Document jgYNvkmO805M05OLwEeNbkzO5
]AR226-1376
: -To .
fIMHneeddsuiesciPnloeseygsine
Medical Departmentant
CSSiararnaeMreoesa son
aren 27, 1551
ARERG -- [376
S(o2,rrenee nto: Sophat)J
mmrert e
<2M .
Blaine C. McKusick, Ph.D.
HENaelsvkkaereokln,l RLoDaaebdloavraarteory19711 Dear Blaine: AcPalrceboaospexyylcoifocnttaahccetidTsuSsCAanidSfecycootruiroehnsapv8oe(en)dfiunnrgottheiarfmimcoqanuetisuitmoinocnarsre.egearxdyilnagsepser1fslunocrroossleksa.ne Sincerely,
rFaD.nGkriffich, Ph.D.
Manager, Toxicology Services 06: KR Enclosure
RITIIVID
wana 1 any
2
EID079613
--
.
. 000039
FfrriA.tabielnd, 4k.0.
sarch 20, 1981
SW
APcatrikagLaDwinreBcutiolrd,inNgIOSE R5o6c0k0viFlilseh,erMsDa2n0c855
beac sir:
Subject: Nooftitchee Ttoox.iEcPASuRbesgtaarndciensg SCeocnttiroonl 8A(cet)
Ptlheeasseubfjiencdt ennoctliocseedsufbomritytoeudrtionfEoPrAmaotniotnhias cdoaptey.of
Ycoeurtwaiilnlpanrottse fofromthoiuxrnolteitcteeraxtotErPaAdetsheatcrweet orregard
iconnffoirdseanttiioanlsbhuosulidnesbse ihannfdolremdatiaocnc.ordTihnegretfoorSee,ctitohins
'
15564)o.f tThne OtchecupcavtonieonaylouSadfeettoryaainnde Htehaalth4Acmtay (h2e9 USC
.
ut3occetpshresioarrgyenteotroasdluicpshucbldloiisscec,locsweuerrtear.ienqueofst thtihsat iynofuorcmoanctiaocnt
VSereyrt,ruly yours,
Che
Fraok A. bel, M.D.
Enclosure
:
CpS ompetttti n sa Sarma sa
~
.
EID079614
.
000100
so.
Some seen GUL) MALL = RETUR QCELYT pioCEsTey
i
MCanter
!
ase
-
Hacel 20, 1561
SRE
CDhoecauisceanlt CToanfcorromlatiOofnfibcievrieion O4MEafn0sfvhiiicrneognSzmcoooefncn,utTtaoslxBi.CdPf.roSotut3eb0cs4tt6ia0onncesAks(nWcHy-557)
i
Gentlemen:
1
Subject: YSAeearcnttolinuouonmroBa(Ccla)ktabnToeoyxliCacacreSbsuobssytlaincceAscidCsonstnrdolCAocvtes(pToSmCmAi)ns
i Pertiunrestane smoniun carbonates 1s + gna snsiees ene i
POIttRlFhneeefraToaEsrts-emou2agb9tejfS9nieiHiocnGctndCaeaTfftmriiftnmoeaonTccngtohitseauhn.diasns3ctMsTaTthroRuibedsoKtpyxaoyRtrlehaotapa,ttoereotndntamditiai8texnc4lddeSaeuhvdrMteeeahd"reSOcPrhrhtFaohialdan1dtud2,ciiRneoangrrn1gseg0sehdfn1eiedensoedstsmoetpnirrcoyrrrSrostoeifuedoscoy s
|
I
Msi
us to
deol, nl relGrenced 8 aed
subuit this information pursuant
oF
to
SEG Lo
Section (e) of TSch
| i|
and EPA's REGISTER,
statement Macch LG,
of interpretation 1978.
published
in
the
TI3ZRal
iHh I!
fFsounrpooacritcmdixTtouunrrmeacthioef1; 8KEhvoCemoOnltoow)s Which canorbeeeemrepssaer ]ny $a5e
ii
th
AFs eprrevioauslyListtatoedtoinnyoutraNovienmdbiecre.19tsuebmeissiion, oSeur smpiores
i ii
TulSihhpsiioascnbhdtohmnia,xrpteeuoLcbameltecLwrosfiubsuhhtaosavmebollceobagocosobunorsryorlabeisulcemacotvneaedctdiudatsnocoaraFrrlhdduoiorscryeuoarlcsabheceeenmstipleaystanttdec:rosnmamsmpheordmceeeicnsreeercrscoyud
ii
available and used us follows:
of
3 rand Pluocuchonical A-cid FC-26 Ecmaullssipfeiceirateayddiprcoidvuectfsn chests
.
