Document VGKL8GZmRNZoENRpmQr7bzKGZ

302 if AR 296 _ 1137 omusToswUaeniAREs =&z 55 104 104 000001 EPIDEMIOLOGIC DATA Title: Identification of Fluorochemicals in Human Sera. I. American Red Cross Adult Blood Donors TEST SUBSTANCE Identity: PFOA and 6 other fluorochemicals Remarks: This is a final report. The preliminary report was dated June 25, 2001. METHOD Study design: Cross-sectional Manufacturing/Processing/Use: N/A Hypothesis tested: To determine levels ofPFOA in the serumofAmerican Red Cross blood banks in 6 regionsofthe U.S. Study period: 2000 Setting: N/A TUoS:talLpoospAunlgaetlieosn,: CSAe;ruMimnnpeoaoploeldisf/rSto.m 6PaAulR,CMNbl;ooCdhabralnoktse,inNvCa;riBoousstgoeno,gMraAp;hiPcorrtelgainodn,sOiRn,the. and Hagerstown, MD. Subject selection eriteria: Unknown Total # of subjects in study: 645 donors, age 20-69 years Comparison population: N/A Participation rate: NIA Subct description: The arly demogapic fos known were age, gender and location. HPeFaOlAt.h efTfheectostshteurdciheedm:icLaelvselwseroe:f7PfFlOuoSr,ocPhFeOmiScAalAs,iMnSh7u0m,anM5b5l6o,odPsFeOrSumA,,iPnFclHuSd.ing Data collection methods: Each blood bank was requested to provide approximately 10 105 000002 samples per 10-year age intervals (20-29, 30-39, etc) for each sex. Details on data collection: Blood sera samples were analyzed using high-pressure liquid cVherrosmusataongreaxpthrayc/teeldeccturrovseprfaryomtaanhduemmamnaspslasspmeactmraotmreitxry(s(eeHrPeLpCor/tEfSorMSmoMrSe)daetnadilesv).aluated Exposure period:Unknown--PFOAserum levels used as surrogate for exposure. D`Tehsecrreipwteiroen/1d0eolrinmeoartieosnuobjfeecxtspofsourrbeotghromuaplse/scaatnedgofreimeasl:es3i3n2eamcahleagdeoncoartse,go3r1y3(f2e0m-a2l9,e d3o0n-o3r9s,. etc.) except the 60-69 age group where there were fever Measured or estimated exposure: NA Exposure levels: N/A Statistical methods: A reliability assessment was done. Geometric means, 95% confidence intervals of the geometric wmeearnesc,alrcaunlgaet,edi.nteCreqnutarratlilteernadnegnec,yraanwdcduimsutlraitbuitvieon90ofthpeercdeanttailbey, aanged,fgreenqdueern,caynddisltorciabtuitioonnws,ere Tproecsaetnitoends.adBjouosttseidrfaopra1n0a-lyyesairs awgaesidnotenrevatlos,caglecnudleart,e amnedanthesierriunmtePrFacOtiSonvatleurmess.foMruclatcihva6riable regression analyses. A reliability assessment was also done for the chemical analyses. Tflhueorgoecohmeemtirciaclmveaalunesda<taLwLeOreQctahlecumliadtpeodiunntdbeerttwheeeansszeurmoptainodntthheatLfLoOr iQndwiavsidausasligsneerd.um However, PFOA had a lotof subjects with LLOQs. Other methodological information: Seven sera samples from the preliminary report were not included in the analysis because the subjects were >70 years old. RESULTS DTehsecrreisbueltrsoefsutlhtse:reliability analysis indicate that there was a strong correlation between the split samples (r= 9) for PFOA. "PTFhiOsAladcikdonfoltogmeneotrmtahleitcryitmeariya fboerd@uleotgo-ntohremgarleadtiesrtrpiebructeionntabgaeseodf osunbjtehcetSshwaiptihrova-lWuielsklteessst than the LLOQ (1.92). `The geometric 1.9-52.3 ppb. meanofPFOAofall subjects was 4.6 Arithmetic means were not provided. ppb (95% CI, 4.3 ~ 4.8). The Males had higher geometric range means was than fimepmoarlteasn[t4p.9repdpicbt(or9o5f%aCdIu,lt4.s6e--ru5m.3f)l,u4o.r2ocphpebmi(c9a5l%coCnIc,en3t.r9a-tion4s.5.), respectively). Age was not an 106 106 000003 `fTlhueorgoecohmeemtirciaclmveaalunesda<taLwLeOrQe,catlhceumliatpeodinutndbeertwteheenaszseurmopatnidonthtehaLtLfoOrQinwdiavsidausasligsneedr.umThere w1e0r%e oqrui9te0%aoffetwhsiusbjreacntgse wbietthwPeeFnOzAerLoLaOndQsth(e<L2.L1OpQpb)t.heIrfetshpeescetivvaelureasngweeorfegaesosmuemteridctmo ebea:ns tbheecamimdepo4.i0nt0b4e.t8weppebn.zeTrhoeasnedvtahleue<sLwLeOrQe;notthesruebfsotraen,titahlelymiddipfofeirnetntbtehtawneethnozseercoaalcnudlattheed using <LLOQ was used. S`aWmhpelnesstrfartiofmieCdhbarylogtetoeg,rNapChi(c6.l3ocpaptbi,onr,atnhgee:hi<ghLeLstOgQeo(m2e.t1r)i2c9m)eaanndfotrhPe FloOwAeswtafsroinmtPhoertland (l3o.c6atpipobn,werraen:ge:Lo<sLALnOgeQle(s2,.41.1)~ p16p.b7).(<TLhLeOoQth(e2r.1P)F-O3A4.1g)e;omMeintnreiacpomleiasn/Ssta.ndParula,ng4e.s5 bpypb T(h<eLLcuOmQul(a1t.i9)ve~9200)%; wBoesrteohni,g5h.4epstpfbor(C1h.a5rl~ot13t.e9()1;3H.3a)g,erMsintnoewanp,ol4i.s2/Sptp.bP(a<ulLL(9O.Q9),(2.1B) ost~on52(.39)..7), and Los Angeles (9.2). Hagerstown and Portland were lower (7.6 and 6.8, respectively). "lTohceatrieosnusltasdjfursotmedafboorot1s0t-ryaepaarnaaglyesiisnt,edrvoanles,tgoecnadlecru,laatnedmtehaeinrsientreurmacPtiFoOn Atervmasl,uersesfuolrteedacihn 6 similar means across the locations (4.3 t0 5.3 ppb). PFOS and PFOA were strongly correlated (r = 63). PFOA had a lower correlation with PFHS (r= .32). pPrFedOiAct(onraotfurPaFlOlSog)i,naadjmuusltteidvafroiraabglee,mgoednedle.r,Aagned athnedirgeinntdeerracwteiorne, nwoatssaigsniigfniicfainctanptre(dpic<to.r0s0i0n1) this model. Study strengths and weaknesses: Blood donors cannotbe considered representative ofthe general population ofthe US. Research sponsors: 3M Medical Department, Corporate Occupational Medicine rCeopnosritsetdeinncyoothferressualmtpsl:esoGefoemledterrilyc imneSaenatPtlFeOaAndlecvheillsdrreenpoirntveadriinoutshislosctatuidoynsa.re similar to those. CONCLUSIONS NA REFERENCE fOllsueonr,ocGheWm,icBaulrsriisn,h1uMm,aLnunsedrba.erg1., AJKm,erHiacnasnenR,eKdJ,CrMoasnsdaedlu,ltJHb,loZoodbedlo,noLrRs.. Identification of Final report. February 25, 2002. Last updated on: 4/15/02 107 000004 EPIDEMIOLOGIC DATA. TSittrlpet:ocIodeenetiifCilciantiicoanloTfriFalluoIrnvoecshteimgiactailons in Human Sera. III. Pediatric Participantsin a Group A TEST SUBSTANCE Identity: PFOA and 6 other fluorochemicals Remarks: The results reported are final. METHOD Study design: Cross-sectional. Manufacturing/Processing/Use: N/A cHsayompmpopltoehuoenfsdiscshitinelsdctrheiedln:dtroeTnpo.rodveitdeermaimnoertehesspeecriufimccuonndceernstrtaatnidoinnsgofosfetlheecdtiesdtrfibluutoirooncohfemtihceasles in a Study period: Child sera samples were collcted from January 1994 to March 1995. The sera samples were analyzed in Spring 1999. Setting: N/A "Total population: Not reported MSuibnjneecstotsaelDeecptiaorntmcerintteroifa:PedTihateriscesr.a sTahmepylewserweeroebtparionveiddefdiotmo 3aMagbey tchlienUincailvetrrisailtoynofGroup A splotisrientpietvonecotpchrcreaoslaetinnctfueeldcttuwirioetnshsasiintgchnhesilnadnirdeanls.yvmTisphitetocmhsilodfreancuwteer-eonrseestipdheanrtysongfit2i3s.staAtlelsoifnththeecUhSi.ldrTehnehsaed "Total # of subjects in study: n= 599 children, age 2:12 years Comparison population: N/A Participation rate: NA Columbia. Subject description: 299 male children, 300 female children from 23 states and the District of 108 10s 000005 Health effects studied: PFOA serum levels in blood, as well as 6 other fluorochemicals. cDhartoamactoolglreactpihoyn/emleetchtordoss:praByltoaonddseemramsaasmspslpeescwterormeectorlyle(cHtPedLCus/iEnSgMhSiMghS-)p.resSseurrae wlieqrueidfrozen at "20 degrees C prior to the request for analysis. Exposure period: N/A Description/delineation of exposure groups/eategories: Blood sera samples were collected from children 2 12 years old Measured or estimated exposure: N/A Exposure levels: N/A wStearteisctailccaullmateetdh.odCsen:trAarlitthemnedteinccymeaanndsd,isatnrgiebsut,iogneoofmtethreidcamtaeabnysaagne,d g9e5nd%erc,onlfoicdateinocneainndtetrhveailrs respective interaction terms. A reliability assessment was also done. Tflhueorgoecohmeentirciaclmveaalunesda<taLwLeOreQctahlecumliadtpeodiunntdbeerttwheeeansszeurmoptainodntthheatLfLoOr Qindwiavsidausaslisgneerdu.m However, PFOA had a lot ofsubjects with LLOQ. Other methodological information: N/A RESULTS Describe results: r`Tahnegegewoamset<riLcLmOeQan(1o.9f)PtFo O56A.1foprpbal.loMftalhee cpahritlidcriepnanhtasdwasisgn4if.i9cpapntbly((9p5<%.0C1I),h4.i7 ghe=r5g.1e)o.meTthreic mean PFOA lovels than females: 5.2 ppband 4.7 ppb, respectively. w`Ahgeenwaansasliygzneidfiacsaantlcyon(tpi<nu0o5u)s vnaergiaatbilveeliyn assismopclieatreedgrweistshioPnFmOodAelisn.both males and females `fTlhueorgoecohmeenttirciaclmveaalnude<astaLwLeOreQctahlecumliaptoeidnutnbdeetrwteheenazsesruompatnidotnhethLatLfOorQiwndaisviadsusailgnseedr.umThere w1e0r%e oqrui9te0%@offetwhissubrjeacntgse wbietthwePeFnOzAerLoLaOndQsth(e<L1.L9OpQpb)t.he Irfetshpeescetivvaelureasngweoerfegaesosmuemteridctobmeeans tbheecmaimdepo4.i3nttob4e.9tweppebn.zeTrhoeasnedvtahleue<sLwLeOrQe;notthesruebfsotraen,titahlelymiddipfofeirnetntbtehtawneetnhozseercoaalcnudlattheed using, <LLOQ was used. 109 000006 P48F)O. SAadnjdusPtFedOAforwaegree,hgiegnhdleyr,coarnrdeltahteeidr(irnt=era7c0t).ionP,FPOFAOAanrdePmaHinSedwaerseiganlisfoiccaonrtrperleadteidct(orr=of PFOS in a multivariable regression model ofPFOS (p < 0001). I9n59b%ooctosntfriadpeanncaelylsiemist, otfhe1m1.e0apnopbf.thWeh9e5n%antaollyezreadncbeyliamgiet,ftohrePyFouOnAgewsatsch1i0l.d1repnpb(awgiet2h yaenarusp)per hgraoduptsh.e hAigghees4t wraasngtehe(1n.e9x--t h3i4g.h2epsptbg)raonudp (cruamnuglea,t2i.v0e 90% value ~ 36.1 ppb; (17.7 90% ppb)ofanyofthe value, 10.1 ppb). age SletvuedlsyisntrUe.nSg.tchhsiladrnedn.weVakenreyslsietsle:deTshcersieptdiavteaianrfeorcmraotsis-osneactbioountalthdeatsaubujseecdtstoisdaevtaeirlambilnee. PTFoOA. date, they are the only data available characterizing serum PFOA levels in children. Research sponsors: 3M Medical Department, Corporate Occupational Medicine Consistency of results: To date, no other data have been collectedon PFOS serum levels in children. CONCLUSIONS NA ORlEsFenE,RGEWN,CBEurris, JM, Lundberg, JK, Hansen, KJ, Mandel, JH, Zobel, LR. Identification of fluorochemicals in seraof children in the United States. Interim Report. June 25, 2001. OTHER Last updated on: 5/07/02 10 000007 io EPIDEMIOLOGIC DATA Title: IdentificationofFluorochemicals in Human Sera. II. Elderly Participantsofthe Adult Changes in Thought Study, Seattle, Washington TEST SUBSTANCE Identity: PFOA and 6 other fluorochemicals Remarks: The results reported are final. METHOD Study design: ~ Cross-sectional. Manufacturing/Processing/Use: N/A sHaymppoltehoefsiesldteersltyedp:erTsoondsettoerpmrionveidteheasmeorruemscpoenccifeinctruantdieornssotafndsienlegoctfetdhfeludoisrtorcihbeumtiiconaolfs itnhease compounds in this age group. Study period: 9/29/2000 Setting: N/A Total population: 238 serum samples from elderly adult donors from the Adult Changes in `Thought study. Senurbojlelcmtenstelpehcatisoeonfetrihtiesricao:mmDuonniotrys-wbearseed63pr-o9s6pyeectairvseolcdo.hoSrutbsjteucdtysowferdeemiednenttiiafiaendddunroirnmgalan (agHiMnOg)c.onEdluicgtiebldecionldlaibvoirdautailvsewleyrbeetthwoeseenwtihtehUn. ookfnWaoswhnihnigsttoornyoafndnGeurroouppsyHcehaialttrhiCcodoipseeraasteiovre dementia. Total # of subjects in study: 238 Comparison population: N/A Participation rate: N/A SSuubbjjeecctts hdeasdcrreispitdieodn:in2t3h8e Saedautltilse--a1r1e8a mfaorle5s3,.312y0eafresm,amlaels.esT5h0e.2myeeaarnsa.ge was 76years. Female Health effects studied: PFOA serum levels in blood, as well as 6 other fluorochemicals. m 000008 cDhartoamactoolglreacptihoyn/emleetchtordossp:raByltoaonddseemramsaasmspslpeescwterormeetcorlyle(cHtPedLCu/siEnSgMhSiMghS-)p.ressure liquid Exposure period: N/A (Dens=c9r3i)p,ti8o5n/+dte0li9n6eayteiaorns (onf=ex2p4o).sure groups/categories: 65-75 years (n= 121), 75+ 10 85 years Measured or estimated exposure: N/A Exposure levels: N/A wStearteisctailccaullamteetdh.odCse:ntrAarlitthemnedteinccymeaanndsd,isrtarnigbeust,iogneoomfetthreidcamtea abnysaagen,dg9e5nd%erc,onlfoicdateinocne ainndtetrhveailrs respective interaction terms. A reliability assessment was also done. Other methodological information: N/A RESULTS Describe results: "The reliability analysis indicated moderately strong correlations for the split samples with PFOA. (=.7). TAhnearleyzweadsiandweepaekndceonrtrleyloatfiaogneb,etthweereenwaegreeannodsyieganrisf'icranetsiadsesnocceiaitnitohnes bSeeattwteleenaryeeaar(rs=re0s.i2)d.ed in Seattle and PFOA. PFOS and PFOA were highly correlated ( = 75). PFOA was less highly correlated with PFHS (c= 36), tPhFatOtAhiswalsacnkootflnoogrmnaolrimtaylmyadyisbteridbuuteedtobtahseedgorenattehrepSehracpeinrtaog-eWiolfskutbejste.ctTshweiatuhtPhoFrOs Aposvtaulluaetse< ALrLiOtQh.metTichemegaenomsewterirce mnoetanporofviPdFedO.A Tfhoer ralalnsgaemwpaless1w.4as~ 41.62.7pppbpb(.95Bo%otCs1,tr3a.p9a-na4l.5y)s.es provided the mean ofthe 95% tolerance limit for PFOA was 9.7 ppb with an upper 95% confidence limit of 11.3 ppb. Sletvuedlsyisnterlednegrtlhy.s aVnedrywelatklneedsessecsr:iptTihveesienfdoartmaaatrieoncraobsosu-stetchteiosnuabljedcattsa iussaevdaitloabdleet.erTmhineesPubFjOecAts cohnalryaccthearriazcitnegriszeerPuFmOPAFOleAvellesveinlsthien Seale region. the elderly. To date, they are the only data available Research sponsors: 3M Medical Department, Corporate Occupational Medicine Consistency of results: To date, no other data have been collected on PFOA serum levels in the elderly. n2 n 000009 CPOFNOCALlUevSelIsOiNnSthese Seattle residents are similar to those found in adults and children in the us. REFERENCE Olsen, GW, Burris, JM, Lundberg, JK, Hansen, KJ, Mandel, JH, Zobel, LR. February 25, 2002. Identificationoffluorochemicals in Thought study, Seattle, Washington. human Final sera. 11. Report. 3ElMdeCrolmyppaanrtyi,ciMpeadntiscoafltDheepaArdtumletntC.hanges in Last updated on: 4/24/02 13 : 000010 PHARMACOKINETIC STUDY Titles Thesex.relted difference in perloroocanose excretion th st TEST SUBSTANCE all APFO) Identity: Perfluorooctanoic acid (PFOA); also referred to as [1-'*CJPerfluorooctanoic acid (ammonium Remarks: Puy was not specified METHOD Methodiguidein folloneds Guideline notnod Test type: Mammalian Excretion `Spectesstraineel tyorplinee: Holtzmatns Sex: Male and female Age and body weanggeohfanitmals wed:Not noted Numberofanimalssexidose: TetCogrtouep:gr4omwa:le7s,fe6mfaelmeasles Routofadministration: Ors gavage a ---- Doses: 2mg ofnonionic fluorineasAPFOinavolun of 2mL Excretion routes, body fds, an tisues monitored and/or sampled during study: Blood and wine Statistical methods used:Ses methods Mc24eenthfhouuogrdsairaoefmnea.rrgkaTsvh:aegAevnriamcaamlmsoewnfetrtwhitprhliaAncPeeFdcO,io.lintTdhoievnibd,luaoilonmdcelwutadasinbagllhiloecwavegdoe0lacenoodtsfawnadcttehresisedbryucfomacrroicldnlseecphteueendcatdfuerre a2aboThleetcoalgeos wrasnreccoorndteedn.t Tohfheonsceruumnarneurcionnetewnatsodfetheenmsienreudmbayndthuerionxeywgaesnbdoertnermrienveedrsaet pH TaFoorcrtccoienaotrniamneoesueshsntiiunqdfiuuesesioonfofA5PF%Omaandniitnoulliin tshteosnweerienaenaensthetthiezfedemaonrdalthaertmeroyrwa]s vceainlwlasedcanfnorulated rTpenorewisiovndegsloboulsaododdoasnseadsmpuolrfAeisnP.e FsTaOhmpalrneods awinerfrielnacwodledlreeecrtgewdia.vsenWshthoeosncaccuohlraleinciatmiaeolns1n0wdae,rbefaocnlolmeopwlilentgaecdl,5lp-srmtoiiponennescqoeufiirdliwibarnastion i2mdimirsatseproerdtansystdedmi.onal cesance (et were performed 161 he aft ofprbencid on he erganic ns 14900011 tInhetahretecruimaullcaatninvuelaetxicornetwiaosn sntoutdyn,eetdheed.ratTshweerreatpsrweepraereddoasseddeisvcwriitbhedafmoirxtthuerecolefarraadnicoeleasbtesleedxcAePptFtOhaatnd unlabeled APFO. RESULTS Detailed resuits: 2fl4uohroiunres(aafsteArPaFdOmi)niisnturraitnieonoanfdthhaeddaosmee,afnemsaelreurmatnsoenxicorneitcefdl7uo6ri+ne27levpeelrcoefnto0.f35tphpem.doseof nonionic. I1n.7maplpems,n9o.n2io+ni3c.5flpueorrciennetowfatshientdhoesesoefrunmo.nionic fluorine (as APFO) was excreted. A levelof44.0 + APFO was bound toa similarextent in the plasma ofmale and female rats (97.5% bound). In females, elimination APFO occurs was markedly reduced by an active secretory by probenecid (from mechanism, which is 5.8 to 0.11 ml/min/100 g), inhibited by probenecid. indicating that `afTtheerApPrFoObe/niencuildi.n cTlheearAaPnFcOe/riantiuoliwnascl1e4.a5ranfcoer rfaetmiaolwearsat0s..22Thfeorrmatailoesw,aasnddecdreecarseeadsetd0 t0o.406.1i2n affetmearles probenecid. CONCLUSIONS "isTheexcaruettheodrsincopnarctlubdyedanthaacttitvhee sheicgrhetAiPoFnOm/eicnhualniinscml.eaTrahnecedercarteioasien ifnemtahleeAsPpFrOo/viindueldinevcildeeanrcaenctehartatAioPFinO fAePmaFlOesthfarnominu1l4i.n5ctloe0ar.a4n6caefstientbhoethadsmeixneisstarfaetrioandomfipnirsotbreanteiconiodfspurpopboertnsecthiids icnodnicclautsieodnp.artTiahletluobwulearr reabsorptionof APFO in both sexes. This secretory mechanism is lacking or inactive in males and `accounts for the greater toxicity of APFO in male rats. REFERENCE Hexnchriejtairovnii,nHth.eR.at.OpPhraocuege,dianngsLdo.fStihnegeSr.oci1e9t8y2.forTEhxepesreix-mreenltaatledBdioliogyfanifdnMpeeedrifrcliunoeer;oon1c7t1ac:n5o0ae-t5e5. 11s 000012 PHARMACOKINETIC STUDY Title: Elimination and Toxicity of Perfluorooctanoic Acid During Subchronic Administration in the Wistar Rat TEST SUBSTANCE Identity: Perfluorooctanoic acid (PFOA) Remarks: Purity was not specified METHOD Method/guideline followed: No specific guidelinewaslisted. Test type: 28-Day subchronic toxicity and elimination study Species/strain/cell type or line: Wistar rat Sex: Female and male Age and body weight rangeofanimals used: Newly-weaned Nuofmanimb als/e sex/dr ose: 6anmals/scx/dose Routeofadministration: Oralgavage Vehicle: 0.9% NaCl solution Doses: 0,3, 10, 30 mgkgday Epexrciroedt,itohne raonuitmeasl,sbwoedrye fwleuiidgsh,eadnodnctiesasuweesemkonaintdo2r4edhoaunrd/uorrinseawmapslceodlldeucrtiedngonstsutduyd:yDduaryisng7tahnedst28u.dy "bTlhoeodbeahnadvitoirssaunedsafmeepdleasndwwearteerccoonlsulmfpretoicmonctowneetrroedlobasnedrv3e0dmrgegkulgarrlayt.s.At the endofthe study period, `wSetrateistthiecaplrimnectiphaoldsstautsiestdi:calSptruodecnetd'usreessuts,edPefaorrstohne epvraolduuacttimonoomfetnhecfoirnrdeilnagtsi.onandFisher's exact test sMaeltinheosdolruetmioanrsksw:asPaFlwOaAystr0e.a5tmmlen/t10o0cgcuarnriemdaolvweerig2h8t.coPnFscOeAuicvoencdeanytsr.atTihoensadimnibnliosotderaenddvuorliunemesoafmptlhees were analyzed by gas chromatography. RESULTS DPeFtOaiAle(dmgre/s2u4lhtrssf'krgo)mwDaasyl7o:werOtnhatnhethseevdeanitlhy dayof the dose in all study three period, the mean groupsofmales. urinary exeretion A statistically of Stiegsnti)f.icaInnttdhiefffeermeanlceeafnriommaltsh,endoanileyofdotshee wtahrseefogurnodupisn aelxlcrtehrteeed gsrigonuipfsiocafntmlaylleesrsaPsF(PO<A0.i0n5thaendurPi<n0e.o0n01, day 7 than they were administered. The mean urinary PFOA concentrationofthe female rats in the lowest 116 116 000013 hdiogsheesgtroduapilwyadsosseiognfifPiFcaOnAtl,y thhieghuerrin(aPr<y0P.F0O1 Athcaonnctheanttroafttihoen mwaalsesaingirmiaflisc.anlIynthhieghgerrou(Pp<r0e.c0e5i)viinngtthhee tmhaelemaalneimraalss.; however, his can be explained by the sigaficantly lower (P<0.05) mean urinary volume of wDietthatlheederxecseuplttisofnorfotmhDea1y02m8g:/kBgygtreosutpdawyhi2c8h, sthheowmaeldesasisgeneimfeicdatnotlhyavleowaelrso(Pr<e0a.c0h5e)d etxhcersetteiaodnyosfate, APtFcOaAchthdaonsethleevaedlm,itnhiestmeeraednaPlFlOyAdocsoen.centrations i the plasma ofthe male ris were significantly lhoiwgehsetr dthoasnetghroosuepo).fth female animals (P<0.001 forthetwohighest dose groups and P<0.01 for he TAeldaettiaviel1e0dbsaotdiystwiecailghatnsaloyfsmisaolfe oartganshwoewigehdtas sdiigdniofticranetvepaolsiatniyvedidfofseerernecessp.onTshee(Pw<e0i.g0h0t1s,oPfetahresolni)v.erA (poPs<s0i.b0l5e,ePxepalrasnoant)i;onhowwaesvetrh,e hsiegndiiffifceanrtendcoeseb-ertewleaetendtdheeccroenatsreolinmathleebsoadnydwethieghlotwsefsotu-nddosie gtrhoeumpawleass Tmotoh re ahbivgiho-udsostehagnrobueptwfeeemnalaen,yoofntehordmoosreedmgirlodupisnf(lP<a0m.m0a1t,ortysif)oc.i were observed in four liver, which tweasts).not significantly diffrent from control females with oly one small chronic focus (Fisher's exact Metabolites measured: None CONCLUSIONS "1T0heimeesanhiugrhienrartyhaenxcirnettihoenmsaugegeasntismatlhsa.ttThheasveexr-argeelarteednadicflferaernancceeoinfpPlaFsOmAaiPnFtOhAe fceomnacleenrtrtastiiosnasbaoruet nbetshteexfpelmaailneedanbiymaalctsivonelyt.ubBulyarthseec2r8etidoanyi,ntbohtehfmeamlaelseakniddnfeey.maTlhees esxtceraedtyesdartoeuwgahlsyatchheiesvaemdebaym7oudnatysof PFOA in 24 hoursa their daily dose. REFERENCE aHcaindhidjuarrivnig, sH,ubMc.hroYnliicneand,miAn.iKstorjaot,iaonndinVt.heKWoissmtaa.r r1a9t87.PhEalrimmaicnoaltoigoynaanndd Tooxxiicctoyloogfyp;er6f1l:6u6o-r6o5o.ctanoic nm 000014 PHARMACOKINETIC STUDY TDiotlge:andARaPtroposed Species Difference in the Renal Excretion of Perflorooctancic Acid in the Beagle TEST SUBSTANCE. Identity: Perfluorooctancic Acid (PFOA) Remarks: No information on supplier, ot number, oF puriyofsubstance testedwas given METHOD Methodiguidelinefollowed: NA Test type: Tnvivo Speciesstrainicll type or line: Beagledogs Sex: male/female Age and body weight rangeof animals used: Not sated NGruomubper1: of6a(n3immaalless/saenxd/d3osfeem:ales) given 30 mg/kg PFOA with continuous infusion of 5% mannitol SGorlouutipon2: a41(.27 mmla/lmeisna.ndP2robfeenmeaclied)wgaisvetnhe3n0amdgm/inkigstPeFreOdAaton3l0ymagn/dkkgeipnttirnavmeentoaubsollyic cages. Routeof administration: Intravenous Vehicle: Notsated Doses: 30 mgkg - sce above (under Numberofanimals/sex/dose) Eaxnedrbeltoioodnsraomuptlees,s body fluids, and tissues monitored and/or sampled during study: Group 1: urine Group 2: blood samples eStdautcitstiiocnaol fmePtFhOoAdsculesaerda:ncPeaiirneedacShtduodgbeenfotr'eesstanudseadffeor daedtmeirnimsitnreasttiaotniostficpalrosbiegnneicfiidc.anceofthe ns 15000015 Method remarks: Group 1: Dogs were anaesthetized with methoxyflurane. Catheters were fixed in both ureters afier laparototomy and cystotomy. Urine was collectaetd 10 min intervals for 60 min. (Dosingandother methods Group 2: described above.) Dogs were kept in metabolic cages afer the injection. Half-ives were determined for cach animal separately. PFOA concentrations were analyzed with a GLC-method. RESULTS Detailed results: Probenecid effectivelyandstatistically significantly reduced PFOA clearance in each dog (P < 0.05 for cach dog). PPFFOOAA ppllaassmmaa hhaallff--lliivveess ((mfaelmeasl)e:s)4:7320a2nadn5d4130h5ouhrosurs Metabolites measured: None. I appears that only PFOA was measured. CONCLUSIONS fBeemcaaluesseohfavteheanstaacttisitviecaslecsriegtniiofnicmaenccehoafnitshemrfeodruPctFiOoAn.ofPPlFasOmAa chlaelfa-rlainvcees bwyerperolboenngeecridin, mmaalleess tahnadn females. "PTFheOaAutihsosrismiallasro icnobmoptahresptehcieesc.leaHroawneceverrat,esthweitachttihvoesteubiunlaatrss,encorettiinogntrhaattetohfe PglFoOmAulainr tihlerarattioanndradtoego.f are quite different. REFERENCE r`eHnaanlhiejxacrrve,tiHo.n,oMf.peYrlfilnueonr,oTo.ctHaanaoriacnaecni,dainndtTh.e bNeevaagllaeidnoeng.an1d98r5a.t IAn;pBreoypnoesne,d sAp.eCc.ieasnddiHf.fAe.renScoellienvtehle:d (Eds). New Developments in Biosciences:Their ImplicationsforLaboratory Animal Science. Martinus Nijhoff Publishers. Dordrecht, Netherlands. 19 000016 PHARMACOKINETIC STUDY Taier Tis Dison shld Eton Pelosi TEST SUBSTANCE A i ld Fl Identity: (1""C]Perfluorooctanoic acid (PFOA, 99% pure, specific activity 5.44 mCi/mmol) Remarks: Synatndphurifeied secodiingzomeethdods described previously METHOD Methotguidetine followed NA Tost ty: Tnvivo Specisatranie ype orn: Sprague-Dawley ts Sex: males and females Age andWbeoidgyhi wlegehtyra=n1g7e0o-f19a5nigmraalmssued: Weieh mes 130155 gos Nrameberooftsn6imoalunexitdos:4 ofaScvhesxnopr seure dsisuion experiments Rout ofadministration: napesioncal Vetice: Propylene lyolwater (1:1 v4) Doses: 4 mgkg. ED ixcryetion routs, bod id, anr d tisues monitored andor sampl, ed duringstudy: ine, plas, Staten methods ued Noted Mthwtrosaehn oon 120 * 000017 RESULTS Males: JTiivses,uepldaissmtari,bKuitidonney--s,Pehrecaertn,ttdeosstes,ofnta(peeprigdridaymmablasuits (pafdo)m, ghaisghtersotcnteomliouwsesmtu)scilnem.onTihteorievderoargnadnsplwaass:ma wademrienitshetrpartiimoan]ryTthisesuheisgohfcdoinsctebnuttriaotni.on i[nSleveeTawbalse e1oxafmtihneesdtufudrythfeorr pienrmcaelnetsagbeysabnyitinmesater onrecirclatng iver perfusion technique -- 11% ofthe PFOA infused was extracted by the fiver ina single pass'. uErliinmeinaantdiofnee-sUarfitnre 2a8ndafyescewsawser3e6.b4ot%hamnadjo3r5.r1ou%terseospfecetliivmeilnya.tioTnh.e aCpupmaurleanttiBvaeleExicfreetfioornwohfolPeF-ObAodiyn liminationofPFOA was 15 days (360 hour). Halflives LiOvrgearn KiPdlansemya HGaesatrrtocnemius FTeasts Blood Hmsa D1a1y3s 2n1s66 9504 229068 19024 211926 5900 ma 58 Females: pTliasssmuae,diksitdrniebyust,ioinve--r,Poevracreinest.doTsheeonivaerp,eprlgarsamam,baasnidsk(ifdnoemyshiwgehersettohe lporwimeasr)yitnimsosuneistoofrdeidsoirbguatnisonw.as: see Table 2ofthe study for percentages by time afte adminisiation] Edlaiymwianast9i1on%,~ wrhienreeawsatshthammouanjtoirnoufteecoesfewlaisminnegaltiigoinb.le.CumTuhleatapipvaereenxctrbeatlioFnioffe PfoFrOwhAoline-ubriondeyafter | liminationofPFOA was <1 day. Halftives - Organ Liver H3s8 KiPdlansemya 2329 Blood 33 mMeettaabboolliiztede.s mSepaescuifriecdm:etDaebfolluiotreisnwateiroennooftPdFisOcAussweads. measured to determine whether it was 21 000018 CONCLUSIONS CmaislemxeisinfleoiemnMiIctEeeviduerssi.snaHtrohywaenevl1ei5rmi,noathtehiroeenPoaFfsOPnAFoOdaoApspweabarseyntothbisGserioveudft,.sreSseuinlctobinnidg,liinthedexicrrfeefttiseonwpheorbsloiets-thbenomcdaeylosf and CCPooFmmOppAoouuinnnmddaealxecprreattpesdwmaebaseiantntehrdaounlsdygbirsleeuateherrseaffgooee r0dmifoofafefrPetPnFtFOiiaOAlA-oaIitinnbdooftcohmnesjtuegxaaebtselst3.ewTfehlois3m,atthhteeopbinaylrosyennxt was not e5n9p5o.mnsaiilnoffoepwosisifbflreeinncksbe(tTwheee ehorssiodisascnudsnseithseirunnopofuFbFlnOiAsrehesxectrdsetioofVn.a)nden Heuvel ta REFERENCE VmaenadbeonlHsemu.venld, Jel.imKiunastliioknso,f BpLef,uVeornoRosatealngohiema,cdMLin.aalnedaPnedtefrseonm,aRrlEt.es.19.91.BiToichseume.diTsoxiibcuotl.ion, 6(2):83-92. 2 2 000019 PHARMACOKINETIC STUDY Title: Renal Excretionof Perfluorooctanoic Acid in Male Rats: Inhibitory EffectofTestosterone TEST SUBSTANCE Identity: ["C]-Perfluorooctanoic acid (PFOA, 99% pure, specific activity 544 mCi/mmol) Remarks: Synthesized according to methods described previously METHOD Method/guideline followed: NA Test type: Invivo `Speciesistrain/cel type or line: Sprague-Dawley rats Sex: males and females `Age and body weight range of animals used: WAegieg=hsti(xmawleeesk)s.= 170-195 grams `Weight (females=) 130-155 grams Numberof animals/sex/dose: 4/sex/dose Routeofadministration:intraperitoneally(ip) Vehicle: Propylene glycoliwat(e1r:1viv) Doses: 4 mg/ke (administered as [1"*CJPFOA one week afte vehicle, 1 beta-estradiol, o testosterone implantation) Excretion routes, body fluids, and tissues monitored and/or sampled during study: Urine, plasma, feces, liver tissue, kidney tissue o`fStvaatrisitaincaclem(eAtNhOoVdAs)u.sedD:unDciafnf'esreencsets bweatswepeenrftorremaetdmetnotcgormopuaprsewienrdeivdiedtuearlmmieneadnbvyalounees-wwhaeynanalysis ANOVA showed differences. (Levelof significance tested was p<0.05.) 123 000020 NC aErarI EaaigAaymemmmimir I Dose "C-PFOA/R)** [ Tive Kidney 1910.12 [ccaassttrraatteedd//vIeThhietcal-eestradiol 10.11 0.03 | 0.020.001 0.08%0.05 | 0.02%0.004 040+0.03 [Plasma | 1485029 0.0102.0106 EI 107005 NT. 16%of doisn4e days. Sr similar to sham/vehicle `Fecalexcretion:Thiswaslessthanurinaryexcretion.Regardlessoftreatment group,the cumulative: `percent of PFOAdose eliminated infecesover 4 days wassimilar in sham/vehicle, casirated/vehicle, `castrated/| Theta-estradiol groups. Excretion was higherinthecastrated/iestosterone group. Sn 0000z1 HHiysatloipnaetdhroolpolgeitcfaonramlaytsiisondi(dantoetstrfeovreaPlFfOoArmabtiinodninogf thoyamallien-esdperciofipc iplrntoetheteinmaallpehak2iud-ngelyo.bulin): oFfemPaFleOsA:weTriessuoebsceorncveendtraamtoionngs:treNaotmseingtngifriocuapnts differencesinliver, kidney,andplasma (sham/vehicle, ovaricctomized/vehicle, concentrations o7v0ar%oiefcttohmeizPedF/OteAstdoossteerionnuer)i.neUrinin4adrayyse.limFineactailoenx:creNtoiosni:gn1i0fisciagnntidfiifcfaenrtendciefsf;erlelncreast;s aellliemxicnraetteeddalbeosust than 0.5%ofthe dose. Metabolites measured: None CONCLUSIONS p`TrhoebseencreeisdusresduugcgeedstPFthOatAteesltiomsitneartoinoenpirnectarsetartamteendtmianlhiebiattssetlhiamtinhaatdioinnocfrePasFeOd APFinOtAheurmianlaer.y eAxlcsroe,tion. Testosterone is a key determinantofthe sex difference in PFOA elimination in rats. Remarks: none REFERENCE pVearnidleuonroHoecutvaenlo,icJ.aPc,idDaivnimsa,l1eWr.a,t:SoInmhmiebritso,ryR.e,fafnecdt oPeftteersstoons,teRr.oEn.e. 1J9.92B.iocRheenma.l eTxocxriectoilo.n7o(f1):31-36. 125 000022 PHARMACOKINETIC STUDY "RTaittlses Covalent BindingofPerfluorinated Fatty Acids o Proteins in the Plasma, Liver, and Testes of TEST SUBSTANCE Identity: [1-CJPecfuoraociod(c1t-"aCnIPoFiOAe) Remarks: 999% pur, specific activity = 51.7 mCimimol METHOD Method guideline followed: Not specified Test type: Tnvivo, Species'strain/cell type or ine: RatHarlan Sprague-Dawley, obained from Harlan Sprague-Dawley (indianapolis, IN) Sex: Male Age and body weight range of animals used: Six-weeks, 170-195 grams Number of animalsisex/dose; Not specified Route of administration: Intrapeitoneal (.p) Vehicle: Propyleneglycolivatr(1:1, vv 1 mike) Doses: 9.4 umole tEexsctreestion routes, body fluids, and issues monitored andlor sampled during study: Liver, plasma, "STthaetilsetaisctalsimgenitfhiocadnst duisfefde:reDnicfefsetreesntcweassfursoemdctontcoolmpwaerreeidnedtievridmuianledmebaynosnweh-ewraeyaannaallyyssiissooffvavrsiiaannccee indicated differences. The level ofsignificance foral analyses wasP < 0.05. Met"hToesdt raneimmaarlkssa:nd test substances ((119-8"7C).PerHfelmuoogrlooobcitann(o2ixc acrcyisdtawlalsizsedy,ntdhieasliyzzeeddaannddpluyroipfhiieldizaesd)d,efsactrtyibeacdidbyfreLeL.bRoeviicnheestearlum Calobmupmiann,ya(nSdt.alLoutiisss,ueMOc)ul.tuRreeamgeednitagaranddessuoplpvleenmtesnwtesrweeorbetaabiinaedinferdofmrAolmdrSiicghnCahCehmeimciaclal `Cofmoupra-nbyow(lMMiillwalu-kQeewa,tWeIr).purWiafticeartipounrisfyisctateimonanwdasa 0p.e2r5foarmmedilbysp(aMsislilnigpodriestCiolrlepd,wMaitlefrortdh,rough McoAn)t.rRoaltesoweorme (inadpipvriodxuiamlaltyehloyu2s1edC)i.n sAus1p2e-nhdoeudrsitgahitnlaensds-s1te2e-lhocuargdesariknaphtoetmoppeerraitoudrew-as inaintained. Food (Purina Rat Chow No. 501122,6 Ralston Purina Co, S. Louis, MO) and water were 126 000023 pbreofovriedeidniatidatliiobnoitfumthtehreoxupgehroiumtentth.e study. An acclimation periodofat leas 1-wek was allowed Cova[l1e-nVt*CbJiPnedritnlguoofroPocFtaOnAoitcoapcriodte(i[n1s-i"nCvIiPvFoOA) was administered to rats in propyleneglycolwater a(1:1n, esvtihevt;iz1edUw/iktgh)Naemtabudtoaselo(f590.m4gA/kmgo,li,p);.tpi.ssAulesdewseirgenaqtueidcktliymersempoosvte-dt,refartemeeznet,claatmspwede,reand cSteonrteidfuagtat-i7o0n.C.MaBclrooomdowlaescurleamrobvienddiinnag wlaigshtdleyteherpmairniendizoendtniesesudelehoamnodgpelnaatsemsa,wwahsiscehpawrearteed by. bacriodu,gshatmuppletso w1e0r%e TwaCsAhaenddwpiutth 3onmLicoeffomret1h0amnionluteetsh.erTo(3r:e1m)o6vteiamnesyaunndbtohuennd3pmerofrleuotriimneasted duesriinvge3d m"LCocfoeutlhdybleaecexttartaec.teWdafsrhoimngthweapsroctoeinnt.inOuende,imfilnleicleitsesraoryf|, uNntiNlanOoHadwdaitsiaodndaledPtFoOtAhe pprreoctiepiintaptree.ciTphietatseamapnldepwlaacsedthiennanesuhtarkailnigzewdawtietrhba1tMh oavceertniicgahctiadta3n7dC1 mtoLsowlausbiuliszeedtfhoerplrioqtueiidn wScaisntiplelraftioornmceodunatcicnogrwdihnigletoaOn.oHt.heLroawlriqyuoettwala(s19u5s1e)d. fPoFrOpAr-otdeeirniavnealdysriasd.ioTahcteivpirtoyteiinnalalnaslaymspilses wwiatshaquaPnatciktaatreddDuPsiMng1a-2P-a3cksaorftdwLairqeupirdoSgcrianmt.ilRlaatdiioonacAtniavliytzyeirnwhiytdhroqluyesnacthescowrarsecdteitoenrpmeirnfeodrimned Hionic-Fluor scintillation cocktail. Binding was expressed as pmol PFOA equiv/ig protein. CovaCl-elntabbeilndeidnPgoFfOPAFwOaAs atoddheedmotgoltoubbiensacnondtaalibnuinmginalibnumviitnroor hemoglobin in 1.0 mLofphosphate abudfdfeedr itno g1 miLavoefph2,4o, s8,phoart1e b0ufA0Mfersoolubtriionn.g tIhfemertehacitoinoinnmeioxrtucryestuepinteow2ermeL.prAelslenetx,ptehreiymewnetrse Pwreorteeidnonweasuspirencgiapiftianteadvwoiltuhm1eo0f%bTuCfA.feoTrfo2remmL.ovTehaenytifmieeeofunibnocuubnadtipoenrfwlausori1nhaotuedr aatci3d7,C. Ssapmupnlaets2w5e0r0erweavoslhuetdiownist/hmi$numtLe foofarc$emtionnueteSstaifmteesr. eSaacmhpalceestowneerewavsohrtsetxepe.d Tfohre|amcietnounteewaansd wtraasnscfoenrtreidnuoeffd.ifnPreocteesinsasraympnlieslwneoreadtdhietinownaalshPeFdOwAit(has5dmeLteorfmeitnhederb2y aldidqiutiidosncailnttiilmleast.ioWnashing. cIoNuntNiangO)Hcoautl3d7beCeixntaraschtaekdifnrgowmattheerpbraottheionv.erTnhieghptr.otBeiinndipnogwdwearsweaxsprheysdsreodlayszepdmowlitPhF|OmAL of cquivimgofprotein. Sele"cTthieonloifvetra,rpgleatsmtai,ssuaensdftoersttihsewaenraelysseilseocftePdFaOsAt-abrigentdtiinsgsuteos pfroorttehiensanalysisof PFOA-binding to oprrottheeiynsarbeectaaurgseettohregyaanrseefiorthpeerrfmlauojroirnatitsesduaesciodfdtiosxticriitbyut(iloinvefroarnPdFtOesAts)i.n rats(liverand plasm) RESULTS Detailed results: `Covalent binding of PFOA to target issues in rats "wTehreecpovoaolleendtbbeicnaduisnegndoattaifmoer-dPeFpOenAdefnotr ccahcahngteisssiunet(h2ehaobusro,luItdeaayn,danredla4tidvaeycsonafcteenrtrtraetaitomnesnot)f tciosvsauleetnytly=b9oduanyds)prsotheoiwnewdetrheatobtsheerrveewd.asTlhiettlteidsisfufeeerleinmcienaintitoinsshuaelfc-olnifceeafotratPiFoOnsAof(aPveFrOagAein the range of2 hours to 4 days. In PFOA-reated ras, the absolute concentrationof covalently bound 127 000024 -- hPaFdOtAhewhaisghseisgtnirfeilcaatnitvleychoingcheenrtriantithoen polfaPsFmOaAt-hdaenriinvethderlaidveiro.aOctFivtihtey ctoivssauleesntelxyambionuendd, ttoheprtoetsetiens. wAphpircohxpirmoatteeilnsy w0e.r4e%omfodtihfeietdestfeosllPoFwiOnAg icnonvcievnotardamtiinoinswtarasticoonvoalfePntFlOyAb,outnids.suTcsowdeerteermine. `haommoougnetnoifzceodvaalnedntsluybjbeocutenddt'o"SC DfSou-nPdAwGiEthaiuntothreasdeiotgisrsaupehs,ynwoitrhadfilouaocrtoigvreapphryot.eiDnubeatnodsthweersem:all detected when 50 Ag protein was separated on SDS-PAGE and the X-ray film was exposed to the gel for up to 2 months at 70C. Cova"lTehnetcobvailenadobifinPdFinnOggAoftoPFheOmAog(l0ohbeimnoagnldobailnbuwmaisn in vitro diminished by the additionof cysteine with no effect of methionine in parallel incubations. Metabolites measured: [1-'"CJPerfluorooctanoic acid CONCLUSIONS bDiensdpsitteo tphreotmeeitnasbionlithcepinlearstnmeas,s loifvtehr,eanpedrftleusotreisniatnaedcfoavtatyleanctidmsa,ntnheer.resAulltthsoiungdhicPatFeOdA-thdaetrPiFvOeAd. trahdeiaomacotuinvittoyfcroaudlidoabcetifvoiutnydascsoovcailaetnetdlywiatshsoacniyatgeidvweinthprportoctieniwnafsolnlootwienngouthgehotrogbaenisceeexntractions, ffoolllloowwiinnggtShDeS-adPdAiGtEi/oanoutfocryasdtieoignreatpohyth.e Tinhceubiantviiotnr,obcuotvanloetntthebiandddiintgioonfofPFmOetAhiwoansinreedtouctehde tihnactubpartoitoeni.nTshulsf,hytdhreylabgirloituyposfmcayystbeienientvoolivnehdi;bitsuPlfFhOydAryclovgarloeunptsbmiandyinbgeotfhpersoitteesionfscsouvggaelsetnetd. attachment of PFOA. REFERENCE aVcainddsetno pHreoutveeiln,s 1iPn.t,heKupsllaiskimsa,, B.L, liver and and Peterson, R.E. testesofras. 1992. Chem Covalent bindingofperfluorinated -Biol. Interact. 82:317-328. fatty 128 128 000025 PHARMACOKINETIC STUDY TAimlm:onCihulmcp"yCr)mPienrfeiEoarhoaoanneodatFeeoar PEotlamssiiunma[`CCIPaerfbluorrooictanReastuslafotneartAedmission of TEST SUBSTANCE Identity: Ammonium ["Clperfluorooctanoate (("CI-APFO) Remarks: ["CI-APFO: specific activit=y 0.51 uClimg, radiochemical purity >98% METHOD Methodguideline followed: NA Test type: invivo Speciesstrain/eel type or line: rat, Chisles River CD. Sex: male Age and body weight range of animals used: 12 weeks, 300-342 grams Numberof animalssex/dose: 5 Routeof administration: intravenous Vehicle: 0.9% Nacl mDeoasens,:anSiimnagllse ndootsetsrewaeterdewaidtmhincihsotleersedtyarsafmolilno=ews:13.a5nmigm/alksgtmreeaatned(wciontthroclhoglreosutpy)ramine =13.3 mg/kg Eplxacsrienat,ioendrboultoeosd,cbeolsd,yafnlduidlsi,vearnwderteismsounesitmoorneidtaonrdeodrasnudm/oprlesdadmuprliendg dtuhristnugdys.tudy: Urine, feces, Sutsaetdisttoiecavlalmueattheosdigsniufsiecda:ncDeoaftdaiwfefrreenecxperebsestewdeeans mtewoangsrousptsaantdaarsdidgenviifaitciaonncse,lTevhelsotfudep<nt0.s05t.est wes `acMceetshsotdorweamtaerrkfso:r2R4athsouwresprreiohroutsoedadimniniinsdtirvaidtuiaoln soafitnheestsesstteseulbsmtaentcaeb.oClairsbmocnag-elsaabnedlefdus[e"dCwJiAtPhFfOree aprsepoabrteadibnyeddifsrsoomlv3iMn.g tChhotleetssyurbasmtiannecewains0o.b9t%aiNnaedClfrtohmeM[e"aCdJJAoPhFnsOons.oluTthieondcoosnitnagisnoeldut2i.o1nmsgw/emrLe), Cadhiool-elsatbyerlaemdinees(dsruibesdtnandcegwraosunaddmriesniinst2e-r6e2d0)aswaassimnilxeedi,na4v%enboyuwseidgohste,(waitehrPaurtiinlaveLian)b. CThwowo.mTLheof h(aed dFoosiitnagms;oltuhteiootnhwearsatasdmwienriestgeirveedntnoocramcahloPfur1i0naaisL.abFiCvheorwa.tsIwneorredgeirvoena4l%owchaocloemstpyarraimsionneoifnthfeeed WTeaidgihotms.etiTchereasvueltrsagoendaonseasbasoluatdemibnaisisst,etrhed r0adciaoclhabgerloeudpdwoesrees w13e.3remngo/tkagdj(ucshtoeldsftoyrrianmdiinvei-dtuarlatbeoddy ainnidmivaildsu)alanadts131.45dmagy/skagf(ecronatdrmoilniasntirmaaltsi)o.n Ufritnhee taensdt sfuebcsetsanscaem.plAeLstwhiesrteicmoel,ltehceterdaattwientreervaanlessftohretized 129 000026 ietdlitem chms udcm ino bydoinnhBeed oetshesdsene dingwsia on. wPst ms desdndod resus tTalerst:owAtf 14dpocsmteshaprNsv osmSsoeifemomntetahensmetmnoooptneoeescrambgeeoofcrAodomsBorcithndrtkiioee1id0a, Preoose tom aacocbsloene dThFcohnn lrslP coereoTiepesaop nspcoon and red blood cells for carbon-14 content 14 days after [14CJAPFO administration are shown in Table 1. Tie1. Ecko Choisy Tseon Cocos Cabo 14 KtLive Ps, `Red Blood Cells After a Single Intravenous Doseof['/CJAPFO Treatment Group = on `CCarboon-n14 cent(uger/gatistsueoirmoL unid) Sl Som oeZEEE 207 Metabo messed None BR `CONCLUSIONS bcpaosssoetofchosyrain rotor fe xr of Reivers Remo:Th srscn peen spayedi stomnbees oFonotv T1wouoE57o35o or pose REFERENCE Johnson, J.D., Gibson, S.J., and Ober, RE. 1984. Cholestyramine-enhanced fecal eliminationofcarbon- 130 50 000027 PHARMACOKINETIC STUDY Title: Metabolic HandlingofPerfluorooctancic Acid in Rats TEST SUBSTANCE Identity: Perfluorooctanoic Acid (PFOA) MRienmianrgksa:ndPMearnfulfuaorcotoucrtianngoiCcomacpiedn(ya,miStx.tPuarueol,flMiNneaSrS1a0n1d.bIrtasnpcuhrietdyiwsaosmenrost) iwnadiscastuepdp.lied by Minnesota METHOD Method/guideline followed: Not specified Test type: Fluoride determinations andultrafiltration studies were utilized--Rat in vivo and in vitro; Human serum-in vitro `Species/strain/eell ype or line; Holtzman rat; Human serum Sex: Rat-female; Human-notspecified Age and body weight range of not specified; Human serum-age aannidmawlesiguhsteodf:soRuartcsewewiagshneodt approximately specified 250 grams, ageof rals was Numberof animals/sex/dose: Fluoride determination--not specified; Ultrafiltrationstudies--Rats serum two aliquots; Human serum-three aliquots Routeof administration: Rats were dosed via stomach intubation `Vehicle: Rats were dosed with an aqueous solutionofperfluorooctanoic acid Doses: Rats were dosed with 2 mg nonionic fluorine as perfluorooctanoic acid; additionally, four rats were fed a low fluoride (<0.5 ppm) diet; Human serum-0, 75, or 1500 ug nonionic fluorine (as perfluorooctanoic acid) uErxicnree,tainodn freocuetsesw,erbeodaynafllyuziedsd,faorndfltuiosrsiudeesdmetoenrimtionraetidonasnda/nodrusltarmapfilletrdatdiuonrisntugdisetsu;dyH:umRaant--sseerruumm, was. analyzed for ulrafilration studies Statistical methods used: Means were statistically compared by calculating Student's value. A P-value of <0.025 was chosen as indicating significance. Method remarks: Fnlounoiroindiecdeftlueorrmiinne,ataisopnesr--fRlauotrsoowctearneoiacdmaicniids,tbeyresdt2ommacLhofinatunbaatqiuoeno.uTshseolauntiimoanlscownetarienpilnagc2edmign of 2i4n,diovrid5u2a.l5mheotuarbs.olIinc acdadgietsioann,dfofuerd rraatscwheorwe (pPluarcienda)inamnedttaabpolwiactecrag(e1spanmdffleudoraidleo)awdflluiobriitduemf(<o0r.4.p5,pm8,) ecotnteanntdodfistthiellfeedcweastaenrdffaocrialipteartieodtdohfe 9a6nahloyusriss. fTorhinsonrieosnuiltcefdliunorainseu.bsAtfanetwiaclrydsetcarlesaosef itnhiyomnoilc wfeluroeriaddeded 131 000028 to the urine containersto experimental period, the inhibit bacterial growth during the urine and feces were collected and collection period. Atthe the anesthetized animals endofthe were sacrificed by Sctaorrdeidacfpruonzcetnuurnet.ilTahnealbylzoeodd. wUarisnea,llsoewreudm,toacnldotfeacnedstwheerseearlusmo woabtsaicnoleldecftreodmauftnedrocseendtrainfiumgaaltisotnoapnrdovide baseline data. cages, and the Twheeigvhotloufmtehseoffeucreisnweecroellreecctoirodnesd,.whAicshmailnlcklundoewdnwaqtuaenrtniteyedoefddisttoirlilnesde the metabolic: water was added to othneicfefcleusosraidmeplaetsp,Hwh5i.0chwiwtehrtehtehfelnuohroimdoegieonn-iszpeedci1f0i.c etlheicctkrosdleu,rrTy.heThieonsicerfulmuoarinddeuirnitnheewdeirfefuasnataelyozfetdhefor pfeecrecshlwoariscdaectiedramtin6e0dCat(pthHe 5f.l0uowriitdeh itnhepefrlfulouriodreooeclteacntoriocdeacaifderisinsootlaatciiodnolfatbhilee ufnludoerridtehebsye dciofnfdiutsiioonns)f.om e"Txhteratcottiaolnfltueocrhinniequceo.ntFeinfttoeefnsmerLoumf,rudriisntei,lalnedd wfaecteesrwwaass daedtdeerdmitnoetdhewiotxhygtheenobxoymgben(-pbrioomrbtorecvoemrbsuestion opfeltlheet osfamfpillteers)patpoearctpualspaafnlduofriirdeed twriapt.hoUutp dtroy0i.n3gminLtohfe osexryugmenorbourmibn.e Lwaarsgepripveotlteudmeosnt(ouap t0o.33-mgrLa)m of S`lsiegrhutmlylomwodiinfifleudorfiodretwheeraenapliypseitstoefdtohnetofetcheespienlltehtatan1d5 lmyoLpohfilitozteadl piroinoirctsotrceonmgbtuhstacitoinv.itTyhbeufmfeerth(oTdISwAaBs, `rOercioovnerRyesseaamrpclh,esInwce.r)ewcaasrraideddetdhtrooutghhe tohxeygcaetnirbeopmrobcepdruiroer.to firing instead of 15 ml.ofwater. Blank and eUlqturialfiiblrtartaitoinonwsitthudaimeisx--tTuhreeopfH9of5t%waoir9a0n-dmi$.%alciaqrubotosnodfiohxuidmea.nSseveernutmy-wfaisveadpjguosftnedonti0o7n.i4cbfyluorine (as mpeLrfolfutohreoocstpainkoeidcsaecridu)mwwaass ardedmeodvetodofnoer daeltiqeuromtinaantdio1n5o0f0thjeg iwnaitsiaaldcdoendcetnotrtahetisoencoofnpde.rfAlfutoerr2oochtoaurn,oi1c0 ualctirdafainltdratthieonreumnatinfiitntgedsweirtuhmacDoinatfalioniXngMpSe0rfmlueomrboroacntaen,oiwchiaccihdrwetaasintsramnoslfeecrureldesto>a5n0,A0m0i0cdoalntoTnCs.FITOhe u`lstarmapfliletrcahtaemwbaesrcwoallsecftleud.shAednwuiltthra9fi5lt%raatier,wa3%s aclsaorbpornepdairoexdidfe,ropmrepsosoulreidzesdewriutmhonbittariongeend,farnodm 1f5oumrLratosf p(edrofsleudorfooroctthaenofliucoaricdied dbeytesrtmoimnaacthioinntsutbuadtyi)on4. anhdoufrrsomaf7e5rmrLe.coefivbiunfgfterhe2ed m(gpHo7f.4n)oniisootnoincicflsuaolriinneetaos which900 pgofnonionicfluorinehadbeen added. RESULTS Detailed results: Employing of 80 1.0 the oxygen SEM% was boobtmabinreedvefrosrepeexrtfrlaucotrioooncttaencohinciqauceid.forThdeetreercmoivneartyioonfoffluootraildeflfuroroimne, 4 recovery upesrefdlausortohoectfalnuooriicdaectirdapwainssiidnecrtehaesoedxytoge9n4bom1b..5%Thweheqnuan1t5imtyoLoffnoTnIiSonAiBc bfulfufoerri,neinwsatesacdoalfcuwlaatteerd, bwyas. dSuibvtirdaicntginbgy tehiethieorni8c0folruo9r4i%de.fTrhoembtlhaentkotfaolrftlhueorpirnoecdeedtuerremeimnpeldoayfienrgaash0i.n3g-girnatmhefioltxeyrpgaepnebrpoumlbpapnedllet and 15 mLofredistilled water as a fluoride trap determine the total fluoride contentofthe feces was 0.13 + 0.020 ug. had a blankof0.40 % The modified 0.043 pg. procedure used to TinheTarbelseul1t.s Tohbteaicnonetdroiln tehxepeulrtirmaefinlttriantiwohniscthudpyeorfftluhoeroboicntdainnogiocfapceirdfwluaosroaodcdteadnotoicanaciisdotionnsicersuamlinaere given solution buffered perfluorooctanoic at pH acid. 7Vi.r4tpuralolvyidaeldofevtihdeenncoenitohnaticthfeluuolrtrianfeil(tarsatpieornflmueomrboorcatnaenobiocuancdidv)eardydleidtlteo the saline solution was ultrafilterable. The addition ofperfluorooctanoic acid to human serum, in amounts 132 132 0000<9 B Ll O s a E yTl RoaA WrL [Aliquotl Nome [Toul | Tonic [Toul| | [oom [oom[TT |[||ESZpper |w8r | | we Jio] RaSerwm [1 TCommolsennr 7 T0002 [on T --- [ - [2[Fermemalsen | 0053 | 132 | 0016 |oz] "Pooledserumfrom normal rats. FT E ar, 133 e 000030 TNaobin2,iU(ra8rPyoTErxcoreoteionnooifofoAcnkand0NRraisonic Faoid Following Adminsation of 21mg Dos of "Time (hr) Tonic* (ug/hr) [eee ` [80 pmzesd | 0| aaesom |_isewne | ess] bT e inoriTrroomenoTwOeR1 Irwe= mreaoedmaoios. eedwToesreal e C"TuMeeerraiondne+edStEeMrie xceton te for the 96houe prod fs no giv soc thes nial were od a low ogeuaBretsaicsotveoredrmadtae sind onnSofrilStars3s.3ogd 9n6shpousolhoawgoinrTeo0l5 3. oF taard35 mesne:stoafd4i5e54of fE .e adm6ihoorr,dhdoosmOeFrosoqnuafyuorfA mwiisoRVienrgsx50c pny rs f Table 3. Percentageofthe Administered Doseof Nonionic Fluorine Recovered in the Urine and Feces. foateer 52.5 and 56 hTswisae Tussi Twssiiz [Time [Une Feces [Tow | Moblin mosses Forfa soos oreos CONCLUSIONS TThetentooionue oaernnwcoeameipolnennt1thse5nsbhori,evaAamsb,noeruaoseepdet2d0eo1srdofnanfoeor aaidmhiTnastarieopenoewfihsoeohoeroedvodrseea,dibdubtend eoceteetoeaiets 3w8iohesosm.axNhbeekthormhitenroeedmnTsahrhdaseidnlm,vseheai tahivoHsoIefpronarrTSthoHrEroSaeofonocodi8i,rAbibhdwegh , med mae oxopossi, conugaed fon REFERENCE 134 134 000031 Ophaug, RH. and L. Singer. 1980. Metabolic HandlingofPerfluorooctanoic Acid in Rats. Proc Soc Exp Biol Med. 163:19-23. 135 000032 PHARMACOKINETIC STUDY Title: Stimulation by oestradiolofthe urinary excretionofperfluorooctanoic acid in the male rat TEST SUBSTANCE Identity: Perfluorooctanoic acid (PFOA); 98% pure. Remarks: The test substance was dissolved in a mixtureof propylene glycol-water (1:1) ata concentrationof 25 mg/ml. METHOD * Method/guideline followed: NA Test type: invivo Speciesistrain/cell type or line: rat/Wistar Sex: male and female Age and body weight range of animals used: age not specified, male bw range 170-300g, female by range 150-180g iNnutrmabpeerriotofneaanliimnajlesc/tsieonx/odfosPeF:ODAo:s6edfewmiatlehs,ve6himclael:es6, males and 6 10 castrated females; Dosed with single males, 10 castrated males treated with oestradiol, and 10 intact males treated with oestradiol Routeofadministration: intraperitoneal injection Vehicle: propyleneglycol-water (1:1) Doses: 50 mgke, single injection Excretion routes, body fluids, and tissues monitored and/or sampled during study: urine, serum Statistical methods used: one-way anslysisof variance (differences between groups), Student's t-test for unpaired data (differences between meansoftwo groups) `Method remarks: Ras `and tap wateradlibitum. were housed in Twenty males metabolic cages in groupsof 5. were castrated atthe ageof28 They were fed days and fier 5 standard rat chow weeks they were. used in the test. subcutaneously eHverayolsfetcfhoendopdearyatfeodr and the 10 14 dianytasctbemfaolreeswtheerteesdt.osUerdinweitwhas00colgl/ecktgedoiensttrhaedicoalgevasldeurraitneg. the96 hours afear single `samples were ultrafitercd dtoosdeeotferPmFinOeA.theBplroootdeisnabmipnldeisngweorfePcFoOlAlecitnedsebryumc.arTdhiea puncture. Serum PFOA contents of ucroinnjeu,gsaetreudmf,oarnmdsoufltrPaFfiOltAratiens were urine measured with were separated gas and cahsrsoamyaetdogforrapPhFy.OATchoencferneteraatniioonn.ic and possible: 136 136 000033 RESULTS Dsteitmauillaetdorryeseuflftesc:t oCanstthreatuiroinnaanrydaexdcmrientiisotnraotfiPoFnoOfAo.estDruardiinogltthotehfeirsmta4lehroausrsh,afdeamsailgenirfaiscaenxtcreted 72+ 5b9o%th(0in-t6a)ctofatnhdecadsotsrea,twedhemraelaessiwnetracetamballetsoeexxccrreetteedPoFnlOyA9in u4r%ine(1i-n6)s.imiAlfatreramhoeunotesstsradfieolmawleeast(me6n1t+, P19F9O%Aanidn 6ur8i+ne1fa4s%teartt2h4ahn,inrteascptecmtailveelsy)(.50T=he13c%astarta2t4ed)m,albeuts nwoitthaosutfasotesatsrafdeimoallterseoartmoeensttreaxdciroeltterdeated mSaelreusmdoufriinntgactthmeawlheoslweatsestco(nPsi<de0.r0a1b)l.y Ahitgthheer (e1n7d-o4f0thteimeess)tt(h9a6nbn,tthheesceonrcuemnotfroattihoenrogfroPuFpsO.A in the F(ePm<al0e.0s5a)nadftienrteacatmmeanlte.s trPaFteOdAwmitahyPeFnOhaAnceexctrheeteudrisnleigvhotllyummeoreexcurreitneed.than control animals up to 72h Uitlstaafniilotnriactifoonrma.ndOavnearly9si8s%ooftfhPeFuOrAinewsaasmbpoluesndinodipcraotteeditnhsati PtOheAseirsunmootfmfeetmaabloelsizaenddainndtaicstsmeaclreetsed in determined in the samples taken during 12 h aftr dosing Metabolites measured: none CONCLUSIONS No conclusions were given. REFERENCE Veixicnreent,ioMn.p,erHfalnuhoirjaorovcit,anHo.i,eJaacaikdoinnabtohe,mJa,laenrda.P. PPehuarram.ac1o98l9o.gyS&timTuolxaitcioolnobgyy o6e5s:tr2a7d4i-o2l7o7f.the urinary 137 000034 PHARMACOKINETIC STUDY "Title: Dispositionofperfluorooctanoic acid in the rat after single and subchronic administration TEST SUBSTANCE Identity: Perfluorooctanoic acid (PFOA) from Aldrich-Chemie; purity was not indicated. Remarks: The test substance was dissolved in . b) 0p.ro9p%ylNeanCelgsloylcuotli-ownatfeorr imnitxrtaugraev(a1g:e1a)fdomrininitsratprearittaiononendal administration. METHOD Methodguideline followed: NA Test type: invivo `Speciesistrain/cell type or line: rat/Wistar Sex: male and female `Age and body weight range of animals used: a) neb)wl1y0wweeaenkesd'/bbwwnnoottspsepceicfiifeide.d Numberofanimals/sex/dose: 2) 18 020 Routeof administration: a) intragavage ; b) intraperitoneal Vehicle: 2) 0.9% NaCl solution b) propylene glycol-water (1:1) Doses: 2b))3,5010m,ga/kngd,3s0inmggl/ekgin/jdeacyt,iond,aivloylduomsees=f0o.r2258mcLo/n1se0c0ugtive days Elixvcerr,etkiidonneyr,oultuensg,,bsopldeyenf,luodvsa,rya,ntdesttiss,saunesdamdoinpiotsoeretdissauned/or sampled during study: serum, brain, `fSrtoatmistthiecaelqumaettihoond(sliunseeard:regTrheessbiioonl)oogfictahlehlailnfelairfereolfatPiFonOsAhipinbettheweseenrutmimaenadnodtcheorncteinstsruaestiwoanosfesPtiFmOaAted ina semilogarithmic plot Mweertehgoidvernemtaaprkwsa:terThaendanriegmuallasrwreatrechhoouwsaedd laitb2it1umC., wTihtehs&edraurmkwpaesricoodllfercotmed9bpy.cma.rtdoia7cap.umn.ctuTrhee.y `cAofnicerendreacatpiiotnastoifon PtFheObAraiinntwhaessesraummp,letidssaunesd,tahnedotlhipeirdteixstsruaecstwsewreeresadmeptleerdmiantendecursoipnsgyc.apTilhleary gas chromatography. 138 138 000035 RESULTS oDtehtearliedsruesualntas:lyz8)edAtwearlethhirgeheedroisnemlaelveelsstihnatnhfeegmeavlaegse(pst<ud0s.,05t)h.e lTehveeldsiosftrPibFutOiAonoinftPheFsOeAruwmasand m0/a0i5n)lypotsoittihveesceorrureml,abtiuoniwvears,okbisdenrevye,danbdetuwneegnitshseudeossaelsaonhdatdhehicgohncceonntcreanttriaotnioonfsP.FOAAsifgonuifnidcainntt(hpe < liinvefr (a7n-t0c.9o9n6l),atkiodnnveeys(o=n0d.933)n,aslplseenH(ov=er0.,95h),eandplunsg (is=n0d.95b9r)aosfcfoenmcaenlter.atNioonssiomfilFaFrOA Corelatd positively ith the concentration inthe serum( = 0.969, 0971, and 0.976, respectively). bh)igAhfetrerininmtarlaepsertihtaonneianl fienjmeaclteisond,utrhiengcotnhceenwthroalteiotnessto.fPPFFOOAA wiansthmeaisaelryumdiasntdriobtuhteedr ftistshuessearsusma,yebdutwere PTiRerO,,kiadbnoeuyt, o1p0e%no, afhneddborsaenwiasssufeosunadlsionhtahde shiegrhumcoonfcefnetmraalteiso,nsc.omTpwaerlevdehoaubrosuatf4t0r%adimninmiasltsa.tiAofntoefr tSewroumw,eelikv,er,baonudtK3i.d5ne%yodefhceredaosseed iwnaasdsitslcoentfinistouhs fssehriuomn,ofinmdailcaet.inIgndifsetmianlcetsp,hatshees.PFTOhAelheavlefl-slinvteshe aalrleiceonocfenPtFrOatAioinnotfhePlFiOvAoifnftehmeasleersudmurwienrget2h4ehfrsatndwe1e0k5 hwaisn efsetmiamlaetsedantdombael6es0,1,rewshpielcetiivnlym.aleTsh,ei wObasserfvoeudn.d PfoFbOeA21w0a1s.noItnfmoaulneds,inatmhoeraesslaiynoafrtrheeltliiopnisdhfiapctbieotnweoeftnhteimlevear.ndSPiFmiOlAarcloenvceelnstrofatPiFonOwAas w1e4r5ehfaonudnd13in0thhewesrpleeefnouansdifrthfeelmiavleers(faenmdalmeasle=s,73reshpaenctdivmealyl.es = 170 1). In the kidney, halves of Metabolites measured: none CONCLUSIONS No conclusions were given. REFERENCE aYifienresni,nMg.l,e aKnodjos,ubAc.h,rHoannihciajddmeivn,isHtraatniodn.P.BPuelalrest.in 1o9f90E.nviDriosnpmoseinttiaolnoCofnptearmfilnuaotriooocnt&anoTiocxiacciodloignyth4e4:rat i653 139 000036 `EPIDEMIOLOGIC DATA. Title: Mortality Among Employees ofa Perfluorooctanoic Acid Production Plant `TEST SUBSTANCE Identity: Perfluoroctanoic acid (PFOA) (`eR.e2.m,arbeknsz:enTeh,eascboehsotrots)wawsereexpaolssoedusteodPoFrOpArodduurciendgaptrtohdeucpltainotn.ofTthheewcohrekmeircasl.werMeaenxypoostehedrtcohtehmesiec.als chemicals as well METHOD `Study design: Retrospective cohort mortality study. ManadnupfraoccteusrsiPnFgO/APr.ocPesFsOinAgi/sUussee:d Tahsearesurwfaasctnanot,inafnodrmitatiisounseind tihneasltaurdgyeonnummebtehroodfsinudsuesdtrtioamlanufacture. applications and consumer products including plasticizers, lubricants, wetting agents, and emulsifiers. H(Myipnontehseostias)tmeasntuefd:actTuoridnegteframciilnietywwheatshaesrsomcoirattaelditwyifthroomccaunpyatciaounsaelaetxtphoesu3rMe tCootPtFaOgeA.Grove: `Study period: The study population worked at the plant from Jan 1, 1947 to Dec 31, 1983. Setting: Minnesota 3M plant that produced PFOA and other chemicals. Ttoottaallwoporpkueldatiinotnh:e C3h5e3m7iceamlplDoiyvieseisonp.art3i9c8ip(a3te4d8 inthe study (2788 males males and 50 females)of and 749 females). these employees 1339of were. this deceased, of which 148 males and 11 females worked inthe Chemical Division. Subject selection criteria: All workers employed for at le6amosntths at the plant between Jan 1, 1947 to Dec 31, 1983. Cdeoamtpharratiess.onWpoompuelnatwieorne: cTonmSpaMrRedanoanllyysewsi:thUt.hSe.Ug.eSn.erpaolpuploaptuiloantiboencaduesaethcraautsees-; aMnidnnceasloetnadaproppeurliaotdi-on Specific Minnesota rates for women were not available. In proportional hazards analyses: non-Chemical division workers a the plant. Preacrotridcsi,praetsiuolntirnagtei:n aSi9x9w.o8r%kpearrstiecmippaltoiyoendradtuer(i3n5g37th/i3s54t3i)m.e Owefrteheisxcploupdueldatbieocna,uvsietalthsetyathuasd(ailnicvoemoprlete dead) was obtained for 100%of the individuals, and death certificates were obtained for 99.5%of those who died. `pSeurbsjoencntelderseccroirpdtsi.onM:eaInndiavgieduaatlesmepmlpolyomyeendtdwuarsin2g7.3thyeesatrusdyfpoerrmiaoldewsearnedi2d7.e6nytiefiaerdsthfroorufgehmacleosm.paMneyan age at death was 56.4 for males and 55.4 for females. Healtheffectsstudied: Mortality 140 140 000037 D1a98t2a,caonldlefctrioomntmheetNhaotdiso:nalViDteaaltshtaItnudsewxafsorob1t9a7i9n-e1d98f9r.omWtoherkSochiisatlorSieecsuarintdyoAtdhmeirneimstprlaotyieoen dfaotra1w9e4r7e- odbetpaairntemdenftrsomfocrotmhopsaeneymppelrosyoenenselprreecsourdmse.d Death certificates to be deceased. wereobtainedfrom the state health Exposure period: The potential exposure period wasfromJan. 