Document 2np2J9omJzxRrvv382keK5r7
Test Substance:
Toxicological Summary Pros
Dietary Acute Northern Bobwhite Study Perfluorooctanesulfonate (PFOS)
Structure:
Remarks:
p1o-tOacstsaineusmuslaflot,niCcASa#cid2,7951,.13,92..32.3,3,4,4,5,5,6,6,7,7.8,8,8-heptadecafluoro-,
The test substance is stored under ambient
caonwdhiittieonpsoawndderpuGriMty
wloats#o21r7g)i.nallTyhedestaemrpmlienewdatso
bteechn9i0q.ue4s9.% determined
Ibny 10
a LsCu/bMsSeq,uen'tH-aHnaMlRy,sis "oFf-tNhMeRestandsubcslteamnecnet,alpuraintaylwysaess be 86.9%. The nominal and measured dietary PFOS
Concentration inthissummaryae based on the 86.9% purty value.
"vTahleueisn-biafseedphoansethreep9o0r.t4w0%spourriigtiyneasltliymactoimopn.letTedheinre2p0or0t0,waasndrerveipsoerdteidn T2o0x0i4col1o0gicraelfleScutmmtaherysruebfsleeqcutenttheserecvhiasinognes ians wsealmlpale inpculriutdyi.ng resTuhlitss from all of the associated reports of analyses of tissues collected during
the in-life phase.
METHODS
MAeStThoMd:StOanPdPaTrdSE885S07..282700(1(9D9r7a)f), FIFRA Subdivision E. Section 71-2, OECD 205, and Type: Dietary Acute Years 1999 in life tet, 2000 for report, 2004 for amended report Species: Norther Bobwhite (Colinus virginianus) Test Phases: Acclimatio-n10days
EPxopsto-seuxrpeospuerrieorde-co5vedrayysp.eriod 3 or 17 days (with th study ending on cither Day or Day 22, respectively)
Test quail Age: 10 days old at test initiation rNeuplmibcaetres oinfcRaecphlitcesattessu:bsTthanecree twreeraetmesinxt Trehpelriecawteesreinfitvheequcaoinltrpoelr trerpelaitcmaetnet,(paenn)d ftorwo (towthailcohfi3n0clquudaeidleiinghtthdeosceongtrrooulpst)r.eatTmheentanainmdal1s0wqeuraeilalilnexcpacohsetdesftorsufbivsetadnacyes,tarenadtmtehnetn held for a recovery period. At Day 8, half the replicates from each treatment group (3 of
1
G20583
lrfeplirceatecsofnrtonumetdhenctonhtrosltuadny nt1 lfrDoamyea22c.h dos level) were sacrificed whi the other F{eeneidnganphdasWeastoefr:theFosotdaya.ndTwhaeteqruaiwlerGedprnoovirdeedceiavd alniybitfuom:rmduorfinagniabcicoltiemattrieoantmaenndt rAnialnytiecaltMtonhihatcocrleiinmga:triToenstorsuebssttapnhcaesecoonfctehneirsattuidyo:ns in feed and quail Iver and serum wre iemminedbyreverse phase HPLC and mss spectrometry Sptoaptiusltaicoanl Mfoerthaodgs:enLCeSx0po(sLuertehal(imceo)nceanntdratLiToOn.th(tLetrmeaallstimien 5th0at% rmeosrutlatslitiyn o5f0a% TionmrgeaahsyeurSeodfaibayspiaovpeeurlAaangtaieloyndsaiifsloyrSn8yasgteivm,en(tShdAaotSs/er)SeTsvAuaTsl:uienPs R0wOe%rCePmcoRarOltBcaulIliTat)ty.eodfLb3DySppa0rpo(ubLilettthoaannlaldfyoossis,3 EFvReOnB.IeTx)posuBroedytimwee)igvahluedsaawewreerecalccoumlpaaterdedbybyprDobuintnaentalsystiesst(uSsAinSgSTTOAXTPSRTOACT o`iftthwaErxece(lDwuonrnkseh,ee1t9s55i;ncGluuldlienyg, r1eg9r9e0s)sioAnlslwoitthhrcosnicaetnisttriactalioenvsaloufaPtiFoOnsS wienrteiscuoensd.ucted ARCovaneisrsuaamgnpetDidaoidnlymaonItdnataakkleeti(tAQoDuIaai)lsoobfuonPdtyRpOweSenifgtohrtaedaiacfthfarwweeenarcteemesanvbteergtarwgoeeudnpomwvaaesrletashntedimdfauertmseatdlieoosnn, oaFfpoteohnde xpos period and the ADI was cletated a follows (Equation 1 ADI (mg/kg/day) Aversa weigh =AverageFeedConsumption gi) (Uirdday) pg on (ppmPFOS) (Equation 1) "mTeeastnsDioetfaPHroebpaarrtatmiioxner:, TNheo tceasrtiseurbwsatasnucseedw.asNommiixneadlddiietttaryy ciotnocetnhterafteieodnsaotfioPnFObSy emidlioinn7thpis.stdy were 0 (como, 176, 35.1, 703, 141, 28, 562, and 1125 parts pee
