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So AR226-1373
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CDhoecmuimceanlt CIonnftorromlatiOofnficDeirvision OEfnfviicreonmoefnTtoaxlidPrSoutboscttainocnesAus(niHciy-557) W4a0shi1ngSttorne,et,B.Ci.,20460 Cont iomons
Subject: APSeumcrattoilmouinourmo8(aCcla)rkbaonTxeoyxliCacatrebSsouxbysltiacnceAscidCsontarnodlCAocrtre(sTo5nCtAi)ns
OPiFlnefaTos-re2m9a9cfEiiGondOnCaftDetuoacPhterhdise3pMStuReKdpayoernht"a,sedniatntidetidlc.eadtMeadr"cOhrtahla1t2,Raonr1ga9le81f.inodseibrirgeSstofudiynoers ttheeratsougbejneicct eafmfieocntisu.n cTahtibsoiyRleapcoertmianxdcurteheprfoidnudcinegss ccheescfrCisseiriiisido AhermairnticJluembpoutb,liosdhedvien tthesAupauscpac1e980oF AAmRarEinLcn ETocOicinis aRUSnEdCISE0TPEAsC'u,sbmiMsttaactChehmies1n6t,inof1fo97r6mi.anttieornpreptuarstuiaonntputboliSsehcetdioninB(tsh)e Tofi7h5s:
efowrraalmixTcourranei ofGF, hoCmoooliosewhicFhashcanOFbehecruepreHsosenco5r7 ine reported on che 18H ventory Arseiprneeviousltysbsdteamtiedoiyn oudrtNovaedsibeenrke19hsautbmiLsosidoenh, ooourleomnsioses wfhiicahtatperhaicocmrsibuhtaaveblebooorn orbosleaetveeddtonotflduiosrcoacvheenipcaatlterenxsposoucreec.ted Tshpoinsdimnigx,tufuroe orf hsomoloagrobuosgylaimconaicuindsGaurrehoreyuelraetenstlydndomtiacereCoirsrtesavailable and uscd as follows: WM Brand Fluncocenical Acid FC-26 cGamlulsspiufciiearleayddiptriovdeucfen cramis
(international marke: only)
APR 23 1981
HASKELL LAB.
EIDOT2034
000016
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Sortacont fe-10 FLUORAL? brand Fluocochemical
Apdrdoitteicvtes used in ehzaical siesiali;
FCLoSUmuOarRntAiaDoccnaBnresaoncdbFoerFynliusaocreosc)hemical
ETSmrrueolmssieeirafetiienrgSraueessdeidal33tisnoscpheesomiifucicaiilsive in
CArEooumnutey CRheaadmol1i9t,eSiKp.nrosPdauucoltri,eonuicTea3ds5i13lp3ie,ctyi,iohceLooscsatutbiejademceattschoWerisogimhisaapytisic61acseeurtsissanSiosiaseisiiiniaisiets
GCCfEhhnaacmsleiocecTnuiiltscecuFenenFatalSiet6iy11L0ioeenxypm.oaskoecdornrpnsSpottooFtsrhi8oemmacsrhuceoulbstyjoedcE+cusryhoapeceneainoni.faFlLpsaaAnrPeffgeirr1uoihsRnitgAsanascssiereieelcrybaeu,s3i6ciSeeeesniiipioiiiiiioyrri:iiieiistsare
re capotsia snmerity
WoSESeEuulreetpcolhcuaiCohnshmumnmlteloeenetsadtiieanssrft.noidrsomqon,vAcsLibsyiFhtnohrAgraoptcrhSsiaIstlnOhiedSnelK1gr,i,novfgtehTootesnhvredeieslncslatusisnisateunodmgmmseiaSpgrchrnsieeizslFeeailnndeiptnrhaee3esrb:syeeeectmtFaspieprleroodsyitnenLoeeagssseraeiwsisiresihFoisrnaeaisiiviir,liii-nsse
1CIn5onvptliiacnnnoeufdndohmeronutithtteuocarhmsimdonoipguiscrlcianaironbnuocryyFilsuCocirenadcmihinuvgntsteecaean:tds,inthLeinesowtiicohvicossPeerreriinss WA tecatorenicicy study in cots. @ A subsaent Lecatogenioity scaly in susbiss.
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EID072035
000017
Document Control Officer
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EID072036
000018
Report Musser: esl Date: ares 12, i:
Oral Rangofindor Study of T-2996CoC in Pregnant Rats
Experinant Yo.: Conductad At:
Dosing Period: Study Director:
o660RR0013
St. Paul, Minnesota January 20, 1980 to January 25. 13:
)
ayDaete r
--_--
2/24alen;
.
2/25/2i1
:
EID072037
000019
tse
.
