ToxicoloDgatye act Xm.T1.. Ecoabseens WFlCo.. MGcrCioeremiiecnk 000170 -- 1 A 26 day percutaneous absorption study with FC-98 was conducted rom October 25, 1979 to December 17, 1979 at Rikes Laboratories, Inc., St. Paul, Minnesota using male and female albino rabbits ranging in body weights from 1.88 to 2.30 ky. The test article vas adninistered by dermal application to ten male and ten female rabbits each a dosage level of 5,000 me/kg body weight for a 24 hour exposure period? No mortalities, untoward behavorial reactions or body weight losses ware noted during the 28 day study. Necropsies ware performed on all animals upon termination of the study with no visible lesions noted. Preliminary serum analysis (see Appendix V) indicates dermal abtorption of FC-98 in albino rabbits, however, due to the limited number of samples analyzed, no concrete conclusion may be drawn. Introduction The objective of this study? was to determine the percutaneous absorption potential of 7C-98 in male and female albino rabbits. The study, which was initiated at Riker Laboratories, Inc., St. Paul, Minnesota on October 25, 1979 and completed on December 17, 1979, was not conducted to Support & government submission or marketing permit and is therefore not regulated by the Good Laboratory Practice Regulation of 1978. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. b23RdiokspearrgeelTiolmxeiivnceailreyytorEaxbnpegeerfuiismneeddnetrinNsott.hu:idsy0w3sa7ts9uAdByc.OoGn3d0u,ctTeedsttoMedtehtoedrmi6n3e9 the appropriate 000171 2. [ey Young adult albino rabbits of the New Zealand breed were used in this Gent. ALL animals wero hold under uacantine for soveral days prior to testing With only animals which appeared to be in good health and suitable as test animals at he initiation of the study used. The rabbits were housed individually in stainless steel, wire-bottonod cages and maintainad on a standard tuboeutory cation" with food and water available ad libitum, Mn initial rongefinding study was conducted using two male and two female rabbits for cach dosage Level. he trunk of each animal was clipped free of seis dni bie Lest arcicic placed on the surface of the intact skin which covered approximately 40% total body surface ares. After administration of the tose article, a flexible plastic collar was fitted on each animal and tho Grunk wrapped with impervious plastic sheeting which will occlude the tose article. The animals were retumed to their cages for a 24 hour period after which time the tost article was removed from the dermal surface of the animals. The animals were observed for pharmacotoxic reactions both during the exposure period (immediately post dose administration, one and two hours) and after somoval of the test article (daily for 14 days following dose administration) with all reactions recorded (fable 3). Initial and final body weights wore also recorded (Table 1). "he information derived from the initial rangefinder was used in determining the dosage level for the 28 day percutansous study. Preparation f 