1, 1947toDec. 31, 1983. CDehsecmriicpatlioDni/vdiesliionneoaftitohneopflaenxt.poEsmuprleogyreoeupssw/chaotewgoorrikeesd: PFOA production was restricted to in the Chemical Division for at least the | month were there cfoornsliedsesrtehdanex1pmoosnetd htwo ePrFeOAc.onsEimdpelreodyeneots who never exposed to worked PFOA. in the Chemical Division or worked Measured measureof moronetshtismoafteCdheemxipcoaslurDei:visCiuomnuleamtpilvoeymeexnpto.sure to PFOA was estimated using the surrogate Exposure levels: Not measured. Employees were considered eitherexposedor not exposed. wStearteisctailccalulmaetetdhoadnsd:coStmrpaatirfeidedtSotUa.nSd.aradnidzeMdinMonretsaoltiatywhRiatteiodsea(tShMrRa)te,s faodrjumsetne.d fFororagweo,mseexn,,aonndlyrasctea,te: 3ratpeesriwoedrsoefadvauirlaatbileo.noTfheemSpMloRysmefonrtm(a5l,e1s0,wearned s2t0rayteiafrise)d.foCra3uslea-tsepneccyipfeircimoodrst(a1l0i,ty1a5,teasndwe2r0eyceaormsp)aarnedd between exposed on unexposed workers using stratified SMRs. Relative risk and 95% confidence cardiovascular diseases, and other intervals selected were estimated for deaths causes using proportional hfarzoamrdalml ocdauesless,(ScAaSn)c.er,Age at first `meomdepll.oymTehnet,apyperaorporfifaitresnteesmspolftohyemepnrto,poarntdiodnuarlathiaoznaorfd aesmspulmopytmieonnst wwaerseteisntcelduudseidnagssctorvaatirfiiaetdemsoidnetlhse with graphical analysisof ofaproduct term between leoxgpovseursruesafnodllloowg-fuopltliomwe-urpeltaitmieo.nships and models that tested the significance `AOtnhoesrolmoegtihstodcooldoegdicthael information: death certificates for underlying causeofdeath for the workers according to ICD 8 dDuartaaticoonlolefcetemdplinocylmuedendtyienatrohfefCihresmtiecmaplloDiyvmiesinotn,. age at first employment, Length of employment durationof employment, at the plant, length of and weemrpeloaynmaelynztedinttohdeeCtheermmiicnealwhDeitvihseiront,hecy haadlaenyeenfafreodctfaofnirrsntuemmbpelrosyomfendtea,tahnsdfargoem aaltlficrastuseemspalnodymferonmt specific causes. RESULTS Describe "The only results: elevated (Faolrthaollugfhemnaoltesiegmnpilfoiycaenets),StMheRSwMaRssfofrorIaylmlpchaoupsoeisctaincd for all cancer, caanndcewrasswebraseeldesosntohnalny | 3 Sdeiagtnhisf.icaWnthleynloewxeprostuhraen setxapteucstewda,sbcaosnesdidoenretdh,e SU.MS.Rsraftoers,alflorcabuostehsothfedCehaetmhiacnadl fDoirvilsliocnanwcoerrksewresraend the other employees ofthe plant 141 000038 In male workers, the SMR were close to 1 for mostofthe causesofdeath when compared to both the wU.eSr.eannodetlheevaMtiendnSesMoRtsa. dWeahtehnraetemsp.loWyheeendelaatthesnciyn atnhed Cdhureamtiicoanol fDievmipsiloonymweenrte cwoemrpeacroendsitdoerMeidn,nethseortea death rates, the SMR for prostate cancer for workers in the Chemical Division was 2.03 (95% CI.55 4.59). The SMR for prostate cancer for workers in the Chemical Division was 2.03 (95% CI 55 - 4.59). This was based on 4 ofemployment idneatthhesC(h1e.m9i7ceaxlpeDcitvedi)s.ionThaenrdeprwoasstaatlesocaancsteartimsotritcaalliltyy.sigBniafsiecdantonastshoeciraetsiulotnswoifth length proportional hazard models, Division was 1.13 (95% CI the 1.01 relative risk fora 1-year increase in employment in the Chemical to 1.27). Itroseto3.3 (95% CI 1.02 -10.6)for workers employed in the wCohrekmeircsalnoDtiveimspiloonyfeodr i1n0tyheeaCrshewmhiecnalcoDmivpiasrieodn wtoastheleostshtehraenmepxlpoeyceteesd ifnorthperopsltaantt.e cTanhceerS(M.5R8).for Study strengths: Vital status was determined for 100%ofthe cohort. `CShteumdiycwaelakDinveisssieosn:emTphleoryeeweassmaaypohteanvteiablefeonremxipscolsaesdsitfoicPaFtiOoAno.feIxnpaodsdiutrieonb,eecxapuosseurmeasnwyoefretnhoetnon- `measured; therefore categoriesof exposure were very broad (ever vs. never exposed). This exposure misclassification `chemicals in the would bias workplace. the effect estimates toward the null. The authors also note that there are Workers were also exposed to other differences in the distributionofage at risk among the Chemical Division and non-Chemical Division workers and that this could confound the eresspuelctisaolfltyhfeorsftuedmya.lesThienraellwcearteegaolrsioess.maTlhlenucomhboerrtsnoefeddesattohsbeinfomlalnowyeodftfohremcaanteygoyreiaerssftoorcmoamleesiannodrder to develop an accurate pictureofthe mortality experienceofthe employeesofthis plant. Research sponsors: National Institute for Occupational Safety and Health Grant and the 3M. Corporation Consistency of results: Currently there are no other mortality studies on PFOA workers C`AOlNthCoLugUhSaInOasNsSociation between employment in the Chemical Division and prostate cancer was observed, the results must be interpreted carefully. Continued follow up of this study or other studies with direct exposure measurements might help to confirm the association. REFERENCE Gilliland, F.D. and Mandel, 1.5. 1993. Mortality among employees oaf perfluorooctanoic acid production plant, JOM. 35(9): 950-954. OTHER "This study is the second updateofthe mortality study. Another update is expected to cover the years. through 1997. Tt has not yet been submitted to EPA. 142 142 000039 EPIDEMIOLOGIC DATA Title: Morality Studyof Workers Employed at the 3M Cottage Grove Facility `TEST SUBSTANCE Identity: Perfluoroctanoic acid (PFOA) and other fluorochermicals `95R0e.m9a5r4k.s: This study is an updateof the study published by Gilliland and Mandel, J Occup Med 1993, METHOD `Study design: Retrospective cohort mortality study. ``Mcaonmupfoaucntdusrsiinngc/ePr1o9c47e.ssiAngp/rUismea:ryTphreod3uMctCroottmagtehiGsrpolvaen,t Mis Nampmloanntihuams pperrofdluucoerdoopcetrafnlouaotrein(aAtPeFdO), a ppoetrefnltuosryonotchteatniccastuer(faPcFtOaAnt).used in industrial applications. APFO rapidly dissociates in biologic media to rHeylpaottehdetsoitshetemsotretda:liTtyoedxepteerrimeinnceeowfheetmhpelrooyceceuspoaftitohneal3eMxpfoacsiulrietytionPCFotOtAagaenGdrootvhee,rMfilnunoersoocthae.micals is `wSatsudfyolpleorwieodd:thTrhoeugshtDuedcy.po3p1u,l1a9t9i7o.n wCourrrkeendtlayt tehmepplloaynetdfowroartkelerasstwe1ryeeaarssiingcneedJaDne.c1,311,94179.97Tahsetchoehrort last dateof employment. Settings 3M plant in Cottage Grove, Minnesota that produced PFOA and other chemicals. Toonteayleapro.puEliagthitoyn:per6c6e7n8towfotrhkeercsohwoerrtewiadesntmiafliee.d. OFthese workers, 3992 worked atthe plantfoat least `cSouhbojretctwasselfecotliloonwecdrittehrrioau:ghADllecw.or3k1,er1s99e7m.plCouyrerdenatttlyheemCpoltotyaegde Gwrorokveerpslawnetfreorassiagtnleeasdt D1 eycear3.1,T1h9e9.7 as their last dateof employment. CMoormtpalairtiysroenfeproepnucleartaitoesn:frIonmS7MrRegiaonnaallysceosu,ntMiiensnweesorteaalpsoopuulsaetdiotno druelaethouattelsargfoervwahriiatteisonwserbaesuesdedo.n regional mortality reporting differences. Participation rate: Death certificates were obtained for 97% (n= 590)ofthe cohort who were deceased. FSoulbljoewc-tupdewsacrsip5t6i.o6ny:ea8rs0,%an(dn=th3e1m8e3a)onfntuhmebeemroplfoyyeeaerss iwnotrhkeecdohaotrttheweprlaenmtawlae.s The 12.1. meen The age at number of person-years at follow-up was 108198. There were 607 deaths identified in the cohort. Health effects studied: Mortality 143 000030 Dyeaatraecmopllleocytmieonntmewtehroedasb:stAracrteevditeoworfecoermdplthoeyewoerwkoerrsk'hniastmoer,ySreScNo,rd3soMfiadennytiefmicpaltoiyoneenuwmibtehra,t dlaatseto|f ebimrpthl,oaynmdendtatisnofofrmwaotrikonhiasntdorvye.riTfhyiostchoehrodratta.wasThleinNkaetditoonarlecDoeradtshfrInodmetxhweaosrigsienaarlcchoehdfoorrtatloluopfdtahtee the wthoerkSeorcsi.alDSiesccurreiptayncDieeasthwiItnhdtehx.e oArigliincaelnsceodhonrotsowleogriesrtecsoodleveddtahenddedaetahthcserbteiffiocraete1s9t7o9IwCeDre.verified in `Exposure period: The potential exposure period was from Jan. 1, 1947toDec. 31, 1997. bDaessecdroipntijoonb/dheilsitnoreyatiinofnoromfateixopn.osuTrheosgreogurposu/epastweegroer:iesde:fiWniotrekPeFrOsAw.ereexppolsaucreed(ijtobos3whexeproescuerlel groups `pgreonbearabtlieonP,FdOryAinegx,psohsiuprpein(ogtahenrdcphaecmkiacgailngdiovfisPiFonOjAoboscwcuhrerreedetxhproosuugrheoutto PthFeOhAistwoarsy opfotshseiblpelabnut)t;with Tower or transient exposures); and not exposed to fluorochemicals (primarily non-chemical division jobs). `Measured or estimated exposure: estimated based on job history information `(1E6x8p5o)s,uorrenloetvelesx:poNsoetd m(e1a81s5u)r.ed. Employees were considered exposed (492 workers), probably exposed u`SstiantgisttihcealPCmeLtihfoedTsa:blSetaAnndaalrydsiizseSdyMsotretmalsiotfytRwaatrieodse(veSlMoRpe)d abnydN9I5O%SHc.onfTihdiesncperoigntrearmvaclosmwpeurteesdeargiev,ed egsetnidmeart,eadnbdyramcuel-tsippelcyiifnigc tShMeRasge,usgienngdesrt,anadcaer,dalnifde tcaablleenmdeatrhpoedrsi.odTthabeuleaxtpeedctpeedrsnoun-mybeearrosoffdfeaotlhlsowaruep to the corresponding cause-specific mortality reference rates. Mortality rates for white Minnesotans were. used as reference data. Other methodological information: RESULTS Dexepsocsruirbeegrreosuulpt,s:26670i7ndtehaetphrsowbeabrleeiedexnptoisfuierdeignrotuhpe,coahnodrt2.9446ionftthheensoet edexaptohssedwegrreouipn.thTehPeFaOutAhors also. eStxrpaotisfeidedgbryoupasm.in1i8m2uwmoorfkeornse-(y1e7adreaetxhpso)suwreere0dePfFinOitAeliynebxoptohstehde fdoerfantilteealsyt-1cxypeoasredanadnd16p7r3obwaobrlkyers (219 deaths) had probable exposure for at least one year. h`iWghheenr aflolrealmpolfoytheescwaeusreesocfomdpeaartehdatnoaltyhzeeds.tatNe omonretoalfitthyeraSteMs,RSMwRerse wseurtsetilecsaslltyhasnig1niofricoannltyatslpig=htl0y5. "The highest SMR reported was for bladder cancer (SMR = 1.31, 95% CI = 0.42 - 3.05). Five deaths were observed (3.83 expected). AthefelawrgSeMinRteswtienree(eSleMvRat=ed1f.o6r7,em9p5l%oyCe1es= i0n.0t2he--de6f.i02n)i,te1PfFrOomApeaxnpcorseuartiecgcraonupc:er2(SdeMaRth=s f1.r3o4m, 5can%ceCr1of= 0th.e03defi7n.i4t2e),PaFnOdA1efxrpoomsuprreosgtratoeupcawnecreer2(.S5MtRim=es1m.3o0r,e5li%kelCy1to=d0i.e03fr~om7.c20e)r.ebrInovaadsdciutliaonr,deimsepalsoey(e5es in deaths observed, 1.94 expected; 95% CI = 0.84 -- 6.03). oIrngtahnesp(roSbMaRble=e2x.p75o,su9r5e%grCoIup=,03.0S7M~Rs15.s3h)o;upladncbreeantoitcedc:anccaenrce(rSoMfRth=e 1t.e2s4t,s9a5nd%oCt1he=r 0m.a4l5e~ge2n.i7t0a)l; and 144 144 000041 o`mbasleirgvneadn,trmeespleactniovmelay.oftThheesSkiMnR(SfoMrRpr=os1t.a4t2e,c9a5nc%erCIin=th0i.s1g7r--ou5p.1w1)a.s 0O.n8l6y(19,56,%aCnId=20c.a2s8es~w2e.r02e) (n = 3). "oTthheerreuwreirnaernyoorngoatnasb.leFeoxucrescsaessesinweSrMe oRbsienrtvheednaonnd-eoxnplyos1e.d89grwoeurpe, eexxcpeepcttfeodr(c9a5n%ceCrIoLf=t0h.e58bl~ad5.d4e0r).and c"oThhoeret.xceOsnsliyn 1prdoesattathewcaasncreerpodretaetdhsinthtahtewdeafsinoibtseeerxvpeodsuinretghrfoiursptwshtiuldey5wawserneotobassesrtvreodngininthtehipsruopbdaabtleed tehxepolsasutrestugdryo.up.HoIwteivsedrif,fiaclulotf0thienteemrpplreotyetheesseinreesiutlhtesr sgironucptwheereexpaosssuurmeecdatteoghoariveesswoemree emxopdoisfuireed (s0ince aPnFdOAp.lacTehdethneemwindteoli2negartoiuopnos,fwehxiploesutrheesfiflumrtphlearndteefmipnleodyteheeschseimlicraelmapilnaentd eimn ptlhoeyneoens-oefxptohseefdirgsrtosutpu.dy "The numberofyears that these employees worked at the plant andor were exposed to PFOA was not reported for prostate cancer. "fTuhretheexrcaensaslmyozretdalbiatsyeidnocnerneubmrobvearsocfuylaerardsiosefaseemnpoltoeydmiennetmaptltohyeepelsanti.n thTehrdeefeinoiftteheex$podseuartehsgrooccuuprwraesd.in (woSrMkeRrs=w1h5.o03,we9r5e% eCm1pl=oy3.02 e in--4j3ob.s91w)i.thThdeefointihteerP2FoOcAcuerxrpeodsuinreemfpolromyoereestwhiatnhlesyseatrhsanbut1<yea1r0oyfears ddeeffiinniittee PexFpoOsAureex.poTsuhree.SMWRhewn t6ha.e9se(9dse5a%thsCwI=ere1.f3u9rt--he20.r24)analfyozredembpylcouymeuelsatwiivteh egxrepaotseurrteh(atnimey-ears of jwoebisghotretdhoascecowridtihn9g ytoeaerxspoofsuderfeinciatteegPorFy)O,Aweoxrpkoesrusrweiwther2e73.y3 eartsiomefsexmpoorseulriekeilnyptroodbiaebolfe cPeFreObAroevxapscousleadr disease than the general population. A dose-response relationship was not observed with years of exposure. S`tSutduideysstartetnhgetChost/twaegaeknGersosveesp:laInttssidnicffeitchueltetxopcoosmurpearceattehgeorrieessulwtesroeftmhoediffiirestd.anAdlstehcooungdhmtohretaploitteyntial fuoprdeaxtpeoassuwreellm.isIctliasssdiifffiiccauiltontowjausdgceerttahienrleylimaobrileitlyoikfetlyheinetxhpeofsiusrtesctautdeyg,oritimesatyhasttiwllehraevdeeofcicneudrrweidthionutthe dmeevaesluorpeeddefxoprostuhreeusp.daAtle,thtohuegyhwesreerunmotPdFiOreActlmyeausseudr.emIennttshewseerceoncdonsstiuddeyr,etdheincthheemiecxaplospulraentmeatmrpilxoyees "wenroen-seuxb-pdoisveiddegdroiunpto. PTFhOisA-weaxspaonseefdfogrrtoutopsm,oarnedatchceurfaitlemlyplcalnatsseimfpy leoxypeoesusreesss;enhtoiwaellvyerr,emtahienseedneinwthe tchaitsegsotruideysidsothneott1t7akdeeaitnhtocaerctciofuincattedsurwaetrieononoftelxopcoasteudrefoorrdelcenegatsheodfeemmppllooyyemeesnatn.d Athneortehfeorrelwimeirteatniootn to oifndcleuadtehd tihnatthheasdtuadys.malTlhneuimnbcelrusoifocnaosrese.xclFuosliloonow futpohefsweodrekaetrhsmocrotuallditcyhaatngCeottthaegaenGalryosvees (faonrdthDeeccaatuusre)s ``snmeaeldlstnoucmobnetrinauned. tAheltchoohuogrth itshsetriellwreerlaetimvoerlyeytohuanng.200Giavddeintitohnearledseualtshosfisntculduideesdoinn fthliusoarnoaclyhseiisc,ailtsisina both animals and humans, further analysis is warranted. Research sponsors: UniversityofMinnesota aCsonssoisntgenicnythoifsruepsdualttse:d cTohheoretx.ceOsnsliyn1prdoesattahtewcaasncreeprodretaetdhsintthhaet dweafsinoibteseerxvpeodsuirnetghrofiurpstwshtiuldeySwwaesrneot coabtseegrovreidesinwetrhee pmroodbiafbileedeixnpcoestuhree glrasotuspt.udIyt .s Hdiofwfeicvuelrt,0alilnotfetrphreetetmhpelsoeyreeesusltisn sciinthceertghreoeuxppowseurree `assumed (0 have some exposure to PFOA. The new delineationofexposures further defined the chemical 145 000042 rpleamnatienmepdlionyteheesnooftn-heexpfiorsstedstgurdoyupa.ndTphleacneudmtbheermoifynteoar2sgrtohautpst,hewsheileemptlhoeyfeielsm wploarnkteedmpatlotyheeepslasnttilalnd/or were exposed to PFOA was not reported for prostate cancer. CONCLUSIONS aFodldliotwiounpdoefawtohsriknecrlmuodretdaliintythaits Caonatltyasgies,Girtoivseilnleeadssmtaollconntuimnbuee.raAnldtthhoeugchohtohretreiswseirlel rmeolrateivtehlayny2o0u0ng. (GOiFpvaerntitchuelraersuilnttseorefststaurdeibelsaodndefrlucranocrecrh,empircoasltsatiencbaontchera,nicmearlesbraonvdashcuumlaarnsd,iscfausrteh,ecraanncaelrysainsdisdiwsaorrrdaenrtsedo.f the liver, and pancreatic cancer. REFERENCE FAilneaxlanRdeeporr,t.B:HD.iviApsriiolno2f6,E2n0v0i1r.onMmoernttaallitayndstOucdcyuopfawtoiroknaelrsHeeamlpthl,oySecdhaotoltohfeP3uMbliCoctHteaaglethG,rUonvievefracsiiltityy. ofMinnesota. OTHER i"Tnhitshestcuodhyordtif(faesrsopfproosmetdheto1699m3onmtohrst)a.litIyn sadtduidtyioinn,thtahte tehxipsoosnuererecqautiergeosri1esyewaerorefemxoproessupreeciffoirc.inclusion `Additional cohort members were included (n = 169) that should have been included in the last study. Itis not clear why these employees were not included in the 1993 study. 146 146 000043 EPIDEMIOLOGIC STUDY Title: An Epidemiologic InvestigationofReproductive Hormones in Men with Occupational Exposure to Perfluorooctanoic Acid `TESTSUBSTANCE Identity: Perfluorooctanoic Acid (PFOA) Remarks: This paper further examines the observation initially reported by Gilliland in his doctoral thesis that total serum organic fluorine may be associated with reproductive hormone changes in PFOA. production workers. METHOD Shtourdmyondeessiignns:erTuwmoofcmroaslse-seecmtpiloonayleesstudatieas,PuFtiOlAizipnrgogdeuncetriaoln medical facility. surveillance and analysisof eleven i`nMvaonluvfeadctaufroiunrg-/sPtraogecepsrsoicnegss/:Usies:olaPtiFnOg Aanwdacsonpvreordtuicnegdtahte the plant by chemical to aansaelltesclturrorcyh,ecmoincvaelrtpironcgestsh,e which slurry. tthoeasdarlyticnagkaer,ead.rPyiFnOgAth,eapcoatkee,ntansdynptahcektaigcisnugr.faTcthaentg,reiasutessteldiikneliinhdouostdrfioalreaxppploiscuatrieontso.PFOA occurred in aHcyipnoart,heasnidsLteeysdtiedg:ceSlilnacdeePnFomOaAs hianslabbeoernatsohroywannitmoarlessualntdinindcorseea-sreedlasteedruimncersetarsaedsioilnlheevpealst,icP,FpaOnAcremaatiyc: Show a similar effect in humans with regard to reproductive hormones, particularly increased estradiol or decreased testosterone serum levels. Setting: PFOA production plant (presumed to be 3M plant in Cottage Grove, MN) Total # of subjects in study: 1993-111 production workers, 1995-80 production workers. Sixty-cight production workers were common to both cohort years. Comparison group/population: Employees were divided into four serum PFOA level categories, 0-<1 pm, 1-<10 ppm, 10-<30 ppm, and 230 ppm, in order 0 determine ifan effect existed at the highest serum levels. Participation rate: Not specified. Subject deseription: Characteristicsofsubjectswere not described. Health effects studied: Potential changes in: estradiol, follicle-stimulating hormone (FSH), 1s7ear-uhmydcorrotxiysoplr,odgeehsytderrooenpeia(n1d7r-oHsPt)e,rforneeestuelsftaotset(erDoHneE,ASto)ta,l testosterone, luteinizing hormone (LH), prolactin, thyroid-stimulating hormone (TSH), and sex hormone- binding globulin (SHBG) hDeaitgahtc,owleliegchtti,onamnedtphuoldmso:naMreydifcuancltisounr;vesitlalnadnacredcobnisoicshteemdiocafla amneddiucrainlaqluyessistitoensntsa;irPe,FOmeAadseutreermmeinnattoiofn; `and several hormone assays. 147 000034 wDeatsainlosuopnpedratlaimciotollfedcetitoenc:tiTonheinup1p99e5r.liAmitthoefdremtoescptriaoynmoafssPFsOpeActirno1ph9o9t3owmeatsry80aspspamy,Wwahseurseeads ttohere udestienramginfelusoerresucmenPcFeOpAolalreivzealtsiionn 1i9m9m3unaonadss1a9y9.5.RaEdlieovienmmhuonromaosnseasysw(eRrIeAa)swsaeyrede.usCeodrtfiosrolDwHaEsAaSs,sayed eFsStHra,diaonl,d p1r7o-lHacPtainndwetrotealastsesatyoesdteursoinne.g aFrmeiecrtoepsatrotsitcelreoneenwzaysmedeitmemrumnioneadssuasyi.ngTeSqHuilwiabsriduemtdeiramliysniesd. uLsHin,g cahcrhommaitlougmrianpehsiccesnacmepilmempuunriofmiecattrioinc.asBsoayu.ndStHeBstGoswtearsonaessweasssecdalvciualaatreadadiotiomtmaluntoesatsossatyeraofnteerless free. testosterone. The same assays were used for both 1993 and 1995 analyses. Exposure period: Not specified dDievsicdreidptiinono/fdoeulrinseeartuimonPoFfOexAploesvuelrecagtreogourpise/se:at0e-g<o1rpiepsm:, F1o-r<1t0hepsptmr,ati1fi0e-d3a0naplypsme,s,anedmp2l3o0yepepsmweinre woridtehrsteorduemtPerFmOinAeilfevaenlesfafec1t0epxpismteodragtretahetehripgahretsitcsipeartuemd ilnevbelost.h ySeeavrse.nty-five percentoftheemployees Measured or estimated exposure: N/A ``cSoteaftfiisctiiecnatls,meatnhdodorsd:inSaryimulamtnivdaprsitarlabtliefeireedgraensasliyosnesw,earnealuysseidsotfoveavrailuaantceea(ssAoNcOiaVtAio)n,s PbeeatrwseoenncPorFrOelAataionnd `wcearchehdoirvimdoende,inwtiotfhouardjsuesrtummenPtFoOrApolteevnetliaclacteognofroieusn:di0-n<g1vaprpimab,le1s-.<1F0oprpsmt,rat1if0i-e<d3a0naplpyms,esa,nedm2pl3o0ypeepsm in boroddeyrmtaosdsetienrdmeixne(BiMfaIn),efafleccothoelxiusstee,daantdthceighairgehteestusseerwuemreleevexlas.miFnoerdmausltbiovtahricaatteegeovrailcuaaltiaonnd, cPoFnOtAi,nuaogues, svaqruiaarbel,esa.ndResgqruaersesiroonotmotrdaenlssfowremarteiofnist.tedTwhiethpoPssFiOblAe ennotnelriendeaars aasscoocnitaitniuoonousfevsatrriaadbiloelu,sfirnege ltiensetaors,terone, ``aanndd bbyoucnodmpteasrtionsgtepraonreamweatsereveasltuiamtateeds.,Nuosnilnigneiarndodse-iarnecsdpcoaonnstteirnoeuloarutsionvasrhiiapbslewse.reSteexpawmiisneesdebleyctmioodnel fit procedures were also used. Study results were analyzed using SAS. Other methodological information: No additional comments. RESULTS DPeFsOcrAibmeearseusurletmse:ntTshewerraengheiogfhlsyecrourmrePlaFtOedAawmaosng0 t--h8e068ppemmpilnoy1e9e9s3wahndo0pa-rt1i1ci5ppatpemd iinnt1h9e95s.tudSyerum during both years. cPoFnOsuAmpwtaisonn,otBhMiIg,hloyrccoirgraerleatteesd. wiMtohsatonyftohfetheemhpolorymeoensehsaodr wPiFtOhAthesefroulmlolweivneglscolvearsiattheasn: 1a0gep,pma.lcoIhnol a1p9p9r3,oxoinmlayte1l3ye1m0plpopymeetso ohvaedrs1e1r4umpplme.velTsh>er1e0wpeprme,oannldy 415eimnpl1o99y5e.esHionwtehvee3r0,ptphemsePlFeOveAlsgrraonugpedinfrom e1i9t9h3eraonfdtohnelhyigheinst1c9a9t5e.gorTiheesr.efoTrhee,miteianliakgeeloyfthtahtetheemrpelwoayseenstinenthoeuhgihghpeoswteerxptoosduerteecctadtiefgfoerryenwcaess itnhe Tdiofwfeesrtenitnrbootmh t1h9e9o3tahenrdc1at9e9g5or(i3e3s.,3ByMeaIrwsaasnsdli3g8h.2tlyyeahrisg,herersipenctthievehliy)g.hesAtlPihFoOuAghcantoetgosriyg.nificantly 148 148 000045 Estradiol 1995, all was highlycorrelated with BMI (c= employees with PFOA levels > 30 41, p < 001 in 1993, and r= ppm had BMI > 28, although 30, this < 01 in 1995). In effect was not observed ginro1u9p9s3;. hoEswtervaedri,olthleevdeilfsfienretnhcee3w0asppnmotgsrtoatuipstiincablolythsiygenaifriscawnet.re 109% higher The authors than the other PFOA postulate thatthe study may nsoctruhmavPeFbOeeAnlseevneslistwiveereenloiukeglhy tboeldeotwecttheanobassesrovcaibaltieoenffbeecttwleeevnelPsFsuOgAgeasntdedesitnraadniiomlalbesctauudsieesm(e5a5suprpemd sPuFgOgeAstinthtahtetCheDhiragth).erOensltryad3ioelmlpelvoeylseeisn tihnehhiisghsetsutdyexhpaodsuPrFeOcAatsegeorruymcloeuvleldsshuigsgehsitgah. thTrheeshyoladlso relationship between PFOA and estradiol nFergeaettievsetaosstseorcoinaetiwoansbehitgwheleyncPorFrOelAatseedrwuimthleavgeelsinanbdotthes1to9s9t3eraonned. 1995. The authors did not report a There were no statistically significant trends noted testosterone, fwoarsPhFiOghAeasntdicnitthhee3r0bpopunmdPoFrOrAeegtreosutpositnerboonteh. 1H9o9w3eavnedr,191975.-HPI,nap1r9e9c5u,rPsForOAofwas stihgenaiufitchaonrtslystaastseotchiaatttehdiswiatshso1ci7a-tHiPoniwn arsegbraessseidoonnmotdheelrsesaudljtsuosfteodnfeorepmopslsoiybleeec(odnaftoauwnedreersn.otHporwoevviedre,d in the report). There were no significant associations between PFOA and cortisol, DHEA, FSH, LH, and SHBG. tShteudreysuslttrseonfgtthhissastnuddyw.eaFkinrsets,saelst:hoTuhgehrtehearreewseevreera2lsdteusdiygnyeiasrssue(s19t9ha3tasnhdou1l9d95b)e,ntohteedpowphuleantieovnasluwaetrien.g not independent. Sixty-eight employees employees who participated in the study participated in both years. in 1995, thus reducing the Second, there were power ofthe study. 31 fewer There were also very few sectional employees in designofthe cither study year does with serum PFOA levels not allow for analysisof tgermepaotrearltihtaynof1a0nppamss.ocTihatiirodn,.thSeicnrcoesst-he half- alicfceoofmmPoFdaOtAioisnsteovetrhaelefyfeeacrtss, othfePaFuOtAh.orsFsouugrgtehs,totnlhya oitnie spaomsspilbelewatshatatkheenrefmoraeyacbhe hsoormmeobnieolfoogriceaalch of the study years. taken in a short In order to time period get more accurate should have been umseeadsuforrecmaecnhtspafrotricsipoamnte.oftFihnealhlyo,rmtohenrees,mapyoohlaevdebbleoeond Some measurement errorof someofthe confounding variables. Research sponsors: 3M Company w`Coornkseirssteanncdyoifncrreesausletds:estArnadieoalrlainerdsdteucdryeraespeodrtteesdtaosntearsosnoecilaetveilosn. beHtowweeevnerto,tatl isedriuffmicourlgtatnoiccofmlupoarrienetihen. results ofthis study to the previous study because serum PFOA in workers was measured in this study. CONCLUSIONS `Tenmtpwlooycereosssw-esrecetnioontaalsptpuadrieenstiinn r1e9la9t3ioannod 1t9h9e5ir, mseigansiufriceadntsehrourmmoPnFalOAchlaenvgeelss aasmhoandgbteheenmparleeviporuosdluyction observed in much lower laboratory than those animals. However, it shouldbe levels reported to cause effects noted that PFOA serum in laboratory animals. levels in workers were REFERENCE OOlcsceunp,aGt.\iWo.ncEtxalp.os1u99r8e, tAonPEeprfildueomriooolctoagniocicInAvceisdt.igJaOtiEoMno.f4R0e(p7)r:o6d1u4c-t6i22v.e Hormones in Men with 149 000046 EPIDEMIOLOGIC STUDY Tpietrlfel:uoAronocetpaindoeimciaocliodgipcroidnuvcetsitiognatwioornkoefrpslasma cholecystokiannidn hepatic function in TEST SUBSTANCE Identity: Perfluorooaccitda(nPFoOiAc) Remarks: METHOD `Study design: 3 cross-sectional analyses based on workers medical surveillance data collected in 1993, 1995, and 1997) Manufacturing/Processing/Use: electrochemical process involving The substance converting the is a synthetic chemical toa surfactant salt shury that and tishpenrotdouacesdalvicaakae.4-stage. (HyCpCoKt)helseiveslsteasntdeds:erTuomdPetFeOrAminleevwelhsetinhefrlauoprooscihteimviecaaslsporcioadtuicotnioexniwstosrkbeertsw,eaenndptloasdmetaecrhmoilneecywshteotkhienrin PFOA may modulate hepatic responses oobesityandalcohol. Study period: Medical exams were performed in 1993, 1995, and 1997 Setting: PFOA production plant, Cottage Grove, MN `Total population: Not specified `Subject selection criteria None specified, although participation in medical surveillance at he plant was voluntary. T74o,tarle#spoecftsiuvebljye.ctTsheirnestwuedrye: 68 pTahrteicniupmabntesrison cfopamrmtiocnipfaonrts1i9n9319a9n3d, 11999955, a2n0din19c9o7mwmeorne f1o1r1,19890,3 aanndd 1997, and 17 in common for all three years. Comparison population: N/A Participation rate: approx. 70% `Subject description: Workers who engaged in the productionof PFOA. No other information was provided. Health effects studied: The effectsofserum PFOA levels on hepatic responses to obesity and alcohol, and CCK levels. sDuartvaeiclollalnecceteioxnammestwhhoidcsh: coPnlsainsttweodrokefrsquveosltuinotnanraiilryep,aprtuilcmiopnataerdyifnubnicetninoina,lhmeeigdhitc,aland weight `measurements, biochemical and urinalysis esting, PFOA determination, and some male reproductive Hormone assays. 150 150 000027 pDertoaviildsedonindaantoathceolrlreocbtuisotns:uHmomramroyn(eOldsateanweetrael,on1l9y98c)o.llected in 1993 and 1995. These results are ``sSleurtuammyblioocxhaleomaicceatlictetstrsanisnaclmuidneads:e (aSlkGaOlTi)ne,psheorspuhmagtlauste,amgylampmyrauvgilcuttarmaynlsatmriannasfseer(asSeGP(TG)G,T)o,taslerbiulmirubin, wdiirgelcytcebriilidreusb,inb,lochoodleusrteearonli,trloogwe-nde(nBsUiNt)y,licproepartoitnienien,s a(nLdDLg)h,ichoisgeh.-dHeensmiattyolliopgoyprtoetsesinisn(clHuDdLed):, hematocrit, hemoglobin, red blood cells, platelets, and white blood cels. tPhlearsmmoasCprCaKy-(31399w3asanmdea1s9u9r5e)adnbdyeldeicretcrtorsapdraiyoi(m1m9u9n7o)ashsigahy.peSreforrummanPcFeOlAiquwiadscdhertoemramtiongerdabpyhy mass spectrometry methods. Exposure period: Not specified. dDievsicdreidptiinoton/fdoeuirnseeartuimonPoFfOexAploesvuelrecagtregoourpise/sc:at0e-g<o1rpiepsm:, F1o-r<1t0hepsptmr,ati1f0ie-d<3a0naplypsme,s,anedmp2l3o0yepepsmweinre order to determine ifaneffect existed at the highest serum levels. Measured or estimated exposure: N'A Exposure levels: N/A ``Sotradtiinsatriycamlulmteitvhaoridast:e rSegriessaimonndwpsittrhaltiafdiejeudstamneanltysfeosr,pPoetaenrtsioanlccoornrfeolautnidoinncgoevfafriicaibelnetss., ANOVA, and Other methodological information: RESULTS 6De4spcprimbe(rraensguelts0:.1T-h$e1.m3epapnm)P.FTOhAesmeeraunm lCevCeKlvin eampllwoayuse2e5se.p5arptgi/cimplat(irnagngien 8t.h8e -18969.77sptgu/dmyl)p.eriTohdewas. hhiigghheesrtiCn CthKesvea2luceastewgeorreiersetphoarnteidnitnhtehceat2eegoxrpioessurgerecaatteergtohraines1l0espsptmha(np1=00p6p)m.. WThheenmaedajnusstweedrfeor50%. `poCtCenKtaianld cPoFnfOoAu;ndheorwse,vmeurl,titvhaersieabdlaetarewgerreessniootn imnoclduedsediinndtihcearteepadortw.eaTkhenergeatwievreeansososctiaattisitoincablelytween csiogmnpifairceandttdoipfafretriecnicpeasntisn wsietrhumlocwheCmCisKtroyrvPalFuOesAfolrevpealrs.ticipants with high CCK or PFOA levels o`rSewriutmhPaFnyOAhelmeavteollsowgeicraelnoortcchoenmsiisstternytlpyaraasmseotceirast,edanwidtnhoanneoyfvatrhieabvlaesl,uessucfohrassuaclhcpohaorlamoertceirgsarweetrtee use, hSeaptaitsitcicraelsypsoingsneisfitcoanotbeastiatnyyaonfdltohreaPlcFohOolA. levels. There was no evidence that PFOA levels modify `iSntdiucdaytsettrheantgtthhescaronsds-wseeactkinoensaslesst:udIyt fsohromualtddboeensontoetdptehramtiCtaCKdiwreacstoannlalyymsiesssourafnedoibnse19r9v7e.d aTshsoeciaauttihoonrs with than trheespneuctmbtoertoimfep.arAtdidciitpiaonntaslliyn,1t9h9e3.numberofparticipants in 1995 and 1997 was significantly lower 151 000048 -- Research sponsors: 3M Company C`moondsuilsatteesnchyepoaftircesruelstps:onTsehsetroesaullctoshoofl this and osbteusdiytayraenidnctohnastitshteernet with carler is positive fcionrdrienlgatsitohnatbePtFwOeeAn PFOA. and CCK levels, "The following explanations may indicate why this study filed to finda positive association between PFOA and CCK values: tis possible that the hepatocarcinogenic effectsofperoxisome proliferators in rodents do not act the "The same biochemically serum PFOA levels in humans. observed in workersmay havebeen 100 lowtodetaneefcfectt. Effects in CCKanriemcaelpstowresrmeaoybsbeerdviefdfeartenhtigbheetrwdeoesnesratthsaannmdohsutmaofntsh.eTsheerruefmolreev,eltshefomuonndkienywmorakyerbse. a more: appropriate animal model to study the pancreatic effectsof PFOA in humans. ""TThhee irantvmolavyemneonttboefaCnCaKpprionptrhieatienimtoiadteilonionrthperosmtoutdiyoonfofpapnacnrceraetiacticcacnacnecreirnihsucmoantnrso,vesrisnicael.acinar cell `malignancies induced by carcinogens in ras, are are in humans. CThOeNrCeLsuUltSsIdOoNnoSt suggest that there is an association between PFOA levels and increases in plasma CCK. tlheavtelPs,FnOoAr dloevtelhseyobssueggrevsetd tihnetphirsessetnucdeyomfohdeuplaattiechteopxaitciictyraetsptohnesPesFOtoAobleesvieltsy oabnsderavlecdo.holtiusse.unlikely REFERENCE hOelpsaetni,cGfWun.ctieotnala.nd19s9e8.rum3pMerFfilnuaolroRoecptoarnto:iAcnaceipdidleevmeilosliongipcroidnuvcetsitoignawtoiroknoerfsp.laSst.maPacuhlo,l3ecMysCtookmipnainny,. Septd. 152 152 000049 EPIDEMIOLOGIC STUDY Titles Serum Perfluorooctanoic Acid and Hepatic Enzymes, Lipoproteins, and Cholesterol: a Study of Occupationally Exposed Men TESTSUBSTANCE Imdeeanstuirtye:d dTuoteatlostehreucmosftlouforainne waaslustyehdezsasaimapnlseusgrr.ogate for PFOA exposure. Serum PFOA was not Rhoewmeavrekrs,:whOernigtihneailrlsy,ereummplloevyeelesswweerreeacnoalnysziedde,retdhe"suen"euxnpeoxspeodsebda"sewdoroknertshihrajdoPbFdeOsAclreipvteilosnhsi;gher than the general population. Therefore, otal serum fluorine was used to classify workers into exposure ous, METHOD Study design: Cross-sectional study Manufacturing/Processing/Use: This plant produces PFOA, as wellaseveral other specialty chemicals Haynpdoltihpiedsimsettaebsotleids:m.ToTdheetseeremfifneecitfswhoarvkeebreseenxopbosseerdvetod PFOA experienced in rodents exposed changes in to PFOA. hepatic enzymes Setting: PFOA production plant- 3M Chemolite plant in Cottage Grove, MN Total #of subjects in study: 115 `Subject selection criteria: Participants were recruited from all employees at the PFOA production plant who were employed during the period of 1985-1989. Comparison group/population: in mean values of the biochemical All subjects potentially were endpoints were compared. exposed to PFOA. Therefore, differences Participation rate: Presumed to be > 80% ``pSeurbdjeacytadnedsc1ri7p%tidorna:nkMe1-a3noza.gaelc=o3h9o.l2d;amy;ea7n4bpoedrycemnatsssmoiknedde.x = 26.9; 76% drank less than 1 oz. alcohol lHiepaolptrohteeifnfse,catsndstucdhoileeds:terPools,siibnlceluedfifnegct:sosfetroutmalglsuetraummylflouvoarlionaecoenlilcetvrealsnosafmhienpaaset.ic enzymes, c(hSolGeOsTte)r,ols,elrouwm-dgehnustiatmyyllippyorpurvoitceitnrsa(nLsDaLm)i,naasned(hSiGgPhT-)d,engsiatmymlaipgolpurottaemiyn!s transferase (HDL). (GGT), `hDeaitgahtcoalnldecwteiiognhtm,etahnodddso:naPtaerdtibcliopoadntssacmopmlepslebtyevadenmiepdunicctaulreh.istory questionnaire,were measured for Exposure period: Unknown. 153 000050 bDaesscerdiopntijoonb/ddeelsicrniepattiioonns;ofhoewxepvoesru,rehogsreouwposr/kceatresgporrieessu:meWdotrokhearvsewleirtelepolracneod PinFtOo Aexepxopsousruerceatheagdortoiteasl wSoerrkuemrfsliwoerrienecllaesvseilfsie2d0-i5nt0otgirmoeusphsibghyertottahlasnetrhuosmeflleuvoerlisnerelpevoerltse.d Einmpthleoygeeneesrawlerpoeppullaatcieodni.ntTohoenreefoofre5, groupsoftotalserumfluorine levels: <1 ppm, 1-3ppm, >3 - 10 ppm, >10 - 15 ppm,and > 15 ppm. `SuMreraosguarteedmeoarseusrteimfaortePdFeOxApoesxuproes:urEexposures were estimated. Total serum fluorine was used as a `Smtualttiisvtairciaaltemertehgroedsss:ionStwreartiefiuesdeadnafloyesvisa,luAaNteOaVssAo,ciPateiaornssonbectowrereelnatPiFonOcAoeaffnidcibeinotcs,heamnidcallineenadrpoints. Fmoarssstirantdiefxie(dBaMnIa)l,ysaelsc,oAhoNlOusVe,Aapnrdocteodbuarcesso wuesereweurseedintoclausdeesdsinditfhfeerreengcreesssiinonmemaondevlasluaess.potAegnet,iablody cmoondfeolunfdietrwsa.s Nimupmrboevreodfccoimgapraertetdeswsitmhoktheedmpoedredlauyswinagscuasteedgoirnictahle vmaordiaeblleass. continuous variable if RESULTS DApepsrcorxiibmearteeslulytsh:alfTohfethraenwgoerokfetrhsefselelrnutmoftlhuoer>ine1 v-a3lupepsmwacaste0g(o0ry2,6wphiplme(2m3ehaand3s.3erpupmm)l.evels< 1 ppm. and 11 had levels > 10ppm. "cThhoelreestwereorle,nLoLs,ignainfdicHanDtLd.ifPfeFrOenAcewsabse,thwoeweenvecart,egaosrsioecsiawthedenwiatnhaHlyDzeLdluesvienlgs uinnimvoadreiartaeteandarliynskeerss.forIn tchheolmeusltteirvoalrioartLe DanLaalfytsiesr,adtjhuesrteiwnagsfonrotalacsoihgonlifciocnasnutmapstsioocni,ataigoen,bBeMtIw,eeanndtoctiaglasreetrtuem sfmlouokriinnge.anTdhere wSeGrPeT,noanstdatGiGstTic.allIyncsirgenaisfeiscainntSdGifOfeTreanncdesSaGmPoTngoctchuercraetdewgoirtiheisnocfrteoatsailngsteortaul sfleurourminfelufoorriSneGOleTv,els in bcoenssiestweonrtkweirtsh(hBepMaIti=c 35 kg/m). disorders. No No cwloinrikcearlscarseepsorotfedlihveepradtyiscfduinscetaisoen daisasgoncoisaetsedowristihgnPs,FoOrAseyxmppotsoumrse were found in these workers. `iSntfuodrymasttiroenngptrhosviadnedd owneatkhneeesmspelso:yePeFsO(Aeg.walesngntohtomfeeamspurleodymdierncettelxypoasnudrteh)e.reTihsenoauetxhpoorssusraete that no afsdvneortsceleclairntihcaatl tohuetrceohmaessbreeelnatfeodltlooPw-FuOpAofefxopromseurreemhpalvoeyebeese.n oIbnsaedrdvietdioinn,tthheeirsteamnpdlaorydeedesv;iahtoiwoenvser, it rnetphoreteredsuflotrs.theMlainveyrpeanrztiycmiepsanwtserien tvheerysthuidgyhwfeorremeamnpyloofytehdeienxpproosduurceticoantoegforciocsm,poinudnidcastiontgheirnstthaabnility PFOA. Research sponsors: A NIOSH grant and the 3M Medical Department Consistency of results: There are no other known studiesofthis kind on PFOA. CONCLUSIONS HPoFwOeAvewra,sPnFoOt Aassmoacyiamteodduwliatthemtahrekfeedchteopaftiaclccohhaonlguesseian nhdumobaenssitays ohnadhebpeaetnicolbispeird vaendd ixnernoodbeinotst.ic `metabolism. 154 154 0C0Cs51 REFERENCE aGnidlclhiollaneds,teFr-oDl.:anAds1t.5u.dyMoanfdoelc. c1u99p6.aSteireuxomponpseaerdfllmuleornyo.ocAtamn.oiJcacoiduaonfdrInhndeupsaattriiclalenMzeydmiecsi,nel.ipo2p9r:ot5e6in0s-, 568. 155 000052 EPIDEMIOLOGIC DATA. Title: An Epidemiologic Analysisof Episodesof Careof 3M Decatur Chemical and Film Plant Employees, 1993-1998 TEST SUBSTANCE Identity: POSF-based chemiuscedaatlthse Decatur plant `Remarks: Episodesofcare analyses are not often used in occupational epidemiologic studics. METHOD Study design: Episodeof care comparison Manufacturing/Processing/Use: The 3M upofthe film plant and the chemical plant. Decatur, Alabama plant began production in The3 major productgroups in the chemical 1961. plant tis are made (prPoOtSeEct)ivies tchheemmiacjaolsr,suplefrofnoartmeafnlcueorcohcehmeimciaclasl, maanndufflaucotruoerleadstaotmDeersc.atuPrerafnlduoirsouoscetdanaessutlhfeopnrye!cufrlsuoorritdoe the production ofa varietyofperfluorinated amides, alcohols, acrylates, and other fluorochemical polymers. wHiytphotlhoengs-itsertems,theid:ghTeoxpuosseureepitsoodPeOsSoFf-cbaarseedmeptrhoodduoctlioognyaatstahes3crMeefnafciolritmyoribniDdeictaytuoru,tAcloambeasmaas.sociated ``wSetruedyanpaelryizoeddsfoErpwiosrodkeesrosfactatrhee epxlpaentriwehncoeowfer6e5e2 mchpemlicoafyloeremdplaotlyeaeset s1 aynedar6b5e9tfwielemnpJlaanntuaermypl1,oy1e9e9s3 `and December 31, 1998. Setting: 3M plant in Decatur, Alabama. T"Tohtealtoptaolpwuloartkieornp:op1u3l1a1tiwoonrwkaesrsnowterreepeolritgeidb.le for the cohort at least 1 yearof employment at the plant). `1S9u9b3jeacntdseDleecc.ti3o1n,r1i9t9e8r.ia:EpiAsloldweosorkfecrasreemwpelroeyeldimaittetdhetoDtehceaitruDrecpalatnutrftoirmaet least 1 yearbetweJeann. ofemployment for 1, Meemdpilcoayreee,slhoinrge-d,tetremrmdiinsaatbieldi,tyorordiwehdoducrhionsgetHheMsOtudcyovpeerraiogde.weHroewenvoetri,n rtehceodradtsaobfaseempalnodyweoeuslodnnot be included in the episodes ofcare for that employes. Ccoommppaarreidsotoncpaocphulotahteiro.n:EmCphleomyiecealcoamnpdarfiilsmonplgarnotuepmspwloeyreeedsefwienreed aancacloyrzdeidngsetpoatrhaetierlpyoatnendtitahlen `workplace film plant exposure to POSF employees eligible fluorochemical for the cohort. prodiction. Group A: Group B: all chemical all chemical plant employees plant employees who worked and all solely ialnltchheecmhiecmailcpallanptlaenmtpalnodyealelsfwiiltmhplhaingthefmlpulooryoceheesmwichaol weoxprokseudreesxccloumsipvaerleydintotthehifriljmobplcanotu.nteGrrpoaurptsCi:n ttohethfeilsmtupldaynto.nsGetrocuopmpDa:readltl opltahnetirwojrokbecrosunwtietrhpehritgsh ifnltuhoerofcihlemmiplcaanlt.exposure for at least 10 years prior `Participation rate: 97%ofDecatur employees were eligible for participation in the study. 156 156 000053 `nStuhbjeecftildmespclarnitp)t.ioTn:he8m2e9a%onftagheeweamspl45o.y1eeisn tihnethcehecmoihcoarlt wplearnet manadle48(.5630ininthteheficlhmempliacnat.l pSliaxnttyapnedrc5e5n8t opflatnhtewcohrekmeircsalhapdlawnotrekmepdloeyxceleussihvaedlywoinrktehedfoinllmypilnantth.e Scehveemnitcya-lsiplxapnetracnedntasoiftmhielacrhpeemricceanltpalgaenotf film workers had high exposure obs. HPeFaOlSt,hceefrfteacitnsesptiusdoideeds:ofMocrabriediwteyr.e cBoansseiddeornedanaipmraiolrid.ataTahnedy eipniclduedmeido:lolgiivcerstaunddiebslaodndPerFcOaAncearnd,. elnivdeorcarnindebdiliisaorrydetrrascti,navnodlvrienpgrtohdeuctthiyvreoiddisgolradnedrsa.nd lipid metabolism, gastrointestinal disorders ofthe wDaastausceoldlteoctpionrmetohaocdovsm:prieThhedensClieivneicaglroCuapriengGroofualplsveipsiitssodienopafticeanrte asonfdtowuatrpeatdieevnte)l,opperodcbeyduIrnegse,nix, Inc. a4n0c0ildliasreyasseersviocrecso,nadintdiopnrse.scrTihpetisoonfdtrwuagrse ucsoeddeicnontshterduicatgsnaosniesp,itsroedaetomfenctaraendarmoaunnadgtehmeeinntdeoxf-mcolirgeibltehan rdeicsoeradseboyrsceoanrdcihtiinogn boanctkhweairnddeaxndrefcoorrdw.ardThine tiinmdeexforretchoerdhecaolntshisctlsoaifmseirtehceorrpdrsotcheadturree croedlaetsedinodictahteive. ofa face-to-face encounter or a pharmacy record for a delineating drug. Exposure period: The episodesofcare that were included in the study were those experienced between Jan. 1, 1993 to Dec. 31, 1998. Dpoetsecnrtiipatliwoonr/kdpellianceeateixopnoosufreesx:powsourrkeergsrowuhpso/ewaetreegoermipelso:yeWdorskoleerlsy wienrtehepclahceemdicianltoorgrfoiulpmsplaacnctosr,dtihnogset.o wflhuoorhoacdhehmiigchalexepxopossuurreej.obs,andthosewho worked at last 10 years injobs with high potential for Measured or estimated exposure: estimated based onjob history information. Exposure levels: Not measured. Employees were placed into exposure categories based onjob description. Sotbasteirsvtiecdaltomeextpheocdtse:d eApirsiosdkersaotfiocaerpeisfoodrecohfceamirceal(RplRaEnptCe)mpplrooyveideesdctohmepeasrteidmattoetohferoibsskebrevtewdeteon the ehxepefcitlemdaenpdicshodeemsicoafclaprleanat meomnplgofyielemspwlaanst ceamlpcluolyaeteeds.frTohmeheeaxlptehctceldainmusmdbaetaroofftehpeis3odMesmoafnucfaarcetufrorinbgoth `Stproupcutluarteiso,nainn tahdejuUs.tSe.d rBaetcioauwsaestchaelccuhleamtiecdaalnadncdofmiplamrpeldanttoctohheourtnsadhjaudstseldigrhitslkyrdaitifof.ereInntmaogsetacnadsegse,ntdheer Fisk ratios were comparable. Therefore, 95% confidence intervals were only calculated for the unadjusted risk ratios Oeptihseordemoeftchaordeolcooguilcdarleipnrefsoernmtatainoyn:and1taslhoiunlciddbenetncoatseeds,thpartevfarloemntancaesepsi,deamnido/loorgmiicspcelrasspsiefciteidvec,aasens (thbeotshofftalwsaerepoussietdi,veaanndditfiaspeosnesgiabtlievet)h.at I2ndiafdfdeirteinotn,dtiyapgensosaensdmcaoyunbtesoafsseipginseoddetsootfhecasraememaepyisdoidfef.er by Ceenrdtpaoiinntsoerfvaicnese,piSsuocdheamsalyab vparroyceadmuornesg asnodftpwraersecrpirpotgironasmsm.ayThneotclbienirceaplofrlteexdibfiolrittyhoefetphiesoldeg.oriAltshom, mtahey differ depending on the software program. 157 000054 EE -- RESULTS nDeesocprliabsemsroefsutlhtes:maTlheeroenplryodiuncctrievaesseysritsekmofanedpifsoordtehse foovrertahlelccoantdeigtoiroynosfocafancperriosrainndtebreesntigwnergerofwotrhs (ovwehriaclhl ciannccleudrecdactaegnocreyroffotrhalelmacloemrpeaprriosdounctgirvoeupssy.steTm)h.e iTshkerraetiwoawsaasngirnecarteesatseidnrtihsekogfreopuipsoofdes for the Ienmcprleoayseeedsriwsiktohfethpeishiogdheesstinanlodngl-otnigmees,t heixgpho-seuxrpeosstuorefleumorpolcohyeerneiscaallsso(wRaRsErPeCpo=rte1.d6,fo9r5m%alCe1r=ep1r.o2du~c2t.i1v)e cfaorncmearlse(rReRprEopdCuc=ti9v.e7,ca9n5ce%rsC1an=d 1t.h1e-s4u5b8-)c.atIetgosrhyooufldprboestnaotteedcatnhcaetr.theFciovnefeipdiesnocdeesionftecravraleswevreery wide ocabnsceerrsv.ed Ofonrereeppirsodoudceotifvpercoasntcaetrescainnccehrewmaicsaolbpslearnvteedmipnlfoyiemepsla(n1.t8eemxppleocyteede)s,o(3f.4whexipcehct4edw)e.reThpriosstate pFlianndtinmgoirsailmiptoyrsttaundty.becHaouwseevearn,extcheesuspdiantperoosfttahtee csatnucdeyrdmiodrtnaoltictoynwfaisrmotbhsiesrfvienddiinng.the Cottage Grove "`Tghreoruep w(aRsREaPnCin=cr1e.a8s,e9d5ri%skCo1fe=pi1s.2o-d3e.s0)foarnndetohpellaosnmgso-tfetrhmeemgpasltoryoimnetnetst,inhailghtreacxtpoinsutrhee ghrioghupex(pRoRsuErPeC = `29m,b9e5s%oCfIeLp=is1o.d7e5s.2w)e.reMroepsotrotfetdhie efiplimsoadnedscwheerrneicaatlripbluatnatbleemplobyeenesi.gn colonic polyps. Similar Icnantcheere(n1t.i5reexcpoehcotretd,)o.nlByot1 hepoicscoudreroefdcianrfeilwmapslarnetpoermtpeldoyfeoresl.iveOrnclaync2erca(s0e.s6ofexcpiercttheods)isaonfdt1heforlibvleardwdeerre. ionbfseecrtvieonds(i0n.9cheexpmeicctaeld)p,labnottehmipnlothyeeecsh,embiuctatlhpelyanwte. reThmeorsetlwyadsuae gtroearteecrurrriisnkog felpioswoedresuorficnaarrye tbrayctthe Same employees. Its difficult to draw any conclusions abou these observations, given the small number ofepisodes reported. Ctohesmeiekcaclarpelafnotredmispolrodyeeresosfitnhtehebihliigahryerxapcotsutrhea,nltohnegir-tceorumnteemrppalrotysmienntthegrfoiulmppwlearnet 2(R%REtiPmCes=m2o.r6,e9l5ik%ely CplUa=nt12w-or5k.er5s).. TEhieghstuebe-ncaetpeigsoordieessotfchaarienfwleuerneceodbstehrisveodbsienrcvhateimoincawlerpleaenptiesmopdlesooyfeecshoalneldit1h4iaisnifsiwlimth `cacsuetse ochcocluercryesdtiitnischaenmdicchaolleplliatnhtiaesmipslwoiytehesc.hronic or unspecified cholecystitis. Most of the observed Rdiiasbketreast,iohsoypfeerpliispoiddeemsioaf,caanrdeoftohrerenednodcorcirnienediosrornduetrrsi,tiwohnailcdhiisonrcdleurdse,dwseurbe-cnaottegeolreiveastoefdthinyrthoeid disease, cinomtphear9i5so%ncgornofuipdse.ncCeoinndtietrivoalnsfowrhtihcehhwiegrheenxoptosiudreen,tilfoinedg-ateprrimoreimbpultowyhmiecnht egxrcoluupdiendcltuhdeedm:ulldhiyspoortdheerssiosf the pancreas, cystitis, and lower urinary tract infections. eSptiusdoydesstorfencgatrhessaonftdwawreea.knTehseserse:sulStseeof"tohtihserstmuedtyhosdhooluolgdiocnallyibnefoursmeadtifoonr"hsyepcottihoensifosrgleinmeirtaatitoino.ns of `dAelmtohgoruagphhtihcesebpuitsoddiefofferceantreexdpeossiugrnesa,llthoewreedafroermaadniryecltimciotmaptiaornisstoonothfiwsodreskiegrns. wEiptihsosidmeisolafrcare are dreaptoaratreed,dinfofticduilstetaoseinitnecripdreetncbee;cathuesreefaorlea,rgtehiRsRpaErPaCmemtearycnaontnontebceessianrtielryprientdeidcaitneahniyghotrhiesrkomfainnnceird.encTeh.e o"Tfhdeisaenaasley.sisInwaadsdiltiimoint,edmaton6yoyfeatrhs.e rAilsskor,attihoesuftoirliezpaitsioodnoefsohfeaclatrhechaarde vseerrvyiwceisdmeacyonrfeifdleecntceloicnatlermvealdsi.cal pCraatcetgiocreizpeadttuenrnd.er Ilnadrigevridouralssmamlaleyrbdeisceoausnetceldasmsoifriecatthiaonn.onEcpeisiondtehseofdactaarbeasmeabyecianucsleudtehethyecsanambee 158 158 000055 dinidsiavbiidulayl several times. Not al employees were included inthe database, suchas hose on long-term Research sponsors: 3M Company Consistency of results: No other morbidity studies have been conducted on fluorochemicas. "CTOhiNsCsLudUySIshOoNulSd only be used for hypothesis generation regarding workers employed at the Decatur plant who ae employed injobs with high exposure to POSF-based uorochemical. ORlEsFenE,RGEWN,CBEurlew, MM, Hocking, BB, Skat, IC, Buri, 1M,Mandel, TH. An epidemiologic analysis o1fe5p,2i0s0o1des ofcaroef 3M Decatur chearical and fim plant employes, 1993-1998. Final Report. May 159 000056 TPietrlfel:uoAroCorcotsasn-osaetceti(oPnFaOlAa)nailnysriesloatfisoenrtuomclpienrifclaluocrhoeomcitsatnreys,utlhfyornoaitdeh(oPrFmOoSn)e,anhde.matology, and ufrliunoarloycshiesmriecsaulltmsefdriocmalmasulreveainldlafnecmeaplreoegmrpalmoyee participantsof the 2000 Antwerp and Decatur TEST SUBSTANCE Identity: PFOS, PFOA Remarks: METHOD Study design: cross-sectional `Mmaannuuffaaccttuurreinpge/rPflruoocreososeitnagne/sUuslef:onyFlaciflliutoireisdeinpDroedcuacttusr., Alabama and Antwerp, Belgium which These fluorochemiccaalns metabolize in the body to PFOS. Hanydpohtohremsoinsatlesptaerda:meTteorpsorofvivdoeluannteaegrgreemgpaltoeyaeneaslyisnisroelfattihoen htoemsaetroulmogPyF,OcSlinaincdalPcFheOmAistlreiveesl,s as `measured in the medical surveillance examinations of Antwerp and Decatur employees in 2000. Study period: March 1, 2000. End date was not reported. Setting: Occupational. 3M plants located in Antwerp, Belgium and Decatur, Alabama. Tcohteamlicpaolpupllaanttioanr:ea 3w4e0reAneltiwgeibrlpe efomrplinocyleuessioannidnSt0he0sDuercvaeitlulranecmep.loyees working in the `Subject selection criteria: Voluntary participation in medical surveillance program in Y2000. Total #of subjects Decatur employees in study: (215 male 255 and Antwerp employees 48 female). (206 male and 49 female) and 263 Comparison population: N/A PDaerctaitcuirpaptliaonntrwatheo: w7er5e%oelfigeimbplleopyareteisciaptaitehde.An7t3we%ropfptlhaenptaanritdic5i0pa%tionfgAthnetweemrpplomyaelees eatmptlhoeyees p`aarntdic7i5p%aotifngthAenDtewceartpufreemmaplleoeymepelsowyeeerse ewenrgeageendgiangperdoidnupcrtioodnucatcitiovnitaicets.ivitOinelsyco1m2p%aorfedthteo 63% ofthe Decaturfemale employees. SSiugbnjiefcictandtelsycryioputnigoen:r tMhaanleDeAcnattwuerrmpaelmepelmopyleoeyseehsa,dhlaodwelrowPeFrOBSMIasn,d wPoFrOkAedlefveewles,rwere 160 160 000057 yPehaorssp,hahtaadseh,igGhGerT,selAfS-Tre,poArLteTd daanidlytrciognlyscuemrpitdeiovnaolufeaslcaonhdolh,ighhaedr lootwalerbimleiraunbianlkaanldinHeDL Values. Comparable results were observed for Antwerp female employes vs. Decatur females. HbaesaeldthonefPfeFcOtsS/stPuFdiOeAd:levTeolsd:etheermmaitnoeilofgtyhe(rheemwaetorceridti,ffheermenocgelsobinint,heRfBoClsl,owWinBgCp,arapmlaetteelrest caomuinnto)t,racnlsinfiecraalsceh,eamliasntirnieesam(ianloktarlainnesfpehroasspeh,attoatsael,agnad mdimraecgtlbuitlairmuyb!int,rabnlsofoedrausre,eaasnpiatrrtoagteen, ctrriegaltyicneirnied,esg)l,ucaonsde,thcyhorloeisdtehroorlm,olnoewsd(etnhsyirtoyidlisptoipmruoltaetiinsn,g hhiogrhmodneens,istyerluipmoptrhoytreoixnisn,e,anfdree thyroxine, serum triiodothyronine, thyroid hormone binding ratio, and free thyroxine). Dsaamtpalecso,llmeecatisounremmeetnhtosdso:fheMiegdhitc,alweqiugehstt,ioannndaibrleo,owdoprrkeshsiusrteo,ruyrqiunaelsytsiiosnn(aDierce,atbulrooondlys)e,ra paunldmsotnaandrayrfdunclcitniiocnaltceshse.misVtarlyueasnudsheedmfaotrorleofgeyretnesctes,rathnygreosidwehroernmootnperomveiadseudr.ement, and Dpaerttaiiclispaonntsd.aTtahecodlalteactwieorn:e sTehlfe-rseiptoer-tsepde.cifQiucewstoiroknnhaiistroerycoqnuteesntt,iodnensaiigrne,waadsmianidsmtirnaitsitoenr,eedtct.o all wUerirnealnyostisprwoavsidoendliyn atshsiessrseepdorft.or DDeactaatournebmlpoloodyceoelslevcitaiosnt(anadmaorudntu,rientec.m)incortosptriocvkidaenda.lysis which tested for urine glucose, albumin, and RBCs. TwSerHe, dferteeerTm4inaenddbTy3awcelroeneddeteenrzmyimneeddboynoirmimmumnuoncohaesmsialyu.miFnToImewtarsiccaalscsualya.teTd4byanmdulTtHipBlyRing T4 and THBR. `PSFerOaSs,atmhpeleesxtwraecrtes ewxetrreacatlesdouasnianlgyzaendifoonr-pPaiHrSin,g PexFtOraScAtiAo,n pPrFoOceSdAu,re.andInMaSdSdi6tion to PFOA and (tpaenrdfelmuomraosocstsanpeescutlrfoomneatmriydaoancdeetvaatleu)autseidnvgehrisguhs-apnreesxsturraectleiqduciudrcvherformoamtogrhaupmhaynesleecrturmosmparaiys. All serum values for PFOS and PFOA were above the LLOQ. Exposure period: Unknown. PFOS/PFOA serum levels indicate exposure. 161 000058 -- Description/delineationofexposure groups/categories: Workers were sraified by plant location as wella by serum PFOS distribution, production status (production vs. non-production workers), and gender. Mean serum PFOS levels for all employees participating in this study at Antwerp (n = 206) and Decatur (n = 215) were 0.96 and 1.40 ppm, respectively. Levels among production employees were higher. At Antwerp, the mean PFOS level ofmale production employees was 1.16 ppm. and 1.63 ppm at Decatur. rMeesapenctPivFeOlyA. lLeevveleslsfoarmaollnegmpprloodyuecetsiowneermep1l.o0y3eaensdwe1.r9e0hpigphmer.at AAnttAwnetrwperapn,d tDheecamteuar,n PFOA level of male production employees was 1.28 ppm and 2.34 ppm at Decatur. Measured or estimated exposure: Serum PFOS and PFOA levels were used to estimate exposure. Satnaatliysstiisocafl mvaertihaondcse,:aDnedsmcurlitpitviavreisaiblmeplreegarnedsssitornatwifeiredeaunsaeldysteos,evPaelauratseonascsoorcrielaattiioonns cboeetfwfieceinents, PFoFrOsStraatnidfiPedFaOnAalyasneds,eaecmhplhoeymaeteoslwoegirceadliavniddecdliinnitcoalqucahretmiliessotrfythteesitrasnedrtuhmyrPoiFdOhSodrimstornibeutaisosna.y. Pcootnesnutmipalticoonn,fcoiugnadrietntgefuascet,oryseacrosnswiodrekreeddiant tehiethaenrapllyasnets, ainncdlutdyepde:ofagjoeb,.BMJ, alcohol MNualttuirvaalrlioagblterarnesgfroersmsaitoinomnosdoeftlhs ewedreepefnidtteendtwivtarhiPabFlOesSw/ePrFeOpAerafnoarlmyezde,d washecnonnteicneusosuasryv,artioables. normalize variables and to enhance model fit. SAS was used to analyze the data. RESULTS Describe Antwerp results: and Decatur employees were different in several ways (see "Subject description" aabnoavley)s.esTwheerreefsotrrea,tiufnieidvabryiagteenadnearlyasnedspwreordeucitniiotinalsltyatsutsr.atiTfhieedybwyelroecaptliaocnedanidnttohqeunartthiolsees d`meapleenpdriondgucotniopnr,odnuocnt-ipornodsutcattuiso.n,Tahenrdeffoermea,letheempPlFoOyeSesv.aluIensaidnditthieoqnu,atrthielseesanaarleydsiefsfaerreentnfootr appropriate for PFOA. Antwerp `"TWhheemnesatrnatPifFiOedSblyevperlodfuorctaillonemstpaltouys,eetsheamtethains wplaasnt1w.1a6sp0p.9m6fpopr mpr(ordauncgteio0n.0e4mp-l6o.y2e4epspamn)d. 0.42 `ppm for non-production employees. The mean for female employees was 0.13 ppm. Mean PFOA serum levels were 1.03 ppm for all male employees at the Antwerp plant. Male 162 162 000059 p(0r.o3d4ucptpimo)n. emTphleosyeeveasluheasdwheirgehesrimgneiafincasnetrlyumdilfefveerlesnt(1b.e2t8wpepemn)pltahntasn.noFne-mparloeduecmtpiloonyeemepslohaydeeas `(1m.u2c3hplpomw)e.r mFeeawnerPoFfOthAesAenrtuwmevraplufeemaatltehsewAonrtkweedrpatpplraondtu(c0t.i0o7npjpomb)s tthhaanntahtetfheemDaelceatur plant employees at Decatur. Male production employees were placed into the following quartiles based on PFOS levels: Q1 ((mmeeaann,'10..1289ppppmm;;rraannggee,0.07.904----10..6461pppmp)m,),QQ42(m(emaena,n,2.06.158pppmp;m;rarnagneg,e 10..6471 --60..2748ppppmm))., Q3 I`nppmmal(reapnrgoed1u.c7t6io--n6e.m2p4lpopyme)esa(nnd =the15l0o),wetshte whaigshe0s.t29qupaprtmil(ermaenagn0e.s0e4ru--m0P.4F1OpSplme)v.elPwraosdu2c.t6i1on e`mAnptlwoeyrepesthianntehmephliogyheeestsqiunatrthielleowweerste qsuiagrntiiflei.canTtlhye(opn<ly0d5i)ffoelrdeenrceanidn cwloirnikcealdcmhoermeisyterairess aftor pSrigondiufcitciaontn (wpor<k.e05r)s dwiafsfeirnenBcUeNs.amoWnhgenmacloemppraordeudctbiyonqueamrtpilloeyoefessewreurmePobOseSrvdeidstfroirbutthiyorno,indo (sTaSmHe,heTl4d, tfrrueee Tfo4r,nTo3n,-pTrHoBduRc,tiFoTnI)eomrpflooyreheesm(atn=ol5o6g).y (HCT, HGB, RBC, WBC, platelets). The Faonrd a4ll qfueamratillee.emTphlyoryoeieds,aBndUhNemwaatsolsoiggnyifriecsaunlttlsywdeirfefenroentts(ihgniigfhiecra)nbtleytwdiefefner1entqubaerttwileeenanadny3of the quartile for females. Decatur "`TWhheemnesatnratPifFiOedSblyevperlodfuorctaillonemsptaltouys,eetsheamtethains pwlaasnt1w.a63sp1p.m40fpopr mpr(ordauncgteio0n.1e1mplo10y.e0e6spapnmd).0.73 ppm was 0f.o9r3npopn-mp.ro7du5c%toifonmaelmpeloeymepelso.yeTehsewmoeraknedfionr female employees production jobs (n= 161)and 63%offemale employees worked in productionjobs. "pTrhoedumcetainonPeFmOplAoyseeersumhaldevheligfhoerramllemaanleseermupmlolyeveeelss tathatnhemDaelceantounr-pplraondtuwctaison1.e9m0pplpomy.eesMa(l2.e34 `Fpepmmalaende0m.p5l9oypepems,hraedspaecmtiuvcehlyh).igThehresmeeavanlPueFsOwAerseersiugmnivfailcuaentalty tdhieffDeercenattubretpwlaenetn(p1l.a2n3s.ppm) wthoarnkeatdtahtepArnotdwucetriponpljaonbst.