Document LJMy5ngKjdawkvMo9yDqvqNkq
t
DuPont Haskell Laboratory
AR226-3372
January 9,1997
HAZARD CHARACTERIZATION FOR HUMAN HEALTH C8EXPOSURE CAS REGISTRY NO. 3825-26-1
Prepared by: LSe. nBi.oBr Rieegseela,rPchh.DTo. xicologist
1
HAZARD CHARCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
. Table of Contents INTRODUCTION....... ................................................. I. 1M.11.A.1M.AMcau.AteALTcIAuotxNeicOTitOryaXlSTItCuodxOiiecLsiOt.y..G......Y.............................................................................................
121111....-111lS....cdeu...bbAAAc.hcccAruuuottctneeeuicIIOtnenTchjDeuoacelxlatariirmotciTinotaynolTxTSToitocoxuixxitdcyiiiicc.et.iiy.stt.yy...................................................................................................................................................
ZZZZZZZIZZZZZZZZVInIVE..0HHHL1HL1...1.ME5364II..11L2...l....23P1....2E22CM...IMRDC...DAHTCbLIIehEe..unnAIEunIpvraCnNtvvomSiSMre.aBmveeHonluIguaeoOssSCdiIbaebAncsttpOuuliinAcLctggmNTiEbchShiLgILaactcroSxrIteiaOttiouhoSviixtnpMRtooynrdnieMGitoooncEna.iiiT..sccennYil..SPuto..osoiDT.y.IoOr.c...fOfnx....eo.e...faCCORh.i....Fr.x..n.cC..a....m88Tr...i.i.dl.A...8.tacssa.S....ya*....lsO.i't.C....tl.i.'...T.EEyO.o.....nT.T...E....on.ff....Fc.......oIff..f.x....o..OeeT.f....x..H....i.eccg.......ci.o.N.....ctt..Uce....i...x.t...tooi..n.....y..M.ti.o...nn...yi.c.......c...n.....i....dtA.....it....h.....t..yT..i.....y....N....e.e..........e.................P.....sL......E...........t.....a......ii.....X......c....v.n.................u.....ae..P................l....rr......O.....a..e..................r......a......S................sL..............U..................e.......................R..y..........................d.......E.................i.............g........................................C.........................................e............................l.............l...............s..............................................................................................................................................................................................................................................................^.........................................................................................................22222..j21.1.1111o12023090.3533. ZZZZZZVIV. DI.1IS. CDUisScSuIsOsiNonOoFfTEaNrgDePt OOIrNgaTnSs..........................................................................................................................................2233
VIVVI.LLV23SI...U3DT.Maui.sMmcSuoAisgrRssniAioYfnis.c.so.ao.n.f.c.cDi.a.e.it.foe.f.d.ef..rCw.e..Sn.i.fc-.eI.en.sC.d..iu8.n.c.i.eSn..d.pf..eeR..ce.oi.Re.d.s.ea.-.nSt...t.p...T..e..u.c...im..f....i..oc....r..S..t..oe....n..H..s....iu..t..im..v....i..a..tn..i..e..R.s.....i..s...k............................................~..............................22224454
Z!REFERENCES............................... ............................................................................" 27
2
HAZARD CHARACTERIZATION FOR HUMAN HEALTH C8 EXPOSURE CAS REGISTRY NO. 3825-26-1
INTRODUCTION dkiosntnofrgoacfrouiwegemdhnsiteetaT-nuncshtdhtaitiiashmenisednmFodcpCciohesu-nerc1mfmiulu4usem3isocnearFtpdoliLecswaUraacfirlOltbulHuooRbaaxrleAzloyyaroDlerticdceftBesaaCrtnrcreaheoidnddaadsfrttoaeocFce(otlaApuensrroFtioaCrzPidoan8Oucti.ihnc;oteHgCnmFaoAoCpiwfcSp1aCer4#lvo83Sex3,frui8w,omr2irfht5aahiict-csue2thamla6ynci-ast1k9.n)n3aWho.am0enw-aiid9txllhe7tithdisu.n0.grf%eoteChdeoi8Csptfhir8ssiae.mtvamelasrroaaynl y I. MAMMALIAN TOXICOLOGY 1.1. Acute Toxicity Studies
1.1. a. Acute Oral Toxicity Numerous acute oral toxicity studies, in several species (rats, mice, guinea pigs, hrdaaotvsgesp)br,oehdeaunvceceobdnenseionstcceloninntidicnuactlhtseeidgirnwrseitsohuflCttos8x. i(Acsiedteym.TianSbitsultedrai1et-is1o)dn.eoTmfhoaensrsietnrsagutleletstdhooasftetnhoeewfv1ba2orirmonugas/nksdgtuotdolide3esr wlaaeodrnhselusaimll.rtegroCmeard8teisclisaiesevpncaeponsreisndta,isvrreiadetloetestvrhbeaaaedptnipomtomenoashirrcoeatevofsoeelbinrvmesreaioerttqidsevue.nerazIatlynhltyemafonaseecewlnuerstaeveiatte,ionlvasrleic,anulgtgottaeossfxatoorinreocadiialntycyetue.oxstupetniontgsoauxalridiecrurigtilyttesan.oteiofArCandl,8ldya,ingtrieduosnwiunaleeltlisaygip,hnitgs ccchpdtwroohyoreaenmedsat-midtertnpmorurgieacccfearhoatwIentenllmrdtsodit1wartehowo4idndriDdthdterdhaiiwaortcdteyiuwshooitsgthenedh)isansxom.tenvonstoPeeohotldsrdhat1te(n-ieirwa-fgXeotinaressil2teutuishdena-mlfCditgtCodmeil1etn8ernheoIedoeanaouflonttnfeosaesofnaEseclffltetetxteuors.ecacrdfrtohAtsaCi6sefato08iswCnso%f'tglns8uiiCetsdehooot8Ryfenrpffdaeewafhlloscibovai1etennns5eolLoe%oracnbDowtwoalrna15i,erv0qd0obisegu0uonietreh0cvafaotttelCome.nursdTi8asobgmlhtdo(/sook4aiiodsulgt7dlyshmus8ereptwtetuirmerdoodeesrunrmg-ityguecp/(kdxhiedrvnogdpeti/eevtra)ofeas.d)iosrtfweimiiePfonpderemsirnedtnr.eoeoreoidronrtatkpthhlioineatsyrgtt
3
HAZARD CHARCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
Table 1-1
SUMMARY OF ACUTE ORAL TOXICITY STUDIES WITH C8
STtyupdey Species
ALD Rat
# / sex/dose
10 Males
(mDgo/skeg)
200,480,670
Vehicle
Com oil
Rmegs/uklgts
480
Reference
HL-65-81
LD Rat ALD Rat
1 Male 1 Male
'i , 12,40, 20, WO',30, 45, 70, i, 1500,22S0
1.0,
1.350,2.1.7,03..240,50..13
,2'6, 40*,6, 11,90,
00,450.670,2250
12&,
Water .................................. 1570................................. HD55-61 Water .................................m ................................. ' T3kI28-SB
LJ0 LDjo oLfDajgoeas a function
Rat Rat Rat
5 0
1100WWeeaannlilninggfemmaaleless 1100YMoautnugreaadduultltfemmaaleless 101M010NaNteuwerwebbaodornurnlftemfmeamalelaeslses
i, 215,464; I0, 25 200",4,45, 5, 67, I'OOO ...............
CAocmetoonile((4690%%)) Coin off
350,400,450.525,670,710 350.400.450.670
2 0 0 ,2 4305,300.402,355.500,400.607,500 0 ,7 2 0 1 3202,250, 305,204,400,208, 405,303,607,307 0
130,180,200,220,240,280,320
Com oil
Males: 680 Females: "430 Males: 470 Females: 482
557830 435336 343 224538
(1G9r8i0f)fHithDa2n9d5L-8ong, ' ' HD788-82
intact adults
1100inintatacct tfemmaaleless 1100oovicahriiedcetcotmomiziezdcdfemmaalleess
10 males
220000..448800..667700 220000..448800..667700
Com oil Com oil
439 491 445090 478 .............................
HD6&-8 * HD-567-8f
LD5O Hazleton Laboratory
LDjo
Com oil
4sf .................. HD329-8
function
3 Males
Not slated
nLEoelertmhvaaaltleaidzte4Od5Pw6Timtahgnin/dkGIgwbOeyTe4kw8ahhtio2chu0r0s'mg/kg
H L 123-65 .........
Ll/jo a).
W eGauninlienagPi-g2 l-daya old
b).
Ylooung a...d...u...l.t..=. . 8-1 0
weeksISoOl,d20Dc,)2. 5M0,3a0t0u',re4(5a6d, u70lt-
>
1
0
weeks
oCldomd
oil ).
Newb...o...r.n....-...<M
2a
T ran'/r'p days ol
im d
a
iM
iaY
............
flU29l-8f *
4
HAZARD CHARCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
Ll.b. Acute Dermal Toxicity
mrcw(7aaarond5abeondd0btbddi0brateiuaitinmrotbcaadsntAbngte/eooitd/dctloknrsyuiwglsndyitt)tenoie)agt,xrdhiremnleieancCesrbaepdmb8loroy.pairarnelelrtCsdthrithetio8eabnexttreiodiiseeoacefaClncirfttmoeah8yscrnieaeenatsvlsaxngierd,pwdor(ecoaruierysarlertarubeecdinrtblomeaiotino.ttfsisoiioebcTsroxnaeeh(nplrpmseloastysribusoieg)ulbd,ndnoriiaoesteb-nsu.ssomdnoeiRfncnrcotveaolhdryadtxare)tostiii,rskocnmadiinattminoeysanldrsdyaiwrahnlhriecoceraesrlwrrbyauiettobedh(aodrrieattfabidnshnlbseehbgeibsnaarositvtvod(fsiereeryadtormhbtiwnstieeaanleeayltseiibnt)kogs,oi.nhlntethIttalhnhornaaasdntrssg, y
Table 1-2 SUMMARY OF ACUTE DERMAL TOXICITY/IRRITATION STUDIES WITH C8
STLtDyupdsoey Skin ALbDssoorption Skin ALbDssooiptian
LDso
Species Rat Rat
Rat
Rabbit
Rabbit
#/sex/dose 5
5 Females
5 Females
(25aMt 7a5le0s0) 4
50300(00mD70a5gon,05/sdk00eg70)500,0
5000 and 7500
15500000,,37050000, 100,1000,2000
Results FeMmaaMLlleeDiLLl5dDoD>sS5k7o0i5=n=06i0>r9r7m5i5t9ag0t/m0ikogmgn/gk/gkg
MLDil5dO>sk7i5n0i0rrmitagt/ikogn LDso=4278 mg/kg
430//44/L4aaeatttht21a100l000000
Reference (KeHHnLLn--e66d58y92,--17899085)
HL-682-80
(KeHnLn-e6d5y9,-179985) R i0k9eR7re9Lp0aoAbroBt Nr0a4oto8. r5ies
Skin Irritation Rabbit Skin Irritation Rabbit
6 6 Males
a5n0d0ambgraodnedinstiatecst
Non-irritating
(1G98ri0f)fith and Long,
500 mg
SMligilhdt--mmooddeerraatteeirirrriittaattiioonnaatt2448hhoouurrss
HL^636-79
I.l.c. Acute Ocular Toxicity mbeomdeordaeEteryacetoeilmryrieitraarltiitooapntianscgtiutytdo,ieitrshiteiinse,ryaaebn.bdIinctsoshtnialjluvaneticbotienveiontifscs.ooTnlidhdueCcste8eodincwtuoliatrhrabeCfb8fie.tceCtys8egsirsapdcrouodanulslciydeedred to rreacpeidderedcoovveerryti.mIen. aPdrdoimtiopnt wtoatshheinegyeoifrtrhiteaetiyoenrsetduudcieesdtthhaetehfafveectbseaenndcpornodvuidcetedda, rmatosre
5
HAZARD CHARCAACSTREREGIZIASTTRIOYNNFOO.E3-8H2U5-M26A-1N HEALTH C8 EXPOSURE
ewxhpiochsewdetoreCm8icdruorsincogpaic4a-lhlyouerviindheanlta4ti2ondapyesripoodste-xexhpiboisteudrec.orneal opacity and ulceration,
Table 1-3
SUMMARY OFEYE IRRITATION STUDIES WITH C8
Species
#/sex/dose
Dose
Results
Reference
Rabbit Rabbit
(11uwnwa2sahsehde)d, 66uwnwasahsheded
(3Imd8.g3)____WUWU_n_anwas_wAAAsha_heasttt_Aedhs271_dhete14_edd7ey-_dday2MNMMCMMeSSe_dyaMe8CCI4eyll_aooysriiyo/ooiieioggyod_m6lrlsotedddddmhhnsia_ndseeeeeyttjv_jcae--uryrruaso_ammaaalrnelnsatn_ttsoceeeccoot_jet-tpwuuddicii_srvvaniloeeei_eraicitrrcvnrtrt_iraaiiiiteseijtssi_tttzuyvraeef_aentracc_iteclciooo_oetroniern_nvrondj_niuefnt_einaiesa_rlcsrl_otisoit_pvap_aitati_ciocsi_ntiy_ty_
._______H__L_-_63;_5_-7_9_____ .
