Document anvNvpZ54LpqLz2brk03yXr9
.
7-394"
28 Day Percutaneous Absorption Study | -.
with ro-12
\a
.
in Albino Rabbits
Experiment No.: Conducted At: Dates Conducted: Conducted by:
Reviewed By:
dot MKLT. Ecbabseens W.Co.. MGerciotrtniiecnk
o979mm0627
SRStai.fkeetrPayuLlEa,vbaoMlruaiatmoterisiooents,aLabIoncr.atory October 24, 1979 to December 18, 1979
160 Ooi
EN
XAS.tduvdaD.ynceOD'diMraTeloclxteiof)cr,slBoSgist ate
3
KSupEervihseorr,s,Acu3t0e
2Ba4te4) Toxicology
00254
REST COPY AVAILABLE . --
A 28 day percutaneous absorption study with FO-129 was conducted from October 26, 1979 to December 18, 1979 at Riker Laboratories, Inc. st. Paul, Minnesota using male and female albino rabbits ranging in body weight from 1.75 to 2.42 kg. The test article vas adninistered by dermal application to ton malo and ton fomalo rabbits at a dosage level of 5,000 mg/kg body weight for a 24 hour exposure period? six mortalities vere noted Which cadirrdd betoen
days two and
28 day study
ctohnrseies.teTdheofunLteotwhaarzdsyb,ehahyvpioosrcatlivrietayc,tipornosstwrhaitcihonweraendnboltoeodddwuarsinngottehde
the urine. onset of the reactions occurred from day 1 to day & and ali
teactions subsided by day 7 or death precluded recovery. Body veisht losses
vers noted in two of the animals which survived the observation period.
Necropsies of animals which died acutely, generally revealed pale, mottled )
Livers and blood in the urine with one animal exhibiting a dark geen spot onthe brain. Necropsies were also performed on animals which survived the study period and revealed no visible lesions, with the exception of one aninal Which had an atiophic spleen. Preliminary serus analysis (see Appendix V) indicates domal absorption of FG-129 in albino rabbits, however, dus 50 the Linited nusber of samples analyzed by the sponsor, no concrete conclusion S------ Introuction
The objective of this studyR vas to determine the percutansous absorption potential of PC-129 in male and female albino rabbits. The study, which vas initiated at Riker Laboratories, Inc., St. Paul, Minnesota on October 24, 1979
2doptraogleinLienvealrytorabnegeufsiendderinstthuidsy sveansdyc.onducted to deteraine the appropriate b Riker Toxicity Experiment No.: 0379330627, Test Method 699
600255
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a
ana completed on Docosbor 16, 1979, was not conducted se support a sovonmont. submission ox marketing permit and is therefore not regulated by the Good Laboratory Practice Regulation of 1978. The fav data generated by the Study Dixector and the Final xeport ase stored in the conducting Laboratory's archives.
00256
reins
FSTCOPY AVAILABLE >
SE
Young ALL
adult albino Skasis wes
sabbits of Held Wer
the New Zealand breed Quasanine ox several
were days
used n this prio to tascing
CE OLY imal wikis appeased SniRALY 8 tho iniLiation Of tho
Go bs study
in good health and used. The rabbits
suitable as vere housed
tase fndivid
SALLY in stainless Laboratory xationd
stock, wire-bottomsd cages and maintained with food and water available ad Libitum,
on
a
standara
A FALLS
fionritciaaclh rdaonsgaegfeinldeivnegl.stuhdyevatsrunckonodfucetaecdh uasniinagaltwvoasmalcleipapnedd tfwroeefeomfsie
Hak and the test article covered approxinaaly 40%
placed on the surface of total body surface area.
the intact skin which After adainistration
of
the the
test article, Crunk wrapped
a flexible plastic collar was fitted on each animal with impervious plastic shesting which will ocolade
and the
atefsttrawrhtiicchle.ineThethoanitemsatlsarwteircelerewtausrnreedmotvoedthefirromcatgheesdefromrala
24 hourperioa'
surface of the
atnheimaelxsp.osurheepearniiomaals(ivmemreediaotbesleyrvpeodstfordopsheasamdnaicnoitsotrriaetiroena,ctoinoensabnodthtwoduhroinwgs)
and after istration)
renoval of the test with all reactions
article recorded
(daily (Fable
for 3).
14 days following dose admin Initial and Final body
weignts were also recorded (fable 1).