(0.07 ppm). There were many more females at the Decatur plant who M(maelaenp,r0o.d5u5ctpipomn;ermapnlgoey,e0e.s11we~r0e.p75lapcpemd)i,ntQo2th(emefaolnl,ow1.i0n1g pqupamr;tirlaesngbeas0e.d76o~n P1.O30Spplme)ve,lsQ:3Q1 (mean'1.74 ppm; range 1.32 2.29 ppm), Q (mean, 3.22 ppm; range, 2.31 ~ 10.06 ppm). d`iWfhfeenremnacleebeptrowdeuecntitohen qwuoarrkteilresswwearseipnlAacLeTd i(nhtioghqeusatrtqiulaer,titlheedoinffleyresnitgnfirfiocmanatll(3p o<th0e5r)s) 16 000060 EE No significant differences between quartiles were observed for thyroid (TSH, T4, free T4, T3, `THBR, FTI), hematology (HCT, HGB, RBC, WBC, platelet), or urinalysis (albumin, blood, sugar). For female employees (both production and non-production employees), there were no significant differences among quartiles for demographics, thyroid, hematology, or urinalysis except for mean platelet count where the third quartile was significantly lower than the 1% quartile, but the 4% was not. `When results were analyzed by numberof employees who had values above the reference range for hepatic clinical chemistry tests and liver enzyme and bilirubin tess, there was a higher percentageofmale Decatur production workers in the highest PFOS quartile for ALT, GGT, and total liver panel than the other quartiles. Most notable were the results for ALT where 8% of employees in the lowest exposure group (Q1)and 28% in the highest exposure group (Q4) had values above the reference range, while the percentages for total liver panel (which includes raelskpaelcitnieveplhyo.sphTahtiasster,eAndSTw,asALnoTt,eGviGdTen,tainndDteoctaaltuarndnodni-rperctodbuicltiriuobnine)mwpelroeye1e8s%(aalntdho3u5g%h,the n was only 54), in Decatur females, or in anyofthe Antwerp employees. However, cach subpopulation had a different serum PFOS quartile distribution. Therefore, they cannot be directly compared. Analyses combining employees from bothplants `When clinical chemistry resultsof all male employees from both plants were combined (both production and non-production) (n = 421) and placed into quartiles (n = 105 per quartile), mean values for triglycerides, alkaline phosphatase, total bilirubin, and ALT were significantly (p < 05) higher in the 4 quartile (mean PFOS level 2.69, range 1.6--9 10.06 ppm) than in the first (mean PFOS level 0.27 ppm, range 0.04 0.42 ppm). It should be noted that the number of Antwerp production employees were evenly distributed among the quartiles while this was not the case for Decatur employes. The highest mumberof Decatur employees was in the 4 quartile. In addition, overall the employees in the 1 quartile were slightly younger, had a lower BMI, and worked fewer years than employees in the other quartiles. `Thyroid results for ths same group indicated that T3 was significantly higher(p < .05) and THBR was significantly lower (p <.05) in Q4 than Q1. In female employees combined for both plants (n = 97), alkaline phosphatase and GGT were significantly higher (p <.05) and total bilirubin significantly lower in Q4 than in Q1. Mostof the Decatur female employees worked in Qpr4odwuacsti9on2%jobfsemwahlieleprmoodsutcotifonthweoArnkterwserapndfeamllaolfetshweormkweodriknendoant-tphreodDuecctaitounrjpoblsa.n. Therefore, `The combined plant data were analyzed for employees who had values above the reference range tfhoersaelkmaelaisnuerpehso,spthheatlaesvee,lsAiSnTc,reAasLeTd,frGoGmT,QIand Qto4t.al IlnivQer1,pa4n%el.ofFtohremeamlpeloeymepelsoyheaedsvfaolruaelsl of above the reference range for ALT and 6% for GGT, while 12% was reported for Q4 for both of these tests. For total liver panel, 14%of the employees had values above the reference range in 164 164 000061 Ql as compared to 23% in Q4. The numbersoffemale employees with values above the reference range was very small (n= ). EOSandPFOAanalyses a"Tnhaelyasbeosvweedraetacownedruectneodt.adTjhuesrteedwfaosr apoptoesnittiiavlecsoingfnoiufnicdaenrts;(pt=her0e4f)orae,ssmouclitaitviaorniabbeltewreeegnrPesFsOioSn and cholesterol and alsoa positive significant (p = 05) association between PFOA and cholesterol. When both PFOS and PFOA were included in the model, neither were statistically significant at p=05. PFOS was not significant with HDL although PFOA was negatively aasnsdocPiFatOeAd w(itp=h H.0D02L). (pW=he0n4)b.otThriwgelryecelreifdteisnwtehreemopdoesilt,ivPeFlyOaAssroecmiaaitendedwistihgnPifFiOcaSnt(p(p==0.10)2). Total organic fluorine (TOF) was highly significant for triglycerides (p= 0009). No significant AasSsTocioarttiootnaslwbeilrieruobbisn.erAvesdiwginitfhicPaFnOtS(,p =PF.O02A),poosritTiOveFaisnsorceilaattiioonn twoaaslkoablsienrevpehdosfporhaTtOasFe,anGdGT, AloLcTa.tioAn wpaossithiivgehlsyigsniigfniicfainctan(t (=p0<40)0a0s1s)ociinattihoenmboedtewle.enBMT3I,acnidgaPrFetOtSes/wdaasy,oabslecrovbeodl.daPylawnetre aDlescoatsiugrniefmipcalnoty.ee(sInovtehreaulnl.ivaHroiwaeteveanra,lyfsoerse,aAcnhtpwleanrtp(eimndpilvoiydeuaelslyh)adT3hivgahleuresmeiancnreTa3seldevbeyls than quartile as PFOS serum levels increased, although the differences were not statistically significan]t THBR, as well as the other thyroid hormones, were not significant in the regression analyses. Mostofthe thyroid hormones, including TSH, T4, THBR, and FTI, were not significantly associated with POS, PFOA, or TOF. However, PFOS, PFOA and TOF were positively associated (p = 04, .01, and .004, respectively) with 3. Study strengths and weaknesses: Cross-sectional design, voluntary participation, the Decatur and Antwerp populations were significantly different in certain demographic and clinical cthhaenmiPsFtrOySresseurltusmalsevweellsl, ahsowienvPeFr,OSemapnldoyPeFeOsAwesreeraunmalleyvzeelds,bPyFPOFAOSselreuvemlsl,evteoltsalwoerrgeanhiicgher fluorine serum levels were higher than both PFOS and PFOA levels and it is unclear how this is aefafcehctsiunbggtrhoeupa,naolnylsyeso,npelamnetapsoupruelmaetinotnastcancnerottaibnepcooimntpairnetdimbeecwaaussecoqlulaercttieldesfoarreeadcifhfetersetn,tafnodr other perfluorinated chemicals in addition to PFOA and PFOA are present in the plants. Research sponsors: 3M Consistency of results: cross-sectional medical suTrhveesilelraenscueltdsataar,e isnotmheatwhalaltofcotnhseimstecnotncwliuthdeththoasteotfhetrheewe1r9e95noand 1997 significant abnormalities in hematological and clinical chemistry parametersofthe Antwerp or Decatur workers. No decline in cholesterol levels was observed as PFOS serum levels increased. "The hormone data collected in 1995 was different from that collected in 2000 and therefore: icnanhneoptabtieccoormlpiapridedcl.iniAcallocnhgietmuidsitnraylvaanlauleyss;ishoofwtehveesre, tdhaetraedwiderneotmraenvyealliamintyatsiiognnsiftiocatnhtecshtaudnyg.es 165 000062 CONCLUSIONS `fTlhueoraoucthheomrisccaolncprloudduecdtithoantatnhdesneodna-tparocdouncttiinoune etompsluogygeesetstdhoatnAontthwaevrepsiagnndifDieccanattucrhanges in sfienrduimngcshoilnelsatebroorla,tolriypoapnriomtaelisn.s, Hoorwheevpeatri,ctehnezsytmuedsy wtheaatkanreesscoenssisshtoeunltdwbiethcotnosxiidceorleodg.ical REFERENCE oOflsseenruGmWp,erBfulruloreowocMtMan,esBuulrfroinsatJeM,(PMFaOnSd)elanJdH.perOfcltuoobreoroc1t1a,n2o0a0t1e.(PAFOcAro)ssi-nserecltaitoinoanl taonaclliynsiicsal cpahretmiicsitprayn,tsthoyfrtohied 2h0o0r0moAnnet,wheermpaatnodloDgeycaatnudrufrlinuaolryoscihsermeiscualltsmferdoicmamlasluervaenidllfaencmealperoegmrpalmo.yee Final report. 3M Medical Department. Last updated: 429/02 166 166 000063 EPIDEMIOLOGIC DATA Title: A Longitudinal AnalysisofSerum Perfluorooctanesulfonate (PFOS) and PReesruflltusorforoocmtaMnaoalteeE(mPpFlOoAy)eeLePvaerltsiciinpaRnetlsaotfitohneto1L9i9p4i/d95a,nd19H9e7p,aatnidc C2l0i0n0icFalluCohreomcihsetmriycaTlest Medical Surveillance Program TEST SUBSTANCE Identity: PFOS, PFOA Remarks: METHOD Study design: longitudinal `Manufacturing/Processing/Use: 3M Decatur, Alabama plant and Antwerp, Belgium plant iHsyrpeoltahteedsitso cthesatnegde:s Tinocdleintiecramlicnheewmihsettrhyeranodccluippaitdiroensaulltesxipnoesmurpelotyoefelsuoorfo2ch3emMicfaaclislitoivees.r time pSltaundtys--p1er9i9o4d/:95T,h1e9r9e7w,earned320t0i0m.e periods during which medical surveillance took place at the. Setting: 3M plants in Decatur, Alabama and Antwerp, Belgium. `Total population: 175 male employees participated in 2000 and at least one of the other sampling periods. Subject selection criteria: Employees participated voluntarily. Comparison population: n/a aPnardti1c7i5papatritoincirpaattee:d i1n0620/0107.5 (2641%%)ppaarrttiicciippaatteeddininal19394s/a9m5p,l1i1n0g/p1e7r5io(d6s3(%n)=pa4r1t,icAinptatweedripn2109,97, DAenctawteurrp2304),, 3De7c%atiunr13959)4/in9519a9n7da2n0d0020(0n0.= 65, Antwerp 45, Decatur 20), and 39% (n = 69, Subject description: Male employees volunteered to participate in biomonitoring offered at the plants. In general, Antwerp male employees were significantly younger, had lower BMIs and a higher daily consumptionofalcohol reported than Decatur male employees. Antwerp male ebimlpilroubyieneasnadlsHoDhLadvlaoluweesrtmheaannthaelkDaelcianteuprhomsaplheateampsleoaynedest.riglyceride values and higher total 167 000064 Health effects studied: To results are affected by PFOS daentderPmFinOeAwhleevtehlse.r workers" lipid and hepatic clinical chemistry Dhiagthadceonlslietcytiloinpomperottheoidnss:(HCDlLin,icmagl/dclh)e,mitsrtirgilyecsearinddeshe(mmga/tdoll)o,gaylkcaollilneecptheods--cphhoalteasstee(rIoUl/(Lm),g/dl), `amgianmomtaragnlsuftearmays!e t(rAaLnTsf,erIaUs/eL)(,GGtoTt,alTaUn/dL)d,iraescptarbtialtieruabminin(omtgr/adnls.ferDaesmeo(gArSaTp,hiIUc/dLa)t,aacloalnlienceted via questionnaire. Ddeestiaginl,s aodnmidnaitstarcaotliloenc,tietocn.:aDnedtabillosodoncodlalteactcioolnlemcettihonodmsetwheordesniontcplruodviindgedq.uestionnaire content, PteFtOrSabauntdyPlaFmOmAonmieuthtoodisoon-fpaainralwyistihsPdFifOfSereadndslPigFhtOlAy each year. In in the serum. 1994/95, the method used The ion-pairs were then `epxetrrafcotremdanwciethlieqtuhiydlcahcreotmaatetoagnrdapthhe-tahbestrrmaocstpiroanyprmoadsusctspweacstrtohmeentrayn.alIynze1d99u7s,intghehsigehr-um samples wtheereneagnaatliyvze-eidobnymoldiequ.id Icnhr2o0m00a,tosregrraaspahmyp/lmeassswesrpeecetxrtormaecttreyd,uussiinnggasnelieocnt-epdaiiroinngmoenxittraocrtiinognin procedure. was used. THhieghs-apmeprlfeosrwmearneceevlailquuiadtecdhrvoemrastuosgarnapehxyt/realcetcetdrcousrpvreayfrtoamndaehmummaasns spectrometry serum matrix. Exposure period: Unknown. PFOS, PFOA levels measured in blood serum. Dstersactrifiipetdiionnt/odseulbipnoepautliaotnioofnsexAp,oBs,uraendgrCo.up"s/Ae"atweagsorcioemsp:riTsheedogfrtohuepsoemfpleomypeleosyewehsowere. p1a9r9t4i/c9ip5aatenddi2n0a0l0l,3aynedar"sCof"scuornvteaiilnleadncteh,os"eBw"hcoonptaaritniecdiptahtoedseinem1p9l9o7yeaensd w20h0o0.participated in Measured serum. No oarmbeisetnitmaetxepdoseuxrpeosduartae:arePFavOaiSlaabnlde.PFOA levels were measured in workers' blood Exposure levels: Mean PFOS levels in Males Antwerp Decatur 199495 187 ppm 262 ppm 1997 1.42 ppm 1.85 ppm 2000 1.16 ppm 1.67 ppm 1199997495 2000 Mean PFOA levels in Males Antwerp Decatur 11..0584 ppppmm. 11.4910 ppppmm 1.43 ppm 1.83 ppm 168 168 000065 Smtiaxteisdtimcoadlemletushiondgs:SASre.peRaetsetdrimcetaesdumreasxiinmcuormpolriakteilnighotohdeersatinmdaotmesosufbjveacrtieafnfceectpafritatmeedtteoras were ccoomvpaurtieadn.ce sAtdrjucutsutreed. rCeogvraersisaiotnesmiondcellusdewderinetbhueilmtobdyelinwterrodeuacgien,g aBlMlIc,ovnaurimabteersoafndaltceoshtoilnigcthe rinks per day, and cigarettes smoked per day. ODetchaetrurm)ewthhoodoplarotgiicciaplatiendfionrtmhaeti2o0n0:0 sAurtvoetiallloafnc1e7y5emaarlaelseomppalrotyieciepsat(e1d0i0nAanttlweaesrtpoannedpr7e5vious oflpupoorrotchuenmiitcoyalumneddeirctaalkaseurlvoenigliltaundcienealxaasmsessinscmeen1t9.94/95. Therefore, ths provided an RESULTS Describe results: PROS results `deWchreenasmienagninsethreumpaPrtFiOciSpalnetvselisn wmeerdieccaolmspuarrveeidllbayncseurivnebioltlahnpcleanytesa.r,WPhFeOnStlheevedlastahawveerebeen aannadl2y0z0e0d),byAnthtewe3rspubacnodboDretcsat(uthroesmepwlhooyepeasrtiinciepaactheodfitnh2eo3r smuobrceohmoerdtiscahladexlaowmesrbmeetawneesner1u9m95 PFOS levels in 2000 than at their yearof entry. `DWehcaetnuarneamlpylzoeydeuessi,ngthmeirexewdasmondoealssmouclitaitviaorniabbeltewreeegnrePsFsiOoSn aannddcsoemrbuimncihnogleAsntterwoelroprand tPrFigOlSycaerniddecshainngmeasleovpearrttiicmiepainntsHoDvLe,r talikmael.inTehephroeswphearteasael,soGnGoTs,igAnSifTi,caAntLTas,sotcotiaaltiboinlsirbubeitnw,een and direct bilirubin. } PFOA results `When mean serum PFOA levels were comparedbysurveillance year, PFOA levels in the employees participating in medical surveillance af the Antwerp plant increased between 1994/95 and 1997 and then decreased slightly between 1997 and 2000. At the Decatur plant, PFOA serum levels decreased between 1994/95 and 1997 and then increased between 1997 and 2000. `When the data were analyzed by plant and the 3 subcohort (those who participated in 2 or more medical exams between 1995 and 2000), there were no consistent changes across subcohort at the Antwerp plant. However, among the 3 Decatur subcohorts, mean PFOA levels tended to increase. `When analyzed using mixed model multivariable regression and combining Antwerp and Decatur employees, there was a statistically significant positive association between PFOA and sanedruamlscohoblyesstuebrcoolho(rpt=, 0th0e0s8e)asasnodcitartiigolnyscewreidreesl(ipmi=te0d0t0o2t)hoevAenrttwiemer.p eWmhpelonyaeneasly(pze=d b0y05p)laanntd, in particular, the 21 Antwerp employees who participated in all 3 surveillance years (p = 001). However, the association between PFOA and triglycerides was also statistically significant (p= 169 000066 w1a02s) nfoortasusbiggrniofuipcaBnt(aesmspolcoiayteieosnwbheotwpeaerntiPciFpOatAedainndbtiroimgolnycietroirdiensgaimno1n9g94D/e9c5ataunrdw2o0r0k0e)r,sThere p`Thhoesrpehawtearsee,noGGsiTg,niAfiScTan,tAaLssTo,citaottiaolnbsilbiertubwiene,naPndFOdiArecatndbilcihraubnigne.s over time in HDL, alkaline Total Organic Fluorine (TOF) results DWehceantuarneamlpylzoeydeuessi,ntghmeriexewdasmodsetlatmisutlitciavllayrisaibglneifriecgarnetspsoisointiavnedacssoomcbiiantiionngbAenttwweeernpTaOnFd and tseerrmumwicthholteismteer(oylea(rps)=w0a0s7)noatnsdigtnriifgilcyacnetr.idTeshi(sp a=ss0o0c8ia)tioovnerwatismem.orHeowcoenvseirs,tetnhtefoirntAenratcwteiornp employees than Decatur employees. aStvuedryy ssmtarlelngntuhmsbaenrdofweeamkpnleosyseeess:paSrttuidcyiplaitmeidtiantiaolnls3insctluuddyeptehreiofdosll(oownilnyg:24%, n = 41) PdiFffOeArent labs were used each year for analysis and different analytical techniques for PFOS and could not analyze female employees due to small numbers PFOS levels in employees are decreasing over time while PFOA levels are increasing PFOS and PFOA serum levels in employees are below those causing effects in laboratory animals Dmeeacnausrerum POS and PFOA levels were significantly lower in Antwerp employees than t`hmeorree aArnetsweevrepraelmcpolnosyiseteesntthdainffDeerecnacteusrbpearttwieceinpatthiengAinntwtehirpstaunddyD(e5c7a%tuvrsm.a4l3e%)populations (cg., csthaetmisitsitcralylpyrsoifginliefsi)cant differences in BMI, age, consumptionofalcohol, and differences in only I measurement at certain point in time was collected for each clinical chemistry test other perfluorinated chemicals are present inthe plants al participants were volunteers Research sponsors: 3M pCroonbsaibsltyenncoty obfe rreespuelattse:d.This is the fist longitudinal analysis ofthe surveillance data and will w"TihtehptohseithiyvpeoalsispoicdieamtiiaonefbfeetcwteoebnsePrFveOdAinanrdodseenrtsum(acnhdolneostteorboslearnvdedtriingplyrciemraitdeess).is Innotadcdointsiiosnt,ent PthFeOaAuthsoerrsurmeploervteltshaitn wthoirskeefrfsecatrheamsuncoht bheieghneorbtshearnveatdtahte3DeMcatCuorttoargAenGtrwoevrepfpalcainlti.tyHwohwereev.er, the most recent data (2000) have not been submitted to EPA for review. CONCLUSIONS 170 170 000067 nAotlosnhgoitwudsiinganlifaincaalntyscihsaonvgeers,acsoinxs-iysetaerntpewriitohdtoofxi1c7o5loAgnictawledraptaa,ondfDleipciadtuorr mheaplaetiecmpcllionyiecaels did ochbesmeirsvterdybveatlwueeesnasPsFocOiAataedndwicthholPeFstOeSr.ol Aanpdotsriitgilvyecesrtiadtiesst.icaWlhlyesniganniafliycaznetdbasyspolciaanttioanndwaaslso by Asunbtcwoehrorpt,emtphleoseyeaesssowcihaotipoanrstiwceirpeatleidmiinteadllto3 tshuervAeniltlwaenrcpe yeemaprlso.yTeehse alnidmi,tiantipoanrstidciuslcaru,sstehde a2b1ove should be considered when interpreting these results. REFERENCE OPelrsfelnu,oGro.oWc.t,anBeusrullefwo,naMteM(,PFBOurSr)isa,n1dMP.e,rfMlaunodreoolc,iJanHo.atAe (LPoFngOiAt)udLienvaellAsnianlyRseilsaotifoSnetrouLmipid a1n9d97,Heapnadti2c0C0l0inFilcuaolrCohcehmeimsitcrayl TMeesdtiRceasluSlutrsvferilolmanMcaelePrEogmrpalmo.ye3eMPaFritniaclipRaenptosorft.thOect1o9b9e4r/9151,, 2001. OTHER Last updated on: 5/7/02 m 000068 GENETIC TOXICITY STUDIES "Title: An AssayofCell Chemical T-2042 CoC Transformation and Cytotoxicity in C3H 10T % Clonal Cell Line for the Test TEST SUBSTANCE Identity: T-2942 CoC Remarks: White powder dissolved in DMSO; composition and purity not indicated METHOD Method/Guideline followed: No guideline number specified. Test type: Cytotoxicity and cell transformation Test system: Mouse embryo fibroblast GLP: No Year study performed: 1950 Species/Strain/cell-type/cell line: Cellsof the C3H 107-172 clone Metabolic activation: None Concentrations tested: 0.1,1.0, 10, 50, 100, 200 g/mL. Statistical methods used: None `Rgermoawirnkgs:inTEhaeglteesBtamsaatlerMiealdiwuams (diBsMsEo)l.veBdeinnzDo(MaS)pOyraennde <an2d0udio-fetphoexysboultuatnieonwwearse uasdeddedastopotshietciuvletures cdoanttarwoelsreanodbtDaiMnSedOinasthaesoflovremnotfccoynttortolo.xiPcriitoyrmteoatshuerepmeernftosrmaasnecxeopfretshseedtbraynpslfaotrimnagti(ocnloansisnagy),edfofsiceiernacnyg.e `tTrhaensafpoprrmoaxtiimoantpeotienntviiatrloo fLtDhSe0tceyttocthoexmiicciatly. doTsheewtarsancshfoosrmeantaisonthaessmaeydwiaans dpoesrefofrormetdheinsttuwdoyopfhatshees: paostseenstsimalen(tpohfacseel2l).trPahnasfsoerm|awtaiosnpienrtfhoermceodlionnysmioxdreep(lpichaatsese. 1T)haendtedsettcehremmiincaatliwoanosfrfeomcoivterdan2s4f-ohromuartsion aafntderstaapipnleidcaattio1n4adnadysthteocsuclotruerefsorwetrraensrfeo-rfmeadteiovne.ry P3hdaasyes2fworas14altsoo1p7edrafyosr.mePdlaitne6s wreeprleicwataesshepder, dfoixseed, (1.0, 10, and 100 g/mL) with butadiene epoxide as a positive control. processed at 38days after removalof the test substance. In phase 2, the cultures were: RESULTS `Overall transformation results: Negative m2 172 000069 Cytotoxic concentration: approximate LD= 50 g/mL. Statistical results: None CONCLUSIONS `fTohcieraeswsaaysmneotheovdisd.enceoftransformation observed at anyofthe dose levels tested in either the colony or REFERENCE GClaornya,l VC.eF.l, LainndeRfoLr.thNeelTseosnt.Ch1e9m81i.calAnT-A2s0s4a2yoCfoCCe.l3lMTrCaonmspfoarnmya,tiSot.nPaanudl,CyMtNo.tonicity in C3H 10 % 3 000070 "Title: Mutagenicity Test on T-6564 in an In ivo Mouse Micromucleus Assay TESTSUBSTANCE Identity: T6564 Remarks: clear, colorless liquid; composition and purity not indicated METHOD `Method/Guideline followed: Protocol No. 453, Edition 17, modified for 3M Corporation Test type: n vivo mouse micronucleus assay GLP: Yes ear study performed: 1996 Species/Strain:Mouse! Crl:CD-18(ICR)BR Sex: Male and female No. animals/sex/dose: Five (micronucleus assay), Three (range-finding studies) `Vehicle(ifused): Deionized water Routeofadministration: Oral gavage Doses: DDoossee Selection Selection Study Study I: I: 1000, 1010, 1510, 2010, 2540, 1520, 2020, 2530 3010 mg/kg mg/kg Micronucleus Assay: 498,995, 1990 mg/kg. Frequency of treatment: Once `Statistical methods used: Analysisof variance; Dunner' t est mRaelmeasr;ksth:eiTrhaegeinwiatasl body weightof the animals was 22.4 8 weeks. Dosing was achieved using -- a 28.3 g for volume of females and 31.0 10 mL/kg. Based 37.7g on the for results oufstihngeddeoisoeniszeleedctwiaotners,tuadnyd, athpeosmiatixviemcuonmtrtooll,eurastiendgdcoyscelowpahsoesspthiammaitdeed aats 82000m0g/mkgg/,kgw.erAe ivmephliecmleenctoendt.rol, sAlniidmesalasndwesrtaeinseadcrwifiitchedMaaty-24G,r4u8n,waanldd 7s2olhutoiuorns aanfdtrGdioesmisnag parnidorbtoonaenamlayrsirso.wTwhaessleixdtersacwteerd,e scpordeeadd ofonr `earnyatlhyrsiosc,ytaend(NsCcoEr)edceflolrrmatiico.roOnunceletihoaunsdantdhePpCoElSycpherromaantiimcalerwyetrherosccyotreed(.PCE) to normochromatic. 174 174 000071 RESULTS Effect on mitotic index or PCE/NCE ratio by dose level and sex: Negative Genotoxic effects (unconfirmed, dose-response, equivocal): Negative Statistical results: Negative Rhoewmeavrekrs,:onAellmaalneimfalrsomian tsheecomnidcarroynudcolseeusgrtoeuspgwraosupfaopupnedadreeaddn2o2rmhaolurismmaefdeiradtoesliynga.ftAerlldoostihnegr:animals aoptpheearveedhincolremaclo.ntTohle positive control induced significant increases in micronueleated PCES as compared sIingtnhsoefdotsoexisceilteyctiinotnhsetdudoisees,elheecrteiownersetumdoirtawleirtieeshaunhcheed15p1o0s,ur15e2,0,hyapnodac3t0i0itmyg,/akngddroosvieglhevaeils. cColsti.nical CoNCLUSIONS "eTrheytteshtrarotciacylnetddeiisd ncoonsiinddeurceed nseiggantiifviecainnttihnecmreoausseeinmimcircornonuucclleeuis ianssbayo.ne marrow polychromatic REFERENCE M17u7l5,0.0H.:45159.963.MMCuotrapgoernaitciiotny, Se.stPoanulT,-M6N56.4 inan in vivo mouse micronucleus assay. Study number 175 000072 T(iCtHleO:)MCuetlalg:enwiictihtyaTCeosntfiornmTa-t6or5y64AsMseaaysuwriitnhgMCuhltriopmloesHoamravelstAsberrations in Chinese Hamster Ovary TEST SUBSTANCE Identity: T-6564, also refered(085 L-13167 and FC-1015-X. Rlieqmuiadrks: The specific gravityofthe test substance was 1.22 g/mL. Substance was a clear colorless METHOD `MethodGuideline followed: Protocol No. 437C, Edition 4 was modified for 3M Corporation Test type: In vito cytogenetics Test systems Chinesehamsterovary ceinclultsure GLe: Y Year study performed: 1996 SWpoelcfi,esU/nSitvrearisnicteylolf-tCyapleilfeolrmlilai,neS;anCFhriannecsieschoa.msCteelrlolvianryhacdelansjapveemraangeenctycclleltliimnee osufp1p2liteod1b4yhDoru.rs, Modal chromosome number was 21 "NTAypDePofame1t.5abmogl/imclacatnidvastoicoinriucseadc:idAarto2c.l7ormg1/2m5.4 induced at iver S9 homogente, 15.0 ui, pus CRaonngceefnitnrdaitnigon--s tested: (0b.o1t6h9w,it0h.5a08n,d1w.6i9t,h5o.u0t8a,ct1i6v9a,ti5o0n:)5, 169, S08, 1690, 5080 pg/ml InitiaWlitshtouduyt--activation: 62.5, 125, 250, 500, 1000, 1500,2000 pg/ml ConfWiirtmhataocrtyivasttiuodn:y 250, 500, 1000, 2000, 3000, nd 4000 g/ml WWiitthhoouutt aacttiivvaattiioonn/'4240..12 hhoouurrss:: 5100,0,10200,0,20400,0,40600,0,60800,0,80100,001,00102,0a0nudg/1m2l0.0 g/ml With activation/20.1 + 44.2 hs: 500, 1000, 1500, 2000, 2250, 2500, 2750, and 3000 pg/ml "Test conditions: Nhouumrbsebreofofreceltsr:eatImnetnhtebmyasienedsitnugdiaebso(ubtot1h.2wixth10a%ncdelwsiftohouttheact1i7v.a8thioonu)r,alslsasywaenrde0c.u8lxtur1e0d fcolrsabfoourtth2e4 a44n.d2ahniobuirotaiscssa.y. The culture medium used was McCoy's Sa culture medium supplemented with utrients 176 176 000073 `NmeegdatiiuvmeoCnloyn.troSlosl:veInnttchoentnroonlasctciovnattaiionnedasosnalyys,tnheegsaotlivveentcofontrotlhse weesrtearctuilclteu,resstewriiltehdceeilosniazneddcwualtteurreat n10o.0nacatibvialt.ioTnnstthuediaecstibvuattiaolnsostiundcileusd,endathiev$e9 aacntdivsaotlivoenntmicxo.ntrols were the same as those in the PacotsiivtaitvieoCnosntturdoiless.: Mitomycin C was used for nonactivation studies. Cyclophosphamide was used in the Otrnelaytmceenltlsgwriotuhps21and1necgeanttirvoemearnedsswoelrveentancaolnytzreodl. grOonuepshuwnedrreeadnaclelylzsedf.roAmtealecahstre2p5liGcealtescruoltmurtehoef positive control cultures were analyzed. dIonnteh.e main study (after range-finding study was completed), both initial and confirmatory sudics were oSftacteilsltsicwailthmeatbehrordastiuosnsedi:n eFaicshhetrr'esaEtxmaencttgTreostup(SwoiktahltahnedcoRnothrollfg1r9o8u1p). waLisnueasredtrteoncdotmepsasroeftihnecrpeearscienng.t `singunmibfeircsaontfactelalps wviatlhueaboerf<ra0t.i0o1ns with increasing dose were also done. Tests were considered to be RESULTS Overall resus: (1)Without activation -- Icnointciaelnttriaatlionnsetgeasttievde)(no significant increasesi cels with chromosomal aberrations observed at 2ab0e.r1r-ahtoiuornscoonbfsierrmvaetdoratycsotnucdeynt-rnaetgioantsiveest(endo.s)ignificant increases in clls with chromosomal 4a4be.r2r-ahtoiuornscoonfpiorlmyaptlooriydystwuedrye~onbesgeartvievde (atnocosnicgennitfricaatnitonisnctreesatsees)din cells with chromosomal 2) With activation -- cInointciealnttrriaatli--onnesgtaetsitvede)(no significant increases in cells with chromosomal aberrations observed at a2b0e.r1r-ahtoiuornscownafsirombasteorrvyesdtautdy25~0p0osuigi/mvle.)(a significant inezcase in cells with chromosomal 44.2-hou confirmatory study ~ positive (a significant increase in eels with chromosomal ianbecrurlattuiroenssdwoassedobwsietrhv2e2d5a0t,22755000,ga/nmd.27A50 plg/smsli.g)niofic,ant increase in polyploidy was observed 17 000074 Guegno)toxiinctheeffpercetss:encPeoosiftiavcetirveastiuolnt. foProscihtriovemofsorompaollyapbleorirdaytiaonndseatndtowroedcuopnlicceaitriaotnoinnsth(e25p0r0esancdce27o5f0 activation. Cdoysteodtowxiitch c5o0n8ce0ngtr/amtlio(nso:thInwitthhe arnadngwei-tfhnoduitnagctsitvuadtyi,onc)o.mpTlehteelcoywteosttoxdiocisteyawawshoibcsherevyteodtionxicculeteuzcetss `wWeirtehsoeuetnaicntitvhaetmioanin study were: Initial - 500 ug/ml 4240..21--hhrr ccoonnffiirrmmaattoorryy ~- 460000 pgg//mmll With acItniitviaatlio-n2000 pg/ml 3204.21--hhre ccoonnffiirrmmaattoorryy ~~ 22205000 ppgg//mmll Sgtraetaitsetricnaulmrbeesruslotsf:chTrwoomocosnocmeanltraabteirornastiionst.he main study (2500 ind 2750 gn) showed significantly sRteatmiastrikcasl:siSgunitfiisctacnacles(iigc,nipfi<can0c.e01wawsasjuudsgeeddruastihnegr tahraunlept<ha0t.w05a.s)sNtroictienrftohramnatuisounalwlaysuasveadilfaobjluedfgoe determine whether chromosomal aberrations wee significantat p< 0.05 n1th25,25i0n,iti1al00r0i,alawnidth1o5u0t0agc/timvla,tiorne,spmeicttoitvieclyinwdheexnrecdoumcptiaornesdwweirteh2s5o%lv,en3t0c%o,nt7ro%ls,. and 96% at doses of `inCihtiraolmtoisaomwailthabaecrtriavtaitoionns,waermietoatniaclyizneddexfrreodmuccutlitounroefs d2o%sewdawsitshee1n2a5t,225500.u5g0/0m,lnwdhe1n0c0o0mupga/rmle.d wIinththe 2so0l0v0enutg/cmonlt,rols. Chromosomal aberrations were analyzed from cultures dosed with 250, S00, 1000, and Iatndtohsee2s0o.f1-8h0o0u,r c10o0n0f,iramanto1r2y00ragl/wmi,thoruetspaeccttiivvaetliyonw,hmeintoctiocmpianrdeexdriedtuhctsioonls wnercoent7r3o%ls,.8C4h%r,oamnodso9m5a%l aberrations were analyzed fom cultures dosed with 200,400, 600, and 800 yg. I9n2t%heat44d.o2s-ehsooufr5c0o,n4fi0r0m,a6t0o0r,yarniadl8w0i0thuogu/tmalctwihvaetniocno,mmpiatorteidc wiintdhexsorlevdeunctticoonntsrwoelsr.e C1h25r%o,mo6s1o%r,n6a3l%, and aberrations were analyzed from cultures dosed with 100, 200, 400, and 600 g/m. aTandth3e02%0.a1t-dhoousrescoonffi1r0m00a,to1r5y00i,al20w0i0t,h2a2c5t0i,vaatinodn,2m5i0t0otgic/min,derxesrpeedcutcitvieolnyswwheerne1c3o%m,pa3r8e%d,wi1t5h%s,ol1v1e%n,t cuogn/tmrolls. Chromesomal aberaions were analyzed from cultures dosed with 1500, 2000, 2250, and 2500 5In39t%hea4t4d.o2s-ehsooufr 1c0o0n0f,im2a25t0o,ry25r0i0a,l waintdh2a7c5ti0vautgi/onm,lmwihtoetniccoinmdpeaxrreeddwucittihonsoslwveenrtec1o4n5t%ro,ls1.7%C,h5r6o%m,osaonmdal aberrations were analyzed from cultures dosed with 2000, 2250, 2500, and 2750 g/m. "aTnhaelyazutehdosrespadreastcerliybebetchaufsoellsoowmiengddoesveialteivoelnss fsrhoomwetdheinprcorteoacsoeld--enednodroerdeudpulpilcicaattoinonanadndsopmoleysplhooiwdeydere increased polyploidy. 178 178 000075 179 000076 CONCLUSIONS `hTahmestauetrhoovrasrsytacteelltshaetxTpe-c6t5a6t4awsainsgcloensdiodseereledvenleg(awtiitvheafcotriviantdiuocn)intghacthirnodmuocseodmsailgnaibfeicraanttitoonxsiciintyC.hinese tRheemhairgkhess:t Sciognnciefnitcraanttitoonxsictietstyedw.asThoebsseertvweodcionntcheent2r0a.t1ioannsdw4e4r.e2halscoonpfoisritmiavteorfyortrciharlsowmiotshomacatlivation at ahboewrervaetrio.ns. The significance ofa positive response in the presenceofexcessive toxicity i questionable, REFERENCE Murki, `Ovary H(.CH1O9)96C.ellMs:utawgietnhicaiCtoynTfeisstmaotnoTry-6A5s6s4ayMewaistuhrMiunlgtiCphlreoHmaorsvoesmta.l Aberrations in Final Report. Chinese Corning. Hamster Hazleton Inc. CHV Study No.: 17750-04370. September 16. 180 180 000077 "RTeivdeer:seMuMtuatgaetniiocnitAyssTeasytwwiitthhaTC-o6n5f6i4rmianttohreySAsasaly mo~nEscehelrilchaia ColiMammalian-microsome TESTSUBSTANCE Identity: T-6564, also refered 0 asL-13167and FCI015X Rsuebmstaarnkces.: The substancewas clear, colores liquid. No othe information was provided onth test METHOD bMaestehdoodnGAumideeslienteal.fo(1l9l7o5w)edandCGHrVeePnroatnodcoMlar4i0e9lR,19E7d6i)t.ion 4. Experimental methods and materials were "CToensftitrympaet:orSyalAmsosnaeylla ~ Escherichia ColiMammalian-microsome Reverse Mutation Assay with a Test system: Salmonella pphimurium and Escherichia coli stains GLe: Year study performed: 1996 Species/Strain/cll-ypecell line: SoaflBmiooncehlelmaisttyrpyh,iUmnuirvieurmsistcyozifnsCaTlAifSoSr,niTaA,IB0e0r,keTleAyI.S3S, and TALS37 from Dr. Bruce Ames, Department EStsacthieorni,cShcioatlcaonldi.strain WP2urA from National CollectionofIndustial Bacteria, Torey Research NMeatHa;bPolOi/cNaac;tiHvPaOti,onl:ucAorsoec.l6o-rph1o2s5p4h-aitned,ucKeCdUrMatgClilve,r $9 homogenate, plus NADP, H0, CRaonngceefnitnrdaitnigon-s tested: Main stu1d0yd--oses from 6.67 0 5000 ug/plte 100,333, 1000, 3330, 5000 ug plate (ith and without activation) Test conditions: Numberofcells: Densityof ester strain cultures were > 0.5 x 10" bacteria per i. N$e9gmaiti.veP(ovsiltiilvee)cocnotnrtorlosl:s: ThTehseesewewreerespeldatboetfhorinaltlheesptreersesntcaeinns dboatbhsnentcheeopfrtehseen9ce mainxd;adbisfefenrceentof chemicals were used depending on the sain being tested. 181 000078 `During system therange-finding study, was determined using S. the growth inhibitory effect typhimurium sizin TA100. (cytotoxicity)ofthe test article to the Cytotoxicity was determined to be a test dcyetcorteoaxsieciitnytwheasmuombbseerrvoefdrienvetrhtearnatncgoel-ofniinedsinpgerstpuldayt.e or thinningofthe background bacterial lawn. No `During the main study, both initial and confirmatorystudieswere conducted. `dTehpeeanudtshoonrs"thceristterraiianftoersatepdo)siintimveeatnesrerveesrutlatnwtaspsetropplrtoeduccoemaptalreeadstwait2h-tohre3-vfeohlidclienccornetarsoel.(tTheheamionucnrtese. had to be accompanied by a dose response for increasing concentrationsofthe test article. Statistical methods used: None indicated Remarks: RESULTS Overall positive results: increases In in tnhuemibneitrisaol afsrseavyeratnadntcsonpfeirrpmlaattoerbyoatshsawyi,thalalnddatwaitwheoruet aaccctievpattaiboln.e anInd tthheere were no cinonSf.itrympahtiormyuraisusmays,trhaoiwneTveArS,3a7noinn-tdhoesaebrseesnpcoensoivfeS9S-mfioxl.d iTnhcirseatsreaiinn nwuamsbreertoesftreedvaenrdtaanlilsdwataaswoebrseerved. acceptable and no positive increases in numbersof evertants per pate were observed Genotoic effects: not confirmed upon A S-fold retesting. increase in revertants occurred in one strain (see Overall Result), but was Cytotoxic concentration: main study. No cytotoxicity obserivntehde range-finding test, and none was noted in the Statistical results: NA Remarks: oSfitnhcee tdhoeseporseistipvoensreescpuornvseeasnedenwawsitnhoSt. rtepyepahtiambuler,iuthmeTtAes1t5a3ge7nto,ccTu-r6r5e6d4atisocnolnysoindeerdeodsneeagtattihveebiengitnhnsing assay. CONCLUSIONS "The authors conclude that under the conditions of the study,T-6564 did not caaupossitieve increase in the numofrbeveertarnts per plateofanytesterstrains, either in the absence or presence of the S9 mix. REFERENCE Lmaiwciroors,oTm.eE.Rev1e99r6s.e MMuuttaatgieonnicAistsyaTyewsittwhiathCoTn-f6i5r6m4ationrtyheAsSsaalym.oneClolmai~ngEsHcahzelreitcohniaICnoc.liFiMnaamlmRaelpoiratn,CHV Study Nos 17750-0-409R. September 13. 182 182 000079 "LTyitmlpe:hoMcuyttaegsenWiictihtyaTCeosntfoinrmTa-t6o3r4y2A,sMseaaysuWriitnhgMCuhltriopmloesHoamravelstAsberrations in Human Whole Blood TESTSUBSTANCE Identity: T-6342; clear, colorless liquid. No othe information was given on solubilityorpuriy. Remarks: METHOD Method Guideline followed: Protocol No: 449C0, Editon No. 2, Modified or 3M Corporation Test types In vitro mutagenicity assay "Test systems Human whole blood lymphocytes GLP: Yes Year study performed: 1996 Species/Straincell-typelcel line: Humaniwhole blood lymphocytes `HMoemtoagbeonlaiteasctrivoamtiloinv:erWsiotfrhaatnsdpwriettrheoauttemdewtiatbholAircocalcotirva1t2i5o4n fforrotmhethneonSs9pescuipfeircnaitnadnutctfiroacntoiofn of metabolizing enzymes RCaonngcee-nftirnadtiinognasstseasyt--ed0:.167, 0.500, 1.67, 5.00, 167, 50, 167, 500, 1670, 5000 gm; IInniittiiaall rriiaall ((wwiitthhoauctatcvtaitviaotni)o--n)25132,75,052,531,01005,,1511001,0,2011501,0,2521001,0,3021501,04p0g1/0mLp;g/mL; C1o6n0f0i,r2m0a0t0oraygiianl;(replicate cultures, without activation, 2.1 hour assay)--135, 250, 500, 900, 1200, `1C2o0n0f,i1m6a0t0o,ry20r0ia0lp(gr/epmlLi;cate cultures, without activation, 46.0 hour assay)--62.5, 125, 250, 500, 900, C1o0n00f,ir1m5a0t0o,ry20t0i0a,l 2(5re0p0l,ic3a0te00cupltgu/remsL, with activation, 2.1 hour ssey and 46.0 hour assay)--250, 500, SFtiasthiesrt'iscaElxamcettTheosdts(uTsheadk:urSettatais.tic1a9l8a5n)altyosciosmepmaprleotyheedpaerCcoecnhtargaen-oAfcmeiltsagweitthestabfeorraltiineoanrs t(raenndd, ainf d atrpepaltiecdabcleel,lthweitpherrceesnulttasgeforfomcvoelhsicwliethcomntorroels.thTaenostneartaibcelrersaitigonni)f,icpancoe wlas yesatpanbdlelinshdeoodrewidhueprdleicype<t0i..o0n1in Abalsefdacutporosnssciteanttiefdicprjeuvdigoeumselnytw.ere taken ino account and the final evaluation ofthe tes article was 183 000080 RemaErxpkesr:imental Design hHeupmarainnivzeendoVuascubtlaoionderrs.oCmultsuirnegslew,enroermianla,theedalwtihtyhma0.l3emdoLnoofrbwlsooddsrmalicnfloasrtee(rd,ose rangecfeinntdriinfguagsesatuyb)eso.rT0.h6emceLllosfwbleorodi/n1c0u.batmedLactualptpurreox(icmhartoemloys3o7maCloanbearrsaltoipoen,swaistshaylso)osine c1a5pms,i.in an atmosphereofabout 5% CO in air. The culture medium used was RPT 1640 (RH Briaonsgceifeinncdeisn)gsauspapyl:emLeontteNdo.wiTtOh610524%,fectharlobmoovsionemaslerbuemrr(aFtBoSn;sBaisoscahye),me1d%, pLhoytt#oEh5e3m3a1g,ludtoisenin (PHA-M; Gibco), penicillin (100 units/mL; Quality Biologicals) and streptomycin (100 ug/mL; dCQueHaiVloin,tiyzLeoBditowla2ot0ge)ircwaalatssa),hcaoenncdseo2nltvmreanMttoiLof-ncgohlfoutiSac0me0ifnmoeg/(tQhmui.aslaiTstshyye.BitoeTlshotgeaircttaeilscstl)ea.rstoDilceuliteoiwnoianszseaddnidwssatotlhevrev(edhPiirncelpea:red at contol, deionized water, wer dosed with dosing volume of 1% (10 uml or this ae. NegaTtnivteheannodnaScotlivveanttioCnonatsrsoalyss, negative controls wee cultures that contained any cells and cule cmoendcieunmt.ratSioolnveunstedcoinntreosltscwuelrtuerceusl(tu1r%esoha1t0,c0onLtani)ne.d deIinotnhiezeacdtwiavatteiroan stsshayhsi,ghtehsetnegative and Smoilxveinntccloundterdo.ls wer the samea described i henonsctivation assays, but withthe $9 activation Posi"iTvhee CpoosnittriovleAcgonetnrtosl agents, which were usd ntheassays,were mitomycin C (MMC; CASH 506070.575,-S1i6gm:a,SiLgomtah,4L0o1t254038H)02fo6r9t)hiennohneacmievtaatbioolnicsearciteisvaatnidoncsycilosphIonspthheamcihdreom(CoPs;omCaAlSH aberrations assays,tree concentrations ofMMC (0.08 nd0.10 g/mL initial and confirmatory cBtrohitarlhos;mMo0.sM1o,Cm0a.al2n,adabneCdrPa0tw.i3eornpseg.d/iOmsLsn,ooltfvhetidrhdeitnrdiwoaalst)eearln.d CPowa(2s0la,n3a0l,ysaznedd5i0n pcgac/hmLo)ftwheereabuesresditooniansdsuacyes. RangTen-fhiensdeinagssAasyss,aycsultures were insted with 0.3 mLofbloods mL culture and were incubated for 2.days pio 0 restment. Assa"yThWeiltyhmopuhtoMceyttaebsowleirceAcitnicvuabtaitoend withthe est artic for 19.5 hours st 37C. The est article was Cwoalshceedmifdreom(ftihnealceclolnscewnittrhapthioonsphat0.1egbu/fmfLe)edwsaasliandedaendd fTrheeshcuclotmuprleestweemredhiaruvmesctoendta2i.n0inhgours Jor AssaIyn WhiisthasMseatya,btohleiclyAmcpthiovcayttieosnwere incubated withthetestarticlefor 3 hours at <37C inthe p2lirve7esreonmfcmge/aomlLaef).SrpaTtrhaleigvuee9r-SDf9raawrcletaeicoytniro(tnMso,mliwexhctiuulcraherh(TSdo9x=ib1ce5oelnuolpg/ryme,lv,IioNnu.AslDLyPotrt=ea0t1e.5d6mwigwt/6ahmsALdr,7eorcailn)voderdi1so2rc5io4t.mricIhnaecid othned5e9oenazvoyimdespotshirboiueghnbaicnidviantgio0nosfersuhmotprvoteidns,antdhehmigehdliyurmeadcitidvneontthearvmeedFiBstSesduprriondgucheedby exposure period. After the exposure period, the ces were washed twice with buted saline. 184 184 000081 CCoootmlapeplehematisedeRcPl(Mli.Inscclotnrceentmreadtiiounm~w0a.s1aidgdiemdLtyowthhieechultwuiress,awdhiechfowrethee ifnscu2b.atheoufrors 1fo8.c5olhloerts. AssaMyitBoatliucstiinodenx was anlyzed from the surviving meaphases present i 1000consecutive cells. dose levels by. analyzing the umber of ChromtohsocmharlomAobseormsatliosn Ahsseaya Wsiatyhs,anedlWiittheoctulMteutraebowleirAeckdvaattocnach dose vel andfo nWCoeinghftiaimvm2ea2t.co0on-nyhtorwuoilrl,h.aproCvsheitsritovmmeocesoonmntaotllh,sabnnerdiatlsioolrnviesanlwteacrnedowaninvtahl.y2sT2e.hd1-oaiemnrdat4th6i.o0cnhlaoouessasyasrrwvaretetedmsaoetns4dudcionisetedhe Seve and om onofthe positive control dose AbeCrulaliuorensAwsesraeyiWniittihaoteudt2MedtaaybsoplircotAcotievaattimoennt with 0.6 mLofwh.ole blood 10. mL cule in p1r5omde,tcrmoinnieadgce boesnToooedfoanysSptareoiRcIolTaArIne na19.t3 inond, c43l.s3 whoeurres.rTahteeduwliethsthweeorte waisrhcedat ipltahcebdubfaerkedonstaolinteh.e CeolmsplTetweoRhoPurVs L1t6r4,0 mheccrl,l wceornnhiarnvges0t.e1dpngdmi. Cdioeldeasniidde,swwaesre TSohaedrsa.tiTohnesS.iTdaebslewe|rceosnttaaiinnedsa su5m%maGriyemosfathesoleuattiomnefnotrshehaendyousflohafechsrboemroastoonmsalassay hou metbolc aeivation AberCautlitounreAswearyeWnitthtMeiid3abdoalycs Apcitirva1t0ieonsment with 06mL.of whol bood/10. mL culturien f15orm3hLocuerntirinfuhge pturbeesse.ncTewoofdhaeysteasfttaeluelaenmtahtei9onr,eahceticonlmairreew.erAincfuhbeat3edhoatur237C eCoxmppoisiee pRePrMiIod1t6h40cemldlsiwuemr.e wOanseh-eednvhigce/mwiLhCboulfefeemreiddaiwans nadddthoctlhescwlaarreersefdeudriintghthe Tlayss2s..0 hours of incubation. The metaphase cells wee arveted and prepared for cyogencic Ha"rTvehstcPlrlocseudspuernesion ws nrifugd, the supernatant was discarded, anhde cll were rated Cweitlhl hwyeportownaischeKdCI3 (t0im0e7s5wMihffore1h0l mprienptarse.d Ainfatsee(tibfgsaeiotnahn arneimcoi!oftae0KC4l0,dh,e $1, wv. Ardross were prepared fom he harvested cells Side Preparation and Saving `WSSiilldihedess3%wweerGreeispnrrednpraioreedldnibdyndcfrooovptpehiSngiaptlphyeeslhiasrvoefsmteidtcuoltuirnedsexonancdlecarneslmiodesso.mTahlessbliedredsownesr.e Alstained Abc"hCreesllimsoowdneaArlneamslaylseritsseadn4fd6rwAgesosroydsEamvloarvlpuaha.otiloOongnyenadndarney cellss,wfiptotshesen,umrboermofccaecnhterpolmeiraetscequurale0 ce levels ofhe tet ail, th negative oma he slot conrl and posi contol 185 000082 c2u5ltcuerlless wweerreeaannaallyyzzeedd ffoorrtchhrodimfofseoremnatltyabpeersorafticohnsrofmroosmotmhaolseabceurlrtautrieosnwsi(tEhv>an2s5,%19c6e2l)s.wAitthleast canharloymzoisngomtahle nabuemrbraetrioonfsm.iCteoltliscwcietlhlsa/b1e0r0r0atcieolnss;wthererarteicoowrdaesd.exMpirteostsiecdiansdeaxpweracseanstsaegsesoefd by mtaibtuoltaitcedc.ellTsh.eCyhrwoemraetniodt,anhdowiesvoecrh,rocmoantsiiddegraepds,iniftohbeseevravleuda,tiwoenroefntohteedabiinlitthyeorftahwedatteastaanrtdicwleerteo tihnedreesulcthsrwoemroesotmabaullaatbeedr.rations. Percent polyploidy and endoreduplicetion were analyzed and RESULTS `Overall results: positive, negative, ambiguous: Negative `Genotoxic effects (unconfirmed, dose-response, equivocal - with/without activation): Negative Cytotoxic concentration: Range-finding Assay Without Metabolic Activation H3e5m%o,ly6s%i,s3w8a%s,o1b5s%e,rv1ed8%p,ri5o7r%t,o waansdh1i0n0t%hwceurletuorbessedrovseeddiwnitthhe 5mi0t0o0tigc/imndLi.ceRseodfucttheiocnusltoufres dosedwith0.500, 1.67, 5.00, 16.7, 500, 1670,and 5000 pg/mL. Range-finding Assay With Metabolic Activation H5e%m,o4l9y%s,is1%w,asanodbs1e0r0v%edwperrieootbosewravsehd iinntmhietoctuilctuirnedsicdeososefdtwhiethcu5lt0u0r0espdgo/msLe.d wRietdhuc1t.i67o,ns50o.f0,8%, 500, 1670, and 5000 pgm, as compared with the solvent control culture ChIrnoimtoisaolTmrailaAlb--eHrermaotlioynsiAssswaaysWoibtsheoruvtedMeptraiboorl0icwAacsthiviatitohne cultures dosed with 2510 g/mL. Rsoeldvuecnttioconnstroofl3c8u%lt,ur1e8s,%,we1r8e%o,b5s0er%v,ed53i%n,thaendcu9lt5u%reisnttrheeatemditwoittihc i1n2d7i,ce2s5,3,as5c05o,mp1a0r1e0,d w15i1t0h,the and 2010 pg/mL, respectively. `Confimatory Trial--In the 22.1-hourconfirmatory tral, hemolysis was observed prior to wash of thhaervceuslttoufretshedcousletdurwietsdho1s6e0d0 awintdh21060000gg//mmLL,. aRnedduacstliioghntsoefvi2d%en,ce1o4f%h,e6m4o%l,ys7i4s%w,a9s3e%v,iadnendt at 9cu3lt%urienstdheosmeidtowtiitchin1d2i5c,es5,00a, c90o0m,pa1r20e0d,w1i6t0h0t,haensdol2v0e0nt0cgo/nmtoLl,cruelstpuercetsi,vewleyr.eIonbstheerv4e6d.0i-nhtohuer c2o0n0f0irgm/amtLor.y Rtieadlu,chteimoonlsysofis59w%a,s o9b3s%e,rv9e8d%p,riaonrdt9o8w%asihnofthtehmeitcualitcuriensdidcoess,edaswcitohmp1a6r0e0dawnidth the solvent control cultures, were observed in the cultures dosed with 900, 1200, 1600, and 2000 ng/mL, respectively. Chromosomal Aberration Assay With Metabolic Activation aInnidti4al0T1r0ialg--/HmeLm.olNyosciesllswawseroebsveisrivbelde pprriioorrftoo wthaeshadidnittihoenocuflCtuorlecsedmosieddwtiotthh2e0c1u0l,tu2r5e1s0d,o3s0e1d0, with 4010 g/mL. Hemolysis was observedpriorto the additionofColcemid to the cultures dosed with 3010 g/mL. Reductions of 15%, 20%, 15%, 43%, 77%, and 95% in the mitotic 186 186 000083 i2n5d3i,ce5s0,5,as1c0o1m0,pa1r5e1d0,w2i0t1h0t,heansdol2v5en1t0cpongtrmol,curletsuprecetsi,vweleyr.e observed in the cultures treated with `ConfirmatoryTrial--In the22. -hour confirmatory trial, hemolysis was observed prior to wash and 5%, prior to harvestofthe 69%, 82%, 97%, and cultures 100% in dosed with the mitotic 2i0nd0i0c,es2,5a0s0,coamnpda3r0e0d0wgit/hmtLh.e sRoeldvuecntticoonnstroofl 15%, cultures, were observed in the cultures treated with 500, 1000, 1500, 2000, 2500, and 3000 g/mL, respectively. In the 46.0-hour confirmatory trial, hemolysis was observed prior to wash `8a0n%dp,ri1o0r0t%o,haanrdves1t0o0f%thien tchueltmuirteostidcosineddicweist,ha2s0c0o0m,p2a5r0e0d, waintdh3t0h0e0soplgv/emnLt.coRnetdruolctciuoltnusroesf,1w5e%re,: observed in the cultures treated with 1500, 2000, 2500, and 3000 pg/mL, respectively. `Statistical results: The test substance `without metabolic activation. did not significantly increase chromosomal aberrations with or Remarks: ChroInmiotisaol mTarliaAble--rNroatsiiognniAfsicsaanyt Without increase Metabolic Activation in cells with chromosomal aberrations, polyploidy, or `endoreduplication was observed at the concentrations analyzed (253, 505, 1010, 1510 pg/mL), `ConfirmatoryTrial--In the 22.1-hour confirmatory trial, no significant increase in cells with `chromosomal aberrations, polyploidy, or endoreduplication wasobservedat the concentrations ainncarleyazseedi(n1c2e5l,ls25w0i,th50c0h,roamnods9o0m0alpga/bmeLrr)a.tiIonnst,hep4ol6y.p0l-ohioduyr,coornefnidromraetdourpyltiicaalt,inono swiagsniofbiscaenrtved at the concentrationsanalyzed (125, 250, 500, and 900 pg/mL). The sensitivityof the cell culture finorthiendcuecltlisoenxopfoscehdrotmooMsMomCa,l tahbeerproastiitoinvse wcoanstrsolhoagwennt,by the increased frequencyof aberrations Chromosomal Aberrations Assay With Metabolic Activation neindaolreTdrupilailc--atNioonsiwgansifoibcsanetrvinecdraetasteheincocnelclesntwriatthiconhsroanmaolsyozmeadl(a0b5e,rra1t0i1o0n,s,1p5o1l0y,palonidd2y,01o0r ng/ml). ``Ccohnrfoimromsaotmoarly Tabreirarlat--iIonnst,hepo2l2y.p1l-ohioduyr, coornefnidromraetdourpylitrcaalt,ionno wsiagsniofbiscearntveidncartetahsee cionncceelnltsrawtiitohns. `analyzed (250, 500, 1000, and 1500 g/mL). Inthe 46.0-hour confirmatory tral, due to toxicity, osinglnyif5i2camnettianpchraesasees iwnecreelavwaiiltahbclehrfoormoansaolmyasilsaibnerornaetioofntsh,epocluylptluoriedsyd,oosredenwdiotrhed2u0p0l0icgat/imoLn.waNs.o observed at the concentrations analyzed (500, 1000, 1500, 2000 pg/mL), except for a weak increaseinendoreduplication at 2000 pg/mL. The successful activationofthe metabolic system wtraesatieldluwsittrhatcedycblyopthheosipnhcarmeaisdeed, itnhceidpoesnicteoivfecceolnltsrowlitaghencth.romosomal aberrations in the cultures CONCLUSIONS The test article, T-6342, was considered negative for inducing chromosomal aberrations in cultured whole bilnodoedpehnduemnatnlylcyomnpdhuocctyetdescocnelflisrwmiattohrayndtriawlis.thout metabolic activation. These results were verified in 187 000084 REFERENCE B`Mluortoid, LHyemmaplhaotchyat.es19W96i.thMuatCaognefniircmiattyoTreystAsosnaTy-W6i3t42h,MMuletaispulreiHnagrvCehsrtso.moCsoormnianlg-AHbaezrerlattoinon,sInicn. W(hCoHlVe). Vienna, VA. CHV Study No.: 17073-0449C0. 