Document x1v9wrOKpxNEKXb9oqEY9oLGg
Al226-/548
Toxicological Summary
Pros
Dietary Acute Northern Bobwhite Study
`Test Substance: Perfluorooctanesulfonate (PFOS)
Structure:
Remarks:
METHODS
poaium sah CASH 2795.335 |-Octanesulfonic acid, 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8.8,8-heptadecafluoro-, Trhedtesutndsuebrsatamnbceitis caownhdiitoenspoawndderur(GM wlats#o2r1g7i)nallTyhedrsammpilnedwa1s pleas be 90.49% byutp LCMS, 'H-HMR, riploiglon ""F-NMR and elemental analyses dCeotnecremninaeidontso ibnehi8s6s.u9%m.marTyhaersnvoamsienaolnatned 8m5e3as%urpeudrtydiveatatrey PFOS vTahleueis nbafsedphoanseherep0o.rt40wa%spourrgtiynaelsltyractoimopnletTeheinre2po0r0t0,waasndrrieepodrted 3008 to rflt the subsent revision. in ample purty This
Toxicological Summary reflects these changes as well as including results from all of the associated reports of analyses of tissues collected during
the in-life phase.
`Method: OPPTS 850.2200 (Draft), FIFRA Subdivision E. Section 71-2, OECD 205, and ASTM Standard ES57-87 (1997)
TYeyapre:: 1Di9e9t9ariyn Atceuteet, 2000 for ror, 2004 for amended prt Specie: Noth Bobwiit Coli virginamss) Test Phases: AF csimatoy n- 10.ays
Post-cxposure recovery period -- 3 or 17 days (with the study ending on
cither Day 8 or Day 22, respectively)
Tost quail Age: 10 days ca est nan gm --------
rS(ewophaliiccoahtfeis3n0cilngucdueasdcthsiitgehstthedsuobcssotmgarnooclueprter.ematTmaehnnet.anaTinhmdearl1es0wwqeeurraeelaflilIvneesxqupaaoeilseopetfrorrsefpeilvipecatdtaeays(,preanne)dmftohroena ld Tor ecovrs pron, At ey 5, lf the relat fom oh esters Sup ( of
|
GOO585
6harlefpwleirceatecsonftrionmuetdheincotnhtersoltuadnydun1tiflrDoamyc2a2c.h dose level) were sacrificed while the other
FteesetdinganphdasWeasteorf:thFe osotuddya.nd Twhaeteqruawilerdeidprnootvirdeecdeivaed alniybiftuommduorfinangtiabcicoltiicmattrieoantmaenndt
during cither the acclimation or test phase of the study.
AwnearleydteitcearlmMionenditboyrirnegve:rTsees-tphsausbestHaPncLeCcaonncdemntarsastisopnesctirnomfeeterdy.and quail liver and serum
Statistical population
Mfoerthaodgsi:venLCeSx0po(sLuertehaltimceo)nceanntdratLiToSnOth(aLtetrheaslulttsimien
50% that
mortality results in
of a 50%
muosritnaglitthye SotafatistpiocpalulAantailoynsifsorSyastgievmen(SdAoSs/eS)TvAaTl:uePsRwOerCePcRaOlBcuIlTa)t.ed LbDySp0ro(bLietthaanlaldyossies,
as measured by given exposure
average daily time) values
iwntearkee,
ctahlacturlaetseudlsbiyn
5pr0o%bitmoratnaalliytsyiso(faSApSop/uSlTatAiTo:nPfRorOCa
PROBIT). Body Software (Dunnett,
weight data 1955; Gulley,
were compared 1990). All other
by Dunncils test using TOXSTAT statistical evaluations were conducted
with Excel worksheets including regressions with concentrations of PFOS in tissues
Average basis and
Daly Intake did not take
i(nAtDoIa)ccoofunPtFpOoStenftoiralcadcifhfetrreenactemsenbtetgwreoeunp
mwaalse
easntdimfaetmeadleosn.
aFpoeond
consumption and adult exposure period and the
quail ADI
wbaosdycalwceuilgahtteddaastafowlelrowes
a(vEeqruaagteidonov1)er
the
duration
of
the
ADI (nghgiy)J= AAveeravgSeFe--EedCT--onesurmepiIo--n (CWb--iOorUdmy))IROConne pmpros) (Equation)
Test Diet Preparation The test substance was mixed directly into the feed ration by
museeadnsinotfahisHosbtuadryt
mixer. were 0
No carrer was (control), 17.6,
used. 35.1,
Nominal dietary concentrations 70.3, 141, 281, 562, and 1125
of PFOS parts per
millon (ppm).
