Document DvwQQx4DbqYXD8QNoQbdK0MoM

EC T3991 18 surat. serevanaons Amerpion sma vn roses } wn wine rants ---- -- Conducted By: Ro dc: L AE e M. T. Case sBeteR vatioE n svorsson ota 3. 197 tn became 7, 197 SSeaDrnooadnde we 3 A b r e m d e 23Z 74z) 00238 Summary 1 A 28 day percutaneous absorption study with FC-128 vas conducted from Octaber 23, 1979 to December 17, 1979 at Riker Laboratories, Inc., St. Paul, Winnasota using male and female albino rabbits ranging in body weight from 1.55 t0 2.90 kg. The test article vas administered by dermal application to ten male and ten fomale rabbits a dosage level of 2,000 me/kg body weishe for a 24 hour exposure period? No mortalities or untoward behavorial xeactions were noted during the 28 day study. Body weight losses vers noted in three fomales at the end of the study. Necropsies were performed on 11 anisals upon termination of the study with no visible lesions noted. Prolininary serum analysis (See Appendix ) indicates dermal absorption of FC-128 in albino rabbits, however, dus to the linited number of samples analyzed by the sponsor, no concrete conclusion may be draun. : Introduction The objective of this study was to determine the percutaneous absorption Potential of FC-126 in male and fomale albino rabbits. The study, which vas initiated at Riker Laboratories, Tnc., St. Paul, Minnesota on October 25, 1979 and completed on Decesber 17, 1979, was not conducted to Support a 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. 2 Azistiioney susetinter sets wacsonductsd to determine the apprepiate 2 Riker Toxicity Experiment No.: 0979A80629, Test Method 699 00239 Hethos BES1 Gurt AVAILABLE 2. Co Youn9 AIL 3AUlt albino ani wor rabbits of held under the New Zasland breee ussantine for several vere days wsed in this peor to coves FUR OnLy RL SE aniaels hich appeared the initiation Gf the to bo study in Sood health and used. The rabbis suitable 2 vere housed cons ntivis LoL An stainless stood, wire-bottomed cages snd maintained on a stanurs Laboratory ration" with food i AnSeiaL xangetinding and water study ves available conducted 2d Libitun. using two male and two fomare TOPICS aL 40d fof Gach dosage devel. the the cost asticle placed on trunk of each animal was clipped res the surface of the intact skin hic op CoVORed approxinacely 40% coral boy he test article, o flexible plastic surface area. Atter collar was fitted on administration of each anima ana le fost Sunk Kapped asticle. Tho with Sapervious plastic sheating which will aninals vers xatumed to their cages for a ocelude 24 hows the period } S"rCiOsEalsW:hicThheinaenimtahles tvesetr.sacrhtiiecrlveedvasforrepmhoavcemdacfortoomxitcheredaecrtmiaolnssubroftahceduorfintghe he on exposure period afte removal of (immediately post the test article dos administration, one and (daily for 14 days following wo hous) dose admin isexation) with 11 reactions recorded weights were also recorded (sable 1). (fable 3). Inteial and finat body he information derived determining the dosage level from the initial rangefinder was used in for the 28 day parcutancous study. Preparation OF 10 male and "ese Conducted 10 in emis aninals for tho same manner as dosing and application of the test areicte the rangefinder study vith the excapeion f the collection of blood samples *PPLCAELOR 41d again on dare 1, 7, from the orbital 14 and 28 atter