188 188 000085 ("TCitHleO:)MCuetlalgseWniitcihtayCToensftiornmaTt-o6r3y42A,ssMaeyasWuirtihnMguClhtirpolmeoHsaormvaelstAsberrations in Chinese Hamster Ovary TESTSUBSTANCE Identity: T-6342 C; clea, colorless liquid. Rcoenmcaerntkrsa:tioTn-o6f344298w0asugs/olmulblienicnulsttuerrielem,eddeiiounmizreedmawianteedr >co4m.p9l5e0tge/lLy (stohleubtleetastuabsptHanocefat7.a5). METHOD Method Guideline followed: Protocol No.: 4370, Edition No.: 4, Modified for 3M Corporation Test types Invitro mutagenicity assay Test system: Chinese hamster ovary (CHO) cells GLP: Yes Year study performed: 1996 Sorpiegciineasl/lSytroabitna/icneeldlf-tryopme/tcheellalibnoer:atCohriyonfesDerh.a5m.stWefro,varUynivceelrlssit(yCoHfOC-aWliBfLor)nifa,rSoama pFerarnmcainsceon.t cTlhle lcienlel,s utismeed oinf t1h2i-s1s4tuhdoyurhsawdibteheanmroedcalloncedhrtoommoaisnotmaeinnkuamrbyeortyopfic21.staTbihleityC.HTOhicselclelslwleirnee hgardowann ainveMrcaCgoeyc'ysclSea. cpuelnitcuirlelimneadnidums,trwehpitocmhywcians,sautpapplpermoexnitmaetdewliyth3710C,%ifntaaln baotvmionsephsecrreoumf(sFbBoSu)t,51%%CL-Oghitnaamri.ne, and 1% Metabolic activation: With and without at liver $-9 Concentrations tested: RInaintigael-tfiianldi(nwgitahsosuatya--ct0i.v1a6t6i,on0).4192,5,1.26560,,4.59080,,1765.06,,4190.080,, 116560,0,49280,01066g0/,m4L9;50 pg/mL; I`nCiotinaflitmiaatlor(ywittihaalc(twiivtahtoiuotna)c--t2i5v0a,ti5o0n0),--1122550,,224590,0,49387,507,465,090905,g1/4m90L, 1990 g/m; CRoenpfeiartmraitaolr(ywtiitahlou(twiatchtiavcaitviaotni)o--n2)5--02,4590,0,49182,501,25204,902,49307,403,73409,8409g7/0mgL./m; SatnadtiRstoihcall m1e98t1h)odwsasuseemdp:loTyheedFtioscheorm'psaErxeacttheTpeesrtcweintthagaeonfadcjeulslstmweintthfaobremrurlattiipolnes cinomepaacrhitsroenastm(eSnotkal agbreorurpatwiiotnhs wthiethreisnuclrtseafsriongmdtohseeso(lAvremnittacgoen,tr1o9s7.1A) wiancsaarlstorepnedrtfeosrtmoefidn.cTreesatsairntgicnleumsibgenriofficacneclleswwaisth established where p<0.01 RemaExrpkesr:imental Design nInegtahteivcehraonmdossoolmvaenltacboenrtrraotliso.nSsiansgslaeysc,ulrteuprleiscawteerceulutsuerdesfowrereeacuhsoefd watoacdohsedsosoef ltehvelpoasnitdivfeor 189 000086 `caonndtrwoli.thT2h0e.0a-bearnrdat4i4o.n1s-ahsosuaryhsawreversetctoinmdeuscitnedthweictohnafi2r0m.a0t-ohroyurtrhiaalrsv.eCshtrtoimmoesionmtahle ianbietriraalttiioanls. were analyzed doses. from the cultures treated at 4 dose levels and from only oneofthe positive control Negative and Solvent Controls : `Inmetdhieunmo.nSacotlivveantticoonntarsosalyssw,enreegactuilvteurceosnctroonltsaiwneirneg tchueltsuorlevsetnhtaftocrtonhteaitneestd aorntlicylecealtltshaenhdigchuelstutre tchoencseanmtreaatsiodnesucsreidbiend tienstthceulntuorneasc.tiIvnattihoenacatsisvaaytsi,onbuatsswaiytsh, the the negative and S9 activation solvent controls mix included. were Positive Control Agents. `The positive control agents, which were used in the assays, were mitomycin C (MMC; CAS# 50- 07-7, Sigma, Loti 60535-19-2, Sigma, 2SHO619) for the Lot#67F0155) in nonactivation the metabolic series and activation cyclophosphamide (CP; CASH series. In the chromosomal aberrations assays, two concentrationsof MMC (0.08 and 0.10 pg/mL, inital and confirmatory ctrhiralos;mo0s.o50maalndab1e.r0raptgi/omnsL,inthtihredCtiHaOl) caenldl.CPOn(e5o.0ftahned d1o0s.0e plgev/emlLs)wawseraenaulsyezdedtoiinnedaucceh. ofthe `aberration assays. Both MMC and CP were dissolved in water. Range-finding Assays In these assays, the cells were culturedfor approximately (+) 24 hours prior to treatment by s1ecedoingn=ta0.sa3uximm1n0arscyeollfst/2h5ectmr'eaftlmaesnktinstcohe5dmulLeoofftchoemprlaengtee-fMicnCdoinyg'sass5aay.cuAlltlurdeosmiendgiwuams. Table achieved witha 1% (10 uL/mL) dosingofeach stock solution and the solvent control culture was dosed with 10 wL/mLofsterile deionized water `Assay Without Metabolic Activation w"Tahsehceudltfurroesmwtehreeceilnlcsuwbiatthedphwoistphhathtee-tbesutffaertriecdlesafloirne17a.n8dhofruersshacto~m3p7leCt.e Tmheediteusmt acrotnictlaeinwiansg Colcemid (final concentration harvested 2.0 hours later. = 0.1 g/mL) was added. The cultures were then trypsinized and Assay With Metabolic Activation In this assay, the CHO cells were exposed to the test article for3 hours at =37C in the presence. omfga/rmaLt)l.ivTehreS$99refaraccttiioonnm(iMxotluerceu(laSr9=T1o5xi/cmollo,gyN,AInDc.P, L=ot1.i50m5g8/3m)Lw,aasndderiisvoecditfrrcoamcitdhe=l2i.v7er of `maavloeidSpporsasgibulee-Dinaawclteivyatriatosn,owfhishcohrthalidvebdeeanndprheivgiholuyslryeatcrteiavteedinwtietrhmeAdrioactleosrp1r2o5d4u.ceIdn obrydetrhefoS9 p`eernizoydm.esAfttherrotuhgehebxipnodsiunrgetpoesreiordu,mtphreocteelilnss,wethreemweadsihuedm tdwidicneowtihtahvbeufFfBeSreddusrailnignet.hCeoemxpploestuer.e McCoy's Sa medium was added to the cultures, which were incubated for 16.8 hours. with ``mCeotlacpehmaisdece(lflis.nalThcoenccuelntturraetsiowner=e0t.r1ypisgi/nimzLe)d,whhiarevheswtaesd,afdidxeedd, faonrdthselildaesst w2e.0rehopurrespatroecdolalnedct stained as describedforthe nonactivationrange-finding assay. `Assay Evaluation Mitotic index was analyzed from the highest five surviving dose levels by analyzing the number of metaphases present in1000consecutive cels 190 190 000087 Aber`rCautlitourneAsswsearyeWiinitthioautetdMbeytasbeoeldiicngAactpipvraotxiiomnately 1.2 x 10 clls (20.0 hour assay) and 0.8 x 10 acefltlrs c(u+l4t4u.r0ehioniutriaatsisona,y)foprerth7e5incimti'alfalnasdkcionntofi1r0mamtoLroyfrcaolm,pltehteeceMlclsCowyer'esiSnacumbeadtieudma.t ~O3n7edCay awsistahyt)hheoutersst.tAilledoastinpgrewdaestearcmhiineevdeddowsietshfaor1a%bo(u1t01L7./7L(2)0.d0ohsoiunrg aofsesaayc)hanstdo4c1k.s8ol(u4t4i.1onhaonudr wtheeresowlavesnhtecdonwtirtohlbcuuflfteurreedwsaaslidneo.seCdomwpilteht1e0MLcC/oyL'osf5taemrediiudemi,oncioznetdaiwnaitnegr.0.T1hge/cumlLtures aCnodleaimri-ddri,edwsaisdepslawceerdebmaacdke.onTtohetshlicdeellss.weArpeprsotaxiinmeadtienly5%2 hGoiuermsslaatseo,lutthieonceflols wtheereanhaalryvsiesstoefd cinhcruobmaotsedomaatl~3ab7erCratfioorns.hoFuorrstihnetthheirpdrteisae,ncoeoneftdhaye atefsetrarctuilctluerieniMnictCiaotyio'ns, t5hae mcueldtiuruems wwietrheout cFeBlSl.s wAefreerrtehfee3d-whiotuhrceoxmppolseutreeMpceCriooyd',sthSeacmeleldsiwuemr.eOwnaes-theendthtwpicge/mwiLtChoblueffeemrieddsalwianse aandddetdhe dcyutroignegntehticlaasntal=y2s.i0s.hour of incubation. The metaphase cells were harvested and prepared for AberCrualttiuornesAswsearyesiWniittihatMeedtbaybosleidciAncgtiavpaptriooxnimately 12x 10 cells (20.0 hour assay) and 0.8 x 10 Gaeflelr c(u4l4t.1urheoiunirtiaastsiaoyn), tpehrc7ulctuareftlhaastkwientroe1t0rematLeodfuncdoemrpltehetecoMncdiCtoiyon'ssofSamemteadbioulmi.cOacnteivdaatiyon `iwneMrecCioncyu'bsatSeadmated~3i7umCwiftorho3uthoFuBrSs.inAltlhedporseisnegnwcaeosfatchheietveestdawrittichlea a1n%d (th1e0$u9LirmeaLc)tidoonsmiinxgtoufre weaatcehr.stAofctkersotlhueti3o-nhoaunrdetxhpeossoulrveenptercioondt,rotlhecucletlulrsewwearse wdoassehdedwittwhic1e0wuiLth/mbLufoffesrteedrislaelidneeiaonndiztehde cells were refed with complete McCoy's 5a medium. One-tenth pg/mL. Colcemid was added to athnedcpurletpuareremdefdoirucmytdougreinnegtitchaenlaalsyts~is2..0 hours ofincubation. The metaphase cells were harvested HarvPersitorProctehdeuhraervest ofthe cultures, visual observationsoftoxicity were made. These observations "iTnhcelucdueltduarnesawsesresesamlesnoteovfatlhueatpeedrfcoentthceonpfrleuseenncceeooff mthitocielclomondoelaadyceerllwsiftlhoitnitnhge icnultthuermeefdlaisuksm.. "iTnhteercpuhlatsuerecselflrsoamndthweedroesetrreaatnegde-wfintdhi0n.g07a5ssMay KwCerIehtyrpyoptsoinniiczesdoliutsion0. cTohleleccutlmtirteostiwcearned.fixed awiirt-hdrainedabslsiodleustewmeertehparneoplargelda.cial acetic acid (3:1, vv) fixative and washed several times before Slid`eSlPirdeepsawreatrieonpraenpdarSetdaibnyindgropping the harvested cultures on clean slides. The slides were stained with $% Giemsa solution for the analysisofmitotic index and chromosomal aberrations. All Slides were air-dried and cover slipped using Depex mounting medium. Anal(yCseillssowfeArbeesrerlaetcitoendsfaonrdgAososdamyoErvpahloulaotgioynand only cells with the numberofcentromeres equal to ethaechmordepallicnautembcuelrtu2r1e a2t14(droasnegele=ve2l0s-o2f2t)hweetreestaanratliyczleeda.ndOnferohmunthderendegcaetlilv,eiafpnodsssiobllvee,ntfcroonmtrol cultures were analyzed for the diffrent typesof chromosomal aberrations (Evans, 1962). At least 191 000088 `2C5elcleslwlsitwherabeearrnaatliyoznesdwfeorrechrreocomrodsedo.maMlitaobteircriatnidoenxswfarsomasosneesosfetdhbey aponsailtyizviencgotnhteronlucmublteurreos.f imistoocthircocmealtlisd/g1a0p0s0,cieflolb;sethreverdat,iowewraes neoxtperdesnsetdheasraawpedracteanatnadgewoefrmeittobfuilactceedl.ls.ThCehryowmearteidnoatn,d `however, considered in the evaluationofthe abilityofthe test article to induce `aberrations. Percent polyploidy was analyzed from the ~44.0-hour assay. chromosomal RESULTS Overall results: positive, negative, ambiguous: Positive s`Guebnsottaonxciecweafsfepcotssit(iuvnecfoonrfcilramsetdo,gednoiscea-crteivsiptoynsfoer,heiqguhilvyotcoaxli~c twrietaht/mweinttshoofutshaocrtitvdautriaotni)o:nT(h3ehtoeusrtse)d both in the presence for polyploidy faonrdthaebsheinghcleyoftoaxnicSt9remaettmaenbtosl.ic activation system. The tested substance was also positive. Cytotoxic concentration: i"Tnhcirseasseecstiionncohnrloymdoessocrmiablesabtehrercayttiooxniscoictcyurorbesde.rved at concentrations at which statistically significant ChIrnoimtoisaolTmrailaAlb--eTrhraetitornesatAmsesntaywiWtihth37M5e0taubgo/lmicL Activation was only slightly toxic, but the 5000 ug/ml. `tarnedatambeonutt w7a5s%hriegdhulcyttiooxnicf,orcatuhseirnegplaibcoatuet c9u5lt%urer.edFulcotaitoinngindmeoandoclealylserancdondfelburiesncwyerfoeraobnuendcaulnttu,re: and only 94 metaphases were analyzable from the culture with greater toxicity (5000 ug/mL). CoFnofritrhmea2t0orhyouTrrihaarlv--est, the confluency ofthe cultures treated with 4970 ug/m. was reduced by (b2o0uhtou7r0h%aravnedst)t,hetmhietroetwiacsinadpepxrowxaismarteedluycead3b0y%43re%d.ucFtoironthien ccuolntfulruesentcryeaatnedd wainth1837%3r0eduugc/timoln in mitotic index. Abe2rr0ahtioounrAhsasravyessWti--tAho3ut0%MerteadbuocltiiconAcinticvoantfilonu;en3c-yHoocucrurTrreedatimnetnhte cultures treated with 2490 ug/mL. The next higher could be examined. dose, 3740 ug/m, was so toxic that oly a small mumberof metaphases 4347h4o0uurhagrvaen/sdtt--hmAe254L59%0ruegd/umclt.iotnreinatmmoennotlraeyseulrtcedoinnflaue3n0cy%orcecduucrtrieodn.inTthhee mcuilttoutriecsitnrdeeaxtewdasw.ith significantly reduced (57%) forthe high dose (3740 ug/L). Statistical results: `ChrIonimtoisalomTarliaAlb--eSrirgantiifoincaAnstsianycsreWaistehs Metabolic Activation in cells with chromosomal aberrations were observed in the cultures dosed with 3750 and 5000 pg/mL. `Confirmatory rial--For the 20 hour harvest, a significant increase in cells with chromosomal `aberrations (simple and complex) was observed fo the cultures dosed with 4970 g/mL. w`Aalst,hnoeuvgehrtthheel4e9ss7,0ngot/emdtLhattrtehaetmpeenrtcwenatsptooloyptloxoiicd tcoelyiselidncsruefafsiecidesnitgmnieftiacapnhtalsy.es for analysis, it 192 192 000089 Chr"oAmosisgonmifailcaAnbteirnrcarteiaosneAisnstahyesnuWimtbheoruotfMceltlabowliitchAcchtrivoamtoisoon;ma3l-HaobeurrrTatrieoantsmweants observed in the coublsteurrveesddionsetdhewciutlhtu3r7e4s0dogs/edmLwi(t7h.35%7)4.0Ag/smigLn.ifiTchaentmiintcorteiacseinindepxerwcaesntsipgonlifyipclaonitdlyywraesduaclesdo (57%) forthe 3740 g/m. dose. RemaRarnkgse:-finding Assay Without Metabolic Activation wInasth<e 5cu%ltcuornefltrueeanttedanwditthhe49cu8l0tugr/e mcoLn,sinsotevdisoinbllyeomfitdoetbircicsealnsdwdeeraedocbeslelr,vefldo;attihnegcoerllamttozncohlead.yeAr s1e6v6e0repgr/emdLuc.tiTohneincetlhlemmounmoblaeyroerfvliosoikbeldeumnihteotailcthcyelalnsdwathseodbesgerreveoedfcinonthfelucuelntcuyrewdaossreedduwcietdh. about 15%; floating dead cells and debris were noted. Floating debris was also observed in the cMuilttoutriec dionsdeicdeswiwtehr4e9a8nagl/ymzeLd,fbruotmotthheercwulitsueretshedcousletdurweitwhas16s.i6m,il4a9r.8t,o 1t6h6e,n4e9g8a,tiavnedco1n6tr6o0l.gil aHnodwecvoemrp,arlietdle0orthneo sroeldvuecnttioconntirnolm.ifoAttic16i6nd0eux gw/aLs,obtsheermvietdotaitctihnedneexxtwalsoweesrsednotisaeollfy 4ze9r8o. ng/mL. Range-finding Assay With Metabolic Activation ``Amnonuonlhaeyaelrthcyoncfellulemnocneowlaasyerredwuacsedobbsyeravpepdroixnitmhaetceullytu8r5e%donsedd wsietvhe4r9e8r0edpugc/tmiLo.n iTnhtehecenlulmber o`fmvoinsoilbalyeermictoontfilcuceenlcles owcacsurtrheeds(uambeouats6t3h%e)s.olAvtenttheconnetxrtollaonwderthdeosmeitoofti1c6i0ndepxg/wmaLs,otnhley somewhat reduced (about 27%). ChrInoimtoisaolTmrailaAlb--eNroratsiiognniAfiscsaanytsinWcirtehaosuest MinetcaebloslwiictAhccthivraotmioosnomal aberrations were observed for tdheeadcuclteulrlesanadnadlebyrziesd, (s7e5v0e,re10I0o0s,o1f5v0i0s,ibalnedm2i0to0t0icpgc/emllL,.)anUdnhsebaoultth2y5c%ellremdouncotliaoyneirns,clflloating umnohneoallatyheyrcceolnlfmlouneonlcaeyweersr,efolboasteirnvgeddeiandtcheellcsulatnudredsebdroisse,daweidhuct1i5o0n0 ainndth2e0n0u0mubge/roLf.viSsliibglhe:tly mitic cell, and about 159% reduction in cell monolayer confluence were observed in the cauplpteuarreesdd0osebdewailtmhos1t0n0o0mmga/lm,Lw.itAh otnhlylaoswleisgthtanraedluyczteidodnoisneothfe7n5u0mbpegr/omfLv,istihbelcelmlitmootnioclcaeylelrss arenldataibvoeuttoath1e5s%olrveednutcctoinotnroiln tcuhletudreegsr,eeoocfcucrornefdluaetnaclel.doSseevleerveelrsed(u9c5t%i,on8s6i%n,mi6t7o%ti,cainndde5x,7% at 2000, 1500, 1000, and 750 g/m, respectively). `Confimatory Trial--For the 20-hour harvest, no significant increases in cells with chromosomal aberrations were observed for anyofthe cultures analyzed (746, 995, 1490, and 1990 ug/ml). A m9i5to%tircediuncdteixonwainsmoibtsoetricveidndaetx7w4a6sgo/bmse.rvTedheatce1l9l9m0ogno/lmaLy;erwchoenrfelause,ncae2w5a%srreedduucctieodnbiyn bout 2To5%coamtpe1n9s9a0tpe,g/1m1L7 amnedtaopnhlayse8s3 wmeerteapshcaosreesdcforuolmdtbheesrcepolriecdatferocumltaunree,oiftnhoerdreerploicsactoerceulatutroetsa.l of f2r0o0mmtehteapchulatsuersesfodrostheids wdoisteh.2F4o9r, t4h9e8,447.416-,haonudr h9a9r5vegst/,mcLh.roNmoossoimgnailfiacbaenrtriantciroenassweesrien acenlallsywzietdh chromosomal aberrations were observed for anyofth cultures analyzed. Percent polyploidy was 193 00090 Osfc1or9e9d0atanthdis1h4a9r0veusgt/tmi.mewaenrde nleothsail.gniTfriecaatntmeinntcrweiatshes99w5erge/nmoLte.d.waTshesetvweorehliygthoexsitc,aprpelsiueltdidnogsiens agbomut,40H%owreevdeurc,titohnstiincmiotnyowlaaysemruccohnflleuesn(caebaonutd 7159%% rreedduuccttiioonniinncmointoftliucenicndyexa.ndAt1874%6 teduction in mitotic inde, compared to the solvent control cultures). ChrInoTimrtoiisaloamla--lCAhberroramteiosnoAmssaalysabWeirtrhatMieotnasbwoelriec Activation analyzed fromthe cultures dosed with 1250, 2500, 3in7c5r0e,asaensdi5n0c0el0lspgwi/tmhLcihnrothmeopsroemsaelncaebeorfrtahteiornastwievrre o5b9smeertvaebdoilnitchaectciuvlattuiroens sdyossteedm.wiStihgn3i7fi5c0ant a(rncdatSm0e0n0t gwa/smLhi.ghTlhyettoxrieca,tmceanutsiwnigthab3o7u5t05ug%/Lr.edwucatsiosnliignhtmloyntosliacy,erbcuotntfeluSe0n0c0ygTo/mLon.e culture aanndd aonbloyut9475m%etraepduhcatsisonweorretahnearleypzlsibcalteefcruoltmurte.h Fcluolatutriengwidtehadgrceelalstatnodxidcietbyr.isHowewreevearb,untdheant mitotic index was reduced by only 13%, compared tothe solvent control cultures. `aCboenrfniartmiaotnosr(ysTirmpilaeln--Fdorcotmhpel2e0x)howuarshaorbvseesrtv,eadsfoignitfhieccaunlttiunrcersedasoeseidn cweiltlhs 4w9it7h0cgh/rmoLm.osoThmiasl tinodxeixc.trTehaetmternetatrmeednutcewditthh 37c3on0fglu/emnc.y bcayuasbeodustb7ou0t%3a0n%d creaduuscetdioan4i3%threcdouncftliounenicnytahendmi1to8t%ic r4e.d1u-chtoiounr ihartvheestm,itnooisciginnidefxi.canTtheinrcerweaassesnoicclealsltsowgietnhiccahcrtoivmiotsyoombaslersvbeedraatti7o3ns0wuegr/eLo.bseFrovretdhe {frorcaatnmyenotftwhaesctu0l0tutroexsicanalyyizeeldd s(u4f9f8i,ci1e2n5t0m,e2t4a9p0h,as3e7s30fogr/anmaLl)ys.isA,litthwoausg,hnetvheer4t9he7l0espsg,/mnolt.ed hat t{hoeripceiryceenvtidpeonlty.pTlhoiedscuclclesisnfcurleaacsteidvsaitginoinfibcyantthley.meAttab3o7l3i0cgsymst,r wthaesrelwuasstaltietldeboyr nthot-l1aorge ienxcproesaesde itno pceyrccleonpthoeseplhsamwiitdhe.chromosomal aberatons (at 20 hours harvest) i the cultures ChroFmorostohema2l0-Ahboeurrrahtiaon rAsnsvaoysesigWsniitfthicoa,unttMientcarbeaosleiscnAcetilvlatiwoint;h-cFhoroumrosTroemaatlmesnbtertions were orhebadstuecortnvileoydnaiinnstmchaoelnlcfunllutunruceys waomnafasmlbeoybtzseaeedprh(va2ers5de0.,sH5oc0ow0ue,lvd1e2br5e,0,tehx2ea4mn9ie0nxetpdg.h/imgFLho)er.stthAdetos42e44,-9h30o7u4pr0gh/gamr/Lvm,esLta,,3w0a%s 50 toxic cphg/rmoLm.osAomsailgnaibfeircarnattiionncsrewaesreeianntahleynzeudmbreoromftcheelcluslwtuirtehscdhorsoemdowsiotmhaSl0a0b,er1r2a5t0i,on2s49w0a,saonbdse3r7v4e0d ainlstoheabcsuelrtvureedsidnohseedcwuilttuhre3s74d0ospegd/wmiLth(73.754%)0.uAg/smig.niRfeilcaanttiviencoretahseesionlpveenrtcecnotntproollysp,ltohiedy37w4a0s g`r/camtLmenttreraetsmuelnttedreisnualbteodutin3a0b%ourted5uc5t%iorn.eduTchteiomnitiontmiconionldaexywerascoanlfslouesnigcnyifaincdantthley 2r4e9d0ucpegd/mL. (575%) for the high dose. CONCLUSIONS "iTrheeatmeesnttasrotifclseh,oTr-t6d3u4r2a,tiwoans(egv.a,lu3ahtoeudras) bbeoitnhgicnltahsetopgreensiecnctoecaunldtuarbesdeCncHeOofcaenls5f9ormehtiagbhollyitcocxticivation `system. Polyploidy was also induced for the highly toxic treatments. REFERENCE 194 194 000091 HMaumlsit,eHreOmavlaartyha(.CH1O99)6.CelMlust:agweintihcaCiotynfTierstmoantoTr-y63A4s2s,ayMewaistuhrMiunlgtiCphlreoHmaorsveosmtas.l CAboemrirnagt-iHoanzseilntCohni,nIensce. (CHV). Vienna, VA. CHV Study No 17073-0-437C0. 195 000092 TLiytmlpe:hoMcuyttaegsenWiictihtyaTCeosntfoinrmTa-t6o3r4y2,AsMseaaysuWriitnhgMCuhltriopmloesHoamrave]sAtbserrations in Human Whole Blood `TESTSUBSTANCE Identity: T-6342; clear, colorless liquid, Remarks: No other information was given about puriyorsolubility METHOD `Method/Guideline followed: Protocol No.: 449C0, Edition No.: 2, Modified for 3M Corporation Test type: Invitro mutagenicity assay Test system: Human whole blood lymphocytes GLP: Yes Year study performed: 1996 `Species/Strain/cell-type/cell line; Human/whole blood lymphocytes MalestapbroeltriecataecdtiwviatthiAornocWliotrh 1a2n5d4wfiotrhtohuet nmoent-asbpoelciicfiacctiinvdautcitoinofnorfommeSt9absoupleirzniantgaentnzfyrmaecst.ionof livers of Concentrations tested: Range-finding assay--0.167, 0.500, Initial trial (withoutactivation) --127, 1.67, 5.00, 253, 505, 1160.17,0,501.501,0,16270,1500,0,25116070p,g/5m0L0;0 pg/mL; Initial rial (with activation)-- 253, 505, 1010, 1510, 2010,2510, 3010, 4010 pg/mL; Confirmatory rial (replicate 1600, 2000 pg/mL; cultures, without activation, 22.1 hour assay)--125, 250, 500, 900, 1200, Confirmatory trial (replicate cultures, without activation, 46.0 hour assay)--62.5, 125, 250, 500, 900, C1o2n00f,ir1m6a0t0o,ry20t0r0alp(gr/epmlLi;cate cultures, with activation, 22.1 hour assay and 46.0 hour assay)--250, 500, 1000, 1500, 2000, 2500, 3000 pg/mL. SFtiasthiesrt'iscaElxamcettTheosdts(uTsheadk:urSettatail.s,tic1a9l8a5n)atloysciosmepmaprleotyheedpaerCcoecnhtraagneo-Afrcmeiltlsagweitfhestabfeorrraltiineoanrs t(raenndd, ainfd atrpepaltiecdabcleel,lsthweitpherrceesunlttasgeforfomcevlleshicwliethcomntorroels.thTaneosntearatbcelrerastiigonni)f,icpaonlcyepwloaisdye,staanbdliesnhdeodrwehdeuprleicpa<0t.i0o1n. in All factors as stated previously were based upon scientific judgement. taken into account and the final evaluation of the test article was Remarks: `Experimental Design `heHpuamrainnivzeendoVuascubtlaoionedrfs.roCmualtsuirnegslew,enroermianla,theeadltwhiythm0a.l3emdLonoofrbwlaosodd/rSamwnLicnutlotsutreeri(lde,ose rangefinding assay) or 0.6 mLof blood/10.0 mL culture (chromosomal aberrations assays) in 15 mL 196 196 000093 caennatrtimfousgpehteurbees.ofTahbeouctel%s wCerOe iinncauibr.atTedhatcualptpurroexmiemadtieulmy u37sdCwoansaRsPloMpIe,1w6i4t0h (loRosHe caps, in Briaonsgcei-efnncdeisn)gsauspspalye;mLeontteNdo:wiTth0610524%,fcetharlobmoovsinoemaslersubmer(tFiBoSn;sBaisoscahye),me1d%, pLhotyttEoSh3e3m1a,glduotsiein (QuPaHliAtMy ;BioGliobgcioc)a,lsp)e,niacnidll2inm(M100L-ugnliutt/ammiLn;eQ(uQaulailtiytyBiBoiloolgoigciaclasl)sa)n.dDesiotnriezepdtwotmey(rc1(i0Pn0regpamred;at CdeHiVon,izLeodthwa2t0e) watasatchoncseonltvreanttoiofncohfoiSc0e0omgr/tmhLis.asTshaey.tTethartteisctlearstoilculteiwoanssadnidsstohlevevdehiincle control, deionized wate, were dosed witha dosing volume of 1% (10 uLmL) for this assay. NeganttivheeannodnaScotlivveanttioCnonatsrsoalyss, negative controls were cultures that contained only cells and culture cmoendcieunmtr.atSioolnveunstedcoinntrtoelstscwuelruerecsul(tu1r%esotrha1t0.c0onWtLainnLed)deIinotnhiezeacdtwiavatteironatasthseayhsi,ghtehsetnegative and Smoilxveinntclcuodnetdr.ols werethesamea described in the nonactivation assays, but with the $9 activation Posit"iTvhee pCoosnittriovleAcgoennttosl gens, which were used inthe assays, were mitomycin C (MMC; CAS# 500670-575,-1S9i-g2m,a,SiLgomat,4L0oHt2#54038H)0f2o69t)hinntohneacmteitvaabtoiloincsearciteisvaatnidoncsyecrlios.phIonspthheamcihdreom(CoPs;omCaAlS aribaelrsr;at0i.o1,ns0a2s,saaynsd, 0th3repegc/omnLce,ntthriartdiotnisa)ofaMndMCCP((200.,03a0,ndan0d.1500gg//mLm,)inwietrael aunsdedcoonfiinrdmucaet.ory cBohtvhomMosMoCmaalnadbeCrPratwieornes.dOisnsoolvfetdheindwoatserl.evels was analyzed i cachofthe aberration says. RangIen-tfhnedseinagssAasyss,aycsultures were iniiated with 0.3 mLofbloods mL culture and were incubated for 2 days prior to ucatment. Assa"yThWeiltyhmopuhtoMceyttaebsowleirceAcitnicvuabtaitoend:with he test arc for 195 hours at ~37C. The tet arile was Cwoalsheeedmifdrom(ftinhalcceolnscwenittrhapthioonsp=ha0t.1e-gb/ufmfLr)edwsaasliandedeadn. fTrheeshcuclotmuprlesetweemreedainudmhacrovnetsatiendin2g.0 hours later. AssIanytWhiistahssMaeyt,atbhoelilcymApchtoicvayttieosnwere incubated wittth est article fo3r hours at 37C in the p2.r7esmengc/eomLf)a.atThvee$r9Sf9rarcetaicotni(onMomliexctuulraer(T9ox-i1c5olloigmy,],IcN.A, DLoPtt= 016.657m)gw/amsL,dearnidveidsofcrtormicthaecid otnidveerotfomaavloeidSpporsasgiubel-eDianwalceiyvartaitosn, wohfsihcohrhaldivbeedeannpdrehviigohulsylryetarceiavteediwnittehrmAerdoicsleosrp1r2o54d,ucIend by tehxepoSs9ureenzpeyrmieods. tAhfrtoeurghthbeinedxipnogsutroespeerruiomdp,rtotheeicnse,sthweemreedwiausmheddidtnwoitcehwaivtehFbBuSffedruerdinsgaltihnee. `CCoolmcpelmetiedRP(fMiInalcuclotnucreenmtreadtiiounm=w0a.s1 agdd/emdLt)wthheiccuhltwuaress,adwdheidchfowretrhee iansctu2b.a0tehdouorrs 1to3.c5olhloeucrts metaphase calls 197 000092 AMistsoatyicEvianldueaxtwioans analyzed from the surviving dos levels by analyzing the numberofmetaphases present in 1000 consecutive cell. ChroTmnetshoemcehrAobemrorsaotmiaonlAabsesmaayt--ioWnitashsaaynsd, WeiptlhiocuateMceutltaubroelsicweArcetiuvsaetdioant cach dose level and for negative `hcaornvteroslts,impoesiitnivtehecoinnttioall,tiaanldasnodlvweintthc2o2n.t1ro-lsa.ndT4h6e.s0b-ehroruathiaorvaessstatyismweesrienctohendcuocntfeidrmwaittohry2 r2i2a.ls0.-hour Cpohsriotimvoescoomnatrlolabdeorsreastions were analyzed from the cultures reed at 4 dose levels and from oneofthe Chromosome Aberration Assay Without Metabolic Activation Culturceesntwreifrugienittbieat.edT2wdoaydsayprsaifortetrocturletautrmeenitnwaittiho0n.6emlLsowfewrheotlreeabteldoowdi/t1h0.th0emtLestcuarlttiucrleeiant 1p5remdeLtermined concentration for approximately 19.3 and 43.3 hours. The cultures were washed with buffered saline. oCoumrpsleatteer,RtPhMeIcel1l6s4w0emreedhiaurmv,esctoendtaainndinagir0-.d1ripedg/smiLd.esCowlecreemimadde,.wTahsepsaicdeeds wbaecrke otnationtehd icnel5ls%. Too aGietmsamsoslcuhtieodnulfeorthoftheanaableyrsriastiofoncsharsosmaoyswoimtahlouatbemrertaatbioonlsi.cTaactbilveat1iocnontains summaryof the CCuhlrtourmeesswoemreeAibetrreatdio2ndAasyssayprWioirth Mterteaabtomlenitc wAictthiv0a.t6iomnLofwhole blood/10.0 mL culue in 15 mL pcreentsreinfcuegeofbtehse.teTstwaoridlayesaafndtrthceul9turreeaicnttiaotnimoinx,tuhree.cuAltRuereshewe3r-ehoinucruebxaptoesduarte=p3e7rioCd,fotrhe3 cheolusrsweirnethe washed twice with buffered saline and the cells were refed with complete RPMI 1640 medium. One-tenth gllsmwrCeolhcaervmeisdtedwaansdapdrdeepdar1e0dtfhorccuylttougreenedtuirciannatlhyesilss.tT~a2b.l0e h1ocuornstoaifnisncusbusmiomna.ryThoeftmheetarpehsatsmeent schedule of the aberrations assay with metabolic activation. "The cell suspension was centrifuged, the supematant wasHdairsvceasrdtePdr,oacneddturhee cell were treated with hypotonic KCI (0.075 Mre)shflory~p1re0pmairneudtefsi.xaAtifvteer(acbesnotlruitfeugmaettihoannaonldgrlaecmioavlaalceotfitchaeciKdC, ,3:1, tvhxe)ce.llAiwre-rderwiadsshiedde3s wteirmeesprweiptahred. from the harvested cells. Slides were prepared by droppingSltihdeehParrevpeasrtaetdiocnulatnudreSstoainncilnegan slides The slides were stained with 5% Ganidemcsoavesrolsuitpipoend.forth analysis ofmitotic index an chromosomal aberrations. Al sides were air-dried (Cells were selected for good morpAbheorlroagtyioannsdAonnallyysciesllasnwditAhsstaheynEuvamlbueartoifoncentromeres cqual to the lmeovdeallsonfutmhebeers4t6arwteicrlee,atnhaelynzeegda.tiOvneechounndrtetdhrecseoolls,lvief,pocsoinbtrloel,, farnodmpeoascithirveepcloinctarteolcuclutlutruereast w4edroese aannaallyyzzeedd ffoorrtchherdoimfofsreonmtaltyapbeesrorafticohnrsofmioosmomthaolseabceurlrtautrieosnwsi(tEhva>n2s,5%19c6e2l)l.s Awitthleacshtr2o5moceslolmsawlere aIbneirtnoattiiocnasl.lsC/e|l0l0s0wcietllhs:abtehrerraattiioonswawsereexprreecsorsdeedd.asMpietortciecnitnadgeexowfamsitaostsiecssceeldlsb.yCahnraolymzaiindg tahnednumber of isochromatid gaps, if observed, were noted in the raw daa and were tabulated. They were no, however, 198 198 000095 cpoonlsyipdleorieddy ianndtheenedvoarleudautpiloincoaftitohne waebrieltaynoafltyhzeedtaesntdartthieclreesoultisndwuecreecthabruolmatoesdo.mal aberrations. Percent RESULTS Overall results: positive, negative, ambiguous: Negative Genotoxic effets (unconfirmed, dose-response, equivocal -- withAwithout activation: Negative. Cytotoxic concentration: Range-finding Assay Without Metabolic Activation 3He5m%o,l6ys%i,s3w8a%s,o1b5s%e,rv1e8d%p,ri5o7%t,o waansdh1i0n0t%hewceurletuorbessedrovseeddiwnitthhe 5mi0t0o0tigc/imndLi.ceRsoefdutchteiocnusltoufres dosed with 0.500, 1.67, 5.00, 16.7, 500, 1670, and 5000 gm. Range-finding Assay With Metabolic Activation 5He%m,o4l%ys,is1%w,asanodbs1e0r0v%edwperrieorotbosewravsehd iinn tmhietoctuilctuirnedsicdeososefdtwhiethcu5lt0u0r0espgd/omsLe.d wRietdhuc1t.i67o,ns50o.f0,8%, 500, 1670, and 5000 gm, as compared with the solvent control culture Chromosomal Aberration Assays Without Metabolic Activation ITnRiertdiiuaclatlio--nHsoefm3o8l%y,s1i8s%,w1a8s%o,bs5e0r%v,ed55pr%i,orintodw9a5s%h iinn tthhee mcuilttoutriecsidndoisceeds,waithco2m5p1a0rge/dmwLit.h the asonldve2n0t10conptgr/omlLc,ulrteusrpeesc,tiwveerlye.observed in the cultures treated with 127, 253, 505, 1010, 1510, `Confirmatory Trial--In the 22.1-hourconfirmatory ral, hemolysis was observed prior o wash of the cultures dosed with 1600 and 2000 g/mL, and a sight evidenceofhemolysis was evident at 9ha3r%vesitnotfhtehmeitcoutlitcurinedsidceoss,edaswciothmp1a6r0e0duwgiitmLtheResdoluvcetnitoncsonotfo2l%,cul1t4ur%e,s,6w4e%r,e7o4b%s,er9v3e%d,inanthde ccuolntfuirremsadtoorsyedtiwailt,hhe1m2o5,ly5s0i0s,w9a0s0,ob1s20e0r,ve1d6p0r0i,oarntdo w2a0s0h0 pofgt/hmeL,curletsupreecstidvoelsye.d Iwnitthhe1466000-ahnodur t2h0e0s0olgv/enmt.conRterdoulcctuilotnusroesf, w5e9r%e,o9b3s%e,rv9e8d%i,natnhedc9u8lt%urienstdhoesmeidtowtiitchi9n0d0ic,es1,20a0s,c1o6m0p0a,raenddw2it0h00 g/mL, respectively. Chromosomal Aberration Assays With Metabolic Activation InTaintrdiia4a0l10--Hpge/mmLo.lNyosicesllswawseroebsveisrivbeldepprriioor ttoo wthaesahddiinttihoenocufltCuorelscdeomsieddwtiothth2e0c1u0l,tu2r5e1s0d,o3s0e1d0, dwiotshed40wi1t0hg3/01m0.g/HemmLo.lyRseidsucwtaisonosbsoefrv1e5d%,pr2i0or%,to1t5h%e,ad4d3i%ti,o7no7f%,Coalncde9mi5d%eintothtehemictuolttiucres indices, as compared wih the solvent control cultures, were observed in th cultures treated with 253,505, 1010, 1510, 2010, and 2510 pgm, respectively. Confirmatory Trial--In the 22.1-hou confirmatory trial, hemolysis was observed prior o wash and prio o harvest ofthe cultures dosed with 2000, 2500, nd 3000 pg/mL. Reductions of 15%, 199 000096 c59u%l,tu6re9s%,,we8r2e%,ob9s7e%r,veadnidn1t0h0c%ulitnutrhees mriattoteidc wiindtihceSs0,0,as1c0o00m,pa1r5e00d,w2i0t0h0th, 25so0l,veanntdco3n0t0r0ol aungdimpLr,iorretsopehcatrivveelsyt.ofItnhtehecu4l6tu0r-ehsoduorsceodnfwiirtmha2t0o0r0y,t2ia5l0,0h,eamnodly3s0i0s0wga/smoLbs.erRveedducprtiioornfoowfa1s5h%, o5b0s%e,rv1e0d0i%n,tahnedcu1l0tu0r%esitnrtehaetemdiwtiotihc1i5n0d0i,ce2,00s0,c2o5m0p0a,raenddw3i0th00thge/smolLv,enrtescpoencttiovlelcyu.ltures, were wStiatthiosutticmaeltraebsoullitsc:scTthiveateisotn.substance did not significantly increase chromosomal aberrations with or Remarks: ChriomoosloTmralisAhb--erNroatsiiognniAfsicsaanytsinWcirtehaosuetinMectelalbsowliitchAccthirvoamtoiosnomal aberrations, plyploidy, or endoreduplication was observed at the concentrations analyzed (253, 505, 1010, 1510 g/mL). c`Chornofmiomsaotmoarly aTbreirarlat--i1onnst,hep22o.1-lboyurocpronelfnidroomradtiourpydlitrayiatli,,onnowsaigsniofbiscearntveidncartetahsee cionncceelnstrwaittihons i`anncarleyazseedi(n1c2e5l,s2w50i,lh5c00h,roamnods9o0m0alg/ambeLr)ra.tiIonnst,hepo4l6y.p0l-ohioduyr,coonrfeinrdmoarteodruypltirciaalt,inono wsiagsniofbiscaenrtved at ftohre icnodnuccetnitornaotifocnhsraonmaolyszoemdal(1a2b5e,r2r5a0ti,o5n0s0,waansds9h0o0wng/bmyLt)h.e iTnhceresaesnesditfirveitqyueonfctyhoefbcelrlrcautliuornes inthe cells exposed to MMC, the positive control gent. ChroInmiotisaolTmrailalAbeNrroatsiiognniAfiscsaanytsinWcirtehasMeeitnabcoelliscsAwictthicvahtrioomnosomal berratons, polyploidy, or endoreduplicaton was observed atth concentrations analyzed (505, 1010, 1510,and2010 ug/ml). h`rCoomonsfoimarlmTaarbietarlroatriyonsI,nthpeo2l2y.p1l-ohioduyr,coornefnidromraetdourpylitcialt,ionnowsaigsniofbiscearntveidncatretahse cionncceelnstrwtiitohns So`iangnlnayilfy5iz2ceadmnet(t2ia5n0pc,hrae5sa0es0es, iw1ne0c0re0el,asavianidtlha1b5cl0eh0rooprmg/oamnsLaol)my.asliIsnaibtnehreorna4et6i.oo0fnt-shh,oepuorclucyloptnluforiierdsymd,aotosorerdyetnrwdiioatrlhe,dd2uu0pe0lt0iocuagtti/oxominLc.iwtayN,so oibncsreeravseediantetnhdeorceodnucpenltircaattiioonnsatan2a0l0y0zegd/(m5L0.0, T10h00s,uc1c5e0s0s,fu2l00a0ctpivga/tmiLo)n,ofetxhceepmtetfoarboalwiceaskystem `wnaesaitlelduswtirtahtecdybcylopthheosipnhcarmeaisdeed,itnhceipdoesnicteoivfe ccolnltrowlitahgecnh.romosomal aberration in the cultures 200 20 000097 CONCLUSIONS `bTlhoeodteshtuamrtainclel,yTm-p6h3o4c2y,tewsacselclosnwsiitdheraenddnweigtahtoiuvte fmoertaibnodluiccinagctcihvartoiomno.soTmhaelseabreersrulattsiownesrienvceurlitfuireeddiwnhole. independently conducted confirmatory tials. MBluoloid, LHyemmaplhaotchyat.es19W96i.thMuatCagoennfiicmiattyoTreystAsosnaTy-W6i34t2h,MMuletaispulreinHagrCvehsrtosm.oCsoormnianlg-AHbaezrerlattoinon,sInicn.W(hCoHlVe), Vienna, VA. CHV Study No.: 17073-0-49CO. 201 000098 GENETIC TOXICITY (IN VIVO) "Tile: Mutagenicity test on T-6342 in an in vivo mouse micronucleus assay TESTSUBSTANCE Tdentity: T6342 iRnedmicaartekds.: Iti clear, colores liquid. The purity and chemical deny ofthe est substance were not METHOD `bMyeHtehdoddlGeueitdael.li(n1e98f3o).lloPwreodt:ocTolhNio.st4ud3y5,wEadsitcioonndu1c7t(endourseifnegremnocdeifgiicvaetni)o,nmsoodfitfhieedprfoorce3dMureCsorspuogrgateisotne.d Test type: Mouse micronucleus assay GLP: Yes Year studyperformed: 1995 `Species/Strain: Mouse/Crl:CD-1(ICR)BR Sex: Male and female No. animalssex/dose: 1ftoreatment groups, for control groups Vehicle (if used): Deionized water Route of administration: Oral gavage Doses: 1250, 2500, and 5000 mk; Doses selected onth basis ofa previous study Frequency oftreatment: Single dose Sitaetirstuincatlramnestfhoromdesdu(swehde:nTvhaeriaannacleyssiwseorfethhoemdoagtenwosusp)erofrroarnmekdtursainnsgfoArNmeOdV(Awhe(Wnivnaerri,an1c9e7s1)weorne heterogeneous) proportions ofels with icronucle pe animal. Ifthe ANOVA was significant ({sPii<mg0en.ia0fn5i)dc,asanetxDudcniofnmfebetirtne'ansttifto-rntoe.smtt(hDunnneegtatt,iv1e9c5o5n;tr1o9l.64)Awnaaslyusseesdwetoredepteerrfmoirnmeewdhsiecphardaotseelygfroorupesa,cihfahnayr,eswtere Rapepmraorxkimsa:teTlhye24a, 4n,iorwme72raehdoloursssedaftweirtdhotshiengapfprroperxitartacetaimonouofntthoeftbohnetemsatsrurboswt.anTceenaanndimeaultsha(n5imzaeldes fadeenimdoanl5iefzsee)mdwaewlaertsee)raw.sesrTieghnereadpnoosdiottmihlveeyccaoosnntstrirogolnlegdarnotiuopmsea.alcshTwhdeoerseen/dahotasrievvdeeswtictotnhitm$reo0lgmraognu/ipkm.galTcsyewcnelaronpeihdmooaslspsehda(5miimtdahelet(shCePa)vn.edhiB5colteh, control groups were cuthanzed afer 24 hours. Afr the bone marrow was collected, it was spread onto 202 202 000099 smliicdreo,nudcrlieedi,aannddtshteapioneldycwhitrhomMaatyc-Gerryutmhwroaclydtes(PoCEl)uatontndoGirimeoomcshnar.omaTthiecseirdyetshrwoecryetes(coNrCeEd)focrel ri. pOenrecetnhtomuiscarnodnPucCleEapteedracenlilmsabl awersoenetsohdreedt.otaTlhPeCfErperqeuesnecnytionftmhiecrsocnourceldeospitdiccfeilesld.waTsheexpnroersmsaeld as requencyofmicronucleiin this striaabiount 0.0-0.4% RESULTS Effect on mitotic index or PCEINCE ratio by dose level and sex: Troiment |Wart|_% Seamed PEs Ratlo PCEINCE [Males 1 Females | Males | Females Vehiclecontrol: |24h| 0.14 10,02 0021002 | 0641007 | 0631005 cp): 1250mgfke: [28T o281005 0.001000 | 0.691009 | 0751017 00.00607100.0020 | 00002211000022 || 00638611000088 | 0591005 2500 mle: [28h10121004 | 0041002 0.641005 0.021002 0.0210.02 0651 0.01 S000 mike 00.026011000047 | 00..01601100.0042 | 0801008 | 00.769411000057 | 0151005 | 0061002 | 0561010 | 0.63006 "Significantly differen from thecomes0p.o1n7d1i0n.g0v3ehiclecontrol (p<0.05. 0.1710.04 | 0.241005" Genotoie effects (unconfirmed, dose-response, equivocal): Negative Sotbasteirsvtiecdal results: No significant incirnmeicraonsucleeatsed polychromatc erythrocytes were gRreomuapraktsh:eD72uhoe0urthoxaircvietys,ttghreoPuCpwEe/rNeCsEigrnaitfiiocsaonftltyheomwaelretshaandtfhemvaelheiscflreocmontthoel5a0n0i0mamlg./kg dose 203 000100 coxcLusions The test teil, T-6342, did not induc significant increas in micronuclei bone marrow foauininidy polychromatic erythrocytes under the conditions ofthis assay and is considered negative in the mouse REFERENCE MTnae.rl,ViHe.nna1,99V5i.rgiMnuita.age3niMciCtoyrptoersattoionnT.-6S.42Painu,anMYn.wo movse micronucleus assy. Coming Hazleton 204 24 000101 GENETIC TOXICITY (IN VITRO) "HTuitmlea:nELvaylmupahtoicoynotefsthe Abilty ofT-7524 o Induce Chromosome Aberrations in Cultured Peripheral TESTSUBSTANCE Identity: T7524 Rpuermitayr;ktsh:e rTehmeaisnpiencgif2ic%grwaavsit|y-omfetthhyele-s2t0psyurbrsotlaindcienownae.s 1.23. Substance was a brown pase of98% METHOD `87M0e.t5h3o7d5/;GuJiadpealniensee Mfoilnlioswterdy:ofOHeEaClDthGauniddeWleilnfea4r7e3;anEdEJCapDainreescetiMvien6i7s/tSy4o8f/IEnEteCr;naOtPiPonTaSl GTuriaddeelianned Industry. Test type: Tn vito cytogenetics "Test systems Cultured human lymphocytes Gp: Y Year study performed: 2000 Specie/Straincell-typelell lie: cell obisined from healthy adult male volunteers "WTiyspteaorframtse,toabbtoaliincedacftriovmatCihoanrulseesdR:ivreart,lSiuvlerzfmeilcd,toGseormmaalnye.nzyAmneismarlosutwienreleyhporuespeadreadt fNrOomTOadXultinmaale (spSeOcPisa)l.ooRamtsunwdeerresitnajnedcatredd lianbtorraapteorriyonceoanldliytiwointsh,Aarsodcelsocrri1b2e5d4inintdhuecSetdainndacrodmOpoielr.atLiinvgerPsrowceerdeurweasshed and minced and supernwaatsausnetdforscivaion Concentrations tested: Without $9- First Experiment: 1000, 3330and 5000g/ml `Second Experiment: 33, 560, 1000, 1300, 1800, 2400,and 3330 gf. 333, 420,560, 750, 1000, 1300, and 1800 pg/ml With $9.1.8% vA) EExxppeerriimmeenntt 21:.1010000,03,333333,3aanndd55000000upgg//ml 205 000102 Test conditions: RacCuunllgttuuerreeFdmieondrdii4unmg,hToweuisrttsh:aanLddytwmiphhheooucay$9ecxurpletosuspreeedsc1i(v0es.el4laemcntdled0o.dooefsa(o9fh1me-agt7hm5y)2mployrechdao3ehnom2ra4gphlguhasun5idim8noyirwner4h.e5 e Fmabiesn)ee.ndceoTonhcfeeScwe9il-ltshmriexlsootfefHdofSo3rh2Si4nbtarhnadpnir4edn3scnhcceiruofbn9Ssmmeilx.uoflA9fe-lmem3ircwsedrheeonorltnsnosexspoas2fee0dr0c.aT2m(70e254n2t4abwuetorwenere fainegdeoifndmodseiaeeyvawfarse2c4hhossaenndf4o8.heBcaystegdeonsitchseeyl.sofdoserane.Tin 1, appropriate EoinFxcpTue-b7ra5it2emd4eniftno'r13:mlhLoycumrlpsuhwoeictyhmteaednsdiwuwemirtoehrocuuatlntSou9tr-heemdrifx2o.r04.A5f2theborrur(s2h4rashn,dtShtaehtceielenlxstpwonrs)ee.d riiBnnadssueepddlwioictnahtteh0emmlsitlHoeBttiSceSdinaddnoedsxesof osirheecmodonordsseytrtaohenggemenifcirinccdisnigndeaex-toyhfaehehtihglehoefwssetsttdcdoyoetsoegeevsneeeltidecsatwseasdsayna,pisprpeopxrdiompatithseetlmydihosteetsenvaeelxsbwhyeetapsspelvreoctxtmeAdcloocnrtlryhole0% e7El5xl2ps4erifoinrtmhe2en4trhe2:snaCca4le8lonsfiwSenrdehmecuabrwseeerndecfeioosr4fe8dSh.oancdeowtritfhhoerSc3maiiHcnBtxhSpeoSpsradensdiennndccuebpaolftiSecdamtien.smllA ecdurd3of esermseeodr aifTum-m, rfoart4m.e4n6t bu(t4werefihxaartvioenstteidmei)m.meTdhieatcellysarfeera2d4fhoarn2d44h5andfi4x5atiownimhe, S9-mix were ot rived afer Chromosome preparation: Duihne as:3 ofculture, el division was rsd by addin ofthe 8srp1ei3nsd0el0entirnphwmiiblaihtnodhrytcphoeolctshuoipnceiirncnea0t(.0a5.n65t% u(wg1s/m)lmpomevdoeidutm.)s.CeclThlhesiredafehteesrarttehiieoncneilnlatgc7uslCt.lurepAsewlleeerewbeycrpeenottsrowioifleulgweeednsifbomyre35ntmm,iinnthe cells were fixed with changesofmano: acetic aid Fat (31 v4). 7iSd9tend6ti%fpirc(ea1pt1aior)naetntihuoamnnbo:lerFtiahxnedrdgaernlodusplweueamnebeeddrr.wopiTpenwdoaodsnece.leaTwnehedersspiirddeeepssahrwiertdewaemlraeerki.emdeSwriisdteehsdhwfeoerNe2O4sTertOi0Xndsity1ud1aynmdix NtwhaietcneorsMtaaonidunnesdtefaondd1rm0y.-o3uTmnhiedndwwryiihhdec$os%v(w1ee4rs)eGclieeamrsead bsyolputiionn gi ainpxwyalteenre.bSelfiodrestweeyrewetrhesnenmbseeddeid amMeltayazpiheadsiewnsdeeprxershc1oo0sr0ei0ncgeu:lltsTu.rheesAmtwihteoaetsritct3nhaednmasiltoyostfaicbcalnechdcocenucleatnustrreanwtiaiosnesdewdteearipunpserdod;ibmhyaeceolhuiyngthSie0nsgt%ctohoenmcnoeurnmstbaeciroomonpfsared {iottheesoilnvdeenxtocfotnhle.solTvheentm. iCutleturiensdetx eofdthewiltohvaesedosre eevedandaloyszewdewraessasbooeutxahmsinseadmor he Chromosome sberatons. oWCfaocsuhnsrttoiumnckgosocovhemrreotmshobsrmotamrikeoenadsbefardrna.dtsicoAontrse:ed.aTstoAn1pr0ae0dvmeentitavipehsIsilee]echwsirtohwmeotrhseeoNmraeOnsTdpoOrmeXlaydsscapodedyredcl>pramiroerotwoeeerxeaanemdixnacamotidineoend obfymigrhet minicSrOosoctoappyhifsoresc,hrnoommoosroememestharprhaaisoenssw.erIehexamuimnbede.roOfenlry maeatphceosless(waipst x4 chcnhdroemdowsoemees25 Were analyzed. Numbers of cls with sberaonsin2d06mbesofseraons wre cao. 000103 RESULTS `Genotoxic effects: T-7524 did not cells with chromosome aberrations. induce a statisticallyorbiologically significant increase in numbers of CWyittohtoouxti$c-9c:oncentrations: 3 hr treatment;24 hr fixation: notoxic dose;highestdose tested 5000 pg/ml 24 h treatment; 24h fixation: 2400and 3330 pg/ml 48 h treatment; 48h fixation: 1300 and 1800 g/ml With $9 3hr treatment; 24 hr fixation: no toxic dose; highest dose tested 5000 ug/ml 3hr treatment; 48 hr fixation: no toxic dose; highest dose tested 5000 ug/ml. CONCLUSIONS `When tested without S-9 and with 24 h continuous treatment, T-7524, induced a statistically significant ninucmrbeeasroe finabtehrernatuimobnse.roHfowcehvreorm,owsohmeen agbaeprsraatrieonesxcaltu1d0e0d0thge/nmumbwehreonfgaabpesrrwaetrieonisnacrleudweidthiinntthheetotal `hciostnotriincuaoluscotnrteraotlmernatn.geBoefctahueseltahbiosraitnocrrye.asTehioscciunrcrreedasaetwtahesmniodtdsleeendoaste1o0n0l0y,pign/cmlludweidthga4p8s,hoaunrd the clahbroormatoosroymaendabneorriantciroenassseeoecn,cuerxrcelduwdiitnhg 4ga8phs caroentwiitnhoiunstthreehaitsmteonrti,catlhceoinntcrroelasreanigsenoofttchoenspiedrefroerdmitnog. constitute a positive response. Bcoansdeidtioonnsothfetahbeovseturdeys.ults, T-7524 is not lastogenic in human lymphocytes under the experimental Remarks: none REFERENCE NPeOrTipOhXe.ral 2H0u00m.anEvLaylmupahtoicoynteofst.heNAObiTliOtXy oPfroTj-e7c5t2N4u0mbIenrdu2c9e20C6h2r.omHoerstoomgeenAbboesrcrha,tiTohnes iNnetChuelrtluarnedds. 207 000102 Title: CHOHGPRT FORWARD MUTATION ASSAY - ISO (T-6889.7) Test Substance: Ammonium Perfluorooctanoate (FL-143) Identity: CAS: 3825-26-1; T6889.7 lRegmar.ks: The chemical was white, crystalline, solid; Lot# 332: at pH 4 -- 7 it was soluble at METHOD: Method/Guideline followed:for GenoBtiooxliocgiitcyalCaErvcailnuoagteinoincoiftyMeadnidcRaelprDoedvuiccteisv--e Ptoaxritci3t:yT,ests OECD Guideline #476ANSO/AAMUISO 109933: 1993 Hsic, 1981 "Test ype: In vitro gene mutation in mammalian cell in culture Test system: Chinese hamster ovary (CHO) cells GLP: Y ear study performed: 2002 Species/Strain/cell-type/cell line: CHO-K1 lineof CHO cells Metabolic acid, activation: Aroclor 1254 induced rat liver S9 homogenate plus NADP and isocitric C1o:1n2c8e,nt1r:2a5t6i,oannsdte1:52stdeid:luTteistonarstoicfletwhaes5dmigss/omlLvesdoilnutciuolntuwreermeetdeistuemd abtoathtwoiptdhoasnedowfithmogu/tmL. activation. SPthaatrimstaiccoallogmiectahloCdaslcuusleadt:ioSntsatPirstoicceadluprreo;gAraNm,OTVaAllaarniddaN,eRw.mS.ana-nKdeRuBl.s TMeusrtrafyo'rsConfirmation. Rteestmead.rkTsh:eTnheegraetiwveerceonntorosligonrifibcoatnhttphreotaocctoilvadteivoinatainodnsn.on-Daucptliivcaattieosonfasesaacyhs wcoanscceunlttruarteion were: dmeedmieutnhyy;lbtehnezpaotshirtaicveenceonftorrolthweaascteitvhaytliomnetahsasanye.suCluflotxuirdees fwoerrteheexnpono-saecdttiovacthieonmiacsaslayfoarnd17 hours fwoarsthheedn2onX-aacntdivsautpiponl-eamsesnatyeadnwditfohrc5omhpoluertseinmetdhieuamc.tivFaotritoyn-eaisgshaty.hoAfutresraenxdpo6s4u%rea,fcterllesxwpeorsuere tahnedcpelllastfeardom1 txhe10nocne-lalcstipvearti1o0n0amnudmadcitsih.vatTihoen acselslasywserreseppeactsisveedlyevweerrye4t-r7yp2sihnoiuzerds,tcoomuanitendt,ain exponential growth during phenotypic expression for6 days. Following phenotypic expression 208 208 000105 ells were grown in hypoxanthine-free Ham's F-12 medium with 10 uM 6-thioguanine, fetal `cboolvoinnieessetroudmevaenlodp.antCilboiontiincgs eaftfaicdieennsciytywaosf2dexte1r0m/i1n0e0dma mthPeetsraimdeitshimfeob9ry pdlaaytsintgo caelllloswinmutant cseolleocntyivfeomrmeadtiiounm. wAitthtohuetenthdoiofguthaeniinnec.ubBaottihonspeetsroiofdc,uplltautreesswweerree fiinxceudbiantemdetfhora9nodlaaynsdtsotaailnleodw. with Giemsa. Only colonies with 50 or more cells were counted. RESULTS Overall results: positive, negative, ambiguous: Negative GNeegnaottiovxeicboetfhfewcittsh(aunndcowniftihromuteda,ctdiovastei-orne.sponse, equivocal - with/without activation): C5y0t%otcoexllicsucrovnicvealntartaatidoinlu:tiBoontohfw1i:t1h28antdo 8wi0t%hoourtgmreetaatbeorlaictadcitliuvtaitoinoonfc1y:t5o1t2o.xicTihteysreandgoesedsfrom were chosen for treatment and are adequate. Statistical results: Negative cRoelmonairekssi:n tTrheaetetdesctualrttuircelsevdsidthnoosteiin ntheadcsotnatutriosltciccualeltluyress.ignPiofsiictainvteianncdrneeagasitneivteheconnutmroblesrroefacmtuetdaanst expected indicating that the test system was behaving properly. coxcLUsIoNs Author'sconclusions re ha th(tCesHtagOen)tdcoeelslsniontcuilntduurceesgheinseismcuotrarteicotnaisnsCihtiende,sehamsterovary REFERENCE SCoardphour,atD.ion2,00B2edCfoHrOd/,HMGAP,RTToxFiOcoRnWFAinRalDReMpUorTtA: T01I-O7N01A9-SGS1ASYub--miItStOed(Tto6:.838M9,.7S)t.ToPxaiulcon Minnesota 55144-1000. 209 000106 E TOXICI Title: An Acute Inhalation Toxicity StudyofT-2305 CoC in the Rat . TESTSUBSTANCE Identity: AmmoniumPerfluorooctanoate; CAS#: 3825-26-1 Remarks: Fine white powder, received from 3M Company; composition and purity not indicated. METHOD Method/guideline followed: Guideline number not stated. GLP: No Year study performed: 1979. `Species/Strain: RavSpraguc-Dawley (211 to 264 grams) Sex (Males/females/both): Both No. of animals/sex/dose: S/sex/group Routeof Administration: Inhalation dReelmiaverrkesd:inTahteotnaolmvionlaulmteeostfco96n0cenlittreartsoifondrwyasair1.8.6Thmeg/tLes,t wmiattheraiatlotwalasofsi1e7v.e9d0 agnrdampsaocfkteedstinmtaottehreial dcuyslti-nldaedreon faairWwraigshptasdussetd-fienteod tmheec3h2a.n3islimt.er gTlhaessfelxopworsautreoefcdhramybaeirr whaoussi16nglittheerst/emsitnuatnei.malTsheforreasnulting d`euxrpionsgurtehepeerixodopfoounsepohunourrre.meoTvh,aelafnrimoamtlshewecrheamobbesre,rvheodurfloyr fabon4rorhmoaulrssiagfntseratre1m5o-vmailnuftreoimntteesrtvaclhsamber, `and daily thereafter for 14 days prior to sacrifice. RESULTS Number of deaths at each dose level (by sex): There were no deaths. dReecmraeraksesd:acDtuivriitnyg, ltahbeoerxepdobsrueraethpienrgi,odg,atsphiesngt,udclyoasneidmeayless,exmhuicboitieddneaxscaelsdsiisvcehalragcer,iamnatdioinrarengdulsaarlivation, breathing. After removal `anogenitalfur (9/10), dry from rales the exposure chamber, red (6/10),redmaterial around nasal discharge the eyes (5/10), (10/10), yellow stainingofthe excessive salivation (4/10), excessive lacrimation (1/10),andbodytremors(1/10) were observed in the rats. Excessivesalivation, 210 210 000107 mlaatcerriimaaltioobnsaernvdebdoadryoutnredmtohresehyaedsaabtattheedtbwyothhoeuornpeo-shtouerxppoossutr-eexopbosseurvraetioobns.erRvaetdionnasaanlddtihsecrhearwgaes(n10o/r1e0d) `yellow staining ofthe `exposure observation. anogenital During the f1u4r-(d7a1y0o)bsaenrdvadtriyornalpeesri(o5d/,10e)xcweesrseivsetilllacsreiemnatatiotnhe(6o/n1e0)haonudr postsalivation `(m3o/i1s0t),ramluesco(i17d1n0a)swaelrdeisocbhsaerrgvee(d10in/t1h0)e,radtrsy. raWleeisg(h8/t1g0)a,indsrayprpeedarmaetdernioarlmaalr.ouNnedctrhoepsnoysfein(2d/i1n0g)s,sahnodwed lung discoloration in 8/10 rats (a higher than normal incidence). CONCLUSIONS I1t8w.6asmyc/onLcflourdoednefrhooumr.thIemsmteuddiyatreesuelftfsetthsatoftthreetaetstmesnubtswtearnceeeixscensostifvaetallatcorirmaattiaotn,a snaolmiviantailone,xdpeocsruearseeod.f yacetlivliotwy.stLaaibnionrgeodfbtrheeatahnion-gg,engiatsaplinfgu,r,claonsdindgroyfrtalhees.eyTehse, pmeurcsiositdenncaesoaflldaicsrcihmaartgieo,ni,rsraelgiuvlaatriborne,amthuicnogi,d s`neaesnaladtinsecchrarogpes,ydirnydircaaltees,tdhratythreedmamtaetreirailalmaaryouhnadvethaepnroosleonagneddomroirsetsirdauleaslaelfofnegctwaitth14ludanygs.discoloration REFERENCE Bio/dynamics Inc. 1979. An Acute Inhalation MN. Project No. 78-7184. Study of T-2305CoCin the Rat. 3M Company, St. Paul, 211 000108 ACUTE TOXICITY Title: Acute Oral Toxicity (LD) StudyinRats TESTSUBSTANCE Identity: AmmoniumPerfluorooctanoate; CASH: 3825-26-1 Remarks: White powder, 3M Lot No. 340; composition and purity not indicated METHOD Method/guideline followed: Guideline number not stated GLP (/N): No ear study performed: 1978 Species/Strain:RatCharles River CD. Sex (Males/females/both): both `Noufanmimalbs/seex/dorse: S/sex/dose Vehicle: 40% acetone/60% com oil Routeof Administration: Oral gavage R21e5m0armkgs/:kgTihena tvesotlmuamteeorifal1w0amsL/akdgm.iniTshteerreadtsatwtehieghfeodll1o8wi0n-g21d8osgealesvtelusd:y 1i0n0it,ia2t1i5on,. 4A6n4i,m1a0l0s0,wearned odabisleyrvtheedrefaofrtemrorfaorlaitytotaanldopfh1a4mdcaoyts.onBiocdsyigwnesigdhutrsinwgetrhee rfeircsotrfdoeudrihmomuerdsiaafteelrydopsriionrg,foatd2os4ihnoguarnsdanadt.7 `and 14 ofthe days. Animals that died on 14 day observation period. study were subjected to gross necropsy as were all survivors at the end RESULTS `cTohmeefaollloopwaciintgyc,lihnyipcoaltshiegrnmsiwcetroetooubcshe,rvaendd: dpeattohs.is,Sipgilnoseorebcsteirovne,dhyatponaecctirvoiptsyy,odfeacnriemaasleds wlihmibchtownee,reataxis, sftooumnadcdhse;adororstsaocmraicfhicsefdimlloerdiwbiutnhdfliunicdluidnecdl:ud1i)ngcodnagrekstrieodn,orpirtetdinfgluaind,d srtedomfaocchisincotnhtealiunnignsg;d2a)rkdirsetdended pinatretsitciunleastefimlalteedrwiailt;h stomachs red fluid; with and 4h)yppaelreedmiisccoolrotrhaitciokneonfedthmucloisvra;oSr) erosionofthe glandular mucosa: red staining around the nose and 3) mmouuctohs.a, Ahnyidmraolmsettrhaatosfutrhveiuvteertuosdaanyd 1m4othtaldedthcioclkoernateidosnotfotmhacehkmiudnceoyssa., Shiygpnesrweemriec glandular observed stomach at all 212 212 000109 treatment levels. Treatment terminal sacrifice did not appear to have an effect upon weightofthe animals that survived to Number of deaths at each dose level (by sex): 100 meg: 1/5 males, 0/5 females. 215 mykg: 0/5 males, 0S ferales. 464 mg/ke: 2/5 males, 3/5 females 1000 mgkg: 3/5 males, 5/5 females 2150 mgkg: 5/5 males, 5/5 females Remarks: CONCLUSIONS LDuDo ((fmeamlaeleratrsa)ts=) =68403m0gm/kgg,,wiwtiht3h9299--5-1165276mmgg//kkgg9955%%ccoonnffiiddeenncceelliimmiitt LD (combined sexes) = 540 mg/kg, with 389 -- 749 mg/kg 95% confidence limit REFERENCE FlIuntoermaadtiFolnuaolroRcehseeamricchalanFdC-D1e4v3elAocpumteentOrCaolrpTooxriactiitoyn.(SLDpiocn)soSrteuddybyin3RMatsC.om1p97a8n.y.Study No. 137-091, 213 000110 ACUTE TOXICITY Title: AcuteOral Toicty StoufTd666y9 inRats (OECD Guidelines) TEST SUBSTANCE Identity: AmmoniumPerfluorooctancate; CASH: 3825-26-1 Remarks:Puynot sated METHOD Method/guidelinefollowed: OECDGuidelines GLP (YN): Y [-- SpeciesStrain: alrbaiiof CniCoD (SDYBRstan Sex (MaleFemalesboth): bn Nuomfsnibmaliesexirloss Ssexdose Vetice disld water RouteofAdministration gavage mcReolmnsadrbukocsdt:yeadtDw1oe,sige2hs.t5o.,fTa 2h5e04rhad ionsudrw0sei0agthmeerdgte0st8w.ae2tr6re9itaelsatena,ddmwieAnilrstdr.oas1tei2oenweaelnesdkaswacoedr.dCaaldyiifnioincirasli1e4orbedsdyeear.svavtMoioloruntsmaelwisetroyef 10 weBChoredecsksswuewbiegerheetscfowneadrnuecstdedevthiecrdr mo1ain0ynDea(emydesm0sd,7oo, asamnnddai14monorngdeaftohr i1f3sdauysvandxocnesthdemd1oroiyn.gAolFl Daaym1s4, 214 74 000111 RESULTS LDSO: Males: > 500 mglkg Females: between 250 and 500 mgkg. Number of deaths at each dose level (by sex): 250 mg/kg ~ none; 500 mg/kg ~ 2/5 males and 5/5 females. Rmge/mkagrkasp:peaArleldannoimramlasl edxuhriibnigtetdhebostduydyweeixgchetptgafionr tthwroofuegmhaoluetsthtehastteuxdhyi.biAtleldarneidm-asltsaitnreedatfeadceast a2n50dor a wtheetaunriomgaelnisttarleaatreeda wwiitthhiSn0204mhgo/ukrgsowfetrees:t rmeadt-esrtiaailnaeddmfiancies,tryaetliloonw.-sCtlaiinniecdalorsiwgentsoufrtoogexniictiatly observed arca, in ypoactiviy, hunched posture, staggered gait, related lesions observed at necropsy, although and excessive at 250 mg/kg salvation. one female hTahderlearwgeerpeelnvoisteessti-nmbaotetrhial akirdenaesysin. thAetgSla0n0dumlga/rkgm,uocnoesamoafltehheadstaomcaacnhn,ibaanldisacdserciognhdfflaenmka,leonheafdeamaclleeahrafdlumiudlitniptlhee dark brown lumen of the bilateral hornsofthe uterus. CONCLUSIONS None were specified beyond the results. REFERENCE Glaza, SM. 1997. Acute Oral Toxicity StudyofT-6669 in Rats. Coming Hazleton Inc. CHW 61001760. January 10. Sponsored by 3M, St. Paul, Minnesota. OTHER 215 000112 ACUTE - SKIN IRRITATION Titles Primary Skin Irritation St--uRadbbiyts TESTSUBSTANCE Identity: T-1395 Remarks: no other identifying information was given. METHOD Note pH of test material: Not specified MAdemtihnoids/tGrautiidoenliannedfoElnlfoowrecde:menSitmiRleagrultaottieosnts,in FSeedcetrioanl 1R5e0gi0s.t4e1r,~ HVoalz.ar3d8o,usNoS.ubs1t8a7n,ceps. a2n1d01Ar9t+i,cle2s7, September 1973. Test Type:in vivo `Species/strain/cell type: albino rabbits Sex (males/females/both): Notspecified Numberofanimals/sex/dose: 6 total `Total dose: dry and after Doses of 0.5g were applicationofwater paltatcheedeonndoafntihnetaecxtpseirtiemaenndt.an abraded site. Sites were examined while Vehicle: Notspecified Length of time but there was no test material is indication about in contact with whether th site animal/cell; was washed. Wrappings were removed after 24 hours. Readings were also made at 72 hours. `Grading scale: Scores for erythema and eschar formationaswea ledelma formation were presented. `Rgermamar(k0.s5:g)Soifx taelstbimnaoterraibablitwsahsapdlatcheeidrohnaiarbrcaldieppde-ddrfyroormitnhteaicrt-bdarcykpsraenpdarfelatnekts,siatnesd, ftihveen tceonvtehrseodfwointeh `Agfatuezre 2p4athcohuerssaanndda7n2ihmopuerrsvitohues cmoavteerriinaglswwaesrewrraepmpoevdedaraonudndthtehedesgirteetoofkeeerpytthheembaaannddageedeinmaplawcaes. recorded according to a standardized scale (the Draize method). 216 216 000113 RESULTS dIentealcltecda.seNsoitcliisnriceaplorstiegdnsthweerperirmepaorrytesd.kin imitation scores were 0, indicating no reddening or swelling Primary irritation score: zero Remarks: There was no indicationof reliability and no QA/QC. CONCLUSIONS Based on the results, the substance was not classified as a primary irritant REFERENCE Gabriel, Karl. Summary of: `Submittedto 3M Company, Primary Skin Irritation Study 3M Center, St. Paul, MN. ~Rabbits. Performed by: Biosearch. OTHER General remarks: detailed report was This summary was based ona summary available. Therefore, the contentsofths report and summary, only limited in reference data tables. No to the protocols and resultsofthe study, ae limited. 217 000114 AC-BYUEIRRTITATEION Tis primary Bye ion St-uRdays TEST SUBSTANCE dent: T1395 [oO ---------- METHOD A-- MeNStoihpoeedrGtal1o9d7e3.iomde Efololomwed SiRmeigni0onssnFoSreettee1s50t0a.42.VoHyuzoaedaous S Substant cesandAvice, -- Speers ypo leine:adit albinorb Sex ualesfomateibothy: Notpid Nuomfsimbabsecxiorse Gigi ose Tota doe: 0.1 ramp, SLeongnthdof m3setnestlmat5e0rica omcoSnntaactlswisth sumac; Observation period: 1, 24, 45, 721, anSd d dey er 30r Secs nS ails wh 3008 ofwr Nor oe fotoonshe ets wr RESULTS Gorn: Wovspsitng 218 ** 000115 Irritation score: Acofnrjusnectci:vaAwlerceor4e,sanfdoriCno1rnreababaitntIhrsscwoerreewzaesro2s, (tfhorroualglhroaubtbihte).obIsnertvwaotiroanbbpietsr,iosdcores for `ACfoenrju3n0cstevc:ae wAlelresc4oarte1f-o4r8Chorsm,eaandanidncIriesasweedrte z6er1os7(2fohrrsalalnrdababtit5s)a.ndIn7odnaeysr.abIbnit| srcaobrbeistfhore score wpearsiod4.throughout the observation period and in 1 rabbit the score was throughout he observation I"ToolmusieBdyttoHaaszsaaersdsotuscsorSieu:bsoStcaonrcniensg.was done according o theIiusGuitdefroraGratdinegEdxe Description oflesions: None Remarks: None CONCLUSIONS "The ony conclusion providedi study was tha the tet substance was not an ocular icant. RwietmhoaurtkasddiTthiiosnaclonicnlfuosrimaotniiosnsounsptehcet sdcuoeri0ngtmheetphoosdi,titvehrsecoirseisoobwsaeyrvteodpdruorviindge tanh isntufdoyr.meHdojwuedvgemre,nt about the results. REFERENCE SGaubbrmiietlt,eKdartlo, 3SMuCmommapraynyof,: 3PMriCmeanrtyeE,ySet.IiPtaualt,ioMnNS.tud--y Rabbits. Performed by: Biosearch OTHER Gdeetnaeilreadlrrepeomratrwkass: aTvhaiilsasbluem.mTahreyrewfaosr,batsheedcoonntaesnutsmomfatrhiysrseupmormtarayn,d oinnlryefleirmeintceedfdoatahetapbrloest.ocoNlos and results of th study, are limited. 219 000116 ACUTE- EYE IRRITATION Title: PrEiyeImritaationr-Rabybit TEST SUBSTANCE Identity: 3M identified the test subsatsaT1n3c95e. Remarks: The test substance was notfurthercharacterized. METHOD Note pH oftest material: Not specified MmaetterhioadlGauriedtehloisenedefsoclrliobweedd:in TSehcetimoenth1o5d0s0.e4m2p-lHoayzearddionusthSeutbessttianngc,esevaalnudatAirotinc,leasn,dAgdrmaidniinsgtorfattihoen taenstd Enforcement Regulations, Federal Register, Vol. 38, No. 187p,. 27019, 27 Sept 1973. Test Type: in vivo `Speciesstrain/cell type or line: Albino rabbit/Not specified Sex (males/females/both): Not specified Numberofanimals/sex/dose: 6/single dose Total dose: 0.1 gram "Test conditions: The not reated and served test substance was instilled into the as controls. The test substance was right eyesofthe not washed from test the animals; the treated eyes. left eyes were. Lfoelnlgotwhinogfatdimmineitsetsrtatmiaotneorfitahleisteisntcsounbtsatacntcew.ith animallcell: The exposed eye was not washed Observation period: 1,24, 48, and 72 hours post-exposure; and 7 days post-cxposure Souctolriinnegd imne"tIhlousdtruasteedd:GuInitdeerpfroertaGtriaondoifngthEeyeresIrurlittsawtiaosn BmyadHeazianradcocuosrdSaunbcsteawnictesh"t.he greding system Remarks: Healthy young adult animals were usedinthis study. RESULTS Corrosive: Not specified sIurbrsittaatnicoen, s6c6orea:nimNaolsoveexrhailblitierditiartsioinistcaotrieonwascsorgievseon.f5Inadnidvi4du/a6lalny,im|alhsouerxhaifbtietreadppcloincjautnicotniovfatehiemitteasttion 220 220 000117 4scc8oonrhteoisunruosefda1ft0ot;rdtihasedpmlriaenymiasiitirnaaittniigootnonwofoftahtnheiemtaielsitsssaeunxbhdsitbcaiontnceejd.ucnIocintjaiuvtnaoc(ntiisivcaaotriiemosintaacntodiroenisns:cciodr5eensnceodoff62-i6ar,ntdraet.sipoe6nc6thiavaednliym)aulsp (0 adneicmraelasseedxhbiybidtaeyd7aocfotnhjeunsctiudvya,eattawthiicohntsicmoer2e/o6 f2an.iNmaolscoemxehiablitieidtaiitsonriwtastioobnssecrovreeds ionfa$naynodf1t/h6e animals throughout the study. o"Tuotollinuesdeidnt"oIlaussstersastesdorGeu:ideInftoerrpGrretaadtiinogn EofyethIerrietsautlitosnwBaysHmaazdaerdionuasccSourbdsatnancceewsi.ththe grading system Description of lesions: Not specified Remarks: None, CONCLUSIONS Rcoenmsairdekrse:d tBhaesteedstosnubtshtearnecseultiosboeftaipsrismtaurdyy aocnudlatrheasnoutrc;e usaegdrefeorwiitnhtetrhpirsetcionngctlhusiroens.ults, the authors REFERENCE 3M Company. 1976. Primary Eye Iiation Study-Rabbits. OTHER fReermearnkcse:0Tthhiespsroutmomcaolrsywanadsrbaesseudsoofnthaesustmumday,ryarreeploirmtit;edt.herefor,the contents ofthis summary, in 21 000118 ACUTE - SKIN IRRITATION "Title: Primary Skin rritation Test with T-3371 in Albino Rabbits TEST SUBSTANCE Identity: Riker Laboratories, Inc. identified the test substance as T-3371. Remarks: The test substance was not further characterized. METHOD Note pH of test material: Not specified Method Guideline followed: ICAO Test Type: in vivo Species/strain/eell type: RabbitNew Zealand White Albino Sex (males/females/both): Female Nuom fanimb als/e sex/dr ose: 3/exposureperiod Total dose: 0.5 gram Vehicle: None Lengthoftime test materialis in contact with animallcell: 3minutes, 1 hour,or 4 hours ``aTnedstflcaonnkdsitoifonesa:chOrnabebidt.ayFoprrioeractho raapbpbliitc,attiwoonotfestthseiteesstwesrubestsealneccet,ed.theThhaeirtewstassitsehsavweedrefrlaotmertalhetobatchke `temsitdlsiinteesofatnhdeobcacclkuadnedd awpiptrhox2i-imnacthelsyqu1a0rceengtaiumzeeteprastcahpeasr.t TThheeptaesttchseusbswtaenrceesweacsuraepdplwiietdht0gaeuazceh owfrtahpe; tehxepno,sutrhee pterruinodk.oAffeearchthaeneixmpaolsuwraespewrriaopd,pealdl wwritahppiimnpgesrvwieoruesreplmaosvtiecdsahnedettihnegtfesotrstihteesdwuerraetieoxnamofintehde for ineversible damage and scoredfor erythema and edema. g`rGardaidnigngscsaclaeleos fTh-e4a.uTtehsotrssiptreessweenrteedaslespoaorbatseerivreridtaftoironthsecoprreessefnorceeorryatbhseemancaenodfecdheemmai,caelacbhubra,seedscohanra, necrosis, and epithelial sloughing. Rroeommasrkwsi:thAfnoiomdaalnsdwwearteerhoofufseereddaindsitbaintduanr.d wire-mesh cages in temperature and humidity controlled m 2 000119 RESULTS Rheosuurlctosn:taTcthepetreisotd.suMbosdteanrcaetepreordyutcheedmairarnedveersdiebmlea,tiasssuweeldlamasagcehefmoilclaolwibnugma, 3-minute, 1- hour, and 4eschar, and necrosis were `fporloldouwciendg fcoalclhowcionntgaacltltpherreieod.contact periods. An endpoint was not achieved due to the extreme irritation Primary irritation score: Not reported Remarks: CONCLUSIONS `eTrhyetchheemmaiacnald perdoedmuac,ecdheirmriecvaelrsbibulren,tiessscuheard,aamnadgenetcorotshies.skIinnaodfeqfueamtaeleinaflobrimnaotiraobnbiwtas;s ipnrcelsuednitnegd miondteher:ate report to evaluate qualityofthestudyand validity ofthe conclusion. REFERENCE Primary Skin Laboratories, IIncci.taSti.onPaTuels,tMwiintnhesTo-t3a3.7E1xipnerAilmbeinnto R#a0b8bi8t3sE. B0190873.9 Safety Evaluation Laboratory, Riker 23 000120 AcuteTorry Tile: Ace On Tish Sry as TESTSUBSTANCE dentin: 3Midentified testseatT1s585 Remarks:Th stiswsnotfehrc. METHOD Mehotiguideline lle Not ciel GLP (Y/N): No Veneta peor 1976 Soo BS i 2000 gs Selemons: Maadflle Number suimslssions Sheen Veh: $0 Route ofAdis: Or Tetsmcooemnados:eEaxmch+sisptnwgaspwnedigSheoendgndmdeoesedT bydictadn maieswsoiofomnhpe cgsmsdubbessntean eemaet woermeSeeocoS o ndo weHonneson of hetbance Remarks: The stwaeredriiv nofodsrotwt fo 28hoespriodos RESULTS LDg: <1,000 mgrkg. Warrofesenthonave tyes. 00mg li,5 Sr Remark61%ofmales 09)ad80% fres4(45) dicot lnovginmioinothe se t ted 224 * 000121 gastric mucosa three surviving aannidmwarlistheixnhgi;bittheednnuombchearnogfeaniinmianlist,alwahnidchfienaxlhibboidtyedwtehiegshetsigns, was not specified. The CONCLUSIONS Remarks: The authors concluded the LD to be < 1,000 mg/kg; I agree with this conclusion. REEERENCE Acute Oral Toxicity in Rats-T-1585. 