Document 3Jd8J4w6555p7EqJ6N93m8e16

o ie 78% 156 Experinent to.: Conducted ats Dates Conducted: Conducted By: 20 bay Percutaneous Absorption Study 7 with re-s9 in Albino Rabbits 097980633 SRStia.kfeertTyaLuaE,bvoaWrliautnaontreiisoeonsr,sLaIbnocr.atory October 24, 1979 to December 18, 1979 a ooi %. bo oanel, 5 3 Bite RStauvdaynceDdirTecotxoircologist Reviewed By: der mKFoInl.. Gcmareseniser WC. ecomick CSupeerviisorn, Aecute ToxicolYoBgadyte ) . 03748 1 --" A 26 aay pexcutancous absorption study with FC-99 was conducted from Octobor 24, 1979 to December 18, 1979 at Riker Laboratories, Tnc., St. Paul, Minnesota using male and female albino rabbits ranging in body weight from 1.78 to 2.35 ka. (h preliminary rangefinder study was conducted to determine the appropriat dosage level to bo used) The test article was administered by dermal application to ten male ana ten female rabbits each at a dosage level of S000 ma/kg body weight for a 24 hour exposure period. No mortalities, toward behavioral reactions or body weight losses vere noted during the 28 day study. Neoropsies were performed on all animals won termination Of the study and no visible lesions vere noted. Preliminary serum analysis (Appendix V) indicates dermal absorption of C99 in albino rabbits, however, due to the limited nusber of samples analyzed by the sponsor, no concrete conclusion may be drawn. ' The objective of this study? was to determine the percutaneous `absorption potential of FC-99 in male and female albino rabbits. The study, hich was initiated at Niker Laboratories, Inc., St. Paul, Minnesota on October 24, 1978 and completed on December 16, 1979, was not conducted 0 SUPPOEE a government submission or marketing perait 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 axchives. 2 Riker Toxicity Experiment No.: 0379A80633, Test Method 699 03749 Hethod and rosutts 2. Cost oung ALL adult albino animal woes rabbits of eld under the New Zealand breed? quarantine for several. vere days used in this prior to costing vECh only aninals Which appeared annals at the initiation of the to be study in good health and used. The rabbits suitable as were housed case Sndivie. S811 in stainless steed, wire-bottomed cages and maintained on & standard 2aboratory ration with food an initial rangefinging and water study was available conducted 2d Libitum. using two male and two Sonate FALLS Hair and or cach ikige Loved. Tho the est article placed on trunk of uch antsal vas clipped res the surface of the intact skin which of covered approximately 40% total body the test article, a flexible plastic surface ares. After collar was fitted on adainistration of each animal and the Crunk wrapped with impervious plastic sheeting which will ccolude the atfetsterawrhtiicchle.tinefhetheantiemsatlsawretrieclereatusrnreedmotvoedthferiormcatgheesdefromrala 24 hour surface period of the ! etnheimealxsp.osurfehepoarniiondals(iwmemreedioabtseleyrvpeodstfodrospehaamdanciontiosxtriactiroena,ctoinoensabnodthtwoduhroiunsge) and after istration) removal of the test with all reactions article recorded (daily for (Sable 3). 