RESULTS
MofeaPsFuOrSedinDitehte Ctoesntcedinett.ratiTohnes:meWailndipfeerceInnttemraetcioovnearly Loifd.thdeetmeartmriinxe-dspickoendcenftereadtiwoanss
94.7%, while the from 92 to 119%
toefstthfeeendomsianmapllevsaluhea.d
mMeeaassuurreedd
cmoenacenntcroantcieonntsraotifonPsFOofS
PtFhaOtSrawnergee:d
<LOQ, 18.7,38.6,71.5, 167,279,516, and 1148 ppm.
Mortaliies and Clinical Observations: treatment group is given (Table 1)
A
summary
of
the
percent
mortality
for
cach
2 CLO545
Texapbolseed1.toCPuFmOuSl.ative rcatment elated percent mortality of juvenile bobuhite quail
"NominaMleasured Average
--
PCoFnOe.S CoPmFeO.S mDaakiley"
Exposure PeriodDays Recovery Period
Coonwmol <GLeOmQT g<hLOQeyT0 20 50 0 S0T0 07 0 70
3716 318867 48s2 00 00 00 00 00|00 00 00 00
3WoolTS 24318 00 00 o0f 00 00f|l0o u0 o0n o0u
5M29sie a195 00 00 100 200 2S00||48 15000 1$000 1800
v1ersge Ty 1akse (ADT me2F5OSS bo0dy We0g 730Gay biaosed oinoDoa|y100050010w0eig1h0n0d T1e0d0
Limtooauiamsitsactaorne(dLn0Gsyfosr PaRmOeSnneheldsinctwhaesc1x1n0doedranny period om Dy 10 oy 22
2Onengucn ewasacumbadse oonn DDeyy 3aalhes ssoutasnnigngaa obrbkeenn oeggon Day .
sOunbeseqquuaeinltliyn ctuhebacnoinztreodlognroDuapyo6.f 3T0wwoasothfeorunqudaiwlitihn tahebrcooknternolleggroaunpDhaayd f5,otanldeswioanss twheartewenroermaaslociinateadppweiatrhanccaegeamnadtebeahgagvrieossriotnh.rouAglhooutthetrhqeuatieslt.in thThecroentrwoelretrenaetimtehnetr rpcpammientt.heedliaett.ed mortalities nor overt sigas of toxicity at PFOS concentrations < 70.3
Ibnrotkheen 1l4e1g panpdm tthreeraetmweanst gornoeupt,reoantemebnitrdelwataesd emuotrhtaanliizteyd(o1n1%D)ayon3 Dsahye7.susNtaoinoitnhgera tmooxritcailtiyty(wwiansgndortoeodp)o.r tHhioswetrveeart,menbty. DTawyo9a,ddtihteiotnwalo qquuaaiilldihsapdlaryeecdovcleirneidcaansdigntsheiorf aapdpeaarnaonrcmealansdppbeeahraavnicoerarnedtbmeehdavteod nnoorrmmaall.ly Aflolr tohtehedrurqautaiiolnionftthhee 1st4u1dyp,pm treatment
aInddtihfeon2a8l1 mpoprmaitireeastmebneti,ng80o%bsemrovreadlitfyor(Vth1e0 dquuraailt)ionwasofobtsheervteesdt.by QDuaaiyl7mwoirtahlintoy rocucfufrerdeadpopneaDraanycse,5,r6edauncded7.reSaictginosnoof tsotxiimcuiltiy (wseorundabasnedrvmeadtiporni)o,r teohdaeragtyh,awnidnigndcrlouodpe.d Jhoasdsnoofcromoarldianpapteiaorna,ncleowaenrd lbiemhbavwieoarkonrestsheanudractoinovnuolsfitohnes.stAufdyt.er Day 3, surviving qual