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TB Thoivesl E orofal T-reIa2n9g0eCefoirn%deer1fovrs.teausdtoyuabsvwtteasqeuoecesnsotndSuSoocrhtaebelsadtetsetttoraotdDoerltovoeigraoyymoinnssetAuedSteyhrerinnuPezopgruea,krts.doseTae
SFEHATAS THA 5 oSagret eSeThivinogiSlimWptsnenIgSgaaArtiiAapnsriab giNnt
."
St e pres,e Th
trains
nathots
,
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Torres wr
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E S Tor AhiotE ia intentrvian r nes Jeoedy wolonts vere. rei corded oL n di--rs 3--61
5D
cE1oo0n0s,otran7n.5t.o3tC0ioteoanrev.o2l5audm2me:ainkoiafsrte%eersmeld/ckoGgusltolfeysnbbsopdyose efewse&.igfihanttar .sbeotnTi-od2an9rr 9aU.aCceCdotvwreey essueosnfusp115e50n:odfed
.
E a AR Are TR AIL adgr Heim intubation on the same days. On day 20 of gestation the rats were
\ a Seiormio0s aenne osobRNEDTE) vier chnemlealiy relatesasLerpaeneats fiossi)et in
Fblioeord Scoanmepleosndtreomdetyhes3e0 orfatsgesitnateiaocnh: dosHsivegrrowephowreiredanstai kceanrebT aefiosret, utireen
Srecimens vere breton anh sobmities vs tha sponsor:
`
Results and Discussion
TTeohrectoorraanldaudrninigntsttheratmieornionofofT-2se9m9s8aCeeqcenaetetiss1.50,(ede10re0s, 7s5ti,hbr5se0shootr1h2o5oscFap/kre/edayr
;
Sarasa Gone aroun (ravi 10. st eerie
3
Ths tro aonprcymant 198 fkarday Tova Bad 8 sre aavers offers on body
li
8[J mivorimens vo. wns -
Etporaoss
|
000020
.
2.
weight on 1). They
day 9 of the study than the prejnant lost a conzidcrable amcunt of weight
high dose dams (Appendic and one was observed io
hove urinary the 100, 75,
incontinence on days 11, 50 and 25 mg/kg/day dose
12 and groups
13. did
The pregnant dams not have abiormal
of
Clinical signs and gained welgnt at comparable levels to the 0 mg/kg/iay
group.
mFgo/ukrg/fdoatyusedsosewergeroeupxsamifnoerdeyferocmhaenagcehs.of AfLoLurofdamtshe inreatdhaebl1e50 featnduse2s5
lsaercgteionleednshacdlefetyse, cdhaacnkgesstcroeanksisrtuinnnigngOf ononee-haorlfwotroe tohfreeth-equafroltleorwsinogf. tas
vaabynortmharloiutgihesthoeccluerncsedor idnistohergasnaimezedloclaetnisonfiabgerstho(sTeabolebse2r).vedTaicn tlheens two
p0r6e8v0iTRo0u0s10t)eroantolcohgaymicsatluldyiesrel( ated
coEmxppoeurnidmse.ntTnNeos:abno0r6m8a0lTiRtOi0e0s3
and ia this
sprtouvdiyouasppesaturdeidesm,oretheprotmeoruantcoegdenitchaneffionctthewaspraevdioeuvselosptmuednitesa.l
In eye
the
albennsormfailbiertsy wfohrimcihngapptehearcedmbrtyoonbael anlenasrrensutcleiuns,devfeollolpomweedntbyof setcheondparriyfary
agebneorrraaltiomnosrphooflotghiecaslecocnhadnagreys loecnscurfriebder ionf thtihse
fotal nucleus. Tae sane rangefinder study with
7-2998C0C.
Conclusion
The objective of teratology study
dwaestemremtiniinngthanis upsptuedry.doseThelevaebloveforresaunltosralsusrsaets:
shit
ttheerat1o5l0oymyg/ksgt/uddyaybudcosueuseleOvfel thweoultdoxibce eanffeacptproofprirautdeucehdighboddyoseweiiyns:a zat
gtaeirna.togeInnicadedfifteicotn otfo ltehaes taobxincormeaffleictty woafs roebdsuecerdvedbodaynd weisighlsikeglaiya,to n5e:
reproduced in a teratology study. .
EID072039 000021
3
Tanle 1 Oral RanWgaenfinBoddeyr SWteuidgyhtofGaiTn-s299o6fCcPCreginnanPtreaRnatasnt Rats
with Standard Deviations (g)
--_ ow ar av a
control
eo ai
7a4e
Lao
L2saevTe
150 my/ke/day
ou Shans
wseuaanaer alead
100 mg/kg/day
Sean WTI
wararean anosw
75 n/ks/day
wo a1 Ge duh
ar 7
aw INL
Wa die
|
)
50 w/ky/dey
de sea 4
nour ue wzamw
25 mg/kg/day
ct a8 wl iw we
2 Significantly higher than the control (Dunnett's test p <0.03)
.