Te information dexived from the initial rangefinder vas used in
determining the dosage level for 10 male and 10 female animals
the for
28 day dosing
percutaneous study. and application of
Preparation the test arsicie
vere conducted in of the collection
the same of blood
manner as the rangefinder study with the exception samples from the orbital sinus plexus prior to
spplication and fox serum which
again on days 1, 7, 14 vas frozen for sponsor
and 28 after initiation analysis. After the 24
of the study hour exposure
P2eu1rinParesRsa,bimteC,howr,ogeRrasl,stoann Purina, St. Louis, o
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:
period
tho
Cost
axticls
vas
remeved.
BESTCOPY AVAILABLE from the dermal surface of the
~~ -. snisals
14 the animale retuned to shel cages for 7+ 14 and 20 day body eights were xocorted
the following 28 das. Imieins, (Sable 2) 23 vere any pharmace.
964 244s noted during eSE003Y va3 conducted on
the 20 day observation period S11 aninale sacrificed on day
(fable 41. 28 and all
A seuss Einatnge
Sxeecuor,dedcom(pboslietio2n).chanreactperroitsotciocls,, parnidnciQpuaalliptyerAssosnunrealacienvsotlavteedmeinntwhsece
contained in Appendices - 1v.
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au 4
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CUE
DERAAL
RANGEPINDER TOXICIVY STUDY with re120
~
ALBINO
RABBITS
Mortality and Body Weight Data
_--. Daoksoe)|
ANonmibmearl IdndiivJ viiddeusaeBlabyos dSyuMbet eelsoorhhts (3) yFuommbweerrTpeesatedd pbeercaednt
k --_-- T =
000 muPooo sooemmasaseseeerss 2Z3.o2sr2 1aa.2a9 Ponsa pet 20s
oa
200
umoo eo
omowazussesss
2.232070s
212.207406
vo omer Zon poe
oa
0
000 o[ Pwo rsam- mess 22p0.e22ds0 23p.d53t1 Po onsen 26 Ze
oa
0
2 eat article vas dosed undiluted
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wa 2
6.
ACULE PERCUZANEOUS ABSORPTION TOXICITY STUDY - ALBINO RABBITS
with PC-120
Mortality and Body Weight Data
| p(onsg/ekdg)
ANnoT immbaelr oole vTigeeeel}BDoRdYy VeigMhBSEts(kg--)--------uNmubmbeerrTDeesatded
-- pDeercaednt
--_ 8 -- hk -
5000 MMmo 998m33005662 22..2400 11..9872 12.718 2z.1a8
110
10
HMo e980350673 22..1402 (22D.a2y4s) 2.-4o-3- 2--.7e5
mMo 30s7e7z 21.7054 21/s0]8 22..0152 22..4300
MMo oomm33003328 22..0384 2i.s15o 21.377 22..2158
HmoM eomm33003339 22..238 21..2983 22..2235 22..4620
5000 Fo 9e82209815 22.1273 ((33DDaayyss)) o-mmn ---- --
5/10
50
FFoo oos8m2s0a3z 22..2030 (21.D6ay1s) 1.56
p-- 1.80
FFo o95m29e60 22..0377 Fass ler
(12.D7a0ys) 2o.o0m5 1.89 2.15
2-.43 2.48
FFo oosse22006377 l2.o0s4 l1.a7l2 22..0056 Fo 982943 2.05 (2 Days) -o--
22./333 pated
2 mest article was dosed undiluted NNLeiecvcreroroppsasinyedsbpleorofdorimnedurionne,anwiimtahlsonwehicahnimdailedhaavciutneglya,dgareknergarleleyn rsepvoetaloendtphaele mobtrtaliend. Awintihmaltshewheixccheptwieorne osfacronieficaendimaulpownhitcehrmihnaadtiaonnaotfropthhiecsstpuldeyenr.evealed no visible lesions,
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ACUTE SERABGPIR TroAxBiLCEIT3Y STUDY- ALTO mS
Semrwyienofrreencztoions
ours ser macnn t"eseEr SactEctet JTThaoettloFolneeetbotstee TGpTorslelueiornTisehbeufsT
00KPWmesemetiisontstem
ors
tit comination
--
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--
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Poeeseilginoinfsicant
--
-
Emx
to sisounsicant
--
--
-
rowerTreeascetriioonns
--
eve
reviled pA vivepiybirs Time when first animal in the dose group exhibited the reaction
ttiche oyf ooult -- -- --
--
-- --
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ACUTE PERCUTANEOUS ABSORPTION TOXICITY STUDY ~ ALBINO RASBITS
wien re-129
Swany of meactions
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Study
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k1Ssinydaxsntierednxeyrgloissatn.snhidetti|icabnotgdniidronuongcsstsofwonifetlchlertohbepsostySurtdeVyucditylfrloasrebadesweaecrnloudlnmcuSawaiohstieaeeuldhisownahsniettamalpsspelensarpiosreraeianeenttneirriyifYdrocori$le2so9reOr5inkvTLaEacW,siL,L
JCCSAooeIinsLsdshuibcclesteowtfhifolultmbrhuoeebnrseeepstmrmuieadcccyrot.orosdweedAo(LpsLiatcsexxawnenuexnla)ldmaicainasla,tiainOoytbnah'peraFiImrtnmehiscat.oniarittnsh,ce.St7osB:eabsbsuethrritmnmsmsecmsoeratesFeoaeribreieneedT,Sn21e0.