(internacional marke: oniy)
Len
:
[EIDO79615
000101
:
i
i
i:
;
i: J: 3 1|i
|i1: :i. i;| 1ii |i !1i |! {i i
io
Document Control OFFicer
-2-
Hugeh db, iva.
"LUORA rind Fluocochemical
(aSmumrofnaicutmanctacbFoCx-y1l2a6tes)
Additive used fa chemical specials
products
FLUSOuReAfaDctaBnrtanFdC-F1l4u3orocheatcal
(ammonium carboxylates)
PEmruolcseisfsiienrg aunsdedaisnacnheaadteetailve 4a
chemical specialty products
CAtounvutey CRhoiamdol1i9t,eStp.eoPdauuclt,ionHNfa5c51i3l3i,ty,theloscautbejdectatchHeimgihcwaalys61areundmanHuufsahc:iizroesc otFromth sume aofcidlociamlployr-tepdeodfurcoemdouprerLluuroocpoeaalnkapnleanctaribnoxAynlcivecrpa,cidBselgaincca. CCihneetsmeoirlcniaiclteereenfatalccytiileioxtnyp.ooscecduArpsptrooixntihmaeasctuleboljsyeecdt sycshteemmio.fcalpsAeprpfdrluourxoiirnmogaatlpekrlaoyndeuc3t6ciaorenbmoprlay:oiysefetasees ate ue exporeed annually.
WJtehoeeopulsachnheautisoceasilnufa.onrdm/,oArtbyphraAotpcreistlsiinn1e,,g, wtephoowsteienltlciuassltuosmaseairrgsinziefaincdtahn3etMseeexmfppiolnsoduyireneegss fwoahnotchheGauvsseui,bi-ne our recommendations for handling and using these products. Ve sre by cans CRooifttAtmhdidrsistleitaotlnergianedfvonirsmtiansfgonaNIcOhSrdHcoaoocfnstahveasielanbelwe.prtealianm.inawreyatnerattoogeanvicisfinCdiongs.
IGuesvtiienwg aofndtmhoeniaccocruicuhgcdpprroeglraimnioauneyFluFoirnodcihnegasicaanlds,inthleinefowlilcohvinogur pornosgeriecss
is planned for the ammonium carboxylate mixture:
(1) A cocatopenicity seudy in cats. (2) & subsequent teratogenicit:y study in rabbits. (3) dCmeovnaetlionapueardl it;nodufsautnrdrcihaealrkhriyegdniuecgneePtrphorecoegesrxsapemossutworheiicmhp9rophvalevaenatnbdeseanrpeifoiyneees. SFbouirstientehcsesecptiuunbtflaoircmoafftiiltoehn.e, iwInenfoarrdmedaittpiiorononv,ipdriwonvegidheaadvesahdneeirlteeilcsneeddisvfecroronsmsiiotdnheeroefcdonCtchiiosdnefnTicdeieoanrlcsicl fsourbsitshesiopnucpionscconosfeqpueeonttcieatlinignftohrealartioprnivsauccyh.as the names of Ji espioyees
~
.
~
-
.
EID079616
=,
000102
Document Control Officer
=3~
March 20, 1621
Should additional correspondence be necessary on this matter, please contact:
LMaarnraygeMra,giKllegulatory Affairs Department
CNoMmmercial Chemicals Division
S3aMinCtenPtaeurl,, M22N3-655-501444 Telephone! 612/733-7062
.
Yours7 truly,
A "f4,a L
GGeroorugpeVLi.ceHPergegsident
:
Chemicals, Film & Allied Products
GLH:sue
Attachments
'
ce: APcatrikngLaDwinrecBtuoirl,dinNgIOSH
R5o6c0k0viFlilseh,erMsDLan2e0855
be: R. GJ.L DEawvairst/T.~ J2.20-Sc1h2o0uerman = 220-126
C.LVD.. GHraAnfsfoineh/=V.22C3.-6McCormick -- 220-2E
GLlLLG. HKergoggh --222203--163
JL..DP.L LLuadzferocred/k-. 2A2.5-5P8rokop = 236-1
WDIIR. PKeiacrkleseon= -53-2423-6
.