BioseaNrcoh.,TIn13c9. R5 eport (Griffit1h9a8n0d) Long,
1.1.d. Acute Inhalation Toxicity hel0si4nehx2i.8tgcoph3drhwoaeaemlsaeyrusc,dsgeroAaedpc/nlLcolotclourmisCevattnCe-tee8estar8i,rx-naldrtpbahtooiioeytao-psdsblnaiauenocwtr(xhdiiAeotpiay.ytnLehlwaAariCtitnnoeied)odxni4dginic8ncichetioiihtsrdtorayrorcnaatouosstansirtnloousiliosyndfoiwn,dii0te.faehi.se8alrilxlceimrnpdhwaogrtrtesosae/iuLttgesbur.hxerehtpn.AahloeovAitdsgseectshtdoboclfneyototoecnhltneloce0onxec.wh8tnioric1aitgnnr,thadmiwgotuiegneiocntx/sthnLdeposdaooCbfs4wf2e8u-tt.ihrh2watehoenmeaudnCenrgonh8da/riL.0pmga.pnAh3Care8loc8rruxaaatninenmdgdaete
6
HAZARD CHARCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOS' URE
Table 1-4
SUMMARY OFACUTE INHALATION STUDIES WITH C8
Species Rat
#/sex/dose 6 Males
0.384,0-h.C8oo1an,r(0mce.ex8gnp3/tLor,a2s)tui2oren,4to.8: ,5.7
Results Reference 4-hLouCrA=L0C.9=80m.8gm/Lg/L (KennHedLy-,1e6t0a-l6,91986)
Rat
5
1-hourexposure to:18.6 mg/L Eye aNinrorditdraeetsaiopthnirsatory
(Griffit1h9a8n0d) Long,
I.l.e. Acute Ejection Toxicity in miceA(3cMut,e1to9x7i9c)i.tyTohfeCL8Dw50hbeyn iandtmrapineirsitteorneedablyinijnetcrtaipoenriitnomneiacleiinsje1c9t2iomn wg/kasg.assessed
1.2. Subchronic Toxicity Studies I.2.a. Subchronic Oral Toxicity
miasdentnnauodziadlnylymilkmegsesipeaycNhesesaatc)ucrav,iimtnehceisvdaebiivsnrtaeotyettueuu,b3ndbshe0iaqeesetpdumuinoaibitgcntsceo/ohkptccnhrgreoodeo/lnnduldlusiaicucivlytsaceeotreedfrrodh.nawrytldCmpitienot8ehaoxrttpnthChirrckeoo8aieiptdtryy(huscrsyseeoc.ts,eenuuTascdTlnheiitandesneb.csthprlrieAaeerntiap1imdssoa-mee5ntaivd)srci.eynlopriTitavsefahltrerr1oesrga0pxtwer0ieieot0secsonoiiupgremolgpshtasfemt(nsCrop,aa8frfitnoonstihdl,rcnimerfthoeetvhiiarxgcaaesiehtrecidi,edooriareneulnsfi.tsdvopoerorrrnbasytess wSehcitcihoninIInvIIea.sdtMdigitaeitcoehndatntohisetmhmesenocufhmAanecritsoimounso.sftuadciteiosnliostfeCd8b.elTowhe,soetshteurdsiteusdaieres swuemremcaornizdeudcitned
7
HAZARD CHARCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
Study Type Species 14-day feeding Mice
14-day feeding Mice
21-day feeding Mice 14-day feeding Mice
9-dose gavage Mice
Wrwr11ee44cicit--oothddhvvaaaaeeyyrr25yyff-ee6wppeedeeddearreiiiinnykooggdd
Rat Rat
Rat
Table 1-5
SUMMARY OF SUBCHRONIC ORAL TOXICITY STUDIES WITH C8
#/sex/dose 5
10,30,(p1p0m0C,3uo0nn0lce,esn1st0rsa0pt0eioc,3nif0ie0d0), 10000
Results w10e0ig%htm/boordtyalwityeiagth>t3r0at0io0;adte>a1th0s at 1000; increased liver
Reference HL 560-81
5
30,300,3000
>10300%0 mincorretaalsietyd alitv3e0r0w0e;igdheta/bthosdaytw30e0ig;hwteraigtihotsloasts>a3t0 (KenHnLe1d2y-,812987)
5 6,0.0!, 0.03,0.i, 0.3', 1,3,10,30 Significantly increased liver weight at 30
(KeHnLne3d2y3,-189287)
5
30
IwnpnorhocnerdaenudacCeseec8ddafwlliuavosercroowdmeecibgainhnote;idcwacitihd,aanseiqmuialal raemffoeucnttwoafs
HL 537-82
5
0.1,1.0,10 mg/kg
WweeiigghhttaltosIsa,nddea1th0 ming1/k0gmg/kg females, increased liver
HL 138-83
5
0.1,1.0,10 mg/kg
Weight loss, increased liver weight in 10 mg/kg males
6 Males
25% TdeifslpoenrsinwgitahgeCn8t as the pSelirgiohdtly increased liver weights following the recovery
HL 56-61
5 Males
30,300
Drtfhelueceocoerrvneideadresyoeldedfvatbheyoelssdf7yoeeuawdntietdnoigg2rh8eptcse(o3raiv0ote03dr0ypa0ptd;m3ai0ynoc7anrnel(ydafi;sn3ee0adlel0lvdiavaantyeedrdtewobsnetleoigdoh)dts at
HL 326-95
8
HAZARD CIHARCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
Study Type Species 28-day feeding Rat
Mice
90-day feeding Rat
90-day gavage Monkey
w90it-hrdepaaceynorvif8oee-derwdyienegk
Rat
Table 1-5 (Con't)
SUMMARY OF SUBCHRONIC ORAL TOXICITY STUDIES WITH C8
(#/seSx5e/xdose)
30, 1(0p0p,m3C0uo0nn,13lce00es0n0s0t0rs0a,p3tei0oc0nif0ie,1d)0000,
Results w1100e00ig0%htamrnaodtriot3as0li0atyt0>afto3>r0f3ef0om0ra0ml;easdl;eeisncracenraedsae>sde3db0ol0idvfyeorwrwfeeeimgighahtlste/bsaotd>y
5
30,100,300,130000000,3000,10000,
w3p10a0en00igl0%oh;btimsunlcaoartrret>aadsli3ifet0fydu;aslcietyv>haenyr1opw0se0eirsi0tgr;aohdnpted/hbaymothdousyfsachwtlee>epiwag3the0oat;ckrdyanteteecisosrsesaaastte>>d
body 30;
5
10,30,100,300, 1000
Daahflttiueg>>ochrr3e1eid0r0aec00seo0;cdnpowcabnenioctnlhedotnyrmbatruwtaailoltaeeinriosgsdnmhioiftnsbfoucsraseerteera>vahfsef3yeed0pdci0etn7er;5tdmirnottacohplrahee2nsya2sf6oeefdfmohlaleidvlpeewasrt;oiwstcheeyriutgemshts
2
3,10,30,100 mg/kg/day
dmf1le0ugc0o/r%kreiganm/sedeaodleyrvbt;aeodlldiostyys(enwaodtee>aipgpe1hpn0tasd0ra;eetndn>tet aisn3ethc0xsr;edanaitofsf>eessri3gei0nnncs(sfeeoe)rmfutmoalxeaisncoidtnylliayvt)e;3r
55 Males
1,10,30, i00
RopTthtawfheofxaeehseefllpidletemrdooa8ecuaNwstticoswsteteOoeliecdinerdygeAaogebllhbcnklyECtuttosehliLldyovdaeoaAiiyr=enetfryhlewtdreoaecy1avrlexco0puytaiio0vge>tdteiveerhpeatxed3rnsrpyapro0eimaytozppata;is1h;encni1u0rtnytgd0hri0icoeva0e;htrdirtteipotNao.n>yaprncOsmCSrmsr1eeeieE80doetarau,Lnnuwlstwrieetmvn=whdilheeneieecid1rpcvlesherwpaettkeoriplweeaans5smnisdraw.tgeioristhoasroertdmlraeys,eivtioaa'nCel1nlro0aoldset;fAivtbeelrels
Reference (LGornifgf,it1h9a8n0d)
(Perkins, 1992)
9
HAZARD CHARACTERIZATION FOR HOMAN HEALTH C8 EXPOSURE CAS REGISTRY NO. 3825-26-1
I.2.b. Subchronic Inhalation Toxicity bi(7niondjdudayriyycwsa, tfaeSionviiglmdelhoopitwl,aafiittrnnhhtcgoeorleipotnahrghseeieascoedlaanrlltacliiloevetsneooiroexfwxniCcpsei8oitigyn)shudsttrhetseute,.edilrniimevcseri,enri.aensdhMeatsheliaaanttsioupthrnlaeeesmbmxlepoanootesdonuhzfreytahmltfoe-eblCislfo8einopoddrfiocfCdalu8utiocvirneeisdtoehrfeelldeirvuvaceetelrisds 5
Table 1-6
SUMMARY OF SUBCHRONIC INHALATIONTOXICITY STUDIES WITH C8 IN THE RAT
Study Type w1i0rtheecaxop4vo2esr-uydraey
(#/seS2xe0/xdose)
Concentration f1o1r,863homugr/sm/d*ay
DorT4ifeoneof2ffhocfdlbhleeosdioocecevaKwtpadyerstvaeyirsiwntvyelowaogreeptcefeertoeyfherdirftegfeeieocdlohscilboedvt;atsvscmiseeanerwtrretcraeviya8erinxenes.r3jpdeaetu;ao(.sRrinmiiensynnoeudcegbpstrrdl/ueorokeie;lvd(bagtshgseyss)eierrernwadirwntnvepugueeilpigdlatgahhstahroemtftd,st42seea,2u8grne-peon1ddpnzaa4oreyyye,cr3mssau2stleii,aoosornnr
Reference HL 253-79
d1wa0yitehrxeapcnoosv8ue4rr-ey 24 ffo,r86,8h4oumrsg//dmay3 DwpinaTDdNdwoennleaxerheeaocOagcdycpeaisrssrgarAemotecroleshnhaeisesaEtrsvaotsuciniessleLsfeoareellt,l.edarrvtundnd=itete8lozloeewooifry4rdvt1fybieom;ie1demtpuccpcihrcmnterluteagawesstwclrbigr/sairmmwielo/ehaerneminsdaeg3eeedascp.3rf,dhi,defefecateetaudsatertocloeretartlitifhccvuvsnt8Cteoene>geo4lur8gdlbostudg8,iisidfilabhlnmemaeilylvriretr1vvmsgheeh3eef/ocerymoedrpoafpdlb;ipl3nvrneiloie;maodenrjwcptutrocerotyarioerdlyvnneyspp,;egaltwehfoersorayysbehil.odul2iaocdl8nawhd-hriuntg (KennHeLd1y29,08H56-)a8l1l et al.,