10 male and 10 female animals for dosing and application of the test article were conducted in the sane manner as the rangefinder study with the exception of the collection of blood samples from the orbital sinus plexus prior wo application and again-on days 1, 7, 14 and 28 after initiation of the study for serun which was frozen for sponsor analysis. After the 24 hour exposure vpouleinParockza,bbiItnc.C,howR,ogelrasl,stAoRn Purina, St. Louis, HO 000172 . 5 : period the cost and tho aninals article was secured co removed from the dermal surface of the their cages for the following 26 daye. animals Inteial, 7. 18 oxic and 20 doy body weighes were recorded (Isle 2) oe were sins notad during the 26 dey obssrvatian period (Sable any 41. hess A gross necropsy as conductod on all anisals sacrificed on day 38 and a Eininge focordod (fable 2). ho protocol, principal persensel involved in the sty, conposition characteristics, and Quality Assurance statement are contained in Appantioss = 2v. 000173 ACUTE DERMAL RANGEFINDER TOXICITY STUDY ALBINO RABBITS Mortality awnidenBordoysWeeishe Daca e TO: r bose anu IvdunBoldyMOINS 05) umber pes percent (v mg/kg) TNumbeFr w pentpepMaer ) THumhber eTesteed eDeead soe wPPIo oosamkens a4inm ib5r Poms 5 pe IZ o 00 nNPooommmsee adaaam iw3ss Pos 3B iE ora 0 nest article was dosed as a suspension in vases . 000174 : TABLE 2 5. ACUTE PERCUTANYOUS ARSORFTION TORICITY STUDY - ALBINO RABGIZS Mortality with ros and Body Weight Data resents Daosred ex Naunmbierma IndividualTestBOondyweigNevehr s (_x9) --eeeeeess-- Ncuinmeoserbgeeasdd pPeercrcent F --_-- er E a 3 T NumberTested Dmeae 500 WWno ooooossweoonwss 2203s0 Zia z2s5 as az24sa7. 2ae.ms or10 `0 wWoaosemses 221as wo smioas ii ziios ise aarmap aaBme3 WWWoo oosmoosowmseosse dal>a 230 2z2z 2s ssme ss sSaoee aa Wo smos 2a as sas ao sorPsseaem Po owwn 223ss dis 2z.o0o0 Le n2a5 se asees a 10 10 PPToooosowmonan z1iessae 1i17sm2 iaee3ss daem am ePPo oowsmseuaaras aaaaonar szzaeus snans roe aaaee Posen ies isd ae aw 22 GAraneyismta7labrltsieacsclsreiinfwgiacsepderdioonosdeddayas 14a dsuuespetnosiaocncidienntwaaltebrack injury inflicted during the NseVcirsoiobpnlseiyeslepseiornfso.rmedAniomnalall982a5n2i5mahlsicuhponwastesramcirniaftiiconedoofnthdeaystLtuduy ereveenamleecdtoncoior paralysis, aise reveaied no visible lesions. 000175 ACUTE DERAAL RNGEFINOER TOXICITY STUDY - ALBINO RABDITS won re-an Simary of reactions T @boarfen) sex resc_ eion thTehseesratGotieecdtT 'an rFaontilnoiienvgiatbioesne e AdFooilnloiwsw itngatbioosen eFToilcieero--tfzg--suab--tesne-- 900MPonNoresasciitgminoiinftsiicnaonontted -- -- . ---- ---- 1000 MPo owKeoreassciitgminioitnfsiiccnamonttted -- see -- -- -- -- 2282 3 % . ------ i ]| ms amma cnasse - se mane || ywoareesin nIse en a EEG GG oi r REDEao--e i aT . ye faker apes No. OU HHSO y . oS SPONSrORm : 3eM TemSeemreecBsiAedTe (heEsmiaedr rrr tree vDiisviisoionn _-- ET el ee neeoye ,amEme Ea CLICTIUEL The objective of thi scat wits be co dasarmine vee pereomemenns smvororie SoEFnO1ha100nzohomhoseuwirt1heSfSaaonaogdpear?nd