Document KzpMO2q7ZkXzy3vERzv0G6eQ

.- BESTCOPY AVAILABLE -oyeH PE RECEIVED | TON COLCGY | iSE E S= o i 8r e B. iso prey Din Homany K. G. Gortner Date E.G. Lampiecht, bum, Bun pate WFnosEGc e olate 03074 . x sntrotuction hO TTies e not ratl,rbayFnagtarennfaeicnoasdmauefmbresereryqcsuiteauEnldvtya?lCouhraveaatmlsiiocnatcleornLadDatiubovcolirtosaestidoyornty,so,cudSdetR.ytikeeriPrnamuilnLr,eaabbbMotirihtaenstn.oeurspiopeteTsarh,ecssnoItdsnuce.dw,yelsevvSeatls. of EBBo eenihinatneiaooobtoenr:atfoTorhye'tshSetuSdatyavnvaadrsadtacoonpudenurdcattaeidncgopiyPnrooacfcecdotuhrredeasnfciefnoarlwitsrhuecphotrhesttuiSdsaifemesat:yintaThiened ne safety Pvatuation Laboratory's record archives. ethos FrFmooraety-eeietignhnhtiaaennseex1 udTmoaacgblsolryoafetrmoeapr.tiiuterutseih,tenaNreIywnAcretMZ,ieufatiwleecairinneadilzliuWysnhegidtiehn/oisnrMemimontinihneekaicnesvdtiuaddweyirt.tihhevedBe0aa.cr5fhemvmieafileneonfalbrepeaofbovoblariesetds ett samen, "me day of insemination vas designated day 0 of pregnancy. ETighcrtompagoruounpdTseaoodrfninatisain2ai0a0m,tailos1n50w,eGrreo1u0p0ds,o.se5d0,Cvoin2tc5hurorrTe-n21t1041mc0ogon/tCkrgo/dldiasysa.onlivmeaTdlesrdeadiolswyeedreinattwo0 seis EEEa yaavirenegeas.droteannaodnodrsuuissrnhaiendrgis.endtdciaiaiyvtisihededtuearitwlahtyrweoaruiignnhgyohra81en8gcoipofnrngessgteaesnnsttttaaitndwiloioestnehssvbbyoosttlhoeuremlaeslrocouafipgnset1.sumbiwa/itAkcLihsLo.nwire HotehettreorAtYsvataienntnasavlvasetntpuweverireaetuaor3bes1eiarbnvidetdehnud.maiidliyTthyefrcolmiognhtdtrasoyllw3eedroefroognoems.t&at1iP2uornhionuwarntilRliagbhbtit/daCrhkow a21tstusevinvilnsgforalnoaibeananlodsrm2aw9leroefcligeneuistcthaaaltniaostniizgeandn.dontBhoegdeysrtavebetbiiisothnstaslvevrdeearyedo29sreeadcnodradcescdaocrhdoninugdtlaeyyr.sus.3, pvriegvnaent!. ins Comcante, vas. examined immediately to determine if the animal was Results ane biscussion First Group of Pregmant Rabbits (300, 150, 100 ox 0 m/ks/day T-3141CGC) hEToteeaitotriaatldwobanddamycieonimospftoruandtodiseoirnnegloeft(efTda-b3dl1ee4at11hC).sa.C AatLNLido1s35e00s0mmoafgk/ak3g0d0/e,dyay1r5ar0baobbirbcist1s00didemidae/dkwgivt/ihtdihaniynthtehe FoCeimrrmmaitennafdtoeudrvasodnayvsetrhyeofFtidofoxtsihicngdt.aoypoTrfheegndaotnwstoingFsuaarbfvbtiievtriangaftou1r0l0ervmaegblsb/ikteos/fdha1ay0d0rmaalgbrb/eiktassd/ydvaedyiseendd. The Sonoita Yesulting deathe soured apd enough co preclude body weisht 2BRikeer Experiment No. 08180331 03075 2. eufsfeedctisn,thcelifniircsatl gsriogunps oafndproefgtneanntnecrraobpbistysfwienrdeingtso.o hiAgLhL toof btehetodloesreatleedvels dduorsiendgata lroawbebritcotmeproautnoldoglyevesltsu.dy. Therefore, a second group of rabbits was Second Group of Pregnant Rabbits (50, 25, 10 and 0 mg/kg/day T-3141CoC) rTheesuolrtalinadcmoimnpiosutnrda-trieolnateofd Td-e3a1t4hs1.CcCOnaet ddoesaetsh oifn t50h,e 025mogr/kg1/0dmagy/kggr/oduapywdasiddnueot toobseanrveidntuibnattihoensetrurdyo.r. OnNeo s2i5gnasndofoneeit0hemrg/akbgo/rdtaiyonraobrbitreseoarchptihoand wneerceropsy Zindings compound of abortion or levels betueen resorption. days six and A body weight loss nine of gestation. ocThceurrleodssininalblodythree weight coincided rabbits were off with clinical signs of feed. The body weight