Document zo18gnL47bO4BJG2LG0RwQJ3

heute Ocular Irritation Test vith 1-3493 . in Albino Rabbits Experiment Nou: 0884280008 Conducted At: RSiakfeertyLaEbvoarlautaotriioens,LabInocr.atory St. Paul, Minnesota Dates Conducted: January 3, 1984 to January 10, 1984 Conducted By: . Reviewed By: . TbO.o.xiWt.caolnVoa.griisorts.a, rJ%k.,oBsS 3 Study Director < XSKe. eFniSormToixiecoylogisptide 3 Acute Toxicology YeDarte yeDate dc Xm.TL.. Ecaosbeens mWo Cao Hoa cormr ick 005207 1. Summary The results of the acute ocular irritation test conducted from January 3, 1984 to January 10, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3493 is minimally irritating (2.0/110.0) to the eye of the female albino rabbit. Minimal conjunctivitis was noted at the one hour evaluation and subsided by the two day evaluation. Corneal opacity and iritis were not produced during the study. Introduction The objective of this study was to determine the acute ocular irritation properties of 17-3493 when instilled into the eye of female albino rabbits. This study is not regulated by the Food and Drug Administration's Good Laboratory Practice Regulation of 1978, although the standard operating procedures of this laboratory adhere to the general principles of this regulation. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 005208 Ri 2. patton ent pevitts young alvin sabbits of the New ealand bresed vere eet to evaluste he ocular frritating properties of the test article. The test method vas potetet steer that of Draive gt gif. Ihe test article vas instilled into the conjunctival sac of the risht ave of each xabbit according to the treataent procedure presented n Sable 1 vith the left eye of each animal serving as a control. At each scoring interval, the cornea, iris and palpebral conjunctiva vers examined and srades for irritation and injury according to a standad scoring aystenl. The maximum possible score at any one examination and scoring period 110 posts, which indicates maxinal irritation and dssage to all thre ocular tissues (cornes, iris, conjunctiva) while a score of zero Snicates no irritation (Table 2). In this scoring systen, special enphasts 4 place upon irritation or damage to the cornea, While less enphasis is placed upon damage to the iris and conjunctiva. ater completion of the test, the scores vere analyzed, and a descriptive eye frritation xating vas assigned to the test article, The critaria used for sssigmment of the descriptive rating wre the frequency, the extent and the persistence of irritation or damage which occurred to the three ocular tissues (fable 3). The individual results are presented in mabe 4. . 2BhCaosmt imeattoicnsTDu1ca0ch6ii0a.nnd, ofinhce. pFemaveyr,of chemicals in Foods, Druge and 005209 - 3. The rating is arrived at by selecting the maximum mean irritation score at one hour, one, two or three days after instillation. If the rate of dissipation of injury does not meet the requirements defined for the Gescriptive rating appropriate for a particular numerical score, the Qescriptive rating is raised by one or more levels. The rating system is presented in Table 3. The protocol, principal personnel involved in the study, composition characteristics and Quality Assurance statement are contained in Appendices I - IV. 005210 re sevitation Test = Albino abbics Teentmnt esenduce imetteuMmbe,Srof lewem s mRmeainitemitbtycoisf (mcoeomnanenc) (oaSptoumeaeten) DsrmtiensiioaiucrmaitiToionnne . me aoe ore ites nme owe, 12,3 i 8a8g BE } . 