Document M4avMxBJNNvggxJ64m5ayeqB7

Expexioans Nos Acute Ocular Irritation Test with T-3421 in Albino Rabbits canazosse REECaENsTD Ee Po nin, L. wy Reviewed By TSoorniyioDtiormeacstor avo DEWNlee, SAitnkeermrcoowtivoontyastr Sr ie psivisae r, `Tomicee logy Testin<g7wees 000122 1 Summary The results of the acute ocular irritation test conducted fron June 21, 1983 to August 1, 1983 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-342) is moderately irritating (40.0/110.0) to the unwashed eye of the female alsino rabbit. A five second and thirty second contact washed eye procedure were also conducted employing a five liter wash. The irritation ratings for T-3421, using the limited contact procedures, were mildly irritating (15.7/110.0) for the five second and mildly irritating (18.3/110.0) for the thirty second contact procedure. Minimal corneal opacity, iritis and moderate conjunctivitis were produced during the unlimited contact srocedure by the one hour evaluation. The irritation subsided to minimal corneal opacity with vascularization (two animals) and slight conjunctivitis (three animals) by the day seven evaluation. T-3421, when allowed a five and thirty second contact, produced iritis and mild conjunctivitis by the one hour evaluation. All irritation subsided by the day two evaluation. Corneal opacity was not observed in any animal Of either treatment group. Introduesion The objective of this study was to assess the acute ocular irritation properties of T-3421 when instilled into the washed and unwashed eye of female albino rabbits. This study vas conducted in accordance with the Food and Drug Administration's Good Laboratory Practice Regulation of 1976. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 000123 = Hothos and mesutts the Young ocular albino rabbits of the irritating properties New Zealand of the test breed" were used to evaluate article. The test method was Rodeles acter shat of Draize ex ail, The test article vas Snstilled into the conjunctival sac of She right 78 of auch rabbit according to the treatsent procedure presented in Table 1 vieh the let eye of each animal serving as a control. At each scoring interval, the comea, iris and palpebral conjunctiva vere examined and Sraded for izritation and injury according to a standard scoring syscerR. The maximum possisle score at any one examination and scoring Berios 110 potnts, which indicates saxinal irritation and damage to ail three ocular tissues (comes, iris, conjunctiva) while a score of sero indicates no ierication (Table 2). In this scoring system, special enshasis is placed upon Srritation or dasage to the cornea, while less enghasis 1s placed upon dansge to the iris and confunceiva. Acer completion of the test, the scores vere analysed, and descriptive eye irritation rating vas assisned to the test article. The criteria used for assignsent of the Cescriptive rating vere the fregsency. the extent and the persistence of irritation or damage which occurred to the three ocular tissues (Table 2). The individual results ace presented in Tables 4cs. BCroosmeteeretiocnabRuo(cp1ce9ha6ti5a)sn:ast,ofInch..a. Sveamfveesry,of5hesicals in Foods, Drugs and 000124 3. The rating is arrived at by selecting the maximum mean irritation score at one hour, one, tuo or three days after instillation. If the rate of dissipation of injury does not meet the requirements defined for the descriptive rating appropriate for a particular numerical score, the descriptive 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. 