1976. 3M Company. OTHER Remarks: This this summary, in summary reference wtaosthbeaspreodtoocnoalssaunmdmraersyulrtseopfotrthseubstmuidtyt,edabryl3imMi;tetd.herefore, the contents of 25 000122 ACUTE - EYE IRRITATION Title: Primary Eye Irtation Study - Rabbits TESTSUBSTANCE Identity: T-1585 Remarks: No other specifications regarding the test substance were noted. METHOD Note pHoftest material: Not specified EMneftohrocde/mGeunitdeRlegiunleatfioolnlso,weFde:derSaelctRieognis1t5e0r,0.V4o2l.~3H8a,zNaor.do1u8s7,Supb.s2t7a01n9c,esSsenpdteAmrbtiecrle2s7,,A1d9m7i3n.istration and. Test Type: in vivo Speciesistratyipne/orcleilnel:Rabbit Albino Sex (males/females/both): Not specified Numberof animalsisex/dose; Gsingledose Total dose: 0.15 Length of time test materiisailn contact with animaicell: 7days Observation period: 1h, 24h, 481,721, 5.4, end 7d. HSaczoarridnogumseStuhbosdtaunsceeds:" Used grading system outlined in "Ulustraed Guide for Grading Eye Iitation by eRyeemasrerkvse;daTshaecotensttols.ubsTtahnectees(0t.m1agt)erwiaalswaadsminnoitstwearsehdeod trhoemrtihghtecyyeeso.feAatcehacrhabobibts,erwvhaitlieont,hethuenttrreaatteedd eyes were sored for comeal opacity and are, iis, and conjunctival redness, chemosis, and discharge. RESULTS Corrosive: Not specified =ri4t;aCtoinojnunscctoirvea:l dCiosrcnheaarlgepa=c3ity and area = 4; Iris = 2; Conjunctival redness = 2; Conjunctival chemmosis `Tool used to assess score: "[lustratedGuideforGradingEveIrtatonByHazardousSubstances." Descriptionoflesions: None 26 26 000123 `rReemmaairnkesd:thTehseamsceortehsrofuogrhaldlatyhe7.raObbniltys awesruemmthaersyatmaeblfeoorfesaccohrecastweagosrygiavennd,owbisterhvnaotidoens.crTihpteisoncoorfetshe effect. CONCLUSIONS `The test substanceis a presented in the report primary ocular to evaluate the iritant and requires qualityofthe study cautionary labeling. Inadequate information and the validity ofthe conclusions. is REFERENCE Biosearch, Inc. Paul, MN. 1976, Primary Eye Irritation Study ~ Rabbits. Philadelphia, PA. 3M Company. St. 227 000124 ee Acute TOXICITY Tite: Acute Dermal Toxicity StudyofT6342 in Rabbits ESTSUBSTANCE Mdentity: T6342 cea, colorless liquid. Remarks: None METHOD 4M0e4thoordDGeurimdaelliTnoeciftoyl.lowOeEd:CDOGECuDiGudiddleloiinneonTbePe2g0si7n1.witMhoestterlsikaenydtdiosnstho0ukdabehiOghE4C-D4 mGnuibdeerlsi.ne GLP: Yes Yearstudy performed: 1995 Specestesin: RabbitsHra(NZW)SPE Sex (malesfemalesboth): Both Numberofanimals/sex/dose: 5 males, femalessingle dose Total dose: 2000 mg/kg Velie: None Routeof administration: Dermal sRuebmsatrankcse:waTsheapriabibdisohathdetihnetahctaisrkicnl.ipTpehdefsrcoem othfeairplbiaccaktisonbewfoarse ctohevearpepdrowpirtihataesaumsoeunptorocfhtahnedtest. occocllaussivaenddrdersessinsgi.ngsCwolearsrwemeorveedu.sedTthoesteesttsaitetshewearneimwaals,heAdfwrithhetap34whaoruraenxdpdoisseppoesrieodp,apteher t{eoswtemla.terCilailniacdamlinoibssterravtaitoinonnsdantdwimcoertdaaliiltyytchheercekasfwefeor m14addeaysst.spBpordoyxiwmeiagthltys 1w,e3r.e5,dnedsr4mihnoudrsbehfoerre {`meiisntmutmaaeltsewraiefatrleerwerauetsmhoaavnpaipzlleidodf,antadheSDteasuty. bm7atjaenrdi0eaeoltntaDedoadyo.n19D.aTyshe3,in7i,ta1l0,dearmdal1di. aAttiohne rcenaddionfg twhaesstmuadyd,e t3h0e 228 25 000125 ------------ RESULTS Number of deaths at each dose level (by sex): none Remarks: All animals exceptionofone male appeared that lost normal weight daunrdinegxhtihbeitfeidrstbowdeyekw.eigDhetrgmaailnsimtihtraotuigohnocuotntshiestsetdudoyf, swliitghhtthteo vmiosdiebrleatleesieornysthweemrae,obesdeermvae,d aatndnecartoonpisay,. and The sdleirghmtaldeLsDqSuOa0miantiroabnb,itcsorwiaascegoruesanteesrst,haann2d00fi0ssmureingg.. No CONCLUSIONS p`TrhoedduecremdaslliLghDt StoomfodTe-r6a3t4e2dwearsmagl irrritatteihoann.a2N0o0t0cmligen/ickaglrisnigmnsaldeurainndgtfheemsatluedryabboirtsv.isiTbhleelteessitosnusbasttance necropsy were noted. REFERENCE PrGoljazeac,tIS.D:19H95W.I A5c0u8t0e03d7e4r.ma3ltMoCxoimciptaysntyu.dyoSt.fPTa-ul6,34M2Ni.n rabbits. Coming Hazelton, Inc. Madison, WI. 229 000126 SKIN SENSITIZATION DATA Tile: AssentofCont Hyperscsi0tT7i5t2y8 inthe Albin Gunes Pig (MximisionTes) TEST SUBSTANCE, ent: T7524 pReamtaerwkist:hPusripteycwiaesgr9a8v%istohfe c1o.3 msin24ivnags Lmehy2pyrlcinan. Subswtsanbrcoew METHOD MeCtohmoidsgsiiodnelDiinerfeoll9owed EECC; OmECeD GutifdoelrihnheedNouembsdam4as06n: Mofgxnseionsand,gstmaamnen1d9e7b0yd Stud duration: sho50udatys Lp am: Year studyperformed: 200 Sposa: Guineapig Dunkin Harley sin Sex Females Number of amaspe due group: 10st group: Sorel group Routeofadministration: Ieaderns snd idesn dinision fe------ Ci1no%dni,cce2atn4it,orna5t9ai,bo1on0ts3:5wS,hti2cahr0i%dnog3sa0en,dwsearines1g0d0e5s,orncondncousnnaistihoonorscrwhetlasnngae1k.9eVffomloettmhnstlTnohrwdeienwgs.smio s Vehicles osinised Ienrducetion emethos3d4:0ne1d8hdoe iecionsof fosconsewnstussed.Dermalecions Derm escons were ssesed 4and 43 hoesA fs expo-------- 230 #0 000127 Main study: Induction (concentration and method): 1:1 Day wi m1i:xtTuhrreeoefiFnrjeecutnido'nss wCeormeplmeatdeeAadtjuvcalnitppweidtshcwaaptuelra,r region: ates1t:1suwbistvamnicxetautr5e %ofco1n0c%enttersattisounb,staanndce with Freund's Adjuvant. `The vehicle was not indicated. Dbeatywe7:enTiennjepcteirocnenstitseso;dtihuims-pdroodveocykle-dsaulmfitled (iSnDflSa)mwmaatsoarpyprleiaecdtieopni.dermallyto aclippedarea aDraeya a8:ndFhiefltyd percent in place twesitthsuMbisctraonpcoerceontcaepne.traTthieondrweasssianpgplwiaesd epidermally to the SDS-treated removed aftr 48 hrs. Induction vehicle: Not indicated. Challenge (concentration and method): Day 22: A fifty percent concentrationofthe clipped flank. Vehicle was not indicated test substance was applied epidermally to the Challenge vehicle: Not indicated. Post-observation period: Sites were assessed 24 and 48 hours aftr induction and challenge phases. wGerraedignragdesdc.aleR:es`uTlhtesswoeurrceeoefvatlhuestsecdaaleccwoarsdinnogttionEdiCcarteidt,ebiuatfboortchlaisrsiitfaitciaotnioannadncdhallalbeelnignegrreeaqcutiiornesments for dangerous substances and preparations. Statistical methods used: None. Remarks: A reliability checkofthe hexylcinnamicaldehaysdae positive test (study date not indicated) was done using alphacontrol. Skin reactions were indicative ofa sensitisationrateof 100 percent for this compound. RESULTS `Toxic Body responselefects weights and body bwyeidgohsteglaeivnelw:erNeosimmoirltaarlibteytowceceunrrceondtarnoldsnaonsdytsrteeamtiecd gtrooxuipcist.y was observed. Induction treatment, and challenge scores: During induction, During challenge, no skin reactions were esvkiidnenetffaecftesrwcehraelleennhgaenicnetdrebaytetdhegr1o0up%sSaDnSd controls. Light yellow staining was seen challenge). The saining did not hamper sactotrhiengeosfttshubesstkainncer-eracetaitoensd. skin sites (24 and 48 hours post Sensitization: A sensitization rae of0 percent was determined. 231 000128 Remarks: none. CONCLUSIONS There was no evidence that T-7524 caused skin hypersensitivity in guinca pigs. Remarks: none, REFERENCE (NMOaTxiOmXi.sati2o0n0-1T.estA)s.sesNsOmeTnOtoXfPCroonjteaccttnuHympbeerrse2n9s2i0t2i7v.ityH0eTt-o7g5e2n4bion sthcTehA,elbNientoheGrulianndesa.Pig 22 22 000AZ9 ---------------------------------- REPEAT DOSE DATA "Title: 5 Daily Dose Oral Toxicity Study with T6669 in Rats TESTSUBSTANCE Identity: The test material CASRN 3825-26-1 was perfluorooctanoic acid, ammonium salt, T-6669 (FC-143), Lot No. 235., Remarks: Its described as a white powder that is 93-97% ammonium perfluorooctanoate. METHOD `Method guideline followed: The dated December 20, 1996 included sitnudthyewraespocrto.nducted in accordance with a company protocol TP678S Study duration: 20 days. GLP (YIN): Y Year study performed: 1997 Species/strain: RayCrl:CDE(SD)BR VAF/Plus Sex: Male Numberofanimals per dose group: 10 Route of administration: Oral gavage cDoonsseescutteisvteeddaayns.d frequency: 0, 5.0, 14.0, or 42.0 mg/kg/day. Doses were administered once daily for 5 Posttreatment observation period: 15 days S(tWaitniesrt,ica1l97m1e)t,hLoedvsenues'esd:TeMsetth(Loedvsenaer,e o1u9t6l0i)n,eadnidn Dtuhnenreetpto'rst amnuldtiipnlcelucdoemApaNrOisVoAn test (Dunnett, 1964). Remarks: Ina initiation; the pdreovtoicaotlitoantferdowmeithgehtpsrobteoctowle,etnhe21a0niamnadls25w0eigg. hTehdebeantiwmeaelns3w0e3raenpdro3v9i5degad tfosotdudaynd water ad libitum. Reverse osmosis water was used as the vehicle and the dose volume was 5 mL/kg. The `acnaigmeaalnsdweexraemoibnseedrvfeodr ctlwiinciecala sdiagynsfobremfoorrteadliotsyinagndanmdoraitbaupndpirtoyx.imaEtaeclhy a1n,i2m.a5,lawnads4rheomuorvsaefdtferroemaciths cdoolsleecatdemdinoinstDraaytiso-n2an(dprdeadiolsye,thtehreoaufgtehr.theBoprdoytwoecioglhsttsatwesertheatmetahesuprreeddodsaeilsy.ampBlleooids csoalmlpelcteesdwoenreDay -1), `6a,n9i,ma1l5,anadndwe20i.gheOdn. DTahye6r,igihvtelaatneirmalallsobpeeroftgrhoeupliwveerrewassaccroiflilceecdt,edanfdrotmheelaicvheranwiamsalr,ewmeoivgehdedf,roamndcach 23 000130 OannalDyazyed20f,orthpalrmeimtaoiylniCnogAanoixmiadlassewearcetivsiatcyr.ifiTcheed raenmdatihneiinglilvievresrwiesreucwolalsctalesdoacnodllweecitgedheadn.d weighed. RESULTS NOAEL (dose and effect): Greattheerltohwaenst42domseeks,tedthbeahsiegdheosnthoisgheertehsetepda.ticApNaOlmEitLoyo]fC<o5A0oxmiadkaese, activity was determined byth study author. 5L.O0 AmgE/Lkg(,dboasseeadnodnehffiegchte)r: heGpraetaitcerpatlhmainto4y2lmCgo/kAgo,xithdeasheigahcetsitvidtyosreeptoesrtteedd. inAstLuOdyE,L of cTloinliecalressigpnosnsweelreeffocbtsserbvyeddoiseanleyveglr:ouAplsl animals survived o scheduled sacrifice. Notreatmentrelated c5.0ontmroalkse): higher hepatic palmitoy] CoA oxidase activity (24 U/G compared to 5 1U/G for p14a.0lmimtgoyk]gC:osAignoixfiidcaasnetlayctrievdiutyce(d39meUanGbcoodmypwaeriegdhttoga$iUnsGdufroirngcdoontsrionlgs)period, higher hepatic p4a2l.m0imtgoy/lkgC:osAignoixfiidcaasnetlayctrievdiutyce(d39me1aU/nGbcoodmypwaeriegdhttogaiUnsGdurfionrgcdoonstirnoglsperiod, higher hepatic sSttaattiissttiiccaalllyrseisgnuisf:icaTnhtecolmopwaerremdetaoncbonotdryolWse(ipght0g.i05n)s forthe mid-and high-dose groups were GRoesmianrgkpse:rioTdh,otuhgeyhsthheowmeidd-raecnodvheirgyhu-sdaolselylvwietlhignrotuhpesfeixshi3bidtaeydsoawfeterr dboosdiyngwewiagshtcogmapilnesteddu.rinTghtehe overall mean body weight gains were not significantly diffrent between any groups. CONCLUSIONS i"Tnhdeicaauttihoonrosfptaetreodxtihastobmaesperdoloinfesriagtniiofni,caatntalilndcorseaeselsevienlsthteeslteevde,ltshoefnpoalefifteoctylleCveolAofox1i-d6as6e9ac1tievsitsy,thaann 5.0 mak when administered to male Crl:CDE(SD)BRVAFPlus8rats for consecutive days. pRaelmmaitrokys]:CoThAeaouxtidhaosredaecstiivgintay.tedHothweevneore,ffeencztylemveelinbdauscetdioonnmsaigynibfeictarnatnsiinecnrteaasneds iintthhe albevseelnscoefofther changes is not clearly indicative of oxic effet, therefore no LOAEL was detemined by this Study. REFERENCE MHaedniwsooond,,WSI.. 1L9a9b7o.ra5toDrayilPyroDjoescteIOdreantlifTiocraitcioint:y SCtHudWy w6i3t2h9-T1-976.6693Min,RSatt.sP.auClo,mMiNng Hazleton, Inc., 234 234 000131 REPEAT DOSE DATA "Title: 28-Day Oral Toxicity Study with FC-143 in Albino Mice; IBT NO. 8532-10655 TEST SUBSTANCE pIedrefnltuitoyr:oocFtlaunooartaed,PFFlOu,orFoCc-h1e1m6i,caFlCF-C12-61,43F,Ca-l1s6o9,reFferCre-d t1oo4arsa3Ps,F@OmAajaomrmcoonmipuomnesnatlt,ofaFmXm-o1n0i0u3m (To-c1t7a4no2iCcaocCi,d,LpoetnNtoa.de2c6a9f.luoro- ammonium salt, CASRN 3825-26-1), Remarks: The purity ofthe test substwaansncoet indicated. METHOD Method/guideline followed: Notstated Study duration: 28 days GLP (YIN): N Year study performed: 1977 Species/strain: Charles River CD albino mice: Sex: male and female Number of animalsperdose group: 10 (Smalesand females) Routeofadministration: Diet - Purina rat chow Doses tested and frequency: 0, 30, 100, 300, 1000, 3000, 10000, 30000 ppm Post-observation period: None Statistical methods used: A test was used to compare mean body weights, liver weights, and liver to body weight ratios among groups, butthe ype of test was not noted. Rmeeamsaurrkesm:entDasiwleyroebsteakrevna.tioGnrsosfsorpbaethhaovlioogriaclerxeaamcitnioantsioonr wmoarstacloitnideusctweedrea mfaidnea, saWcereifkilceyobnodayl wseuirvgihvting nmeiucter.alItbwuaesresadtefodrtmhaaltin"aforrepfruetsureenahtiisvteopsaetthoofloogrigcaenxsaamnindaottihoenr."tisHsouewsevwears,roermgoavnesdexanadmipnreedsewrevrede ninot specified. Liverweightsand liver 0body weightratioswerecalculated. Microscopie examination was b`uctontdhuectreedsuoltns,liivtehrsefarnoamlyesllessawcerrifeicceodmpmliectee.dS,armepnloestofinclilvuedresd.and blood were sent to 3M for analysis, 25 000132 RESULTS 'NOAEL (dose and effect): none; effects at all doses. nLeOcrAoEsiLs c(dyotsoeplaansdmiecffveacctu:ol3e0spipmd(uhcetpaptroocleiflelrualtaironh;ypcerretraospehdy;fhievpeatwoecieglhltu,lairncdreegaesneedravteiorntabnoddory `weight ratios; body weight loss). Tosi responseefects by dose level 31000ppppmm::(sicnecrLeOasAeEdLf)iver weights cyanosis hepatocellular degenersion andlor necrosis bile duct p5r0o0lpifpemr:aomnu;shceuplaatrocwelelkulnarehsypceorutgrhopehdyf;urc,ytcoypalnaossmiisceppiudtovcaeclulollaesr;dbeogdeyncwreaidgohntalnodsor neceosi; bile duct proliferation; body weight loss h31e00p00a00toppcppemml::lulmmaruusshccyuuplloaarrrrowweepaahkkynn:eecssysst;;oroplouaugsghmheiecddvffaurrc;u(ocblyeeafsnoor(sebiedsf;eoharetsphaddteuoarctiehnlgbluywledaareydke5g1))eneration and/or necrosis; 10000 ppm: muscular weakness; roughed fur (before death during week 1) 30000 ppm: muscular weakness; roughed fur (before death during week 1) Statistical resus: T(8h)eBfooldlyowwienigghptalroasmse:ters wre significantly diferentfom controls(a alevel ofat eatp < 0.05): 13000pppmm::mfaleesmataawtewleekeesks1+4; fematawelekes2s-4 1300000pppumn:: mmaalleess aatnwdefeekrsnl1e.s4atfwemeaelkes1a(awneimeaklss 1di3ed afer week 1) (1B30)00Appbposmmo::lutmmeaalllisvsearanwddefifgeehmmtaalilenescsrease: Not reported at other doses because mice died befor day 25. (3)0Replpamt:ivfeemliavleersweight increase: N1o0t0rpeppmor:temdaalteosther doses because ice died before day 28. Remarks: Body weight was suppressed in dose-related manner increased amounts of food were c310o00n00spuppmmpe:md aaanlldtmhhioiucggehheerfx:ocoeadpltlwma1asmtlaeelsweaadnsidealdfsewomiastleheeisnn.d2i6eddwaiytshoifnestthienfg.i9rdsaytsof esting. S3h0oawnedd1e0n0laprpgmemtecnstt garnoduopsr:diosnceolaonriamtiaolndoiefd|ionremaacrhegrlovupe.oNbo huielnrlsdleaatnhismaolcscusrarerdi.fcGerdosasfprat2h8odluopgey 236 #6 000133 CONCLUSIONS No concluwserieoginvesn by the study authors, lRoesmsaesrkins:micAlelfemdic3e0,fe1d00A,PoFrO30l0osptpwme.ighAt.doRseed-ruecltaitoendspainttbeorndywawseisgehatngianinthweedreeprfeoslsleodwebdodbyy wweeiigghhtts. Rpaetlhaotliovgeiacnaldeaxbasomliuntaetiloivneorfwkeiightdsnowereroetyhinescrreoarsgeadnsinbmeisicdeesfeldiv3e0rspips mnootrdmisocruessAedP.FTOr.eaGtrmoesnst.related cdihsacnogleosrawtieorneoofbs1 eorrvmedorinetlhievelrivleorbsesa. moHinsgtoalplatAhPolFoOgitcreeaxtaemdinanaitmiaolnosfinlclluAdiPnFgOentlraeragteedmemnitceanrdevoeraled daicfcfoumsepacnyiteopdlbaysmfioccaelnltoarmguelmtiefnotcoafl cheyptaotpolcaystmeisctvharcuooulgehso.utDtehgeenlievreart(ipoennalnobdu/loarr nheycpreorstirsoopfhhye)patocytes. and focal bile duct proliferwaatsialosno noted in mice within all groups. REFERENCE RCheipiosrtto,pIhnedru,stBr.iaalnBdiMoa-rTieasst,LAabJo.rat1o9r7i7e.s,2I8n-c.DaSytuOdryalNoT.oxi8c3i3t2y-1S0t6u5d5y,w3itMh RFeCf-e1r4e3ncien NAol.biTn-o1M7i4c2eC,oCFi,naLlot 269. 237 000134 REPEAT DOSE DATA Titles 28-Day Oral Toxicity Study with FC-143 in Albino Rats. TEST SUBSTANCE pIdeernftliutoyr:ooFcliaunoartaed,PFFlOu,orFoCc-h1e1m6i,caFlCF-C1-2164,3F,Ca-l1s6o9,reFfeCr-r1e4d3t,ooarsaPsFaOmAajaomrmcoonmipuonmesnatlt,ofamFXm-o1n0i0u3m (octanoic acid, pentadecafluoro-, ammonium salt, CASRN 3825-26-1), T-1742CoC, Lot No. 269. Remarks: Purityofthe test substance was not indicated METHOD Method/guideline followed: Not sated Study duration: 28 days GLP (YN): N Year study performed: 1977 `Species/strain: CharlesRiverCD albino rats Sex: male and female: Numberofanimals per dose group: 10 (S males and $ females) Routeofadministration: Diet - Purina rat chow Doses tested and frequency: 0, 30, 100, 300, 1000, 3000, 10000, 30000ppm Postobservation period: None Statistical methods used: body weight ratios among A test groups, was but tuhseedtytpoeocofmtepsatrewamseanont bsopdecyifwieeidg.hts, liver weights, and liver to `Rceomnasrumkpst:ionAnwirmaelsdewteerremionbesderweveekdldya.ilLyifvoerrcwlieniigchatlss,ibgnosdoyfwteoixigchittsy,. anBdodliyvewrewiegihgthatntdo fboooddy weight sruatrivoisvwiengreradt.eteIrtmiinseadteatdttehramtitnhael sstacurdiyficien.cluGdreodssa pcaotmhpolleotgeiceaxlaemxianmaitniaotnoiofngrwoassscpoantdhuocltoegdyoanndallAa w`ceoimgphleetdetsoedte@teorfmitniessrueelsatainvde organs were examined, but the specific lst is organ weight then stained for histopathologic not supplied. examination. Livers were Samples of liinvcelrusdeadn.d blood were sent to 3M for analysis, but the result, ifthe analyses were completed, are not 28 28 000135 RESULTS NOAEL (dose and effect): none; effects bserved at lowest test dose: LOAEL (dose and effect): 30 ppm (increased liver weight and hepatocyte hypertrophy) oTfoxteisctirnegs.poTnhseerleefwfeerctesnboypdroesmeatluerveeld:eaAtlhlsaonrimoatlhesrgcilvieninca1l0s0i0g0nsorof30t0ox0i0ciptypmin dtihcedotwhietrhignrotuhepsf.irsMtawleeesk. oatr3m0o0reppwemrsehsoiwgneidfisclaingthltylyrerdeudcuecdedinbaoddyoswee-idgehptegnadienns.t mBaonndeyr.weRiegdhucgaeidnsfoaomdoinngtaakeniwamsaefveidde1n0t0a0mopnpgm. aatmsonfegdacllitmhaerle10a0n0d ofrem3a0l0e0tpesptma.nimTarlesa.tmTenhte-rperlimtaerdymolerspihoonlcogoicncshiaonsgfetfsoecinadlthtolmiuvletriwfeorcealocbysteorpvleadsmic emunlltairfgoecmaelntto(dhiyfpfeusretreonplhayr)ogefmheenptatofohceyptaetsocaymtoensgwaansimsaelesn ianmeosntggarnoiumpasl0s,i3n0t,eastngdr1ou0p0sp3p0m0,an10d00, and 3000 ppm Ssttaattiissttiiccaalllyrseisgunlitfsi:caDnitfafer1e0n0c0easnidn b3o0d0y0pwpeimg.htAbbestowleuteen ltihveercownetioglhasnwdetrreeastimgneinfticgarnotulpysinwcerreeased for minaclreesasated30fo0rpmpalmesanadt 3in00f0empaplmes.at 1000 and 3000 ppm. Relative liver weight was significantly bReesmiadresksli:verGsr.osTshepamtahiolnoegfifceacltewxaasmfdoicadlntootmruelvteiaflocraclatcmyetnotp-lralsamtiecdenelfafrctgsemiennktoidfnehyespaotrocoyttheesr oarmgoannsg oafnihempaaltsocfyotde3s.00 Tphpme.seIvneraitnyi/dmeagtfeeedof1t0i0s0supepimnvoorlmvoermeentthoefetffhescet wlaessiomnusltwiafoscmalorteo dpirfofnusoeunecneladrignemmeanlte cfoesnttraonlimsaolns.ly bAbescoaluusteeoflivbeordwyeiwgehitgshtinrmeadulcetsioatn 1in00t0heahnidg3he0r0d0opspemanairmeanlso.t significantly different than. CONCLUSIONS "The authors gave no conclusion. Rweeimgahrtkgsa:insAlwlearneimraeldsuciendtihne t1h0e,g0r0o0uapnsdre3c0e,i0v0i0ngpp1m00g0roorupmsordieepdpbme.forReedthueceenddofofotdheintfairkset wwaeesko.bsBeordveyd in rats fed 1000 ppm or higher ina dose-related manner. TrReelaattmieventlirveerlawteeidgchhsanwgeersewienrcereoabsseedrvinedmailnetshefeldiv3e0rspapmmonorgmalolrAePaFndOftermeaalteedsafneidma3l0s0.pTphmeosrevmeorriet.y of effects was more pronounced in male test animals RMeEtFriEckR,EMN.CaEnd Maris, A.J. 1977. 28-Day Oral Toxicity Study with FC-143 in Albino Rats, Final 2R6e9p,orSte,pItnedmusbterria2l9B,i1o9-7T7e.st Laboratories, Inc. Study No. 8532-10654, 3M Reference No. T-1742CoC, Lot 29 000136 REPEAT DOSE DATA Titles Ninety-Day Subacute Rhesus Monkey Toxicity Study TESTSUBSTANCE Ipdeernitliutoyr:ooctFalnuooartaed,@PFFOlu,oFroCc-h1e1m6i,caFlC-F1C2-61,43F,C-a1l6so9,reFfCe-r1re4d3,tooraassPFaOmaAjoarmmcoomnpiounmensatlto,faFmXm-o1n0i03um (octanoic acid, pentadecafluoro-, ammonium salt, CASRN 3825-26-1) RMeNm.arTkhse:lotTnhuemtbesetrsoufbsFtCa-n1ce43usuesdedinitntihsisssttuuddyywawsasob3t4a0i.neTdhefrtoemsttshuebssptoannscoerw,a3sMa. Company, St. white powder. Paul, METHOD Method/guideline followed: Not stated Study duration: 90-day GLP (Y/N): No ear study performed: 1978 Species/strain: Rhesus monkey Sex: Male and female Number of animals per dose group: Two per sex per group Routeofadministration: Oralgavage Doses tested and frequency: 0 (control group), 3, 10, 30, and 100 mg/kg/day, 7 days/week, for 90 days Post-observation period: None bStyatsiexs.tiTcahlemteetsthsowdesruesceodm:paAlrledstbatyisatincaallysainsaolfysveasricaonmcpea(roendet-hweatyreclaatsmseinfticgartioounp)s, Bwairthtltehte'cotensttroflorgroup, homogeneity (1960) using and the appropriate t-test (for equal or unequal Dunnett's multiple comparison tables to judge sviagrniiafnicceasn)ceaosfddeisfcfreirbeencdebs.y Steel and Torrie: Rweermearukssed: iTntehnismastluedyt.heTshues mmoonnkkeeyyss (w2e.r6e0ho3u.s9e0d kign)diavniddua1l0lfyeimnahlaenrghiensguswimroenmkeesyhs,("2s9q5ue-ez3e.8t0ypkeg") cwaagsesfeadntdwmiacei/ndtaayinaenddifnraestheampppelraetsuwree,rehufmeiddi3ttyi,maesn/dweliegkh.t cWoantterrolwlaeds eanvvaiirlaobnlmeeandt.liPbuirtiunma. MPorinokretyo tCeshtow `msounbskteayncseiandgmionoidsthreaatlitohn,wetrhee sstealfefvcetteedrfionratrhieanstcuodny.duTchteedteasctocmopmlpeotuenpdh,yssiucsapleenxdaemdininat0i.o5n.% OMneltyhocel, wvaosluamdem.inTihsetesraemdebvyoglauvmaegeoaft af0.r5%eqMueetnhcoyceolf7 wdaasysg/iwveeenktofotrhe90vedhaiycsl.e Aclolntdrooslegsrwouepr.e gInidvievnidiunaalcdoanilsyt.ant doses were based upon the body weights obtained weekly. The monkeys were observed twice daily for 240 240 000137 `cgoennderuacltephdyisnitcahleacpopnetaorlanpceer,iobdehaanvdiomro,antnhdlpyhdaurrmiancgotthoersiucdssi.gnBs.loGoednearnadluprhiynseicsaalmpelxeasmiwnearteioonbstawienreed for a`Anfatleyrscisomfprloemtiaollnmoofnthkeeytsetonscubesdtuarnicnegadthmeinciosnttrraotlipoenrpieordi,odt,healn asguarivniv1iangnmd3onmkoenytshswearfeteansetsutdhyetniizteadtin. wadirtehnaSlesm,msypllaenen,(pPihteunitcayrcyl,iKdiidnneeyHsC,)t,esetxessainogvuairniast,eadn,dabnrdainncrwoeprseiewde.igAhtedn;ecrreopprseys,entthaetihveeartitssluievesr,were cwoalslewcetiedghiendbuafffterrefdixnateiuorn.alH1i0st%opfaortmhaollion.gyBwyaesspweerrfeorfmiexeddoinn Rtuhsfsoelll'owfiinxgatoivreg,anTsheftrhoymraolildmopanrkaetyhysrionid tchoerocnoanrtryovlesasnedlst)r,edatumoednetngurmo,upls:euad,rjeenajlusn,uamo,rtca,ecbuomn,e,cobrlaoinn,,teecstoupmh,agkuisd,neeyyse,s,ivgearl,lblluandgd,ers,kihne,art (with `pmaenscernetaesr,icrolsytmapth/untoedreu,s,etrirbojpuhnacrtyinognea(lboInyemmpahrrnoodwe),,msaalmivmaaryrgylagnlda,ndm, bnearrves(pwiintahl mcuosrcdl,ep)i,tusiptlaeryc,n, iSdteonmtaicfhy,intgestattetso/oo,vaarneds,antyhyirsosidu,esp(asr)atwhiytrhoilde,sitohnsy.muHsi,sttroapchaetah,oltoognysiwl,asonpgeuref,orumreindaoryn btlhaeddfeorl,lovwaignignso,rgans gfarlolmblaaldldmero,nkheeayrst i(nwtihteh ccoonrtornoalraynvdestsreelast)m,ednutogdreonuupsm:,aidlreeunma,lsj,ejauonrutm,,bconeec,umb,racion,lonc,sorpehcatguum,s,keiydense,ys, mliuvsecrl,el)u,ngs,plSekeinn,,pmaenscernetaesr,icprloystmaptheantoedreu,s,ritrbojpuhnacrtyinogne(ablolnyemmpahrrnoowd)e,, msaalimvasrry ylasnlda,ndl,unmebravres(pwiintahl cord, pviatguiintaa,ryi,dsetnotimfaycihn,g tteatsttoeos,/aonvadrains,ytthyirsosiude,s(psa)rawtihtyhrloeisdi,ontshymus, trachea, tonsil, tongue, rinary bladder, RESULTS NfrOotAhyEeLme(sdiossweearnedoecfcfaescit)o:nal0l(ycoonbtsreorlv)eadnadt3bomtgho/fktgh/edasye--dSoosfatgestloeovle,lm. odetromaartkeed diarchea, and LadOreAnaElsL, (bdoonseemaanrdroewff,ecstp)l:een3,0amngd/klgy/mdpahy--nColdiens,iacnadldseiagtnhsosf.toxicity, adverse histologic changes in the. Tleovxelisc. rTehsrpeoensmeolenfkfeeycstsibnythdeos3e0 lmegv/ekl:g/Tdhaeyrdeowsaagsengoromuorpt,aalnitdyaalt 4thmeo0n,k3,eyasndin1t0hmeg1/0k0g/mdga/ykgd/odsaaygedosage group, dicd during this study. 3domsgagkegl/edveal.y-- Soft stool andlor moderate to marked diarrhea, frothy emesis were noted at this p1a0lemga/nkdes/wdolalye--nTfhaecefodlulroiwnignwgeseykmp7,loanmds wblearceknsottoeoldsiduorniengmwoenekeky1:2.anorexia during week 4, t3h0esmeg3kgmodnakye--yTshwreeree manoonrkexeiycs. dAileld4dmuroinnkgewyeseiknst7i,s1g2r,oaunpds1h3oofwetdheslisgthutdyt.oFmordoemrawteee,kan4,d sofomtehteifmaecse asenvdergeu,mdsecwreeraesendotaectdiviintya.ilI4nmaoddnikteiyosn., sOwtohlelrensyfamcpet,oemyess,obasnedrvveudlvian,saomewleallal pallor st`omoolnsk,edyeshyidnrcaltuidoend,tphteosfioslloofwtihneg:eyeemleisdiss,,anatdaxlioas,sobflabcokdy weight. The surviving male had dpleactreleeatss.edPnruomtbhreormsobifneirymtehraoncdytaecst,idvaetcerdeapsreodthhreommobgilnobtiinm,edweecrreeaaslesdo ihnecmraetaoscerdi.t,Thaensdeininccrreeaasseeds walekraelianpeppahroesnpthaatta| smeonletvhelbsuattwoenreemmouncthh m(3o6r5evmsar59k7edinatthtehrceoenmtornot)hsw.hicThhepreerswisetsed# idnectrheeaosneein surviving male (3v6s 8051 IU inthe control) at3 months. SGOT levels were reduced at one. 21 000138 ee mthoentcohnt(o5l9).vsS29GPUT/lwainstehleevcaotnetdroat) a| nmdoninthth(e4o4nve saurcvoinvtrionlg mvaallueeaotf31m5oIntUh)sa(n8d8 avst345mo[nUt/lhsin (14665vm5g3/110I0Uml)i.nthTeotcaolnptrrooltegirnouapn)d. alChboulmeisnteirnotlhiinatnhiemoanlewseurrevirveidnugcemda:letotwaalspreolteeviantewda(s254.05v2sv5. aDucrointnrgotl hlevpealthooflo8g.i2c1a8l/s1t0u0diemsl,athnd ftoolalloawlinbgumcionmwpaosun2d.-00elvaseadcsonytmrpotlolmevselweofr4e.8ob2segr/v1e0d0imnl. myaploecealnldufaermiayleofmtohnekebyosn:e mmaarrrkoewd,lainpiddmdoedpelertaitoenoafttrohpehyadorfenlaylmsp,hloiigdhtfotlolimcoledseorfatthee spicen and Iymph nodes. t1h0e0mstukdy. Idneayd--ditiAolnl,mtohenkmeoynskefyrsominthtehis10g0romugp/ksgh/odwaeyddtohseasguemleevseilgdnisoedftdouxriicnigtwyeaesktshe2 of dmoosnakgeeygsrdoouspe(dan3o0remxgia/,dfaroyt.hyHeomewseivse,rp,altehefsacieg,nspaolfetgoxuimcsi,tysowboslelrevnefdacien tahned1e0ye0sm,gd/ekcgr/edaasyed aocbtsievirtvye,dpirnostthaet3i0onm,gb/okdgy/dwaeyigdhotsalogses,graonudp.boDduyritnrgemtbhleinpga)thsoplpoegiacraeldsctaurdlieesr,ihnteh foSltluodwyintghan was cdeopmlpetoiuonnodfetlhaeteaddrseynmalpst,osmisghwterteo moobdseerravteed ibnypmoacleelalnldarfteymaofltehmeonbkoenyes:mamrarorwk,edandidfmfuosdeerlaiptied atrophyof lymphoid follicles ofthe spleen andlymph nodes. Stthaeti3s0timcaa/lkrae/sdulatys:doTsahgeerelewveerledaurtiinsgtcwaelelky s1i3gnoiftfihceansttuddeyc.reTasheesfienmbaloedymowneikgehytsfoorftthhee m30almeg/mkogn/kdaeyy.s at dStoastaigsteiclaelvleylsaingndiftihceanmtorviakreiaytsioonfstihnes1e0x0-gmrgo/ukpg/mdeaayndwoesiagghetsleovefal wfeerweoarlgraenasdyocdceuardreadt tbheitswteimeen. the caobnstorloulteanadndexrpeleartiimveenhteaalrtgrwoeuipgsh.tTohre fsetamtailsetiscailnlythseig1n0ifmigca/nktgv/adraiyatdioonssagweergerotuhpe (fpol<lo0w.i0n5g,: pd<ecr0e.0a1s,ed raensdpeicnicvreelays)e,d dreelcarteiavseepditaubistoalruytweebigrhatnfwoerimgahltefsorinftehmeal3esmgi/nktgh/ed1a0ymdgo/skagg/edgaryoduops(apg<e g0.r0o5u).p (Tphe<s0e.01), valatreiraattiioonnss.were ofunknown biological significance and were not accompanied by morphologic Rgreomuapr(k1s1:7 Fv5ol8l9owmien/g1o0n0emmloinntthhoefcornetaotl)m.enT,hgeluacuotsheowrassofstihgneifriepcoarnttlaytreilbeuvtaetetdhiisn0th.e s3inmggl/ekhgi/gdhayvalue f1o1r2,m1a0l5e,#a7n3d6612w0hmogh/a1d00a vmia.luGeloufco1s31e.leTvehle otinhetrheth1r0eeamndon3k0emygs/ikng/thdeay3 mgrgo/ukpgs/dwaeyregr1o0u4pahnadd1l2e2vels of m8e1/,190,08m3l,,nrdesp6e6ctmivge/l1y,00afmtlrionntehemoconntthroolf,tr3e,a1t0meanntd. 3A0tmtehrkege/mdoanythgsroofuprsersestpmeectni,vegllyu.coSseGPleTvewlsaswere e"Tlhdevraetewderientnhoe t1r0eaatnmden3t0emlagt/eddcahyangdeosseingruoruinpaslyastis| msotnutdhs, batutanwyerteimceompperairoadblseudtioecdo.ntrol at 3 months. CONCLUSIONS "mTahrertoewst,ssupblsetean,ncnedcaluysemdphclniondiceasl,saingndsodefatthosxiicnitmy,alaedvaenrdsefehmiastloeltoghiecsucshamnognekseiynstwheheadnreandamlisn,ibstoenreed at dosage levelsof 30 and 100 mgka/day. Remarks:Thetet substance was not sufficiently characterized. REFERENCE 22 242 000139 M3oMnCkoemypTaonxyi,ciItnyteSrtnuadty.ionLaalbRoersaetaorrychstaunddyDneuvmebleorpm1e3n7-t0C9o0r.poration. 1978. Ninety-Day Subacute Rhesus 243 000140 TCiytnleo:m2o6l-gWueseMkonCkaepyssu.le Toxicity Study with Ammonium Perfluorooctanoate (APFO) in TEST SUBSTANCE Identity: Ammonium Perfluoroctancate (PFO); Perfluorooctanoate (PFOA) Remarks: APFOa White Powder; Lot 332; 95.2%pure METHOD Method/guideline followed: No guideline followed. Study duration: 40 weeks, 26-week treatment period, followed by 13 weeks recovery. GLP (YN): Year study performed: 1998/1999 Species/strain: Cynomolgus monkeys Sex: Males Numberofanimals per dose group: 6 animals/group for groups 1,3, and 4; 4 animal/group or group 2. Routeof administration: Oral capsule D`moeskegs/tdeasytefdoarn2d6fwreeeqkusencyofadministration: 0 mg/kg/day, 3 me/kgday, 10 mefke/ or 30120 Post-observation period: 13 weeks SAtNatCisOtiVcaAl,mecotvhaordisatues-eadd:jLusetveednmee'asntse,s 5f%ortvwaor-itaanicleedhoprmoobgaebnieliittyy:leAveNlOVA, Dunnett's test Rtoexmicairtyk.s:WhDeosnidnogosifnagnwiamsalrsesinumtehed3o0nmDga/ykg2/2d,aaynidmoaslesgrreocuepivweads2s0tmogp/pekdg/fdraoymadnadysthi1s1-gr2o1upbewcaasuse of designated the 30/20 mg/kg/day. foAnrismiganlssowferpeooorbsheeravlethd otrwiacbenodraimlaylfboerhmaovritoarl;itfyooadndcomnosruimbupntdiiotnywaansd awsesreseseexdaqmuailnietadtiavtellye.astOpohntchealdmaiilcy: ``weexraemirneactoirodnesdwweereekdloynbeefboerfeorteheinsittaiartoifotnorefattrmeeanttm,enotnaDnadydu|orifntgrweeatemkesnt26aanndw4e0e.dByotdheyrcwaefiegrh.tBdlaotoad astnadrtuorfinreesaatmmpelnetsawnedraet csoplelceicftieeddfoinrtcelrivnailcsadluhreinmgattorleoagtym,enctliannidcalrecchoevmeriys.tryB,loaondd suarminpalleyssiwsebreefoarlesothteaken "fTohrehfoorlmloonwiendgeotregramnisnawteironesweighed at scheduled and unscheduled sacrifices; paired organs were weighed spaerpaatrhaytreoliyd:.adOrregnaaln (t2o),bobdaiynw,eeipgihdtipdeyrmciesnt(2a)g,eskiadnndeyor(g2)a,nitvoerb,rapianncwreeiagsh,ttreasttiisos(2w)e,raendctahlcyurloaitded(.2) with 244 244 000141 "dTuhoedfeomlulmo,wienpgiidsisduyemsiswe(2r)e, ceoslolpehcatgeudsf,oreyheisst[oppraetsheorlvoegdy:inaDadveidnso(n2'),safoirxtaat,ivbera(i2n),,cefecmuumr,wciotlhonb,one `lumnagr,romwes(eanrttiecruilcarlsyumrpfhacneoodfte,emadmismtaalreyndg)l,angda,llpbalnacdrdeears,,hpeiatrutitlarey,up,rojsetjautne,umr,ecktiudmn,eyssal(i2v)a,rylegslioannsd, liver, t[hmoarnadciibc,ulaanrd(l2u)m,bsacri)a,tiscpnenrv,e,ssteemmiunmalwvietshicbloen(e2)m,asrkreolewt,alstmoumsacclhe,(etshtigsh[,(S2)inp,resspeirnvaeldcionrdBo(uciernv'iscal, Solution, thymus, thyroid (2) with parathyroid, trachea and urinary bladder. Brelcooovde,ruyrifnoer PanFdOfAcecosncweenrteractoilolnecatneadlydsuersi.ngInWaededikti2ona,nbdleovoedrwya2swceoelklesctheedrefarfotmerthdeurainnigmatlreiantmGernotuapnd tchoaltlewcatesdswaicrtihfoiuctedanitnimcooargiubluanntd,cmoandiinttiaoinn.edAnatimraolosmwteermepenroattufraes,teadnbdefaolrleowceoldltcoticolonts.. SSaammpplleesswweerree coenndtrryifiucegedanwditshhiinpapnehdotuor3oMfcfoolrleacntailoyns,iss.erum was harvested and sored at ~10C to ~30C until packed `sWahcoilfeceb,lodoidviwdaeds icnotloleacptperdofxrimoamttehleyveeqnuaalcsaivzaoedfesaamcphleasnoifmasleratumbo(tcholslcehcetdeudlweidtahonudtuannsfcihceodaguulleadnt), wC.hoWlheoblleoobdloaonddwpalsascmolaluecstiendg fprootmastshieuamnEimDaTlsAianstthheecoannttircoolaggurloaunpt,atStaemrpmlineaslwsearcerisfitcoereudsiantg--s1o0dtiou3m0 hweapsarcienntarsifaungaendtaicnodagsuelpaanrta,teOdnei-nthoalpflawsamsatarnadnsrfeedrrbeldoiondtoceclrlsy.otTuhbeesplaansdmpaooalnedd.reTdhbeloroedmacienlilsngweornee-half pfrooozleendoannddrtyraincsefetror3edMinftoorcproysosfiubbleesf.uAtlulresaanmapllyesisswere stored frozen at -60C to ~80C until shipped Acotllleeacsttio2nmfLoroPfFuOriAnedeatnedrmainaletaisotns5.goAfnfiemcaless wweerree cnooltlfeacstteeddabtetfhoeresacomleleicmtieoans. bUlroionde fwoarssecorlulmected on w1e0t3cMe;fobroatnhaluyrsiisn.e and feces were collected overnight; stored at 10C to ~30C wat shipped on dry ice A`Thneosna-fmoprlmeawlians lwieveirgshaemdp,lleawsahsfrcoozlelnecitnedlifqruiodmneiatcrhogaenn,ismtaoraetdbaott6h 0schCedtuol~e8d0anCdaunndscshheidpupleeddfsraoczreinfiocen. dry ce to 3M for analysis. `aTchteivriitgyhatnlaaltyesreasl.loRbeeporefstehneialtvievre wsaamspcloelsolefctleidverr,ormigehatcahnadnliemfalteasttense,carnodpspyanfcorrepaaslmwietroeylcoCloleActoexdidfarsoem: each anima for cell proliferation evaluation using proliferation cel nuclear antigen (PCNA). Alilqluaidvaniiatbrloegebnilaen(dusptoore5d matL~)6w0asC ctool~l8ec0teCduanttbilotshhispcpheeddutloetdheanUdniuvnesrcshietdyoulfeDdusnadciefeicfeosr,bfilleasahc-ifdrozen in determination. "tThheepdreecsitsuidoynttiomaenpaelryizoed,blcoololdecftoirotneDstaoysste3r5o,ne6w6,a9s4m,aadneda1f8t3eratnedrmriencaolvsearcyriDfaicyes. A2l2i0q,u2o4ts8oafnpdl2a7s6mawefrreom sent to Ani Lytics Inc. where they were analyzed for testosterone. Rleoswulotrs:noNfOoAodELcon(dsousmeptainodn,efmfielctdllyevien)c:re1a0semdg/tkglgy/cdearyi,ddeesa;tha;ndhympoodaecriavtieyt;o wmeairgkhetdloisnsc;reeaswesorinnsoefreucmes; eanndzycmreeatcionneceknitnraastei)oannsd(ia.mialsdplarytiantceraemaisneodtrsaenrsufmerbalsee,alciadniconnecaenmtirnaotiiroannsferas, sorbitol dehydrogenase, 245 000142 LOAEL no food c(odnossuemapntdioenf;femcitlldelvyeli:nc3r0eamsge/dktgr/idgalyyc,erdiedaetsh;;mhoydpeoraactieivtioym;awrekiegdhtinlcorses;asfeeswinorsenroufmeceensz;ylmoew. or ccroenacteinnteraktiinoansse)i.ac.naadspmairltdatley aimnicnroetarsaendsfseerrausme,bialleanaicnied acmoinncoenttrraantsifoenr.ase, sorbitol dehydrogenase, and n`Tooxfiocodrecsopnosnusmepbtyiodno;semilledvlely:i3n0c/re2a0smegd/tkrei/gdlyacye:riddeeast;ha;nhdypmoialcdilvyittoy,mowdeeirgahttelloyssd,ecfreewasoerdnaobsfeocleust,elow or `noenaetctoeprhmiilnactoeudnti,n tmootarlipbruontdeicnoncdointcieonntraantdioonnaendforalwbuhmointcroenactemnternattwioans. sTtowpopeadnibmeaclasusneotfhitsoxdiocsietygrhoaudp, mildly increased scrum bile acid concentrations. `Sbtaotdiystwiecialghrtescuhsa:ngSetsatfiostriGcarloluypsi4gnwiefriceanstiglnoiwfeicranbtoldyylwoewiegrhtthadnurcionngtrWoelsedkur2ifnogrWGereokusp 47,a9niamnadls2;4.mean Spteartciesntitcaaglelsy significant increases in mean absolute liver in animalsfromall dose groups at terminal weight and mean liver-to-body weight sacrifice. Mean liver to brain weight was significantly sacrifice. increased in animals in the 10 mg/kg/day dose group. No effects were noted at recovery Remarks `Two animals, one male from the 30/20 mg/kg/day dose `group ware sacrificed in moribund condition during the gstruoduyp. aTnhdeomnaelmeailnetfherom the 3 mg/kg/day dose: w3e0i2g0htmlgo/sks,g/fdeawyodronsoe fgercoeusp, lwoaws osracnroifficoeoddocnonDsauymp2t9i.oTnhiasndantihmeaelnteixrheibbiotdeyd wsaigsnscoofldhtyopotahcettivoiutcyh,before. cdleiantihc.alTshiegnasniomfallimfirtoemd uthsee 3anmdg/pkarga/ldyasyisdoofstehgerhoiunpdwlaismbssa,craitfaixcieadaonndDhaypyoa1c37t.ivTehibsehaanviiomra,l fsehwowfeecdes and no food consumption. tMhaelyeslogstivweenig3h0tmdgu/rkign/gdwaeyefkro1omfDtaryesat1m-e1n1t.hBaadsceldinoicnalthseisgenssoigfnfse,wtrfeeactemsenatnwdalsowstfoopopdedcoonnsuDmapyti1o1naanndd `wgarsounpotwarsestuhmeneddeusnitiglnaDtaeyd t2h2e. 3W0h/e20nmtgr/ekatgm/ednatywdaosseregsruoumpe.d,Ofthtehdeorseemwaainsilnogwaenriemdaltos 2i0n tmhgi/skggr/oduapy,;otnhliys 2`mtgo/lkegr/adtaedy twhaiss dhoasleteldeovenl Dfaorysth4e3r(emWaeienkin7g),2636w(eWekeseokft1r0e),atamenntd$.1 (TrWeeaetkme1n2t)ofrteshpreecteivmeallye.sClgiinviecnal30s7i2gn0s `iTnhtehaenseimaanlismaalpspeianrceldudteodrtehcionvearppferaormanccoem,pfoeunwdo-rrenloafteecdese,ffleocwtsowrintohifno3odweceonkssuamfpetriocne,ssaantdiowneoifght loss. treatment. Mean body weight changes were notably lower during Weeks 1 and 2 for males receiving 30 mg/kg/day. wDuarsirnegswuemeedk 2, at ths change was statistically significant. Treatment was stopped on Day 20 mg/kg/day on Day 21, mean body weight changes were significantly 11 and lower when than it cloonwterrolfsordutrheinmgalWeesekinst7h,e930a/n2d02m4,g/Okvge/rdaalyl mdoesaengbroodupy.weight changes through Week 27 were notably. `"gTrhoeurpe twhaast waansinccornesaisdeedreidnctiodebnecteorefatlmoewntorrenlaotefdo.od consumption for animals in the 30/20 mg/kg/day dose. `There were no consistent or clearly dose-related effects on estrone, estradiol, estriol, thyroid simulating hormone, or testosterone that were seen in any treatment group over time. In general, thyroid hormones. 246 246 000143 TwreirfeoddoetchryeraosneidnebergeimnaniinnegdodneDpraeyss3e5ditnharnoiumgahlDsaiyn t1h8e31i0notrhe303/02200mgm/gk/gk/gdadyosdeogsreogurpo.uTpost.al hyrosin wonasthdyercorxeiansewdasbemgoisntnipnrgoonnouDnacyed33atiDnaayni3m5alisn aadnmiimnailsstaedrmeidni1s0toerre3d071200mmgg//kkgg/dAaPyFaOndpDerayday6.6 Tinhe effect aonbismearlvsedadcmitihneirstienrtehde3a0st203 mmgo/nktgh/sdoafy.doTshienrgeoarfed,urtinhgetfhfeecrtebceovgearnytpohdaismeinofitshheanedxpreerciomveentr.y vNaoschanges in chlocestokinin concentrations were seen over time in ther dose group. t"Troeraotmmeanlteswafsrosmtotphpee3d0b/e2c0amugs/eokgf/pdoaoyrdhoesaeltghr,ouhpa,dtmhoednereatseactroifmiacrekdeodniDnacryea2s9edansderounme efnorzywmhe.om ccroenacteinnteraktiinoansse)(i.an. daaspmairltdatleyaimnicnroetarsaendssfeerrausme,baillanaicnied acomnicneonttrraantsifoenr.ase, sorbitol dehydrogenase, and Autr3inmalgy/siksg. /Adta3y0o/r2010mgmkgg/k/gd/adyayt,heArePFwOerhslnigaohtefinfdccrtesasoens ihnemtaritgollyocgeyri,decocaognucleanttiroant,icolnisniacnadl cmhielmdisttory, or `"mTowdoeraantiemadlescrienasthees 3in02ab0somlgu/tkegn/eduatyrodpohsilecgoruounpthoatdamparrokteedilnycoinnccernetarsaetdisoneraunmdeanlzbuymmienacctoinvcietnitersatainodn. mildly increased serum bie acid concentrations. r"Tehceorveerwyaspenroioedvidence ofpersistentordelayed tox effects on clinical pathology tes rsuls during the Eornhteasntceseodfcerlaltperodliafneirmaatliso.n was equivocal in the liversoftreated monkeys; it was not seen in the pancreas "sTahcreirfeicwee,riennclotudrienagtmlevnet,raedlraetneadl,mascprleoesnc,oppainccroremaisc,raonsdctoepstiisc.cThhaenrgeesweinreannyootrrgeaatnmsenat.trheeltaetremdienfaflects on ltievremrinwaeligbhotdcyhwaeniggehstsscoernonat taebrsmoilnuatle soarcrrielfaitcievweeorregarnevweersiigbhltesaoverretciomvee.ryThsearcreifniocetrinadtimceantti-negltahttedthe `macroscopic or microscopic findings at ecovery sacrifice. Oefsotphheagtewaolmaanldesgassatcrricifliecseidoninsathmatorwiebruenidncdoicnadtiitvieono,fathneimnajlueryftrhoamt otchceu3r0r/e2d0dmugr/inkgg/ddoasyindgosaendgrloivueprhad lesionsthatwere presumed tobedue toth test material. Thecauseofdeath in the male from th3e `mg/kg/day dose group was not determined. Ngrionuephsu1n,d2r,ed3 faonrdty4saenvdenselnitve1r, s3eMra,fuorriannealaynsdisfedcuersinsgamtpheletsrewaetrmeenctolplheacsteedoftfrhoemsmtoudnyk.eOyfstihnet9re4a7tment rSaemcpolveesr,y 2p0ha2sweeorfethseersutmu,d1y9a,wteortealolifve9r, 2s7a2mpwleersefurroimneGarnodup2s721 waenrde3fweceersesspencimteon3s.MDfuorrianngaltyhseis. OF athnedseu,ri3n2ewsearmeplseesrwuemrsepeacniamleynzse,d4atw3eMr;e lfievcearl, s2a8mwpelrees wureirneesahnidpp2e8dwteorCeenftecreesAsnpaelcyitimceanls,LaSbeorruamt,orliievserfor analysis. Samples were analyzed for PFOA. eStehryal, alcievtear,tea.ndExutrriancetswewreereexatnraalcytzeedduussiinnggahniognh--ppaeirrfionrgmarnecaegelnitquaindcdhmreotmhaytlo-gerrarp-bhuyt<yleecttherros(pMraByE/i)anodrem `amnadsslisvpeercwterroemeqturaynt(iHtaPtLeCd-bEySe/xMtSe/maMlS)cailnibtrhaetimounlt(iwpiltehoruetspaonnisnetmeomnailtsotrainndgarmdodree.ferPeFncOe)A, lwehvielle itnheseurraine a`asnsaalyyssiwsewraesbpeelrofwortmheedlobwyerinltiemrintaolfcqauliabnrtaittiaotnio(nwi(thLOaQn)inftoermtahlesctoamndpaorudnrdefoefreinnctee).resA;llinblsaonmkes iinnstthancleivser u07 000144 tfhleuobrloacnhkesmiwcearlesaibnouvneexthpeosLeOdQmfoonrkseeyrasaenraduarnidnleivsear,mprlaebsb,itBseecraauasnedthleivreerwwearseuesneddoagsenosuusrrloegvaetles moaftrix. `exMtornakceteyduwriitnhe wacaestounsietdiefo,rfsitlatenrdeadrdtihzraotuigohnaangdlaQssCacsraomdpilseesfiilnetrh,epuarsisneedatnharloyvsiigsh. FeccaarlbosnamSpPlEescwoelruemn amentdhacnololle.ctTedh.eTchoembcionleudmnesxtwraecrtesewleurteedewviatphoraacteetodnittoraillemofsotlldorwyendesbsyasncdetroenciontsitliitaustceodrwbiitchacmiedthianrol 0a fsiunratlovgaotleusmteanodfa2rdmLbu.tTwhaessuasmepdloenslwyetroemaonnailtyozretdhueseifnfgiceileencctyroofsptrhaeyeLxCt/raMcSti/oMnSp.roTcHedPuFrOeSanwdawsaussenodtas 3. used to calculate the amountof PFOA in the est samples. Msaamtpilxesspwiekreessapmipkleedswwietrheeptrheepramroednkferoymacnodn/torrolrasbabmiplseesoafatsaerian,allivceornacnendturraitnieonwoifth25e0ac-h50b0atcnhg./mSLe.ra aLpipvreorxsiammaptleelsyw6e0rnegsipmiLk.edThateselelveevleolfs aapppprrooxxiimmaatteeltyhe25ba0cnkgg/rgoaunndd luervienlessianmtphleessrwee,rleivsepriakenddautrine of the Group 1 (0 mg/kg/day) monkeys. LHoowwevleevre,lstohefsPeFleOvAelswewreereofstiegnnidfeitceacnttleydlionwtehre tsheaan,tlhiovesre,fuoruinnde ainndthfeecleoswo(f3thmeg/Gkrgo/udpay1)adnoismealasn.imals. PFOA was found in the sera, lverurine and fecesoftreated animals; levels increased with dose. AflrtohmoturgehatPedFaOnAimwalasswdeetreectsiegdniifnitchaentsleyrhuimg,helirvetrh,aunrtihnoesaensdeefneciensotfhceocnonttrroolls.anPimFaOlA, lleevveellss inn ttihsesuseesra of t3e6s.t1aunigm/amllsiinnGcrreoausepd2wiatnhimdaolsseabnudt d1e5c9r7ea+se2d39o2vpegr/timmLeidnuGrrinogutpre4aatmneinmt.alSseornumDalyev9elts0w5e2n.5t from9.11426 + hurginmeLanidn Gfercoeuspal2soa.nd $1.5 + 77.6 ugimL in Group 4 during Weeks 26:27. This seems to be the case for oLnevDelasyi9n athnedu5r1in.e6%we1r3e.77,31.50.9%.4378.51.,2,2a2n1d&1192.42,+a2n7d.900u9:g+ 2r0e9spuecgt/ivLelyiinnGtrhoeuspessu2,m3e,garnodup4srDeuspreicntgi.vely W7e4e3k6.256.4I,n t1h5e.4fe%ce1s0,.2PaFnOdA5le6ve+l.s7w36e.r7eulges/sigtnhaGnrtohupsli2m,it3,ofaqnudan4tritaetiosn ipthedeucrcoinntgrtWoleiaenikvm2alaesn,dalwndeyre 2St9o2p.p4ed1,35P,F4O3A.0le4ve36l.9s inabnodth1u0.r3inea20n.d8 ufegcegsduferliln0gWleeveelks2t6ha.tAwsermeigchotmbpaereaxbpleectteodc,onotnrcoel tlreevaetlmsenDtu.ring GWereokusp338s-a3m4p,lelse.veTlsheirnethiesnfoeceexspolfatnahteicoonntforrotlhaenhiimaglhslweeverles 0o.f27P9FO+A0s.e7e32n uign/tgheanfd e0.oc3f8e7th+se0c.o3n7t2roiln aalntihmoaulgshdiutriinogbWveioeuksl2y2.exPcFreOtAedaipnpbeoatrhs tuoribnee parnedfefreecnetsiatlhlryoeuxgchroeuttedtrienattmheentu.rine rather than the feces PSeFrOuAm ilnevGerlsouipn s3earsucmoamlpsardeedcrteas0e.d07o3v8er t0i.m0e0d2u5r6inigtrheeccoovnetrryonlstdiurtihnegyWreeaeckhe4d0.1.18 + 0.827 pg/mL. Iontestdiifmfeicpuelrtio0d,dWraewekan2y7,fifromrcwohnicclhusdiaotnasfaobroluitvecroamnpdarsaetriuvme claevnelbseicnolmipvaerreadn.dAsterthuimsspioncte,tlheevreelsisionnly siseornulmyatpipseaornefoibmeehipgohienrttahaainlatbhloesefoirn ctohempfaivreri.soTniasndsbneoctaausdeefdionsitiinvgoe sfttahteeemeenatnhimoawlesveinrtbheec3a0u.s2e0there m27g,lksegrduomseangdroliuvperhaledvesltsopinptehdebGyrWoeue4kp 1a2niamnadlstahrsemsaiymilhaarve affected levels in these animals. At week Dhiugrhienrgtthhaenltahteeypaerreioatds3o0f/2t0remagt/mkegn/td,aiyt.apTpheiasrsmatyhtbelebveelcsauatse10domsgi/nkggo/rdatyrienesaenriumma,lusriinnethaend30f/e2c0es are make dose group was stopped during treatment, on Days 43, 66, and 81 respectively. This may have 28 28 000145 aafvfaeicltaebdlePfForOtAhelelviveelrs,ilnevteilsssuiens Gfrrooumpan4iamraelshiignhGerroatupWe4.eHko2w7evtehra,n tihnetyhearoeniencGormopuarpast2ivaendsa3m. pAlte Wtheaet kis 27, PFOA levels inthe liverare 15.3 +3.02, 14.0:+ 7.55,and 42.8 + 63.3forGro2,u3,pands4 respectively. The PFOA level in the control liver at Week 27 5 0.177 0.0730. By Week 40, levels in the livers from Group 3 animals are 0.114 3 0.0441 and the levels in the control are below the limits of detection. PleFveOlAs ilnevtehlesuirninseearruemsahreowsnhoinwnTaibnlTeasb3leasnd1 a3nAda1nAd;lleevveellssiinntthheefleicveesr aarree sshhoowwnn iinn TTaabblleess 42 aanndd 42a4.; Individual animal values are presented in Tables 1, 2,3, and 4 respectively. Values in Tables 14, 24, 3A and 4A are group averages + the standard deviation associated that group at each time period. 249 000126 A ad dd dB ll Group?| 105709M |0.645|029 |<10Q|<t0Q|" 0.19116207|0275|0275 |0263| 00 [7ios7aM [0.37 |0230 |0125T<10Q|0.105 [00994| 0.156[<L0Q |0244| me/kg/day[1057ISM |<10Q|0.0785[<LOQ|<LOQ|"0.0919|0.064 | 0.0981[<LOQ |0.0950| Control [7105718M |00889 | 0347 I<LOQ [<LOQ | 0.129 170.139170153 <10Q | 0.165| [Ciosr2om1<tog1o.16710001<t0Q | 0.28 | 0.14010.18 [<to0 |o193| [ios2smT0040| 0.114 T<L0Q|<t0Q | iioT0oses| 0.105T<t00 |0138| Tp T SF fE oe owen me/kgday[T05T00M |oar |osm| 1 UT TP Control [Tios7laM|odo8[020 | 1TTT 1 7 [CrosTismTo.10110.0045 |0.153| 0127 | 0.0943 |00680| 0.0795|00711|0.0719| [TiosTisMT0206[0206T0200T 0.161| 0.125 |0.004 |0.142| 0017|0756| [CrosmomToesT0308TT 1-71T 7 1771 7 Tosmsm ToesToe | 1 1 11 1 11 Timi So brewe o v} e mghgaay[Tosom|ote1 11 1 LT1 1 osoem[rn11 1 1T 1 T 1 [Coszom neTTTT 1 [osm -- TT] replacement) 250 000147 Das Tae 1A PFOA Concentrations in the Serum (g/mL)ofTreated Animals GT Cow Ty Tmt 0A.v0emmg/pkegr/dsady | a3vmgg/ckgs/dsahy | M10emmg/ektg/Sda)y | 30A1e20nmsgs/ksgs/dpay Townzamn[mal| ems |Toran| Weeks ----<ioo | sirezis|wiesms|isesono | Westy orseo0s | 7oe=zs| %06=365 |ta0-7s | Weals |ons=o0m |eese0 | onseias| mosses | [WeWaearr --omiGzo0n0si T mroeraeatss1 1wteousaseiss| |aSersieisc || [ea Vessa [omomnimzzoommosr| | Ns TT nmseu.rsenr[wmns WeWeeasssss[ooormrmieorszzooooooimsssT [ |_N _T |osooare aimmTs n wnn s]] Wess Tommzomar| dete ow 3RL08eQi~s= NLrioemSiptaormfQpoueidniaatgiroonup averages the sandar devon ssid vith tht gop. VDaestarwsictohuantSoDoifb15%one Soto avenge fori ample recovery Th aver fortified sample recovery PFOA Concentrations in thTeaLkieve (ug) ofTsted Aris Gor] ToT Tg Got -- QAovmegmkegrdssdy|| aSvmmggkegdsatyh || A1v0emnagkegdtasyh|| 3A02v0emmeskegsisdpay M[TWmeepone -- T--w-- T -- ---- _ w--TT --w 1 | Ewe Goo1 % Jomo I & NRLSe0OsQu=l2tKLoioneiSteoafxmpQpruelisesnetdiaasigroonup averages the sandr evsion sociated with ht group Dfoarttaifairede ascacmuprlaeteretcoowvietrhyiwnaosne9S0D%owfitthheanavSeDroagfe 2fo6r%t.ified sample recovery. The average 251 000148 PFOA Concenttions itheTUarbilses(sgnofTested Anis OAv0eCmrmggoehg]2i5sDy|| A3vmeTerlmTggedseSyh|| aIveorGamgerpkoesdTsdy || 3A0v2eT0nmogpeTrkSgpey [WestT2 00d=0006i8| d8s-158| aviwoar tis=1i1_] [[WWeessss oi<ttszoooi[ 0T--WT W oosseeiozoomms| [T --_wns | [WelzTooTN oiusom |T| [Weise aom=oomt| [oo zooie |_ns | [ [W We ed ss t TTTr<olo0T TNw s T[oTommssizooonie[| NNs s ]| LN0RSeQs~ts=LNiamoeiSetamofxpQluepinirisaegtroosnup vergetshesandrd devin sociated with that group. Dat are accurate to within one SD ofthe average fortified sample recovery. The average fortified sample recovery was 88%withan SD of 17%. 232 000149 ~~] Grow Gow? Tow Tom? 0.0178 0.0894 CEE Ta S TS 0.00892 [Weeks2834| 027920732| Ns [o3sreo3n| Ns | fortified sample recovery was 117% with an SDof 22%. Reference `Thomford, (APFO) in PJ (2001) 26-Week Capsule Toxicity Study Cynomolgus Monkeys. Study performed by with Ammonium Perfluorooctanoate Covance Laboratories Inc., Madison 000150 REPEAT DOSE DATA "Tithe: Ninety Day Subacute Rat Tosicity Study TEST SUBSTANCE `Ipdeernftiiutoyr:oocFtlaunooraatde,FlPuFoOr,ocFhCe-m1i1c6a,l FFCC--114236., FACl-s1o69r,efFeCr-re1d43t,o aosraPsFOa Amaajomrmcoonmipuomnesnaltto, famFmXo-n1i00u3m (octanoic acid, pentadecafluoro-, ammonium salt, CASRN 3825-26-1) Remarks: White powder, 3M stock no. 98-0211-0008-0 Lot 340; purity ofthe test substance was not indicated. METHOD Method/guideline followed: No guideline number stated Study duration: 90 days GLP (Y/N): No Year study performed: 1977-78 `Species/strain: Charles River CD rat Sex: Maleand female Numberof animals per dose groups animals/sex/group. Routeof administrations Dietary Doses tested and frequency: 0, 10, 30, 100, 300, and 1,000 ppm. Post-treatment observation period: None Sgtraotuipstwicaasl pmeertfhoordmsedubseyda:naSltyastiissotifcalvaarniaalnycseis(ocnoem-pwaaryi)n,gBarretsluelttt'osfttehteftorrehaotmmeongtegnreoiutpyosfwviatrhitahnecceosntarnodl the appropriate t-test (for equal or unequal variances) using Dunnett's multiple comparison tables to judge significanceof differences. Rmaelmeasrwkass: 2I2n2it-i2al54aggeoafndtthheeteisnittainalimwaelisgwhtaosfntohte gfievmeanl;eshowwaesve1r5,1t-h1e79mge.aTnhientiteisaltbcohdeymiwceailgwhtaosfmtihxeed. with 500g offeed at weekly intervals. toxicity and for mortality. Individual The body treated weights animals were observed were recorded weekly. twice daily Blood and for clinical signs of urine samples were cboilolcehcetmeidstprryio,rurtoinsatlyusdiys,inaitnidatsieonraunmdsaamtpl1aesn.d F3oomodnctohnssoufmptrteiaotnmwenats to evaluate recorded. Ahtem9a0todlayosg,y,the animals pweerrfeosramcerdifoincedthaenfdonlelcowrionpgsioerdgafonrsmfarcormosrcatospifcroamntdhmeiccornotsroclo,pi1c00e,xa3m0i0n,atainodn.1,0H0i0sptoppmathdoolsoegygrwoaupss: badrraeinnawlis,thlucnegr,vihceaalrtcowridt,hlcuomrboanrarsypivneaslscelosr,d,aopretrai,phseprlaelenn,emreves,enetyeersi,cpiltyumitpahryn,otdhey,rotihdymwuist,h bpaornaethwyirtohid, 254 000151 kmiadrnreoysw,(usrtienmaurym)b,iasdadleirv,areystgelsa,ndo,vasrmiaelsl, pinrtoessttaitnee,su(tderuuosd,esnkumi,(jmeajmumnaumrylgelaun)d),coalnoyn,tipsasnucer(esa)sw,itihvegrr,oss llievseironssa.mLpilveesrsfrformomalrladtsosferogmrotuhpes1w0earnedf3r0ozpenpmanddosseengtrooutphsewseproensaolrsofoerxaanmailynseids.microscopically and RESULTS NMaOleAs:EL30 ppm Females: 300 ppm LMaOleAs:EL100ppm (decrease in food consumption, liver sions) Females: 1,000 ppm (iver lesions, increased liver weight) R"Tehmesaerkdesa:thOs nweerfeemnaoltecionnstihdee1re0d0 (a0nbdeontreeaftemmeanlte rienlatthede.30A0lptphmegrraonuipmdailesdsduurrviinvgedcoulnleictsicohneodfubleldo.od. sacrifice "iTnhtehreecwoanstraolsiggrnoiufpi)c.antFoeodducctoinosnuimnptmieoannwbaosdyrewdeuicgehdtiinnmmaalleessiinntthhee110,00,0300p0pamndgr1o0u0p0 (p3p6m2 ggrvosup4s6,6but the differences were not statistically significant. Menadleosftihnethterc3a0t,me1n0t0,pe3r0io0d.endTh1e,0v0a0lpuepsmwegrroeu7p.s95h,ad7.s0i5g,ni7f.i1c6a,n6t.l7y2r,eadnudce6d.9n4umibnetrhse coofenrtyrtah,r3o0c,yt1e0s0,at30th0e daonsde1g0r0o0uppsp,mbugtroeurpse,srteastpiestcitciavlellyys.igMnaifliecsanhtaadt rtehdeu3c0e0d plepumkogcryotuepvoanlluye;s lceoumkpoacryeted vtaoltuheescwoenrterol1s0.n64,all s8i.m8i8l,a0r.3p3h,e5n.o3m5e,n7o.6n3,waasndsc8e.n06wiinththheecmoongtlroolb,in10v,a3l0u,es10w0h,ic3h00wearned r1e,d0u0c0epdpamt aglrloduopsse, lreevseplecstbiuvtelwy.ereA tSihgenciofnitcraonlt,at10t,he301,01p0p0,m3d0o0seanldev1el00o0nlpy.pmHegrmoougplso,brienspvecatliuveeslyw.erTehe1r6.e2,wa1s4.n7,o 1s5i.m0i,la1r5.e4f,fec1t4u9p,o1n3.t1hein hematological parametersoffemale rats in the study. wMearleesstaattitshteic3a0l,ly1s0i0g,ni3f0i0c,anatnadt a1l,l0b00uptphme 1d0o0seplpemvedlsosheadlevienlc.reRaespeodrgtleudcgolsuecloesveellsev(emlgs/w1e0r0em1)21,wh1i2c0h, l1e3v6e,ls13w4e,re14e3leavnadte1d3i5nmmga/l1e0s0amtlthfeor1t0h0e, 300,0,10a,n3d011,0000,03p0p0madnod1se,0l0ev0eplsp;mmegarnouvpasl,ueressaptec9t0ivdelayy.s wBeUreN. 2i0he.4c,on2t3r.o9lsa.ndAl3k5a.l1imneg/p1h0os0pmhiatfaosretwheastherleeevadtoesde ignromuaplse,sriensptehceti1v0e0l,y,30c0o,mapnadre1d,0t0o01p6.p2mmggr/o1u0p0s;mtlhefor cloenvterloslsw.erFee1m4a7l,es20s4haonwded21n2osTiUmi/lfaorchtahngtheesciengrboiuopcsh,ermeiscpaelctmievaelsyu,recmoemnptasr.ed o 104 TU/ forthe Nfeeimtahleers mfarloemsanllorgrfoeumpaslesshsohwoewdaedhaingyhetrrefartemqeunetncryeloaftoecdccuhlatngbelsooidn iunritnhaelyusriisnepatrhaamnedtiedrsmaalletsh.ough "eTnhlearogneldylgirvoesrss wnheicrcohpssyhoowbesedrvvaatriyoinngwdaesgrneoteesodfinsumraflacseadtitschoelo1r,a0t0io0np.pNmeidtohseer lfeevemla.leTshefsreomantihmea1l,s0h00ad ppm dose level nor males orfemalesfrom the lower dose levels showed such effects. 