I.2.c. Subchronic Dermal Toxicity
bpTidnoreajerdubsmyrleeyanw1lcaT-eeen7ixhdg)o.pehlfoetsSC,ssuiuii8mbonr)cnceidh.rlsaeeriAraotnestnorectimhcdotehmidlnielevipervoedamerrratriawhs.lloatetMontoigxtxohehiiacefctsistibtuh,tyylreionesodomtcuedfrederChmnaie8astaselohf,ls-fadelibsixneflbrpeopmoeoolesaadfunslCrfmeselu8xtauspoitdenoruinisdedtzuhdieyereeimslenrttvaeoottsehtClieihssn8er(d5aipfi-ntce7rdaaoeidntddciadviuanyectrgisaevobsfsefotbruloleiildtvodfi(ewuteshrcseieenedg
leads to the conclusion significantly different
that
the
rates
o
f
absorption
o
f
C8
by
these
two
routes
are
no
t
10
HAZARD CHARCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
Table 1-6
SUMMARY OF SUBCHRONIC INHALATION TOXICITY STUDIES WITH C8IN IH E RAT
Study Type dway1it0rhedcaoonsve8e4ry
(#/Sspexec/dieosse) 15 Male Rats
Co(nmcegn/ktrga)tion 2hdoa0yu,2sr/s0w/0de,a2eyk0,050 for 6
(Rmegs/uklgts) bheleSTDfwprioenofyvekhohfclzdpreielesoiniyoyerccoevlmwrhitwidwtresrvrreeirdeboeonieysltiepurabigag.gictehstntherahiefwyedotdftr4saeinvaaapc2ascsentarea-ttded>sdstdt>istav>wniwe2l2yeeln0e2i0crdotcr00erh;eee;of0chttgilsoo;eieniimevrcvfspcenteCeareaaverertb8teyordaia2lrncsueipslnej0elrieuaydiblt;rnlrfhluirpytngeoeeel;loadvrratibhersen4oaldemroc2ctsurrou<iaedecbdl2acatal,iesyor0oesv0ndeo.irnfy
Reference (KeHnLne5d8y9,-189085)
Range-finder d1a0wyeirxlebpcaoosv1ue4rrey
4s(psReecaxibfnibeoidtts) 10 Rabbits
100,1000,2000 Late1th0a0l to 4 of4 at 2000,3 of4 at lOOO, 6 of4 510d0ayfosr/w6eheokurs/day, Rfm1l4uea,ovleareisnrnsdaeinb2ldle8ev1dree0alds.y1usw,c1oet2ifro.et1nh5,eia.n4sntb,ud6od.3d8yJy,,54rwfe.o6serpipgfepehcmmtt;ivaBfeloelloryso.adt 7,
RiM0k9ea7rr9cLR0haeAbp1oBo5rr,0a1t4t9o88r5i1e, s,
1.3. Developmental Toxicity Ttwreearesabruteloeltcg1oeDO-nn7edv)i.vuneecrTraltaohelltpde,sm.CtooreH8incgioltisaanwrlnaietolfovytdxecteriho,vcenbietsleyroiecdpssaetmuuurlsedete.dinettTthsaohlehbetaroeevaxsuediucndbliiitetqtsyieuownsentelcauyroldehnsyqtaduiuzundaecirsrtedaetsiodtosduniiinsadnbtdronalieoctt,shtaateacednodcddnoitfthnriiarocambentbpaCtitlhta8ssestm.(uoSdiregiigeehsitnbael a aliwfencselilirslobtnteueseeterasemrserdtancseoeitt.tlndiritenoiaeaTImfinlctnttnlhh,istymoted.etahnheanetfeI,lewrdiyinirkmslnsooeCudtsdinnbinat8liersusrr-aeeeeermodtiaeaecqtrukhlsdbtiuargeoaroeittirnuehrpnnfsdgnvhitaqisntesdlfeuhtiraresyuneaetrteesldegtoumibthifadif%eraoaloytastchnnes,e,ttcedor.ttwiahohnostE%epeeiernoryxblcleoeine,taitntinassfmao,.pstsnniahinpdanTaniesnalldahtsttrwgeeteleeii1r.arontaa3asldnyatPtktriimlorooetoieohblfnnnfpecrststssothehmaicuwsarnelsoobgiaeicreunnhnalrrygtsoegobeteihhrssbrdBsmcateiteeotohtoatsldiepeuoef.liroyaiontcmnBisfsfewe';fitonssisnhoen-tptaefherercriendrlxidfoundooaetidfgoslldfsstloekuhotobfdrhewesegeueilsotaneiaasesnenteglnsaygaidhizlfeal:feeoti,arlecadcatnriadarafdltgalestiioedcntohtnisndast are considered to represent stress-related changes indirectly related to C8-administration.
11
HAZARD CHARCAACSTERREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
Table 1-7
SUMMARY OF DEVELOPMENTAL/REPRODUCTTVETOXICITY STUDIES WITH C8a
(S#p/deocisees)
Concentration
Rmegsu/klgts
(# notRspaetscified) b2y5,g5a0v,a7g5e,100,150 mg/kg Rcableinndoiucrcameldsailmgitniaestseoarnftta2ol5xbiaocndidtyyw1a5te01ig5h0t;geayien and
Reference 3(1M98R1)eportM-601
25 Rats11 100 mg/kg by gavage
Mwabeanitogerhrmnt agalaldiitneie;asnthoosb,dsdeeevrvcereleodap.smedenmtaaltteorxnaiclibtyodoyr
(StaHp1Ll9e18s-,48e)2t aL,
12Ratsc 100 mg/kg by gavage
wMvoiceaauibtgleiahlrrintteyagfl,afgdeincreo;tasnwthootsbh,asrdletaeertvcreaer,etdoiao.rsnedsdeivmneplaotoepsrmtnpaealnrtbtu.omNdoy
(# notRspatescified) 0b.y05g,a1v.a5g,5e0,150 mg/kg
Mopenriwmemorbepoaspimbrctegoleerraharydvsnntlsouesftaioa.tcdnlottrgiidixmonveianecaaar,ttsttlinhriloifatsoganecacrssato1,,ttb1..umc1npoNF5oasr0erolp.me;toae/DCfralfea8efllmeetgIwencnrartsotmaleeossfasiinrnn,nafodooeitnidivrtondaft,geironisteagbwslse,,eare 06813TMRR01ep1o0r,t1981
Rats
bO'y.1i4nh,1a.l2at,i9o.n9,2 mg/n?
Mtopeombrxoasbicteceerriryvstnyoseaid-anlftegdint9eaa.aal9rttnth;iofyNsaxoaciocttfsti2ttehwy1rea;weteoroaexvgspoeeoorbntbssimecsedereavrgftveefreedrodncuotaaspnltswl2;e1enr;es'.
(SHtaLp1l98e88s,41e)-8t 1aL,
18 Rabbits b1y.5g,5av,5ag0emg/kg
RC8edwucaesdnomtaetmerbnraylobtoodxyicwoeritgehrattgoagiennaict"50,
TMo3MxayicP2itr4yo,1Sd9uhec9et6t,
a. bdc...
e.
PAPgSTFrdtatcrhibaorouaubehaevsencsparsengitaerrtssrghrmsingieifagndpsenaiewtarericeunifomtcoonerrihtauercrndntrsoeiedpagafsorddain.crttewcnasoooti,seTlynunewtytDrdsahhpretdheretieoaps6isoirisy.enn-rieglt1nwesoi2Tmhdd8scc,1ateeahaoitisddhornydelsolieaeifte-yf3nfidnypdsfnm5cgseotcrcarbiieerespidgiereysngdeesoeonntnoesangsgintfn-arfttrcariatpoincooshecevmateckulaniaoracssyepno.gtotuf.lof.enteenidmdigfntoWnsiasdei.cdnclkdihhriasneedeeaikblgrlaaneteeeerysdtgdleraedesreialtdaitis6oteafntm-iinltfnob1otfoihedn5iencntneidaotonddteiinmgigninfrnfdapsrgcfpgoteriwsaoodeur"sagugeapfsorensnrnosenondcancaemsienionaciascgdotdtctdyenecmfhic.dmoiea1foinPiwnn3cancsgriobatiriseretdnirntohgbrsaettalnrselrsdoytoea.iimerolndnglmgnatiradsyrr.easoiameaeilbunfdthaoepbgolririf'gomts'io,snhsrroaiwmttfdtchhiieoccoeaerausnte3itetrsorirdo,elgneoornardaiwostneateiuhnedndpterhdad-brailnristeynei*hivbsmdehetuyila1gdl3ahsyr.e
12
_____________H_A__Z_A__R_D__C__H_A__RCAACSTREERGIZIASTTRIOYNNFOO.R3H82U5-M26A-1N__H_E__A_L_T__H__C_8__E_X__P_O_S__U_R__E
1.4. Reproductive Toxidty
No information is available on the reproductive toxicdty of C8
L5. Mutagenidty
teste
It has been demonstrated (See Table 1-9).
that
C8
is
n
o
t
mutagenic
in
a
variety
o
fm
utagenidty
Study Type
Table 1-9
SUMMARY OF MUTAGENICITY STUDIES WITH C8 IN THE RAT
Study Description
Results
Reference
Mutagenicity assay
ATcmeAserste1aav5byi3soei7ldai,cieTnaDASc4t.1iv5tyya3ept8aihos,itanm,n.wdwiTtihuAma1n0(dT0w)Aai1tnh5do3uS5t.,
Negative
Imn ivcirvoormmcoleuusse
m3h6o0mau0rrir,cs8oew0a/s0ftew,exaranwsddoeesvr1iea0nld0gu0o.astmeeddga/wktgi2tha4n2,4d08b0oa,4nn0de07,2 Negative
Charboemrroastioomnal AcwhsirtsohamyaenoddsofwmoriatahlboaiublitetmryrateottiaoibnnodsluiiccneaCcHtivOatcioelnls. Negative
traMnsafmormmaaltiiaonncaeslslay Aacnesldslsac.yyetdotfooxriccietlylitnraCns3fHorm10aTti1o/n2pcootleonntyial NLDo e=vi5d0engc/emoLf;cleolwl trcayntosftoorxmicaittyion
L(GLBirFItitfPoefbinrto1.hB9j1ea8icon,01tnd)29eL70ti88oc3ns;8g,, CoM1m7ai3ny8g81H-60a,-1z49l5e95t6o, n,
CoA1m7pi3rni8lg82H-50a,-14z93le97to,6n, MPianAUtnhpneLirsvioaletb9ra,s,1EiTt9yn28v9o1i4fro2n, .