000125 ae Syn Session et =A AESS aint R--W_--I_NS aeIWpniaItrEya Scmmme,a SewlSiem, S BnieswO ssoane BU 6 me a ete wm HLisg ed gE rms mes cim twews w cimmhn nd 88 aa a 2 Hah2 =Ig Table 2 Eye Irritation Test - Albino Rabbits GradinSgcalteheofSewveeriisthytedof ScOocruelsar fLoersions TiOscsuuleasr Conjunctiva Redness (A) Description VReesdsneelsss d(erfeifneirtseltyo ipnajlepcetberdalabcoovnejunnocrtmiavla. only). vMeosrseeldsiffnuoste,easdieleyperdisccreirmnsiobnler.ed, individual Diffuse beefy red. ACnhyenosswieslli(n5g) above normal (included nictitating membrane). SObwveiloluisngswwietlhlinlgidswitahboputarthiaalfl-celvoesresdi.on of the lids. DSiwseclhlairnggewi(tCh) lids about half-closed to completely closed. aAmnoyunatmooubnsterdviefdferinentinnferromcannotrhmuasl o(fDoneosrmnaolt ainnicmlauldse).small aDdijsaccheanrtgetwoitthhe moliidsst.ening of the lids and hairs just cDoinsscihdaerrgaeblweitahremaoiasrtoeunnidngeyoef. the lids and hairs and Score (A+B +C) x2 Total maximum = 20 Cornea popaacciittyy -(A)Degree of density (area which is most Sdecnasteterisedtaorkendiffforusereaardeian,g).details of iris clearly visible. iEraissilysldiigshctelryniobblsecurterda.nslucent areas, details of Opalescent areas, no details pupil barely discernible. of iris visible, size of AOpraeqaueo,f CiorrinseainvIinsviobllvee.d (8) GOrneeatqeurartteharn (oonfe-lqeusasr)tebru,t not but zero. less than one-half. GGrreeaatteerr tthhaann tonher-ehea-lqfu,artbeurts,leusps ttohawnhotlhereaer-eqau.arters. Score equals Ax Bx 5 Total maximua = 80 tris vFaolldusesab(o3)ve normal, congestion, swelling, cciormcbuinncaotrinoenalofinajneycttihoenreo(fa)n,y oirrisallstoifllthreesaectiorng to No rleiagchttio(nslutoggilsihghtr,eachteimoonrrhiasgep,osigtriovses). destruction (any or all of these). score equals A x 5 Total maxizun = 10 Note: Tchoernemaa,ximiurmistoatnadl coscnojruenctiisvat.he sum of all scores obtained for the 00127 5. rDraacieze 1 2 3 1 2 a3 ' 2 3 1 2 3 a 1 2 a3 1 2 ILABLE os * 000128 missue | period Li) ornea(0-A)| 1 bay eve swammsion nisr - momo wannres BEST COPY AVAILABLE Sawn Salons|sbioia [5595 [3wsez Hoan n ma fw Im Jw |wa] 00-0 | B04) | 200-0|Boa| Zotar Cornea (0-A) STI jot | 00-4|B00 | ToT4 oT sor Cornea (0-A) [7 |v ws wm |= 00-0 |200-0 |000| 2000|200-0 "0 wn `onjunctiva ornea (0-A) [| wo lno ln] 8(2-1-1) |8(2-1-b)[ 12(2-2-2)|8-1-1 | 8-1-1) Tov |ietiav oT Te TT Te | Coe] Kor Comes Compunctive os : A EPI------ bT EromeE e ] 3 a e 3 T r = | = Fornea (0-A) = cgg8&el or ee se 3 ve (= vpw w .: a- --_-- i) Konjunctiva : = os T c|in weE f y : o T ] = pica [eae] : . J rn mon sw ao rs ans bfe iresTt oy r w ? w Nm: e p ] 7 > | onfunc=tinve (Li vm on w dew |w 22 | sg fois g le] wm Rg F To en [oc eo | mel : eT : oT ve EosE EE [ TE vv Fonjunctiva A= Area S =Swelling iid > BESTCOPY AVAILABLE Riker ExperimentNo: 2208 ssecoo=m PROTOCOL 10. TEST: ___fAoceutOeuOciulpair graotniotneTnestt SPONSOR: OM. (omiizaial Chemical ~~ CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, Inc., St. Paul, Minnesota vestamol Tse piigion conRoLammOE LM 00000 PROPOSED STARTINGICOMPLETION DATE OF Tes: _5:8%= 