DInaythe7. 56S2igpnspmofttroaxtimceintyt,obmsoertravleidtyprwiaorsofirdsetaotbhseirnvcleuddeodnaDafyle3dansdppreeaarcahneede,1r0e0d%ucbeyd rweeaacktnieosns,tolostwiemrullii,mbleriiarggiyd,.dperporsetsastieonp.ostwuirnegandrdocopo,nvullosssioonfs coordination, lower limb
3 6005.57
DInayth4e. 11S2i5gnpspomf ttorxeiactimteynto,bsmeorrvaelditpyriwoarstofidsetatohbsienrcvleuddeodnaDrauyffl3edanadppreeaarcahnecde,1r0e0d%ucbeyd wreeaacktnieosns,toansdtimluolwie,rlleitmhabrgriyg,ididteyp.ression, wing droop, loss of coordination, lower limb
dBiocttharyLC$Sd0asyaLnCdSLOTwSa0s f2o1r2PpFpOmS PwFeOreS dweittehrami9ne5d%bcyonpfriodbeintcaenailnytserivsal(Toafbl1e582).to 2T7h8e cppomn.sumTpthieonsldoapteaocfoltlheecctoendcednulrriantgiotnhere5s-pdoanyseexcpuorsvuerewapseri7o.0d4.werBeoduysedwetioghetstainmdatefoaond LavDeSraOgebadsaeidly oinntaAkveeroafgePFDOaSilyandInatankeadd(iAtDiIo)nalofproPbFitOSanawlaysses61wamsgcoPndFuOcSteKdg. bTohdey "`Twheeigshltoipdeaoyfwittheh daos9e5-%rescpoonnfsiedecnucreveinwtaersva8l.8o8.f 4T8hetoL7T7S0m,gesPtFimOaSt/ekdgwibtohdythewei1g1h2t5idpapy.m wPhFeOrSe t3r0e%aummeonrttadlaittay wwaass o3.b0s6erdvaeyds.at Tdhaiys3reasnudlt 1a0gr0e%edmowrittahlictuymuwlaastiovbesemrovretdalaittydadyat4a (Table 1),
oTafablpeop2u.lEasttiiomnaotfesjuovfentihleelneothratlhecronncbeonbtwrhaititoenquoafilPsF.O*S (LCs) and the lethal time (LT)
Effect metric Time
TCs0
Day 3
LCS (ppm) 1593
95% CT :
S3i1op7e
DDaayys6
p3r1e9)
232586.-464782
a39m2
DDaayy2$2
22112
115588..227788
77..003366
TT50
2D8o1spepm LTSO64(1Gays) 59659%7.C610
S9lo5p4e
1516225 ppppmm
430768
417.- 548
680259
RTT eres stmated by PottslsGASSTAT PROC PROB
bBooddyy wWeeiigghhttsforInqucaoimlpsarinistohne t1o7.c6o,nt3r5o.l1s,otrhe7r0e.3weprpemnotraepaptmaernetnst.PFHoOwSevreelra,teqdueafiflecitnstohne c1o41m,pa2r8i1soanndto5c6o2ntrpoplsm(tpr<a0t.m0e1r)tfsorhaDdaybsod0-y5.weWihgihltes tthhaetrewwearse asisgantifsitciacnatlllyyrseidgunicfeidcainnt wreadsucntoiolnoningebroadpypawreeingthtbyatDPaFyOS15c(on1c0edntaryastipoonsst e>xp7o0s.u3rep)p. , tAhsiswbaosdyobwseeirgvhetdrfeodrucbtoidoyn owbesiegrhv,edsiagtnicfiocnacnetnttrraetaitomnesnt>-r7e0a.t3edpepffmectPsFOoSn.bodHyowweeviegrh,t agfatienr fDraoym D,ayno0 ttroea5tmweenrte. treerlmaitneadtieofnf.ectsEffoenctsboodny bwoediyghwteiggahitn owrebroedynowteeidghatt gaaniyn ccoonucledntnroattiboen dtehtreorumgihnesdtufdory t2h8e1s,e5g6r2oupasn.d 1125 ppm rcatment groups aftr Day 8 due to most of the quail dying in
4 600543
d`iTcatbalrey3c.oAnvceenrtargaetiboondsoyfwPeFigOhSt.(g) ofjuvenile northern bobwhites exposed to various