1.6. CSirordc Toxicity and Oncogenicity
The chronic to feeding studies in rats
xidty and oncogenidty (see Table 1-10).
o
f
C8
has
been
investigated
in
two
2-year
13
HAZARD CHARACTERIZATION FOR HUMAN HEALTH C EXPOSURE
CAS REGISTRY NO. 3825-26-1
__________
Table 1-10
SUMMARY OF CHRONIC TOXICTIY AND ONCOGENICITY STUDIES WITH C8 IN RATS
#/sex/dose (mean daCiloynicnetnaktrea,timong/kg/day)
Results
Reference
50 0(0,3,10.,53,0a0ndpp1m5 mg/kg/dav)
DcRvhNoayBeonlpcutCserecuercsotmar.onsoupesIpdnitnhdicotbyesrno,r,e,ehaddidesneyemtgcowderoenblegiaeievslgroeecahbrdattiiwrogancnat,eianmaixagonnihgadadtne.shnnd,Deeilcfmiceov.rcaooertdrseoicacsse.reiltld
R0(A2i8kp1erCrilLR1aD9b80o11r-aMtorayy 1983)
156 Males 0 ,0-pair-fed, 300 ppm
DpcInoaecnncrscreueraemasaseptedidtciiobnancoc.iiddnIyeannrwcccreeeeialgolshafetddligeveanesiortnr,maLadanesidyo. dlfoliegovdceellsl. and
DuPont MR-5686
mtreeaatnmbeoInndt-ytrhewelaeotiergdihgitinngcaarliensatsuaenddyin,inifnoc-erleiifanescefidiinnednficnoegosdo fccaootnnassxiusiamteidpntoifoefnma idanloemsse.aldNeesop, eainnndcdreeanatssdleiegichnrtemasoertianlity wycsalelrpiyc0Hcto0eiainetoluervrotueoaqt,nv2ylctoouame3naesadnlud8ertwrfnretr0hrsesyrioi1aoitttvilainavwrpe,sthbdCoedraooils,veesraseolseeneecRoct,hclenerrrcniyddcyatrgeripgeerd0oisnoo,ltvfmrmdhedil0enbogmpe3ow(nerti1ltcesrcsse0owiddifooetm2els,ycvoo0g.huoir,n)dah.bueaeol.seoepaCofuo.yreninTnmsntopob3Hstpatu8eHladoehsnmb0ipyeno-cmon,evrs0orrcfrfdoww,feooteopoeoawoiornrplbrLgnearonhemeaerevdpessrcvfdopestiateevemeohpnipy2yetlhpddrhsedoheeocre-pdvypsere,ygmpiaucirehei,,denmniiegietatnsdhfnenacieacmatoCvdfmrcaetainloeiortoaece-eeptnl8hacfroensaosllaadieeegiynt,lwtgccnslfultvolee)ehittoweraedtvudoiacelnioeo,twrdcotesrreemaryeispwaeeeagvriadsratrnglnlnawt.itioaoaasleiwcrcoidseculolsrnivfaTuuesitscefmlanfzifsaeusfae)clthooleresoalr,hgrstcasiae,edeceersniwfogdrsotnnftrtvcLs2sha.noeeeuabeeouie.tn-egsedudtnrrhscBtynritepyyeeuyneooHvihteemvadnaotwrc,dgniaohavhsetveietsenoigrbfrhewepieiraaonooongscddsaesdal.cmetiecceetetfntocrtueoiryarloslHoaaoeeuerlvldeinttcultiwnxnedveociyccenvelfast,doelaaa.eolefofactdaaaldoolmlrrnrfoeuteeurtTneoiepcstiudlnfdaoatpdftaehoaoutcrnrioiyetuohrtfameenlhnemptcmhsyfuatsdtstaearieu2orunottnoe(iracwtroibmlnRahlwdmamcreysroalyceoos-iniefiogt(rodernteerkiosl0ataaeerioeuoedscieocesnnfrlr/snnlgiar5oraitdg.tfrdwszohotciilb0eLoteetcmelemrbeuAhuedys,d,banaod3eteredo,eilbsscsbuef/erbtsyCeifefeo5ovlgpwefdiwyrosx,tfr0neae8hovueleafopitinadi-d,oietitymcgtnladneunshdoiaadutpehcnsctm.drobnntcf,aessttrgayoilerdoeoteohrfsnoyts,sheodllarteoygrfo7leawewsiows/atfei52oe.aetndee0r-srd1ydfe-oa,te
mf^haTnhisemseocofntudmstourdfyorimncaltuidoned(DmuaPnoynmt MecRha-5n6is8ti6c, eCnodopko,ienttsatlo., h1e9l9p4d).etIenrmadindeitfioone to foe pardolliibfeitruamtiocno(nBtr-oolx,iadasteicoonnadctciovnittyr)olawndasceplalipr-rfoeldifetoraftoioenC(8BgrdroUu,p6.-dPaeyrooxsimsoomtiec pumps)
14
HAZARD CHARCAACSTREERGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 E'XPOSURE
wmlMtpcaIsttcccauhrnriceooorceegeetreotolmiimnararainlnelfrvertttsaptinerabeapeaifucomortirddtiiosyzrtencolvfciueseirratlanweeon.ddaianantf,lrtg.itsfdelaT,etrosaurhl-estth.IynnhuraharenloeaedatemtBepaotlirldtreoals1mLairafeotrvotniatesHeei,nriwoemte3rclsdiweenndttlle,Bahhivieecoa6srnvorevaeresa-,efc(eneot,ecL9rnlerBrarxhirlaetde,Hovsswihi-o1tafdleoteeeweiasw)2eadcxrs,setoitdieee,ietfasgiigd1roforsadnvnhaienaL5tnlewnddtatttliu,sori,hief,io1tc,leiionyeweitcrnalsrv8hcldrseaeinCeeehegtliinisenagpsrrai8nsttLevp,nnenli.-iLcymLeedcreftogerfielcSrybeiceoe2slueyntdleysaad1iraladcvr6eimdantsgnuierimre-titengevimddgeocnioaoiedncxterrngcshdfhneaecileeadtelhdoltrtsdriltlhseatelnoreusCu,3satmriaraciwm.dnua-s8mottemeonmi-mntHaadoetsodnhrsolronepieleiCecspnsnanraterht8ltaCiapootehtLmos(-enpplpv8FetladeicprreSe-raneSyceortucertelterptaHdxhasyaemireatonitiuorrsae()gemtvitttmlitdelnoaeoocewaecastnksgrdlveattsbttashrediei.loecnaecgtlselalisspydiatrpIsnndsnt.oornli.era2uoocwsuoer(Hrc0TetollCopvleaeco-imlenht.afrCcteleonpieoleletvmlpuCKtiar,nlatrnepaaahttaese8e)ilru)tatsecss,iseialnmwdootteFdi0,rtlcinnnveahSedo-t1r.esdooreeHrtrsnmleheisxapsot,vote.tiaihaohlidnetl,ctenCasaiacoCnttl8hieo-8.dn-
n . METABOLISM bwodCbexeilfo8soecCpr,onrkwo8edenNsthrielionsetuiitClveomaeved8ntamel,arseiriwnaovomilnueuhreanassearntrsanmssuetpt.uafesoeasdxRracciperniaeteeoudbsspssrlb.rhoiefnoieadwtAgdmsvwludepy(acbdo.lblatoeirietnkCvtihehotee8annwrsmsaacesthlahloxsslittoyneocueswh,drsh)ssu,peiatcnefudrsetoxdetfmadchideerulmaaeosictlntneaheetvhglsareeCaevsCs'/t8e2te1di8-,gm4bli.ida-aeflontSeienifrdnneeoienxgmitcsnhoahtlahonmnaulwevdedmeeuelhsnayxcpaan.ticmneessrcM.deegsiteftMwriiefseoceriaenedsctthait(reafsbaorfenupeonxtdrhritpedehedamonlxnisysscceeepe1renxdeso.xte5tshcosiioyr)atfeinevoCtaeeonr8rs. H .l. Animal Studies asntuHdrieaTsbhbaeirtese.sxucSmrteumtidoainersiazhneaddvbdeeisaloplswoos.iitniovnesotifgCat8edhathsebienefnluiennvceestoigfartoeudteinorfaetex,pmosicuere, .hTamhessteers wiLwIn4aCejhebriceloientrinIaomItothn.oltae..rdlayeleF.isvtdeehMermcuart,dagaall1beeMe.ls1xea%ecenatrxdafeictbtnfeeroeerdtmlthi1esoe7admnlpdeleylRasarysa2seestm0psn%iotanwiratatoelhn1lrfyeed-t2hfa1l0eoed0mwm0a(1%daei9lnmre8iobssi0un,fte)wdti)rsd.ietheeedirtaleeerdadcamdtdatiiobo3nlls6iaeesbdt.leeearRvlyeeesaddldmsdCioioan8aslecebostybtihhvyieaenr2dttro4ias2rshv.g8uoea%enunorrsseou(,ssRfidtihukeeers 2ospb4es,ce4ir8evIsI,e7.1wd2.ieb,n9r.ea6Sd,seotaxusneddddyif1bof2eyf0rregahnatocevue,asrmgsieinpcwoeths,itteh-hdaeom1x0scsimrnteegtrgi.so/,knAagnanCdnimd8ra,adbalisnbspwditosue.srrieitMniotehanealenondafsnrafadcedrcfiieeofismlcawebadleee,rleeaadnncdioCmlb8laleowlcsoteedordfeaaentadch
15
_____________H__A_Z_A__R__D__C_H__A_RCAACSTERREIGZIASTTRIOYNNFOO.R38H2US-M26A-1N__H_E__A_L_T__H__C_8__E_X__P_O_S__U_R__E___
thiossuuresspwosetr-edoasnianlgy,zeandd. rTahbebiutsriwneoarendsafcerciefisceodfraatb1b6i8tshwoausrsa.lso collected at 144 and 168 tthhee tafdmTmahieonfifsestmaecraerldiefidrcaoets.aeTn, rdheemspmaelacelteihvareamltysa,tnaedtrththhaeedtfiemexmceraoeletfeshdaacomrvisfeitrce9er9.h%aBdooetfhxtchsreeextaeeddsmo39ifnraiasnbtedbri6etsd0%doosef at teahhxnoecduirrrfesettiempsdsoaustlhete-sedmaoCitsc8itenhagerset(rtiHaamipLneied6odl2yf-ss8auan2bcd)srticafioncmteia,plolaenmtleyloyeuxancstsrtehoteifntfgheem2 t1ao%lteaorl aaftdthamneidandmismtaelireneihdsatremardesditoedar.octsTievhaiettym1i2na0le
to proHte.clt.cr.aCtshforolemstythraemacinuete, dosing (HL 828-81).
alenthoanl-aebffseocrtboafbCle8awnihoenn-eaxdcmhainngiseterreesdinw, withaisnd2emhoounrsstroafteCd8
metfoelicaemelienisn,grAaauwttrsisioeniatncehno,odn1o4fdmCr14se-iCtCcxueh-8dCaw.yl8eTewdr(h1eaae0sgirccim.vhoeognSnl/diekmucsghctiylbtoaerylardelmygstto,aiynvDirenaaogmvdweeiie)dsnxtfenirgoo(a1mItto0een0rnta0hhEteasmxneacgcfnhef/daketngchmgtebeiocyefRelgice(mhaHsvoiinLnalegaws4teit0)ayo5s2nra-4a8oml2hsfio)oCn.uea8rAbosvlndeaiauftthtoltethere rheexodhrunacsleeadtfhtaeeirra,dcwousetiernelgeotwbhsiatelhrevCfef8decn(tHooLsfiCg4n08s5.-oW8f2eh)n.ehnarnactsedanedlimmiincaetiwoneroefgCiv8e,nvDiaotwheexfecreess,iunri2n4e or
istc1vhth9u.eo)8dlc4ayeon)sTw.ndtoycatrehfsaunemctrnortiahnnwtedeioreuinrincnetcovefredefedsCaitsnid8egirdfaeaottttesush.ntcehdoIeennilnuitmtashitenhiinsieonaslfgttiiucvo4hden%oyr,ol,epcrfsalhCtatyoss8rlmeawvsmaeit,ayrianertanhedmdetoorfisneeeeceddnefbhwsolaobrintoyh1cd4e914.cCd8Cea8-lfylCoessl.l8d(imJT(oa1hinh3nedn.a3stdoimoencn,gr,ee/aktagstahe,l.dib,ryd
oexfpCo8snuf.rrloe.,mda.nthdAeinbsehloraioleadstioooffnmeexxappleeoriasmunrdeenf.etsmwaales (cpornedguncatnetdatnodenvoanlu-patreegthneanutp)traaktes afonldlocwleianrganocrael
bbcwoftchollloreooaaelmlasoolobrpddddwalToooenlCioumsehcne8dvneego;dewlbuineltnmypshasvhttsewe2rauaarlkn4cilsattahueephhftdmoiiimaoodnlnfubln,ooodr1ewlrswelrech.oxioliotswepnAhlfuaoogieprrnsdwaxmeuagonpalrfsyucetaokeee.l.sst-rruiroiePApcenrafrelesgceepCssslhgiseoond8eanrnogidtaafdisrlrloneeao1ndntl-mw6o2aodo-ntsahohtfidashsnooefeedngufxu.eeo.rbprcmsnTiolTtno-pshobphohuoenlraderoseselstosaogt;-arltdtnmoatfirhoeatfwleeeeennadmvettgmemrerwexaalcanelsptiltetsn;eeeohrratarssaainranhualatnodorslsnedwrtmafcaarovpeeetpaleipdsrlirlmouadaetsuwtrllieretyeamaeninlintdctnitstsglloeicamcnataharalp:reaaClseppanlide8lenrgyeagrfbedraklsloetotsimhoned
16
__________h_a__z_a__r_d__c_h__arCaAcStReErGiIzSaTtRiYonNOfo. 3r82h5u-2m6-a1_n__H_E_A__L_T_H__C_8__e_x_p_o__s_u_r__e___
levels following either oral or inhalation exposure (HL 593-91). Specifics ofthe experiments are summarized below.