ceihtahnegresnooforallfewthsrteoeolcsompionudnidcatlienvgelsthe between days six mg/kg/day group (aTnadblenin2)e. ofThgeestcaotmipoonundw-ertereastiegdnifriacbabnittslyredcifofveerreendtfrforommthtehe 0 gineisttiaatlionweiwgehrte lgoasisnincgausmeodrebybodcyompwoeuingdhtadtmhiannistthreat0iomng/akngd/dbayy dgaryoup1.8 of conclusion The objective of determining an upper dose level for an oral rabbit teratology s5t0udmyg/kwaas/damyetdowsiethltehveelsweocounldd bgerouapn oafpprraobpbriitast.e hiThgeh rdeossueltisn asugrgaebsbtitthat the atebrsaetnocleogoyf cstoumdpyounbdec-aruesleateadtodxeiatchse.ffect of body weight loss occurred in the 03076 soe aro 0 ma/xa/day wompsay somaway 100 mg/kg/day ora anaeeeet sbtyotnayatsoef tT1 3a14o1y in Rtbits Te 060 001 swcontattononwt oaon = oo oo 1 100 un uw 00 oo ea 1 1 1 o o apbermot ww ea ve oo ao ow o 5/6 mg/kg/day oo ve ompaay oo oo oo oo 0 o os swum 0 0 a oo 0 oo ao o o ompvaw 0 oo oo oo 0 0 0 o oe 2 itmmeuebateionoexcsork and vas terminated from tots 8g8 33 . : a Table 2 ral RangeMfeianndeBrodyStWuediyghotf TGa-i3n14o1rCoLCosisn Rabbits AY & so 12 15 18 23 0myST/AkNg./dsDyEV 41.g1g 25.144 49.361 SE 49.6 24 34.3 157 58.4 50SmTaA/Nk.g/dDaEyV 16.407 37-.c4e52.283 89.396 96.593 452.139 25 SmTgA/Nk.g/dDaEyV 4S.3641G-c1.048118.-17 76.e4a 477.31 S21153 10 mSTaA/Nk.g/dDaEyV 23.gq6 62-.:5a26.402 72.136 20.357 621.878 2 significantly lover than the control (Dunnett'st test p < 0.05) 03078 . 5. Appendix IOnrdailvidRuaanlgeBfoidnydeWreiSgthutdsy o(f)T-a3n1d41MCeoaCn BiondyRaWbebiigthsts With Standard Deviations ORY 3 6 $s 12 15 18 28 MG/KG/DAY - MNiIBE 22114487 2213653522319760 21566 2459 2202 2235 2348 NNIIBE 22115405 224167%7 22415257 22511860 22526758 22730049 22636179 22936612 NNAABB 22116643 22447547 2252101% 22522024 22159212 2216817% 22266335 22387511 STANM.EANDEVAS2E285317203.17518253.16S19253.46724214.04221264.25636285.855 oAY 3 6 9 12 15 18 29 50 MG/KG/DAY | 001188 22115521 21557854 22603326 12596795 22061287 12962202 2177870 220925%5 || 001188 018 22115534 2165 22519185 2523 22614633 2565 22510110 2545 22502279 2595 22250640 2685 22628949 2756 22649633 3029 018 2166 1878 1891 1621 1889 1961 1993 2162 || STANM.EANDEV322227943325326532292.5733272.60535253.15241233.70943215.697 03079 6. tr Appendix I (Concluded) IonrdailvidRuaanlgefBiondydeWreiSgthutdys o(f3)T-a3nd141MCeoaCn BinodRyaWbebiitgshts With standard Deviations AY 2 6 5 12 15 18 29 25 MG/KG/DAY Pip PP1B6 2155 2156 1929 2100 1572 2141 1963 2162 1951 2103 2008 2142 2055 2164 2266 2458 2157 1725 1753 1745 1561 1707 1816 2037 Pip PPiipB 2156 22116678 2149 22900800 222019@8 2526 12902771 2727 12704154 2901 11994713 2962 12918241 3051 22236553 3087 STANM.EANDEV2S2S1.47835271.83834280.74443250.65544221.2674231599236224.11 AY xe 3 12 15 18 28 10 MG/KG/DAY 018 QQ1BB 2159 22116616 1699 2118243 12724066 1825 12706568 1841 12707425 1844 11893541 1887 11896759 1538 22028232 2153 QQiiBp 22116625 22154615 22262318 22166280 22260003 22257412 22352905 2256362% Q1B 2170 2088 2135 2117 2175 2233 2237 2480 STANM.EANDEVI1200.73431271.27730210.95829281.07027251.20127271.56622263.443 i 03080 - BEST COPY AVAI ABLE DISYRIUTION 11ST wn. 7. case E.G. Gortner (orsuinal + 1) E.G. Ww. C. Lamprecht MeCornic+h . D. Griffith > F. A. Ubel (5) 03081