RESULTS
MGFeaPsRuOrSedinDitehte Ctoentcedinett.ratiTohnes:rWaindipeerceInnttemraetcioovnearly Lodf.fhdeetmeramirneadpickoendcenfterdatiwoanss 5f4r.o7m%5,2w1hoil1e1t9h%e toefsttehendomsianmapllevsaluhea.d mMeesassuurreedd cmoenacenntcroantcieonntsraotifoPnsFOofSPtFhOaSrawnegree:d 000, 187,386,715, 167,279,516, and 1138 ppm. Mreosrtmteantlgsroaunpdi Cgliivniecnal(TaObblseer1v).ations: A summary of he percent morality for cach
2 620584
Teaxbploese1t.do CPuFmuOlSative treatment-related percent mortality of juvenile bobwhite quail
Noma Mest AE
om
PCFonOcS. PCoFnOc.S DIaniialkye. ExposurePerioDdays RecoveryPeriod
(ppm) pm) (mgkgdwy1 ) 2 3 4 ST6 7 8 2
Co1nt6rol <L1O8Q7' 1 86
<4L8O%Q 82
000
00 0
00 0
00 0
00[00 0[0
00 0
00 0
000
703 7s 28 0 0 0 0 000 00
18s41 s1l6279
4619749
000
000
0100
2000 250 00 [04[80
181000 S11H00
1
100
efr2asge aT mkaes (RDF i22P5ROSE Bo0yWeig0h per309) b1u0s0ed n10D0a]y10030bod1y0w0eigh1t0n0d f1e0d
c$eommamnoinsecuredins cman eel in hecxtended recovery period rom Day 0 Day22.
LOimeitqoufaqluawnatsitcautibonni(zLdOoQ)n fDoeryPFOaSfcinstuheandiient gwabsr1o.k10enpplmonDay 5
* One quail was euthanized on Day 3 after sustaining a broken leg.
Osunbeseqquuaeinltilnytchuethcaonnitzreodl ognroDuapyof6. 3T0wwoasothfeorunqudaiwl iintahbetrcookhnetnrolleggroonupDhaaydSf,ooatnldewsiaosns hwearte.wenroermaaslsociinataepdpweiatrhanccaegeamnadtebeahgagvriesosriotn.hrouAglhlooutthetrhequatelst.in tThheecroentrwoelrterenaetimtehnetr preaotmmentthireedlinatt.ed mortalities no over: signs of toxicity at PFOS concentrations < 70.3
Ibnrotkheenl1e41gapnpdm tthreeraetmweanst gornoeutpr,eaotnmeenbti.rdelwataesd emuothraanliizteyd(on1Daoy1n3D%aafyt)e7r .sustNaoiniontghear mtooxritcailtiyty(wwiansgnodtroeodp)f.or tHhioswterveeartm,enbt.y DTawyo9a,ddtihteiotnwalo qquuaaiilldihsapdlaryeecdovcleirneidcalansdigatsheiorf haapdpeaarnaonrcmealanadppbeeahraavnicoerarnedtubmeehdavteod nnoorrmmaall.lyAflor tohtehedrurqautaiiolnoinftthhee s1t4u1dyp.pm treatment
Ianddtihteon2a8l1 mpoprtmalittrieeastmebneti,ng80o%bsemorrvteadlitfyor(Vth1e0 dquuraait)iownasofobtsheervteesdt. by QDuaaiyl7mwoirttahlintoy orucfcfulrerdeadpopneaDraanycse,5,r6ednucded7.reSacitginoson ftotosxiimciutly (wseoruendoabsnedrvmeodtpiroino,r 0letdheaartgyh,awnidnigncdlruodoepd, laodssnoofrcmoaolrdaipnpaetiaorna,ncleowaenrdlbiemhbavwieoarkfnoerstsheanddurcaotnivounlsoifotnhse. stAufdtye.r Day 9, surviving quail
IDnaythe7.56S2igpnpsmofttroexaitcmietnyt,obmsoertravleidtyprwiaorsofirdsetaotbhseirnvceluddoedn aDaruyff3leadnadppreeaarcahnecde,1r0e0d%ucbeyd rweeaacktnieosns,tolostwiemrullii,mblertihgairdgiyt,y,dperporsetsastieonp,oswtuirnegadnrdocopo,nvu10l5ssioonfs coordination, lowes limb
3
:
600585
In the Day 4.