wSEaaetleeeresoofffofreeSsresp.te2a08TdnLSiienbbthsenrPd,eamerrSOeoUsPrtunotLOALwtIiLYicon STS TEL RE CDi imvi bectioped tres of had ScoolrltaerhweiollLTehehlfeiietrteSad osan ncoacrhean2iBmaalmnandSmmtomhmempecaerracnekbiewlcreah;pTpheeadtiweirTtihisidmpeeurnlveyious rSeerala s RELIaErSe,y FfneTrneime tmnedh wRiihebenofrrlaonne fTor T penton" FSSFRFoeiIrlEnotoTtinereSTB rEstTSeoSneT TSS SaTcSr) oIT(eteS TrIInaimLeiielrPbeempaHcmeiaedinsttianSnddnedo7ybdliohene3eod4mse,ssoLeeninevntddee2hrf,8sopdlareyamelbnieaon,lalwsbdreeer RA cho Brurr ina my abbiceChow,rRalston Piurninag, tst.oLnous, HitsisoeurtSTIR S , lfe oe2 vavhg ly wA o OF 000s. } M =4 Sst COPY Avaric . 000178 La AaPrPmTaTa+n(conbt vimmon vo. 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SSPPESONTASOTRh:Se3tBMTbuLSgg3Sa1Ed1oBxicopiertapyciioanngLuitibyearia:ntgors;tayH,ore TabeTeReTTo Esra 5 Diva CTEoSTOALRTIMCLCE:L ~ TEST S:YSTEM AND SOUNCE: PNeolw-beraoluasn,aIwnhci.teRoAgTeErAs,R Aeraksanesles mensetid Body Wilh Range: 2. 4 CIHCHAVES aTSSnhyhdeteetgsmhebniesferoesareltivcaaehvreatsoisiflcalstseehiniissiiinttsyita.vluibdtiyyngwoiflclazbabbsiupvoutn.osea,kpapbhroiorsxttieomraieteersstthsseaotapecmsuiteeedadtoereomtler,EstooEniiec PLTGSSnoan.sd'rotmonixilolylneeedhdo.ruosaoesdmnesuimsibwnoeikrtusehdtdafnCeodoaacmxrkdoaav3niL.dzaesa-yneteresrhcooclfaofgneeyrsebdyinahaseeamTlptiehrreamonednrnw.eimgohot,ueminitdtilt be (c5o03o5%gs,,2a0s2SeauseraauoiadxEslSIloTyf )C9tRhaerSIic5aeigrTece.lr"EsticpThlPoa.0cer0du)UnohknnicaothfhreUar1ic)arhrtsaaoceries,meoOssFfpSehSvnehitetl)etnnboeaacdcCeoohscoahsgpeeSeenrfilLimee7avdLe0lts0wio"l TfFyrionuoanSSeaehpdseEstSAi}orhnteainicbaleeed,oawsd|iamlAgilfenibsletoevaredelmdsitwnhtiihelaeltoeLxrboisesadtidsotacyorutmitoehcfenlteshaeanda.itmaeanslgses.e.ppiitstaeresessronnmewiionioalnteeolecrssiL,tl,cLPioivoOoervLdaell rCLLhhreaapsrgsraSiynpehiioa TucoSsoonlSupl,mlanareSs'stEiwctCio1lsGthhtebeeeeirtricanldcgeamcsiweenhdsiiscCnfth'orriaatuiaicdohn2S4acnoehfitomuuatdslhae'eanxttgpne.eessttenreres:ssetnhpierauerrssir,yrvoSecPaTiPclEeeesEiMLetbhlYe VL{TrBoEaiutetIireoTnpsfaTol"onsliiaohldSi1ao(LFimnbmeeedoibtaestwseeitlrlyveardoBtouitctoTlreod'mbMouhv(saeBrdasmialafymcrioontfmiooaxrttihrs1oa4tdrideeoascnyeesstsLooSnmsgoeh.ermhpoeesacsneasSoerrriaCsrledsr iWuh"i]ch 10 2IS0itItlhoaetlReiaoukiebLrel bLreaebc1oaorrpdapretredooa.xrciitmeiasMotneeAsdr.cabhceiuiv"tneAegsl,mrTeeSadceuoi.raddneaPdcal.saett.ahnaImdlnnitdtehoiesssrretiFiarfrnrmaasseSrvhaeanntdteSmoeedrcsteoarlcaemilnoi,s0 2 gmPeuesrtiincoaonllRoaafrbbwiritelsticdhuobawel, worRreansltstfsooxrntitPnhuserei.ndau,ratSit.on looufist,re Misseussosuriso reduce'oral in- =ay E Fedy Sides Ze, BEST COPY AVAILABLE 2 Yess. " 000179 ": Rake nent No. : AAPmPeEnNdDmIeXntI to(.Copnrcoltuodceodl) * Experiment No Ain? ~S8T2Ae0 Ld enel0BeY, ; 2.00 10. Frocy Gund Lal ve cand ate sone ghmdor L Studyt ixectord its 2. Mey Uae bn 6ne 10 TE man TR dn doped, Dion TPEEPS. WAY Aolrke slit dude smn Cone DSo eudyBDoirredctlour nJ -- gondbin_ nual lnduo T5Dat7e 9 bod