in the Riker Laboornastiobriyl'istyArocfhitvhees,sposen.sorp,euatnd.ertmheerfoorta)m remit tary O58 Whic8h,
PiTuhnregienscatoilolRnaarbobwfiitlrlechsobiwde,u'avloRranolssetf.oornarPtuhtreiionGtaue,fatSit.onLouftst,heissesauneso reduce oral
So2r0es Milosinielle fps fBaatge Study Birebcor
\ ate
00263
-
APPENDIX 1 t(aCkoenrtinxueecd)imens wo. SQN)
Picor
sseionssora:cutm_e( Doepunay pmuoixdpcgistyt(hwaiggetimnginelg) seady
J 10.
BEST COPY AVAILABLE
CONDUCTED BY:
TEST ARTICLE:
Safety Evaluation Dad
Laboratory,
Wiker
Laboratories;
Tne
ST.
Paul
MDoivniesieo
coTFEnoStTrrooSLYs.STsESMmmAbNDeSOtUR7CER: ANoeNwGH ZE ealG and
WShiiste
ATbifo7RGABB7TC7Z
Serr
re
-
Pel-Preez, Inc., Rogers, Arkansas Numbers
EEE
Rob esRange: 2,4 her i
OUJHCTIVE: | sOTFhyestteohnbejeftcoetrsitvtehaeritorifclsteehnissiintsiatvulidbtyiynowoilfrlabrbebisetpsot.nosea,pRparhboibxsittiosmraitwceearlethdesaetalace,uctteeedasdeaosromfaelhnoatnoedxsiieicnigty
and general availability.
METHOD:
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dhbtoaehmieaxagoseaussntidsgoinfdetedhWeoaLfteCnsuttmhebaecrraetgdiec.leearpTlhtaeacg,etdrwuohnnikchtohfewielaslcuhrfcaaocnreimrdoaesflsiwtpbhiioetlnoulmdi.bnetaacccEthaaircndhspkeaaidfnnriiamFeatrseledciwncisgoleile
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PTfhlreaomsttietchset casoprlotlniascrgl"re.iwlillAlftbbeoer faaiddtmmtiienndiissottnrearcteaidcohntaoonfitnhatelheaannitdmeaslttshaeFriitnlfierctdulhmewe,itfvhaeoarnmFtphleiresexeicmnphiiriceovhceenss.
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apsotsuerrerpeemroivoadl tration) with
oa(flilmtmhreeedaicattteiesotlnysaprboteisictnlgedosr(eeadcraomairdaldmyceiodntf.ioosrxtirc1Ia4ntiritdeoiaanayc,lstiooafnnnosedllfbaoinwonditanh)gtwGbdouoordshiyenagswaeutemhienaimeesn-
awirltliclaelsowilble in the Riker
Lrbeeacboaorprdpaertdoo.xriimeasTtheAedr.cahciuvAtelesl,mreadStwi.adnaPtaluaelt,ahnaMdlindtnhoeesseofti(anL.aDlSO)repoofrtthweilt:enlmsvemesstor
2 purina Rabbit Chow, Ralston Purina, St. Louis, Missouri
2 Tgheesticoonllaorf wrielslidubaelwotrenstfaorrtitchleesduration of the study to reduce oral in-
1] Sponsor 7)
ate
Study DiVkaelcle
spb Ba
c00264
BEST COPY AVAILABLE AAnPePnENdDnIeXntIto(CPornoctluodceosdli)ps Erwerimont vo. ANYAROLY)
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000266
APPENDIX 111
1.
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.
C00267
APPENDIX IV
14.
ality Assurance Statement
This study is not regulated by the Good Laboratory Practice Regulation of 1978 and therefore a statement signed and prepared by the Quality Assurance group is not applicable. This study was, however, audited by the Quality Assurance group.
In addition to the data audit, different significant phases for studies underway in the Toxicology Laboratory are inspected weekly on a recurring cycle, and the facilities are examined by Laboratory Quality Assurance on a three month schedule.
00268