H. l.e .l. (female rats)
Oral administration-Blood levels of C8 as a
function oftime post-dosing
plbeplvomeoldsatpoC2ef8a4feklaemenvddaealles1t6ro3a80ftsh1po4gpuimpvrpseam,nrteaw1s-spe2ienrhcegtolsieuveereoslnry,ad1.l5rdComop8spieines.duattebosso2for6bllpeodpwmainnbdgyraa8dpmhidoilunyrissct,lreaaantirdoentdoofr0fo.C7m8at.nhdTeh0e.0s4e5
n.l.e.2. Oral administration-Blood levels of C8 as a function of dose (female rats)
-rf1erol6am2te0pd.p1tCmo28t.-hleTe1v8haeemplspsoa3mum0n. metTodihnfoeCusetr8eersseapfdsoopmlnoliosnnewsisewitnewagrseaadslid.nomebasinre.risvTterhadteiaolten2vo4elfh2oo.fu5Cr-s81w5ini0ththmbelgob/olkodgolrdeavinsegldesidrraefncrotglmying3
II. 1,e.3. (female
Oral rats)
administration-Blood
levels
o
f
C8
as
a
function
o
f
number
o
f
doses
hpdf1eoipfamumfneradsrfleeo21n1Br6rta.1ldatosCnaoondsfodoedn1slllc,e31oevr1wpenepdstilrpnsmoaegsit;ncieoratseifn,tvepsr2emee4laasyatpth.ele1eodA5curtoamirtvrts3sa,ein0ll0gyua.im7.vtdeemiaCsnnnufi8dno1tedil0vslsoot.er8eCwrasstp8iiunnopcsognmot.1an;1adTcpadmenhpondeeitsnarnaeairtusstttimo1oroa6nfbat8iCsceohcwr8nuooewwmufrreeteusrrr,el1eeaa06tnt1.em0ao4i4ntnea5dcnntot2hadsnn5esd1dbpio7dl0peoep.ms1ropan0d;mboaloyttffo8r appear to influence the C8blood level.
H
.l.e.4. Oral adm female rats)
inistration-Blood
levels
of
C8
following
a
single
25
mg/kg
dose
(m
ale
and
Time followi(nhgousrisn)gle oral dose 12V864i8
MBall2652eo3330oRdatLsevels oFf Cem80a.0(210pl.66e47p5Rma)ts
C8 is retained in the blood o fmale rats to a greater extent than female rats.
H
.l.e.5. rats)
Inhalation
exposure-Blood
levels
o
f
C8
as
a
function
o
f
tim
e
post-exposure
(female
eaxppporosxuirCme8taotlee1lvy0e7mls0gopfCp9m86/mpatp.8mThwohueerrlese,vo5eb2lspewrpavmsedma1ta52in4mtahiinonuuetdresst,hafronoldulogdwhroi1npgpheoadusrti,onfg0ell.e3l 9t6o-phpomurat 168
17
HAZARD CHARCAACSTREERGIZIASTTRIOYNNFOO.R3-8H2U5-M26A-1N HEALTH C8 EXPOSURE
h0tgsoi.oi1nvubgeorllnoseropt1iidonmmshsteaa-g)eml/.axmtppCi3oloi.8nnsTugiesrhxfeaope.blollsTaosougwhrrbipeisenh.dsgaasaamen6eds-eghreaeonpnuiferdorilalnyllohpcwalaleiatnatterigoernodnrwfearxlaopesmxoopstbuhosreseeurb(vrlreeoadwothdiaensorrntfahoftaestnmoebxaasplseeoirnrsvageetdlsdetfohdoeolelrsoieetwhdaeiutrneag a II.l.e.6. inhalation exposure -Blood levels of C8 as a function ofdose (female rats)
inThiamlaetifoo(nlhloeoxwuprison)sgusriendgolese 2A284
0.100m..2281g54/FmBo3lllooowdiLngeveexlps1ooms0fu1.47Cg5r7e/68mto(3pCpm8 )at
10 m16750192g9/m3
salmowouenrtfToohafneCro8ebsispneohrnavsleeeddi.astAltinhteethalroeawhtieg3r0hlemcvoeinnlscu.etenTstr.haiCtsio8snubgulgoseeodsdt,sltehmveaecslssleiavarereaondvcireeerrclaotltayedrsiesilnsaottemhdeetwo hthaet clearance system.
H.l.e.7. Inhalation exposure -Blood levels exposure to 10 mg/m3(male and female rats)
o
f
C8
following
a
single
6
hour
Time follow(inhgousrisn)gle oral dose 2A284
M111l1e3584R7277atBslood LevelsFoefmCa18675l0192e(9pRpamte)
followinCg8iinshraeltaatiinoendeixnptohseu'rbel.ood ofmale rats to a greater extent than female rats
n.l.e.8.
(pregnant and
Oral administration-Blood non-pregnant female rats)
levels
o
f
C8
following
a
single
25
m
g/kg
dose
Time
follow(inhgousrins)gle_o_r_a_l_d_o_se______ A28
Pregn32a1366nBtlRooatds_L_e_v_elNs oofnC-p8re(pgpnman)331t91R0 ats_______
female rCa8ts.clearance following oral dosing is similar in pregnant and non-pregnant
18
_____________H_A__Z_A__R_D___C_H_A__RCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-YN H'_E_A_L__T_H_C__8_E_X_P_O__S_U_R_E___ exposEuLrelec.o9n. cOernatlraatniodnIn(phraelagtnioanntefxepmoasluerrea-tBs)lood levels of C8 as a function ofnumber of
Time folloowfi(2nh5gomusrigsn)/gklge oral dose 2V2844
1
Blood ex3p31219o8sure
L6Feevoxelnpn3l1loods7d2wsaouifrneCgsS
(ppm) 10
exp1111152osures
....T..i..m...e..ef..xo..pl.l.oo..sw.u..ir(nehgto_osrinn1s0g)l.me...gi.n./.mh..a.3.l.a..t.i.o..n................1
Blood
exp--osure
LeFvoelllsoowfinCg8
(ppm) 10 ex5p3osures
a.____n_d__=__n_o__t_d_o2n_e______________________ 90___________________nd_________
dte1oxo0psaceocoscsn,Wuutsrmheehecsuer.unleatictaveopemipnienptahhararesilnatbogtlioobtohnedeeaoCxlpof8powlrseeeuvrgrieennlsasgn(so6tefrehatnohtsuearftCso2/l8dlaoabnywldo)ionw8dghelrroeeeuvpnreesola,sttf.edodiBlflfooleowrraoeildnnogtl.rev1iCn0eh8lcsaodlfanootseliloesocnnwuotiitnvagep1opreoaarlr
(21H9aL*ndd6aH41y-lh8.ofo2.fu)p.TrrseAhpgeonsasainbtn-gidclliyoety.sdionMogfsae,14taeoCnrfn-dC1ad0l8ebmctlorogeot/arkdsagenadsnl4fbdCeerp-ttCwlha8recoeewunngat4ashlaatlhdneemdvep8ilnlsahiscooteufenrrIe4tsaCdpw-toCosat8sp-driiennogvcsnrieneasagtnis.gteradatetbsdeotiwnn etrheantes
Time folloowfi1n0gmsign/gklge oral dose (hours) 248
Levels ofC8
(pg equivMalae2t11ne022trsn/amlL blood)
(pg equivaFle0en33.t7tasl/mLtissue)
H.2. Human Exposure icwaCdnopu8domperubrktposlootDohxrohsiiieamsedittgldeoalehrerotnmeyvCfvleyiit8innhlrstoabehftonllieCouomfoosn8aaerdsoawmnolncteoehifwvoreolkeneemrle.vrgserieaTc(wlpn7ahteih0lhceroprfpfhoorlwpoiurugmmdgoahushr)eeicrodnssteuu.tiemogltbAentgolvh.oepveesopTelt2sddrshowte%lfxhermeiovamyrmteeaeflajaslfotturoehiromnlueiyrtnyowfo9dlcnuo0ohiio%frntekortmohwerocireinosfhcvgrteaehkamlxpelesuperiaorseocirrsasowegelrdavdipe.tnemhrtoiroMctyadhiCfuonsellu8cneoltodoiiwitonrnoailngrntyaiiveennssigwtteoasf
19
HAZARD CHARACTERIZATION FOR HUMAN HEALTH C8 EXPOSURE CAS REGISTRY NO. 3825-26-1
meliemni(nUatbeedl., eFtraolm., 1th9i8s0l)i.mited data it is hypothesized that the 14-life ofC8 is 1.5 years in
Group L(N>Ian2obd0Promurlyaasaenttoraltirhrawsyuleompcxroekaprnnesotorrsssonuelnrrseae)l
Number analyzed from publish48ed literature
49
Blood Organic Fluorine Levels 000...(000P114P---"002...)010830 1.00-71.00
HI. MECHANISMS OF ACTION pplsaiuecafersntioccoixenrnpeismartoCietbimasc8lpleeeaiossstcno.inisnntSiohabhmterlometiturcofetmeo-xttareiaobcrdnrmosdieelfiirsfznvaeteautcaedrdt,is2oiiaen-ounysrfsdehaCeatahsfr8vaf.feestehcCbbetasd8een.eeipnnntrhgosecsdhotfuounecwddmeyunsacilthtneoeedrrppaaairttno,stov.dpmeurTescetsheigugeahmamletyaipna,baliglentyiddcrda,uieutLceimeesstyeomhdceithoghpareeacnteliioslclmn, gasneordf14-