255 000152 Bpoptmhgarbosuolpustaenadnidnroenlaetifveemlailveeriwnetihgeht1s,0w0e0rpepsmiggnriofiucpa.ntCloymipnocurneda-sreedliantmeadlleisveirnltehseio3n0s,o3c0c0urarnedd 1i,n0a0l0l mtoalleigrhattshiynpetrhter1o0p0h,yo3f00heapnadto1c,y0t0e0spipnmcegnrtoruiplso.buTlharesteo mliedsizoonnsaclonrseigsitoendsooffftohcealaftfoecmtueldtilfiovcearll,ovbuelreys.sliIgnht some instances these lesions wre accompanied by increased amount of yellowish-brown pigment irnecsiedmebnlcienganldipsoefvuesrciitnyionftthheeclyetsoipolnsaswmaosfhmeopraetopcryotneosunacneddoaccmaosnigonmaalllyeirnatssinatustohieda1l,0l0in0inpgprcmelldsi.etTarhye.. level. CONCLUSIONS s"iTghneitfeisctanstubrsetdaunccteiornesiunlttehde innumabseigrnoiffiecrayntthrreodcuyctteisoninimnamleeasnatbo30d,y 1w0e0i,gh3t00inanmdal1e0s0a0t p1p0m0,0 apnpdm,liaver lesions in males at 100,300and 1000pp. REFERENCE Goldenthal, E., D. Jessup, R. Geil, N. Jefferson, and R. Arceo. 1978. Ninety day subacute toxicity study: Fluorad Fluorochemical FC-143. 3M Company. Study no. 137-089. 256 000153 REPEAT DOSE DATA Title: 1(3C-AWSeeNok.Di3e8t2ar5y.T2o6x-i1cii)ntyMaSlteudRyatwsith T-5180, Ammonium Perfluorooctanoate TEST SUBSTANCE lIidgehnttliytcy:oloTr-e5d15p0o,sAemrmonium perfluorooctancate (APFO), CAS No. 3825-26-1, Lot No. 115. Itisa Remarks: Purityofth test substance was not indicated METHOD `cMoemtphloida/ngcueidweilthinHeazfolleltoownedW:iscGounisdienl,inIenc8.2-(1HW(Iso)urpcreotnooctolspTePci9f3ie2d1).daTthedeNstouvdeymwbaesrc3o0n,d1u9c9t0e.d in Study duration: 13 weeks GLP (YN): Y Year study performed: 1993 Species/strain: RauSprague-Daviey, Ce.CDEBR Sex: Male Numberof animals per dose group: 55ineach group, except pair-fed controls, which had 45 animals Routeof administration: Dietary mDoesaensctoemstpeoduannddcfornesquumepntciyo:n a0t(wpeaerk-f1d3 oanfd n0.o05n,p0a4i7r,fe1d.4c4o,natnrdol4)971,m1a0/,k3g0i,doary)10f0edappdmb(uampp.roxFiimfatteeen eaxnciempatlpsapier.fgerdoucopnwterroles)swaecriefcseacdraitfi4c,ed,aafnedr 1133 wweeeekkss.ofTthreeartemmeanitnianngd10waeneikmsalwsitpheorugtrtoruepat(malelntg.roups Posttreatment observation period: weeks hSteatteirsotgiecnaelimtyeotfhovdasriuasnecde:aLpev5en0e.0'5s,ersatnswfaosrmuasteidofnosewsetrefour svadritanscteabhiolmiozegetnheeivtayr.ianIcne.casAeNs oOfVA was pMoedriffoiremdedTounketyh-eKhroammoegretnesotuwsasoruasendsffoor mpaeidrwdiastea.co1mfphaeriAsoNnOs VbeAtwweaesn sgirgonuipfsi.canOtn,eG-awmaeysAaNndOHVoAwewllas husoerdmotoneanvaallyuzees,boordgyanwewiegihtgsh,s,cuomruglaanti-voe-bbooddyywweeiigghhttpgearicnesn,tafgoeosd,caonndsuomrpgtain-o{no,-bclrianiincawlecihgehmtisrattriyo,. B(eoxdcyepwteipgahitrs-,fdcucmountlraotlisv)eubsoidngs twheeiSghAtSgapirnosg,raanmdafcocoodrdcionngstuompHtWioInmveatlhuoedss.werGeroaunaplcyozmepdafroirsaolnsgwroeurpes 0ev1a1l,u1a0t,ed30a,t athned51000%ptpwmo-tAaPilFeOd pwreorbaebciloimtpyalreevedl.oItnhehecoannraollysainsiomfaltsheindathta,naonnipmaailrs-fiendggrroouupps,ewxhpiolseed the daa fom th par.fed control animals were compared (0 nia exposed {0.100 ppm APO. 257 000154 R`Aetmsatrudkys:iniMtiaaltieonr,attshewearneimuaslesdwteorcehaarpapcrtoexriimzaettehleye4f1fecdtasyosfotlhdeatnedstwseuibgshtaendce18o1n0te2s2ti9culg.ar Tphhyesiology. alipbpirtoupmri0attehaemaonuimnatlosf. thCeontteesotlsugbrsotuapnscoefwpaasirt-hfoerdoaungdhlnyomnipaxre-dfweidtrhatrsodweenrtecmhaoiwntbaeifnoerdeopnraovibdaisnag diiteatd ndioettacroyntcaoinncienngtrtahteitoensotfstubhsetatnecset.suAbsltadniccet;stwheerreeafatsesra,yweedewkeleykalnyalfyosretshewefrirestpfeorufrowremeekdsontotdheetceornmtirnoel dtiheet and one test diet, elected sequentially. "daTtharowurgheourtecthoerdsetdudoyn, tanhimfairlsst awyer,ewoebeskelryvetdhetrweiacfeerd,aialnyfdoosnitghnesdoafyotfosinceicyr.opsIyn.divFiodoudalcobnosduymwpetiigohnt cdoaltlaewcteerdefcroolmlc1t0edandiamiallysf/ogrrpoauipr-afteedagcrhosucphseadnudlewdeseakclriyfifcoer wneornpeaairn-afleydzegdrfoouprse.srSaedriulm, fsoaamlples atensdtossutbeerountea,ncluotuesinaidziipnogsheotrimsosnueesw,eraendcotlelsetcmtaetderfiraolmcconatcehnta.niAmtalnaencrdofprsoyz,esnafmoprlpeosossfilbilveetre,sttemsattees,rilaulngs, r`aensiimdaulesa/ngarloyusipsa.t eAacshecstcihoendoufleldivsearcwraifsicoebttahinleidvefrrwoamsalalsasnaiymeadlfsorattcheaclhevseclhoefdpuallemdistaocyri]fiCceo.AFooxrid5ase as oanf tirnedaitcmaetnotro,faspewreollxaiso1m0eapnriomliaflesr/atgiroonu.p aFtifttheeeennadniomftahlse/g8r-owuepewkerreeconveecrryoppseireidoda.ftTrh4e,m7a,carnodsc1o3piwceeks `seuxrafmaicneastoifontsheinbcrlaiundeadntdhsepeixntaelrncaolrds,utrhfeacneoasfathceavbiotydya,nadllpaorrainfaiscael, sthienucsreasn,iaalndcatvhiteyt,htorhaeceicx,teambadlominal, aprnodstpaetlev,iccocaagvuiltaetsinagngdlavinsdc,eruar.ethTrhae) wbrearien,wleiivgerh,edl.ungOsr,geasnt-etso,-abnoddyacwceeisgshotrypesrcxenotraggaenssa(nsdemoirngaaln-v{eos-icle, blersaiionnws,eibgrahitn,raltiivoesr,welurnegsc,altceusltaetse,da.ndTahcecefsoslloorwyisnegxwoerrgeanesx.amEilencetdromnicmriocsrcoospcicoaplylywa(swhalesnopurseesedntt)o: evaluate tissues from the brain, liver, ungs, testes, and accessor sex organs RESULTS NOAEL (dose and effect): 1.0 ppm LOAEL (dose and effect): 10 ppm T4odxuiectroessepvoenrseelneefcfekcstosrebsy, dbuotsaellevoetlh:erOanneimaanlismsaulravivtehde u1n0ti0lpspcmheddousleedlesvacerlifwiaces.saNcroifcilciendicdaulrsiinggasweoefk. toxicity were observed in any groups during treatment of recovery. i1n0cprepamse--dhabisgohleutrehaenpdatrieclaptailvmeitliovyelrCweoiAghotxs,idaansde haectpiavtiotcye,ldleulcarreahsyepdermteraonphbyody weight gains, 30 ppm -- higher hepatic palmitoyl CoA oxidase activity, decreased mean body weight gains, increased absolute and relative liver weights, and hepatocellular hypertrophy hi1g0h0eprphmep--atilcopwaelrmbitoodyylwCeoigAhtosxiadnadsecuamctuilvaittiy,veinbcordeaysweediagbhstolguatiensa,nldorweelratfiovoedlicvoenrswuemipgthitos,n, hepatocellular hypertrophy, and elevated estradiol levels Sctuamtuilsatticiavlerbeosudlytsw:eiHgihgthgdaionssecaonmipmaarlsedex(h0ibhiotseed cooftnshiestneonntlpyaisrig-neidfigcraonutpl.y lTohweerybaoldsoscwoenisguhmtesd.and S1i0g0nipfipcmanetlxyhilbeistsefdohoidghtehranhetphaetniconppaalimirt-oeyd)cConotArolosxiadtawseeeakcstiv|itaineds 2t.hatAnwiermealsstaattisdtoicsaelllyesveilgsnoiffi3ca0ntaantd 258 000155 weeks 5, 8, and 14. Animals fed 10 ppm had transiently higher hepatic palmitoy] CoA oxidase activity that was statistically significant at week 5. Absolute and relative liver weights were significantly higher in the animalsofthe high dose group than the pair-fed controls at weeks 4,7, and 13. Remarks: Though statistically significant increases in hepatic palmitoy! CoA oxidase activities were rdeeppoerntdeedndtuarnindgretvreerastimbelen.t, nIoncdriefafseerdenacbesowlaustesaenedn arefltaetritvheelSiv-ewr ewekigrhetcsovaenrdy hpeerpiaotdo.celTlhuelaerfhfeycpterwtarsopdhoysewere observed in animals fed 10, 30, or 100 pp; absolute and relative liver weights were significantly phriogghreersisniotnhoefahneipmaatlosceolftlhuleahrihgyhpedrotsreogprhoyudpidthnaonttahpeppeaairr-tfoebdecoanftfreocltsedatbwyetehkesle4,ng7t,hoafndtre13a.tmeTnhte. The changes observed are suggestive ofa test material effect on intracellular metabolism and may be aafstseorcitahteerdewciotvherpyepreorxiiosdo,mwehpircohlifienrdaitciaotne.s tThhaetrtehewaefsfencotsewveirdeenrceeveorfsiibnlcer.eaAsneidmlailvesriwnetihgehthsiogfhadnoismeaglrsoup exhibited consistently significantly lower body weights and cumulative body weight gains than those of tatheweneonkpsaiIr-afnedd2c.onOtvreorlalglr,ounp.o sTighneifyicaalnsto dciofnfesruemnecde isnigmneifaincafnotloydlceosnssfuomopdttihoannbtehtewneoennpaniorn-pfaeidr-cfoentdraonlsd pair-fed groups was noted. Though there was no statisicaly significant difference, the estradiol levels in the high dose animals appeared to be elevated at week 5 CONCLUSIONS. "The study author concluded that the no observed adverse effect level (NOAEL) for the test substance when fed ad libitum 0 rats for atleast 13 weeks was 100 ppm and that the no observed effect level (NOEL) was 1.0 ppm. ``mRaeymabrekcso:nsIindearneidmaaldsvefresde,10i,n3c0l,udainndg i1n0c0repapsme,d atbhseorleuptoertanddesrcerliabteisverfeiavtemrewneti-grhetlsa,tehdeplaitvoecreelflfuelcatrs that hypertrophy, and significantly increased hepatic palmitoyl CoA oxidase activities. On the basis ofthese findings, the LOAEL was 10 ppm and the NOAEL was 1.0 ppm. REFERENCE Palazzolo, M. 1993. 13-Week dietary toxicity study with T-5180, ammonium perfluorooctancate (CAS No. 3826-1) in male rats. Hazleton Wisconsin, Inc. Madison, WI. 3M Company. St. Paul, MN. 259 000156 REPEAT DOSE DATA Title: Two Year Oral (Diet) Toxicity/Carcinogenicity StudyofFluorochemical FC-143 in Rats TESTSUBSTANCE Identity: Fluorad Fluorochemical FC-143, also referred to as PFOA ammonium salt, ammonium perfluorooctanoate, PFO, FC-116, FC-126, FC-169, FC-143, or as a major componentof FX-1003 (octanoic acid, pentadecafluoro- ammonium salt, CASRN 3825-26-1) `Remarks: The test substance,a white powder, was analyzed prior to the start ofth study, after adeptpercotxaibmlaetcehlaynognees yweearreffrooumndt.heTshtaertcoofmtphoseisttiuodny,anadndpuartitthyoeftterhmeintaetstiosnuobfsttahnecedowseirneg npoetriiondd.icNaoted in the main bodyofthe study report. METHOD `Method/guideline followed: Guideline number not stated Study duration: Two years GLP (YN): Yes Year study performed: 1981 - 1983 `Species/strain: Sprague-Dawley rat [Cr:COBS" CD(SD)BR] Sex: Maleffemale Numberofanimals per dose group: The control and high-dose groups contained 65 rats/sex and the low-dose group contained 50 ratssex. Routeof administration: Dict Doses tested and frequency: LowH-idgohs-ed:os1e.:3 m14g./2kgm/gd/akygl(maayle(sm)a,le1s.)6,m1g6/.k1g/mdga/ykg(/fdeamyal(efse)males) Posttreatment observation period: None `Statistical methods used: Bartlett's test for homogeneityofvariance was used to analyze the test data. If tghriosutpesttowtahse cnoonttsrioglngifriocuapntuastinaglpahatw=o-0t.a0i0l1e,d tDhuendnaettatw'etreestfautrtthheeraalnpahlayz=e0d.b0y5 sciogmnpiafricianngcecalcevhelt.reated `Ryeeamrairnkcsl:udTeedst15anraitmsa/lssexwferroem3b9ottoh4t1hedcaoynstorfolaganedwhhiegnh-tdroesaetmgernotupbse.gaAnl.l Aannimianltserwiemrteerombisneartvieodn adtaiolnye. t`ahnrdopuhgahromuatcottheordxoiscinogbspeerrviaotdi.onWs.eeBkoldyyphwyesiigchatlseaxnadmifneaetdicoonnssiunmcpltuidoend pwaelrpeatrieocnorfdoredanwyeemkalsyseosr pbir-esent wpeeerkfloyr.medEyaet ethxeamoinnea-tyieoanrspeursiiond.g inCdliirneicctalopphatthhaollomgoyscdoepteyramnidn/aotriosnlist ilnacmlpudbeidomhiecmartooslcoogpyy,wecrlien.ical (serum) chemistey and urinalysis. Tests were conducted on samples obtained at 3, 6, 12, 18, and 24 260 000157 `months from randomly selected animalsofeach dose group. Hematologic tess included total red and cwhheimtiesbtlroyopdacrealmlectoeurnstsi,nchleumdoegdlotobtialn,bihleimrautbionc,ritto,alanpdroatediinf,fearlebntuimailn,whbiltoeobdluoroedacneiltlrcooguennt.(BCUlNi)ni,cagllucose, alkaline phosphatase (AP), creatine phosphokinase (CPK), aspartate aminotransferase,and calcium. MUertianbeotleisctseixnacmliundaetdipoHn,s isnpevcoilfviecdgcroalvlietcyt,iaolnobufmuirni,ngelaucnodsef,ecbaillsiraumbpilne,s.occPuolsttbmlooordteamndexkaetmoinneast.ions were `performed on allanimalsandthe weighs ofthe adrenal glands, bran, teste, heart, kidneys, liver, spleen, w`aenrdeutceorlulsecwteedreanredcoobrsdeerdvferdommic1r5osrcaonpdiocmallylyseflreocmtetdhersatesa/nseixm/aglrsoup. Samplesofmany different issues. RESULTS S"Guernveirvaalllyr,atseusr:vival rates fo the FC-143-treated rats were good during the full two yearsofthe study. Fever deaths were seenin high-dose males and females than in the controls. Neoplastic effects: Percent Neoplastic Lesions in Males [em |ow [om | [Pheoch[ ro4 mo[ cyto 8 mabTen8 ign ] Pheochromoeytoma, malig. | 0 |2 J0 T ] `Hepatocellular carcinoma. [TmTe [wiry 7 [Adenoma 13T736 21| [Leydigeelladenoma | 0 | a4 Tar C-cell adenoma oo T&T 5% [CeSoeulrclee:aTracblien1o9ma [510[0] "Significantly different (p <0.05)from controls 261 000158 Percent Neoplastic Lesions in Females I C ew T tw[m-- m] [PhI eochromosyiomabern| --4----0-- [02 | E{HeTpsiocsilarwsinoms[0] -- 5] 3 || [[AAdednecwcoamreainems 515[5 0 0 ] ]| [[FCborcoiandeonmoana >20 || 0&[aw0 || [Lmphangiosaeoms | 0 | 0 | 2 || M[iAgCodo.loso--no--ma----T --------m ----2--1 --T ----% --o -- --] T --------o| [CoSeolurl:caTmaiblneo9ma T0010] Simifanty diffrent ( <0.05) from coils Srtoatmistciocnatlraonlaslypsi<s0.o0f8n)c:oplasti effets (i. percent hat was statistically significantly diferent F[MeamlaelsAe(s1(4136.m1 imkg/ehkyge): -- Levene ooll demons nets Nonncoplstc effects: NOAEL (dose and effet: none LOAEL (dose and effect): t1h3e smpukdgiaduathyor(smailmepsl)ie--dbaanseadsuupaotnisoanliovfairy glaenid nsawaidtehnstussp(eroctteetdhat routbr--eako--fsa--lod--acty_oadenis vil infection however, te presence of i1.n6 cmeg/kgS/mdeayal(f5emaGles) ~ based upon ovarian tubular hyperplasia (and 262 000159 Percent Non-neoplastic Lesions in Males [hC dregar ww T T wTm [[oSdimlsaoridiaytpecenrsiissa1 4[ m 3T m w || fleNiwort, throne --s ] 5% 2} S Ther F EO -- |I I Hepatocellularalt.basophil.[ I 4 A |--2-- --1---- 1c2 | [NT ewPowrtsalimsonomcesr infil 74| T 01 e | ouew || [(CTlvoelgarmasopiags | %0 |wear|| [CChreemvoamstamgoemonfl| [2B 0 | | ae [a] r] [P|nVeauscmuolnarimninemreanlsiiztaitailon1| %86 | 8 tor | | _o_ a || I I a-- ---- -- -- -- Ww T T=se ThCyreolidype 2 15] 3 ] r omereasT------ -- -- = SalSivialryentsg,landchrome 31 Ei Spleen 1 [CHemoSSosuirdciee:roTsmaisbeidZi0fffrentc(1 <0.a05)nfromtco3 nryols1% 7] a 263 000160 Percent Non-neoLepsiolnsainsFetmailces [Noe dularbyperisa r 0i[ I " --6 ----5-------- [CusHHeoyppdsereopsglsaesltnnilceanmroaidtobeanso[ ph. |T 0[ 6 3 1 0[1 |546 5 | I Portalmono. cela-- l, |I3%-- | ---- 3ier | [News 1 lo |___p---- 4] [[aClHveemoolnabramagceropha| ges 3[ | 2w |3 w [[Vpaesrcvualsarmmoinneoralmizfation [|a 26[ae| e g 5 [Pacumonin mersital 14 | 6 | is [NI aseularmin. |------ CG0 oayw TBTw i [ThTyzouid rple 0Te a Ge& ceolbpeina C--o ----[ ---- 5 17] [Cotegmas --[-- 1mw| [h[cSneavranamGolpalyd [Bm[5 [SoSoilndeniis, chrome | 7[3] 5 | CheSnouorcse:ioTobses30 1%[eT a | "Sigdinffrientf(p<0i.05c) raomcnoirtls 264 000161 Liinsdticoaftsetda;tipst<i0c.al0l5y):different non-neoplastic effects (increased compared with controls, unless MaClherson(i1c3smigal/akdge)nits (salivary gland) PInetreirvstaistciuallaprnmeounmoo,niianfillu. nugn)g")" Hemosiderosi (spleen) MaClyessto(i1d4.d2egmegn/ekrga)t:ion (liver) MPeograallomcoyntoonsuicsl(elairverc)ll infilation (liver) AHlevmeoorlrahramgaecr(loupnhga)ges (lung) VCahsrcounliacrsmiianleardaelniizdast(isoanli(vtaesrtyisgelpainddi)dymis) Perivascular mono. infil ung)" FeVmaaslceusla(1r.6 minmegrkaeli)z:ation (lung) TCuhrbounliacr hmyypoecraprldaistiias"(ovary) PHeermiovsaisdceurloasrimson(os,pleinefinl). (ung) FeMmeaglaelsoc(y1t6.o1simsg/(kliev)e:r) THuebmuolsairdehryopseirspl(asspilae(eonv)ary) "Decreased incidence relative to controls `Genetic toxicity studies (study type and results): None Remarks: "feDmoaslee-s.elated decreased in mean body weights in excess of 10% was observed in high-dose males and "thMreoaunghfoeuetdtchoensstuumdpytwiohnen(acsogmrpaamrsedditeotkmgalbewc)onwtarsolinfcereedacsoednsiunaml ptioofn.theOvFeCr-a1l4l3tthreeavtaerdiamtailonesswere ehilgaht-eddotsoetmhaelveasriraetliaotnivientboocdoyntwreolisghftoratmhoenfgisgtryoeuaprso.ftAchteuastludmye.an feed consumpiion was decreased in "-DAosseta-triesltaictaeldlyoscicgunrirfeincacneot f(pa<t0a.x0i5a)idnefcermeaalseesinwaresdtbhlooondlyceclllipniacraalmseitgenrsobwsaesrvneod.ted in the high-dose: mAalsetsataisstcicoamllpyarsiegdniffoictahnetc(opnt<r0o.l0s5,) increasei relative liver and kidney weights was found in high-dose males and an increase in relative Kidney weights was found in high-dose females. 265 000162 HUirsitnoapraythfionldoignigaslienfcfleucdtesdwiencrrenaosetdeiinnctihdeenicevranodfhsievgehr-idtoyosefmaallbeusmianndanfdemoaclceuslt blood inal male and fpermoanloeunccoentdroinl amanldeFsCt-h1a4n3-intefaetmealdegsraotuphseatte1r2m,in1a8t,iaonndof2t4hemonstthusd.y These findings were more Rbeattwseeginvtehnetihsetteastndarstieccloened xmopntehsroiftaeshunsspcteucdetye:dhdoowuebvrere,aktohfespiraelsoednacceroyfoaadveinriutssw(aSsDAo)tvciornalfiimnmfeedc.tion CONCLUSIONS TheTsrteuadtymrenetsueslaartedsuchmamnagreiszewderaes ffoolulnodwsm:ore commonly in males than in females ofcachofthe two sttruedaitemsendtemgornosutprsa,twihnigcahhwiegrheersrueptpeonrttieondobfyFaCr-l1i4e3pbhyarmmaalceoskitnheatnic "The est mateial was considefreemadlte0s.be carcinogenic in the at, inducingtesticularLeydig cel tumors Based on decreases i body wienitghhetmgaaliens, ainncdremaasmeminarliyverglaannddktiudmnoeryswienifgehmtasleasn.d toxicity inthe hie3m0at0oplpogmi(camlaalned:hep14.a2 tmigc/ksgy/sdeamys;, ftheemLaOlAeE.L mfgo/rkmga/ldaeya)n.d[fTehmeale rats LbaOsAedEuLpofnor;mtahleeLrOatAs EisL1.f3ormfgem/adlearyatsifssal1i.v6amrgy/gklga/nddasyiiafilnadcerneiatsseissin thhyepeirnpcliadseinace(smoafyabteaxrieavearsiclbilnei)caalresibgans)eadnudpoofn,ovarian tubular "Thedtoesset-icduelpaernLdeenytdiignccreelasaedseinnonmeoap(lpas<t0i.c0a5and nhoing-hnedoopslea)staincdlveassicounlsawremrienesralfiolzlaotwiso:nofthe testes (+ 9th0yr0o5idaCtehilglhaddoseen)omas in low-dose males tmhayrmomiadrCyeglllanhdypfeirbprloaasdieanionmhaisghin-dfoesmealfeesma(lpe<s0.05a high dose) slaulnigvalreysiloansndinsmaaliasdn(ipt<s0.in05maatlhsig(hp d<o0s.e0)5 at ow and high doses) + omveagrailaonctyuobsuilsarihnytpheerpllaisioavfimneafleremsalaensd(fpe<m0a.l0e5s a(tp l<o0w.a0n5dathhiigghhddosoesse)) with incresses in relative l+icvyerstwoeiidgdhetgaennedrealteivoantiaonndsopforstearlummoneonnzuyclmeeaarctcievliltiiensfiilntrdaitciaotnivientohfelilvievrerotofximciatlyes (p <0.05 at Tigh dose) Rreesmpaornkses:0 Itnhfltueesntcseoubfsptotaenncitieanlovirlaelri.nfeScitailoondiancrmyaolaedeSnpirtasgvuier-uDsa(wleSy aDtiasAcbooVtmhmd)oosnesviornaltihnefection oinffFec3t4i4onrafto;unedvanlouactoinosnisoft2en9t idnifcltuceoncnetoolfvriaatlgrionufpescation5odinfbfeordeyntwleaibgohrta,tosruirevsivwailt,horantduwmiotrhporuetvvailreanlce (Rao, etal, 1988). REFERENCE 3FlMuCoroomcpheamniycaRlikFeCr-1L4a3bonratRoartises,ExInpce.riTmweontYNeoa.r0O2ra8l1C(RDiOe0tL)2T.oxiSct.itPya!ulC,arMcNin.ogSenEiHcQi-t1y0S8t7u-d0y3o9f4, Oct. 16, 1987. 266 000163 Rao, G.N. , weight and Edmondson, J. and survivalofFischer 3H4a4seramtsa.nTJoKxi.colIongfilsute,nc8e:o1f6v,ir1a9l88i,nfectionson tumor incidences, body 267 000164 REPEAT DOSE STUDIES Title: MechanismsofExtrahepatic Tumor Induction by Peroxisome Proliferators in Male CD Rats: TEST SUBSTANCE Identity: Ammonium perfluorooctanoate: Remarks: The substance was 98-100% pure. METHOD Method/guideline followed: None Study duration: 2 years GLP (Y/N): Unknown ear study performed: 2001 (publication date) `Species/strain: Crl: CD BR rats from Charles River Breeding Laboratories (Raleigh, NC). Sex: Males Number of animals per dose group: 156 Routeof administration: diet Doses tested and frequency: 0, 300 ppm Post-observation period: None S`taamtoinsgtigcarloumpestwhaosdssiugsniefdi:canOtn,ep-avirawyisaneacloysmipsaorfisvoanrsiawnceer.e When corresponding made with Dunnett' F-test for test. The differences Bartlett's test ffoorr heqoumaolgemneediitaynosfavnadriMaanncne-wWashiatlsnoeUpyertfeosrtmfeodrp.aiNrownipsaeracmoemtprariicspornosc.edures included Kruskal-Wallis test R1.e3m,a6r,k9,s:12,H1o5r,m1o8n,aalnda21nmaonwtlahssycaofsnedruiicntisteidatiinono10ftrahtes.stBuldyo.odSwearsucmolwlaesctperdefpraroemdtahendtaflrovzeeinnaanbdoutthen analyzed for testosterone, estradiol, luteinizing hormone, follicle stimulating hormone,andprolactin concentrations. All samples were analyzed simultaneously in duplicate. Rats were euthanized at interim timeperiods (1,3, 6,9, 12, 15, 18, and21 months). Testes, erpeimdoivdeydm)i,dperso,staactcee,sasnodrylsiveexr gwlearned w(eAiSghGe)d.unit with fluid, coagulating gland/seminal vesicle (with fluid 268 000165 gAlta2n4dimsoenmtinhasl, vseusrivcilveisnwgirtahtslwiedrerneemcorvoepdsi,edp.rostBartuen,,ephiedaritd,ymliivdeers,,spalnedent,esktisdnweeyrs,eAiSeiGguhneidt,actonaegcurloaptsiyn.g lLievseiro,nstestes, epididymides, pancreas, and organs with gross lesions were examined microscopically for sScioxraetds/group were selected for evaluationsofcel proliferation. For each tissue type, 1000 cells were aSnixd aLtesygdirgoucpellwepreerosxeilseoctmeedsowrasevmaelausatuiroenodfatpaelrionifsroimmetpirmoelipfoeirnatst.ion.f-ooxxiiddaatitoinoanctaicvtiitvyitwyafsrom liver determined using the methodofLazarow (1981). RESULTS Toxic responses and effects: dBeocdryeawseeidgihnt,thfeoCod8 cgornosuupmvpetrisouns,thaenaddsluirbviivuaml:conFtreoolmgtreosutpd.ayTshe0de6c3r0e,asbeoddbyowdeyigwhetigwhatswseisgnpirfiicmaanrtillyy cduoemptaorreedduwcietdh `thfeoocdonetfrfoilcigenrcoyu'p. (Ostnatidsatyica7l1s4igonfitfhiecatnecte,nsoutrviinvdaiclaitedt)h.e C[H8emgartooulpowgiacsalincchraenasgeeds were discussed ina separate article.) <Li0v.e0r5:) Rwehleanticvoemlpivaerrewdeiwgihtthsoannedorhempoatrieccooxntirdoaltgiroonupasc.tiCvi8typwreordeucseidgnaisftiactainsttliycailnlcyresaigsneidfiactaanlt itnicmreesas(ep (p<0.05) in incidenceofhepatocellular adenomas (10/76, 13% vs. 280, 3% in controls). TIensctiidse:ncTeesstoifs Lweeyidgihtgscewlelrheypsearipsltaisciaallaynidgaaidfeincoamnalsywienrcreeaalsseods(tpat<is0t.ic0a5l)lyatsi2g4nimfoicnatnhtslyiinnCc8r-etarseeadt(edp<rats 0.05); the incidenceofLeydig cel tumors was 8/76(11%) as compared to 0/80 (0%) in controls, P18a,ncarneda2s1: mPoanntchrse.atiIcncaicdiennacreoceflapcrionlairfecrealtliohnypwearslpsatsaitaisatincdalaly sdignieficwanantslosyiignnmcirfeiaacsaensdtl(ypi<nc0r.e0a5s)eadtin15C,S craosmb(ipn<ed0.i05n)c.ideCnacrecoifnaocmianawracselolbsaervdedeinoannndecCoaSr-cmiirneoaameadwraats8(/no7t6s(a1s1t%i)cawlhyerseiagnsiftihcaatntof)t.hTehecontrol was 080 (0%). aSte1r,u3m, 6h,o9r,maonnde12memaosnutrhesmecnotmsp:areSdertoumcoensttrroaldigorloucposn.ceTnhterraetiwoenrweenroe csiognnsiifsitceannttldyifefleerveantceedsi(np s<e0r.u0m5) testosterone, FSH, prolactin, or LH concentrations inth treated rats when compared tothe controls. Statistical resus: Statistically significant results are reported above. WRheemtahrekrst:heAmafumlml aarnygegolfaonrdgtaunmsorasnodbtsiesrsvueesdwiansthneoetaerlxiaemrimnueldtihdisotsoelosgitcuadlyly(.3MT,he1r9e8f7o)rew,atsiisnudnuckendowinn this study. 269 000166 CONCLUSIONS `The study demonstrate that C8, (tests and pancreas) in CD rats. peroxisome proliferator Data from this study also siungdguecsets thhaet tpheaaistnwdiueclctliaosnoexftLreayhedpiagtcieclltumors. tumobyrCs8 is a result of a sustained increase in serum estradiol concentration Remarks: none Last Modified: 7/03/01 REFERENCE `Beixctgrealh,epLa.tBi.c,tHuumrotr,iMn.dEu,ctFiroanmbey,peS.rRo.x,i0s"oCmoenpnorr,o.lC.i,afnidenmJr.aCla.eCtCoDookr.rats2s0.01T.oxiMceolcohgiacnalisScomifsences. 60: 44-55, 3(pMe.rfFliunoarloroecptoarntanoef*amTmwooniyeuamr ocraarlbo(xdyilea)tet)oxiincirtatys.anVdolc.ar1c-i4n,oFgeMn/icRiItKy EsRtuEdyxopf. fNol.uo0ro2c8h1eCmriocoa1l2F;CS-E1H43Q1087-0394, Oct. 16, 1987. 270 000167 DEVELOPMENTAL TOXICITY "Title: Oral Teratology StudyofT-2998CoC in Rats TEST SUBSTANCE Identity: Ammonium Perflurooctanoate (APFO) or T-2998C0C (FC-143) Remarks: Purityof the test substance was no indicated. METHOD iMsestuhedodinGJuainduealryi,ne19f6o6ll(o"wGeudi:deTlhineepsrfoocreRdeuprreocdoumcptliioensSwtiutdhietshefogrenSearfaeltyreEvcaolmumaetnidoanotifoDnrsuogftshfeorFHDuAman UEvsael"u.atiTohneLsatbuodryatwoarsy'csonStdauncdiaerddaOcpceorradtiinngg0Prtohceed1u9r7e8s.Good Laboratory Practice Regulations and Safety GLP (VN): Yes Year study performed: 1951 Speces/Strain:RatSprague Davley-derived CD Number of animals per dose: 22 Route of administration: Oral gavage aDnodsi1n5g0rmegg/ikmge/ndsayFiAvPeFgOroiunpswaotfer22byfigmaev-amgaeteodnSgperstaagtuieo-nDdaawylse(yGaDt)s6w-e1r5e. adAmicnoinssttearnetdd,os0e.v5o,lu1.m5e, o5,fS mg was administered. Doses: 0,005,1.5,5, and 150 mg/kg/day oSftarteissotripctailomnestthso,dsnuumsbede:r oDfiumnplnaent'atieosn sfiotresdaanmdanndupupmowfebicgohertpso,rranuumtbee;r oCfhfietsuqsueasr,enfuomrber percent abnormaliies. Rreesmuasrkosfa--rDaentgaei-lfiannddindgisstcuudsys,aannyuspipgeorifdiocsaentlepvreoltoocfo1l50pamrga/mkeet/edrasyawnads dseetvifaotritohnes:defBiansiteidveonsttuhdey in `mwgh/ikcgh/fdiavye AgrPoFupOsoinfd2i2siilmleed-mwaalteedbSypgraavgaugee-Doanwlgeesytartatisonwedaryesa(dmGiDn)istred 0, 0.05, 1.5, 5, and 150 6s-i1g5n.s oDfotsoexisciwteyr.eIanddjiuvsitdeudalacbcoodrydiwnegigthotbsowdeyrweeirgehcto.rdeDdaomnsGweDre3,m6o,n9i,to1r2,ed15o,naGndD203..20Anfiormacllisniwcealre snaucmibfeirceodfocnorGpIoDra20tebay,cenruvimcbaelrodifslvoicaabtlieonaandnnotnh-evoivaabriieesf,etuutsres,,aunmdbceonrotefnrseswoerrpetieoxnasmiitnese,dafnod ntuhember oAfppirmopxliamnaatteiloynointes-.thiFredtuosetfsh wefreteusweesiwgehreed afnxdedseixneBdoaunidn=ssubsjoelcutteidonfoanxdteerxaamlignreodssfonrecvriospcserya.l am 000168 `uasbinnogrmaalliiztaireisn bedy.free-hand sectioning. The remaining fetuses were subjected to skeletal examination RESULTS NOAEL (dose and effect) ~ maternal and developmental: The NOAEL mg/kg/day. The NOAELfordevelopmental toxicity is 150 mg/kg/day, the for matemal highest dose toxicity tested. is 5 LmgO/kAgE/dLay(,dobsaeseadndonefsfteacttis)t-icamlalytesirgnnailfiacanndt rdeedvuecltoipomnesnitnamle:anThmeatLeOmAalELbofdoyr mwaetieghrtn,alattaoxxiiac,itaynids d1e5at0h. No signsof developmental toxicity were observed at any dose level. `siTgonxiifcicraenstpornesdeulcetfifoencstsinbmyedaonsmealteevrenla-lmbaotdeyrnwaeli:ghtSsigonnsoGfDma9t,e1m2,alantdoxi15c;itayncdonastiasxitaedaonfdstdaetaitsht,icaallllayt the high-dose group of 150 mg/kg/day. Toxic response/effects by doselevel -developmental: developmental toxicity were seen at any dose level. No satstcally significant signs of Statistical results: `Maternal data: Statistically significant reductions (Dunnett's est, p<0.05) in mean maternal abvoadiylawbeliegfhotr wotehreerosbisgensrovfedmoantegemsatlattiooxnicdiatyys(a9t,ax1i2a, aanndd d1e5a.thN).o statistical information was Fetal data: A statistically significant increase (Chi-square, p<0.03) in ane sternebrac missing was observed atthe highest dosed-groupof 150 mgkg/day. Rem--aAdrditkionsal informationto adequately assess the data: oSnigGnsDof,ma1t2e,rannadl toxicity LS a the consistedofstatistically high-dose group of 150 significant mg/kg/day. reductions in mean maternal body weights Mean matemal body weight on GD 20 csiognntsinoufemdattoermeamlaitnoxlicoiwteyrotchcaunrrcionngtroonlsl,y aatltthhoeuhgihgthh-edodsieffgerreonucpeiwnacslundoetdsattaatxisitaicaanldlydseiagtnhifiocbasnet.rveOdthienr three rat to affect dams. No other effects were reported. Administrationof the ovaries or reproductive tract contactofthe dams. APFO during gestation did not sppear A`grsoiugpnioffic1a5n0tlmygh/ikggh/edrayi;nchiodewnecveeirntfhestusskeeslewtiatlhvoanrieatmiiosnsianlsgosotcecrnuerbrreadeiwnatsheocbosnetrrvoelds aatndthtehheiogthh-edrostheree dboesteregartomuepnts.(raetlastiemdi.larNoincsiigdneinfciecabnuttdlioffweerrentcheasn btehetwheiegnh-tdroesaetegdraonudp)coanntdrotlhegrreofuopres wwearsennototceodnsfiodreortehderto dtheevemleoapnmennutamlbepraroafrmeestoerrpsttihoant isnitcsl,udiemdpltahnetmateiaonn nsiutmesb,ecroorfpmoraalelusteaanadndfemmealaens,fteottuasl waenidghdtes.ad Lfietkuesweiss,e, afetal lens finding initially described as a varietyofabnormal morphological changes localized to the aarnedaotfhetrheefoerembnroytocnoanlsinduecrleedust,owbaestrlaetaetrmednett-errlmaitende.d to be an artifactofthe free-hand sectioning technique m 000169 CONCLUSIONS Comment on authors conclusions and whether you agree: Conclusions are summarized aboveandthis reviewer agrees. REFERENCE Gorter, E. Experiment 1981. Oral Teratology Studyof #0681TROL10, December 1981. T-2998CoC in Rats. Riker Laboratories, Inc., St. Paul, MN. 273 000170 DEVELOPMENTAL TOXICITY "Title: Oral Teratology Studyof T-3141CoC in Rabbits TEST SUBSTANCE Identity: Ammonium Perfluorooctanoate (APFO) or T-3141CoC (FC-143). Remarks: According tothestudy authors,theanalytical report (AppendixIV) demonstrated that Tt3h1is41anCaolyCsihsa,stahne aCnsalaycsiidswwaisth9i7n.s6p%ecaifnidca9t8io.n4s%,oifs tshtaeblteesatnsdubisstraenpcreespernet-asttivuedoyfancdompmoestr-csitauldym,aterial. By respectively. METHOD i`sMseutehdoidn/GJuaniudaerlyi,ne19f6o6l:loAwGeudi:deTlhienepsrfoocredRuerperocdoumcptliioens wStiutdhitehsefgoernSearfaeltyreEcvoamlmueantdioantoifonDsorfutgsheforFHDuAman Use@ `Typeof study: Developmental Toxicity GLP (YIN): Yes. Year study performed: 1981 `Species/Strain: New Zealand White/Minikin rabbits Numberofanimals per dose: 13 Routeofadministration: Oral gavage D5o0smignkggr/edgaiymeAnP:FFOouirngdrisotuiplsleodfwa1t8eprrbegyngaantvaNgeewonZegaelstaantdioWnhdiatyesr(abGbDi)ts6w-1e8r.e aAdmcionnissttaenrteddo0s,e1v.5o,l5u,maend of1 mig was administered. Doses: 0, 15, 5, and 50 mg/kg/day Srteastoirspttiicoanl smiteets,hondusmbuesredo:f iDmupnlnaenttra=tisotntseisttesfoarnddanmumabnedrpoufpcwoeripgohrtas,tneusm;bCehroi-fsqfeutaurseeste,sntuwmibtherYaotfes correction for percent abnormalities. Rreesmulatrskosfa-Dreatnagiel-fiannddindgissctuusdys,aannyupspigenridfoicsaentlperveoltoofco5l0pmagr/akmge/tdearyswaansdsdeetvfioarttihoensd:efBiansiteidveonsttuhdey in whichfourgroups mg/kg/day APFO of 18 pregnant New Zealand White rabbits were administered 0, 1.5, in distilled water by gavage on gestation days (GD) 6-18. Pregnancy 5, and 50 was established in afoclhlosweexduablylyarmtiaftiuciraelfienmsaelmienbaytioi.nv.wiintjhec0t.i5onmiofpoiftpuoiotlaeryd sluetmeeninzicnogllheoctremdofnreoimn moardleerrtaobbiintd;ucteheovdualyatoifon, insemination was designated as day 0ofgestation. A constant dose volume of1 ml/kg was administered. 274 000171 oInndGivDidu3a-l29bofdoryawbeniogrhmtsalwcelrienimcaelassiugrnesd. oOnnGGDD3,396,,9t,he1d2o,e1s5,we1r8,eaenudth2a9n.izTehdeanddoctsheweorvaeribesse,ruvteerdusdaainldy contents examinedfo the number ofcorpora ues five and dead fetuses, resorption and implantation ASsiubtrelsv.oivoaFdlesthuesaceks.mwewPrpauespesltxawakeemerinenfesrduobfmsoersqiguxreondstosleyapbernuiotorhrmaatndliizoteidesasniadnanednxgpdalmaticnedehdionnefaGrn3Dv7is1Cc8eariannlcduabn2ad9t;osrkaefflioevrteaarl2ss4abmnhoporlumearlwiatsics. itankfeonrmfartioomntwheassaumneavaaniilmaballesaotntGheDim29e. oAfltlissamrepvlieesww.ere sent othe sponsor for analysis. This RESULTS dNoOsAeEsLted(,dofsoer amantderenffaelctt)ox-icmiattyewransalinadincdatdede.velAopNmOenAtEalL:fAorNdOevAeEloLpmoenftS0almtg/ikcgi/tdyayc,outlhde hniogthbeest hesitgahbelsitsdhoesdesince signs ofdevelopmental tosicitywere seen at ll doses, with statistical significance t the aLtOanAyEdLes(edolseveela.ndThefefeLcOt)A-EmLaftoerrndaevlealnodpmdeenvtealloptomxeinctitayl:isN0o msgig/nksg/odfmaayt,ebransaeldtoonxidcoitsyewreerleieodbserved increases ina skeletal variation, with satiscal significance atte high-dose group. sTiogxniicfircaenstpornasnesi/eenftfcrtesdubcytidoonsseinlebvoeldyBwmeaitgehrtngaali:n oSnigGnIso)f6.m9awtehmeanlctoomxpicairteydcoonsciosntterdolosf;sbaotdsyiwceailgyht gain retumed to control levels on GD12-29. "dToosxei-crerleatsepdoinnscereeafseecisnabyskdeolseteallevvaerliaBtidoen,veexltorpamiebnstoarl S13ignisbo,fdweivtehlsoapimsetnctaallsiogxniicfiicyanccoensaitsttehdhoifghadose group ofSO mg/kg/day Statistical results: M<a0t.e0m5a)lbdeattaw:eeSntatgiessttiactailloyn dsiegyni6f.i9cawnterreedoubcsteirovnedininmethaenhibgohdeystwediogshetd-ggarionusp(oDfunSn0emttg=kseesdta,y. After gestation 9, mean body weight gains were comparable to control animalsfo all dosed-groups. Fetal data: Dose-related increases in a skeletal variation, extra ribs or 13* rib, with statistical significance m(Dauknendetaty=,s atensdt, 1p,60.%05a)t atmtghkegh/idgahy-)d.oseAgrstoautpist(i3ca8l%lyasti5gn0ifmigc/akngt/idnacyr,ea3se0%(Dautn5nemgt/-ksg/tdeaty,0.2005%)aitn1.153 ibssumedoccurred inthe mid-dose group ofS mgkgday Remarks - Additional informationtoadequately assess the data: GSIiDgn6so.9fwmahteenrncaolmptairceidtytoccoonnstirsotlesd; bofodstyatwiestiigchaltlygasiingsnirfeitcuarntnetdratnosiceonnttrroeldulcetvielosnsoninGbDoId2y:2w9e.ight ain on cAodnmtiennitsstroafttihoenodfocAs.PSOixddueraitnhgsgoeccsuartroend dduirdinnogttahpepsetaurdy(:0 hafofwcetvetrh,e iovvaeriocftshoef rseipxrdoedautchtsivweertreacattiibuted 10 gavage errors. No clinical or ther reatment.rlatd sgas were reported. Nfeomasliegsn,ifdiecaandtodriflfievreefnecteussewse,raendnofteetdalbweetiwghetesn. coLnitkreowlissae,nthterreeatweedrgeronuopssifgonriftihceanntudmibfeferreonfcmeaslreespoarntded for the number of resorption and implantation sites, corpora ues, the conception incidence, abortion at, 275 000172 uornrtehmear2k4abhloeu.r mTorhtealointlyyisnicgindoefncdeeovfelthoepmfeenttusaels.toxGircoistsy cnoencsriosptseydaonfadsdkoeslee-traellvaitsecderianlcreexaasmeiinnataisokneslewtealre 3va0ri%ataiotnS,megxktealdiabys,or2013%aitb1,.5wimtgh/sktga/tidsatyi,calansdig1n6if%icaatncmegaktghidhaiyg)h-.dAossteagtirsotuipca(l3l8y%siagtn5if0icmagn/tkg/day, siingcnriefaisceainnce1o3f"tihbiss-esfpfuerctreids uonccceurrtraeidnisnintchee imnibdo-tdhostehegrioguphoanfSdmlgo/wk-gd/odsaey;grhooupwse,vetrhi,stehfefebcitoloocgciucrarled at the same rate and was not statistically significantly different from controls. CONCLUSIONS cCoonmclmuesinotnsoonftauhtehaourt=hsorcsotnhcaltutshieonfsinadnindgowfheetxhteariybosu, aogrr1e3e": iTh,isinrethviisewpearrtdicouclsarnosttuadgyreaerewniotth thseign of adneavteolmoipcmaelntvaalritaotxiiocnitsyi. dWifhfiilcueltit0isagsreeses,d tthheatitnhceidbeinocloegoifca1l3siginbifiinctahnicsesotfuadny salhtoewreeddiancdiodsee-nrceeloafted tihnecrreefaosreewiistehvsatlautaistteidcaalssaigpnoisfsiicbalneceinaditchatihoingohfedsetvdeolsoepd-mgernotuapl, oisnitchiey.absenceofmaternal toxicity, and REFERENCE, CGoormtpaaenry,.E.RGi,kEe.rGL.abLoarmaptroerciehst,,IMn.c.T.StC.asPeau.l,1M98N2.. OErxaplertiemreanotloNgoy.s0t6ud3y1ToBf0T3-93S1,41FeCborCuianrryab1b9i52t.s. 3M 276 000173 DEVELOPMENTAL TOXICITY "itl: The Embryo-Feal Toxicity and Teratogenic Potential ofAmmonium Perfhuorooctanoat i the Rat TEST SUBSTANCE Iadmemntointiy:uAmmpmerofnliuourmoopeetrafnlouaotr,oaocmtmaononsituen(ApePrFfOl)u,oproecanprtylaaed, ePFcO,aFfCl-1u16oa,crFiCod-ao1m2cm6,otnFaiC-nu1mo6s9ai,ltcF,C-143, oara major component ofFX-1003 (CASRN 3825.26-1) 5R5e1m4a4)r.ksI:s pTuhreittyewstassub>s9ta5n%ce,heAPcFonOta[mCiFn(anCtFs:)pr(eCsOeOntNHw,e]e, [wCaFs,b(tCsF:n)e.dCOfOrNoHmL3]Man(Sdt.PPFaOulA, MisoNmers. No inhibitor, carriers, or additives sere present. DegradationofAPFO was considered insignificant unless the temperature was to exceed 250C (unpublished Du Pont data). METHOD MethodGuideline followed: Not specified GLP (Y/N): Not specified Year study performed: 1984 Species'Steain: RaSprague-Davley derived, Cel:CD (SD)BR strain. rNauumsgbreoruporfiaaln.imTawlos apdedridtoosnea:l,Fpoarit-hfedinghraoluaptsio(n6pdoarmtsi/ongroofutph)e,swteurdey,atddoedtitaolEsxwpietrhim1e2nmtat1 e(derfaetmoalloegy), e`axnpdotswuroegproorutpison(6ofdtahmes/sgtruoduy,p)25wearned a1d2demdatteodExfpemearliemernatts 2at(edaacmhs eaxlplooswuerdetcoolnicteern)t.raFtoironthweegraeviangcel-uded in Experiment |(tratology) and Experiment 2 (dams allowed to fitter, respectively. Routeofadministration: Inhalation snd ral D1o2spirneggnraengtiSmpernagliuset-Dalalwwlietyhruantistpse)r: gFrooruptheexipnohsaeldattioonApPoFtOiobnyofwhtholes-tbdoyd,ytvhaeptowrointhiallastcioonns0i.s0t,ed0.o1f, 11d, 10t, athned 1205amngd/m25' 6mgho/umrsg/rdoauyp,so,nwGerDe 6a-d1d5e;dtw0oeaacddhitniaoinlalIgnthre ouposra(6ldoarmtsonpoerftgrhoeups) tthaut2wd5eayren,dpai1r2S'pArPaFgOuei.nDcaowlmeyoilabtysgfaovratghee ofinrsGt aDnd6-s1e5cond trials, respectively, were administered 0 and 100 mg/kg/day Doses: For inhalation exposures: 0, 0.1, 1, 10, and 25mg/m',with two additional groups pair-fedtothe 10 and 25 mg/m' groups; for oral exposures: 0and 100 mg/ke/day. Statistical methods used: The ltr was used as the experimental unit for he purposeofsatsical `tehveailunactiidoenn(cSetoafpplreesgannadncHya,secmlianni,cal19s7i4g;n,HaasnedmmaantearnndalHodegaatnh,w1a9s75d)e.tTehrmeisniegdnibfyicuasneceoftofhdeifFfiesrheenrc.eesxaicnt pcroonbsaubmilpittiyotnesmto(Snigegeblr,ee19d5i6n)g. oAtstawnod-wbaeytwaenealnygsriosuopfsv.arDiuannnceet'wsasteustse(dSeteoldeatnedctTodrirfifee,re1n9c6e0s)inwafseeudsed to test the statistical significanceofdifferences between the control and APFO groups in maternal body 2m 000174 wsiegingihftic,anitn.boTdhye wpreeisgehntcgeoaifn,caonndceinntfaeteidocnornesluamepdtrieosnpownhseens tfhoer othnee-inwhaaylaatniaolnyspiostoifovnoarfitahnecestwuadsy was dstertuecrtmurianledalbteyraJtoinocnskhbeeetrw'esentetshte(cJoonntcrkobleegrreo,up19a5n4)d. tTheheAPsiFgOnifgircoaunpceowafsdidfefteerremnicneesdibnyinacpipdleinccaetioofnofthe `FiMsahnenr-'sWehxiatcntepyroUbatbeistli(tMyatnenst awnadsWahpiptlnieeyd,(H19a4s7e)m.aWnhaennd mHooerle,t1h9a7n4)7.5T%heticlsevoeclcuofrsriegdniinfitchaendcaetas,eltehceted sweavserpal(0r.e0p5r.odVuacrtiiavbeiliintdyicbeosuwtermeeacnaslcwulaasteedxpfroresssoemdeasessutalnsdafrrdoemrrEoxrpeofrtihmeenmte2anda(SmE)s. aIlnoawdedidtitoonl,ite). Rcoenmsiasrtkedso-faDentaiinlhaalnatdiodnisacnudssananoryalsipgonritfiiocna,nctapcrhotwoictohlwpoarraimaeltsoersexapnedridmeevnitast.ioTnsh:e Tfihset srtiauldywadesstihgen dtearmastowleogryepaolrltoiwonedofttohleitsetruadny,ditnhewhpiucphs wtheeredasmacsriwfeirceedsoacnridfaiyce3d5opnosGtD-pa2r1t;umw.hilFeorintthheeisnheacloantdiotnial, the 'poArPtFiOonboyftwhheolset-ubdyo,dythveatpwoor rinahallactoinosni(s0t.e0d, o0.f1,121,p1r0e,gannandt2S5pmragg/ume'-6Dahwoluersy/adiays,poenr gGrDou6p-1e5x.paIsnedthfeo oardamlinpiosrtteiornedo0ftahnedst1u0d0y,mg25kga/ndda1y2ASPprFaOguien-cDoarwnloeiyl baytgfaovragtheeofnisGtIaDn6d-1s5e.coFnodrtbiaoltsh,rroesuptesctoifvely, were bardemdi,nitshteryatwieonr,e freamnakleedswwietrheinmabrteeeddionngadnayass-bnyeebdoeddybwaesisghatndanwdheasnstihgenendufmobgerrooufpsmabtyerdotfaetmiaolneisn woerrdeer osrfrouapnsk,.wFeirnealaldy,detdwotoacdadicthiornaiall. groups (six dams per group) that were pair-toftehde10 and 25 mg/m' Faobrsetrhveetdedaatiollyofgoyrpaobrntoironmaolfctlhienisctauldsyig(nrsi.alOonne)G,Dda2m1,stwheerdeawmesigwheerde osancrGifDice1,d6b,y9,ce1r3v,ic1a6l,dainsdlo2c1atainond aannidmealxawmaisneedvaflourataendy. grTohsesoavbanroirmea,liuttieersu,s ainvdercownetiegnhttsswweerreeerxeacmoridneeddafnodr tthhenreupmrboedrucotficvoersptoatruasoufteesa,ch slievxeeadndanddeeaxdafmeitnueseds,forreesxtoerrnpalt,iavoinsndceiramlp,laanntdatsikoenlestiatles.altPeuraptsio(nls.veTahnedhdeeaadds)owfearlle ccoonutnrtoeld,anwdeihgihghe-ddaosned egyreosu.p fetuses were examined for visceral alterations a wel as macro- and microscopic evaluation of the Ftroiraltorianl tuwpo,toiGnwIDhi2c1.htThewdoadmasywsebreeforaeltlhoewexetpdeclitteedr,dathyoefppraorcteudruizteiowna,seatchehsdaammewaassthhaotufsoerd in aDnaminsdiwveirdueawleciaggeh.edTahneddeaxtaeomifnpeardtfuorritciloinniwcaalssniogntsedoannDdadyessi1g,n7a,te1d4,Daanyd 122poPsP.t-pOarntuDmay(PP2)3.PP aElalcdhapmuspwwearse ssaucbrsiefiqcueedn.tlPyuwpesiwgehreedcaonudntiends,pewcetiegdhfeodr,aadnvderesxeacmliinniecdalfsorigenxstoenmaDlaaylster4a,t7i,ons1.4, apnordti2o2nPaPn.dTohneDeayyesso2f7tahnedp3u1psPePrfeor atlhseogeaxvaamgienpeodrtoinonDaofytshe15staunddy.17PuPpPsfworertheesiancrhiafiiacteodnon Day 35 PP and examined for visceralandskeletal alerations RESULTS 'NOAEL (dose and effect) - maternal and developmental: devIenlhoaplmateinotna:l Ftooxrictiitayl iosn1e0-mtghe/Nm.OAFEoLr tfroiralmtawtoem--atlhetoxNicOiAtyEiLs |fomrgm/amt'e;rmtahle NtoOxiAciEtLy ifsorImg/' the NOAELfordevelopmental toxicity is 10 mg/o'. 278 000175 porOtriaoln:oftAhNeOsAtuEdyLucsoeudldonnloytobneeddeotseermlievneeld.foreither maternal or developmental toxicity since this LOAEL (dose and effect) maternal and developmental: Inhalation o(crontsiiasltionngoefwethte aLbOdAomEeLnsf,orcmhartoemrondaalcrtyooxircrihteyai,s c1h0rmomgo/r?hi,nobrarsheedso,natnrdeaatgmeennet:raellautnekdepctlianpipcaelarsaignncse.), aisn2d5simggn/imfi'c,anbtarseedducotniornesduicntifoonosd icnomnesaumnptfeitoaln baonddybwoediyghwtesigahntd;athsetaLtiOstAicEaLllyfsoirgdneivfieclaonptmiennctraelasteodxicity incidenceoffetuses with partially ossfid stemebrac FcoonrsitrsitailntgowofwettheabLdOoAmeEnLs,focrhmraotmeordnaaclrytooxrirchietsy,isch1r0ommogr/h?in,orbrahseead,oantraenagtemneednrtarleluantkeedptclaipnpiceaalrasnicgnes; the LweOiAghE.L for developmental toxicity is 25 mg/m', based on satsticaly significant reductions in pup body porOtriaoln:oftAhLeOsAtuEdLy ucsoeudldonnloy obneededtoesremlienveeld. for thermaternal or developmental toxicity since this Toxic esponseleffects by dose level - maternal: Inhalation `consAutm1pt0iaonndan2d5bmogd/ym'w,eitrgehattmaetn2t.5remlga/tme'd,csltiantiicsaticsailglnysosifgnmiafitceamntalintcorxeiacsietsy,iannidverredwuecitgihotnss;inleftohoardgy and death Oral `ConsumptAi1on0,0remdgu/cktgi/ondsayi,n tbhoedoynwleyidgohstegtaeisntse,d:ancdlidneiactahlss.ignsoftoxicity, reductions in food Toxic response/effects by dose level - developmental: Inhalation A125 mg, reductions in mean feal and pup body weights and statistically significant increases in the incidence offetuses with partially ossifid stemebrac. oalA100 mgkgiday, the only dose tested, no signsofdevelopmental toxicity were observed. Statistical results: inhalation - maternal AasCsi1g0neadn)d, 2si5gnmigfi/cman'trreedautcmteinotnsreiantfeododclcionniscaumspitginsoonf(2m1a.t8em+ma0l.4t6rvisci2t3.y4 (no0s.t3at8isitniccaolnstirgolnsi)f,icaanndce 4s1i.g2n5ifmicgamnt'r:edsutacttiisotnicsalilnybsoidgnyifwieciagnhttinwcirtehassetastiisntimcealansiglinviefricwaenicgehtats 2(5twmo-gt/ami?le(dDuMnanentnt'Wshittens,ey0<U0.0te5s)t;, P<0h.al0a5t)i;onle-tdheavregylo(p4moeunttaolf 12) and death (3 out of 12 dams). 279 000176 sAttat2is5timcagl/lyms,igrneidfuiccatnitonisncirnemaseeasn(pfe=ta0l.(0p4=b0y.t0h0e2)twaon-dtapiluepdbMoadnyn-weWihgihttnse(ypU= 0te.s0t2),inanthde incidenceoffeuses with partially ossified stemebrae. Oral:mAatt1e0r0namlg/kg/day, the only dose tested: clinical signsoftoxicity (no statistical sriegdnuicftiicoannsceinabsoigdnyewde)i,grhetdsucgtaiionnss(ipn<fo0o.0d5)c,onasnudmdpetaitohns((n3oosuttatoifsti1c2aldasmisg)n.ificance assigned), OdrNoeavlsteatlisotipcamlleynsitganilficant differences were noted between rated and control groups for any of the parameters measured. Remarks -- Additional information to adequately assss the data: InhalationExposure "Trial One: Tmrge/amt'maenntdecloantseisdtceldionficawlestiagnbsdoofmemnast,ecrharlomtooxdiacictryyfoorrhteraia,lcohnreom(otrebrianoolrogtyh)eso,ccugrerneedraalt 1u0nkaenpdt25 aTphpreeaeroauntceo,fa1n2ddlaemthsardgiyedindufroiunrgdtarmesatametnhteaetn2d5omf/thse'ex(poonsGurDe p1e2,ri1o3d,(ahnidgh1-7c).onFcoeondtactoinonsugmrpotuipononwlya)s. s(irgeniafticaanntdlyparierd-fuecdedgraotubpso.thS1i0g.nainfdic2a5ntmrge/dmu'ct;ihonosweivnebro,dnyowseiiggnhitfiecarntedailfsfoeroebnsceesrvweedraetntohteesde between sciognnciefnitcraanttioinnsc,rewaistehs istnamtiestaincalivseigrnwiefiicgahntcseawertehesheiegnha-tcothnecahnitgha-tcioonnceonnltyr.atiLoinkegwriosuep,, sUtantdisetricatlhley ciondnidciattieodn.s otfh study, a NOAEL and LOAEL for maternal toxicity of| and 10 mg respectively, was bNoodycfwfecitgshwtserweeroebsseirgvneidfiocannttlhyedmescirnetaesendanicn otfhper2e5gmnga/nmc'yogrotuhp ianncdidinentcheocfoenstrropltgornosu.p paMier-afned 2a5l mre/lavte.d efAfedcetst;aihloedwemviecrroisncotphiccovnitsrcoelraglraonudpetyhaetewxaasmipnaait-ifoendo2f5tmheg/fne'tu,sessdtaitdisntoitcarlelvyesailgnainfyictarnteatment tihnecrsetausdeyd,ianNciOdeAnEceLofafnedtuLsOeAs EwiLthfopradteavellyopomseinftiaeld soeximceibtryaoefw1a0saonbds2r5vemdg./n'U,ndreersptehceticvoenldyi,twioanss of indicated Trial Two: Cdleisncirciabledsifgonrsotfialmaontee.maMlattoeimcailybsoedeynawei1g0htangdai2n5dumrgi/nmg'twreeartemesnitmialta2r5inmtgyp/emawndasinlceisdsetnhcaenacontthroosles, rasaltmtenthtahteo2d5iufmfgrg/emnhc.e wNaosontohterstrateiasttimceanltlyresliagntiefdiceanftf.ecItnwarddeitrieopno,rt2eodu,tnoofr w12edraemasnydiaeddvedrusreienfgfects 'noNtOeAdEfLoraanndyLoOfAthEeLmefaosrumraetmeernntalsotfosriecpitryodouf1ctiavnedpe1r0fomremannc,e.resUpencdteirvehlye,cwoenrdeitiinodnicsaotefdt.he study, a 280 000177 SwiegingshtofondeDvaeylopImPePnt(6a.l1 tgoxtici2t5ymign/hms' gvsr.ou6.p8cgonisniscotnetdroolfss)t.atisOtnicaDlalyyssi4gnainfdic2an2tPrPe,dupcutpiobnosdiynwpeuipghbtosdy cPoPn:t9i.n7uegdatto2r5emmagi/norlovw5e.r10t.h3aninccoonnttrooll,s;alDtahyou2g2hPtPh:e d4i9f.f0ergeantce25wamsgno't svta.ti5s0t.i1calilny cSoingtnrioflisc.antN(oD.ay 4 seixganmiifnicaatnitonefoffectthsewyeerse.reUpnordteerdtfhoelcloownidnigtiexotnerofntahleexsatmuidyn,ataiNonOoAfEthLe apnudpsLoOrAwEitLh ofoprhdtehvaellmoopsmceonptiacl toxicityof10.and 25 mg/ny, respectively,were indicated. OlExposure "Trial One: 4"T0hreoenoGutDof122)5. dClaimnsicdalisdidgnusroifngmattreeartnmaelnttooxfic1it0y0imngt/hkegdAamPsFOthadturdiiendg wgeeseatsiiomnil(aorneodtehaotsheosneeGnDwi1t1h; cionnhtarloaltsi.onNeoxpaodsvuerres.eFsoigondsocfotnossuimpcliiyownearnednbotoeddyfwoeriagnhytsofwtehree rreepdruocdeudctiinvterpeaatreadmaentiemrsalssucchomap5ared to `trmeaaitnetdenaanndcecoonftprroel ggnraonucpsy woerriencniodteendcefoorfefestoalrpwieiognhst.s, Loirkeiwnitshee,innocisdiegnnciefsiocafnmtadliffofrermeantcieosnbseatnwdeen variations; nor were thre any effects noted following microscopic examination ofthe eyes. "Trial Two: Sefifmeicltasroonbsreerpvraotdiuocntsivfeorpcelrifnoicramlasnicgensofwienraennyootfedthfeorftethaeldoabsmesrvaastiinonrsiawleornee.notLeidk.ewise, no adverse CONCLUSIONS sCuopmpomretnedtboyntaheutdhaotra's conclusions and whether you agree: The author's conclusions appear tbe REFERENCE TPerroavtiodgeenfiulclPcoitteanttiioanlooff sAtmumdoynrievuimewPeedr:flSutoarpoloecst,anRoEa.ieet(aPl.FO1A9)83.nTthheeREamtb.rFyuon-dFaemteanltTaolxiacnidtyApapnldied TMoexdiiccoilnoeg,y.Ne4w:a4r2k9-,44D0E. 1Th9i7s1study wes performed at Haskell Laboratory for Toricology and Industrial 281 000178 REPRODUCTIVE TOXICITY STUDIES Title: ORAL (GAVAGE) TWO-GENERATION (ONE LITTER PER GENERATOIN) REPRODUCTION STUDY OF AMMONIUM PERFLUOROOCTANOATE (APFO) IN RATS ~ARGUS RESEARCH LABORATORIES STUDY NUMBER: T-6889.6, 2002. TEST SUBSTANCE Identity: Ammonium Perfluorooctanoate, CAS No. 3825-26-1 SRoelmuatrioknss:ofTthheeteesstt ssuubbssttaannccee wwaesrerepcreeipvaerdedonweNeokvleymabtetrhe7,te2s0t0in0gafnadcisltioraenddaprreopoamretdemfpoerrmautluartei.ons `wceormeposstiotrieodnorefftrihgeertaetsetda,rptircolteeicteodnffriolmwliitghht.theInSfpoornmsaort.ion regarding the purity, identity, strength and METHOD Method/Guideline followed (ie, OECD 414, etc.): The requirementsofthe U.S. Environmental Protection Agency (EPA) were used as a basis for the study design. `Typeofstudy (one-generation, two-generation, etc): Two-generation reproductive toxicity GLP (Y/N): The study was conducted in compliance with the Good Laboratory Practice (GLP) regulationsofthe U.S. EPA and the Organization for Economic Co-Operation and Development (inOtEegCrDi)ty.ofTthheerestwuedyr.e nQouadleivtiyatAisosnusrfarnocmetUhneitGLfiPndrienggusladteiroinvsedthfartoamfftehceteidnstpheectqiuoalnistdyuorring the conductofthis study have been documented. Year study performed: 2001 `Species/Strain: Sprague Dawley rats Sex (males/females/both): Both Number of animals per dose; 30 Route of administration: Gavage DPoFsOiSngbyreggaivmaegne (foirstsialxlwweietkhsupnriito)r:toFainvde dgurroiunpgsomafl3ti0ngr.atTspreerastmeexntpoefr dtoheseFgOrmoauplewerartes caodnmtiinniusteedruendtil amnatdilnagctwataisonc.onfirmed, and treatmentofthe FO female rats continued throughout gestation, parturition, Doses: 0, 1,3, 10, and 30 mg/kg/day Paerneemraattiionngaetxspwoesrueregipveerniotdesftosrubmsatlaensc/efeomnaeledsai(lPy,abnedgiFn1n,iinfgaaptpraoppprrioaxtiem)a:telMyalsiexawnedefkesmoafleagPe 2% 000179 (maatl1eesaasn7d0fdeamyaslebsewfeorrecgoihvaebnitdaotisoang)esanodncceondtaiinlyu,inbgeuginnnlitnhgeatdwaeyabneifnogre(saapcprrifoixcie.matFeIlyge7n0erdaatyison before cohabitation) and continuing until the day before sacrifice c`Sotnatsiusmtipctailomnedtahtoa,dsduurasteidonsCoofntgienstuaotuisondaatnad(dbeoldiyvewreyigthtes, abvoedryagweesifgoht pchuapnbgeosd,yfweeeidghts and pBearrcetn't smaTleestfeotfusHeosmoorgpeunpesitaynodfmoVraarliiatnyc,e aanndd cAunmaullyastiisveofsVuarrviivaanlc)ew(erAeNOanVaAly)zewdheusning a(ppp=r0o.p0r5i)at,eD(uin.etBta'rslTeets'tswTaesstuwsaeds fnootidseingtniiffyichanetstoartips>t0ic.a0l01s)i.gniIftichaencAe NoftOhVeAinwdaisvisdiuganlificant gcraosuepss.wheIrfethteheAKNrOusVkaAl-wWaasllniost Taepsptrowparisatstea,tiis,ti=cally0s.i0gn0i1fitchaentKr(ups<ka0l.