Document zzkK0eMMmK7N3kgodk1oYjKY0
.. HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE
TrehGe Li apts cc: G. Kennedy
W. Krauss
TFor:on:ChaGrrleegsSyRkeeisn,harVdHtD,GSM.p
october 29, 1987
AR226-1717
Two-YeaFrluToorxoicchietmyi/caClarcFiCn-o1g4e3niicnitRyatsStudy of
studyIchoanvdeuctreedviebwyedthethe34paCtohmopalnoygyanpdorthiaovnesseofvertahle ccohmrmoeninctsrartegarding their findings.
the noIn-anmeoipnlaesstsiecntifailndianggrseemgeinvtenwiitnhthtehereipnotretr.pretSapteciiofnicoaflly, "theeystionicdredaesgeedneirnactiidoenn"ceaonfd hneepcartoiscis"wmaesgaclloecyatroseivsi"d,ncveacuooflahteipoant,ic mpehtoaspbhoaltiassme,andasptaorxtiactiety.aminThoetraenlsefveatriaosne aofndsearluamninaelkaalmiinneotransferase linesmioanlse. ratTshe (a30bseanndce30o0f peplme)vatceodrrehleaptaetdicwietnhzymtehseseinhitshteolfoegmiaclaels reflected the relatively less severe liver lesions in this sex. patholTohgeirsetap(pR.earGseilt)o ahnadvethbeeenstusdoymedidriescatgorreem(eL.ntSbibeitnwsekein) twhiethstudy Trheegarpdasthotloogtyhereipnotretrpdreestcartiiboendofthesomselioghtthleyr ninocnr-enaesoepdlasitniccidelnecseions. ohfypeardprelnaasliano(d30ulaarndhy3p00erppplmasifaema(l3e0s0) ppams m"asleecso)ndaarndilyovacroimpaonuntdubular ernedloatgeedn,ousprosbtaebrloiydst"h.rougWhhiltehe I FtCe-n1d43toalategrreede wliitvhertmheitsabolism of eifnfteecrtpsretaasti"oenq,uivtohcealS"tudwaysdinrotectuonrre'assocnhaabrlaec.terization of these carcinAollmasofantdhethheepaitniccidennecoepla(smmasleso:bse3r,v1e,5d; infemtahliess:stu0d,y0,1w)e*redid n(omtaleasp:pea1r,0,t2o; befedmoalsee: r0e,l0a,t3e)d*. waTshesliingchitdelnyceinocfreansoeddu,larthohuygpherpnlotasia esftfaetcits,ticiafllrye.al, AswasinadicsaetqeudelainOfthethereploirvte,r dtehgisenehryapteiropnlasrtaitcher atlhtaenraatipornes-ne(obpalsaospthiilcicc,hanegoes.inopThheiliicncianddencveacoufolahteepda)tocayltseo did not suggest a pre-neoplastic effect. * 0 ppm (Control), 30 ppm and 300 ppm, respectively page 1 of 6
3
consiAdelrtehdougtho tbehecsatrucdiynogreenpiocrt icnontchleudreadt" th(aptage"FC2-51),43 itis fnaoitled ptoathaodleoqguyaterleyporetxpl(apiangeth1e23)f:ollowing statements from the appended
- i"Inncidfeenmcaele inratmsa,mmatrhyerefiwbarsoadaensotmaatsistaticatlhley 3s00ignpipfmiclaenvtel.i"ncreased - r"eIlnatmeadleocrcatusr,rentcheereofwabseniagnstaLteiydsitgicaclellly tsuimgonrisficoafntt,hecotmepsotuensd
at the 300 ppm level."