.
.
EID072040
000022
`
Te 2 ORraatlerTaanfgoFcoirnduonrcsSwtiusyh BorfoTC-h2a9n9g8e0sCtionToPbrueseasntFrRnaitnaasd
[5I0 manasa ns
L@os
tose Gren nascar)
pst
B oLusaftetsusensotaxeaxnaimniendedfbreocmauesxceheoyfe Afsocuhritdeacsseure descsoyed in sectioniis
.
.
EDo72081
000023
:
Appendix T
:
t
Oral Rangefinder Study of T-2998CoC in Fiognant fats
IndiwviidtuhalStBaonddyarUdeiDgehvtisati(o9)n afnodr MPeraengnaRnodty RWatesights
---
Gay
Te = ar 1% a
OHO
NMiikk FTaAeY wAmed ZZEiDa 2Z0i1m dZeiwo 0 ET sGuisn MMLIEE Ialws zLieps pCAeF Zcooe uZUs Luewb DZweid MIR Zae 1m 221 257 zB Zul eR
STRMEANLEY 14820 10Z.I1 2214%3 AZeSd AZLRL BiEd HOH FREGHA FURS
Mik 320 Awe Shr one ah ann m2
.
_--
----
T= ow dx av
[EUR
Oui fuk
zZoidoZLeeri Z@diE ESMLe
Qik Ck
Ifo Zar
avr pe
Am Zi:
ZA Zee
SamMERICL ALwZ 1T2LSE Apwe HOH PREDHAIT HUHACE
Qa Ou
i Zin
Swe dmb
IE den
ame iw
2I9S7T eEEl Z34T0
Za 222
Eas GV
1d 30E
2T0Y% A6mVa F1E6D1
Zuma Ae
dw Sle
0G 4d
EID072042
N
000024
.
Appendix I (Continued)
`
Oral Rangefinder Study of T-2998CoC ia Pragnant Rats
Individual Dody Weights (9) with Standard Deviation
and for
PrMeegannanhtudyRaWtse'ights
--_--
ss
ZT do a5 aw
Bw dT
FAR Fab
Ea 2Ee
ddd 214
dE gla
4 lll
giEw
IIESW
EINVL
FBIlEe
za IDR
er Zuo
Ide clu
Zhe Zab
FAP Ze
Zaw Sem
dud Zl
FIM Fak
Zz EAE
Eh dmi
Lld Qlw
Zid Zan
24 261
Zw wd
led iv
MEAN por ZeZ pv Zed EE Zh STEM DEY Ile ZL% 304 296 SHE ALD
-
--_
Bay
--
se = az 1% mw
75 HGALBOHY
aWikk 3TT3L2 aAmMrE fZuir: 2E4X3E 2289%3 ZVeL FIdde GVilk 3Z3I0 EOAlPS dELnE IEeMnL Z2e3dS ETelw d4de Cur IZ am 1h Doh Zaa wed 1a wae Zan dew Ql 4 280 feo 28h
MER AB Zp 213 203 29D ad
-
EU LEV Low L142 2 dad dn Edun
EID072043 000025
: )
.
Appendix 1 (Concluded) Oral Rangefinder Study of T-2993C5C in Pregnant Rats
IndwiivtidhuaSltaBnoddayrdeDiegvhitastio(ng) faorndPMreeagnnanbtodyRatWseights
eTeeee maez rane Bi BAG BRikk ITZ6IToaAvmP bsaam 2z1i:e afuvnn zveds siwu KRaikk 333as 21020 D1u3i6 zrirs 2Ze7 Zniwa uLesv RRiikk 338300 118372 ZIii x a z2eev nooed G1arsd STHMERLev L1i5d0 13e0l5 15Zi2 20s.u4k Zahe4 Thue6
x e=w 12 iu 25 HEAL SSiAcR zZ4aZr Z21u%r Z2ias ziaes zZek ZIodd DEuwn SSiikk IId4su zaosot 2201s5 z2z3r: 224G3c LZioee lleBd Sik isi Tov z3r o2ze 2s ov Gs STHIMLERIGEV 1Z1o4 AZzz8 1254.34 129.82 4a0wn5 1e2s9
NOH ERECT FTALE Sik Bal M87 Zoi ms 20 208 23%
EIDOT204
000026
DISTRIBUTION LIST E. G. Gortner (original + 1) E. G. Lamprecht R. A. Nelson + M. T. Case W. C. McCormick + F. D. Griffith F. A. Ubel (5)
)
EIDO72045
000027