HI.1. Investigation of C8s' Effect on the Liver. ismimatogTaeVnrtscnluafhtausi-edrntdsodiltoatsmeoasyycegcftpsrmilhhoeawaattlrursaiootteHaoeaaetsdtntrndshsnhmIiywd.escyec1werfialeaoici.e5naaanlircnrssd-tr..etathetodeuoirsdvtuEBawbpeCdioincclaleteaaae8stuystcmesescci-fl,aodimuedttinocurinnrmvtoodnaidso.ccinnesusa,trTeytierfcipmCrnlieaearheyawvt8sdmitrineceeecfoahdhodrsdutixsnooaterlUiitdduigstpsghn1aciomDaatbaslo,htmtpt3tehcPo.eperCey,eme-yotInpgtosh8npolce,lrriesuocevdogcah7hcdrheonnoaoturoredlefidnowsyoirmpsatrommnromyiannanniatsfneiostiyetcocCrtaewtdPlr,antlbop8iry4tttinthasisoth-5ohpiodtnese(nr0crmussPe5csohpfeccaa0oreelesreotesirlossemfmutnaaaeodlihssbtiinrgoefseeycrlaetner,adapttCrr,h,iwttliaoorsek8ceaaetl,net/iiyinnlkvlnipraatidnodegeovgiLtddifupeamr,vbhipeercnlceo1emaseostaap9idsrptrovftimoo8apyifocinfxet7htnociwtygaci)cohsasm.ctleedooeeretonIiiednmifovggCnebig.ztihfieeai8ytptcntythCsln-amhrybe.tiovlzaersyeielppcerinssnahrafh,tsetilarueetumrain.tddansatgiytsemtrie,ooasaiytnnsl.e and feedIHin.gl.sbt.udCie8sinact rveaarsioedussetirmume peositnratsdiuopl ctoon2cyeenatrras.tioTnhsisinw2a-swaececkomgapvaangieedstbuydies, increases in liver weights, and hepatic p-oxidation activity (Cook, et al., 1992; Cook, et uwsacwdeylsa.earity,uniosgs1mgceh9ohsct9rtefsuao4s,tbrlm)tster.lueaiaesrrSdtuehmPiidmeon4edlch5neleeb0etspepvtweatreewnatrilodztosehcyixeboymuinylstp,eoeesassmtstno,itsmrdeau4angphdu0greiilmnooaeptvllsaiigtneafteitsngCchrtdiaa8aagtth/rroakootetrhgmimpsoe/adainanitattniawdacycssuaraepecesrraoeaaocccsmbdotetiouinavvicttdnihiaettuyysdsPcee.(d-trLeaouAodcximsutiteisd,ov-ieeagdidstttneyiteoarpi.tfalneei.dIc,nrnamiad1ocne9vlittnini9ivtlsetr6iinoiatainyef)tec.aCalxrernFep8acdaoesoisurnteriprcmrsteraeteleoreaatn.nltsltyisieovsner
20
HAZAR"D CHARCAACSTREERGIZISATTRIOYNNFOO.R3.8H25U-2M6A-1N HEALTH C8 EXPOSURE
daruoemtoataasdeirceycttoecfhfreocmt oenPd4i5e0liivnetrhteoeinndcroepalsaesmsyinctrheetisciusloufme.stradiol through induction of
I.2. Investigation of C8s'Effect on Testicular Leydig Cells
wti2gonh-efhveynLieeotceseathtysoritgdexfiBeasiligece,teevidwcctdayiaenh.t,ulegilasTscteshunshtCemourerend8usos-ytmrupguiilrgedtnoenseidesnoritusanetrotcassstxediuu,sdiimam:conaClm(odnhc8raoobifrnpnroeimrczccroremeaeoddnuanautbsstraceieealoe-dltCsnomioi.8awnnenwcdssi,iiudanawpsetcenhprndecioe)caerghmstoaeaitenfiihcvnttehoeuhsarirtmenninpciossmuamhntliaooacrfldrloatLyu-rrtl-eoeamtyumrtemdemsaidgtotgiaearcrsstoeefetowsldalrfctmmthoutirmeafvactiiocthoyrtanos,nrwiisnsamians
undeascaseticlprnoeaexgsdnsoidhoonueIrleInym,Ltacsa2inhenn.daxaclc.rldoeheeFrnaogcosgrraeiueeonssrant,wsieinesceeushnigggieodnghpnaetasyassettdsiricntuoohmt(mfra3ott-trapoteehlxiseaneittdorm(daashettteCiseconrGr(ntoCew)naao,sceigoetthcikovio,nnuinetdpytctae,etaosonatlto.rnt,5rosda01tpet9siimrone9orn-g2nurs)eemC,.lbeCm8aco/haskodaiygnynllc/hgedweenahnegydotiregurpamheetriotxtoosodp,nnueasearcnoi(lemdGefdsrenideonrloHntasst,)eai,v-toer the level of the testes, due to a decrease in the conversion of 17a-hydroxyprogesterone to androstenedione.
teiaiionnnxfvhfhdveeiiiibbcsrvtiiteotittcgsieomutatslnesytte.iis2incadtsou.gfbr(fsleBeL.atvecreiUreteiyonrgLsdnsteieeiineblgyr,gslpdceetriiie.tongtliadlaIvclsnu.lie,itcfltrsl1tlhoouis9oe,lii9andniit5nn,eh)vwdv.voiitirhvrfTvmrioooolheomueasnttnshiueindCnedlg8veeyei-vx,xtitrsesrvvooeeliisavrlvasutoaotetmunedssdddttruaiuLaeindndstdeisdiedye.utssedec,AmsideCgtdeioa8ccdmnrueiwostollimtlaonarsrasnsafittarteneraolaxdtlsmetyaeetrm,hdsautathcitintnthteitiCeaarvadelt8ibattffyhtildoeluiwiirsdtirdyeiartcssaottlafsyb,Cia8lnittdyo
iieannscccttrriraveedaiatissyoeeldlsew.ivneAerelesdstdwirniatacidrorieenoanalsolleletydva,eafhlfnesedpcaattreeetidscptiiracnirumotlhamaerraitilnetyastsetdeirussa,etcmitttioiuavlisinctfyclluerw,eidoaastrsrefaisanntics:nrfeoTaarrhsmoeemdisneawgtdahgasirteleoeawsacurttghiovgmfieatyasctt.taotshreaat
were the
dwfsutiehrnerecicotthtidloeyonrgaIsIiefne.f2nve.veCecisrtt.irasLolP.eprwyIeetdrvawoisigoxacuicsosseonthlsmdlteufureucdepntfieeorcdostr.ielowiTfpneihrtrtohiaosptCopsotrr8susoedsdd(hyiunotchscwehaluoetLddwpeieynaerddgodixtigChriesa8cco)tet,mpleldeeftirufropeemxrccoitotslloroyisfnme.arLfeAafeetpoycsrrdttosuiLl,gdifieynecyreidganlieltvgsonertcessoert,ailaaglll,satemtairnagy TacllhasoisssianoldsfouccosemuLgpgeoeyusdntisdgtshc, eadltilrcetoucmmtlypoormsuoninddisvfiywvothhi(ecLhsitude,irroeeticdatolly.g,ea1nf9fi9ecc6ftbuL)n.ecytidoingocfeLllefyudnicgticoenllisninvitvriotrom.ay
21
HAZARD CHARCAACSTREERGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
m .3. Investigation of C8s' Effect on the Pancreas pvriTcp-qso6(rfnOtieeaja4uhtutflnryire3ttbelldooropertswoehqxihd(ueeruayataiaetisstnngmmmpnaowoSmwddietmsei,ieirhggeimpincpevntieehpthhciltesunaravaphlirWhamsebainlrgvics.anoliia,oumotosphpyl/mtira1tnseaerfisadf9ntyerntCsraboheC9rvpictiabnx8y-7esneC1tc)uoii)soccs,pno.4Ktctloriheta,nua,g)hms6onaltrdameee4clctteecevnoi3iprenoosetecpa,tctosmnlahhanrshcumtsoose.chimagicllornsoaieigCefon,gsfilceeasewnc8ryCisrmtsornaitsmhtde8cwattta2iiooo'htescdstsu-kriafchheyssnm(tithniuemeihoatannahoiminantntarrvehvdpbisoyrsifseeliteemaermanrbriceblosgpdbetdeameefeeyoprydioernrneaentinrbobesogrdliCxiepsyesrnn'sbiicho)CacssdtstiounogrealiKilyenwdensmconaigointdlfbntesoeelnhitlisoWsvtoenpde,tomwehgraifptylonpero/hspa(ceyclr.rCeiCnotlolfhattucmCeToCCdhs-drr1umehKCKehapi4cneatdeKoaaAoer,gspes6ear)CrpiwcasfCet4toarrtiCcrpioeee38nryceKrcrane.'cpopeses,c.rsTdtelphefc(oeiAouaatohnoivroncrtlnelmeaiierelWcnrbdlnsoeosohuitadf.rlayfdicceobbsitIeteirhtienianytlsetedhdia,osv.-rid1einnv4,o, IV. CLINICAL REPORTS OF HUMAN EXPOSURE IpwbfeaVlxrelue.otc,.owrdee1ruelei9.endcea8neein.0ncd()dgoHt.Cheutevhen8aiet,laleiatvtnrhiseooedswrrncmseaernmelaflzerlooaynrnmsmaingnoegngtthhoeSeoe.rxGmrsaCGefmal8ueTlixolneawaraxbomtpaiocoosihrnnsateheustmoderwe.rimycelAeartoveeldssseo.tdtlffsirNtfreiereoosaqrnuneuhaldgetelselntayodatl,ltnyfhenrdmooepbnmrprolceloobol0oaylu.edt0enimo3etleesnstrvsooerheedf7lilsapa.t6eot3wesmfMdtaorgsterpo/gsomluaeab3nlxnstie(ptcUrtovhsbeauedtrle, et RIctoVoen.Cscu8Lllut(bssFi.ovaAfeybeelsrvowtuiodeddeayntchwcheeearm,os 1fmis9at8anrd1yoe)t.ceocsuftiWpnagatis(oShniGanlOglytTorn,eLlWaDteoHdrk,hsAeePaml,thapnlpodryobebiellisermupboaitnemn) otiinnadglliycwaeotxerpkdoenrsosedextopoCse8d. viIwtjhs(TwgaTnnhVGeaonlhhfapeuecrrdoi.senerritmtllreiaeel.nocmiicedmonlepwonf.aTndgabfonaynaeethuAaesdllidsc.ttiyocuaotiwtlnatrvnitsTcxoivhoonsoeetaiheioefodelnsdslyldeaucnoiyMaoglsigaanaca0vtanfhcsmieotaamssiigeaghnoCfisootanliaooudinaccnm8cdtlcelbsiiagaaviailom2lnba,stteceni16etten1aite1dcacdthHp9gdw5gosle9pwiasDlhninewu6mnomncoieiL)ttdccoeanr.mh,aiamrrmwgwajnkClSfootlrohieayiueidr8enotnrserlthoeegsanupeatrrrmrmtaenehaabgaaedxdttuemnansyeiuCpmtctndhslwodceofo8petCsaeearosefpytindnrellxeen8eaarudnrrkiuoavstowoceitseevetfcrsoineretiilbp3CsenycsesrCyo..tene83wtaoon8rzTan)pcsaifsey.nldtooonhetcremcimIscessoerrnrniaceoehepttoepmuiosnaaoCovfto,psenflseiCaul8eeaniiwlsanedtcpty8alsiindxet.oavosoeadvaoespencfxAsmeolCdrfiadspyaoluoaleeispo8tltnndccaeyceosoawrdiisdruipsa(ebetsnsiriwitaaooasotseenesisessc,n.drvieeirhituast.evahddoTytunmtreaPemlfdahoaodusdtsrsefnnhstcaoliregoCuCwnnheelsieaconsofe88ticrcoi,hrtrilarhitizieuirloinintnnieissnimtesnceoc,ttosesslrgranaeltterelenrudoasaavddletssd,euyeerCildddos8y...l
22
HAZARD CHARACTERIZATION FOR HUMAN HEALTH CS EXPOSURE __________________________ CAS REGISTRY NO. 3825-26-1 _____________________
bTaCehs8tiewgasnpeeeiprfneeicashauresnlmtttsososimgtuelgooogbdefiinfstoyt, xtmhhiecaepitatayCntici8cneaalhflnuufdemlcaitmrasnvmmos lauautlnmetehreree,epasCrpno8oddnllueesvceuteskilvosteocohyxbotesernemcrovoboeuindonettsiisncaswtnh(idGitshtihslClatiu8ltadtwnhyde.aslaHinovodbewsr eiesrvvneerod,t. Mandel, 1993).