5. rable 2 FTEGiaosmueers Bye Irritation Test - Albino Rabbits GradinSgcalteheofSeWveeirgihttyedofScOoeruelsar fLoersions Description -- rGraatdee ETVeestsmTeelrssTd(erfeifneirtseltyo ipnajlepcetberRdalEshcoovnejue nnocrtmiavla. oe nly). e SEE\R NVoerses:eldsitfnuoste,eadsielsypordisscreirmneiobnler.ed, individual Dittuse poaty red. 2 5 CeCrhieonenosa.tsT1aiv(ne3)yrtianbgovewitnhorpmaarlti(aisncslvuedresdionnicotfittahteingliamse.mbrane). 21 SereeiLtiinngg vviitthh l1i1a0ss aabboouutt hhaaliff--cclloosseedd.to completely closed. 45 DHmloaeechaamrsogimenste(ta)vietdfeirnenitnnferroncannoirnmeasl O(fDoneosrmnaolt ainnicmlauldse).small \ DaDiaio3aeaemchaearnretgeevtowiitctnhhennTooittdssett,eenniinngg of of the the 1ids 1ids and and hairs hairs Just and 2 5 Conaiderabie ares around. eye. Score (A+B +C) x2 Total maximum = 20 Cornea oodpeanesceirty1sM(thnaexgerneeforofredaednisnigt)y. (area which is most eBTrrnietsinleysr1edidisshceoelrrynaiiobfblfseucsureceedaa.nresai,ucednettaialrseneo,f diertiasilcsleoafrly visible. 21 Oeppaviescbeanrtelyardeaiss,cernnoibdleet.ails of iris visible, size of Soadue, iris invisible. 3 4 SGGrereee"satqeourfarCetoehrranne(aoonFeI-nlqveuosasl)rvteedBru,t(5)nbeott lseesxos. than one-hal. 2) rGreenatteerr tthhaann tonhee-ehea-lqfu,irtbeutr.s,leusps thoanwhotlhereaer-eqau.arters. :5 Score equals Ax Bx 5 Total maximum = 60 sets values (0 ' CCFTiooorlmedbTsuiimnacaanobteroinvo(eensallonufoarsimniaajenelnyc,tsticheooencn.rtgeieo(osfatn)ni;yoinosi,frpioassslwliestltiloiviflenl)gt.,hreessectoifng 1 Vdoestrreuaccttiioonn taonylioghrt,allhemoofrrthhaegsee,). gross 2 Score equals Ax 5 Total maximum = 10 Note: TChoerremsa,ximTurmistoatnadl csocno?urmectiisvat.he su of all scores obtained for the 005212 = 6. Table 3 - Eye Irritation Test - Albino Rabbits BaCsleadssoinficEayetioInrroiftatTieosnt PMartoepreiratlises Rating Range Definition ------------TM!# Non-Irritating 0.0 = 0.5 Tboy mtahientoaniendtahyisreraadtiinngg,muasltlbescozreerso otherwise, increase rating one level. PNroanc-tIircrailtlayting 50.5 = 2.5 Tboy mtahientoaniendtahyisreraadtiinngg,muasltlbescozerreos; othervise, increase rating one level. MIirnriimtaaltliyng 52.5 = 15.0 Tboy mtahienttahirneethdiasy rraetaidnign,g amlulstscboerezsero; otherwise, increase rating one level. . mIirlrailtyating 515.0 = 25.0 Tbyo" mtahientsaeivnenthdiasy rraetaidnign,g amlulstsbcoerezsero; otherwise, increase rating one level. MoIrdreirtaatteilnyg 525.0 - 50.0 . Tdoaysmaimnutsatinbet<his10raftoirng6,0% scoorremsorbey osfeven tmhuestanbimeals2.0. AlIsfo,sevmeenandsaeyvemneandayscosrceoreis < < 1200, buthten< 6no0%anofimaanlimaamlosngshtohwosescsorheoswing sifcorreastin>g 10iscatno ebexcemeadintaaisnceodr;e of 30 otherwise, raise rating one level. SeIrvreirtealtying . 50.0 - 80.0 Tdoaymsaimnutsatibnet<his30raftoirng6,0%scoorremsorbey osfeven tmhuestbaneim<als4.0. "AIlfso,semveeanndsaeyvmeneadnayscosrceoreis <Sco40resbu<t 3<0,608thoefn ntoheananiimmaallsamosnhgowthose sohfo6wi0ngifscroarteisng> is30 tcoanbeexmcaeiendtaianesdc;ore otherwise, raise rating one level. ExIrtrrietmaetliyng 580.0 = 110.0 FE ------_ 005213 maiz orn anRrTaTION TEST- NBT EARTTS wien 7-302 BEST COPY AVAILABLE Tpinieeam5e3|7 serine cin angunctio = | pToaw ko mero|7 wa -- Poomann| 3pbuoren cis enguctive S on| go geen Bee