Treatment Body Weight Body Weight Body Weight Body Weight Body Weight
(Cpoprma)l Da20y201%
EDaEy]$
3Da5y8
9Da1y 015 D2asy1232
3157.16 2210211
33114a3
0s 3943
688 6555
757 8927
710413 2200+411
a30e5s2
3743 meas
60+ 83
924 7922
281 562
2200411
116805222
10n+4
3sm
5m5
112s 201
m
nm
m
m
7S3aotdsyntoitwceaapillgyihdciafebrrleepndotrutfefdrooam10mc0oan%tnmolonrgdtraoSluatpnindprne<ds0vt.m0no(tDgnruonuo,nnweer1c)w. eb
Ivnaraisoeucsosnpdasnestooffatniamleysdeusr,intghethgeroswttuhdyr,atienscflourdicnagch0-t8redaatymse,nt8g-2r2oudpaywse,reancdalc0u.l2a2teddayfso.r GJirnocwartihzerdataend(1t/hdeany)fiwttaedsteostthiemabtoeddywwietihghatgdeantearaclolglercotwetdhdumroidneglth(eEqsuuadtyi.on 2) that was
W= Woop"
(Equation 2)
Where: Wi is the body weight () ofa mallard at time ()ofthe study Wo8isthethoevebroadlyl gwreoiwgthht (a8t)eo(f1a/dmaayl)lard at the onsetofthe study (1=0)
tis time (days)
Data from the 562 and 1125 ppm PFOS treatments were not included, since all quail had
d7i0e.d3 bpypDmaywe8r.eFonortDastyat0is-t8i,catlhley gdriofwfetrhenrtatefsroofmthtehequcaoinltrionltrgeraotwmtehntrgartoeup(Tsoafbllees4)s. thIann
aDgaryee0m-e8ntgrwoiwtthh
trhaetebsodthyatwewiegrhet
rdeadtua,ceqduafirlomfrtohmattohebs1e4r1veadndin
281 the
ppm rcatments had controls. However,
after Day 8 (Day 3 of the recovery period) the quai in the 141 and 281 ppm treatments
rthoanw
oart
eaquraalte10tha7t0.w3apspemquiPvFaOlSe.nt
tTohethoaveorbasllergvreodwtinh
quail rates
from treatment for quail in the
groups less 17.6, 35.1,
c7o0n.t3r,ol14g1r,ouapn.d 281 ppm treatments did not differ from the observed growth rates in the
5
GROG HG
Table 4. Growth rates (1/day)
Days
0
for juvenile Tnroeratthemrenntbogbrwohuipt(epqpuma)ils exposed to PFOS. * 6 ssi 03 ia om
008t10o02822
000.00068530593 000.00056850153 00000086838991 000.000857287823
Growthrte cmtby nea regression: (LnBodyweighGhgrowth
000.000666422843 000.000571294680 me 3 ep)
tFheeedexCpoosnusruem(pDtaiyosn:0-5T)hoerreecowevreerynopePrFiOoSd-r(eDlaaytse6d-2ef2f)ecotfsthoensftuedeyd. cAonrseudmupcttiioonn idnurfienegd consumption was noted. at the 281, 562 and 1125 ppm treatment groups during the bOexvopedorysaulwr,eeitghpheetjrduiavoyednfio(lrDeatqhyuesaislt0u-da5yv.)erabWughteidlteahetcshoeenrseruewmdapustctiaioosnnlsirgahtwteedorefecraepnapostreoxsiitnamttaihtseetilecyaeld0ly2c9os5ingsnguimffipceiaeintdo.sn inactleuddiungrtihnetchoentrroelcovery period, this result was observed in all wcatments groups.