to
Although be applied
it to
wtahseseapptruomoprrsi,atetheforrehfiesrteonrciecsalcitiendcidiennctehedasttaudy
rIephoarvte waeprpeendweedak.the Icnonotrrdoelr tioncisduepnpcleemednatta tdheeripvuebdlisfhreodm lHaistkeerlalture,
LB)a.borTahtiosryh'isstmoorsictalrecdeantta 1i3nclcuhdreosnic954ratmalsetudaineds94(7ApfpeemnadliecesCrAl:CanDd
tSeprrmaignuael-lDyawlseaycrirfaitscedwhiucnhtilwer2eyeatarsleaosftag1e.year of age but not
the nuImnbetrheofcasreatsofamsamtmhaerydentoummiornsa,tori,t risatmhoerre thraenalitshetictistosueuse nuunmdbeevre,lopseidnceorunaetxraompihnieedd mgalmanmda.ry gTlheandinucisdueanlcley oifndifciabtreosadenomas 4(2u8s)i*ngce50rtariantlsyassutghgeestdeednomaincaotmopro)undinrtehleateFdC-1e4f3fecstt.udyIn(20i%t,s a3r8%g,ument aofgaifnisbtroasducehnomaansefifnectth,e htihegh-sdtousdey rfeepmoarltesst.a.t.e..s wtahsat si"mtihelarintcoidence Tthheat Prreepjoeratnedreffeorrenucnet,reahtoewdevearg,ingreproatrsted(Parnejeiannc,ideetnceal.of13o7n3ly)."24% 1f8i1brofaedmeanloemarsa:ts,Inanadnytchaesye,werseincteermthienalPlryejesaancrisftiucdeyd iantclu1d8e-dmonotnhlsy, miatmmwaasryantumionrapdpartoapriiastecomhpiasrteodrictaol HraesfkeerlelncLea.borafthoenry'tshehiFsCt-o14r3ical croenltartoeldsef(fAepcptend(i4x2%C)v,s. th37e%re [dpo=e0s.3)n)o.t appear to be any compound
was aTlhseo siungcgreeassteidveinofcidaenccoempooufndLeyedfifgectc.ellThaedensotmuadsy r(0e%p,ort48,cit1e4d8)* ntowromarlefberaecnkcgersounidn iitnscicdeonncteentoifonLeytdhiagt c1e4l%lwatsumoirnsliinneSwpirtahguet-hDeawley rcaotnss.ideTrhiengfirtshte rsmeaflelrenncuembe(rAnvoefr,raetts a(l9.6)), watsheofmulltiitptllee vsaalcureifices, oalnddertheratdsura(t2i4o-n38omfontthhessotfudyage()38 fmoorntchosmpaofrisaogne).withThetheuseFC-o1f43the snotudLyeydriagtstu(m1o3r-s25wmeornethosbseorfveadge)inistheque1s2t-i23onambolnet,h oelsdpecriaatlsly(0s/2i8n)c.e The second reference (Hazleton Laboratories) was stated as
*'0 ppm (Control), 30 ppm and 300 ppm, respectively page 2 of 6
documentation latter figure
of is
da raLmeyadtiigcaclellyl ditfufmeorrenitncifdreonmceourof ow2n8.7e8x.periTehnicse
and
wPaartrhaonltosgysoDmeeparstkmeepntti,cissma.ys tInhatfactth,eirSid198J4oneisn,cidcehniceef dofatatheshoRwaezdleton
2a-2L4e8ydiign cienldlivitduumaolr sitnucdiideesn.ce oOfur1o08wn (h3i0s/1t9o8r)i,calwitdhataa r(aAnpgpeendoifx B),
dCeommopnasrtirngatetshisantointchiedenFcCe-14O3f L6.e1y%dig(5c8e/l95l4)tuwmiotrh iancirdaengneceof(A1p-p1e2n%d,ix
hC)ighs-hdoowsseagrsotuaptis(t3i00calplpym).signCiofmibciannitngitnhcereaHsaeske(lpl=0.a0n4d) Hainzlettheon data
d(i8f8f/e11r5e2n)t gfirvoemsthaen FiCn-c1i4d3enciencoifden7c.e6%,ofwh1i4c%h (ips=0.n0o9t).statistically
In conclusion, study report failed
it to
is my opinion that adequately address
the the
FC-143 chronic possibility of
rat either
mdaimdmanroyt gilnacnldudoeraLceoyndicgluscieolnl wchaerrcienotgheenepsaitsh.ologThiestpcaltehaolrolgyystraetpeodrt
hIinsadidnitteiropnr,etatthieonauotfhortheofbitohelogsitcuadly stiexgtnifdiicdanncoet oafpplhyisapfpirndoipnrgisa.te
hItistsohroiucladl bedamteanttioonreedfuttehatthereliimapblliecathiiosntsoriocfalthedatpaathfoolrogcyhrorneipcort.
LroadbeonrtatosrtyudideastahawsasgennoteraalvlayilanboltebeteonRipkuebrlisLhaebdoraatnodryt.hat the Haskell
evidenBcaesedthaotn oFuCr-14e3xperreiseunlcteedatinHaanskeilnlcreLaasbeoraitnorayn,y ttyhpeereofisranto mammary tumor.
incideTnhcee eofffecLteydoifg a ceclhlrontiucmorosralis exsptoilslureunctloea3r00 anpdpmmiognhtthebe caopnptrrooplrsiataendlythteermHeadskeelqluivhoicsatlo.ricaClompcaornetdroltodabtoat,h athe14%stuidnycidence nison-snuesoppicliaosutsi,c epfafretcitcsulanroltyed ipnrelviigohutsloyf. theAlptohsosugihbleI psteerrsooinda-lrleylated tbheelieevveidetnhcaet itshenoLteygdriegatcelelnoutguhmortso abreedepfrionbiatbilvye.compIouwnoduldrelated, appreciate the opportunity to review the testes on this study.
Jones, (Haskell
L(aHbasz.l)e.tonOctLoabbse.r).20,Tel1e98p7h.one
conversation
with
C.
Keenan
WPeriesjbeuarngegrD, JHP.ecSkhpaomntaJnC,eouCsasTeuymoArE,s iGnrisSwporladgueDP-,DawWleeiysbuRratgseranEdK Sanwdiss Mice. Cancer Research 33:2768-2773 (1973).
LAensvieornsMR,inCoBhaernrieBJr,-ReLaartetduadMaaleCPSapnrdaguFeo-sDtaerwleSJy. RaAtgse.-AsEsxopceiraitmeendtal Aging Research 8:3-24 (1982).
page 3 of 6
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