sinus plexus prior to initiation of the study for sesum which vas frozen for sponsor analysis. Actes the 24 hous exposure PruortinpareRca,bbinteC.howr,ogeRrasl,stownm Purina, St. outs, Ho 600240 RR IBESoTCOrPYaAVwArIiLoABOLa E ct oe nite rea 10 ha can fon he oho 5 ve smn, ecoantt w(orteco5n.ta100ons1arobtosiisvniote ironnastA1mao0n8 eSem esr mention chomentson 1 tir someon see 00241 ABLE | ACULE DERMAL KANGEFTNDER TOXICITY STUDY - ALSTNO RABBITS a wien rc-120 Hortality and sody weigh bata BEST COPY AVAILABLE ---- Dosed (nina (mg/kg) Number Individual sody weights 0) gant Dey Number yuo pie Number Tested go Dead 000mu ssmaaassees PF onzeas 220.364 2l07 1i1li1ss0se esas 2l00 Tiss 000m sosmsesrs F spacas 2.23206 1% (22a.2y5s 1157 onaez 2 2 1000 mo osmmeeors oma 22.a32 2l03 221.5179 ier Po sae 2120 iiss os a 2s oss 2 est article was dosed as a suspension in water 000242 s. NCU GAEANOUS AUSOUVTION TONICIRY. SIWDY ALBIN RABBITS wien re-120 a TT bose pauper (mg/kg) bas Numberx 000 WWwo oosoomooo WWWooooomomeooons WWWoooomomemeenonss Wooo Individual Body weights (kg) Fr TA ty 25 2zzss32 2s23ass eaassss 22al8es8s aaasoaos eaadas aaaes adamrs addoenrs ueYamss 2nz0es 2a2ea dee ie aa am -- Numberx TeTe:sted Dead oo o 2000 FPPPooo9w8no2e9sn6r9 13da.9man5 1dd3.aa7aee9 2ssz.0ase5 2szz.eie4re8 0/10 PTPoooomommenn swidasane LdLeeea zazaoa. aa2rk3 FPPoooooomSmmasmm gdaeam Laienmre aznaaw:m 22i3s 2 Test article was dosed as a suspension in water nNeecctroopprsiyes perforsed upon termination of the study revealed no visible lesions 600243 mace 3 ACUTE DEAL RAGEFINOER ToRICITY STUDY - ALSO RABBITS wien renize sucony of msctions Epospe TtexT macsiT on teirmeisraftfoneecsted eFosbilnomiisnvgattiooesne mn Tae tterim e ns boew nFiezebectryoeabtense g 500MPoLwetogsmiettet 712 oo2ys3a Dneeyist2a termination g esction B = am PHoowCosssicitgninioitnfiiccaanntt -- -- a= -- esction -2 Ies-- crion -- - Pw somticant -- -- 22= reaction == = ~ E TTiimne vwhienn nfoirasntlnasnlimailn hinetdhoesedosgerougproeuuphiebxLhtiebditesdhetrheeacrteiaocntion mance 4 ACUTE PERCUTANEOUS ABSORPTION TOKICITY STUDY ~ ALBINO RABBITS wien re-126 Swear of Reactions p(oasfkeg) Sex smaceion Miser afTfeTcted FollovTimngeebowse Meni borsd assinisviation eFom llcsim ng boa se Atnistiatien FTiomlsleioitngovbaotse & 200M wocesscitginoinicant To significant -- -- a -- -- -- S Tosction a= A = Eg 2 = Apempzx 1 kr wneeiman vo.: of Gagobag TTSePSuONnTSUOCRI:ESDi3nR1gYlTe SDaotCseoetym2m0EovbnaaleyuraPtsui.rocnutLaahnbacosorauaisttoalAr)ybl,soorrIopktceiororn TSatbuodryateries. TES The BE 4 8. Divisior SCOENTTRASORLTSIACTRA LFEI:CALE: SOEUGeEo:onpogw alana White ADEs HeE-- bTe FRI ILL Pol Ves, Inc. Hogers, Atkansas sMeurabor: Ta ia se alg CISHCIRVE h[hLauLensedtnlsitsbnyjigsultceatnonidfvofgotarhonufctrhttaewhliiiztsovahsarititsulitdacoynlrioiwtciialiellny.uwbseiebitnioondaseeatmbeebraimltien:sebstoRhraepbtbpiieoernscutemaernnecaoiubosoeiomaCenbeercoedr2pP2aEteEn FIO hcatsaresnoidlgloanennedlidmyarlaohsoo,munssuenswdbeioltrvihecndiesdctoaa0rnaEdtxatoarangdn,dawwWilahratierec-grhmereowsifhclfolelcroaengdyesabydinLhitebeatmlepteehmr.aacnadmreebcohsdnyodwmepmiaginhistit,edsw,ilbSOlanbe GahnUidEnsithdceegveotrfeisnttghaoacnGtpuidrceo.lxinaaTptphelelieytdru10na0sk colar will bo Fitted o