14 days following dose admin Initial and Final boty weights vere also recorded (able 1). he information derived determining the dosage level from the initial rangefinder was wsed in fox the 28 day percutancous study. Preparation F 10 male and vere conducted 10 in female animals for the same manner as dosing and application of the test articie the rangefinder study with the exception of the collection of blood samples application and again on days 1, 7, from the orbital 16 and 28 afer sinus plex prior to initiation of the study fox serum uhich vas frozen for sponsor analysis. After the 24 hour exposure freutrinperess,Rmalbit e.Choswo,seRrasl,stosnn Purina, St. Loui)s, Ho uTTSo 3. period the test article was removed from the dermal surface of the animals end the animals returned to their cages for the following 28 days. Initial, 7 14 ad 26 day body welghts wore recorded (table 2) as were any pharmacoLone sins noted during the 20 day obscrvation period (Fable 4). A gross neexopsy was conducted on all animals sacrificed on day 26 and all findings recorded (fable 2). fhe protocol, principal personnel involved in the study, corposition characteristics, and Quality Assurance statement are contained in Appendices I - Iv. ' 03751 mo 1 ACUI UEIOAL KANGA DIAC HOXICIEY SHUDY = ALON RABBIZS " Hoztality wien and ves Boy Height Daca Doosrkes) nNmibnear ISVe ERELbs eByodyuWt mbeeris 09) Ruombbeerre Tepsotsesdepebn recaednt rr Deere r te 000 owWPo omsomanesees i2ii.o4o5 i2fee0r [.- ie un os o 2000 EWFMooo 9ooo8nmm25eee9snn2 2pi1.25ta5 2ibi.e0hnt2 1000 LFEnPooo] 9ooo8m2nme5n8ees7 2ifi.3eda6 2iii.2nan2 0/4 ' 0/4 2 mest article was dosed undiluted 03752 mo 2 ACUI PERCUTANEOUS ABSORPTION TOXICITY SIUDY - ALBINO RABBITS Mortality wien reas and Body Weight: bata -_-- (b"mogs/keg) x ania Number --- Individuesatl5 Sodbayy weights = (xg) 35 TMaeNmmbuemprbeerrTDebeessstdaed percent Dead 0mwWooooawwmawonee 2i20om0e LLimnm b23o0as0 2haea5 ome 0 WwWo ooewwesss 2a21sna lsLsms 22Lesas bableess nWwoooomwwoesn L2ao2eva Lddeaar 2221a%5 ahbaab Wooo 2: an 2a be sorPPooomssmememe 222.s900 Pooomwn ae usllemas ie 2220s;0 bey aa2mm0 ba PProooooswmmeeenmn 2v232o52r Poms 2a 3lle3es ise d2iomes 1s a2baaa bes PBoosomameeo 2203ss aLiass 2Lea bsisos ono . 2 est article vas dosed undiluted Nneecctrooppisiyes perforsed upon termination of the study revealed no visible lesions 03753 EE moe 3 ACUTE DER RANGEPINDER TOXICITY - ALBINO RABBITS SewrienozfoR-a9a9cticns Dose. ) Sex pesction HeiswaerrAtotseecdted pFTeositilnoiovsfitniGgaatpsiotosne CeAsbssaFtoiilnolinosvtoiifngaFtatiososenetion 5.00 MPhoo`osssiictgoinnoiinsfsiiccaanntt -- -- -- - Follaatoifng dubsotnre ee -- 200 TMooTessciitgginnoiinfssiiccaanntt = = Tosctions 100 MPNoressaicitgoinnotinetsiiccamntt -- -- Tesctions -- -- - -- -- - . se ane 238 3a , ACUTE PERCUTANEOUS ABSORPTION TOXICITY STUDY ~ ALBINO RABBITS wien re-99 Swrary of masctions DGoosPeg) Sex sssction HWesebbaerrAfbfoescstaed pPionbilnoivsitnogatbioesne MFoolilnoissitngitSioorne 5.000 Nroeascitginoinfsicant -- se PoTesscitginoinfsicant -- - Fiozlelevoifngousbtosne -- -- 2 . a38 E* a ATvoeecNoDrI,X Ifaker- Experiment No. I-- OUTTHEBObu4S CTSPOSONNEDSUOCRT:ESDi3nBHgY_:le_SCDaofpseretnye20nEevbaralcyueaibtoeiroenuCtLhaanbtcoomruaastolAryb,sorRpitkieornLSatbuodryatories, TEST ARTICLE: _ FC- G9 Tne SE Paul MDiimvpisoiiocn TJ CEOSNTTD RSOLYASSRTAIAECNLDIENSOGU/LCEyO:yMrIyNeLSwOENoUalNaEn--dOFWhSitYe:MineLRgaBBIER gg ex rE Pel Free, inc.. Kogers, Arkansas wNeaimgbhetr: Ran"glee:iip373 Jr OIHCELVL: HEOD: tphoetenotbijaelctiofvetohfe ttohsits fest systen for their asrttuidcylewiilln historical handling and general availab