WEoLEF.l SKcioewhnle --2C2h3e-6molite
5FL.0A.L SUboerle/nDs.onE. -Ro2a2c0h-2
1| .
:
EIDO79617
-
:
000103
Report Number: sol
.
Date: March 12, 19
Oral Rangefinder Study of T-2998CoC in Pregnant Rats
\
[I
i!
conducted Ac
sostng rerio:
Study Director:
J
.
se. Fast, Himmesote samsacy 20, 1580 co Sanass 25, 198
.
:|
_ zhZyLw men2L/e E29S13t
iW.
`
2fossz%y
`
:
\
-
.
25
g
. . EIDO79618000104 N
. Introduction 1
:-
Tslhetivuesdlyorvofaals Tc-su2pn9og9ne8stoCironeCgd?erbfyorst3auMaCsruobmsmveaesqruceicnaotlndCourhcaetlmeidctaetloradtDeoiclvoaigrsyimoinns,etudStyth.e inPuaoupflea,tss.doseThe
Minanesota and vas coStn.ducPtaueld,byMintnheesoStaaf.etyThEevalsutautdyiownasLacboornadtuocrtye.d in
e
aPcrcoocreddaunrcees wfiotrhsutchhe a copy of the tinal
sStaufdeiteys.EvaTlhueatisotnorLaagbeorlaotcoartyi'osn fSotrandthaerdrOapwerdaattiangand report is maintained in the Safety Bvaluation
Laboratory's record archives.
Hothosn
.
RTiihnvideriresycB-rsriienxeidniatntigazleyL-ambaroteremadotvoeSrdpyrfavrgeourmee-Dtuahesweldsehyiipndepritinhvegedbstouxfdeeysm.albeyThAreantisaaanlifmraColamsreChvaerrsles
.
psetrasrotninneglatandthpelatcoepdanind dose groups by vertical
rwthooersk.riancgTkhdeoovfnr.actasgeLsvaetreferrohatohuetsheeSdtuldeifyntdiDvitoirdeurcatiolgrlhytasinsigned
A
htaenmgpiernagtusrteaiannldeshsumsitdeietlycacgoenstrowiltlhedwrioroem.meshPurfilnooarsLabaonrdatforroyntsChoiun na d
|
wTaitoenre/weesreen cayvcaliel:able ad Libitum. The lights vere on a 12 hour
||
hfoer Sanhinaosriaaasvecrheinioobastervseigdned:ailyBotfsrovmeidsaynts3 vtehrreougrhecodmaymen20onofdosveesta3scio01n
ih; e
c9ion.n1uG2to,arnnt15odioalnnedanv2do0laudowfa:ingoeifssttae5trmielod/nkdgaainlodfytbhboeydyorravatselldidnontst.eudbatTai-co2cn9o9rUdaCitencgdlovysaessweoSifungsp1ua5n0,ded
;i
g1e00s,tat7i5o,n.50 Aorco25ntnrgo/lkeg/rdoauyp otfo g6roruaptss orfece6ivreatdsononlydacyosrn6oitlhobuyghora1l5 of
iLI..
vikanistllueebxdaataibioynnecodenrviitmcheaedllsaadtmieesllyodacyatsto.iodnetOnearnmddianyeeac2h0ifouftteherguessa,tnaitmiainlocnlwuadtshiengprreaitgtsnsancwteo.rnetents,
i|
Bf0ee6ct6au0usTseResO0w0ti8wtoahnpdrteevr0ia6otBuoOsgTeROnt0ie1cr0a)tcohwlaiontgghyescshtienumdiitcehaselll( yensreolfaEtxtephdeercioemmyepeonutnadNsofse:vresfuelttuesdes in
ti e
waebrneormaallsiotiteask.en at day 20 of gestation and examined for sve
!