toaoftsacilnagcblhoedcaydonorisrsmaeuagsrefpwaoiconelfdlS4bbeouAaecsmiKeimsephTeknaorseroirtneesncyye"oCimttrelopA0ClnYe, ofbpeeeleatCesotplaiilrceetncisetchdeludecktiwofnirglt,dhebiwerhirccehamgoewnvsieledlfa:ocrhcoaacPnlriu2in4doaerlhottuahosendetthxteephsoetaspuatorretecwiinspckaleterwirirooenpdr,puaegMnteeswredeeiusmnaieieonnntePeiltrlCoioisulSi ad1anfu1atrleiyrgnsiisnt.hieticAaotnigdorunoocsmtsoftnohfeetchroetorhopbsisttysuatdlwuyidlysfloiarnsbuesswecelrlouolnmcdauwasschtiaecaldhnldowanianlgilaamilanlblesaonnfsirdemecatergssiefyisfemoosrr3deossToAaroenc%easrha3s0y.lL pukooiisdgsnhietbyrsloesaWnsidfluflbtiounnbrdeoeinmmrgsaiaccrorrwrooidslwocldo(pbsiaotscorrewemuexcmlao)lmridnaewasditlilaaonnnydb.opchifasiIrsxnmueiaedtcioaistlnai,mope1ii07so:0sbsooeirffgfneeLriesevseorar:eftomsrapemreerbc'se)atfoLrosin 4cino4n1dthuecbteRiotfkheertrheeLsapbsootnurdsayit.obriyl'iAstLyLArrocfahwitvhdeaest,as,poStno.stohrPe,arutat,nhdaMntihtneheefrBialne:essTasmnearsrserweilrtaerrrionns'iHeahnce.hg %PTiuhnregienscaotliloRanarbboiwftilrlCehsoibwed,uawloRrantlesstftoornarPttuhirecilndeau:,ratSit.onLooufist,heMisseseoduyrtso reduce oral SponAsor CNP eral fone wDaaten Stay Director ZZee 000246 : rr wiker experiment wo:. CAATLJL AMHaLrdo| n(Contd) Je. TSCEooSnnTvs:uoCnTA:EcDutseOTn:DooSgmaaflonryToaExtivecailrtuyaitiKooannsgoLfaPibgordlaitnoogrynS.tuedKyi)ker TAbOTaTorTos; They SE Feel HDoimvess TEST ARTICLE: J(Y. [i WEE SYST AND SOUCY: PNeelw-FFrodlearn,dIWnhci.beWoAyorRs, GArkansas N(ewrbearys: sZT prog REWinger, 214 OWIECTIVE: MEO: Tsohfyestteohnbejetfcoetrsitvtehaeriotrficlsteehnissiintsaitlvubiditynyowoiflrlabrbabiestpsot.nosea,KpAphrBiobsxAtiLomSraitwceearlethdesaotalace,uetteeedasdeaoyromfatlhneatrvodaisscieintg and general availability: chzoaenntdroaonnllilmyaeldhso,uusoesmdlseicwntietsdhtanffdoraoomrldaawnildraer-wgaontreesrhcocoloafngfyeesrbeydinahesdaelLmtipnheirtaaunvmda:rweeiaEgashcdth,hsuwnmiiildmlietlybwe il hbtaehiexaosausntidsgindetedheoaftensuttmhebaerrctaegidec.ieearPThteagA,trwuhnikchhofewiele alchceaonrirmeaoslpfonfwdhielltrobaeacccealridsTpeahdff2 iFneendssoofs Aandionomtisy.maagaaleddssdeiqtuwoiifaolt4nldal(lybFerdc)oah,sdaamrVgiaenciitsaeltreneivrzeeelds twthihelelTtobemxgesi/tckdigota,cyrutmoihefconlwteetevhdeaert,afnesdsiutfpFpailtrlehtemeidseconlwteiad,ltoshdaaogegsearaiigteilPoonLvrsoaolvltesolsds Tpfhlreaomsttietcshte casoprlotlniascrglsre.wwiillAllftbebore aatddtmmoiidnniissottnroareteaidcohntoaonftihneatlhaenanitdme.aslttshea.ritnEEiuctmthtee', wfaoeramFplorenexcihimiicvehed Wtiiimmlpolervtbeiheoursetceusptrlnacsadtritcitcolsethheweeiitlrilngcbaegwehsriecmhfoovwreidlalf2o4rcocmhlotuuhrdeeedxtephreomsauflraesstpueArrrfitaoicaceieaorfftetrhe~Twhhaeinciamhnails aTvhofestuerradnripemomarolivsoadlwiol(flimbtmeheedoibtasetesetrlyveadprotsiftcolredoPsh(oadraamidalmcyiontfioosxrtirc1a4trideoaanvc,etioofnnoesllbaonowdtihngtuudsroishneogursset)mnieanniossr a"Erixtlaitlicolanel)swoiwliblothrbeeacloalrpdpreredoa.xcitmiaoTtnhesed.baceuitAnaLgLmreerdcaowiraddneadtl.aethaanIldnidtthoiesaelfai(nnLadDlSOf)rienope)forttbnowesyiltlweesrtbsehesst in the Riker Laboratories Archives, St. Paul, Minmesota. 