4/32 TEST SYSTEM: Famale New Zealand Write Albino Rabbits SOURCE: _-- OBJECTIVE: METHOD: f(Tochroetmhoeebaijr.esceitnfissvietaiovnfidttyictsoontjreuasntncwitiisvl,ab)hetiosfotodreitcaelrumsien,eeatalhbseieniootfrihaoabbnnidsip.notgRenaatnbidbaligtoefnweterhraeol.feassvteailaleracbitlceidetyt.ao6thteneoc1u6l5a1r Stesstuosns wrThohioecmhsanwiwilmilahclosfrorwieols,dpobanenddhtoowuaasteecdrarodifnfaefsrfteiadxneddaadfrodItwhueiro.eu:tmseEisdahechocfaatgnheiesmaclaingweti.lemTbpheeoraattseusstrieganraeicndldsa whnuiumlimbdbeietriyenecdionisteardrolitlnaeggd the conjunctiva sac of the ight eye at a doseof 1.1 wi the contralateral eye of cach animal bs(eaerdvdeitxniaogmnaialnsesadcoracionnndgtrigonlrtaedrAvetadls1 fomraryabteioanddaenddtoinfjuutryhearccchoarr_dahicnotguerrfsiozaenadtshetaonrdualrda rsecaocrtiinognsa)7 ,ysttheamisosfuDersdaaiwyzisel ea1tssdaieig.enmeAedfdetrontcehocemepstlseeastriyaornbiyolf.tthheEeysettesuetd,xyatmhdieinraesctctiooorrn,esswmwaiaslyhebbdeaaycnaaerlryipzeerddo,coueatdnuwrdietash dieehnesiacairidpnigovfeasyo8sdiaunimdnaft3ui0cornseesrccaotainind,g Sc3toonartneaidcmtianlpsetrhpieoedRriwkpiertrohcLeaadbu_orrIea.Xto_rA_ile1s_r'laAw.rrcdhiaitava,wgaSetsn.hePraoauvtlee,drMaibnys netsh5oei tas.tuc dy r. ectopreraionddwtilhlebfeincaonrdeupocrttedwiulsibneg 2 oOPPfuurrtbiehnie:ahUeRnAadibtpbbeiyrdttSiCthhlaetoeEwfds,i.thoRrailasS ltoCno-mPlumorifitCnaea h,eemStoi.fycTLaohuleishA,sMsFiooscnsidoasut,riiorn eof,FoaonddanCodsmteutgicOff1icia9ls ~87=57T=-1 JUN 131983 TeI, 5. C. eCornick :/ W Sponsor 65-33 Date SAFETY EVALUATION Die comm 3 "laf `Study Director ate 000132 BEST COPY AVAILABLE Acer Ixpariment No.: _0BBIEB028E = rir em TT =udy director acs .- - TEL SimectE er mats . TT =udy Simseser mss N wud bvicecter ats s. 000133 study birecrer dats 12. seemnonx 11 BE; STeapy,AVAppyg Principal rarsicipating personnel Involved in the study "~ 0. 1. Markos, 35, Bs X. 1. bens, 85 x. b. otvaliey, 5s Gc. mecore --_-- -- Soar Dieter isuepasrivoisgoyr meting rin-- ge-- r Ssupetrvisaor rn 00134 | 13. session uss BESTCOPY AVAILABLE rest and/or Control Article Characterization kT2oss (ectiv-or) T3951 1. hreenitSdaemhtarictelyeniseaerrieasnnagaeeihd,ooncsuumneoinfftoertdmhietaysL,iroefconapno1aSseisticoonn,Mtgr,poulriCtsy3isoiftaozS teshserpopO ver- 2. hTee metahodE of syachh esis or oTrheigimnecoafodthoef bteisotssaansdy c(oLnftrzoplli`csdabssicea)nieiss, - fired 3. tTrherseee ailm] obfe atehetercmeirnteaanaassorofcZJ onsSol u supbostan ncesornek vscuhoeedwnodfet[er F hTereabove information and documentation are located in the sponsor's rer iAi2.4 s/sTre/e83 cc LD todo 23C2E w-c- he A 230-2 ' ll. Peakoe 223-656 S Ranty ms SC = ' Jar 311983 JHB EN La HS . V oa) Laie coi 000135 14. APPENDIX IV QUALITY ASSURANCE STATEMENT Acute Toxicology Laboratory Studies Study no.: _ 0883EB0286 This short term study was audited by Compliance Audit and the final report examined against the raw data on August 29, 1983 | The results of the audit were reported to the study director and to management on _August 30, 1983 In addition to the data audit, different significant phases for studies underway in the Acute Toxicology Laboratory are inspected weekly on a recurring cycle, and the facilities are examined by Compliance Audit on a three month schedule. Smpliance Audit August 30, 1983 000136