d"Tiacbalrey5c.oAnvceenrtargaetifoenesod fconPsFuOmSption (FC) ofjuvenile northern babwhite qual exposed to
Treatment
TC
TT
TT
(ppm)
Days 0-8*
Days 8-22
Days 0-22
0(Co315n17t6rol)
000.333112175
000.211278732
000222161138
01431
00340417
02021491
00222870
281
0376
0230
0202
ver15g16e22sed compo0g0.n62801s0r bodyweg mNaNAApPer
NNAA
RA sp dt 00a %my
GihreosrsemNaeincirnogpsbyi:rdsHawlefroefntehcerospusrivcidviongn qDuaaiyl 2w2erfeolsluobwjicngtetdettotneremcirnoaptsioyn.on ODnayDayan8d, coonnesibdierrdeidn ttrheeat7m0.e3nterpeplamtetdr.eatAmesnitngwlaesbinrodteedutwhiatnhizaedslfigrhotmlythpeal281livperpmbuttrtehaitsmewnatswnaost coobrsreerlvaetded10withhavetreaatlmaecnkt-roeflamiuesdcleeffemctassson'anbdodgyenewreailghtth,inntehsiss. necSrionpcsey tfheisnedinfginwdiansg ncoencsriodpesryedfintdrienagtsmetnhtatrwelearteedu.nrTehmaerkraebmlaeining quail that survived to Day and 22 had
dAeladqudaurlintghathdeiesdtuddyu,ritnhge tnheecrsotpusdyy wreesrueltssuibnjeccltuedded0thaingcroonsditnieocnr,opossy.s oFformuqsucaliel fmoaussn,d calotnesrieddersepdle0enbceoltorre,atumteonltyrseilatoeftdi.ssues and pale organs (Table 6. These findings were
6 [I
"sTtaubdlyew6i.thGrPoFsOsS.pathological observations
Finding Cr``oAAbbpdd,oommeiimnnpaatllyccaavviityy,,asutoomleysaiustotlhyrsoisughout EFmraacctiuarteeddleg GGilzzatrradcctoenmtepnttys bile said HHeeaarrt,paanlteeriorporion motled white color IKneteels,tipnraolmcionnetnetnts trike KLiivdenre,ysp,alpeaalned motied LMuosscsuolafrm-usskcelleetmaa,spsale SSpmlaeleln,inblstaactkure SSpplleeeenn,, dsamrakl,lgarnedypoarlegroeryb-bhrown "NTohitnRemarkable
from quail that died during te dietary acute
TK owraNTr) e1a4t1ment Ge2r8on1up (opSnpemi)2) nTiISg
0o 0 o00 022 201s 421
o i0o102 0sw0
o oo o 21 s1 d0
~~ 0oo0 01 02 01
o oo o 0132 100
00 01 00 20 00
00 01 40 70 90
00 00 30 01 00
00 oo
1 0
3 1
2 2
0o_o0 0104 2
CfoorncqeuanitlrathtaitodnisedofduPrRiOngSthien Tstiusdsyueasn:dLfiovrerthcoosnecesnatcrriaftiicoend dtatsataurdey ptreersmiennatteidons.epaSreatreulmy dquaatialwtehrate dailesdo dcuorlilnecgteDdayfsro0mtq0u7alofatthstusdtyudtyerwmeirneataionns.yzeLidvefrorsPamFpOlSescocnotlelcnt,eadndfrtohme dlaivtearacroencpernetsreanttieodnsin tThaatblwee7r.e Dgureraitnegr tthhisanper1i1o0d,umgorgtaPlFiOtyS.in qIunailthwea1s1a2s5sopcipamtedPFwiOtSh rpepamtmterne,athmeinst,conthciesntlreavteliownawsasacahcihciveevdedbybyDaDyay5.3. Swihniclee bfiorrdsquwaeireinntohtes2a8m1plaendd i5n62a Seyvsatleumaattitchemuapntnaekre,aandphdiasrpmoasciotkiionnektiincetiacnsaloyfsiPsFoOfS tihnetdheastea qcuoaulld not be conducted 0
? Gootot
w`cTaabtlmeen7t. rMeelaatseudrmeodrtcaolnicteyndturraitnigontsheoafcuPteFOdSita(ruyg/sgt)udyi.n *the liver of select quail with
TTDay
Tat Nomim2l51PROSConconnatSo6m2 ppm TS
43 NNoommoonraalliyy NNoommoorraallltyy NNoottaammalhyzzeedd 11326((NN-eT3))
s6 NNoommoorrtaallittyy 224092((N=NI=)1) 213256 ((NN--11))
-:
7 11 QN-1) 139 (v=) 1 (Nt
-