2 purina Rabbit Chow, Ralston Purina, St. Louis, Missouri 2 Gheesticoonlloarf wriolslidbuealwotrenstfoarrtitchlee.duration of the study to reduce oral in SponAso)r A N Bate wot, Seuay pike os 00247 1.5 da he REs YCH ARapendnent.I_ to(CPonrcoltuodceoRdli)ker Experiment No.: OFANBI,0G 2. tdpsAQKiDn OFome), byasp(o09 edue . a > a dat XD Study DivrieactDorin 7 ol Tate 220s 120 west kg mando Limite 00 130 conde gua nid due oe cals Ah ade Thin 3 Lbs nerd a Study Director d 119-30 Zod WF glo So ale, unre J Date I) - a Nous Nn dbo ob gna L Study Diveo ctes dDateWa Cavum Gmabuois aud) deen TANG chapOTha Rake uf To lhSI] : 5. _-- TSE tudyADirO ector n Tf Datfeo _--_-- . --_-- 5. . _-- a. --_-- -_-- Bizector ate FPFEFETETPTTT eet .--_-- ---- --- Difecter Tate --_-- Director Tate o0R48 BEST COPY AVAUinLciApTMa) epnoIx 11 Particippaatciinngg Personnel Involved in the Stuyy 4- 11. a ee Xo Lo Ebbons, Bs K. D. O'Malley, Bs be. V. Pothapragada 6. . Pecor twewen Supervisor, Acute Toxicology ASdtvuadynceDdirTecotxoircoligist Comercial Chemicals Chemist ASnuipmearlvisLoarboratory 00249 AeemNDIX137 12. 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. BEST COPY AVAILARLF 00250 . APPENDIX TV BESTcopy AVAILABLCE on QualityAssurance Statement This study is not regulated by the Good Laboratory Practice Regulation of 1978 and therefore a statement signed and prepared by the Quality Assurance group is not applicable. This study was, however, audited by the Quality Assurance group. In addition to the data audit, different significant phases for studies undervay in the Toxicology Laboratory are inspected weekly on a recurring cycle, and the facilities are examined by Laboratory Quality Assurance on a three month schedule. 00R51 CO wicker ey RA: Feb bL Griffaith - 220-21 ApeENDIX 'FiSTCOPY Avan ag/e 4. "KL. EBBENS - RIKER SAFETY EVALUKTION LAB - 703.1 fe MNT he WC. MCCORMICK - MEDICAL DEPT. - TOXICOLOGY SERVICES - 220-2 JFUCN-E1282,3, F1C5-81029 and FC.o8 SKIN ABSORPTION STUDIES ON FC-143, FC-95, FC-99, FC-134, FC-135, 3M mPtelhneotaidsooenremcdaolncsoitmdopesoriucnitdthsiy,s/skainnaaubtshoorrpitziaotnionstufdoirosyocuarndluacbeonrsatoorryttho Sroeilcedase ) Plffirooverremla?imnioiuntnnsadorebfyreaesrntsooasrocudonmtphtlesheaafttmlepudlcoehraeonacdnshatelwumyidilsiclieasslnoaitanrdneiaboclb.ayetsiieinnsgcluoidfsosltuheidensicenrreuamnresisanamcbpollp?elsote S{CShaohelaalpaeoansuin,nmdalsSoI|ednueTtrhiyseeteynsooetcurounhcmcoalrvduteaastiiganoennaeshnraeaclntoyensdciasrandadirrneegsnsecetsos.mpsuatbErhsFiiestriisbmvraeiitimsnseorrooirraessatTttley)yr. psorHaoecvyer, `"tthahnkeiyoru fcoormpylouironpatsiheonucled ifnotthhietslhdemauTptameyuroi,unirngSespaamkplaersywoiplinbo. noeasra Se lone LZ WO: 1h 00252 atICAi L rdahinm23z 0-20ine / 15 . fee be Winter = 236-28 APPENDIX V (Concluded) REST COPY AVAILABLE. ACNOAMLMYETRICCIAALL LCAHBEMRIECPAOLRST D0I1V4I6SIO__N_ to W. C. MCCORMICK - 220-26-02 LALLY, Fun V. POTIAPRAGADA AND V. BUNNELLE - 236-3 func RIKER SKIN ABSORPTION STUDY --_-- Ge June 9, 1980 i0ty, AYnr ou 0 AyLn oi ast ss Reference: C1o5m6m6e9rcial Chemicals Division Analytical Request aFnoarlylzaecdk. of time, only a selected set of serum samples was TOTAL , ppn Coapound DoyFlemaleDuay28 pay1MalesDay 28 FC-129 Fe-134 ve-128 rc-98 Fe-135 rc-95 rc-99 26.1 02 69.6 181 11.4 23.3 ws 2 * wh 16.5 1.6 0.5 26.4 93.1 219 93 6.9 20.8 2.3 1.6 0.9 128.0 0.3 130.2 5423.15 u19s8 17229..71 676s venales Males boy 7. Day 14 Day 28 bay? Day 14 bay 28 FC-L43 10.1 12.1 3.5 5.4 6.8 hab Heh oF Analyning Oxon Bob/Ge Tou lg Clon ed tue om D. F. Hagen, Anal. Blochem; 87, 545, 1978). 70V.ABubnunnnedllele VAB/he rn . A v. Pochaptagada Read and Reviewed by be b, Winter a 0053