1125 ppm Signs of
ttorxeiactimteynto,bsmeorrtvaelditpyriwoars(0fidrestatohbsienrcvleuddeodnaDrauyffl3edanadppreeaarcahnecde,1r0e0d%ucbeyd
rweeaacktnieosns,toansdtimluolwie,rlleitmhabrgryig,idditeyp.ression, wing droop, loss of coordination, lower limb
BdiottahryLC8S-0dsayaLndCSL0TSw0ass f2o1r2PpFpOmS PwFeOreS dweittehrami9ne5d%bcyonpfriodbeintcaenailnytseirsval(Toafbl1e582).to T27h8e
pcpomn.sumpTthieonslodpaetaocfotlhleeccteodncdeunrtirantgiotnhere5s-pdoanyseexcpuorsvuerewapseri7.o0d4.werBeoduysewdeitoghetstainmdatefoaond
average daily LDSO based
oinntaAkveeroafgPeFDOaSilayndInatnakeadd(iAtDiIon)alofproPbFitOSanawlaysses61wamsgcoPnFduOcStKekdg.
The body
w"Tehieghstliodpeaoyfwtihteh daos9e5-%rescpoonnfsiedecnucreveinwtaersva8l.8o8f. 4T8hetoL7T7S0m,gesPtFimOaSt/ekdgwibtohdythweei1g1h2t5idpayp.m
`PwFhOerSe t3r0ea%tmmeonrttadlaittay wwaass 3o.b0s6erdvaeysd.at Tdhaiys3reasnuldt 1a0gr0e%edmowrittahlictuymwulaastiovbesemrovretdaliattydadyat4a
(Table 1).
Toafablpeop2u.lEasttiiomnaotefsojufvtenhielelneothratlhecronncbeonbtwrhaittioenqouafilPs.FO*S (LCso) and the lethal time (LTso)
`Effect metric Time LC50 (ppm) 95% CL
Slope.
LC50
Day3 Days
1,593 82
356-672
3174 am
Day 6 Day $8
319 212
228-448 158-278
3923 7.03
Day22
212
158-278
7.036
750
Dose 281 ppm
LTS @ay) 641
95% CL 5697.61
Slope. 954
562 ppm 1125 ppm.
478 3.06
417.548 .
829 605
TT by FST GATS PROCTOR
BbooddyywWeeiigghhtt:foIrnqucaoimlpsarinistohne t1o7.c6o,nt3r5o.l1s,otrhe7r0e.3weprpemnotraepaptmaernetnst.PFHoOwSevreelra,teqducafiflecitnstohne
141, 281 and comparison to
S62 ppm controls
treatments had body weights (p<0.01) for Days 0-5. While
that were there was
significantly a statistically
reduced in significant
rweadsucntoiolnoningebrodapypwaereingthtbyatDPaFyOS15c(on1c0endtaryastipoonsst >ex7p0o.s3urpep).m, tAhsiswbaosdyobwseeirgvhetdrfeodrucbtoidoyn.