V. EPIDEMIOLOGY
wwwheerreeererVoeCbv.tl8ia.ieainawn.nteehdAdde.o.rmteOhOtorevnorretlsfayrplaluteilhtolcyotrthoisfvecoeeolnwlmocuhowmpoho-bouwuerpntor.dmroksOfoeadrfdrteteahfalometihtry1as6n8swm0tuuafkodasncnysottiuwhgwrsnaenosdifdr.micemRaaanodtehtreclseoyo,r(l1fd3e7es6s7m8so8tdnphewl4aoa2nyoth1erek8ecxeseperramesttic)fpatwiecl3odeaMy.rteeeTsephslaent
observed-to-expected ratio for cancer deaths was 1.0 (Ubel, et al., 1980).
aifnenvmdeaesltmeigVpwalt.ooeyrdkm(eGresniltelmailtlap.anblodp. ylaaeInndndtbawMerthewaetnrreodeeesnCpl,e811c9a9t4ni9v7d3e)ao.nctodhTheh1ore9rft8lcum3oo.horooTrtcrhatolecmitoaypnlloss-ticuusantduedydss,eoaasrfsre2etaml7an8tadi8noamunrdfsaaihzclieetpudabrnmeeddtow7wr4teaee9lrnietymortality riw2peeagpCnam.mrser0cte8osoenrr3pa,osesee(ilttctaliSroah4aniasntyaMeteeteouttmidrhincmbRoceegeacsnas)bnneauenawbetrcuxlcnviretespaesdnetoresrowdo-nCmfms0sefoeapp8.oet7odntrehnrpo5droctgitrsasvpair2oftflloreoasiidiotcertuttryuueyxdipmScdnpuwcMtaytecaairehnoctnloraRieedntpcounesnernw0fddgearoc.whtno5daodresd8temmedoehaaan.r0iepetktsndh.hrnIa7sosatfscor7hocentlfcahierdrfrdinniooeanwntidpmtrocepoeroatfdotrnhaemlp-osloemewsrtstexeotatneuainarpsttmaalde.httoeettaiusicspTeatoe.caerlshnodasancTsielsnycggau.hhcmeSnnrgeeiroMcisgerrmfuetneeimoRprctsu.wra.tisoysnntAatrfIhottsonbpama3frnreltt-oithpoofthCvdyoenreiso8ulegeieddcswgmxxmttiniacispenoaieeetdofceynnsaisrcs.as,ceeianesaida1Gsn,cnhs0tgtrreicylhevyeryepieaoleenraosunawtetprehtshedethroeseteiofsre
VL DISCUSSION OF ENDPOINTS VI. 1. Discussion ofTarget Organs dwnepofeeefcgreiirgsocohtdssrt.iesswT,gEohhaevreerfdeiptpdhladereetiesnomsmlccivaeoeorelfonylrrus,fotlthaaaruarenrtgtpedheeaydoittnpofotdoeterourgxbtxcarpeotinoicporsifethnuoyvyrroeew,Orf.lsaipSviTseb-ehnrliroeneodxdwtheiueesghcovpeeemiadnndteoeetaorsntnaoxt(itxmiiriconaicinattssily,ttsyuaiinwndsmcdieterharemseneaiiispnlcfeierevmsoseotviosrnnindialfnykesivd)emi.enywricsMcreioeetnah,raznrshayayeumtrdsmoe,elcfaisaotv,nnhvesdeer.srey
In contrast with the rodent, the target organs in the monkey were the
23
HAZARD CHARACTERIZATION FOR HUMAN HEALTH C&EXPOSURE . _ _ ____________ CAS REGISTRY NO. 3825-26-1___________________________
gtthoaesmtlrioovdienirftyedsottheinesanhleotprtaaactpitcpaenaandrdtthoimebrmeetauicnpuerliromeesanprdoyonttasheregtleoiatxloseryngsoatnbemiiont(ihcGusrm(iGfafniitlshli,laaennxddpoLasnoudnrgeM,to1an9C8d80el)a,.p1Wp9e9ah6ris)le. VI.2. Discussion ofDifferences in Species-Specific Sensitivities
The indnoHnn ofperaxisome proliferation by xenobiotics is generally determined aipicscnnsperacoelttaslrhlcne,iteifuadeiemmnssore.cagiortmiWsienrosaap.nDhsnrieidTinNlseiahpnAalrersaoitssmhptryoshevanceaaotitnneahclosdutteeimms(vmdiiniseewticnicadeloeinustenhddan,o:rioslnfeiiifnvtcgpypceeamrerroretrgtafaoaiirpcnsxnoeue)iw,spsrloaoaeitrmnxhrrleo;iynesxpaouspinremsmerdondoebmslolsiiievmtfeirieenv-arisrenant,phattdLeioneocevtnitaylofhyfidilficsunsiegemnocpnntcoheeze-tedyrolunelmo,fnosrppaimegfneosoaer,dnrnonomsp.xoirvainPsaane,ocse.cgmrraroouenesxianssitin;iseacoacalalmrnpeciaeignssea,r
VI.3. Tumors Associated with C8 in the Rat ipaaLopacnsrrbeoreiosetrsmnyhoolernidcexemfririevpigrasroceaotCaoecendtrtmeld8towplpel.rlhewhdras,iPaespoaithnsfeornfraeoorobdtvoimlhoueniexpefe,ndeieapbnadsunrnaoencadotctemdeotoenronecmtaberfhaaasloeopoitrss(ricsnrnaccoioatsgslnralotsctiiorwoclaiffaeageiicdtnbiatereiteaaaorhsnddattrt,feoettafcwestdoreuei,ssseiblmw,uHtlhi.ieobnnioCfcfsaHreerceFgsapeuttyCeutieorsnpnim-rrn.fee1eordrracno2Hxpauotc3rilslocssme,,a.otwwmsiiopmnoiHeaefoenvteernoufheeoneepnefrycifod,rtnlelohapimsci,vleltlftiatioeosrfehasieerfraalii,eerlsatcdayaL.ratetaeuoerorlpSecleymrfaceetdtpiytouovnnieepggmret,rtlernpoyhaoeasoirxnelzporiiidseksrelsf,daoinriWtlnoayomtetxnopwryaediCaiesbpnctofp8spaeem:ale-elln1ayxeircv4psre,o6etraso4,ut3ibrc)ee proliferators. VI.3.a. Significance of C8-Induced Rodent Tumorto Human Risk
VL3.a.l. Liver Tumors peroxisoTmheeapbrounlidfearnactoerosftodarteaspinodnisciavteessptheactiethse(rreatissaanhdempaictoec)airncicnhorgoennicicsthuadziaersd, wo fhereas thqohuafezefeacstearidrohcnaeinaspsboaelgtesoes.cnmaTircehcnhientaeoszhpgaoireddunelitmdcobienofeolfoencgco-rtynsessdoipdafoteaCnr,ed8adilanbnngeedisgtpollieitgmhcieibiertlseep,d.es,ruosctxrhiosanosgmhlyeu-mspuraopnlpisfo,erirtsaftceolaertsafrfeloyerrheulemvaannce
VI.3.a.2. Leydig Cell Tumors Leydig cell hyperplasia and adenomas are commonly observed in laboratory rats. TFap3hp4er4oinrxcaiimtds.eantIecnleyco0of-n1stp2ra%osnt,tbafyneee2oryuaetseaLrisenyohdfuiagmgcaeen, lsal nhaddaseranbnoegmeenassrfeirpnoomCrtreald:pCptDorobxeiBmaRpatprearlotysx6riam4n-ag1tee0sl0yf%r0o.4minp er
24
HAZARD CHARCAACSTREREGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH C8 EXPOSURE
msptarurrimieoglldgnriwuoeocnstitgea(ae0Lsnss.ee0ouyg0cbid0issai0tgta4eTncd%theiwlai)ls.lititduAshimfslLftuoeheprroyespudnoigincrghterecoaidenddlbeltiyhnrtueetecmsspttuioucdsrodecimigmeeepspintobaieblrusoiiistglsoiaytinrynediohascftuosarmomofmdramoenemnosw.tnshclyoaatnmintdepgnhoeuuusotmneuddassn,btsthyhtaeohtudLcmaleetayaandrlsiygacnedll Ltakttdahhhnnloeateidoeysstielrwdtioi-htsnirhnwgeegtehrCtscehetpleeh8ifnaovloecdtlanesranenesorsaonedetrfnnud,eatod-mhoulsgetscesahveoerereonaisrenrossnboh.empcsftyoeeeaTseprxrytnomhvoioscxteett.aehdhicmrsmeIuoogrtsemam.imiincnzsahTpegeonioadhmepfsnuertisipncroonsaeadomlfpfidnsrefotretea(noorytsreneodfau,artttutcmpauotbcohpmrteeishnracootcrisdohnearoonCeisgcmgsshhn8eaieopdo)nintlsletpeudearpsarmtcfeotirpohsclodopyereidurrsptrsuoscuuntlvcpeamoloeierbLpaitodilaeenecratoyioecomgdudrmffeeitaioftn.gaprhfregselHecteesirhenitsedoseelnolwiolinqyttssfueumepusvem-aaenrxeenefrodcrpeots,rhieetpxtsiyracatoisbtn.tsietniysoiovdssmoem.edeaI,stf in
VL3.a.3. Pancreatic Acinar Cell Tumors rttoshhehfaleoeenupvvtlaaidhdnneebccCnrele8iecvttaeoraesentrhhaadtutnauemotdmdtthhaaosnreeiremsrsp.hpciayleaTnarpncroholrnxyeetohimatsetotoisbemcpicezeaheecrcadopoinnxrmtiooasismprlopilcfmereoeotrleefdall-ttutyupoucmrrrmeousoltlodiherfrodeiesgrsnoaeaeorntuoteteutrpshm-iriHosnoordidomrsuswunoccveoeneivdaatienulaLrlcnytedrhdmeyieefadrrefsiseedegtroiiseasconitenaedtld,lmgp,tareuetonrhmcodwehxortiaheinrnssfegoio.rsmwermefeeotsihrgeiehnyt W . SUMMARY mcghmiatidnhnosuieohggcerivlndnrah/ohemeleeewlaeaaaora3tpscalippaeCou(atomesmidttn8gpoed1eiesatenhi0eonancxtcar0xtsoihmpaistu0idyaloc6rmaem,lteis8aoltniudoy0trgixcirridmao/eoetirkeicsinstfgtogroao7,aCt/.fotka.rtCi6t8exngoIumn8midanimicnsucnpictgiotutintaroya/lhrtomlgensdraedweajutoi3uurnibn)lioranc.ttibahtctnemc.ihlOdttiatoseinaIovrrn4flaalxeeisisn-tlvveciihorcdasvheeaol.inrirertctud,ssdyorTli.rpainbCnwshlAaiAklicet8neicLeitsncnfahliseCeinrltavaeeLsotsqboaodeiDcfusgsriofutn,soeneh0rloagorafse.m'pnf8uSrsoertdserutiamcfuoaftptbttefdannsgoabegsig/assxecitLeituittstinsenscebci.igiiyoncngoctChyefinrftrtraxhycaCpo8wdoee.trm8suwnoenr,aridptaacCer1luraslt7soyo8ctft8idbeuoorSpudemsdunrueccoinsmbgreeeddvcads/doukhesencdmcdgrdloooeeo.aiitnndrwnlattdfiCocaitdmreatn8mobosasehele8eadass rhatshohtsneudespmdoesaicnauetiintbsacssstTaheieaoshfaqpfnwesuepabcreeeentnealslldtere,adnvtaposeanrtvhoenbdepebcetlieahofdibonepteoclrsmmeeeuhfnlseiouionsnomrlitoketfioagvtbshnfyeeerevhtdoosweeaderraeteaunalenltn,onhithrnnlepoagivsevsfeepretnlsoouertoxnimdtgtiusossaoimoxvetromivesocretirseonars.-a.gdpplReurAeioncnerUteogvscdxaoefperismbosdrtoyaisibgntmepoiagnlerteia-otrt-ihtotrpnilseoxredotniluoosilevoiorfceemefnodrrio,neanltticphovvlruerieov-rdrioelneigfdiarteshounraawcadtetstiodhntrrsoavnniintgdro
25
HAZARD CHARACTERIZATION FOR HUMAN HEALTH C8 EXPOSURE
__________________________ CAS REGISTRY NO. 3825-26-1
_________________
heaevrepeanfrttoos,cmawxhchiicanhnogglefeiasndiicntohtfatizheaelriddveetvor.ehlTouphmmeasenensht.eoEpfavLtiideceycndhciagenicgseelasllsaaonpdpaecpcaaurntmcoruealalattteiicrntgahcteihnhaaotrrtchmeeollinntauitlmicaootirnnstgrol otAcChofd8athtdheotiexhtritpteoesosnstesuatuidelslrxiyeeat,snrapadnorhdofpegwaparndaoacvtmrirekcersetasurmsesm.hoeAouxnrmpilsttoohapsronoeinudshggeethoaltihltttChethle8ehesepofeafrrreloentcvhlotaisodt.ciefoaCrnncos8ihn-eeiopvxgsipdenoneesniececddheatwoozofabarrekdnectaroossnshaofunicrmdmiarateeindotrs,no.isbtpeisetwclitkeiveeenly
opportuOniftyprfiomraerxypcoosnucreerinn itnhehuwmoarknspilascteh,easnlodwthcelmeaoradnecraetoe-fhCig8hfarocmutehtuomxiacnitbyl,ood, the regardless ofroute of exposure.