uSAnallllyzhePadRrOadnSidecdnonntcaehnertremastieuonntsbrogefrepobourirtpdesodntihnsatupnnietesreodfsiudayb,. dTwhe0etsawnueaimglehyr..iTnShpoermdeeattSahPerIeiEpSrehsWeeenrtuaCnomampveorsboaftgeseeafrmoplrealsl
R8easnuldtsDaryom22lsivheorwantdhatsePrFuOmSanraelmyasienseodfpsraemsepnltesficorlltehceteedxpforsoumresuprevriivoidng(Tqauabille o8)n. DNaoy mcoonrcaelnittryatiwoanss=a4s1s.o2ciiagt/edml wPiFtOhS.liver concentrations = 45.0. g/g PFOS or serum
Table 8. Measured concentrations of PFOS in the liver and scrum of bobwhite quail
collected at Day 8 and Day 22oftDhaeys8tudy. *
Day
Dose Group (ppm
GTivger)
Se(rgumm)
(Tuigvleyr
Spe/rmum)
Con1t7r6ol
1<8L504Q376
<<LL00QQ
30225144008010
0122023 589128
30.31 435084444665 3410248339112 21902084135260 72267244421475
218411
70NA3 A53E5a691 23589=3684 401S1<1d
*NAALCimSniototonpfpcquleaanotbiTltas:tisopnamo(pLil0edGs)wsermLeeOnsoQts-cnl0l.d0e0cS8reagd/nmdl G(sereum)V, LO7G~TDeOwgee.g(Bere)
"qTuhaeilawvearsag0e.5r1a5tiooonfDacyonc8enatnrdat2i.o4n2soonfDPuFyO2S2. inTbhleoordelasteirveulmy tgoretahtatdiifnfrleivnecre(bSIeLt)wefeonr tsheeruDmaythatawnadsDoabyse2r2veSdIL acrraotsiso walalstdreuaetmienntpargtrooupst.he lInowpacrotniccuelnatrr,attihoensseorfuPmFPOFSOiSn cqounacneinttartaitoinontshuisnrtehdeuci1n7.g6tahendS:3L5.r1atiop.pmFitnraelalyt,metnhtegrrwoueprse wneorseiglneisfsictahntanditfhferclnimcietsoifn t10hethSeismraatliosbaemtpwleeensimzealaendanrdelfaetmivaelley mgarlelaatrdvsa.riaTbihleitlyachkatofwsaisgnoibfiscearnvceedwiansbdoutch isnerpaurmt arenpdortlievdersepParFaOteSly.concentrations for all treatments. ~ Therefore these ratios were not
TcohnecenrterlaattiioonnsshmiepassubreetdwoenenDayPF8OaSre gtirveeant:ment dose and liver and serum PFOS
8
GhiEnz
Liver PFOS (g/g) = 0.5087*(Dose, ppm) - 3.0744.
Serum PFOS (ug/ml) = 0.3399%(Dose, ppm--) 0.6851
R= 0.9585
R= 0.3985
cAosncewnittrhattihoensSoLn Draatyio variability observed in
s,. the
thTehries wwearse serum and
dnuoe live
tsoexthsepescmiaflilc sdaimfpfelreensciezse r PFOS concentrations. F
ainn or
dsererluamti serum,
vaenlyd the
glrievaetr small
bsiarmdpsltehastizdeiewdapsridoure0inDapyar8. toThtheevfaarcitabtihlaittysienruthmecdoantcaenitsraaltsioonrsefwlecrteednionttmheearseulrateidveilny
wcsoemnarcleelntncrooaettfifaoinnci.aelnyTtzheoedfrdeselitantecireomnigsnrhaiotpwitobhnet(awRne?de)nfdoPerpFutOrhSaetdisooensreummaanPydFtOihsSasvuceeocnsocinegcnnetinrftiacrtaaintotinlosynstoaolttnerreDedaa.tymet2nh2te
srietluaattiioonnsships, and the information. gained would not be applicable (0 environmental
Ppoesrtioedxp(oDsauyrse,$t2h2e).conTcheinstrdaetciroenaosfe PwFasOSmoisntthleikleilvyerdudeecrtoeatsweod tfhacrtoourgs,hogurtotwhtehrdeiclouvteiroyn. aisndtheexcsraemtieona.t lIonwearddbitoidoyn,bturwdaens alesvseulsm.edTotheasttitmheatbeiotlhoegilcoasls omfecPhFaOnSismfrofomrleilviemridnautiotno "dTehpeurfaotliloonwifnrgommodqeualile,vaalusaitmepslteheornaee-ocofm[poasrsotmfenPtFOmSodferlomwalisvere:mployed (Equation 3).