woebisgehrtv,edsigatnifciocnacnetnttrraetaitomnesnt->re7l0a.t3edpepffmectPsFOoSn.bodHyowweeviegrh,t agfatienr fDraoym D8,ayno0 ttroe5amweenrte-
treerlmaitneadtieofnf.ectsEffoenctbsoodny
weight gain body weight
owrerbeodynowteeidghatt
any gain
concentration could not be
through study determined for
281, 562 and 1125 ppm treatment groups after Day due to most of the quail dying in
these groups.
a
G50586
dTiaebtlaery3.coAnvceernatrgaetbioondsyowfePiFgOhSt.()ofjuvenile northern bobiwhites exposed to various
Treatment Body Weight Body Weight Body Weight Body Weight Body Weight
(Cpopnmt)ro.l 176
Da2y00+7* 2141
0Day4s ea
Deays8 ass
PDa1y 0IS 828
RDayD22 [i
730531 020:211 3310s22 33792233 6052x54 78992247
218411 22002=11 ewsese dIsessa 832s3 795252
15262s 2200s211 16m022
mnm
mm
mm
naBaotynttweaenpaclTioedpnuof0lom1m0c0eo%mmeoSgnrloauypnndre0s.Ge0nt(e rDpuonmo Tmee8r)r. e.
vInariosuescosnpdanssetooffatniamleysdeusr,intghetghreoswttuhdyr,atienscflourdienagch0-t8redaatymse,nt8g2r2oudpaywse,reancdal0cu.l2a2teddayfsor GVirnoewartihzerdaatend(1tdheany)fiweadsteostthiemabtoeddywwithea dgiaenteagrcaollhlgercottwetdhdumroidneglth(eEqsutuadtyi.on 2) that was
W, = Woep
(Equation 2)
`Where: W`Wyoiisstthhee bbooddyy wweeiigghhtt ((gg)) ooffaammaallllaarrddaatttthiemeon(ste)tofotfthheessttuuddyy (1=0) gissthtiemeo(vderaaylsl)growth rate (1day)
dDiaetdabfyroDmayth8e.SF6o2raDnady101-285, pthpemgPrFoOwS rtarteeasotmfetnths wqeuraielnionttirnecaltumdeendt,gsrionucpsaolfl qlueaslthhaadn a7g0.r3eepmepnmt wweirthe tnhoetbsotdatyiswtieciagllhyt ddiatfaf,reqnutalfrformomthteheco1n4t1rolangdro2w8t1hprpatme t(rTeaabtlmeen4t).s haIdn aDfateyr 0D-a8ygr8o(wDtahyr3ateosftthhaetrweecroeverryedpuecreidodf)rtohme tqhuaatilobisnetrhveed14i1n atnhed c2o8n1troplps.m tHroewatemveenrt,s hgraenwoart eaquaatletoth7t0.w3apspemquPivFaOlSe.nt oThethaotveorbalslergvreodwtinh qruaatiels ffoiromquatirleatimnentth.e g1r7o.u6,ps35l.e1s,s c7o0n.t3r,ol14g1r,ouapn.d 281 ppm treatments did not differ from the observed growth ates in the
5
:
GNO587
`Table 4. Growth rates (l/day) for juvenile northern bobwhite quails exposed to PFOS. A
Days
0
176
Treatment group (pm) 351 703
141
281
008 81022
T0803 00549
0.0803 00555
00839 00589
00773 00542
00623 00624
0.0140 007%
01022
00639
X Grorateswcuitmathed by incar
00681 regression:
(Ln
00681 Body weight
00628 (9) growtathe
00648 0.0526 (me)+ y-imereep).
FtheeedexCpoosnusruem(pDtaiyosn:0-5T)heorrerewceorveernyopePrFiOoSd-(reDlaaytse6d-2ef2f)oecfttshoensfteueddy.cAonrseudmupcttiioonn idnurfienegd
cexopnossuumrpetiopneriwoads
noted (Days
a0t-5t)hebu2t81,the5s6e2
and 1125 reductions
ppm were
tnroetatmsetnattisgtircoaullpys
during the significant.