buaselebitnionodderetarebnbriamtlisn.eabstohRerapbtpbiieotrnscuswtteaurndceioeussse.loeanbeesesoropbebt.ioonne ility. yStharonodtolanenldiymarlohsoo,mussesdweiltiehnctsfetdoaonfddraoramdndawwilazatere-grneersohfcfocelarogenedysbyinhteeamlptehraatnudreboadnydwneiugshits,itywicllonbe Soaankusditsnsiigtdonhegeevdeotrfoaisntntauhanorbtociargceeld.e eaaTprhpeltiaegt,drunawskhiaocfhsicwnaicglhlleacndoiormasraaedlgseplwoioinblfdiltSuEmb0.OoaQc.Ehcaiapcrmghdaerdaaknfsfiimiraeveoledowtrirtsorlheteelneee cploalsltairc? wshiololtibnoagp,fpirwtohtxieicdmhaotnweilclylac1oh0c4calntuiodmteaallthabenoddtyteshsteuraffraotcuiekclaewr.reaaspMpmeeRd be returned co their cages for a fesibre picric swiitmhaiismpierrvsiouisoe ab[feetsoctrolalrietnciitctelideatwifiorlnolmobftehethreeomrobsvitetudad.ly siPnru2si4orhpoluetrxoutsehxeapnoadspupralegiacbianetrioioncnd,daabvfleteersredm3siechimsesinranwiillile for serum which will he frosen for sponsor Kaadinupdarnlireynysgeisast.nhde FbAicoonnndgdeirunocmgstsas.rrwonoifewlclrtohbpeesysrtweucidolyrldaesbdeweaclnoldndutascitsesadulelosananmiapmllalleesanosifamcalrliisvfeiwrch,eischsopneimeassa.yaiLeSe6a.in, upeotsgshitbslewiflulturbee rmieccroorsdceod(psiatcsernweuexmla)lminwaasitlilaonnyb.ephfaiIrnxmieatdcioaitln,ox1i07c,% conduct of the study. ALL raw data, other than b14u,ffaenrded26fodramysibne'dsfor signs noted Garin the iinllthebeRitkheerrLeasbpoornastiobirlyi'tsyArocfhitvhees,spSontsorP,aula,ndMitnhtmeheesfoibenlsao.lodreapnoarttyesrisliSemees wmiecehn = TiPhnugereisnctaoilolRnaarbobfwiitlrlcehsoibwde,uawloRranltesstftoonrarPtthuiercinldaeu,.ratsti.onLooufist,heMsistsuoduyrito reduce oral SponCs.orhele Lo) unl \WT/9atfaes Study Director \ Bats 03756 . wong 1 fowinkerutnxdpocinent No: CY LE.oo - CSsrEoow:suonAr:utBTUuBrCmagelirToonxEeiacvtiootssyteiNoDansLLtDaobnmodoirniagttSeoEslH)ST TaSTRCSETeR Te os ARICLES FOO0 FANT iDive isio FROmOSSvIaSnEAWRDASNOaG1URCES:TOneNw HSeaOto-- Ens WGh-- eYe, N-- TA RT- E g Pel-rrocs, inc., ogers, Aekansss Sesesen SIT ) Body Weight Range: 20.4 kes OWICHIVE: AETIOD: nTSOfhyaesttoeghmebenjouLfrcooatrilivteaahvroavoriifcllastophniisisiiinttsiyatv:ulidbtyiyngwoilflabrbebiestpeot.nosea.pFpahrbiobsxititomeraitweceeasl.thsdeeotaoecm,uiteeedasdeaorromfailhomasscodaxisiiecnigy biCreoaennatdsroasomnililgmlyanededhsdo,ruaosoelmdMusucnikbvnoiertsdehtdanffcdraaoadrmrsdaCavagniL,draerW-wghmaeietrcsehhrcoVolcIfoaLfngLyeesrcebodiyrnarheedssaeplTniotponhetdreaasntrndaa:"rewaeiaaBgacchcddth,Meamwtmifiidieliaalcetydbweiilnl htahiexGaunEdLidtoheOftesttheacSatgiec:le Tphlea.cetdruonnk otfheeasucrhfaacneimaolf vtihlelLbnetacctioorbeesn Fmeresincpoie Andnnooiyst"naagaaleddssdeidtWuoiifaoltnli/ally(bo(dC_oaT,sdaamsXgiaenc(itaaLGtreeTvrae,ecldJs awtAsihlolEtobmxeseis/ekdrgaot,rcytuimohcefolnwetethveeeda.rt,abnsodibeftmEisLterLheeeeitdsmeeilwoeidsdtohsaaggceareyiisctrlpaeievvoceedlvlsearsdlie wTIpfihrnl1eoap1nsotrtbivetoscihteorucsaaSortptilopnirlaucnagrlosredt.iwcwitiolAlslflhtthbeoeeba.reltri1aanccgddammogiiwdnenhisiisscottnhfreoarrveteiaidlacolhn2t4oaoocnfhtciohimueeethsdleoa.eannixttdmpheaoosltshsuteraeesirntcePhieatorrhccniehiomdwfmuoaeirr"mFtaleerrreesTcuwoeeahs.iaiev,cmehndina STVFhoiteumouorarsntihremepamolorLsvioaosldtwiola(lfritmitbmuchooldeoifbawastiseeltlrlyveadorbstetif.crolreedmoPochv(eaedrdamaiadlfcymrooitfmnooirxtsihtee1r4ardtdeeieraovmcneatliooSnneSgsvulreofbmoaoidctnehetuuossfroirmfnergeerimtohaohiorioautlrs