C=Crep
(Equation 3)
Where: CCayisistthheeccoonncceennttrraattiioonnaat tihmeeon(s1e)todufricnigmithneatciloinmi(nagt/igo)n phase (ug/g) kis the overall elimination rate constant (day) tis time (days)
scTothnuecdeyonvt(errDaaatlyilsonel8ii-nm22i)nl.iavteiroInplroiastteeidcmopansosrtaaannfttun(tckot'i)ornweamosefmetbsietmirematdthueartdinbtgyhetdheeetsetcrilmmiiamntieindnatgieotlnhiempishnlaaotspieeoonofftrahttheee cexocnrsettainotn.taTkehsesienttowaoccporuocnetssleosssmesayfrdoimffetrwoin ciomnpcourrtraennctepbraosceedssocsn,aggre,owstehx,dailnudtisoenasaonnd. mFoarnntehirs saunaclhystihast, tithewaosvearasslumcelidmithnaattiboonthorprlooscsescsoeusldacbteedreipnreasncnitneddepaesndfoelnltowbsu:t additive
Kektg
rInectohridseedqudautiroinn,g thie tshteudgyrowwhtihleratke'thwaatswaessteismtaitmeadteads ftrhoemobvoerdayllweriagtehtomfeadescurreeamseentisn wmaeasscusrteidmaltievder(PkiR).OSBcaosnecdentornattihoensm.eaOsniceedkl'ivaenrdPgFwOeSrecocnaclecnutlraatteid,ontsheanedligmirnoawttihonrartaetse f1r7.o6m,3D5a.y1s,70t.3h,rou14g1h 2a2nodf2s8t1udpypmperPiFodO.Seltirmeiantamteinotns r(aTtaebcloens9t).antTshweearveeersatgiemaetleimdinfoartitohne
9
Cubs
ersatteimoaftePdF0OSbe(baapsperdoxoinmaltiveelryco1n2.c8endtaryast.ions) was 0.0542 day" with the half: ie in liver
Table 9. constants
fGorroPwFtOhSrianteb,oblwihvietrePqFuaOilS.
*elimination
constants
and
excretion
rate
Treatment (ppm)
Grodwatyh!Rate
day!
d3ay)
(Co1n7t6ron
00.00555959
= 0.1253
= 0.0698
73013
00.00558492
0.01.1615023
00..01506613
281411
00..00769284
00..00988310
0000128027
perRioTd (Dacyson81s0i2s2)w.er sed on at derived rom mesmrement made Gung he recovery
oSbesreurmvecdoncfeonrtraltiivoerns oPfFPOFSOScodnicdenntortatbieonhsa.ve inDaurmianngnerthtehatrwecaosvecroynsispteernitodw,ithmethaant
concentrations 10 7.27 g/ml
of in
PFOS in the 17.6
the serum and 35.1
ipnpcrmeatsreedatfmreonmts<, LreOsQpecttoiv5e.l8y9.
g/m and from 3.04 In contrast, PFOS
c2o6n.c2emntgr/aLtioovnesritnhesesraumme otfimqeuapielriofdr.omInthaedd7i0t.i3onptpomthterseeaitnmceonntsidsetcernecaiesse,dtfhreovmar4ia1b.i2littoy
tinremaetmaesnutregdrouspcsr,ummackoinncgentitradtififoincsultontoDeavyaluatweastrreealtamteinvtelryelgarteeadt d(iCffVer>enc1e0s0d%u)rifnogr tahlel
recovery period. conducted with the
Asesruam rdeastual.t,
kinetic
analyses
to
estimate
clearance
times
were
not
CONCLUSIONS:
o`TnheAdDicItarwya8s-da6y1 LmCSg0 PwaFsOS2k12g pbpomdy(Clw=ei1g5h8t-d2a7y8 p(pCml=) w4h8i-l7e7thme g-dPayFOLSDkSg0 bbaosdeyd
weightday). weightday).