`bOovderyalwle,itghhetijduaveynfiolretqhueasltuadvy.eraWgheidlea tchoenrseuwmapstiaonslirgahtteodfecraepapsreoxiinmtahteelfyee0d.c2o9n8sgumfpeteidogn
rate during the recovery period, this result was observed in all treatments groups,
including the control.
Table 5. Average feed consumption (FC)of juvenile northern bobwhite quail exposed to
dietary concentrationsof PFOS
Treatment (gpm)
FC Days0-84
FC Days 8.22
FC Days 0-22
(C1on7t6rol)
00331215
0011872
0218 0211
351 03
0317 0401
0227 0241
0263 0280
141 281
0347 0376
0219 0230
0227 0282
562
0.681
12s
0200
NA NA
NA NA
TcFNRoAvern=aNgoestfaepupdlicmablpe dute toi100voe%nnmasorJalibtyo.dy weaona pnb
GthreosrsemNaeicnrionpgsbyi:rdHsawlefroefntehcerospusriveivdinogn qDuaaiyl 2w2erfeolsluobwjiencgtetdesttotneermcirnoaptsiyono.n ODnayDayan8d, oconnesibidredreidn ttrheeat7m0e.n3t-rpeplamtetdr.eatAmesnitngwlaesbinrodteedutwhiatnhizaedslfirghotmlytphael2e8l1ivperpmbuttrtehaitsmewnatswnaost ocobrsreerlvaetdedtowihthavetreaatlmaecnkt-roeflamtuesdclefefemctasssonanbdodgyenewreailghtth,inntehsiss. necSrionpcsey thfeisnedinfgindaisng cnoencsriodpesryedfintdrienagtsmetnhtatrwelearteedu.nrTemhaerkraebmlae.ining quail that survived to Day 8 and 22 had
Adleladqudauirlitnhgatthdeiesdtuddyu,ritnhge
tnheecrsotpusdyy
wreesrueltssuibnjeccltueddedtothaingrcoosnsditnieocnr,oplsoys.s
oFfomruqsucaliel
found mass,
aclotnesrieddersepdleteonbceoltorre,atamuteonltysreilsatoefd.tissues and pale organs (Table 6). These findings were:
6
na588
`Table 6. Gross pathological observations study with PFOS. Finding "Abdominal cavity, some autolysis Abdominal cavity, autolysis throughout Crop, empty EmFraaccitautreeddleg GI. tract empty Gizzard contents bile stained `Heart, anterior portion mottled white color Heart pale Intestinal contentstar lke: Keel, prominent LKiivdenre,ysp,alpeaalend mottled Loss of muscle mass Muscular-skeletal,pale Small in stature: Spleen, black Spleen, small and pale or both Spleen, dark, grey or grey-brown `Thin Not Remarkable
from quail Conwol N=) 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
that died during the dietary acute
Treatment 141 (Nd) 0 0 0 0 1 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0
Group (ppm) 281 S62 1125 (NB) ON) N-10) 227 01 1 2s2 2 5s 8 0 [I 1 10 251 100 02 1 02 0 1 30 020 oo 0 0 479 0 [I 3 [I 010 132 012 042 1 o_o
Concentrations of PFOS in Tissues: Liver concentration data are presented separately for quail that died during the study and for those sacrificed at study termination. Serum data were also collected from quail at study termination. Liver samples collected from quail that died during Days 0 0 7 of the study were analyzed for PFOS content, and the data are presented in Table 7. During this period, mortality in quail was associated with liver concentrations that were greater than 110 ug/g PFOS. In the 1125 ppm PFOS treatment, this concentration was achieved by Day 3, while for quail in the 281 and 562 ppm treatments, this level was achieved by Day S. Since birds were not sampled in a systematic manner, a pharmacokinetic analysis of the data could not be conducted to evaluate the uptake and disposition kinetics of PFOS in these quai.