BL angunetina [v-- oenaity 2mmm o o DAaLmoWsWs E Saee www {some | 0wo o o o oo Suen | soo | sion| 20-00 no | oe ee Le le Lewe oo 0-00) 0s oe To To--To To L1 es || o oo |i oe oe pee v To Lf o 0o0o [oe Te [oo o Jo [ee | oe 0 o 0 Fee o oI. vo0oo0 Cmongudnetmiva: Ta ' 2- BESTCOPY AVAILABLE repmony x Riker Experiment No." PROTOCOL - res: Acute Ocular Irtation Test SPONSOR: aM_(nmercislChejesds Division CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, Inc., St. Paul, Minnesota TesTARmOLE_ Teta contROLARTOLE ft PROPOSED STARTING/COMPLETION DATE OF TEST: be de TEST SYSTEM: Female New Zealand White Albino Rabbits SOURCE: Li "ries + rue [oho th OBJECTIVE: METHOD: {(Tfchoroertnhoeibajr,esciteinsvseiaotnfidtyhicosontjierusinttcawiniiltvlsa,b)hoiostftoordiectaelrumsien,eeatalhbseienoioifarhtaaibnboidntispi.ontgRenaatbnibdailtgosefnwteehrearloteassvtealialeractbtiielcdtyt.aosthteheoctuelsatr styissstueesm. TWfhhoieocmhsanwwiimilahclosfrorwoieldsl@pboaennddhoowuaasteecdraroidfnfaesfrfteiadxnedadadtrodlitwbhiietruoemu-.tmseEisadhechocfaagtnheiesmacliangweit.lelmTpbheeeraattseusstrieganrtaeidncdlea whnuiumlimbdbieetryienscdtoineltaerdrolitlnaetgdo tS{haeedndciiontngojnua8nlcisacvoarlcionsntgarcoilon,fertAvhaels1 igmhatyeybeeaatdadeddosteooffuther charhaocwlesrwiaizntehdtth_heeoc_counlt_arral-raetae.crtail-onys_)e, to_fhee_aics_hsuaensdiamwyailsl Se examined ang graded for imitation and injury according to a standard scoring system of Draize ecGftosnsdatilealgec.ntmeAedpftdeferorinohcedocemwepistitseahsattraiyao1rntbiyo*c=flteth-heEey_stetesuet_d,xyat_mhdiienraewsctcatioosorrhn,essowvmwaieaslrlyhaebbdes aecnyaaerlryipizeerd_do",oc"ueattdn:uwdr_ie_tash pdeteehnrseticaoraiidiipdnwtgiiovlfeabseoo5ydeciaouinnrmddriuft3calt0utioeornsdeesruccasetoiiinnnnd,gg StoarneidmainlsthpeerRikperrocLeadbuorrea.torAlilesr'aAwrcGhaitvae,gSetn.ePraautle,dMbiynntehseotsatudy director and the final report wil be 2 b DPPruuarbiilsnieas:hReaAdbpbpbirytaitCshhaelooEwdf,itthRoareilasSltaofCneo-tmPymuirofitntCaeh,eeSmtoi.fcTLaohluseisiA,nsMsFiooscosidoasut,riioDnruogfsF,oaonddaCnodsmDertuigcsOf(f1ic9i6a5l)s of the United States. - PEC dE thele Sponsor cafDaetes" othe eign Study Director } : * fer Date fo ---- 005215 5. APPENDIX IT Principal participating Personnel Involved in the Study Nase . D. HM. Markos, Jr., BS X. L. Eobens, 5S K. D. O'Malley, BS G. C. pecore Function TSotxuidcyolDoigriesctt,or STuopxeircvoilsoogry Testing sAecnuitoerTTooxixciocloolgoygist SMunpiezravlisLoarboratory 005216 R 10. APPENDIX IIT mis study is not regulated by the Good Laboratory Practice Act of 1576 and therefore information pertaining to coaposition characteristics 4s not applicable for inclusion in this study. 005217 . 1. appENDIX TV his study is not officially regulated by the Good Laboratory Practice Regulation of 1976, and therefore a statement signed and prepared by the Conplisnce Audit department is not applicable. he standard operating procedures of this laboratory. does adhere to the general principles of this regulation. The Corpliance Audit dupartment does inspect different significant phases for studies undervay in the Acute oxtcotogy Laboratory on a recurring cycle, and the facilities are exnined on a three month schedule. In addition a select number of Research & Development studies are routinely picked at random from the Archives by the Compliance Audit departnent for review. 005218