-0W5a)l,liDsunTne'sts wMaesthuosedd.ofIn MthuelrteipwleerCeogmrpoartiesothnasnw7a5s%usecsd,toFiishdeer'nstExtahcetstTaetsisttiwcaalssuisgendi.fiAcalncoetohfetrhneatiunrdailviddeulailvegrryoudpast.a If diensvcorlivbiend.g discret data were evaluated using Kruskal-Wallis Test procedures previously Remarks - Decal and discus any significant protocol parameters and deviations: EGOeneration: "BTohdeyFOweaingihmtaslsofwFeOremaelxeamriantsedwetrweicreecdoarildyedfowrecelkilniycadlrsiingngs,thaebodrotsiaognes,pperreimoadtaunrde tdheelinvoernietsh,eadnadydoefaths. saancdriftihceen. oBnogdeystwaetiigohntdsaoyfsF(OGDf)em0a,l7e,a1t0s, w1e4,re18r,e2c1o,radneddw2e5e(kilnyecdeursisnagryth)eapnrde-oannldacctoahtaibointdaatyiosn(pLeDr)io1d,s5, r8,i1n1g,15t,heatnrdea2t2metnctapmeirniaold,bwohdiylweeiinghFtO).feFmoaoled rcaotn,svuamlpueisonwevrleureescoirndFeOd mwaeleeklaytsduwrienrg trheecorded weekly precobabitation period, onGDs 0,7, 10,14, 18, 21, nd 25 and on LDs 1,5, 8, 11, and 15 sEscterdouulsecdyccloibnagbiwtaastieovnapleuraitoedd adanidlycobnytienxuaimnignuatniioncoonffviargmiantailoncoytfomlaotgiynbgegbiyntnhingpr2e1sednacyesobfefsopreertmhein a eVsatgrionuaslcsemleaerwoarscaosnsfeisremadt.ion ofa copulatory plug. Onth dayofscheduled sacrifice, the sageofthe oWniethmianlcearcaht dpoesrafgeemaglreourpat,.cTohneseccouhtaibvietaotridoenr pwearsioudsceodn0sisatsesdigonfaparmeanxtailmguemneorfat1i4ondaryatss. {0Fecmohaalbeitrattsion, `iwnidtihveidvuiadlenhcoeuosifnsgp.ePramreinnt&alvafgeimnaallessmweearreoervacloupautleadtofroyr plelnaggtwhoerfegdeestsaitginoant,edferatsilGitDy i0ndaenxd, agessstiagtnieodnto ainnddexl,enrumdbureirngantdhesepxoostfpoafrftsupmripnegripord lliitetre,sniuzmebaenrdovfiaibmipllayn,tavtiiaobnilistyici,ndgeexn,elraacltactoinodnitiindoenxo,ftpherecednatm Survival, and sex ratio. Maternal behavior ofthe dams was recorded on LDS 1,5, 8, 15, and 22. FmaOlgeenraetrsa,t.i.onaafntiemraclosmwpelreetisoancroiftfihceedcboyhacbairtbaotinodnipoeiridoed;asapnhdyxLiDati2o2no(rdafyem1a0l6e0rat1s1),0noeftcrhoepssiteudd,yafnodr ewxealmiasneidntfeorrnaglreoxsasmliensiaotniso.noGfroisssuneescraonpdsyoriganncsl.udeIdndeixvaimdiunaaltoirognaonfsewxetreemawleisguhrefadcaesndanodrgoarnif-itcoe-s,bo5dy wtheyimguhst,anlidveorr,gaadnr-etnoa-lbrlaainndwse,ipgihtiraartiyo,suwteerreuscwailctuhloavtiedduoctrstahendbrcaeirnv,ik,idenefysc,idspildeyemn,isva(rwhioel,eeasntdes, cuaidn)d.),Triisgshtueespirdeitadiynmeids,inprnoesuttartael abnudffseermeidna1l0%vesfiocrlmeasl,i(nfwiotrhpocsosaigubllaetihinsgtlolaongdicsalanevdawliutathiaonndinwciltuhdoeudt the 283 000180 ptiitghittaerpyi,diaddyrmeinsa,l galnadndpsr,osvtaatgei.na,Hiustteorluosg,iwcialthexoavmiidnuactti,ocnerwvaisxpaenrdfoovramreideso,nritgihstsuteesstriso, msem1i0nraalnvdeosmicllyes, SHeislteocltoegdicraallsy.erAlslexFOfrgoemntehratcioonntrroaltatnhadthdiigehddoorspageeagrreoudpsm.orAillbugnrdoswserleesiaolnsso weexarmeienxeda.mined Hviatsstohlaotgiecxahlibeixtaemdinraetdiuocnedoffthee trepbroydcucittievrefoirlgianngstionmathtee,lcoowncaenidvem,isdi-rde,oose dgreoluipvs hweaasltchoynodfufcstperdinign; or mfoortiwlihtiyc,haensdtrmoourspchyoclloigcytywoerrsepeevramlunautmebdeirn,tmeotlileiftyc,aourdmoepripdhiodlyomgiys wofeFrOe agletenreerda.tiSonpemramlenuramtbse;r, tiemsptliacnutlaartisopnerimtaetsiwdecroencreenctorradteidonis wFeOrgeeenvearlautaitoendfienmathlee lreaftts.tesRtast.s Tthhaet dniudmnboetrdealnidvedrisatrliibtuetriwoneroef eSaxcarmiifinceedd tooncGoDnf25iatnhde aebxsaemnicneedofifmorplpaongtnaatniocnyssittaest.us.AUgrrosofnaepcprsoprseynolfythneontphroergacniacn,taabidsomwienrael and pweelrveicsavcirsicfeircaedwoans paenrefsotrimmeadt.edFdeamyal2e5 rotfgseswtiatthioount.a confimed mating dat that did ot deliver ier fAetmsaclheeadtusl,edblsoacordifsiacem,plaefste(1c0ommpalleetsiaonnodf1t0hefecmoahlaebsiteaatcihofno perhieod1i0naFnOd m3a0lemgr/aktsg/adnadyodnoLseDg2r2ouipns:FO3 meaclteisonancidte3sftheamtalliveefrosamhpelecsonwreorlegarlouop)colwleercetecdo,lbluecttneod aontdhrfrdoezaelsfowrefruetuprreoavniadlyesdisa.ndTthhee mreetuhlosdisd not appear tobe available at the time ofthe report. EGLeneration: "eTxhpeecFtIedgelnaecrtaattiioonnbpeuhpasviinorcaacnhdlgreorssweexrteercnoaulnptheydsiocnacleadnaoimlya.liePsh)yswicearl sriegcnosrdiendclfuodritnhge pvaurpisatciaocnhs dfaryo.m Peuxpabmiondeyd wfeorigthhtespwreeseencreoefcnoipprolends.LeDPdsup1s, 5t,ha8t,d1i5eadnbdef2o2r.s eOxnamLiDnat1i2,onalolftFIhgelneerratfioornpmuaplevipaubiplsiwtyeorne LleDsio1nwsearnedefvoarltuhaetecdaufsoerovfitadlesattaht.usAall iFsIhg.enPeruaptsiofnouranidsdweeardeowneaLnDesd2o1n0L2D2 w2e2rbeaesxedamoinnoebdsfeorrvgerdoss growth and viabilityofthese pups. Agrtowupe)anwienrge(sLelDec2t2e)d,ftowcooFnItigneuneerdateviaolnuaptuiposn,perressuxlipnegriln t60r0petortaglrroautsp((36000mraaltes paenrds6e0x)faesmsailgenpeduptso ptehre iFIvegednoesraagteiognropuupps.s nAott sleelaetcttewdofomralcoenptuipnuseadnodbsweorvafteimoanlefopruspesxupaelrmlaitteurr,awtihoennwpeorsesisbalcer,ifwiecerde. seTlhercteeed. phuepasd apterthseexlepveelrliotftterhweefrreonaelx-apmaiineetadlfsorutgurroesasnldeseioxnasm.inNaetcironoposfty hincclruodsesd-ascstiinognleedcrborsasi-nsefcortiaopnpoafrtehnet hwyedirgohceedpahnaldy.heThbreaibnr,as,plesepnl,eaenndantdhytmhuysmufsrfomrotmheonthereoeftsheeletchtreedepsueplsecpteerdspeuxpsppeelristexrwpeerelerertwaienredefor possible histological evaluation. All remaining pups were discarded withoutfutherexamination ThheeiFrIesgpeencctriavteiFonOrgaesnewreatrieognisviernestahendsadammes.dosDaogseagleevselweofrtehgeiveesnt sounbcsetdaanicley,anbedgiinnntihngsaatmewemaanninnegraansd cpaotnetnicnyu,inbgegunitninlitnhgeodnaydabyef2o8reposasctrpiafircteu.mF(ILDge2n8e)r.atFiIongefneemraalteioanimsawleerreaesxwaemrieneedvaflouraatgeed ofofrvaaggienoafl parcephuetidalsesexpuaarlatmiaotnu,rabteigoinn.niAngtaobnledoafyr3a9ndpoosmtpuanirttsumwa(sLDus3e9d).1BaosdiygnweFiIghgtesncwrearteiornecaotrsd0edcwohhaebnitraattison, oSinbelimnagsl,e arnatalpteerrnfaetmeaalesirgata.mernatnwdeosmmaadses.ignTmheentco0habciothaatbiiotnatpieornioredscuolntseidsitnedthoe afpaimrainxgiomfuFmI ogfen1e4radatyiso.n 284 000181 Body weightsofthe F1 generation male rats were recorded weekly during the postweaning. period and on the dayofsacrifice. Body weightsoftheF1 generation femal rats were recorded weekly during the postweaning period to cohabitation, and on DGs 0, 7, 10, 14, 18, 21 and 25 (if necessary) and on LDs 1,5, 8, 11, 15 and 22. Food consumption values for the F1 generation male rats were recorded weekly during the dosage period. Food consumption values for the F1 `generation female rats were recorded weekly during the postweaning period to cohabitation, on `GmDaste0r,na7l,f1o0o,d1o4n,1o8r,ab21ouatnLdD251a5,ndfooond LcoDnssu1m,5p,ti8o,n11vaalnudes1w5e.rBeencoatustaebpuluaptsebdeagfitnertLocDon15s.ume rAattss,cbhleodoudlesdamspaclreisfi(c1e,0 amfatlerescoamnpdle1t0ifoenomfatlehseccaochhabfiotratthieon10pearnidod3i0nmmga/lkeg/rdaasyadnodsoengrLoDup2s2;3inmfaelmeasleand f3ofretmhaelFesO gfoernetrhaetcioonntrwoelrgerporueps)ewnteerdeicnotlhleecrteepdoratn.dTfhreozmeentfhoordfsutsuercetainoanlcysiitse,tbhuatt olnivleyrtshaemspleersumwearnealaylsseos ctohlelreecptoerdt, bu no other details were provided and th results did not appear to be available at the time of bFi2rtghesnaernadtigornoslsitatletresrawteirones.exEaamcihnelditaerftwrasdeelviavleuraytteodfiodrevntiiafbyiltihteynautmlbeeasrtatnwdicseexeoacfhpudpasyo,fstihllei2n2h-sd,ayl.ve dpiossttapnacretwumaspemreiaods.urDeedadfopraulpsloibveseFr2vegdenaetrtahteisoentpiumpessownerLeDrsem1 oavnedd22f.rom the nesting box. Anogenital RESULTS pNaOreAntEalLm(adloessecaonudldenffoetctb)e deftoerrFmOi,neFd1,sianncdtFr2ea(tamsenatpperloaptreidateef)fe:ctAs NweOrAeEsLeenfoar tahlel dFoOses dteestteedr.minTehdesNinOcAetEreLatfomrenFtOeplaartenetdalefffeecmtaslewser=e1s0eemng/aktga/ldladyo.seAs tNesOteAd.ETLheforNtOhAe EFILmfaolreFs1cgoeunledrnaottiobne fteesmtaedl.es = 10 mg/kg/day. The NOAEL forthe F2 generation offspring = 30 mg/kg/day; the highest dose cLoOnsAiEdeLre(ddtoosebean|dmge/fkgf/edac~yft,o)trheFOl,owFe1,stadnodseFt2es(taesd,abpapsreodproinatsei)g:nifTihcaentLiOnAcrEeLasefsorinFtOhepalrievnertaalnmdales is kisicdonnesyiwdeeirgehdtst-otboe-t3e0rmmign/aklgb/oddayy,wbeaisgehdtoanndsitgonbifriaciannwteriegdhutctriaotnioss.inTkhiednLeOyAwEeiLghftoraFnOd pkairdennetyalwefiemgahlte-sot`geernmeirnaatliobnomdyalwseiigshctonasniddteorebdrationbweei| gmgh/rkagt/idosayo,bsbearsveeddoant tsihgenhifiigchaensttddeocsree.asTehseinLbOoAdELwefiogrhFtIs and bweoidgyhtwseiagnhdtignaitnhse,raatnidosoinfteirvmeirn,alKibdohedyy,waenidghspsl;eaenndwesiiggnhitfsi-coa-ntbrcahiannwgeeisghi tsa;bsaonldutbeaslievderonansdigsnpilfeiceannt, adonsde-druerliantgedthreedeuntcitrieondsosiinnbgopdeyriwoed.igThhtseiLnOdAbEodLyfwoeriFg1htgegnaeirnastoiobnsefrevmeadlepsriiosrctoonasniddedruerditnogbceoh3a0bitation ``mmagt/ukrga/tdiaoyn,, dbeacsteedaosenssitantbisotdicyalwleyisgihgtniafnicdanbtodinycrweeaisgehstignapionss,twaenadndiencgremoarsteasliitnya,bdseollauytse ifnoosdexual dceotnesrummipnteido;n,unadllerobtsheercvoenddaititohneshoifghtehstsdtoudsye,tnesottedr.eatAmeLnOtAelEaLtefdoreftfheectFs2wgeerneeroabtsieornvceodualtdannoyt bdoeses tested. Toxic responseleffects by dose level ~ parental/F1: 285 000182 oTbosxeircveefdfeicnttshienhFiOghg-ednoesreatgiroonupa.niSmiaglnsi:fiFcOanmtarleedsu;ctStiaotnisstiincablolydysiwgeniifgihctanatnidncbroedaysewseiinghcltingiacianl wsiegrnes were rmegp/okrgt/eddafyordomsoestgorofutphs.e dAobssaogleutpeerfioooddacnodncsounmtpitniuionngvuanltuielstweermrienaaltsioonsiogfntihfeicsatntuldyyriendtuhceed3,d1u0r,inagndth3e0se wpeerrieodosbsaetrtvheed3i0nmtgh/ek3g,/1d0a,yadnods3e0grmogu/pk,g/wdhialyewsiitghniinfitchaonsteisncarmeeaspeesriiondsr.elaAttivneefcrooopdscyo,nsstuatmipsttiicoanllyvalues osfigtnhiefilceafnttarneddurcitgihtoncspiidnitdeyrmmiidneasl,bloedftycwaeuidgahtespiwdeirdeymsiese,nsaetmi3,na1l0,veasnidcl3e0s (mwgi/tkhg/adnady.witAhbosuotluftlueidw)e,ights mprgos/tadtae,yp.ituTithaerya,blseofltautnedwreigihgthaodrfetnhaelsl,ivseprlweeans, asingnitfhicyamnutslywienrcereaalsseodsiingnailfidcoasntel-ygrroeudpusc.edKaitd3n0ey dweecirgehatssewdeirnetshiegn3i0fimcga/nktlgy/diancyrgeraosuepd.inAtlhleo1r,g3a,nawnedig1h0t-mog-/tkegr/mdianyaldobsoedygrwoeuipgsh,tbuatndsirgantiifoiscawnetrley rsiegdnuicfeicdafnotrlysionmcereoarsgeadnisnaatllthterehaitgehd dgroosuepgs.rouOpr,gaanndwesiiggnhitftioca-nbtrlayiinnwcereiagshetdrfaotrioostwheerreorsgiagnnisfaicmaontnlgy all otfretahteedadgrroeunpasl.coIrntcerxewaeserdetohbiscekrnveessdainndthpero1m0iannednc3e0omftg/hkeg/zdoanyadgolsoemegrruoluopss.a aFnOdfveamcauloelsa;tiTohnoefwetihgehciesllosf Kthiednleefytwaenidghritgthot-kbirdanieny,weaingdhtthweerraetisoisgonfitfhiceasnetloyrrgeadnuwceeidgahttst-hteoh-itgehremsitnadlosbeodoyf3w0eimggh/tkga/nddayo.f the left sTiogxniicfiecfanftettrseaitnmtehnetFeIlgaetneedraetfifeocntasnaitm3a,ls1:0,FaIndma3l0esm;g/Nkegcr/odsacyorpaincgeixnagmfirnoamtitoann raerveeaasliendtshteatliastteircaalllaynd smiegdniifaincalnot,bedsosoef-trheelaltievderdteocrmeoadseersaitnetteorsmiingahltbdoildaytiwoeniogfhtthsewpeerleviosbosfervneed.orTbhoethabksiodlnuetyes.weiStgahttissotifcatlhley rliigvhetr kainddnesyplseweenrweersiegnsiifginciafnitclayntdleycdreecarseeadsiendtahteal3l0tmrgea/tkegd/gdraoyupds.oseTghreouapb.solTuhtee awbesioglhuttseowfetihghtleoffttahned/or tthheypmruosstwaates, ablraoinsiagnnidfliecfatntaldyredneaclregalsaendd iwnetrhees1ig0naifnidca3n0tlmygd/ekcgr/edaasyeddoinsethgero3u0psm.g/Tkhge/dabasyolduotseagweeiggrhoutpo.f t`Thheetreartmiionsaolfbtohdeywewiegihgthstsofwtehreesseigmniinfailcavnetsliycliensc,rweiastehdainnald witthreoauttedflguriod,uplsi.veTrhaendralteifosaonfdtiheghwteikgihdtnseyosfto stihgenIifeicatensttliys,iwnictrheaasneddawtit3hmogu/tkthg/dtauyniacnadahlibguhgeirn.eaThaendrathtiosroifghtthteeswtesigthottsheofttehremilneaflt cbpoiddyidwyemiigsh,t,efwtere. c1a0umdga/ekpgi/ddiadyymainsd, hriigghhetr.epTidhiedyramtiisosaonfdtbhreaiwneoigthheofttehrmeisnaelmibnoadlyvewseiicglhets wwietrhelsiigdniftioctahnetlbyraiinncrweeaisgedhtat owfetrheeilnicvreerawseeidgahtt-|tmo-gb/rkagi/ndwaeyiaghntd whiegrheers,igwniitfhicsanitaliysiicnaclresaisgenidfiincatnhcee1atmg1/akngd/d1a0ymagn'dkgh/idgahye.r dTohseagreatios aglrloturpesa,teadndgrtohuepsr.atTiohseofratthieosolefftthanedsprilgehetnkwiedingehyt-wte-igbhrtasi-ntow-ebirgahitnwweerieghstigwneirfiecasnitglnyifdieccarnetlayseidncarte1ased in m1g0/akngd/d3a0ymagn/dkgh/idgahyer.,Tahnedtrhatiorsatoifotsoheftlehfet atnhdymruigshtweeisgthets-twoe-ibgrhati-now-ebirgahitn wweeirgehstigwneirfeicainntclryeadseecdreianstehdea3t tmeesktsg/odnlayy) aannddh3i0ghmegr/kdgo/sdaagye.grToruepsa.tmTehnetsreelraatteidosmwiecrroessciogpniicficchanatnlgyeisnwcreeraeseodbsaet r1v0edmgi/nkthg/daadyre(nrailght a`gnldanidnsotfhehilgivhe-rdoofsaenainmiamlasltsr(eactyetdopwliatshm3i,c1h0y,pearntdr3o0phmygan/ddvaacyuo(lhaetpiaotnocoeflltuhleacrelhlyspeorfttrhoephayd)r.enaFlI cortex) ofebmsaelrevse;dSitnathiisgthic-adlolsyesiagnniimfailcasn(t4i.n7cvreearsseussi5n4thinacvonetrraogle).numStbaetrisstoicfaelsltyrsoiugsnisftiacgaenst dpercr2e1asdeasyisnwbeordey dwueriignhgtspraencdohbaobdityawteioingh(tregcaoirndsewdeorne tohbesderavyecdohianbhiitgaht-idonosbeegaanni,mawlhseonnFdIaygsen5e0raatnidon57raptoswtewreean9i2n-g1,06 dduaryisongfdaugrei)n,gapnrdedcuorhianbgiagteisotnatainond adnudrilnagctgaetsiotna.tioDneacnredalsaecstaitnioanbsionlauntiemfaolosdrccoantseudmwpittihon30wemgr/ekogb/sdearyv.ed 286 000183 Toxic `Tonic responseleffects by dose effects in F1 generation level offspring (FI/F): male pups consistedofsignificant reductions in pup body winecirgehatseosnian preeratlmitetnert-brasliasteind the 30 deaths mg/kg/day (7 anima group total) woenrdearyespo1r,t5e,dainndF81omfallacetsatiinont.he Significant high dose group of 3d0aymg1/0k7gp/odsatyw.eaOnninegr,atbuwtatshmeomraijboruintdysoaftcrhifeicFeId moanldearyat3s9wpeorsetwfeoaunnidndgeaadndoanndoatyhser2w-4aspofsotuwnedandienagd. on cBoohdaybiwtaetiigohntsanadnddubroidnyg wteheigehnttigreaidnosswinegrepesrtiatoidstiincaallllytsriegantiefdigcarnotulpys.redStuacteisdtpicrailolry1s0igannidfidcuarnitnrgeductions pinosbtowdeaynwienigg.htBsowdeyreweoibgshetrvgeadinast w1e0raenadls3o0smiggn/ikfgi/cadnatylydrureidnugceddayisn t8h-e153,02m2g-2/9k,g/2d9a-y36g,r4o3u-p50o,nadnadys501--55,7 15-22, weight 36-43, 57-64,and64-70 gains were observe for ptohsetewnetainreindgo.sagSteatpiesrtiiocadl(lydasyisgni1f-i1c1a3nt,podsotswee-arneilnagt)e.d rAebdsucotliuotnesfionobdody cpeornisoudmp(dtaiyosn 1v-a7l0uepsoswtewreeansiinggni)f,icwahnitllye rreeldautcieved faoto1d0caonndsu3m0ptmigo/nkgv/adlauyesdwureirnegstihgeniefnitciarnetlpyreicnochraebaisetda.tion Sotbasteirstviecdalilny hsiiggnhi-fdiocsaentadneilmaaylssinvseresxuusaclonmcautrurreanttiocnon(ttrhoelasv(e5r2a.g2eddaayysooffparegpeuvteiraslusse4p8a.r5atdiaony)sowfeargee, r`ewsepiegchttivoenlya)p.erTolxitiecr ebfefseicstsininthFeI3g0enmegr/aktgi/odnafyemgarloeuppuopnsdcaoynssi1s,t5e,daonfd sigonfifliacctaanttirone.ducAtnioinnscrienapsuepinbody thriegahtemsetndt-orseeloafte3d0momrgt/aklgi/tdyay(.6 anStiamtailsstitcoatlally)wsiagnsiofbiscaenrtvdeedcrienaFs1esfienmabloedsyowneipgohsttsweaanndibngoddyaywsei2g-h8tatgatihen:s wDeecrreeoabsseesrivneadbisnolhuitgeh-fdooosdecaonnismuamlpstoinondawyesre, ob15s,er2v2e,dadnudr2i9ngpdoasytswe1a-n8i,n8g-,1a5npdodsutrwienagnilancgtaatinodn.during lactation in animals treated with average dayofvaginal patency) 30 mg/kg/day. were observed Statistically in high-dose significant delays in sexual maturation (the animals versus concurrent controls (36.6 daysofage versus 34.9 daysofage, respectively). Statistical results: FinOtgheenheirgaht-idonosmeaglreouapn.imaSilgsn:ifSitcaatnitstriecdaulclytisoingsni(fpicsan0t.0i5ncorreaps<es0.(0p1s) 0i.n0b1)odiyn cwleiinigchatl asnidgnbsowdeyreweoibgshetrvgeaidn `were reported 30 mg/kg/day fdoorsemogsrtooufpts.heAbdsooslaugteepfeoroidodcoannsducmopnttiionnuivnagluunetsilwetreremailnsaotisoingonfiftihcaentsltyudryediunctehde 3, 10, and (p< 0.01) during these relative food periods at the consumption v3a0lmuegs/kwge/rdeaoybsdeosrevegdroiunpt,hewh3i,l1e0,siagnnidfi3c0anmtgi/nkcgr/edaaseysw(ipt<hi0n.0t5hoosre ps 0.01) same in p3e,r1i0o,dsa.nAdt3n0emcgr/okpgs/yd,asyt.atiAsbtiscoallluytesiwgneiifgihctasntorfetdhuectliefotnsan(dp<ri0g.h0t1e)piinditdeyrmmiidnaels,boldetycwaeuidgahtespiwdeirdeymsiese,n at `wseermeinaallsvoessiigcnliefsic(awnittlhy arnedduwcietdho(upt<f0l.ui0d5)o,rprposst0at.e0,1)piattui3t0army,g/[kegft/daanyd.riTghhteaadbrseonallust,e swpeliegehnt,oafntdhtehlyimvuers w0.i0s5 soirgnpi=fi0c.a0n1tl)yiinntchreea1s,e3d, (apn<d01.001m)gi/nkgal/lddaoysed-ogsreougprso.upsK,idbunteysiwgeniifgihctasntwleyrdeecsirgenaisfeidca(npt<ly0i.n0c5reoarspesd: (p< 0i.n0c1r)eaisnedth(ep3s00.m0g5/kogr/pdsay0.g0r1o)upi.n aAlllltroeragteadn gwreoiugphst.-toO-rtgearnmiwneailgbhto-dtyo-wberiagihntwaenigdhrtatriaotsiowsewreerseignificantly significantly reduced for some among all trated groups. organs at the high dose group, and significantly increased for other organs wFeOigghetnse-rtaot-itoenrmfienmaalleboadniymawlesi:ghTtheanwdeoifgthhtes olfetthkeidlfnteyanwedirgihgth-ttkoi-dbnreayi,n waenidgthhtewreartieossoifgntifhiecsaentolrygraenduced (=0.05or p< 0.01) at thehighestdoseof 30 mg/kg/day. 287 000184 JFIitgebnaesriastiwoansofofbssperrivneg:d iMnatlhees;30Simggn/ifkiec/adnatyregdruocutpioonnsd(apyss0.1,015), ainndpu8pobfoladcytawtieoing.htSiognniafipcearnt hinicgrhedasoesseignrwoeuapotmfen3t0-melga/teddadyea.thOsn(e7 arantimwaalssmtootrail)buwnedresarcerpiofritceedd oinnFd1ayma3l9espoisnthweeaning and daneoatdhoernwdaasysf2o-u4ndpodsetawdeaonnindga.y 1B0o7dypowsetiwgehatnsinagn,dbbuotdtyhewmeaijgohrtigtayoinfsthweerFeIstmaatlisetircaatlslywere found tsriegantiefdicgarnotulpysr.edSutcaetidstpirciaolrly0siagnndifdiucarnitngrecdouhcatbiiotnasti(opnsa0n.d05duorripng< t0h.e01e)ntiinrebdoodsyiwnegipgehrtisodweirn eal Bobosdeyrvweedigahtt1g0aainnds w3e0rmega/lksgo/sdiagynidfuircianntglydaryesdu8c-e15d,(2p2<-200.,052o9r-3p6<, 40.30-15)0,inanthde5300-5m7g/pkosgt/wdeaayning. ogrropu<p0o.n01d),aydsos1e--8r,el1a5t-e2d,re3d6u-c4t3i,on5s7-i6n4b,oadnydw6e4i-g7h0tpgoasitnwsewaneirnego.bsSetratviesdtifcoarlltyhseiegnntiifriecadnots(apg<e0.05 (pepr=i0o.d01()daayts110-a11n3d p3o0stmwge/akngin/gd)a.y dAubrisnogluthtefeonotidrceopnrseucmophtabiioantvieolnuepserwieorde(dsaiygsni1f.i7c0antly reduced 0p.o0s1t).weaStnaitnigs)ti,cawlhliylseigrneilfaitcivaentfdoeoldaycson(spu<m0p.li0o1nivnasleuxeusawlemraetusriagtniifoinca(ntthleyaivnecrraegaesedday(opfs 0p.r0e5puotripl< vseerpasruast4i5on.)5 wdearyesoofbsaeger,verdesipnechtiigvhe-ldyo).seFaenmiamlaelss;vseirgsnuisficcoanncturrerdeunctticoonnstro(lps<(05.20.12)dinapouyfpabgsoedy iwnecirgehatseoninatrpeeartlmietnetrrbealsaitseidnmtohrea3l0itmyg/(6kga/ndiamaylgsrtooutpalonwadsayosbs1e,r5,veadndin8oF1flfaecmtaalteison. An (opn=p0o.s0t5weoarnpi=ng0.d0a1ysi2n-b8oadtythweehiigghhtessatnddosbeoodfy 3we0imgghrtkgga/idnasy.weSrteatoibsstiecravlelydsiingnhiifgihc-adnotsdeecarneiamsaelss 0o.n01d)ayisn a,bs1o5l,ut2e2,faonodd c2o9npsousmtpwteiaonninwge,raenodbsdeurrivnegd dlaucrtiatnigond.aySsig1n-i8f,i8c-a1nt5 dpeocsrtewaesaensi(npg=a0n.d05duorripnge 00..0032)) sleacxtuaatliomnatiuraantiimoanls(hreeaatveedrawgiethda3y0omfgv/akggi/ndaayl.patSteantciys)tiwcaelrley soibgsneirfivceadntindehliagyhs-d(opse<an0.i01m)ailns 0.04) versus concurrent controls (36.6 daysofage versus 34.9 daysof age, respectively) oFrI pge=ne0r.a0t1i)otnraedautlmtenatnriemlaaltse:dMeaflfeecst;s Natec3r,o1s0c,oapnidc e3x0ammgi/nkatgi/odnayrervaenagliendgsftartoimstitcaanllayrsisgniinfitchaentlat(epr<al0a.n0d5 s`imgendiifaincalnotb(espo=f0t.h0e5 olirvepr=to0.m0o1d)e,rdaotsee-troelsaitgehdtddeiclraetiaosnesofitnhteerpmeilnvailsobfodnyeweoirgbhottshwkeirdeneoysb.servSteadt.istTihcaelly aalblstolruatteedwegiroguhpss.ofTthhee albisvoelu(tpe=w0e.0i1g)hasnodftshpleeelenft(apnsd0/.o0r5roigrhtpK=id0.n0e1y)s wweerreessiiggnniiffiiccaannttllyyddeeccrreeaasseedd(atp< d0.e0c1r)eaisnetdhe(p3=00m.g01k)gi/ndtahye d1o0saengdro3u0p.mgT/hkge/adbasyolduotseewgerioguhptso.fTthheeatbhsyolmuutsewwaesigahltoofstihgneifpircoasnttaltye, brain `agnrdoupl.eftTahderernatailosgloafndthweewreeigshitgnsifoifctahnetlsyedmeicnraelavseesdic(lpe=s,0w.i0t5horanpd<wi0t.h0o1u)tinfltuhied,3l0vemrg/akngd/dlaefy adnodsargieght `Kgirdonuepsy.sTthoethreattieorsomifntahlebowdeiygwhetisgohfttshweelreefstiegsntiifs,icwaintthlyanindcrweiatsheodut(ptshe0t.u0n5iocra apl<bu0g.i0n1e)aiannadltthreeraitgehdt hteisgthiesrt.oTthhee treatrimoisonafltbhoedwyewiegihgthst,oftwehreelseifgtneipfiidcaindtylmyisi,ncorfeasceadud(pa<e0pi.d0i5doymips,=r0i.g0h1t)paitd3idmygm/iksg/adnadybarnadi.n htiogthheer.teTrhmeinraaltiboosdoyfwtehiegwhetigwhetreoftsihgenisfiecmainntally vienscircelaessedwi(tph<l0i.0d5toorthpe<br0a.i0n1)weatig1h0tmwge/rkeg/indcaryeaasnedd at | lmigv/erkgw/ediagyhta-nod-bhriagihnerw,ewiigthhtswtaetriestisciaglasiifginciafnilcyanicnecr(epa<se0d.0(5p)<0a.t011)ainndth1e0 m|gm/gk/gk/dga/yd.ayTahnedhriagthioesrofdtohsaege 0`g.ro0u5ps,oarnpd<th0e.0r1a)tiiosnaolftthreealteefd agrnoduprsi.ghtThkiedrnaetyiowsoeifghtihse-stpol-bereaniwnewieghitg-h{to-wberraeinsiwgeniigfhictanwtelryeisnicgrneiafsiecdan(tply wdeecirgehatsweedr(eps<ig0n.i0f5icoanrtply<d0e.c0r1e)asated1(mpg=/k0g./0d5aoyrapnd<h0i.g0h1e)r,atn1d0 atnhdr3a0timogslokftgh/deeyt.hyTmhuesrwaetiigohotf-toh-ebrlaeifnt 288 000185 aThnedsreigrhattitoesstweesrweeisgihgta-itfioc-abnrtaliyniwnecirgehastewde(rpe<in0c.r0e5asoerdp i<n t0h.e013)magt/1k0g/mdga/ykga/nddayhi(grhiegrhtdeossatgseognrloyu)pasnd 30 mstgag/edsapyer.21Fedmaaylsewse;rSetaotbissteircvaelldyisnihgniigfhi-cdaontseinacnriemaasless ((4p.<7 v0e.r0s1u)sin5.t4heinacvoenrtargoelsn).umSbteatrissotifcaelsltyrous sdiogsneifainciamntaldsecorneadsaeyss(50pa0n.d0537oppos<tw0e.a0n1i)ngi,n bdourdiyngwepirgehctoshaabnidtabtoodny(wreeicgohrtdegduonnstwheerdeaoybcsoehravbeidtaitnihoinghbdeecgraena,sweshe(np<FI0.g0e5neorrapti<on0a.t0s1wienraebs9o2l-1u0t6fodoadyscoofnasguem)p,iiaonnd wdeurrienogbgseesrtvaetdiodnuarnidngladcutratiinogn. Significant precohabitation and daring gestation and lactation in animals treated with 30 mg/kg/day. Fre2lagteendeerfafteicotnsoofnfsapnryinogf:thUendoebrsetrhveecdonpdairtaimoentserosftwheerestnuodtye,dnio stthaetiFst2icgaelnlyersaitgniiofnicoafnfts,prtirnegatmentRemarks: Pesrtirourstsotmaagtesinpge,rt2h1e dstauydsyianuhtihgohr-sndoosteedanaimsaaltss(t5c.a4lvyesrisgunsif4i.c7anitn iconnctrreoalsse).inFothretahvisercaalgceulnautmibone,rsthoef ncaulmcbuleartoiofnicnadnepbeenudseendt oasccaursrcerneceensofofreesftfercutssionntthhe 21esdtrauyssocyfcolbe,sebruvtaatimornewadsetdaeitleerdmainnaeldy.siTshsihsoutlydpetohefn abnealcyosnidsucthtaetdsthoodweetdetmhienree wwheertehneoretfhfeercetsisotnruthly aensterfufsecct.ycl3e;MthCeormepvaenreyn(o20d0i2f)ferreecnecnetslyncothmeplneutmebdearnof cfoenmadluecstewditbhy>th3edUySasEoPfeAst(r2u0s02o)rawlistohd>em4ondsatyrsoatfedditehsattrutsheirnetwheerceonntorodlifafnedrehnicgehs dionstehegreosutprsu.s cyAcnlaelyses `cyacmloensg(tRh)e, cuonnetrvoelnacnydclhiinggh (dIoRs;edgerfoiunpesd.asTbhreecfypcelreisowdesrweietvarleuagtueldaarsphatatveirnng) eoirtpheerriroedgsuolafrpr4.o5lodnagyed dpioessstirbulsy(pdseefuidnoepdraesgn4a-n6td,a(yPdSiPe:stdreufsinpeerdiaosds6)-gerxetaetnedreddaeyssotrfusl(eduekfoicnyetdesa)so3roprersidsatyesntoefsctormuisf(iPcEd; sdmeefairnse)d, adsifoferrengtreiantearndyaoyfstohfecpoarrnaimfeiteedrssmmeeaarssu).redThe data are summarized in below. The two groups were not Ovarian Pattern R R-i . PSP PE Type Irregularity Total 34ddaayyEsditersutrsus no pattem 1C8ontrol 10 2 2 61 1 APFO 2(030mgrkg) 9 1 2 6 1 Tthheusw,atyhiniwnhcirecahsethientchaelcnuulamtbieornwoafessdtornues,staangdeispsenrot21biodlaoygsictahlaltywmaesanniontgedfbuly th study authors is due to Parental Males (0) 289 000186 OclnieniFcOa smiaglnesr(aemiancitahtei3on0,mcgo/lkdg-t/-dtaoyucdho,seangdroduepcrweaassesdacmriofircedacotnividtay)y.45Neocfrtohsecosptuidcyedxuaemitnoaatdivoenrisnethat ascnhiemdaullreedvseaaclreifdiace.palSetaatnidstticaanlllyivesri,gnainfidcranetditnesctreesa.seAsllinoctlhienricFaOl sgiegnnesrawteiroen amlasloeorbastesrsvuerdviinvemdaltoe rats in the high-dose group that included dehydration, urine-stained sbdominal fur, and ungroomed cost. Saingdnicfoinctainnturiendguucnttiiolnsteirnmibnoadtyiowneoifgthhteasntdubdyodiyn twheeig3,ht10g,aianndwe3r0emrgep/ordteadyfodromsoesgtrooufptsh.e dAobssaolguetpeerfiooodd cwhoinlseumsipgtniiofnicvaanltuienscrweearseesalisnoresliagtniivfeicfaonotdlycroendsuucmepdtdiuornivnagltuheessewepreerioobdssaervtehdei3n0thmeg/3,kg1/0d,aaynddo3s0e group, mgkg/day within those same periods. Nasosetsrseeadtmiennctl-urdeilnagt,ednuemffbeecrtssowferdeayrseptoortiendseamtianantyed,onsuemlbeevresl foofartansytohftathmeatmeadt,infgertainlidtyfeirntdileixt,y pnaurmabmeertserosf rpraesgwniatnht craotnsfpierrmerdatsmaitnicnoghadbaitteastidounr.inAgttnheecfriorsptsya,ndnosenceoonfdthweeeskpoefrcmophaarbaimteattieorns,eavanldunatuemdbe(rspseorfm `number, motility, or morphology) were affected by treatment at any dose level. Amgt/nkegc/rdoapys.y,Asbtsaotilsutticealwleyigsihgtnsifoiftcahnet rleedftucatnidonrsigihn tceprimdiindaylmbidoedsy,wleefitghctasudwaeerpeisdeiednymaits,3,s1e0v,inaanldv3e0sicles s(iwgintihfiacnadntwliytrheoduutcfelduiadt,3p0romsgta/tde,apyit.uitTarhye, albftsoalnudteriwgehitgahdtreonftahlse, ssepimeienna,lavnedsitchleysmuwistwhoeurtefallusiod was siingcnriefaisceadntilny arlledduocsee-dgirnoutphse. 10Kimdg/nkegy/wdeaiyghdtossewegrroeups.ignTifhiecaanbtsloyluintcerweeaisegdhtinofthtehe1,li3v,earnwdas10simggn/ikfigc/adnatlyy dweoisgehgtroaunpds,rabtuiotsswiegnriefisciagnntilfyicdaenctrleyaisnecdreinastehdei3n0almlgt/rkegat/eddaygrgoruposu.p. OArlglaonrgweainghwte-itgoh-tbtroa-itnewrmeiingahl braotdiyos woregraenssiagnmiofincganaltlytrreeadtuecdegdrfoourpss.ome organs atthe high dose group,andsignificantly increased for other Norogatnrse,awmeinht.trhelaetxecdepetfifeocntsofiwnecrreesaeseendatthnieckcnreospssyanodr purpoomnimniecnrcoescooftphiceezxoanmaingaltoimoenrouflotshaearnedproductive vacuolation ofth celofthe adrenal cortex in the 10 and 30 mg/kg/day dose groups. SpreersuenmtainnallylsissamfoprletshetFesOtegde,nienrcaltuidoinnmgacloenstrsolasm.pCloendtartolthmeaelnedsohfacdohaanbiatvaetriaogne scohnocweendtrtahtaitonPFoOfA0w.a03s4% 0m.g0/1k4g8/duag/yldPoFseOAg.rouTpsr.eated males had 51.19.30 and 45.3412.6 ugl, respectively for the 10 and 30 Parental Females (FO) NNootrtreeaattmmeennttr.erleaatteedd defefaetchtssowreraedvreerpsoertcelidnifcoarlbsoidgynswweeigrhetsr,epboordteydwienipgahrtengtaailnsf,eamnaldeasbastolauntyedaonsderleelvaetli.ve food consumption values. Tnahteurrealwdeerleivneoryteasntdmelnet-rreolbasteerdvaetfifoecntsswoenreesatfrfoeucstecdyeblyictirye,atmmaetnitn,gtohtfier,titlhietynpuamrbaemretsoerfs.daNmosndeeloifvtehreing (Hintutmerb,etrhoefdduaramtsiowniotfhgeosnteatoifonm,orthe laivveerbaogmespufoprsinmuplmabnetraotfiponresgtnsanpterradtesl),ivtehreednulmtbre,rstohefdgeasntsatiwointhindex 290 000187 smteiallnbobrinrtphupwse,igdhatmsswweirtehcaollmppaurpasbdlyeinog,colnitvreoblosrnamaondngstailllltbrorenatpeudpgsroviuapbsility index, pup sex ratios, and N`weecirghotpss,yanadndorhgiasnt-otpoa-ttheorlmogiincaallbeovdayluwaetiigonhtwrearteioaslwsoeruenrceommaprakarbalbel.e oTecromnitnoall bvaolduyeswfeoirgahlsl,troeragtaend `t@hreosuepso,rgeaxncewpetigfohrisk-iod-nteeyrmainndallivbeordwyeiwgeihgsh.t The and owfetihgehtlseoftfktihednleeyftweaingdhtr-itghot-bkriadinneyw,eiagnhdttwheerreatios of swiegingihfticwanatslyalrseodusicgendifaitcatnhtelhyirgehdesutceddosaeot3fa3n0d m1g0/mkgg//kdga/yd.ayT.he ratioof iver weights-to-terminal body Rinesaullltssaomfpltehse steesrtuedm, aenxacleypstisinincoFnOtrgoelnserwahteiroen tfheemalleveesl sampled on was below LD the l2i2mistshoofwqeudantthiattaPtiFoOnA was preseat (r0e.s0p0e5c2t8iuvge/l1yf).ortThreeat1e0danfdema3l0esmgh/akdg/adnaayvedroasgeegcroounpcse.ntration of 0.37+0.0805 and 1.02:0.425 ug/l, F1 Generation - Males Ntroeaetfefdecatnsdwceornterroelpgorrtoeudpsatwaenrye dnoosteedlefvoerltfheontuhmebveiarbsiloiftpyuapnsd sluarctvaitviionngipnedircelsit.terN, tohedipfefrecreenntcaegsebemtawleeen s`piugpnsi,filcitatnetrlsyirzeedauncdedavienrtahgee3p0upmgb/okdgy/dwaeyigghrtoupeprointdearyast b1,irt5h,.anPdupofboldayctwateiiogn.ht Oonftahepeprulpisttenrecbraospissiweads.. abtrawien,ansipnigc,ennoansdtattihsytmicuasllaynsdigtnhifeircaatnito,sorefatthmeesnet-orreglaantewdediigfhfesretnoctehsewteerremionbaslebrovdedy wfoerigthhet waenidghbtrasoinf the weight dSiogsneifgircoaunptoifnc3r0eamsegs/kignt/rdeaayt.meOnntererlaattweadsdmeaotrhisb(u7ndansiamcarilfsitceodtao)nwdearye3r9eppoorsttedweiannFiIngmaalnedsainnotthheerhwiaghs found dead on day 107 postweaning, but the majorityofthe F1 male ats were found dead on days 2-4 postweaning. oSftaetnitsitriecalploystsiwgenainfiicnagntpeirnicord.easTesheisneclsiingincsalisnicglnusdoefd taonxiicnictryeawseerdeianlcsiodeonbcseoerfveadnniunlFa1r cmoanlsetsridcutrioinnogfmtohset tail at alldoses,with and 30 mg/kg/day in statistical significanceatthe the numberofmale rats that w1,er1e0,eamnacdi3at0emdg;/akngd/adasyi;gnaisfiigcnainfticiannctreianscereiansteheat 10 imgn/ckigd/ednacyeo.furine-stained abdominal fur, decreased motor activity, and abdominal distention at 30 `Bcoodhaybiwteaitgiohntsanadnddubroidnyg twheeigehnttirgeaidnosswinegrepesrtiatoidstnicaalllyrseiagtneifdigcarnotulpys.redStuacteisdtipcrailolrytsoiagnnidfidcuarnitnrgeductions pinosbtowdeyanwienigg.htBsowdeyreweoibgshetrvgeadinast w1e0raenadls3o0smiggn/ikfgic/adnatylydrureidnugceddaiynsth-e153,02m2g-2/9k,g/2d9a-3y6g,r4o3u-p50o,n adnadys501--58,7 15-22, weight 36-43, 57-64, and 64-70 gains were observe for pthoestewnetainreindgo.sagSteatpiesrtiiocadl(lydasyisgni1f-i1c1an3t,podsotswee-arneilnagt)e.d rAebdsucotliuotnes fionobdody `pecroinosdum(pdtaiyosn v1-a7l0uepsoswtewreeansiingngi)f,icwahnitllye rreeldautcieved faoto1d0caonndsu3m0pmtgi/okngv/adlauyesduwreirnegstihgeniefnitciarnetlpyreicnochraebasietda.tion wStearteistoibcsaellryvesdiginnifhiicgahnt-d(opsse0a.n0i1m)adleslavyerssuins sceoxnucaulrrmeantturcaotnitoronl(sth(e52a.v2erdaagyesodfaaygoef vpreerpsuutsia4l8.s5epdaaryastoiofna)ge, respectively). 21 000188 N`poreagpnpaanrceynitnedfifceecsts(nwuemrbeeorbosferpvreedgnoanncaineysopfetrhneummabteirnogforratfesrttihleittympaatreadmeatnedrsraitsncilnudcoihnagbifetrattiiloitny,and rweistphecctoinvfeilyr)m,edthmeantuimngbedraotefsddauyrsintgo tihnesefmrisntawteee,kt.heNnoumsbaetsrotifcaaltlsy stihgantimfaictaendt,, atrnedattmheennt-urmebleatreodferfaftescts were observed on anyofthe sperm parameters (morility, concentration, or morphology). ``Nmegc/rkogs/cdoapyircaenxgaimnignfartoimon(arnevaeraelaesdisntatthiestliactaelrlaylsaingdnimfiecdainatntrleoabtemseonfttrheelaltievderetfofecmtosdaetr3a,te10t,oasnldigh3t0dilation ofthe pelvisof one or both kidneys. Sotbasteirsvteicda.llyThsiegnaibfsioclauntte, dwoesieg-hrtesloaftetdhdeelcirveearsweesrien tsiegrnmiifniaclanbtoldyyinwceriegahstesdoafnpdartehnetaablsoFl1utmealweesigwhetrsoefthe sKpildeneenyswewreeresisginginfiifciacnatnltylydeicnrceraesaseeddatinaltlhter1eaatneddg3romugp/sk.g/Tdhaeyadbossoelugtreowupesigahndsosfitghniefilceafnttalnydd/eocrrreiagshetd in t1h0ea3n0dm3y0/kmgg//dkagy/ddaoysedogsroeugpr.ouTpsh.eTahbseolabustoelwuetiegwhetioghfttoheftthheympurosstwaatse,ablrsaoisniagnnidfilceaftntaldyrdeneaclregalsaendd iwnetrhee s`isgincilfeisc,anwtiltyhdaecnrdewaistehdoiunttfhleui3d,0 lmigv/erkga/nddalyefdtoasnadgeriggrhotupk.idTnehyesrtaotitohseotfterhmeinwaeligbhotdsyofwetihgehtssemwienrael stihgentifuinciacnatlaylbiungcirneeaaseadndintahll rtirgehattetdesgtriosutpos.thTehteerrmaitniaols obfotdhyewweeiigghth,tswoefrtehseiglneiffitceasnttsl,ywiintchraeansdedwiatth3out `empgi/dkigd/ydmaiys aannddhbirgahienr.toTthhee rtaetrimoisnoaflthbeodwyeiwgehitgshotfwtehree lseifgtneipfiidcaindtylmyisi,nclreefasceaduadta1e0pimdgi/dkygm/ids,ayriagnhdt hmigg/hkerg./dTahyearnadtihoisogfhetrh,ewiwtehigsahttiosftitchael ssiegmniinfailcavnecseicaltes1 awnitdh1f0lumigd/kttg/hdeay.braTinheweriagthiotsowferteheinlcirveearsweediagtht1offot-bhreailnefwteaingdhtriwgehtrekisdingneiyfiwceaingthltys-itnoc-rberaasiend wineitghhet|wmegr/eksgi/gdnaiyfiacanndtlhyigihnecrredaosseadgien garloutprsea,teadndgrtohueprsa.tiTohse rtahteiorsaotfiotsohfetshpeletehnywmeuisghwte-itgoh-tb-rtaoi-nbrwaeiinghwteiwgehrtewseirgenisfiigcnainftilcyandtelcyredaescerdeaaste1d matg/1k0ga/ndday3a0nmdg/hkigg/hedra,y.anTdhe rdaotsiaogsoeftgrhoeupsl.eftTahnedserirgahttiotseswteesrewesiigghnitf-itcoa-nbtlryaninwceriegahstedweatre10inmcgr/ekags/eddaiyn t(rhiegh3tmtges/tkigs/odnalyy)aannddh3ig0her mg/kg/day. Hmiisctroopsactohpoilcocghicanegxeasmiwnearteioonbosfertvheedrienptrhoedaudcrteivnealorgglaannsdswoafs huingrhe-mdaorskeabalnei;mahloswe(vceytro,ptlraesamtimcenhty:preerltatreodphy `tarnedatveadcwuioltaht3i,on1o0,ftahned e3l0lmsog/fktgh/edaayd.renNaol cotohretrext)raeantdmeinntt-hreellaitveedr e(fhfeepcattsocweelrleulraerpohrytpeed.rtrophy)ofanimals FI Generation ~ Females Ntroeaetfefdecatnsdwceornetrroelpgorrtoeudpsatwaenrye dnoosteedlefvoerltfhoerntuhmebveirabsioliftpyuapnsd sluarctvaitviionngipnedircelist.terN, othedipfefrecreenntcaesgebemtawleeen apluspos,silgintiefricsainztelaynrdedavuecreadgienptuhpe 3b0odmyg/wkegi/gdhatypegrroluitpteorna dbaiyrtsh.1, P5,upanbdodoyfweliacgthattioonn.a Opferthleittperupbsasis was nweecirgohptssioefd tahtewberaaniin,ngs,plneoenstaatnidsttihcaylmlyussiagnnidfitchaentr,atrieoasotmfetnhte.sreeloartgeadndiwfefiegrehnscetsowtehereteorbmsienravlebdofdoyr twheeight and brain weight. 292 000189 Adanysin2c-r8eaatsethine thriegahtemsetndt.orseeloafted30momrga/lkigt/dya(y6.anNimoalasdvteotrasle)cwlaisnicoablsseirgvnesdofintrFe1atfmeemnatl.erseloatnedpostotxwiecaintiyng were reported for any dose level during any timeofthe study period. aStnaitmiastliscaolnlydsaiygsni8f,ic1a5n,t2d2e,c2r9e,as5e0s,iannbdo5d7y pwoesitgwhetasnainngd,bdoudryinwgeipgrehctogbaaibnistawteirone (orbesceorrvdeedd ionnhtihgeh-ddaoyse cDoehcarbeiatsaetsioinn baebgsaonl,utwehfeonodF1cognesnuemrpattiioonn rwaetsreweorbese9r2v-e1d0d6udrianygsodfaaygse)1-,8,an8d-1d5urpionsgtgweesatnaitnigondaurnidnglactation. `prceocnoshuambpittiaotniovnalauneds dwuerriengcogmepstaartaibolneaancdrolsasctaaltliotnreianteadnigmraoulpss.reated with 30 mg/kg/day. Relative food oStbasteirstviecdalilny hsiiggnhi-fdiocsaenta(npi<ma0l.s01v)erdseulsaycsonicnusrerxeunatlcmoanttruorlasti(o3n6.(6thdeaayvsoerfaaggeedavyeorsfusva3g4i.n9aldapyastoefnacyg)e,were respeciively). Nofodaefyfsecitnscwoehrabeiotabtsieornv,enduomnbeerstsroofuastcyscltihiattym,aotreo,nfaerntyioliftythinedmexa,tirnatgsawnidthfecrotinlfiityrmpeadrammaettienrgs d(antuemsbers dhuorwienvgert,hestfairtsitstwiecaelkloy sficgonbifaibciatnattiinocnraeansdesnuinmbteheraovfreartasgepnruegmnbaenrtspoefresrtartouinscsothaagbeistapteiorn2).1 dTahyesrienwheirgehdose animals (47 versus 5.4 in controls). ANlulmbnaetrursaolfddealmivserdyeolbisveerrivnagtilointserws,ertheeadlusroaatpipoanorefngtelsytautniaofnf,ecatveedrbagyetsrfeoartmiemnptlaanttaantiyodnossietelsevpeelr delivered lniutmeb,etrhseogfesdtaamtsionwiitnhdesxil(lnbuormnbepruopfs,ddaammsswwiitthhoanllepourpmsadryeinlgivaenbdorlnipveubposr/nnaunmdbesrtoilflpborrengpnuapnst waetsr)e, the comparable among treated and control groups. Npiotittraeraytmaenndt-trheelartaetdioesofffetchtsewpeirteuiotabrsyerwveiegdhot-nttoe-rtmeirnmailnablobdoydwyeiwgehitgs.ht aTnhdetaobstohleubtreawieniwgehitgohfttwheere Sdiigfnfiefriecnacnetslywedreecrreeapsoerdteadt 3fomrgt/hkega/bdsaoyluatnedwheiigghhers,obrutradtiidosnfootrsohthoewraordgoasnes-reevsaplounasteed.. NNoootthreeratment. related effects were reported following nectoscopic and histopathologic examinations. F2 Generation Offspring Nreolatterdeaetfmfeencttsrewlearteedreapdovretresdefcolilnliocwailnsgingenscrwoesrceopoibcseexravmeidnaattiaonny,dwoistehltehveele.xcLeipkteiwoinseo,fnnoo tmrielaktmienntdsotsoem-arcehspionnpsuep(s3/t2h8a,t w6e/2r8e,f1o0u/n28d,de1a0d/.28,Tahnedn6u2mb8eirnso0,f1p,u3p,s10f,ouannddc3i0thmegr/dkega/ddaorysdtoisllebogrrnoudpisd,not show a rneostpseicginiivfeilcya)ntalnyddtihfeferreefnotrefrwoemrecounntlriolkse.ly Arbelsaotleudtoe wterieagthmtesnot.fthTeerbmrianina,lsbpoldeyenwaenigdhtthsyimnuFs2apnudptshewerrateios oafntdhceosnetroorlgagnrowuepisg.hts-o-terminal body weight and to brain weight were also comparable among treated Ntroeaetfefdeactnsdwceornetrroelpgorroteudpsatwaenrye dnoosteedlefvoerltfhoerntuhmebveirabsiolfitpyuapnsd sluarctvaitviionngipnedricleist.ter,Nothedipfefrecreenntcaesgebemtawleeen Apnuopgs,enlittarlsdiizsetaanncdesavmeeraasguerpeudpfobroFdy2 wmeailgehatnpderfelmiatelrewphupesnomneaLsDusre1daonndL2D2swe1,re5,a,lso15c,o0mrp2a2r,able `among the five dosage groups and did not differ significantly. 203 000190 CONCLUSIONS DfeomsailnegFwIitohffAspPrFinOg.atT3h0emagu/tkhgor/sdoafy atphepesatrueddy tcoondteelanyd tthheaotnhseetdeolfsaeysxuianlsemxautaulramtaituornaitniobnot(hprmeaplueiaalnd sdeepcarreaatsieodngoerstvaatgiionnaall paagte,enacyv)aroibasbelervwehdiichhtihgehy-dhoasveeadneifmianlesdaarsetdhueetitmoethien dfaacytshfartotmheesveidaennicmeaolfs hmaatvineag ginestthaetiFoOnagleangeeraatpipoenaurnetidlteovbiedednecceroefasseedxuianlhimgaht-udroasteioanniimn atlhse aFtIthgeenteirmaetoiofna.cTquhiesiatuitohno(rtshetatiemethwaht en mseoxruealimmamtautruarteiotnhawnatsherecaocnhterdo)l,gwrhoiucp,h itnhewyhibcehlitvheermeewaanst ntohesaingniimfailcsanitndtihfaftegrernocuepiwnesreexuyaolumnagteurraatniodn. Iwnitohrdtehre tdeoltaeysstihnissehxyupaolthmeastiusr,atthieonauitnhoorrsdecrotvoadreitderthmeindeecwrheeatsheesrionrbnoodtybwoediyghwteiagnhdtsinangdesgteasttiaotniaolnaalge rageeduwceerdebodcyonwteriigbuhttiangttfhaectotri.meoWfhaecnqutihseitdieolna,ysthiendsiefxfuearlenmcaetuwraastitoinllwseirgneifciocvaanrti,ebdutwiatthtthheeps<ig0n.i0f5icantly vnoetrseunstipre=ly0..0W1.heTnhitsheinddeilcaaysteinthseaxtuhael dmealtauyraitnisoenxouablsemravteudraattitohnewhaisghpadrotsley grreloautpedwoerebocdoyvewreeidgwhi,thbut sseesxtuaatliomnaatluraagteiaontbheettwiemeenofcosnetrxoulaslamnadtuhriagtiho-nd,ostehearneimwaalss.noThsiisgniinfidciacnattedsitfhfartetnhceeeiffethctomfdeeloafyoendset of sexual maturation could possibly be atributed to decreased gestational age. "iTnhcereaaustehsorisn athlesoavceorvaagreindutmhbeedreocrfeeasstersouins bstoatghebsopdeyr 2w1eidgahytsatnhdatinwegresetaotbisoenravleadgeatwtihtehhtihgehsdiognsiefoifcan3t0 mg/day and found thatth difference between rcaed and control animals was sill significant. a`fWfheicltetihteistikmneotwonsaenxudaclommamtuornaltiyona,ccwehpettehdetrhaotrcnhoatnggeesstaitniotnhaelbaogdey, awseidgehftisnoefdobfyfstphreianugthcoarns, palrsooviadffeedctbsytthheetaiumtehoofrasctqouissuiptpioornt itshipsurreellaytisopneschuilpa.tiAvded,ietsipoencailallyl,ycsoivnacreitnhgertehewdaeslanyoidnatsaexual `simgantiufriactainotncwhiatnhggeesitnattihoenlaelnaggtheoifpgreosbtlateimoantiact 3f0rommg/aksgt/adtiasyt,icablassetadnodpnoitnhte.auStihnocres'tdheefrienwitaisonnoo.f t"igemsettaotisoenxaluaalgem"a,tutrhaetidoenc.reaTsheesreifnogrees,tasteixounaallmaagteurwaotuilodn hisavesesteontbiealdlyuebemionsgtlcyovtaorciehdanwgietsh iintself. Smteirle,leyvoefnfeirfsaraenlaetxipolnasnhaitpiobneftowretehnegoebssteatrivoendaldealgaeysanidn tseixmuealtomsaetxuuraaltimoantuirnahtiigohn-wdeorsee sanhiomwanl,s,it but does not diminish its significance. REFERENCE YAomrmko,nRiGu.m 2P0e0r2f.luoOrroaolct(aGnaoviacg(e)APTFwOo-)GiennReariast.ioAnrg(uOsneReLsitetaerrcPheLraGbeonraetroartiieosn,)IRnce.prPordoutcotcioolnNSutmubdeyr:of 418-020, Sponsor Study Number: T-6889.6, March 26, 2002. 3M Company, 2002. Submission dated September 17, 2002 to USEPA, AR 226. 2U0S02E.PA 2002. Memorandum from Dr. Ralph Cooper, NHEERL, to Dr. Jennifer Seed, dated October 2, 294 000191 ee Ecotoxicity Study TTOEXSITCSIUTBYSTTOANACQEUATIC PLANTS (SELENASTRUM CAPRICORNUTUM) Identity: Perfluorooctanoic acid, tetrabutylammonium referred to as PFOA tetrabutylammonium salt, salt; may also be t`ceotmrpaobnuetnytloafmmLo-n13i4u9m2p.er(fOlcutoarnooocitcaancoiadt,e,peNn2t8a0d3ec-a2f,luoorraos-,a major t`Reetmraarbkust:ylTahmemo3nMiupmrsoadltu,ctCiAonSl#o9t5n6u5m8b-e5r3-w0a)s 2327. The test sample is rneufmebrreerd itso8b4y1-tThHe.teTsthiengpulraibtoyroaftotrhyeassaLm-p1l3e49w2a.sTnhoet sTu.Rf.ficWiielntbluyry study 4ch4a.r9ac%tetreitzread,buatlytlhaomumgohnciuurmrepnetrfilnufoorromoacttiaonnoaitnedi,c2at7e.s9i%t iwsaatesro,lautnidon2o7f.2% isopropanol. teTshtefsoulblsotwainncge sinuamnmairsyoparpopplaiensol1wattheetressotsluatimonpwlaietshainmciosmtpulreetoeflythe characterized concentrationsof impurides. Data may not accurately. rMeElaTteHtOoxDicityof the test sample with thatof the test substance. TMeestth:oAdc:utUe.Ss.taEtiPcA-TSCA Guideline 797.1050 GYeLaPr:cYoemspleted: 1995 Species: Selenastrum capricornutum oSfouTrecxea:s OartiAguisntailnl,y mfarionmtaTihneedCiunltcuurletuCroellmeectdiiounomfaAtlTg.aR.e WaitltbhuerUyn,iIvenrcs,ity Marblehead, MA. EElxepmoesnutrebapseirsi:odg:ro9w6t-hhoruatres. `ETPeAst-roergcaonmimsemnsdleadbsotreartiloeryencruilcthuerde:meAdlgiauemcfuolrtuartelseawsetr1e4gdraoywsinprgioirn UtSoS. tSetsattiisntiitciaatliomne.thods: The average specific growth rate was calculataesd tnahteunraatlurlaolgolfotgohfetnhuemnbeurmobefrcoelflcse/lmlLsa/tmL0hatouthresedxipvoisduerdebpyterhieodexmpionsuusrtehe `pseurbilodr.actTihngetpheercternetatcmheantngaevefrraogmetshpeecciofnitcroglrowwatshcraaltceulfartoemd bthye control aspveecriafgiec specific growth rat, dividing the difference by growth rate in the control, and multiplying that the average value by 100. The EprCoSc0edvuarleue(sBrwuecreeacnadlcVuelrastteedcgb,as1e9d92o)n. aThnoenlNiOneEaCr rweagrsedsesitoenrmeisntiemdautsiionng. a`gpraorwatmheitnriecacohnete-swtavyesasneallyatsitsheofvenadroifatnhcee atensdt. the average specific TDielsuttCioonndwiattieonrss:ource: The algae medium was prepared to U.S. `EnuPtArierntecsotomcmkse,ndTehde cpoHncoefntthreatisoynnsthbetyiscpailkgianlgmdeedioinuimzeadt tweastter with initiation was 7.5. Stock and test solutions preparation: A 16 mg/L primary stock 295 a_------------------ EE ------------ 000192 asomlouutniotns woaftshipsresptaorcekdsionlustteiroinleweenrreiacdheddedmeddiiraec.tlAypptroopdriliuattieo.n water to formulate solution was the test media. also prepared A 1,000 mg/L and evaluated. isopropyl alcohol stock Exposure 100 mLof vessels: 250 mL test solution. glass Erlenmeyer flasks containing NAguimtabteiorno:frCeopnltiicnautoeuss: a3t 100 pm NInuitmibalearlgoaflccoenlclelnotardaitnigo:ns1.0:XFive1p0l4uscealnlesg/amtLive control Lighting: ~400 fi Water chemistry: from continuous cool-white fluorescent lighting 7P.H5 -ra1n0g.e4:((co0n-tr9o6l heoxupross)ure) 77..4471.06.4(1(61,m0g00/Lmgex/pLoissuorper)opy! alcohol exposure) 2`T3es.t4t-e2m3p7eraCture range: (096 hours) RESULTS ANotmeistnawlascopnecrefnotrrmaetdiosnism:ulBtlaanneokucsolnytrwoilt,h1i.0s,op2r.o0py,l 4a.0,lc8o.0h,ol1,6a.0commgp/Lo.nent that represents 27%ofL-13492, at 4.4 and 1,000 mg/L. 2E4l-ehmoeunrtEvraCl1u0e (agnrdow9t5h%ratceo)n=fi<d1e.n0cemgin/tLer(vCaTl:not calculable) 2244--hhoouurr ErCS0 ErC90 (growth (growth rate=) rate) = 15 (9.8 >16 (7.7 316)mg/L ->16) mg/L 48-hour 48-hour EC10 EXCS0 (growth (growth rate) = ate=) <1.0 mg/L (CI 14 (8.2 -- >16) not calculable) mg/L 4782--hhoouurr ErC90 ErC10 (growth (growth ate) rate) = = >16 mg/L (CI not calculable) <1.0 mg/L (CI not calculable) 72-hour ErCS0 (growth rate) = 7.1 (4.1 ~ 11)mg/L 9`762--hhoouurr EErxCC1900 (growth (growth rate) rate) = = >16 mg/L (C1 <1.0 mg/L (CI not calculable) not calculable) 9966--hhoouurr EEXrCC9S00 ((ggrroowwtthh rraatte)e=)= >4196(m3.g5/~L6(.C7I) nmogt/Lc.alculable) 9A6l-gahlougrroNwOtEhC:was1.n0omtga/ffLected by isopropyl alcohol concentrationsof 4.4 or E1l,0e0m0enmtg/vLa.lues are based on nominal concentrations. 296 0193 Biological observationsafter 96-hours: `NCoomnciennatrlation,| NMuemabner |PIenrhcibeinttion vi | IPnehricbeinttion via mg omfLCells per | Density Growth Rate [Control "T2000 --[----- - [ro Tisnmoo [5 To | o"hr Tseso 56 0 ] [a0 Tisoo0 Tor Tso | [Bo Teaoo0 Tes Tse | Oe Toro "Tog Tso Control response: Satisfactory Biological observations after 96-hours for isopropyl alcohol: Nominal Mean Percent Cmogn/cLentration,|oNfuCmebllesrper || Ivinahibition mL Density [Control TT249000 [| [T 4a ieoo10 5 0 `Ombesaenrsvaoftdiiocnso:tAmligcarlosceclolpceocuonutnstisnweiatchhatehsetmvoecsystelomweetreer.deAtfetremri9n6edhobuyrs ooffetxhpeoaslugraee,othtehree fwlaseksniornsitgheenscoonftargoglroergaatniyonte,stflroecactulmaetnitongrooruapd.heIrnence: amdodriptihoonl,otghyerwehweenreconmopanorteidcetaobltehecchoanntgroels.in cel size, colo or dReetveerrsmiibnieldittyoobfeGalrgoiswttathicInbhaisbeidtioonn:thEeffreescutoltfstohfthteesptossutb-sdtefainncietiwvaes.test exposure. RSuebmsatrakncse:RTeemsatirnkgswfaiesldc.oTndhuectvaelduoesnrtehpeomritxetduarpeplays dteostchraitbmeidxitnurteheaTnedst not the fluorochemical component alone. C"TOheNtCesLtUsSamIpOlNeS96-hour ECS0 and 95% confidence interval for S`ceolnefniadsetncreuminctaeprrvailcoofr3n.ut5u~m 6w.a7smdge/tL.ermTihneed96t-ohboeur4.n9omogb/seLrwvietdheaff9ec5t% ``cAolngcaeengtrraotwitohn (nNthOeEvCe)ssfeolrstchonttesatinsiunbgstiasnocperoipnyslolaultcioohnolwwaass1.n0otmgaf/fLe.cted. aitn4.L4-13or4912,0c0a0nmngo/tL,,byinidtiscelaft,inagcctohuatntthfeorcotnhceetnotxriactiitoynooffLi-s1o3p4r9op2ytloaallcgoahco.l Nthoe stiesgtnssoolfuatigognrse.gaTthiiosne,sftlsocucbusltaatnicone,woarsaddehteerremnicneewdetroebneoltgeidstiantaincy of P`aSuulb,miMtitnenre:s3otMa,C5o5m1p3a3ny, Environmental Laboratory, P.0. Box 33331, St. 297 000194 DReAliTabAilQitUyA: LKlIiTmYisch ranking 2. Thestudy lacks analytical measurement onfottessutffsiucbisetnatnlycechcaornaccetnertirzaetdi.ons in the test solutions and sample purity is 208 000195 re eave Ee ------------ ce REFERENCES `MTAhi,s sattutdhye wreaqsuecsotnodfutchteed3aMt TC.Ro.mpWainlyb,urLyaLbaRbeoqruaesttorniuemsb,erInc., NMa2r3b3l2e,head, 1995, OTHER GOeNnLerYalNrOeMmIarNkAsL: TTEhSeTmaCjHorEcMoInCcAenL for trying to determine CONCENTRATIONS the validity were used. for this test is that OPPT recommends tchhaetmmiecaalsucroencdetnetsrtacthieomnitcoawlhciocnhcetnotrtahteitoensst boreguasneids,m5s0atrheatexopnoesecda.nIafcicturiastdeeltyedremtienremdintheatthtehetest vnaolmuiensalcacnonbceenatnrdatmiuosnts baereaodnjluys,tefdordeoxwanmwpalred5b0y%5of0t%h.e Imfaenaasluyrteidcaclomnceeansturrateimoennst,stohfestooxmiceitsyort hvoaldatbileietyn,faunrdnisohtehde,r wpheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcmoivegrhyt rlaotwese,ratnhde tacatkueailntteostacocroguanntishmydrolysis, `exposure concentrations. `Psuormietytoesftsthiet atepsptemaarteedritahlatal1s0o0i%s atemsatjcohremciocnaclewrasanudsewda,sfnoototshuefrfiscaiecnhtleymicchaalroacftleersiszeerd piunrtihtiys test, Tn (otahpeprrotxesitmsa,tfeolryn8o5o%b)viwoauss ussteadt.ed Wraeatseorn,. a Isnolfvacetn,t3(iMsoipnrtohpeainrosl)umomra&rcyoomfbicnaacthiotneostfbstoatte:h "wDaastausmeadyinnot aadcdciutriaotne,lyiftrheilsawteatsoxaic"ittyypoifctalh"eTteSstCsAamspelcteiownith4 trheavtioefw,thIewtoeustldsurbesjteacntcteh.e"se1satgurdieces,wiptehndthiinsgcornecceeirpnt. ofIn madeddiituimo.nal information on purity and studies on analytical measurementsofthe test chemical in the test 299 000196 Ecotoxicity Study T`TOEXSITCSIUTBYSTTOANACQEUATIC PLANTS (SELENASTRUM CAPRICORNUTUM) Identity: referred Perfluorooctanoic acid, tetrabutylammonium to as PFOA tetrabutylammonium salt, salt; may also be tceotmrpaobnuetnytloafmmLo-1n3i4u9m2p.er(fOlcutoarnooocitcanacoiadt,e,peNn2t8a0de3c-a2f,iuoorroa-s,amajor tetrabutylammonium salt, CAS #95658-53-0) rReefmerarrekdst:o Tbyheth3eMtepstriondgucltaiboornaltootrnyuamsbNe2r80w3a-s2.23T27h.e TT.hRe.tWesitlsbaumrpylsetuisdy `chnaurmabcetreriisz8e9d,0-aTlHt.hTouhgehpcuurrirteynotfitnhfoermsaatmipolneiwnadiscnaotets siutfifsiaciseonltultyion of 4is4o.p9r%optaentarlabutylammonium perfluorooctanoate, 27.9% water, and 27.2% teTshtesfuoblsltoawnicneg isnuamnmairsoyparpopplainesoltwtahteertseostlustaimopnlweitahs ianmciomsptluerteoelfythe rcehlaartaecttoexriiczietdyocfontcheenttersattsiaomnpsolfe impurities. Data may not accurately. with thatof the test substance. METHOD TMeestth:oAdc:utUe.Ss,tatEicP:A-TSCA Guideline 797.1050 GYeLaPr:cYoemspleted: 1995 Species: Selenastrum capricornutum o`fSoTuercxea:sOartiAguisntailnl,y mfarionmtaTihneedCuilntucurletuCroellmeectdiiounomfaAtlTgRa.eWatiltbheurUn,ivInecr.sity MEalrebmleenhteabda,siMs:A.Algal cel count (cells/mL), and specific growth rate. ETexsptosourrgeanpiesrmisodl:ab9o6r-ahtoourrys culture: Algac cultures were growing in U.S. EPA-rccommended test initiation. sterile enriched mediumforat least 14 days prior to Stthaetniasttuircaall methods: logofthe The average specific growth rate was calculated as numberofcells/mL at the exposure period minus the `natural period. lTohgeopftehrceenntucmhbaenrgoeffcreolmlstihme.coantt0rohlouwrassdciavlicdueldatbeyd bthye exposure sauvbetrraagcetisnpgetchifeictrgeraotwmtehntraatvee,rdaigveidsipnegcitfhiec dgirfofwetrhenrcaetebyfrtohme atvheercaognetrol sEpCeSci0fivcaglrueoswtwherreatceailncutlhaetceodntbryolp,roabnidt manualltyispisl.yiTnghethNatOvEalCuewabsy 100. The adveetreargmeinsepdecuisfiicnggaropwatrhamreattreiacnodntehe-wnauymbanearloyfsciseolflvsa/rmiLaninceeaacnhdetshte TveessstelCoantdtihteieonnsdo:fthe test. EDiPlAutrioencowmamteerndseodurccoen:cTenhteraatligoanes mbeydsipuimkiwngasdepiroenpiazreeddwatoteUr.wS.ith niuntitriiaetnitonstwoackss.7.5T.he pHofthe synthetic algal medium at test Stock and test solutions preparation: A 160 mg/L primary stock 300 000197 asomlouutniotnswofatshipsresptaorcekdsionlutteioinlweenrreiachdeddedmeddiiraec.tlAypptroodpirliusttioen water Etoxpfoorsmuurleatveestshelste:st25m0edmiLa. glass Erlenmeyer flasks containing 50 AmgLitoaftitoenst:sCoolunttiionn.uously at 100 pm NInuitmibalearlgoaflrceeplliclaotaedsi:ng3: 1.0 10 cells/mL. LNiugmhtbienrgo:fCocnotnicneunoturastliiognhst:inFgiavte3p8lu0s afln-ceguastiinvgeccooonlt-rwolhite Wflautoerersccehnetmlisatmrpys: 7p.5 H~ra1n0ge8:((co0n-tr9o6l ehxopuross)ure) T7e5st-8te4mp(e1r6amtuLre reaxnpgoes:ur(e)0-96 hours) R2E3S4U-L2T3S7C ENloemmiennatlvcaolnuceenatnradt9io5n%s:cBolnafnidkecnocnetrionl,te0r.va9l9:,2.0,4.0, 8.0,16.0 mg/L. 2244--hhoouurr EECCS100 c(ceellll ddeennssiittyy)) ==>41.16((01-.79.-0>)16m)g/mL.g/L 2244--hhoouurr EEXCCOS00(c(eglrlodwetnhsirtya) ==t>e>11)66mmgg//LL.((CCIlnnoot ccaallccuullaabbllee)) 4488--hhoouurrEECCISO0 ((ceellll ddeennssiittyy)) == 71..12 ((600.98.9--6)1.m6)g/mLg/L 4488--hhoouurr EEXCC9S00((cgerlodwetnhsirtayt)e)==>>1166mmgg//LL((CC1lnnoottccaallccuullaabbllee)) 7722--hhoouurr EErCCI100((eglrlowdtehnsriattye))==02.9(1.6(<0.929.8~1)m.9L) mg/L 7722--hhoouurr EERCCSS00((cglrlodwetnhsiatty)e==)2.11 ((191.4--51.58))mgm/gL/.L 7722--hhoouurr EEXCCO900c(eglrlodwtehnrsati)=t=y8>.)146(4m.5L~ 1(6C)l nmoet/Lc.alculable) 9966--hhoouurrEECCIOO((eglrlodwethnsriatey)=)= 12.43((<<00..999-9 234.)6)mmgg//LL. 9966--hhoouurr EEICCSS00((cgerlodwetnhsirtayt)e)==2.8.4((15.097-.174)) mmgg//LL 9966--hhoouurr EE-CC9900((ceglrlodwetnhsiattye))==6>.016(3m.g5/-L>1(6C)1 mnogt/cLalculable) 9966--hhoouurr NNOOEECC ((cgerlowdtehnsriatty)):: 20.909mmgg//LL CEolnetmreonlt rvaelsupeosnswee:reSabtaissfeadctoonrynominal concentrations. 301 000198 Biological observations after 96-hours: NoComnicennatlration,| NMuemabner |PIenrhciebinttion via| PInehricbeinttion via mL omfLCells per | Density Growth Rate [Conwol "32[0 = 70 ]-0 ----0| [oso aemo0 [13 [a2 [207 aas0000 24 [5 [a0 ssio00 Teo 30 [80 Tieoo00 Tos sz | Os Tero Tos Tes | Ombesaenrsvoaftdiiornesc:tAmligcarlosceclolpceocuontusntisnweiatchhatehsetmvoecsystelomweetreer.deAtfetremri9nedhobuyrs ooffetxhpeoaslugraee,0tthhereeflwaesrkesinno stihgencsoonftargoglroergaantiyont,estfltorcecautlmaetnitongroorupa.dheIrnence: a`dmdoirtpihoon,lotghyerwehweenreconmopnaorteidcetaobtlheecchoannigreols.in cel size, oloror Rdeevteerrsmiibnieldittyoobfe GalrgoiswttathicInbhaisbeidtioonnt:hEefrfeesutlotfstohfethteestpossutb-sdteafncneiwtvaestest exposure. RSuebmsatrakncse:RTeemstairnkgswfaiesldc.oTndhuecvtaelduoens rtehpeomritexdtuarpeplasy dteostchraitbmeidxitnurtheeaTnedst not the fluorocheical component alone, CONCLUSIONS "STehleenteassttsraummpclaep9r6i-choorumrutEuCmSw0asanddet9e5r%micnoendfuisdienngcetwiontecravlaclulfaotrion mceatphroidcs.onTuhteumtewsatssudbesttearnmcien9e6d-thooubre E2.C9SmOgf/oLrSweiltehnaas9t5ru%mconfidence iEnCteSr0vaflorofSe1l.e0n~as7t.r7ummg/cLap,rwihcoernncuatlucmulwaatsedduestienrgmicneellddteonsbiety8..4Tmheg/9L6-whiotuhra 9ag5g%regcaotnifoind,enfcleocicnutleartviaolno,for5a.9d--her1e4nmcge/wLeurseinnogtegdroiwntahnyatoef.tNhoe tseisgtns of s`oSluubtmiiotnst.erT:h3isMtCeosmspuabsntya,ncEenvwiarsondmeetnetramlinLeadbotorbateoarlyg,iPs.aOt.icB.ox 33331, St. PDaAulT,AMiQnUneAsLotIaT,Y55133 Roefltieasbtisliutbys:taKnlciemicsoncchenrtarnaktiinogns2i.Thtehsettuesdtysollacuktsioannsalayntdicsaalmmpelaespuurreitmyenist not sufficiently characterized. REFERENCES "MTAhi,s sattutdhyewreaqsuecsotnodfutchteed3aMt TC.oR.mpWainlyb,urLyaLbabRoerqauteosrtiens,umIbnce.r, MNa2r8b0l3e-h2e,ad, 1995. OTHER 302 ---------------------------------- 000199 O`GNenLeYralNOreMmIarNkAsL: TTEhSeTmaCjHorEcMoInCceArLn fCorOrNyCiEngNTtoRdAeTteIrOmiNnSe twheervealuisdeidt.y fOoPrPthTisrteecstoimsmtehnatds cthhaetmmiecaalsucroencdetnetsrtacthieonmitcoawlhciocnhce0ntrtahtitoensst obreguasneids,mssoatrheatexopnoesecda.n aIcFcituriastdeeltyedremtienremdintheatthtehetest vnaolmuiensaclacnonbceenatnrdatmiuosnts baereaodnjluys,tefdordeoxwanmwpalred5b0y%o5f0t%h.eImfeanaasluyrteidcaclonmceeansturrateimoennst,sthofestooxmiecitsyort vhoaldatibleietny,faunmdisohtehde,r pwheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcmoivgehrty rlaotwse,ratnhde tacatkueailntteostacocroguanntishmydrolysis, exposure concentrations P`uSroimteyotefsttshiettaepsptemaarteedritahlatal1s0o0i%staesmtajcorhceoncmewrianscaunasdewlda,sfonrotosutffihcaicehentelmryiccshaalroafctleesrsiezriepndurtihtiys test, Tn o(tahpeprrotxesitmsa,tfeolryn8o5o%b)viwoaussussteadt.edWraeatseorn,. Isnolfvacetn,t3(iMsoipnrtohpeainrosl)umomraarcyomobfeinaacthiotnestoftabtoet:h"wDaastausmeadyinriot aadcdciutriaotne,lyiftrheilsatweatsoax"itycopiifctahlye" TteStCsAamspelcteiownit4hrtehvaiteowf,thIe wtoeustldsuebjsetcatncteh.e"se1satgurdieees,wiptehndthiinsgcroencceeirpnt.ofIn madeddiituomn,al information on purity and studies on analytical measurementsofthe test chemical in the test 303 000200 ee Ecotoxicity Study TOXICITY TO AQUATIC TEST SUBSTANCE PLANTS (SELENASTRUM CAPRICORNUTUM) `IadsePntFiOtyA: aPemrmfolunoiruoomctsaalnto,iAcmamciod,niamummopneirfulmuosraolto;ctmaanoyaatles,oPbFeOre,ferred to FpeCn-t1a1d6e,caFfClu-o1r2o6-,, FaCm-m1o69n,iuormFsCa-lt1,4C3.AS(O#ct3a8n2o5i-c2a6c-i1d), Remarks: The 3M FC-143, referred to production by the test llaobtonruamtobreyrawsaNs2840237-.4.ThTehteesTtRs.ample is `Wniotlbsuufrfyicsiteundtylyncuhmarbaecrteirsi$z9ed5,-TaHl.thTohugehpucrurirteynotfitnhfeorsmaamtpilone was indicates 3.5% C6, it is C7, a mixture of96.5-100% test substance and C9 perfluoro analogue compounds. and 0 -- METHOD Method: U.S. EPA-TSCA Test: Acute static Guideline 797.1050. GYeLaPr:cYoemspleted: 1996. Species: Seleriastrum capricorutum o`fSTouerxcae:sOartiAguisntailnl,y mfarionmtaTihneedCuilntcuurletuCroellmeectdiiounmofaAtlTgRa.eWailtbhuerUyn,ivInecr.s,ity Marblehead, MA. EExlpeomseunrtebapseirsi:odA:lg9a6l-cheolulrcsounts (cells/ml),andspecificgrowthrates. Svtaaltuiesstiucsaeldmteotehsotdism:atCeeltlhedeCn1si0ti,esE,CgSr0o,wtahndraEtCes9a0ndvapleurecsenatndin9h5ib%ition cSotenpfhiadne.ncTehleinmiotosbwseerrevecadlceuflfeacttedcounscienngttrhaeticoonm(pNutOeErCs)ofwtawsarceaolfcuCl.aEt.ed uAsnianlgytoincea-lwmaoyniatnaolryisnigso: fpHvaarnidatnecemp(eArNaOtuVrAe). Test Conditions: mAlegdailumn,utprrieepnatrmededbiyumsp:ikUi.nSg,dEePioAn-irzeecdowmamteerndwietdhsntuetrirlieenetnrstiocchkesd. ``TShteocpkHaonfdthteestsysnotlhuettiiocnsalpgraelpmaeradtiiuomn:atAtes1t,0i0n0itimagti/oLn pwraisma7r.5y. s`taomcokunstosluotfiothniswastsopckrsoeluptiioannsrwteeerriedlaedednerdicdhierdecmteldyiat.o dAilpuptrioopnrwiaatteer tEoxfpoorsmuurleatveestsheelst:est25me0dmiaL. glass Erlenmeyer flasks containing 50 mLoftest solution. ANguimtabteirono:frSehpalkiecantceosn:ti3nuously at 100pm Initial algal cell loading: 1.X0 104 cells/mL. NLiugmhtbienrg:of~4c0o0ncfenitrfartoimoncso:ntFiinvueopulsuscoaoln-ewghaittieveflcuoonrtersoclent lighting `PWHatrearngceh:em(i0st-r9y6: hours) 57.5.