Bflrioocomsdtdhsoeasmepslaeamsnad rfaarttosmdoatnyhrec2e0ayorfa2t0sgeofsitnagteeiasoctnha.tidoonsL.eivegrrToheusppepwcleiamrsedmnsstasvkaeemnrpslebseafloasrned tatLkhieevner
specinens were frozen and submitted to the sponser:
t
Results and Discussion
|:
TSegh3eie/sgtRrhaosatttr/gisaaollanydi)uanrddiaoodnimicgnedciustsnrthorrerteeadeptoeibmorCeunirtloewtdosefteoainfTnd-1o2aar9nyg9ysa8nCdo6oegCaaetnnhadests.i91s5o0Af,(tdgoa1ex0ys0ist,c'a6te7i5fto,fhner5coi0tungtoohrfh1e52r5eo1dfm5ug0c/ekdg/bdoadyy
Te two nonpregnant 150 ma/ka/day rats had a mere severe effec on body 3
A
Expericent No. cssomools -
2 rc-1a3
in
EIDOT9619
2
.
000105
eFiivgehtoSinionfarfdyaayrei9nacoofcnotntihsneiednescrteaubdolyne dtahamaynosunt1th,eofp1r2evgeanlnagdnhtt13.haingdhThoendeospervaesgdnaamGnsbtie(rAdvpaempdsencotiofx
.
2He01]00.7T5i,ina50aannddsa25inmead/kwoe/idgahyt daotsecogmrpoaurpasbledidlenvoetlshatvoetahebno0rmmagl/xs/dar
Group.
.
IiFooiuiranrfeaasttyusehdseasdveesrygeraoucephxsaanmgifenoserdecyofernoscnihsaetnaigcnehgs.ooff AofLonLueroofdrammtsohereinreoftahdeatbhle1e50fofalenltdouvsie2ns5g: orei leas clofis, dark streak running one-half to thrse=marters of the
eSIvTeieoareeisa.tsitheecstantoeoclclouesrnyrsesaotfudindiiesstoher( gasanmiezedEloxcplaeetnrsiiomnefniatdseNsotsh:o(sTeab0cl6eb8s0s2T)rR.vOeGd0T8hienanldtehnes tuo
{.
EDCEriaauovyTiaomsa0sp1p0es)atruodeindesmc,ohreeatiheeparlotlneyvruanrtecolegadetneitdchaecnofmfipenocuttnhdvesa.psroTehveidoesuvbserloosrptsmuaedliniettsa.ileseyIenin thtehis
||
FaJEmoinvceiaotFaiilboientryss vofhfoircmthihnegapstpeheceaornsedadabrrytyoolnbeaenlsanlfeinavsrerrnesuotcfleitunhse,defvfeeotllaollpomwmeeindctlebuyosf.sethceoTnhdpearirsmyianrey
I
2msesraa}ceccarphological changes sceurred in this rangefinder study vita
conclusion
.
hrTeereaotebojleocgmtyhi/vsxetaurddoyfaywdaedsteesmreemtilneiivnneglthvainosuludpatpuebdrey.danoseTahpeplreavobeplorvieaftoerreshaunilgtohsradlsousgergateisnt 4chFaatt Cetatology study bucause of tha toxic effect of reduced bods weignt
-
eCfeiabntreoogdueconeoidsadidneittfaieoccnterotafototllheoengsytoasxbtinucdoyr.meaflf-ietcyt owfasrecdbusceerdvedbodayndweiisghltikeglayin,fotbhee
.
.
.
.-
3 .
[EID079620
3
.
000106
.
s
.
wie 1
Oral RaNngaenfinWSdoisetyrh NSStetaiungyahaorfGaai1one2sv9ioa9ft8iFo0rnesdinn(a3)PntreRmaatnst fats
.. _ :
-- e+ ax av 20
]|
Control
azze 714g 7251 a28se7
150 mg/kg/day
L"i1 aneEeE inen
100 mg/kg/day
SETS EAL 17 1m 88
75 mg/kg/day
WZhe atasl F21an1Ftava
:
40 ma/rasday
EwEae EaN a a
25 naka/ay
E wae zP a. ose
2 Significantly higher than the control (Bumett's test p <0.05)
:
.
.
| = seem 1
.
%
. :<
EIDO79621 0001 07 .
<
.
Table 2
Oral Rangefinder Study of T-2998CoC in Precmant Rats
|
Ratios of Fetuses with Eye Changes to Fetuses Examined--
\
High Dose Grow
Low pose Group
(150 mg/kg/day)
(25 mg/kg/day)
.