TBhaesendo omnorttahleitryedcuocntcieonntraotfiobnodwyaswe70i.g3htppatmD(aory238,.8thmegNPoFOOSb/skegrvbaobdley
Adverse PFOS/kg
Effect body
Concentration weightday).
(NOAEC) was determined The Lowest Observable
to be 70.3 ppm (or 23.8 mg. Adverse Effect Concentration
b(oLdOyAEwCe)igbhatsdeady)o.n bTohdey w8e-idgahyt aNtoDaOybserwvaasbl1e41Adpvpemrs(eeqEufifvealcetntLetv0e4l4.(7NmOgAEPLF)OSa/nkde
wLeorwees4t4.O0bsaenrdva7b0l.e3 Augdlvge,rsreespEefcfteicvtelyL.eveTlh(eL8O-AdEaLy)NOvaAluEeLs baansdedLOonAEliLvervaclounecsenbtarsaetdioonns
nseereudmedcownhceenntrianttieornpsrewtienrges4e1r.2umanPdF4O1S.5vaulgu/emsl,rerleastpievcetivteolyc.ondHuocwteivnegra, rsioskmeascsaeustsimonenits
with monitoring data. concentrations did not
The source of follow the trend
this caution is observed with
du liver
to the fact that serum concentrations, wherein
PFOS. PFOS
floerveleslidmeicnraetaisoend idsurtihneg sthaemerecaotvelroyweprhasbeo.dyItbiusradsesnumleevdeltshatfotrhebobitohlolgiivcearl amnedchsaenriusm.m
However, the data indicate that this assumption may not be true and that the mechanisms
10 G6ORDY
othfreeslhiomlidnavtailounesfr(ogmeomtehetsreicwmoeainsosfueNsOmAaEyLnoatndbeLOsiAmEilLar). arTehseumNmOarAiEzLe,d L(TOaAblEeL,10).and
`Table from a
1n0o.rtNhOeAmEbCo,bwhLiOtAeEqCua,ilaancduttehrfeesehdoilndg
doses study
(TD) *
of
PFOS
derived
Endpoint Dietary (ppm)
NOAEL 703
_TOAEL Tat
TD 103
ASveerruamg(egD/aiml)y Intake (mghg/day) 2a32.8 4ar4s7 a3r2s6
LiAsvTcerrvuaml(uPieRgsO)wSerceonBcaesnetdraotniohnserrcedboacsieodnoonf Dbaoydyw4deit4g.0ht Feed7q0ue3r Tveran5d56
N`SOeAruEmLanadndliLveOrAeEffLetalvualcusefsoradeiemteaasnudrtehdesADuIeavralruees.portaed dietary concentaions.
DATA QUALITY: Reliability: Klimish rankin=g 1
REFERENCES:
Dtruenantemtetn,tsCwW.iacot1n9t5r5ho.l.AJ. Ammuletri.plSeatic.omApsasroci.so5n0s:1p0r9o6c-e1d1u2r1e for comparing several
GLaClSla0ghsetru,dyS.wP.i,thCatsheey,NoCrSt,herBeaBvoebrwsh,it1eB.,AamnednVdaend Hroepvoernt,, WRi.lLd.li2f00e4.IntPerOnSat:ionAaldieLtiadr,y Project NO: 454-103.
Gulley, D.D. 1990. TOXSTATRelease3.2. The UniversityofWyoming.
HBaonbswehni,tcKs. (2S0e0r1a. aAnndalyLtiviecra)l. RReepvoirstioonf D1.at3aMforEnPvFiOroSnmDeinettaarly LLaCboSr0atSotruyd.yRienpoNrotrthNeor.n FACT-TO1X29-.
SAS Institute. NC. USA.
1999.
SASISTAT
User's
Guide,
Release
8.02
Edition,
SAS
Institute,
Cary
WPuabglniecra,tio.nGs.Inc.1,97H9a.milFtuonnd,amIeI.nt4a6l1sp.of Clinical Pharmacokinetics. Drug Intelligence
OLaTstHEchRan:ged: 05/04
n
reson