7 670589
Teaabtlmeent7..reMleaatseudrmeodrtcalointcyendturraitnigontsheoafcuPteFOdiSet(auryg/sgt)udyi.n *the liver of select quail with
Day Tat "Nomina2l81PFOS ConcentratiSo6n2s (pom) 1125
3 Nomorally Nomorally | Notamlzed 138 (ND)
45 NNoommoormaalltyy N2o0m9o(mNa-lDt)y N1o26ta(mNl-y1e)d 126-(N-3)
6 7
NL omomQaliy
13290(2(NN--2)
213151(8N1=))
-.
quaAilllhPtROdSedcoinnce3ntrreasttiomnnstrgerpoourtpeodninsupneictisfioefdWdaEy.,Twhetnwuemibghetr iTnphrectdhaeasirseprestehen naunmabveerraogfesaomrplaels
nly an no themmr ofbirds st wer ubjeidfo aalyss. Somesampleswere composi.
R8easunldtsDafyo2m2lsivheorwantdhatsePrFuOmSanraelmyasienseodfpsraesmepnltesafceorlltehceteedxfporsoumresuprevriivoidng(Tqauabille o8)n. DNaoy mortality was associated with liver concentrations = 450. pg/g PFOS or serum concentr=a41t.2ipogn/msl PFOS.
Tcoalbllecete8d. aMteDaasyur8edancdoDncaeynt2r2aotfiotnhse osftuPdFy.OS in the liver and serum of bobwhite quail
Day
Dayz
DospemGr)oup T(i5/v0e)r
Segr/umm
TGievoe)r
Segr/umm)
Control <L0Q
<L0Q 0212009 0122025
351716 21588552436756 30<4053Q92 3229525+018516 518297+2142187
710431 40740346 4a1s2i43a1]1 215080e4638249 20652:421445
T * Lio2of1quentiaion (LOG)N.ALOQ= 0008 gm4rE 6um),LOQ-0.033l9g3 (iver) -- i
NA ot splice samples were ntcollected
q"Tuhseilawvearsag0e.5r1a5toonoDfacyonc8enatnrdat2i.o4n2soonfDPaFyO2S2.inTbhleoordelasteirvuelmy tgoretahtatdiifnfelrievnecre(bSeLt)wefeonr stheeruDmaytha8tawnadsDoabyse2r2veSd:Lacrraotsiso awlastrdeuaetmienntpargtrotuopst.he Ilnowpacrotniccuelnatrr,attihoensseorfuPmFPOFSOiSn cqounacneinttartaitoinontshusinrtehdeuci17n.g6thaendS.L3.5.r1atop.pmFitnralelayt,mehnetrgerwoueprse nweorseiglneisfsictahntanditfhfeerleinmcietsoifn ttohethSe:Lsmraaltliosbaemtpwleeensimzealaendanrdelfaetmiavelleymgarlelaatrdvsa.riaTbihleitlyactkhaotfwsaigsniofbiscearnvceedwiansbdouthe sinerpaurmt raenpdortlievdersepPaFraOtSelyc.oncentrations for all treatments. Therefore these ratios were not
TcohnecenrterlaattiioonnsshmiepassubreetdwoenenDayPF8OaSre gtirveeantment dose and liver and sem PFOS
8
60590
Liver PROS(ug/g) = 0.5087*(Dose, ppm-) 3.0744
R= 09585
Serum PFOS (ug/m) = 0.3399*(Dose, ppm) ~ 0.6851
R-03985
AcosncewnittrhattihoensSoInL Draatyios3,. thTehries wwearse dnuoe tsoexthsepescmiaflilc sdaimffpelreensciezse ianndserreluamtivaenlyd glrievaetr svaarmipalbielistiyzeobwsaesrvdeudcinintphearsetroutmheanfdactlitvehraPsFeOruSmccoonncecnetnrtartaitoinosn.s wFeorre sneortumm,eatshuersemdaliln bids that died prior to Day 8. The variability in the data is alo reflected in the relatively csomnaclelntcroaetfifoinc.ienTthoefrdeeltateiromnisnhaitpiobnet(wRe)enfoPrFtOhSe dsoesreumanPdFiOsSsuceocnocnecnetrnattriaotnisontsootnreDaatyme2nt2 rweelraetionnosthipasn,alaynzdedthseinicnefogrrmoawtitohnagnadindeedpuwroatuilodn nmoatybehaavpeplisciganbilfeictaontleynvailrtoenrmeednttahle situations
pPoesrtioedxp(oDsauyrse,2t2h)e.conTcheinstrdaetciorneaosfe PwFaOsSmoisntthleikleilvyerdudeecrteoatswedo tfhacrtoourgsh,ogurtotwhtehrdeiclouvteirony aisndtheexcsraemteiona.t lIonwearddbitoidoyn,biutrwdaens laesveslus.meTdotheasttihmatbeiotlhoegilcoasl moefcPhFaOnSisfmrfoom leilviemridnauteiotno d"ehpeurfaotliloonwifnrgommodqeualile,vaalusaitmesplteheonraet-eocofmlpoasrstomfenPtFOmSodferlomwalisvere:mployed (Equation 3).