16/16
1/152
22FOonuerfeftoutsusensoteexxaammiinneeddfbreocmauesaecheyoef
four dams
architecture
destroyed
in
sectioning
A
.
0
-
:
z
0
= seems
t
EIDO79622
.
=
-
000108
v
.
CT A
A A 8
Oral Fangefinder StuAdyppoefndTi-x299I8C5C in Pregnanc Rats
s-
Individual Body Weishts () and Mean Body Weighcs
with Standard Deviation for Pregnant Rats
i-- 2
sR rer e e B
HA Gn
NK TIE as 223 204 zee wr se
NLR 347 dm 214 228 20 292 7h
NNiIkK 33d13 2A6m7r L2A3? Looev Z29s% s2eBu sZees
NR 346 190 231 257 280 211i 269
VERN 130 20 Zar zea zs: ues
SNIOANN.FRDEEGHVAN,7.7F1T0.L311510.5115 3.2
WK SE A80 m osm ay ae ze
.
S - vii nw emt.
150 EAGAN
.
otoiiwkr ISain Iuunvz: i2aeass Zsmibs fao0sar sduaessi wideuanr
GR aT es Zi: zee ee Zre Ie
NSTOAMNMPERAENOGENVAN4T1%3P01r 72.154E aZese 725% a2b6a7 b3d81 Gomi 3x2a lderl ezmye 6awhe adwoee A2ha 2z4e
*_
--_ oeemm--------
Ce See
>
EID079623
me. 000108
oral RangefinderApSpteunddyixofIT-(2C9o9n8tiCnGuCedi)n Pragnane Rats
:
IndiiviinduaSltaBnoddayrdWeDiegvhitastio(ng) foafndPMreeagnnaBnotdyRaWtesights
EE .
-- Te_-- vl 1 e my w --
RTT
.-
VUPaiknri332h6 TED
M4e8Ar4
18oL8wL53n
26ae1sw6
Z2ms0aee9v
z2uae5esss
o3wa2nmz?e
:
tpinn Fig ieees ifirs 2si zeefi 26s J7o1s
.
THEnewOV Ss5e5x 7z1a%z 2z0474 2206.s6 14H.e5r 34685
A Say Tes =z mw
75 MGAKG/DHY
-
"
-
.
wtakk w3m3 aIsEe zZai zZzi 2aeeys e2wh adaes
`
G(PGiioarbrf
33333a as
AZraPela2e
GYeu:s 2a
z2tEa1eiSesi
2Z3eSni 268
EGrIe 2
e34e8 Zar
Wemn asa zm zw aus ovr Bad
.
STAN LEY dow 4401 12 2 424 10d Luu
`
z
t
=
mem
.
EID079624
.
000110
: Appendix I (Concluded) a
Oral Rangefinder Study of T-2998CoC in Pregnant Rats
\
IndwiivtihduaSltaBnoddayrdWeDiecvhitastio(n5) faonrdPraeagnnanBtodyRatWseights
L
-- S65 e 12 y 1 ww
S00 HGKGARY
Je
RRIiRk. 332367 148737 22011% zziis: 223053 2257%6 imea
1
RRiikk RIR
3333s% 212766 21u91% 226125 226337 a29a4 eJuTb 348 187 226 245 Zev sea 376
KIR 350 192 223 242 276 Tew lor
A
STH.WEANDEV 1495.14 1Z5v.i6 182.326 202.415 22e. s2 35s.y6
Ss ewws 12 iv aw
A
25 MGAKG/DRY
.
SSiikk 3a4z3 u21v5 2z3i54 zeaep 228735 3T0o4a 3z8o%r
SSIiRk 3344a5 12080 220185 z22373 224585 22972a 336498
[le
Sik 3u1 my 233 238 268 307 3%
|!
STAMNENDEV 121.043 1Z22% 125.443 1256.82 15w.ey3 123.04
I
:
wo
NON PREGHANT ANIMALS SIR 341 137 203 215 220 228 238
= rem
Zia
-
7
.
}
3
8
EIDO79625
000111
`pistRIBUTION LIST
.
E. G. Gorter (original + 1)
E. G. Lamprecht
R.A. Nelson + M. T. Case
W. C. McCormick + F. D. Griffith = P. A. Ubel (5)
2
i
.
:
|
.
EID079626
|
000112