we Aly olan wQl Neo (00) we iad jo gun of aearl T ). DN Oman (pa) ot vty gy we do asia 0" Gude Cadud 1%-30 iq Ado E -- 5. ws nn oe i sat pesT easo2 m DaoireAcipemnp5Date conven oanhligun ll rm chmgPibuom dat 1h oufrydod) Go J . teen 5 [ StudP yDirm ectoWte L77y 7Sgats : ee a. _-- -_-- --_-- 5. _-- TTT ame --------ww -_-- -- 3EST COPYAvia 000150 .. . , APPENDIX IT Principe) raxticipating Personne) Involved in the scuay i. e MNaOme [---- eswucnctttieonn Supervisor, Acute Toxicology .o. o'malley, bs 0K.oV. PothLaepyragada 6. c. recor MdvancedToxicologist StCuomdmyerPciiraalszChsesmoilceasls Chemise ASnuipmearlviLsaobroratory VVoLEL AepENDIX 111 +. Composition Characteristics This study is not regulated by the Good Laboratory Practice Regulation of 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study. 00018< APPENDIX TV. Quality Assurance Statement Co. This study is not regulated by the Good Laboratory Practice Regulation of 1978 and therefore a statement signed and prepared by the Quality Assurance gEOuP is not applicable. This study was, however, audited by the Quality Assurance grou. In addition to the data audit, different significant phases for studies undesuay in the Toxicology Laboratory are inspected weekly on a recurring cycle, ana che facilities are examined by Laboratory Quality Assurance on a three month schedule. 000183 con . Fooab e ubei r eLagm, ' 1a. Aver 5 Ko 1M. be Co BBUENS - RIKER SAFETY GVALUTION LAB MCORNICK - MibICAL DEPT. - ToxiGoLoGY 203.1 sERvicES - 220 TL FJGU-N1E262I,5S,O"RFTPCoT-1mI2O9NanSdTUDFI-E0S8ON FC-145, F-95, FG-9, -2 Foi,Fe-135, 3 Umoienncteioocmnsaeogdy. ciocemipororuinetidhtsiy.s/saknin aaubtshoorrpitziaotnionstufdoirosyocuranldaubcoernatoorryltSoabroelveease PChfioooevmrseap"oimunauntsnacdefebTMaerersnftoo3rco3uodmmtphtleahoamttFpeldutoharenodcshtwauimdliilcoaslnoatarneabelb'yesittnnsgelooSgfsessutohdin'diranesaarnneispnaocmorpmlpelsete tCnSraoanrtaanyiyncodnacCotrmeseytyeSooucraohnnaclvldeunestigaaoonnnaasonlarylucsytoisensidcse'iarnanaddirirnecagastnscoeetsomsseubrfssFaiirsCpairloincsthoxtoifecciThtoysTt..0Howover, | T2h0anktThheyeiolrur cfcooirmmppylyoeoutrriootnpaCtOsilrietonuucilend inWnohtetnhhiotslhdemaurpte.tmeyaroi.unrisngLcheispneemrepseseratyonr1loSynigobreb.arnoaaldyezred Selon LZ WOMki: 000184 BEEN I . crisis tise hehe 1. arveniie (Goneiudods f CoRcLr AL umr NicaLse Drarsiion WW. C. HCCORMLCK = 220-28-02 fan V. POTHAPRAGADA AND V. BUNNELLE - 236-34 ow KIKEK SKIN ABSORPTION STUDY Gwe June 9, 1980 LEN Soyy 1g," o. 0% Eoin Sefereace: Ceomemesrcial Chemicals Divinion Aneiyeicas Kequors pForrLuick of tine, only a selected et of ser susples vas Compauna ner rIeT matBoor m 00 ApeLpymYai,ehy a FvvCo-me1i2zi9e rose 02 26.1 aw69ea.s6 1i11e.6s4 sw23es.e3 ! wu ma ms ss rroossss ro-9s 09 mzem @s wis 10 amoersa wen ge renatessim mdsees ons --_-- ber. Dayle Wawa Day 28 as bay? sa Day a6 ew ey 26 a Het 0 O57nnMaWgeon,mAntioBtiooemenCsom1"rS4f3." 1st5 o20s. Benmalle snd AB he wPh id v. vethertupits bRyead yeanwdinRtoevrio. Ht Gy BESTCOPYFAAVvAaILABLE 00485