Co=GrewTM
(Equation3)
Where: CCaisistthheeccoonncceennttrraattiioonnaattthimeon(s1e)tduofreilnigmtihnateiloimni(n1a8t/i8o)n phase (g/g) ct'isstthimeeo(vdeayrsa)l elimination rate constant (day)
"cTohneceonvteraatliloneliinmilniavteironplaotteedcoansstaanftun(ckt"i)ownaosfetsitmiemadtuerdinbgy tdheetecrlmiimniinnagtitohneplhoapseeoofftthhee scotnusdtyan(tDatyaskes8-i2n2t)o. acIctouinstilmopsosresanftrotmo trweomecmobnecurrrtehnat ptrhoeceesssteism,atgerdowetlhimidinlauttiioonn raantde eFxocrretthiiosna.nalTyhseisse, ittwwoaspraocsessusmeesdmtahaytdbioftfhrpirnociemspsoerstaanccteedbianseadn oinndeagpee,ndseenxt, abuntdasdedaistoinv.e manner such that the over all climination o loss could be representeda follows:
Kelty
Irnectohridseedqudautiroinn,g thies tshteudgyrowwhtihlerakt'thwaatswaessteismtaitmeadteads ftrhoemobvoerdayllweriagtehtomfeadsecurreeamseentisn mweaassuesrteidmaltievder(PksF).OSBcaosnecdenotnrattihoensm.eaOsuneeedkl*ivaenrdPgFOweSrecocnaclecnutlraattedi,onhseanedligmirnoawttihonrartaetse f1i7.o6m,3D5a.y1s,70t3h,ro1u4g1h 2a2nodf28s1tupdypmperPiRodO,Seltirmeiantamteinotnsr(aTtaebcloens9)t.antTshweearveeersatgiemaetliemdifnoartitohne
9
r0591
reastteimoaftePdFOtoSbe(baapsperdoxoinmaltiveelryco1n2.c8endtaryast.ions) was 0.0542 day' with the haliff in liver
Table 9. Growth rates, liver PFOS elimination constants and excretion rate
constants for PFO in bobwhite quail. *
Treatment "Growih Rate
T
3
(ppm)
(day)
(@ay')
ay")
(Co1n7t6rol)
00.0055959
0.1=253
0.0=698
0313
0000558892
00..11615023
00..01806613
281411
00..00769284
00..00893810
00.00128027
peRrTiTod Daycosns8t1a0n2ts).were based on dts derived Tom essrerent adeQui he recovery
o`Sbesreurmvecdoncfeonrtraltiivoenrs oPfFPOFSOScodnicdenntortatbieohnasv.e inDaurmianngnerthtehatrweacosvecroynsispteernitodw,ithmetahant concentrations of PFOS in the serum increased from <LOQ 10 5.89 g/ml and from 3.04 1co0n7c.e2n7traptgi/omnls iinn stheeru1m7.o6faqnudail35.f1rompptmhet7r0e.a3tmepnptsm, trreesaptemcteinvteldye.creIansecdontfrraosmt,41P.F2OSto 2in62memagsu/rLeodvesrertuhme scaonmceenttirmaetpieornisodo.n IDnaaydditwioanstroetlahteisveeliyncgornesaitst(enCcVies>, t1h0e0v%a)riafboirliatlly rtreecaotvmeernyt pgerroiuopds., mAaskinagreitsudlitf,fikciunletti0c eavnaalluyasteestrteoatemsetnitmarteelactleedardainfcfeeretnicmeessdwuerrinegntohte conducted with the serum data.