aWiEnxix'tlailttciholeanel)sRwioikwlebilrethbLreaeabclaoolprrdparertedooa.xrciitmeiasoTtnheAsedr,ebaheciiuvAnteLgesL,mrreeadcStiwo.radndeaPdatt:uaelt,ahnaIdMlniistdtmhoieeasslesftia(ennL.adolseE)roenposofrtbtoewslisicsoosrtegsato 2 purina Rabbit Chow, Ralston Purina, St. Louis, Missouri 2 hGeesticoonlloafr wrieslildubaelwofrenstfaorrtitchreo.duration of the study to reduce oral in- a2L/8 te SuDdWbideuell wy,% 03757 2. The SAed APPENDIX 1 Riker (Congluded) Experiment vr we re CFI ARIK : Yoo ces dna oli i " ow Le pon 3, " | dupe E = in & 19/ * a. Ig, capdde Ae sled A Abe meiobd Cane wl be . . -------------------------- Heuee Study Direc Date ' .-- --_-- ----------m - -~ . _-- --_-- on .o -_---- c \ -- Te 03758 APPENDIX 11 1. Principal Participating Porsonncl Involved in the Study ee Ne ame, e PFuumncettioinn Ke Te Ebbonsi, ns Supervisor, Acute Toxicology K. b. O'Malley, BS Dr. V. Pothapragada 6. c. pecoxe SAtduvdayncDeidreTcotxoircologist Commercial Chemicals Chemist Supervisor Animal Laboratory 03759 APPENDIX 111 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. 03760 appmox 1v . 13. Quaiity Assurance statement This study is not regulated by the Good Laboratory Practice Regulition of 1978 and therefore a statement signed and prepared by the Quality Assurance AGsrsouurpanicserogrtouapp.plicable. This study was, however, audited by the Quality In addition to the data audit, different significant phases for studies underuay in the Toxicology Laboratory are inspected weekly on a recurring acyctlher,eeamnodntthhescfhaecdiulliet.ies are examined by Laboratory Quality Assurance on 3761 tena Core pone : IL Dok Ricker 48a - EELbA GUbeei+r20-- 52120.0 1a. J [1 Ke be C. EUS - RIKER SAFLTY VALUATION LAD MCCORMICK - MDIGAL DEPT. Toxtcouocy 205.1 seavices - 320.2 FU SFuCnE-iI1283A,3V,SOFCU"-ToT1tI25ONanSdTUeDoSnON Fo-1a3, 1-95, c-09, re.150, Fe-13s, 3 mnPelneotaisomenecedocncsooimmdpieorcuntdhsi:s Hainnaaubtshoorrpizaotni'onStfudoirosyoeuranldasbeorrnatoorry kto LOH Tolease CPNFooovmrremp"oineunnsdaoosf"ahsrtooiSdoehRP1LS6Oa%tmFopldltteoharenaodclshtyWeuisndiiicesas1oat"rLenbaeb"toyiiennr?cgleJidEses%gueedgdn'1ienroeannSiiEnnRccPoammSpplroce compounds. The serum data Cnaicates analysis spearmint, TET M"CdoarCncanahwkahiayenroyru cfcoCoo4onrum7cpp5royln8eoetuteOricUoopnnaSNctSalihvruooesnuacilhedoennihosenretucnttohahnidtcoshelesrmnhaauisirrponercugtosynssoco.sunotairmsnpsgeFauhorfipmifsatiirictpvieeeaetsncotnexrreigincSo1iAuatTgybS,hle,,ltTooOHvoRweMervOerr, ' Felon4 wa:kan 03762 tWeAtLe troikvut-i2b36ie2z riz mzn C7 Lo bl Winter - 236-28 : 1s. APPENDIX V (Concluded) COMERCIAL CHEMICALS DIVISION ANALLAYBRTEPOIRTC14A6 L TW. GC. MCCORMICK - 220-26-02 Fast V. POTHAPRAGADA AND V. BUNNELLE - 236-3A SEUETY i1g, NoC Subyect RIKER SKIN ABSORPTION STUDY _-- Bae June 9, 1960 ot70aws) 4 Keference: Commercial Chemicals Division Analytical Request 115669 ' aFonralylzaecdk. of cine, only a selected set of oerun samples vas TOTAL F, ppm Compound DaylFemaleDsay28 Dey Malesbay 28 c-129 ve-134 26.1 69.6 0.2 18a us 23a 8 zi ! ve-126 c-98 "ees 16 0s 264 931 Le ws e-135 re-95 69 20.8 0.9 128.0 2.3 7.6 10.3 10.2 re-99 5423.15 mwaulss w7e2.a7 e7siss vemales Mules bay 7. Dayl4 Day28 Day? Day 14 bay 28 Fo-143 wa 12a 35 sa 68 ho Hrd of Aunlynbis Oxon How/G Tost nue Clon Hel lle mi D. F. Hagen, Anal. Biochem; 87, 545, 1978). 70. Benne VA bunnelle VAB/he - B foo V. Pothupraguda Read and Reviewed by be by Winer Ht 03763