26
HAZARD CHARACTERIZATION FOR HUMAN HEALTH C8 EXPOSURE ______________________CAS REGISTRY NO. 3825-26-1 _____________________
REFERENCES DiiPnnt Co.. Haskell Laboratory Report NumbersfHD: 55- 61, Acute Oral Test.1961, H. Sherman. 56- 61, Subacute Feeding Study.1961, H. Sherman. 123- 65, Effects ofFluorocarbon Disbursing Agents on the Livers ofRats and Dogs. 1965, J. R. Bames and H. Sherman. 124- 65, Two-Week Feeding Study.1965, H. Sherman. 128-68, Acute Oral Test.1963, S. B. Fretz. 160-69, Acute Inhalation Dust Toxicity.1969, F. O. Tayfun and R. S. Waritz. 253-79, Inhalation Subacute.1979, G. T. Hall. 635- 79, Eye Irritation Test in Rabbits.1979, D. F. Edwards. 636- 79, Skin Irritation Test on Rabbits.1979, D. F. Edwards. 659-79, Skin Absorption LD50- Rabbit and Rat.1979, D. F. Edwards. 589-80, Rat Skin Absorption Subacute Study with FC-143.1980, L. S. Silber. 682-80, Skin Absorption LD5o-Female Rats.1980, J. E. Henry. 205-81, Subacute Inhalation Toxicity ofPentadecafluorooetanoic Acid, Ammonium Salt.1981, S. D. Nash and M. A. Britelli. 291-81, Oral LD50Test in Guinea Pigs.1981, J. A Hall.
295-81, Oral LD50Test in Rats.1981, J. A. Hall. 329-81, Oral LD50Test in Mice.1981, J. A. Hall. 560-81, Mouse Feeding Study - 14Day.l981,L. S. Ford. 565-81, Acute Oral Toxicity Comparison Test in Rats.1981, L. Hinckle. 567-81, Oral LD50Test in Rats.1981, J. E. Henry. 593-81, Ammonium Perfluorooctanoate Blood Levels in the Female Rat1981, Kennedy, G .L .
27
HAZARD CHARACTERIZATION FOR HUMAN HEALTH Go-EXPOSURE _________________________CAS REGISTRY NO. 3825-26-1 ___________________ __
600-81, Liver Weight Comparison in Castrated and Ovariectomized Rats vs. Normal Rats.1981, L. Hinckle.
537-82, Fonrteen-Day Feeding Studyin Male and Female Mice.1982, J. E. Heniy.
788-82, Acute Oral Toxicity ofFC-143 as a Function ofAge.1983, L. Hinckle.
F1e3m8-a8l3e,sC.1-988L3,ivCe.rNW. Weigyhlets. in Rats and Mice: Oral Administration to Males and
DuPont MR 5686, Investigation of Hormonally-Mediated Mechanisms for Xenobioticinduced Leydig Cell Tumors in Male Rats. (1989).
3M Co. Reports:
Personal communication, J. Long to PJ. Gort, January 8,1979.
3M Report M-601 (1981).
3M Report 0681TRQ110,1981.
3M Product Toxicity Sheet, May 24,1996.
Biosearch, Inc. Report No. T1395, March 4,1976.
Coming Hazleton, 17388-0-455, May 16,1996.
Coming Hazleton, 17388-0-437, April 25,1996.
Hazleton Laboratory America, Submission, Fiche 536984).
Inc.
2-6-87
(Submitted
to
EPA,
TSCA
8eCAP
LRiitktoenr LBaiboonreattiocsry; LDBraIgPrMojeetcatb2o0li8s3m8,RFeepborruta1r-y201,1(1997880.).
Riker Laboratories, Report 09790AB0485, March 15,1981.
Riker Laboratory 0281CR0012, April 1981-May 1983.
University of Minnesota Environ. Path Lab, T2942, April 9,1981.
Published References: Bpeirefglueol,rLoo. Bct.a,nRo.aCte.oMn.LLeiyud,iMg c. eEl.lHfuunicttt,ioann:dInJ.vCit.rCo,oionkv(i1v9o9, 5an).dEefxfevcitvsoosftuadmiems.onTiuomxicol. Appl. Pharmacol. 134:18-25.
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HAZARD CHARACTERIZATION FOR HOMAN HEALTH C8 EXPOSURE . . ^___________________________CAS REGISTRY NO. 3825-26-i___________________________
Cook, J. C., M. E. Hurtt, S. R. Frame, and L. B. Biegel (1994). Mechanisms of Texotxraichoelpoagtiiscttfuambsotrraicntd!u1c4ti.on by peroxisome proliferators in Crl:CDBR (CD) rats. CTadoofxotnikcn,omJl..aCAsb.n,ypSla.-mMPhm.aMormnuiuarrcmaoylp.,e1Sr1.fl3Ru:o.2Fr0or9ao-mc2t1aen,7oa. natde:MA. Ep.oHssuibrtlte(1en9d92o)c.riInned-urecltaiotendomfLeechyadnigismce.ll FRaeyseurlwtseoafthbelor,oWd b. iEo.c,hLeimveisrtsrtyutdeystoinfgW. DasuhPinogntto, EnpWidoermksioelmogpyloDyeiveissieoxnpoosfeCdotropCor8a:te Medical, January 15,1981. pGeirlflilluaonrdo,oFc.taDn.oaicndadJ.dSp.rModauncdtieoln(1p9l9a3n)t. MJ.oOrtcacluitny.aMmeodn.g3e5m:9p5l0o-y9e5e4s.of a GeAnimzllyielmrainceadsn,,lFJipo. ouDpr.nraoantledoinfJs.I,nSad.nuMdstacrinhadolelMels(et1ed9rio9cl6i:n)Ae. S2se9tru:ud5my60op-ef5ro6fcl8uc.ourpoaoticotannaolliyceaxdpdosaenddmheepna. tic pGerrifflfuitohr,oFo.cDta.naonadteJ.. AEm. L.oInndg.(H19v8g0.)A. Assnoicm. Ja.l4to1x:5ic7i6ty-5s8tu3d.ies with ammonium Je[o1li4hmCnis]nopanet,riofJln.uDoorf.o,coSac.rtbJa.onnGo-ai1bt4esooinnr,rpaaonttsdaasRsfit.ueEmr .aOd[ m1b4einrCi(s]1ptr9ea8rtf4iol)un.oCorohfooacmletasmntyeorsnauimulfmoinnea-teen. hFaunnceddamfe.cAalpnl. Toxicol. 4:972-976. KApenpnI.ePdhya, rJmr.,acGo.lL..8(11:938458)-.3D5e5r.mal toxicity ofammonium perfluorooctanoate. Toxicol. KInehnanlaetdioyn. JTr.o, xGi.dLty., oGf.ATm. Hmaolln,iMum. RP.eBrfrluitoterlolio,cJt.aRno.aBtea.mFeds,. aCnhdaHn.. CTo. xCihc.en24(1(1928)6:).1325 1329. K3am0e0nm.noendiyumJr.p, eGrf.lLuo. r(1o9o8ct7a)n.oInactereaansderienlamteodusfleuloivroecrhwemdgichatlsfo. lTloowxiincgolf.eLedetitnegrso3f9:295 Lprioul,ifRe.raCto. rMs .o,nCr.aHt Laheny,daigndceMll.fEun. cHtiuorntti(n19v9it6roa.). FTuhneddaimre.cAt epfpfIe.cTt ooxfihceopl.a3ti0c:p1e0r2o-x1i0so8m. e Lpaceiurtio,vxRiitsy.oCimn. Meadp.u,rolMtlimf.eEarl.aetHoCrur,rlta:tCm, DJm.BCoRn. iCu(ComoDkp),erarafntlsud.oLrFo.uBonc.dtBaanmieo.gaAetelo((n1Cl9.89T)6,obox)ni.chEoeflpf.ea3ct0itc:o2af2rto0hm-e2a2t8a.se
29
\
." HAZARD CHARCAACSTREERGIZIASTTRIOYNNFOO.R38H2U5-M26A-1N HEALTH_C__8_E__X_P_O__S_U__R_E_
O(W1h9ryv9en7tmh).-.M1J4.e,D6ch4.,a3nS. i.sTRmo.sxFifcroaormltohege,yRpaa.nnHdc.rABeapetplilcliJeordn.,cPDohg.aeSrmn. iLcacoeonflfgoeagcetycsk1oe4fr5,th:G4e2.p5Se-.r4oE3xl6liis.ootmt, aenpdroJl.iCfe.raCtooor k mPpeaorsortpoxhoisoro,lomTg.eiPcpa.,rloKslti.ufePdr.iaeLtsieooen,f.MamE.xmApo.enrPiimeurmenn,ptaaenlrdfaimuPo.irJMo.oGoclitelaclniueolsaa(rt1eP-9ia8nth7do)u.lcBoegdioyhc4eh7pe:am9to8icm-a1le0ga9na.ldy and Pleevreklisnms,iRd.pGer.o(x1i9so9m2)a. lInpvroelsitfiegraattiioonnoinfathmemraotn.iuTmhepTerofxluicooroloogcitsatn1o2a(t1e)e:f5fe2c. t on hormone tSetraaptolegse,nRic. Ep.o,tBen.tAia.lBoufargmemss,oanniudmWp.eDrf.luKoerronosc(ta1n9o8a4t)e. (TAhPeFeOm)birnyoth-feertaatl.toFxuicnidtyamanedntal and Applied Toxicology 4:429-440. Uexbpeol,seFd. Ato.,flSu.oDro.cShoermenicsaolns,-aanpdreDlim. Ein. aRroyarcehpo(1rt9.8A0)m. H. Ienadlt.hHsvtaet.uAs sosfopcl.aJn.t4w1(o8r)k:e5rs84 589.
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