CONCLUSIONS:
o`Tnhe AdiDeItarwya8s-da6y LmCgS0 PwaFsOS2K12gpbpomdy(CIw=ei1g5h8t-d2a7y8 p(pCml) w4h8i-l7e7thme g8-dPaFyOLSDkSg0 bbaosdedy `weightday). The no mortality concentration was 70.3 ppm (or 23.8 mg PFOS/kg body wAedivgehrtsdeayE)f.fectBaCsoencdenotnratthieonre(dNuOctAiEonC)ofwabsoddyetweerimgihntedattoDabey 780.,3 thpe pNmo(oOrbs2e3r.v8abmlge (PLFOOASEKCg) bboasdeyd woenigbhotddyayw)e.ightThateDLaoywe8swtasOb1s4e1rvpapblme(eAqduivvearlseentEtfofe4c4t.7CmogncPenFtOaStkigo.n body weightday). The 8-day No Observable Adverse Effect Level (NOAEL) and wLeorwees4t4.O0bsaenrdva70b.l3 e uAdgv,ersreespEefcfteicvtelLy.eveTlh(eL8O-AdEaLy)NOvaAluEeLs baansdedLOonAEliLvervaclounecsenbtarsaetdioonns sneereudmedcownhceenntrianttieornpsrewtienrges4e1r.2umanPdF4O1S.5vgal/uems,rerleastpievcetivteolyc.ondHuocwteivnegra, sriosmkeascsaeustsiomnenits with monitoring data. The source of this caution is duc to the fact that serum PFOS `lceovneclesndteractrieoansseddiddunroitngfotlhleowretchoevefrryenpdhaosbes.ervItediswaisthsulmiveedr tchoantcetnhterabtiioolnosg,icwahlemreeicnhaPnFiOsSm fHoorwecvleirmi,natthieodnatias itnhdeicastaemtehatatthlisowaesrsubmopdtiyonbumradyennoltevbeelstrufeoranbdotthhatlitvheer maencdhasneirusmm.s
10
"0592
otfherlesihmoilndatvailounesfr(ogmeomtehtesreictmweoatniossfueNsOmAaEyLnoatndbeLOsiAmEilLa)r.arTehseumNmOaAriEzLe,d L(TOaAblEeL,10)a.nd
`Table 10. NOAEC, LOAEC, and threshold doses (TD) of PFOS derived
franoorthmern bobwhite qual acute feeding study *
Endpoint
NOAEL _TOAEL TD
Dietary (ppm) Average Daily Intake (mgkgiday)
703 23.8
441471
21063
Serum (ug/m)
a2 as ara
LiAvTerval(suggw)ere sed on the eductionofbody4w4eig0ht
703 Geatd quail
556 Liver 1nd
NOSeAruEmLPRanOdSLcOonAcEenLtrvaatliuoenssfaorredbiaesenddontDheaAyD8Idaats. reporid a dietary concentrations
Sera andlivereffect values ar measured issue valu.
DATA QUALITY: Reliability: Klimish rankin=g 1
REFERENCES:
Dunnett, CW. 1955. A multiple comparison's procedure for comparing several treawtimtheacnonttrosl. J. Amer. Statis. Assoc. 50:1096-1121
Gallagher, S.P., Casey, C.S., Beavers, J.B, and Van Hoven, RL. 2004. PFOS: A dietary PrLoCjSe0ctsNtuOd.y:w4i5t4h-1t0h3e.Northern Bobwhite. Amended report, Wildlife International Ltd.
Gulley, D.D. 1990. TOXSTAT Release 3.2. The University of Wyoming.
Hansen, K. Bobwhites
2001. (Sera
Analytical and Liver).
Report of Revision
Data for PFOS Dietary 1. 3M Environmental
LCS0 Study Laboratory.
in Norther Report No.
FACT-TO1X2-5.
SAS Institute. NC. USA.
1999.
SAS/STAT
User's
Guide,
Release
8.02
Edition,
SAS
Institue,
Cary
Wagner, JG. 1979. Fundamentals of Clinical Pharmacokinetics. Drug Intelligence Publications Inc., Hamilion, 11. 461 p.
OTHER: Last changed: 5105/04
n
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