-49.-6 (7con.tr4omlg(e/x1Lpoes,xupr0oes)0ur0e) 304 ------------ EE EESYE cc 000201 Test temperature range: (0-96 hours) R2E3S5U-L2T3S7C `ENloemmiennatlvcaolnuceenatnradti9o5n%s:cBoknfciodnetnrocle,i6n2t,er1v3a0l,: 250, 500,1,000mg/L. 7722--hhoouurr EExCCILOO((ceglrlodwetnhsirtayte))== 341700((131800-4-4$050))mmgg//LL. 7722--hhoouurr EEXCCSS00((cgerlodwetnhsirtayt)e)==5>210,0(20500m~g/1L,0(0C0.1).mgn/oLt.calculable) 7722--hhoouurr EErCC9900((cgerlodwethnsriattey)=)=>>11,,000000mmgg//LL((CC..1. nnoottccaallccuullaabbllee)) 96-hour ECO (cell density) = 97 (77- 120) mg/L. 9966--hhoouurr EErCCSL0O((ceglrlodwetnhsirtayt)e)== 321200((218600--325800))mmgg//LL. 9966--hhoouurr EECXC9S00((cgerlodwetnhsirtayt)e)==1>,10,0000(083m0g/-L>1(,C0.0L0)nmotg/caLl.culable) 96-hour 96-hour ENXOCE9C0 ((cgerlolwdtehnsriattye)):=6>21m,g00/0Lmg/L (C.1 not calculable) 96-hour NOEC (growth rte): 500 mg/L. Element values based on nominal concentrations Biological observationsafter96-hours: `CNoonmciennatlration,|MNeuamnber |PIenrhcibeinttion via| IPnehricbeinttionvia mg ofCells per | Density Growth Rate mL [Comrol 1d07000 |--- 1-. | [fe Tiasoo [3 To | [" 30 Tia[o 20 0T0 6 0| [so 953000 "Tae iz | [S-- 00 TaaTz eo 0[20 5 0| Lodo Thsooo Ter Tao `COobnsterrovlatrieosnpso:nsAel:gaSlatcieslfaccotuonrtys in each test vessel were determined by ofmeeaxnpsoosfurdei,retchtermeicwreorseconpoesciogunsnotfs wagigtreh2gahteimoonc,yflloocmceuelra.tioAn ofr a9tdheheroeunrrcse: oafddtihteioanl,gatheteorethweefrleanskosinonticteheabcleocnhatnogreaosnliyn cteeslt rsiezae,tcmoelnotrgorroup. In morphology when compared to the control. RdeevteerrsmiibnieldittyoobfeGalrgoiswttathicInbhaisbeidtioon:thEeffreescutlotfstohfethteestpossutb-sdteafnncietwvaestest exposure. CThOeNtCesLtUsSamIpOlNeS96-hour ECS0 and 95% confidence interval for mSeetlheondass.trBuymccealplridecnosrintuy,tuitmwwaass3d1e0te(r2m8i0ne-d35u0si)nmggt/wLo,acnaldcublyatgiroonwth rate 305 ------ ee 000202 ---------------------------------- EE------------------ c1e,ll0d0e0nsmigt/yLa.nTdh5e0906-mhgo/uLruNsiOnEgCgrwoawsthderatteer.mNionesditgonsobef6a2ggmrge/gaLtiuosni,ng tfelsotccsuulbasttiaonn,ceorwaasdhdeerteenrcmeinweedretonobteeadlgiinstaantyio.fth test solutions. This Submitter: 3M Company, `Paul, Minnesota, 55133. Environmental Laboratory, P.O. Box 33331, St. DReAliTabAilQitUyA: LKlIiTmYisch ranking = 2. The study lacks analytical `measurementoftest the sample purity is nsoutbssutfafnicceiecnotnlcyecnhtarraatcitoenrsiziend.the test solutions and TRhEiFsEstRuEdyNCwEasSconducted at T.R. Wilbury Laboratories, Inc., Marblehead, MA, at the OTHER requestofthe 3M Company, Lab Request number N2803-4. `General remarks: ONLY NOMINAL Themajor concern TEST CHEMICAL for trying to determine CONCENTRATIONS the validity were used. for this test is that OPPT recommends `tchahtemmiecaalsucroencdetnetsrtacthieomnitcoalwhciocnhcetnotrtahteitoensst obreguasneids,mssaortehaetxpoonseecda.n aIcfciutriastdeeltyedremtienremdintheatthtehet.est `nominal concentrations `values can be and must baereadonjluys,tefdordeoxwanmwpalred5b0y%5of0t%h.eIfmeaanasluyrteidcaclonmceeansturrateimoennst,sothfe toxicity some sort vhoaldaibleietyn,afunrdnoisthheedr,phwyesicocuolcdhecmaliccuallatpercohceemsiscesalthraetcomviegrhyt rlaotwese,ratnhde atcatkueailntteostacocroguanntishymdrolysis, exposure concentrations. eae 306 aa -------------------------- 000203 Ecotoxiciy Study Title: Multi-Phase Exposure/Recovery Algal Assay Test Method TEST SUBSTANCE IAdmemntointyi:umPeprefrlfulourooroocotcatnaoniocataec,idP,FaOm,mFoCn-i1u16m,saFlCt;-1m2a6y, aFlCs-o1b6e9,reofrerFrCe-d14to3.as (POFcOtaAnoaimcmaocindi,um salt, pentadecafluoro-, ammonium salt, CAS # 3825-26-1) `Rceommaplrektse:ly cThhaera3ctMerpirzoedd,ucatlitohnoulogthniunmfboremrawtiaosn 3i7n.diTchateetietsitsasammpilxetwuraeosfFC9-61.453-.10T0hpeerpcuernittytewstassunbosttance. and 03.5% Ce, Cy, room temperature. and C; perfluoro anelogue compounds. The chemical is soluble in war at ambient METHOD AMeGt.hoPdagynuei.de(lasindeesfcorlilboewdeidn:UMSoEdPifAie6d00f/r9o-m78a-n0d18m)odeled after ASTM-E-35.23 Draft No. 2, OECD; Test type: Static: GLP (Y/N): No Year study performed: 1981 Species: Selenastrum capricornutun (7 day old stock) Supplier: USEPA ~ ERL in Corvallis, Oregon. `Measureofgrowth used: biomass i cell ry-weight (mg/L); cell count (no.mL) CMoanicnesntturdayt:io0n,s1u0s0,ed1:80R,a3n2g0e,-f5i6n0d,in1g0:000,, 100, 250, 500, 750, 1800mg/L (nominal 1000, 1500 values). mg/L; Exposure period: 4,7, 10, and 14 days Analytical monitoring: There was no `There was no information on detection information mitsofthe ochnetmhiecmaleaosruirmepmureinttieosf.the chemical during the test. Statistical methods: model 3M Sixcur ECS0 values and 95% confidence limits were calculated using the linear regression -------------- 307 Siti -------------------- 000204 T-Teshtecaolngdailtciuolntsu:re was stored inthe darkat4 before use. was 277,000 cellsmL. The inital algal cell count in the stock culture wa~ siMstiahynsle.lrsmTih(niiesnronarulgtarnniuietcnr)tiesmntetasdniedsausrmednwtmiaiatslifteohnretaldmigleaudleingturmofwotwrhaa.lslTuoshpeeedrapftHoironuwslatstrhaitdnjguu/ssttdsedtail(ng7ga.e5al4ign.ace0.l.udTihpnirgistowhreatsprupesrpeeapr1aatrhieoden ofEsxtpoocskursoeluvteisosnesl.s were 250 mL Elenmeyer flasks with S0 mLoftet solution and stoppered with autoclaved fou pgs. c-aDnudrliensg th1e0t%e,st,antdhecutletmupreersawtuerte waagista2t3ed+w2iCt.h Tchoentliignhutowusasshbaykifnlugoprleasctefnotrmiallum1i0n0atripomn of 400 ft -- IAnligtaiall There rwaelacgsoalvneolroyiandrfieonsrgpmowanatsiseonw1.ao0snxedvi1al0ultuciaoetnleldwsf/eomrlLloswoiunrgc et,hceoenxtpaomsiunraentpse,rioofdsc.hemistry ofthe wate. "Three replicates wre taken at cach dose. nRoetmparreksesn:tedp.H values were acceptable according to OPTS Harmonized Guidelines. Water hardness was RESULTS Dose associated with each endpoint (as mg/L): ECs0s Number of Days Exposed Cell Dry Weight (mg/L) Cell-Count (uo.cellmL) 47 10 17409G(a5-71-31480))! 4915.96) 43092(81..7450)) 275.50) 1 7325147) B(14sn 195% Confidence Limits NumberofDays Exposed ECI0s Cell-Count (no. cells/mL) 4 7 10 95% Confidence Limits Number of Days Exposed 5367) 33024) 29(1-5) 52-8) ECo0s Cell-Count (no. cel) 4 624 (CLL. not calculated) 308 000205 ---------- 7 10 14 195% Confidence Limits 238836 ((1C510-n5o9t0)calculated) 307 (CL not calculated) `Was control response satisfactory (yes/no/unknown): unknown Statisticalresults, as appropriate: No p-values were reported rReesmuasrpkesnd:edAifntefrreesxhpnousturrieenctemaeseddi,utmheinaltghaealbceslelnscreeocfovtehreedteasntdsurbesstaunmceed. logarithmic growth when CONCLUSIONS cAomnmfiodnenicueminpteerrfvlauloorofo1c4ta0no8a1temegx/hL.ibitas 14-day ECS0 (cell count) valueof43 mg/L with a 95% q`uSaulbimtiyttteerstsi'ngreatmatrheksi:meThitewaausthcoornsduictnedd. iaHocKwleiavmeitrs,cehthreasntkuidnyg loafc2k.edTihnefosrtmuadtyiomneeotns ttehset scruibtsetrainacef.or purity and actual measurementsofth test substanceisolution. REFERENCE Elnabarawy, Test Method. MT. 1981. 3M ReportNumber T0e0c6h.niPcraoljeRcetpNorutmbSeumrm9a9r7y0,03M0a0l0t0i.-PhOacsteobEexrpo1s6.ure/Recovery Algal Assay OTHER `deGteanielreadlrreepomratrwkas:s aTvhaiilsabsluem.mTahreyrewfaosreb,atsheedcoonntaenstusomfmtahriys rseupmormtarayn,d oinnlryefleirmeintceed tdoattahetapbrloest.ocoNlos and resultsofthe study, are limited. `CTHheEmMaIjoCrAcLonCcOerNnCfEorNtTrRyiAngTtIoOdNetSerwmeirneeutsheed.valOidPiPtyTfroercthoimsmteesntdiss tthhaatt mOeNasLuYreNdOtMesIcNhAemLicTaElST `tchoentceesnttroartgiaonnissbmes uasreede,xopostehdat.Ionfeitcaisndaectceurrmaitneelyd dtehtatertmhienneotmhienatelstcocnhceemnitcraalticoonnsceanrteroantliyo,nftoorwehxiacmhplteo I5fa0n%aolyftitchaelmmeeaassuurreedmceonntcseontfrsatoimoens,sotrthbtaodxibceietyn values can furnished, be we acnodulmduscatlbcuelaatdejucshteemdidcaolwnrwecaorvderbyyr0ate%s, aacntduatlakteestinotrogaacnciosumntexhpydorsoulryesicso,ncveonltartaitliitoyn,s.andAsotihteirspwheysairceoocpheermaitcianlg pirnotcheessdeasrkthoant mthiigshitssluoew.er the 309 000206 INVERTEBRATE TOXICITY "Title: Acute Toxicity to Aquatic Invertebrates (Summaryofthree 48-hour studies in dict) TEST SUBSTANCE Ipdeernftliutoyr:ooPcetrafnlouatoer,ooPcFtaOn,oiFcC-ac1i1d6,,aFmCm-o1n26i,umFsaClt;-alo1sro6FrCe-f9e1r4,r3e.d to(OacstPanFoOicAaacimdm,opnenituadmescaalfti,uaomrom-o,nium ammonium salt, CASH 3825-261) `Rceommaplrektse:ly cThahreac3teMripzreodd,uaclttlhootunghumibnefrorumsaetidownaisnd3i7c.atTedheittweastssaammpilxetuwraesofFC9-61.453.-10I0t'%s tpeusrtistuybwstaasncneo.t `and 03.5% C6, C7, and C9 perfluoro-analogue compounds. METHODS Method/guideline followed: Not stated Test type: Static GLP (Y/N): No Year study performed: 1952 Species: Daphnia magna `age = First-Instar young length =0.5- 1.5 mm `Supplier: USEPA-ERL Duluth, MN Concentrations tested: nominal concentrations 0, 10, 30, 100, 300, 1000 mg/L in two tests; 0, 10, 100, 500, 1000 in third study; Exposure period: 48 hours Analytical monitoring: No monitoringofthe test substance concentrations was done `Statistical methods: Chi-square test was used Test conditions: "Ditelsuttsi(otnhweatteemrp.usiendtwhaesthciarrdbtoens-tfiwlatserneodtwgeilvlenw)a.ter (all three tests), with a temperatureof24C in two ""TTewsot sroelpultiicaotnesswweerreemtaadkeenfrom a common stock solution with a concentrationof Sg/L. 310 000207 E"xNpuomsbuerroefveDsasepllsiwaerwee2r5e01m0-L20glpaessrbeepalikceartsecontaining 200 mL est solution (6 cm in depth) "Wat"eTremhpemrainsgteyd dfurroimng22t-he24tCest was as follows: DpHOwwaass88.2f-o8.tphepemtfsoienswthsiicnhwihtiwcahsirtewpaosrtreedp(ormteeadsunrdedfaotr4w8hihcohurist)could be read (measured at 48 hours) wRaesmnaortksp:respenHteadn.d Ihnafrodrnmeastsimoenaosnurdeiemtenwtasswaesroennoottpprreesseennttede.dfo dilution water hardness durin the test RESULTS D1o0s00eomfge'ach endpoint (35 mg/L): 48-hour ECS0 ranged from 126 mg/L (with CL. 6 0 183 mL) to > Remarks~:Lowest est substance concentration causing 100% mortality was 500 mL (from both ~ Mortalirteypolifccaotnetsroolfas swiansgl1e tes0it) o%ne replicateofone test ~ Abnoma responses included marked reduction in locomotion at 1000 mg/L in on fest Wsaatissfcaoctnotrryo,lgrievsepnotnhseeisnaftoirsmfaatcitoonrypr(osveisd/end.o/unknown): It appears that the contol response wis aSstsatoicsitaitceadlwrietshulCtsh,i-assqauparperoeptrsi)a,teb:ut tisSuonmcelesatratwishtiacatllhyeysirgenfiefrictoa.nt results are presented (p values CONCLUSIONS, "sTuhgeaetsestttshaamtptlhiesrdeifsfuesre(nic.e mahey lbaergdeucratnogdeifinfeErCenSc0esvainludeist). were inconsistent. The authors `inSculbumdiintge:rs"threemmeatrhkosd: wTahsenoKtlmdeissccrhiberda,nksianmgpfloer ptuhreitsytuwdayswnaost 3p. roSpeevrelryaclhraeraasctoenrsiwzeedreanidndliaccatkeedd, canoanltyrtaidciacltceoancfhiomtahteri.onTohfteeautthsourbssatalnocneoctonctehnettratthieoynsc.onTdhucetyedastohensottueditehse svpaelcuiefsicfarlloymtomuvliapneetesdtest. EReCvSi0e5w,enros"inrfeomramraktiso:n oAnltdhioetusghistphreeasuetnhtoerds indicate that diet may be the causeofthe differences in 31 000208 ee REFERENCE Nstoutdieensowuegrheicnofnodmuacttieodnebxyctehpet3wMhaCtomsupbamnityt,erEsnviincrloundmeeinntatlheLiarbroerfaetroernyc,eSste.ctPiaounl,, wMhNi,chcostmaptlese:te"Tdhefsreo:m May to June, 1982" OTHER `General remarks: detailed report was aTvhaiilsasbluem.mTahreyrewfaosreb,atsheedoconntaenrtseoftpahinosdorsnulmtymalriym,itiend data ables. reference to No the protocolsandresults ofthestudy,are limited. ``TThEeSmTaCjoHrEcMoInCceAnLfCorOrNyCinEgNtToRdAetTeIrmOiNneS the validity were used. for this OPPT est is that ONLY NOMINAL recommends that measured test c`choenmciecnatrlatcioonncetnotwrhatiicohnstobethuesteeds,t osorgtahnatisomnse acraeneaxcpcousreadt.eIlyfdiettserdmeitneertmhienetdestthcahtetmhiecnaolminal `concentrations be and must be are only, adjusted forexample 50%ofthe measured downward by 50%.Ifanalytical concentrations, the toxicity measurementsof some sort values can had been afnudmiosthheedr,pwheysciocuolcdhecmeilccuallatperoccheesmsiecsatlhratecmoivgehrtylroawteers,tahnedatcatkuealintteostaocrcgoaunnitshmyderxoployssuirs,e volatility, concentrations. 32 000209 ------------------------------------------------------ INVERTEBRATE TOXICITY Title: Chronic Toxicity to Freshwater Invertebrates (Daphnia magna) TEST SUBSTANCE pIedreinltuitoyr:ooPcetrafnlcuaotreo,oPciFaOn,oiFcC-ac1i1d6,,aFmCm-o1n26i,uFmCs-a1lt6;9a,lsoor referred FC-143. to as PFOA ammonium salt, ammonium (Octanoic acid, pentadecafiuoro-, `ammonium salt, CASH 3825-26-1) R`ceommaplrektsel:y cThhaera3ctMerpirzoedd,ucatltlohtounguhmibnefrorumsaetdiownasin2d6i4c.ateTdheit wteasst saammipxlteurweasofF9C-61.453-.10100%stpesutristuybswtaasncneot and 0-3.5% C6, C7, and C9 perfluoro analogue compounds, METHODS Method/guideline followed: USEPA-1982, OECD 1981 Test types: Semi-staic life-cycle toxicity GLP (Y/N): No Year study performed: 1984 Species: Daphnia magna `Age = < 24-hour neonates Supplier: 3M Environmental Laboratory St. Paul, MN Concentrations tested: Acute test: Chronic test: 0,5, 8, 13,22, 36, and 25,40, 63, 100, 160, 250, 400, 630 60 mg/L, nominal concentrations, mg/L. (Resuls, however, were based on mean measured concentrations ~ se below) Exposure period: 21 days Analytical monitoring: Not stated SCtoartpi,stDiuclaultmhe,tMhoNdsr:ecaAlccuutleatteedst:staPtirsotbiicst ainnal1y9s9i8s.. NCOhrEoCnsicatnesdt:LOmEovCisnwgearveergeangeeraantgeldeumseitnhgoTdo.xstAastc.l Rfoerprsuordvuicvtail.onCw5a0s5no(rfomrarleapnroddhucotmioogn)enwoeurse tgheenreerfaotreedDuusninnegttI'CspTpersotgwraams. usSeud.rviFviaslheErC'Ss0T5eswtewraes used `generated using "Trimmed Spearman-Karber'. 313 000210 Test conditions: "Dilution Dilution water water csohuermciestwrayswaaesratedcarbon iltered well water halakradlniensisty:: 224300 mmgg//LLaassCCaaCCOO33 pCHO:D: 7084mg ""EMxepdoisaurreenveewsaslelisnwfoerrmeat2i5o0nrmaltigloansasl:beamkeedrisu(mcownatasicnihnagng2e0d0omnLcoefevseorlyuttiwoon 0dayasdepthofsbout 5 a~Amm;b1ieanntimlaalbpoerart4or0ymlii,ghntoinagwraatsiounseddur(icnogotlh-ewhtiette)fluorescent, at ambient levels, 16 hours per Four repdlaiyc)ate beakers were used ""TWhaetreerwteermpee2r0ataunriemdaulsripnertchoentceesnttwraatsi2on2(+5 2peCr replicate) dAailsyusbpaesinssionoffish food and yeast containing me dry solids per 1 ml mixture was fed on a hRaermmaornkisz:edpgHuiadnedlihnaersdsnteasts mtheaatshuarredmneenstssoshfowualdtebedaumrianxgitmheumtesotfe1r80emngo/tLpraesseCnateCdO.3Aldsuor,intghethOePtPesTtSif wcahteemriswtarsy poroiorhiogh.the test was indicativeof during the test, the hardness valueof240 mg/Lofthe dilution RESULTS Doseof each endpoint (as mg/L): 1144 ddaayy NNOOEECC ((sruerpvriovdaulc)ti=on6)0-mg/mLg/L 2211ddaayyNNOOEECC ((sruerpvriovdaulc)ti=on2)2=mg2/2Lmg/L 2114 ddaayy IICCSSO0 ((rreepprroodduuccttiioonn)) == 4430 ((2385--4486)) mmgg//LL eAnldlpoeilnetmevnatluceosnacreentfrraotimotnhsewreeraenablaysseisd oofntmheeadnatmaebaysuArsecld Ccoorncpe.ntrations and the reported Remar ks: m- gAl/lLsturrevaitvmienngtsf,irssturgveinvearlawtiaosnsdtaatpihsntiicdasllaypdpiefafreerednntofrrmoamlathetnheegeatnidvoefctohnetrtoelt.groIunp.the 36 and 60 t~hNeecoonnattreosl (stDaurtnendetto'b)eaptrtohdeu1c3e,d2o2n, D36a,yan7.d 6Re0pmrgod/uLctcionocnewntarsatsitaotnisstaifctaelrly1s4idgnaiyfsi,caanntdlyinditfhfeer3e6ntarndom60 m- g1/0L0%tesmtorstoalluittiyonwsaas 2tn1otdoabyss.erved at any dose ~ No mortality was seen in the controls 314 000211 ee `Was control mortality. response satisfactory (yes/no/unknown): Yes, based on the fact that there was no Statistical results, computer printouts. as appropriate: However, lackof It appears information some made trheessueltdiafrfeicsutlattitsotiicnatlelryprseitg.nificant, based on CONCLUSIONS `There were no adverse effects on survival or reproduction at concentrations< 22 mg/L for 21 days. `Submitters' according to trheemmaertkhso:doTlhoegyKlaivmaiislacbhlreaantktihnegtwiamseo3f.tThehestsattuodfy was the apparently test. well conducted Reviewers' remarks: none REFERENCE 3M Company. Chronic toxicity to freshwater invertebrates. [No other information available] OTHER `NGoendeertaalilreedmraerpokrst:waTshiasvasiulambmlea.ryThwearsefboarsee,dtohne caosntuemnmtasorfythreipsorstumamnadroyn,lyinlirmeifteerdendcaetatotatbhlees. protocols and resultsofthe study, are limited. tAhlesoa,cuatneatceusttewaesstnwotasvecroyndculcetaerfdr,opmotsshieblsytuadsya. range-finding study. However, the purpose of `"TThEeSmTaCjoHrEcMoInCceAnLfCorOtNrCyiEngNtToRdAetTeIrmOiNneS the validity were used. for this OPPT test is that ONLY NOMINAL recommends that measured test c`cohnecmeinciarlatcioonncetnotwrahtiicohnstobethuesteeds,t soorgtahantisomnsearceaneaxcpcousreadt.elyIfdiettiesrdmeitneermthienetdestthcahtetmhiecnaolminal b`ceonacnedntmruatsitonbse aardejounsltye,d fdoorwenxwaamrpdleby5050%%o.fthIefanmaelaystuircaeld mceonacseunrtermateinotnss,ofthseotmoexiscoirtty hvaadlubeesecnan `faunndiosthheedr,pwhyesciocuolcdhecmailccuallatperoccheesmsiecsatlhartecmoivgehrtylroawteesr, tahnedaactkuealintetsotaocrcgoaunnitshmyderxoployssuirs,e volatility, concentrations. 31s 000212 INVERTEBRATE TOXICITY Title: Acutetoxicity to aquatic invertebrates (Daphnia magna) TEST SUBSTANCE Identity: Perfluorooctanoic perluorooctanoate, FC-116, acid, ammonium FC-126, FC-169, salt; also referred to as or FC-143. (Octanoic PFOA ammonium salt, acid, pentadecafluoro-, ammonium ammonium salt, CASH 3825-261) Remarks: The is purity ws not 3M production lot number sufficiently characterized, was 390. although cTuhrreentetstinsfaomrpmlaetiwoansinFdCi-c1a2te6s, a it iswhaimtiexptouwrdeeorfy7s8o-lid. 93% test substance and 7-22% CS, C6, and C7 perfluoro analogue compounds. METHODS Method/guideline followed: Not sated Test type: Static GLP (YN): No Year study performed: 1987 Species: Daphnia magna `Age =< 24 hour neonates. Supplier: 3M Environmental Labs. Concentrations tested: 0,100, 180, 320, 560,and 1000 mg/L, nominal concentrations Exposure period: 48 hours Analytical monitoring: None because concentrations were nominal. Statisticalmethods: Probitanalysis Test conditions: "Dilution water source was carbon-filered well water with the following chemical characteristics: Temp was 21C . DpHOwwaass79..94 ppm "Test solutions were prepared by direct weights addition Stabilityof the test chemical solution was not noted 316 ESS meeeeeveeese -------- 000213 "Exposure depth) vessel was a 250 mL Pyrex glass beaker containing 200 mL test solution (10 6 em ""WaNterucohmefmdibaspthreynidrdusripnegrtreestp:licate was 10 DO control: 9.0 mg/L P1H000 mg/L exposure: $8 mg/L. control: 80 1000 mg/L: 8.1 Temp 2c Remarks: No other detailsofthe test conditions were presented, including water hardness. RESULTS Doseofeach endpoint (as mg/L): 43-hour ECS0 was 221 mg/L (95% CL: 186-261) Remarks: r-eLploiwceastets)test substance concentration causing 100% mortality was 560 mg/L at 48 hours (both - There was no mortality in the controls ``mWoarstacliotnytrol response satisfactory (yes/nofunknown): Yes, based on the fact that there was no. Statresiultss,atsaipprcopraiatle: Notpresented CONCLUSIONS `The 48-hour ECS0 was determined tobe 221 mg/L (witha 95 % C.L. of 186-261) `Submitters' remarks: The data testing. However, sample purity quality was not Klimisch properly crhaanrkaicntgerwiazsed2.anTdeisttliancgkmeedtantahleytcirictaelricaonffoirrqmuaatliiotny of test substance concentrations. Reviewers' remarks: none REFERENCE 3MCompany. April 30. 1987. [Report tile no given] Lab Request Number E1262-1. Completed on OTHER GNeondeertaalilredemraerpokrst:waTshiasvasiulambmlea.ryThwearsefboarsee,dtohenacosntuemnmtasorfythreipsorstumamnadroyn,lyinlirmeifteerdendcaetatoabtlhees. protoancdroeslultss ofthe study, are limited. 317 000214 T"TEheSTmaCjoHrEcMoIncCeArnLfCorOtNryCiEngNtToRdAetTeIrmOiNneStwheervealuisdeidt.y fOorPtPhTirteectoimsmtehantdOsNthLatYmNeaOsMurIeNdAteLst `cchoenmciecnatrlactioonncetnotwrahtiicohnstobtehuesteeds,t soorgtahantisomnse acraeneaxcpcousreadt.elyIfditeties rdmeitneertmhienetdestthcahtetmhiecnaolminal `bceonacnedntmruastitonbseaardejuosntleyd, dfoorwenxwaamrpdleby505%0o%ft. hIefanmaelaystuircaeldmceonacseunrtermateinotnsso,ftshomtoexiscoirttyhvaadlubeesecnan afunrdniosthheedr,pwheysciocuolcdhecmailccuallatperoccheesmsiecsatlhartecmoivgehrtylroatweesr, tahnedatcatkuealintteosaocrcgoaunnitshmydcrxoployssuirse,. volatility, concentrations. -- 318 000215 `TOXICITY TO INVERTEBRATES Title: Static Acute Toxicityof EX-1003 to the Daphnid, Daphnia magna TEST SUBSTANCE `Idaemnmtoitnyi:umPeprefrlfulourooroocotcatannooiactaec,idP,FaOm,mFoCn-1i1u6m, sFaClt-;1m26a,yFaCl-so16b9e,rFeCfe-r1r4e3d,tooraassPaFOmaSjoarmmcoomnpiounmensatlot,f FX1003. (Octanoic acid, pentadecafluoro-, ammonium salt, CASRN 3825-26-1) Rsuefmfiacrikenst:ly Tchhaera3ctMerpirzoeddu,ctthioonuglhotavnauimlbabelrewiansfo2r3m2a7t.ioTnhiendpiucraitteyodfitwthaesteastsoslaumtpiloeno,fF<X-4150%03a,mwmaosnnioutm perfluorooctanoate, 50% analogue compounds. water, <3% inert perfluorinated compound, and 1 -- 2% Cand C; perfluoro- METHODS Method/guideline followed: OECD 202 Test type: Static GLP (YIN): Yes Year study performed: 1990 `fSrpoemciaens:inD-ahpohunsiedcsulutsuerde itnhatthweatsestmawienrteailneessdutnhdaner24tehstoucrosndoiltdioatnsthfeorstaatrtloeafstth1e4tdesaty.s.ThPeriyorwetroetepsrtoindgu,ced dNaepwhnHiadmspwsehrierem)aiunntdaeirnesdatiinc 1co0n0di%tidiolnust.ioDnurwiantgerac(ccollilmeacttieodn,fdraopmhwneildlsswaetrEenvniotrotSryesatteedmsforindHisaemapsteoann,d `wyeearset,ftrreoeoutfcahpopwa,reanntdstihceknfersess,hiwnajtuerriaesl,gaanSdelabennoarsmtarlaimticeasparticthoernbuetguimnnoinncgeofdatihley bteesft.orDeatphheitedsst. were fed Daphnids were not fed during the test. `Supplier: EnviroSystems-daphnids, 3M-test substance `Concentrations tested: concentrationsofthe test A screening test substance were was 0.1, performed 1, 100 and prior 1000 to the mg/L; definitive toxicity test. Nominal the numberofreplicates was not iwnedriecautseedd.: Fo0r(tbhleandekfcionnittriovle)t,es1t5,0f,o2u5r0r,ep4l0i0c,at6e0so0,fcaancdh10of0t0hmeg/fLol.lowing test substance concentrations Exposure period: 48 hours AnalyticDailssmoolnvietdoroixnygg:enT,esptH,sucbosntdaunccteivciotnyc,enatnrdattieomnpserwaetruerenowtermeeamseuarseudredudrainndg the study. recorded daily in cach test chamber containing live test animals. 319 000216 (ShtSeattei4sp8thi-achnaol,um1re9t8Eh3Co)d.ssT:(hbeRaespserudolbotisnto,ifmmtmohovbiitnlogixziaacvtietiryoantg)ees,st iowrnegrleinnioenamtrienirnaptlreecrtopeondlcaebtnyitorsnattamineodtnahsroodfdstwtahateisstteuissctealdsutfbeosctchaannliccqeuul.easte "cToelsltecctoenddiftrioomnsw:elWlataetrEnuvsierdooyrstaeccmlsimiantHioomnmopfttohne, NesetworHgaamnpisshmisr,e,anWdaoterrawlatsiacdijtusytteedsttinsg,hwaardsness of a1c8c0limmga/tiLoanspCeraiCoOd,(2a4n-dhoauerrsatperdioirno500t-hegaelsltonntpioaltyieotnh)y,ltehnedtialnuktsiopnriwoartteoretsetmpneirtatiuorne.waDsur1i9n.g8tCh.e No tsetsotcvkessosleultsiwonitwhaosutptrehpaurseed,ofasa tshoelvteentt.sTubhsetastnacbeilwiatysofadtdheededsitrseotlluytitoondsilwaatsionnowtaitnedriccaotnedt.aiNneodmiinn atlhe cveopnlciecnattreastoifonesaocfhtehestceostncseunbtsrtaatnicoenwweerree 0us(ebd.lanTkwecnotnytodla,ph1n5i0d,s2w50e,re40r0a,n6d0o0m,lyanadnd10e0qu0amlgly/Ld.isFeobuurted `oafmtohngtfeostursorleuptliiocant(esappofreoaxicmhatreelaytm7ecntm.deEpxtpho)s.urTeevsetsvseeslssewlewreer2e5r0amndLomllayssarbaankgeerdsicnoanntaiinnciunbgat2o0r0ml. dduertienrgmitnheed:48-Cohnoduurctteisv.itDyur8i0n0g~th9e0t0eus,mhthoesf/oclmlo(wcionngtrwolaetxpcohseumriesatrnyd r1a0n0g0esm(g0/L 4e8xphoosuurrse))weprHe8.1 81.020(0cmognt/oLleexxppoossuurree));,D.i3 ssol8v.e4d(0130090.m09a.5emxgpo/sLu(rceo)ntTreomlpeexrpaotsuurree),1959.1---290..51mCL(.co(nt1r0o0l0emxeplos.ure and eaxcpcoesputraeb)l.e Aleevrealst.ioAn w1a6s-hnouorlriegqhutiarendddSurhionugttdhaersktupdhyottoopmeariinotdaiwnasdiasustoolmvaetdicoaxlylgyemnacionntcaeinnterdatwiiotnhscaoboove awhpiptreoxfilmuaotreelsyce0n.t0l1i8ghgtsL.that provided an intensityof 45 Es" mi. Loading rate during the toxicty test was. Remarks: No additonal comments RESULTS Doseofeach endpoinStcr(easenmign/gLt)e:st: LC= 1000 mg/L, NOEC = 100 mg/L D=e5fi8n4itmigv/eLte(st9(5b%asceodnfoindeinmcmeablielviezla=ti4on0)0:--241-0h0o0urmEgC)s >1000 mL, 46-hour ECs R1e0m0a%rksusr:vivFaolrathae soctrheeernitnegstteedstc,oanfcteenrtr4a8tihoonusr.soFforextphoesduerfei,nittihvreetewsat,sl6l0t%estsuvrevsisveallsamtai1n0t0a0imnegd/aLcalnedar aapnpaevaerraangceewtehtrowuegihgohutt (tbhleotsttueddyd.ry1)0o0f%0.s0u0rv0i7vgalaotctchuererenddoinftthhee cteotm.sL]oaexdpionsgurret.eCdounrtirnogltdhaepthonxiidcsithya(des wreassulatpepdrionxiam4a8t-ehloyur0.L0C1x8pgo/fL.33Exmpao/sLuraeondfad4a8p-hhnoiudr tEoCths orfef1e6rmenLce.toxican, sodium dodecyl sulfate, Was control response satisfactory (yes/na/unkaown): yes Statistical resultsas, appropriate: No additonal comments C"TOheNeCsLtUsSamIpOlNeS48-hour ECS0forDaphnia magna was determined to be S84 mg/L, witha 95% confidence intervalof400 1000 mg/L. 320 000217 ee `sSaumbpmliettpeurrsi'tyrweamasrnkost:prKolpiemrilsycchharraancktienrgiz2e.dTaensdtinnog mateteetmsptthweacsrimteardiaeftoor cqouanlfiitrymtetsetsitnsg,ubHsotawnecveer, concentrations. Reviewers" remarks: The submitters' conclusions appear to be accurate, based on the data. REFEREEnNvCiEroSystems, Inc. 1990. Static Acute Toxicityof FX-1003 to the Daphnid, Daphnia magna. Hampton, NH. EnviroSystems study number 9013-3. OTHER `General remarks: ONLY NOMINAL The major concen TEST CHEMICAL fCorOtNrCiEngNtTo dRAeTtIeOrNmSitnwheervealuisdeid.ty fOoPr PthTisrteesctoimsmtehnatds tchhaetmmiecaalsucroencdetnetsrtacthieomnitcoawlhciocnhcetntrtahteitoensst boerguasneids,mssoatrheatexopnoesecda.nIafcictuirsatdeeltyedremtienremdintheatthtehetest nvaolmuiensalcacnonbceenatnrdatmiuosnts baereaodnjluys,tefdordeoxwanmwpalred5b0y%o5f0t%h.e Imfeanaasluyrteidcaclonmceeansturrateimoennst,sothfestooxmiecitsyort hvoaldatbileietny,faunrdniosthheedr, pwheysciocuolcdhceamliccuallatpercohceemsisecsalthraetcmoivgerhyt roawtees,ratnhde tacatkueailntteostacocroguanntishmydrolysis, `exposure concentrations Pteustr.ityTonfstohmeetetsetstmsaittearpipaeaarlesdo itshaat m1a0j0or%ctoesntccehrenmaincdalwawsasnoutsesdu,fffiocrieontthleyrschaarcahcetmeirciazledofilnesthsiesr purity (approximately 85%) was used. was used in other tests, for no obvious Water, a solvent stated reason. In (isopropanol) or fact, 3M in the a combination of summary ofeach both test state: "Data Tagree with may not accurately relate toxicityofth this concen. In addition,ifthis was a test sample with thatofhe test substance." "typical" TSCA section 4review, I would `rmejeeacstutrheemseensttsudoiftesh, pteensdticnhgemreicceailptionftahddittesitomnaeldiiunf.ormation on purity and studies on analytical 321 000218 AQUATIC PLANTS TOXICITY "cTaitplre:icGormouwttuhm and Reproduction Toxicity Test with N2803-3 and the Freshwater Alga, Selenastrum TEST SUBSTANCE `Ipdeennttaidteyc:aflPueorrfol-u,orCoAocStaRnNoic33a5c-id6;7m1)ayalsobe referred to as PFOA, FC-or2FX-6100,1. (Octanoic acid, Rlaebmoarartkosr:y aTshNe2830M3-3p.rodTuhcetipounriltoyt onftumhbeesrawmapsle2w69a.sTnhoet stuesftfiscaimenptlley wchaasraFcCt-e2ri6z,edr,efaelrtrehdoutgohbcyurtrheenttest information indicated perfluoro-homologue citowmpaosuandmsi.xtuTrheoe fte9st6s.a5m~pl1e0w0a%steastwshuibtsetpaonwcdeera.ndA0ss--ta3t.e5d% bCyet,hCeys,ubamnidtCtyer, the wsaatmeprl:eisporperpoapraantoilonsodliurteicotni.onIsn gtihveepnrtoototchoellaambeornadtmoernytw,eritewtaosdistsastoeldvethtahte test material in the sample was a 50:50 combined with isopropanol in a 50:50 ratio prior to use. METHODS Method/guideline followed: USEPA-TSCA Guideline 797.1050 Test type: Static: GLP (Y/N): Year study performed: 1995 `lSepasetci1es4:daTyhseparliograetowetrheedaecfcilniitmiavteedtesitn. sTtehreiles,uben-rsiacmhpeldeomfeadligaaaenudsmeadintotaiinnoecudlaattetemstedcionadaittitohnesstfaorrtaotf the definitive testwas froam 10-day old culture. Supplier: Austin. The supplierofthe algac culture was the Culture CollectionofAlgae at the UofTexas at Measure of growth used: numberofcells/mL, growth rate Cusoendc:en0t.r0a5t0,io0n.s5t0e,st5e.0d,:anFdor50thmegr/aLng(et-hfeinnduimnbgetreostf, rtehpelifcoaltleoswwiangsncoontcesnptercaiftiieodn)s.oFfotretshtesduebfsitnaintcievewetrees.t, `iosnoepdriolpuatniooln awnadtetresctosnutrbosltaanncde f(iNv2e8n0o3m-i3n)awlacsonccoennstirdaetrieodnstowebree1u0s0e%d itnestthseusbtsutday.nceThdeur5i0n:g5t0hmeixture of p(e5r0f%orNm2a8n0c3e-o3ftahned t5o0xi%ciitystoepstr.oApllaneaosunlld)tstewsetrseubrsetpaonrcteedasb-ortehcoeinvtehde(bNa2s8i0so3f-3tewsittshuobusttiasnocperoapsa-ntoels)t.edThe a0s,-3t2e,st6e3d,c1o3n0c,en2t5r0a,tiaonnds 5w0e0rem:g/0L,.63T,hr1e2e5,r2e5pl0i,ca5t0e0so, faendac1h00c0onmtgro/lL;antdheteasst-croencceeinvterdactoinocnewnterraetiuotnisliwzeedre: under static test conditions. Exposure period: 96 hours 322 000219 --------------------ee---------- ---------------- ------ee-- e eee---------------- PAnHaliynteiaccahl tmeosntivteosrsielngw:asComnecaesnutrreadtiaotntsheobtefhgintneitnsguabnsdtaenncde wofetrheeneostt.meIanscuurbeatdodrutreimnpgerthaetusrteudwya.sThe `wmietahstuhreedteasntdverseseclosr,dewdasdacloy.ntiTnhueoutselmyperreacotrudreed.inarepresentative vessel ofwate, which was incubated eSsttatiimsattieca7l2-meatnhdo9d6s-:hoCuerlECdesnosivtaileuse,sgarnodwt9h5r%aec,oanfniddpeenrcceenlitmiitnsh,ibwietrioencvaallcuuelsa,tewdhuiscihngwetrhee used to bocibensloelmriivmeaLdl,i-nfttfheeercaptvo-elcraoatngicoeennstpmreeacttiihfoioncdg((rNSotOweEtpChha)awnt,ae1s,9c8aa4)ln.cduAtlhaletencdoalmuciusnliaalntigcoonpnsacwreaenmtreretartpiiecornfosoonrefm-tewhdaeuyseaisnntaglsytushbiesstonaufnmcveab.reirTahnocefe.not(hAeNtOesVtA), the number ofcells/mL, and the average specific growth rate in cach test vessel at the end of "cToemsbticnoindnigtdieo-niso:niTzhedewsaigtaelrmaenddinuutmriweanst sptroeckpsa.reWdaatcecrorudsiendgftoortUhSeEaPccAlirmeactoiomnmoefntdheedtceostncoerngtarnaitsiomnssanbdy. afunosredaa(ltlhtetohpxeiHcdoiitlfyuteenhste.tisAnygncthwheeatmsiiccstaaellrigclahel,amreaencdrtiiecruhimezdaattmieotdneoisfaa,inaitdrijeauptsietosenedwnoaatsai7vt.e4a)rs.gaeAtmlppglaHeloofmfte7e.dsituwmmietdwhiaa0s,.1uasMnedHdwCfao]trecrpurluitsoureridtnogt,o fmcooenrdcmeiunultamrtaetiintocenlsstu:dmeed0d.ic4aa6,,dwm0.ai0su8m,pe(ar0nf.do0r01m04e2dm.mLgP/,hLo)srpeahsnpodercotluiesvae,dln(yi.0t.rH0a8teea,mvga/ynL)dm.ecthOaltloshreiddreetpeowcteterenetdidaielnttcehocentteddailmauitenntathneatsnfodwletlreoewsiantgor sbaoceltluiotvweiotinnhogefrtlehedvieeelnottefsatdnesdtueb0csttibaoennc.setTa(bhalsee-uttneessdtteesrdu)sbwtsoatrsaangpcereea(pnaasdr-etrdeescbteyiinvcgeodc)mobnwdiaintsiinoangsss.Nu2mA8e0d13t0-o030h(amavsg-e/teLapstpuerrdi)tmaaynrodyfss1ttoi0cl0ke%, e1fno0rr,im0cu0hl0eadcteemletldhsie/amt.Le.stAEpmxpeprdooipsaru.irAaetlvegeaasesmeowluesnrcteosndosifisttshrtiiebdsuotseftdo2c5ak0msoomnlLugtitgohlnraeswes rrEeerpllaeidncdmaeetdyeoedrfirefealccathslkystocroednaittlamuietnniitonnagtw5ta0htemerLattooefotfest sdoalruitnigont.heTetsestt.veTshseelpsHwoefrethreantdeotmsloyluatriroannsfgoedrtohnea 2r5o0t,ar5y00s,haaknedr a1d0j0u0stmegd/0L e1x0p0os1uprmeicnoancneinntcruabtaitoonrs ahwfoefurerecst)ienwdetthrheeersaausnrgfvoeilvolaolfwsa:n2.d9p-s4H.u0barsteatqeusnet=nigtn7iget.ir4aot~wiotn1h.0o3Afst(hctoeanttarelogdlacbe.yxTpthhoeessumrueeba)ms2,iu.tr9-eed, w3h.ai0tse(rl1oc0wh0e0pmHmisgmt/raLyyevhxapalouvseeusrae(d)0v,-e9rm6seelayn t`meamipnetraaitnuerdewainthgeco=ol2-3w.h5it-e2f4luCo.reAsc2en4t-hioguhrtslitghhttapnrdov0i-dheodura diagrhktpihnotetnospietryoiofdswpapsroaxuitmoamtaetilcyal3l8y0 fcoooutnctasndwlietsh. aAhlegamloccyetllomceotuenrt.s in each test vessel were determined daily by meansofdirect microscope a`cRceempatrekds:raWnagteefrohSra.rdcnaepsrsicwoarsmunottumintdoixciactietdy.tTeshteinpgH(7f.o5r+ma0.n1)y. eAxsposstuarteedcbonyctehnetrations was ouside the sIuabbmoirtatteorr,ytahnedretaheppperaorcsedtourbeecaondidsuccrteepdanbcyytbheetlwaeboernattoherysatompplreepparreepathreattieosnt sdoilruetcitoinosn,s given to the RESULTS mDdgeof/siLen)i,tofiebveaasscethdudoeynn,dttpehsoeti9sn6ut-bh(saotsuanrmcgEe/CLas)s:t(enTsedhdeas(Ns5Oo0cE%iaCNte2fd8r903t5h-%e3rcaaonnngdfei5-df0ein%ncdeiisnlogipmsrittousp)daynwowalas)sa1n58d00 9mm0gg//mLL.g(F1o2r(5t6h3-e2-50130 mg/L), based on test substance as-received. The 96-3h2o3ur NOEC and LOEC values were 125 and 250 000220 ---------------------------------------------- am1b3l0aem1ruespercetsipveecltyi,veblays,ebdaosnedsatnsthuebfssttasnubasstsanecde.asTrhecei9v6e-dh.ouTrhNOclElCgarnodwtLhOdEotCa valruees vwesre o63eand cTaabplieco1:rmCeultlegmrowth data ofacute toxicity test with N2803-3 andthe freshwater alse, Seenasiram cos`nNtcoeemnntitrnaeatdli,on| Hours `Numberofcells/ml,x10"(hour) IPnehria cbietniton|a TnPheirbceiniton mg/L. [Camm [ 0 [a*r smem[wm %] en Density ne Growth [S osToTNiSTiJ T e[s2 u ise 7 CoSw0T1i0o1E=<Tio0 |JE<<iSioTo[|<E=St0oT |==ECoio |B1t0To0 || 110000]] ciRhheeamnsaggreaksesi:tnocAtehleesTirzs6,kchoonltuohrrs,oofrecoxmnpotorospluhroel,oagntyyhewfrhsetwnerccroanmmoepnaitrgernofoouft.ahgeIgcnroeangtdaodlt.iionTn,hltohoceafrttwiooorfnNe,2n3oo0ro3at-dhc3ecwrletnes of (eSWrtarmedi,bneyteta.h01sb9m9i5a)tldeeg,maobni,oslsnootgtiecdaaltcdhaata1,g0e0bn0earsmaetdeodbnoLyfhSeparepe. rlvoipsouosfaiehcaexnopplodostodfoeatfligiaveebfooptsrrEooxwppss,o]sTea.hcsaAhcsoilng oPifnNHd2im8caa0ty3e-dh3hv.teTtcehsatssceuodbnsicteanniucetincoonncoofefintSragatpiroognspoyshkwoovhaeo1hli2g5nhemtrehlec.osnetcceucnchreeamdiiocpnaHsl vodafcleueotsttsuab4oc.t0acnncoedT.utlTonihweeetrostwtehocetlyow Concentration of et Subsiance served 10 cause 100% moray was 250 mel Was contrl response satisfactory (sesnofnknown): yes Statistical results, as appropriate No additional comments concLusios ThmLe,NObaCsedforntthesrasnugbestfainncdeinagcsituddy,wasnd590 mmLe.l,Fboarsteeodnef6i5n1iuvbessatnudcye,1t0heT9e6e-hdou.r ETChaeg9w6a-sho1u5r0 T'sNpOeEcCiealnyd.LOEC values were 125 and 250 mg/L (as-tested) and 63 and 130 mg/L (as-received), pcSouenbcmaeintsttreartsbi?eonrdieinmstaechrrsekpstanKcslyomubiiecothnwsea.eknSitanmegpsl3ae.mTpphuleretspytrueidspyanroaltatciskousnfadinceaeleynitdioycnacslhmagreaacvsteurr0iesemde.ntAbodfodseistttoonsnuablas,tdatnhtcnreee 2 000221 hpraovceebdeuerne caodnvedruscetleydabfyfetchteedlsbbyoriantiotarly loowprpeHparvealtuheestiensttshoeluhtiigohnes.r tSeutrvsiuvbasltaanncdegcroonwcetnhtorfattihoensalgae may fRuervtiheerweirnsc?reraesemdargkrso:wthThienhcibointcilouns,iwoanss calpepaeralryfsotabteedsuapspaorptoesdsibbyletshoeudractae.ofTehrreorl.ow pH, which may have. REFERENCE FTrRe.shWwialtbeurrAylgLaa,boSrealtoerniaessi,ruInmc.ca1p9r9i5c.orGnruotwutm.h MaanrdbRleephreoaddu,cMtiAo.n STotxuidcyitnyuTmebsetrwBi9t3h-NT2H8.03-3 and the OTHER O`GNenLeYralNOreMmIarNkAsL: TTEheSTmaCjHorEcMoIncCeArLn fCorOtNrCyiEnNg TtoRdAeTteIrOmiNnSe twheervealuisdeid.ty fOoPrPthTsrteecsotmimtehnatds cthhaetmimceaalsucroendcetnetsrtacthieomni0calwhciocnhcetnottrhatifoensst obreguasneids,mssoatrheatexopnoesecda.n aIcfcituriastdeeltyedremtienremdintehtththetest v`naolmuiensaclacnonbceeantnrdatmiuosntsbaereadojnuys,tefdordeoxwanmwpalred5b0y%5o0ft%h.eImfeaansaluyrteidcaclonmceeansturrateimoennst,sthoef stooxmiceitsyort vhoaldaibleteyn,faunmdisohtehde,r pwheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcmoivgerhytrlaotwese,ratnhde atcatkuealintteotacocroguannitshmy.drolysis, exposure concentrations. 3s 000222 ee TOXICITY TO INVERTEBRATES Title: Acute Toxicity of N2803-3 to the Daphnid, Daphnia magna `TEST SUBSTANCE pIdeennttaidteyc:aflPueorrfol-u,orCoAocStaRnNoi3c3a5c-i6d7;-m1)ay also be referred to as PFOA, FC-26, or FX-1001. (Octanoie acid, `Rseammpalrek,sF:C-T26h,e w3aMs rperfoedrurcetdioton bloyt tnhuemtbeestrlwabaosra2t6o9r.yTahseN2t8es0t3s-u3b.stTahnecepuwraistyaowfthhitee spaomwpdleer.waTshenottest ssuubisctiaennctelyancdha0ra--ct3e.ri5z%edC,e,alCts,hoaungdh Cavyapielrafbllueoirnof-ohrmoamtoiloongiunediccoamtpedoiutnwdass. amixtureof 96.5 -- 100% test METHODS Methodiguideline followed: U.S. EPA-TSCA Guideline 797.1300 Test type: Static: GL (Y/N): Yes, with one exception: the stability ofth test substance was assumed, but not verified Year study performed: 1996 `LSapbeocriaetso:rieWsatienrMaursbeldefhoeraadc,cMliAm.atiDoanpohfntihdes etemsptloorygeadniisnmtshweasstuddeyiowneirzeedlewsasttehranco2l4lehcotuerdsatolTd.R.TeWsitlbury sdapyesc.imTehnesowreigrienaplrocudlutcuerde wbaysadoublttaidnaepdhnfirdosmtAhqatuawteirceRmeasienatracihneOdrguanndiesrmtse,stHcaomnpdtiotino,nsNHfo.r Dmuorrientghan 7 aacbcnloirmmaatliiotni,esdeatphtnesitdisniwteiarteionn.otTthrearteewdafsorndoismcoarstea,litthyeyduwreirneg ftrheeeo4f8 ahpopuarrsepnrtesciecdkinnegsst,heinsjtuarriteso,ftahned test. `dTahielycudlutruirnegwaacsclsiumpaptliioend. wDiatphhnaiydesaswte/rreountotchfeodwdmuirxinagntdhethteestf.reshwater alga Selenasirum capricornutum `sSuubpsptlainecre:. T.R. Wilbury Laboratories supplied the test organisms. 3M, the sponsor, supplied the test `(aCso-nrceecnetirvaetdi)ownesrete:st0e.d0:50F,o0r.5t0h,e 5s.t0a,ti5c0s,carenedniSn0g0tmesgt/,Lt.heFonromtihneasltactoinccdeenftirnaittiivoenstoefstt,htewotersetpsluicbastteasncoef `1a3c0,h 2c0o0n,ce3n6t0r,at6i0o0n,waenrde1u0se0d0. mTgh/eLf(otlelsotwedinags nao5m0i:n5a0l mcioxntcuernteorfattieosntsswuebrsetauntcileizaend:d i0so(pbrlopaannkolco)n.trTohl)e, nominal and 500 mcgo/nLc.entrationoftest substance (as-received) in solution was 0 (blank control), 65, 110, 150, 300, 326 000223 Exposure period: 48 hours Atensatlsywteircealbmaosneditoonrinnogm:inaTelstcosnucbesnttarnatcieocnosoncfetnetsrtatsiuobnsstawnecre.e nDoitssmoelavseudroexdydguerni,ngpHt,hecostnudduyc.tiAvliltyt,oxaincdity tteemmppeerraattuurree wineraebemaekaesruorfewdaatnedr rienccourbdaetdeddialmyoningetahcehttesetstvcehssaemlbsewratsharteccoonrtdaeidnceodnitivneuaonuismlaylsd,urTihngethe test S`atvaetriasgteicmaletmheotdh,oodrs:binLoCmisalanpdroEbaCb:ilivtayluweisthwenroen-clailnceualratiendt,erwpholeantipoonss(iSbtleep,habny,p1r9o8b3i)t.analysis, moving Test conditions: L`WTaRte.r uWsieldfbourryaLcacbloirmaattoiroinoesfitnheMatrebstleohregaadn,isMmAs.anWdaftoerralwlastoxaidcjiutsytteedsttoinghwaarsdndeesisonoifze1d60wa~te1r80comlgle/cLteads tCharCoOug;haanpdarsttoirceed fiinlt5er0,0u-lgtarlalvoionlpetolsyteertihlyizleern,eantadnkasc,tiwvhaetrede citarwbaosn.aeArcahteemdiacnadlcocnhtariancutoeursilzyatpiaosnsoedaf breeplroewsetnhteatlievveelsoafmdpelteeocftidoilnoutrinoontwaptreesrendte.teTchteedtierstonsuabts0t.a0n3cemgw/aLs;parllepoatrheedr pboytecnotmiablincionngtaNm2i8n0a3n-t3s,wearse rdierceecitvieodnsfrgoimvetnhetospthoensloarb,orwaittohryiswoeprreoptaonodilsisonalve50t:h5e0tersattiom.atHeoriwaelveinr, t5h0e:5t0eswtastuebrstiasnocperoppraenpoalrastoilountion. a`Trheisre5p0o:r5t0edmioxntaurneacwtaisvethiengnrceodniesnitdebraesidsto(abcetiv1e0i0n%grteedsitesnutbistathneceesdtursiunbgstthaencteoxaisc-irteycteeisvt,edbumtinlulsretshuelts `iusnodperropsatnoorla)g.e Tahned tteesstisnugbscotnadnicteiownass. Faosrsutmhedtetsothoargvaenaispmusr,itmyeoafsu1r0e0m%enatcstimveadiengdreudriienngttahned7tdoabyessptraibolre 1a0dtihsesosltavretdoofxtyhgeednefcionnicteinvtertaetsitowniotfhatN2l8e0a3st-93.1inmdgi/cLa.tedAa1c0u0lt0umregt/eLmpsetrocaktusroelurtainognewoafs1p9r.e5pa2r0ed.5byC and `ficnoamlbvionilnugm2eo.0fgo20f0t0hemLt.estTshuebstteatncvees(s5e0l:s5w0emriex3t0ur0eomfLNg2l8as0s3-be3aakenrdsitshoaptrcoopnatnaoli)neadn2d5d0ilmutLioonfwtaetster to a asodlduetdiotno(daipluptriooxnimwaatteerdeinpttheswtavses9seclms)todfuorrimnugltahteettesets.t mAeppdrioapwriitahtethaemouusentosfoaftsholevesntto.cTkwseonluttyiodnapwehrnei.ds wveesrseelisndwiesrcerirmainnadtoemllyyaanrdrcaqnugaeldliyndainstirinbcuutbeadtoarmaonndgltoowsoelryeplciocvaetreesodfdeuaricnhgttehset c4o8n-cheonutrratteisotn.DuTreisntg the dmegf/iLni,titveempteesrta,ttuhreef=ol1l9o.w4in~g2r0a.n7geCs, wceonrdeuecsttiivmiattye=d 5f7r0om-m6e1a0sumrheomesn/tcsm:,dpisHso=lv8e.d3 ox8y.5g.enA=186.-7ho--ur8.l8ight `wahnidteS-fhlouuorredsacrekntphliogthotpsetrhiaotdpwriotvhidaed15a-lmiignhuttientternasnistiytoiofn5p8erfiooodtcwaansdlaeust.oAmeatriactailolnywmaasinntoatieneqduiwrietdh tcoool. maintain dissolved oxygen concentrations above an acceptable love. aAcshtatciocncteesnttwraatsiocnonadnudct1e0ddawpihtnhi3d9sr0emplgi/cLatiesowperroepaunsoeld.anTdhaisdtielsuttwioanswcaotnedruccotnetrdoli,n aTmwaonnreeprlisciamtielsarofto the test with N2803-3. Measurements made during the 7 days prior to 2in0it.ia1t2io0n 9ofatnhde iasdoipsrsooplavneodlotxoyxigceintyceosntc.enTthreasteiomneoafsautrelemaesntt8s.3inmdgi/cLa.teTdahecutelstturveestseemlpsewreatruerrearnadnogmeloyf aesrtmiamnagteeddinfraowmamteearsbuartehmaenndtsthdeurliignhgttihnetetnessitt:ydwiasssol13ve-d205; f=oo8t.1ca-nd8i.c5s.mgT/hLe,ftoellmopweirnagturraen=ge2s0w.e4r-e 209C, conductivity = 530 - 540 umbosiem, pH = 8.3 -- 8.5. 327 000224 Remarks:No additional comments RESULTS Doseof`eBaacshedeonndpeositnstu(basstamngc/eLa)s:-reLcCeiivead:nd ECq values and 95% confidence intervals 2244--hhoouurr CLCisgo == 52000 ((337000 - >459000))mmgg//LL 4485--hhoouurrELCCiyyy == 340600 ((330500 450600)) mmge//LL Based on45t-ehstousrubNstOaEncCe=as-1e8s0tmedg/(L50:50 atoofN2803-3:isopropanol): 22d4--hhoouurr LECCa:s ==1$04000(7(46000~-91700)00m)g/mLg/L 4488--hhoouurr LECCs == 780200 ((760600--798200)) mmgg//LL. 48-hourNOEC = 360 mg/L Robesmearrvkesd:anDdurtihneg48t-hheotuorxiEciCty:taensdwCitiho39va0lmuegs/wLeirseop>ro3p9a0nomlg,/Ln.o mFoorratlhietyscorreesnuibnlgetehsatl e(f4f8e-chtosuwresrpeoste1x5po%ssuurrev)i,vatlhearteSw0a0smagt/leLas(tsu9r5vi%visnugrvdiavpalhnaitd0s(ebxlpaonskecdotnot5r0o0, m0.g0/5L0,w0e.r5e, ainmdmo5b.i0limzge/dL). ADlusroi,ntghtehree was. `deexfpionsiutriev,e ttohxeiccointyttreosltdwaipthhniNd2s80h3a-d3a,nna0veirnsaogleuwbleetmweaigthe(wbralsointeoadt)elodfd0u.r53inmggt.h Ttheet.teAsfttseurb4st8ahnocuers of c(o2n8t0r3o-l3d)urdiindgntohtecdaeufsienit1i0v0e%temsoortalsictryeeantinngytecto.ncTeanbtlreat1iodneptiecsttesd.cuNmuolamtoirtvaelipteyrcweants moobrstearlvietydoifntthhee definitive test. `Tabl1e. CumulativePercentMorality Was control. Nominalatested satisfactory | concentration (mg hows hows response [ Blankcomrol T7770 0 we 71To| 20 17 T 0 -- ] [se 7170--T70 | [eo700 15 | Cow15Ts (vesinolunknown): Yes | Statistical results as appropriate: No additional comments CONCLU"TSheIOasN-Sested test substance (N2603-3) 48-hour LCS0 for Depa magna was determined to be h8o0u0rmEgC/SL0wfiotrhDaa9p5hn%icaomnfaigdneancweaisntdeertvaelromfin7e0d0t--o b9e2072m0g/mLg./LThweitahs-2c9st5e%d tceosntfsiudbesntcaencinet4e8rv-al of 38 000225 ee w6a6s0 ~367080mgm/gL/.L.ThTehe48a-sh-otuerstLdCtSeOstfsourbDstaapnhcnei4a8-mhaogunra,nob-aosbesderovnedt-heeffceocntc-ecnotnrcaetnitornoatfieosn t(NOEC) 4s6ub0stmagn/cLe.iTnhseol4u8t-iohnouwraEsCdseoteforrmiDnaepdhtnoibaem4a0g0nam,g/bLa,sewditohn ath9e5c%onccoennftriadteinocneoifntteesrtvasloubfst3a5n0ce-- in s4o8l-uhtoiuorn wnoa-sodbesteerrvmei-nceffdetcot-bceo3nc6e0nmtrga/tLi,onwi(tNhOaE9C5)%focotnhfeidteesntcesuibnsttearnvcaleoifn s3o0l0ut-io5n0w0amsg/1L5.0The mylL. ``cSounbcmeintttreartsi'onrseimnatrhkest:estKlsiolmuitsicohnsraannkdinsgam3.plTehpeursittuydyislnaoctkssuafnfailcyiteinctally mcheaarsauctreermiezendt.ofAtdedsittisounbasltlay,nctehere p`arpopceeadrusrteocboenadudcitsecdrebpyantchyebleabtowreaetnortyhetosparmepplaereprtehpearteasttiosonludtiiroencst.ions given to the laboratory and the Reviewers' remarks: The author's conclusions appear to be supported by the data REFERENCE OTHER `TDRa.phWniidl,buDraypLhanbioaramtaogrineas., MIanrc.bl1e9h9e6a.dA,cMuAt.e TSotsuidcyitnyoumfbNe2r80$932--3THto.the O`GNenLeYralNOreMmIarNkAsL: TTEheSTmaCjHorEcMoInCcAenLfCorOtNrCyiEngNTtoRdAeTteIrOmiNnSe twheervealuisdeid.ty fOoPrPthTisrteecstoimsmtehnatds cthhaetmmiecaalsucroencdetnetsrtacthieomnitcoalwhciocnhceontrtahtitoensst boergsaendis,mssoatrheatexopnoesecda.n aIcFciutriastdeeltyedremtienremdintheatthtehetest vnaolmuiensalcacnonbceenatnrdatmisonts baereaodnjluys,tefdordeoxwanmwpalred5b0y%o5f0t%h.eIfmeanaasluyrteidcaclomnceeansturraetimoennst,stohfestooxmiecitsyort vhoaldatbileietny,faunrdniosthheedr, pwheysciocuolcdhceamliccualaltpercohceemsisceaslthraetcmoivgerhytrlaotwese,ratnhde tacatkueailntteostacocroguanntishmydrolysis, `exposure concentrations -------------- 329 eS ase ------ 000226 AQUATIC PLANTS TOXICITY "Title: Growth capricornutum and reproduction toxicity test with FC-1015 and the freshwater alga, Selenastrium TESTSUBSTANCE IAdmemntointyi:umPeprefrufllourooroocotcatnaoniocataec,idP,FaOm,mFoCn-i1u1m6,saFlCt;-1m2a6y, aFlCs-o1b6e9,reFfCer-r1e4d3tooraassPtFhOe Amaajmormocnomipuomnesanltt, of FC-1015. (Octanoic acid, pentadecafluoro-, ammonium salt, CAS #3825-26-1) Rinefmoarrmaktsi:onTihnedicteasttessaitmipslae 3is0F%C-s1tr0a1i5g.ht IctasrpbuornitcyhawiansvneortsisoufnofifciFeCnt-l1y4c3hairnact0er%izweadt,ert.hoTuhghe c3uMrrepnrtoduct ltoetstnsuumbbstearncwea.s D"aHtaOGweEr2e0u5s.e"d Dtaotcaommpaayrenottoxaiccciutryaotfetlyhereblrataencthoexidc/isttyroafigthhtechteasitnsaammpmloenwiiutmh thatofthe `pearmfmlounoriouomctpaenrofaltueorhooomcotalnoogatmeixitnuFrCe-1in01F5C.-14v3. what is supposetdo be the 100% straight carbon chain METHODS Method/guideline followed: OECD 201, USEPA-TSCA, Guideline 797.1050 Test type: static GLP (Y/N): N Year study performed: 1996 Species: Selenastrum capricornutum `Supplier: Universityof Texas at Austin Measureofgrowth used: algalcellcounts (cells/mL),celldryweights Concentrations used: 0, 210, 430, 830, 1670, and 3330 mg/L. replicates at each concentration were tested. The concentrations were nominal. Three Exposure period: 96 hours. Analytical monitoring: none Statisticalmethods: Probitanalysis `Test Conditions: The algae were grown in sterile enriched nutrient medium per USEPA 1978 guideline and were `mutrients allowed essential 14 daysforacclimation to the conditions. The for algal growth and also served as the diluent nutrient medium provided all mineral for all algal operations. The pHof this synthetic algal medium was adjusted to 3330 mg/L stock solution was prepared 7.5 by prior to diluting use in assays. 3.33 oftest For preparationofthe test solution, a substance in 1 liotfwaeterr. Aliquots 330 000227 wuseerde wtehrene a2d5d0emdLd.iEcreenymoeydeirlsuicoonntwaiantiengi1n0t0esmt iv.estseesltsotlouctrioenaatnedstcsaoplputeidonwsi.thTihneveerxtpedosgulraessvebesaskeelrss. T1h00e pvems.selFsowuerrheulnodardeeddfwoiotth-caanndiineitsoiafl cloingchetnitnrgawteiorneopfro1v.0idxed10b*ycceonltiln.uoaunsdcosohla-kwehnitceonfltuionroeusscelnytat l7i.g4h-t7i.n6g.(3T3h3e0 wmagt/eLrecxhpeomsiusrter)y paanrdatmeemtpeerrsamtueraesu=re24d.d0-u2r4i.n2g tihnecuebsattoirn)c.ludTehdr:eepHrep=li7c.a5-t1e0s.o8ft(hceontrol) and eAxpppeernidmiexntfowrepraerapmeerftoerrmseda.nd Mdeetaescutrieonmelinmtitsso).f dTihluetioonnlywactheermicchaelmidsettreyctweedrewaaslsiorpoerafto0r.m0e3dm(gs/eeL Rwietmhairnktshe:acTcheeptpaHblrearnagnegef.orWthaetceonhtarrodlnwesass,oduutrsiindgetahcecespttuadbyl,ewalismnitost, biuntditchateod.ther tested sample was RESULTS Doseof each endpoint (as mg/L): Val2u4ehs cEaClScu0la=te2d5u1s0in(g13c4e0l-c3o3u3n0t) (mcgelllLs/mL): 4782hhEECCSS00>= 23034300 (m1g19L0-3330) mg/L 9966hh ENOCESC=0=1291800m(g1/7L10-23m6g0/L) 96 h LOEC = 430 mg/L 2Va4lhueEsCcSa0lc~ula1t7e0d0u(s6i7n3g-t3h3e00a)vemrgag/eLspecific growth rate: 3782hhEECCSS00>>33333300mmpglLL 9966hh ENCO5E0C>=3433300mmgg//LL 96h LOEC = 830 mg/L RHoeumrsa.rkBsa:seAdlioqnuogtrsowofththoebs3e3r3v0edmgin/Lthteesrtecsoolvuetriyonphwaesre,etdhiluetfefdecwtitohnaallggaallmgerodwituhmwaansdfcouultnudretodbfeor 72. algistatic `Was control response satisfactory (yesno/unknown): yes Statistical results, as appropriate: none CONCLUSIONS FfaCt-e 1v0a1l5ueeoxfhi>b3it3s309m6Lh.ourTEhCeS906 cheolurcoNuontOvbasleurevoefd 1E9ff8e0ct(1C7o1n0c-e2nt3r6a0tmiogn/L()NaOnEdCa) 9is6 2h1o0urmEgC/LS0fogrrcolwlth cceolulnctoaunndt 4a3n0d $m3g/0Lm. fLor gorrowgtrhorwatteh. raTeh.eTLhowietsetstOsbusbesrtvaendceEfwfaesctdCeotnecremnitnreadttiobne(aLlOgEiCs)atics 430 mL for Smuebemtistctreirtesr"iafroermqauraklsi:tyFtoerstdiangt.a rHeloiwaebivleirty,, ithilsacsktsudiynfwoarsmaatsisoingnoendtha Klpuirmiitsyochftrahtintgeotfs2u.bsTthaencsetuadnyd atchteu4a8l mheoausrurvealmueenstswoefrethien aexmcoeusnsotfof24teshtosuurbvsatlaunecs.e in solution. Also, no explanation is given ss (0 why. 51 000228 Reviewers' remarks: none REFERENCE fr`eWasrhdw,atTe,rNaelgvai, uSsJe,l.eannadstRr.umBocearpir.ic1o9r9m6u.tuGmr.owTtRh.anWdilrbeuprryodLuacbtoiroantotroiseisc,itIynct.estLawibtRheFqCu-e1st01nSumabnderthe P1624. 3M Company, St. Paul, MX. OTHER General remarks: ONLY NOMINAL The major concen TEST CHEMICAL for trying to determine CONCENTRATIONS the validityfortistest i that were used. OPPT recommends cthhaetmimceaalsucroendcetnetsrtacthieomniocalwhciocnhcetnotrtahteitoensst boerguasneids,mssoatrheatexopnoesecda.n aIcfciutrisstdeeltyedremtienremdintheatthtehetest v`naolmuiensaclacnonbceenatnrdatmiuosnts baereaodnjluys,tefdordeoxwanmwpalred0by%o5f0t%h.e Imfeanaasluyrteidcaclomnceeansturraetimoennst,sthofestooxmiecitsyort had been furnished, volatility, and other pwheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcmoivgerhyt rlaotwese,ratnhde tacatkueailntteostacocroguanntishmydrolysis, `exposure concentrations. tPeusrti.tyTonfstohmeettesetstmsaittearpiapleaarlesdo tishaatm1a0j0or%ctoesntccehrenmaincdalwwaassnoutsesdu,fffiocrieontthleyrschaarcahcetmeirciazledofinletshsiser pwuarsituys(eadpipnrooxtihmearteesltys,8f5o%r)nwoaosbvuisoedu.s sWtaatteedrre,aassoonl.venItn ifascto,p3rMopinatnhoeirlr)sucmommbairnyaotficonaocfhbtoetsth sTtaatger:ee"Dwaittah mthaisycnoontcaecnc.uraIntealdydriteiloant,itfotxhiicistwyoastah "ttyepsitcsaal"mpTlSeCwAitshetchtaitoonf4threevtiesetw,suIbwsotaunlcde." rmeejaescturtehemseentstsudoifest,hepeesndticnhgemriecceailptionftahdedietsitomnealdiiunmf.ormation on puarndisttudiyes on analytical APPENDIX `Cmhemeicaal sureomf deilutniontwatser Parameter: Detection Limit: Metals AAlrsuemniincum BCoardomnium Chromium Cobalt Capper Tron Lead MNeircckuelry Silver Zine 00.101mmg.g 0.5 mg 00..00100m2gmlLL 00.00305mmggl/LL 0.03 mg/L. 0.005 mg0l.L0003 mg/L. 00..0032 mmggl.L 002mg 332 000223 CNhilotriede FlTuoourlidoreganic carbon OTortgaalnopchhoisoprhionreouPessticides OTrgoaxnoappheosnpehorous Pesticides DiTmEePthoate PCMBosnocrotophos 0I0m5 gmgNIL 0m1mggL 003 mel 02p5 oll 0.5ug20481 2200ugp 05 ug EE 000230 INVERTEBRATE TOXICITY Title: Acute toxicityofFC-1015 to Daphnid, Daphnia magna TEST SUBSTANCE IAdmemntointyi:umPerpfelrufolruooroocotcatnaonioeataeci,d,PFaOm,mFoCn-i1u16m,saFlCt;-1m2a6y,alFsCo-b16e9,reFfCer-r1e4d3too asasPtFhOeAmaajmormocnomipuomnesanltt,of FC-1015. (Octanoic acid, pentadecafiuoro-, ammonium salt, CAS #3825-26-1) Rinefmoarrmaktsi:onTihnedicteasttessaitmpslea 3is0F%C-s1t0ra1i5g.ht IctasrpbuornitcyhawiansvneortsisounffoifciFeCnt-l1y4c3hairnac8t0er%izweadt,ert.hoTuhgeh c3uMrrepnrtoduct ot number was "HOGE 205." METHODS Method/guideline followed: USEPA-TSCA, Guideline 797.1300 Test type: static GLP (YN): N Year study performed: 1996 Species: Daphnia magna, less than 24 hours old, wet weight = 0.35 mg. Supplier: initial brood stock from Aquatic Biosystems Creopnlciecanttersaatticoancshucsoendc:ent0r,a4t3i0o,nw7e30r,e1t2e0s0t,ed2.000, and 3300mg/L. The concentrations were nominal. Two Exposure periods 48 hours Analytical monitoring: none Statistical methods: Probit analysis "mTges/tLC(oansdCitaiCoOn)s:, wThhiecdheiisowniitzheidndtihleutaicocnewpattaebrleursaendgei.n tThehetewstatwearswaadsjupsatsesdetdotahrhoaurgdhneaspsarotfic1u6l0a-t1e8f0iler, aulltkraalviinoilteytosfte1r0il8izmerg,/aLnadsaCctaiCvaOt,edacnadrbiotnc.onWtaaitneerdu<s0e.d01fomryth/eLtpeastrthiacudlaatheamradtnteesrsaonfd1<716 mmgg//LL taontdalan ofrorgapnaircamceatrebrosn.anFdurdtehteerctmieoansluirmietms)e.ntTsohefdoinlluyticohnemwiactaelr chemistry were also detected was iron at performed 0.03 mg/L. (sce Appendix Test solutions wdeeprteh)crweearteedubsyeddiarseectxpwoesiugrhtesveasdsdeiltsio.n.ThGelyaswserbeealkiegrhtsly(3c0o0vemrLe)d dcounrtianigntihneg e2x5p0ermiLmenttes.t sTowluotiroenpl(i9cactmes, ach of 10 daphnids, wer tested at each concentration. Cool-white fluorescent lights at 130 foot-candles: 334 000231 -- rT------ | pa -- pweerrieodusweadsfmoarilnitghatiinnge.d tAhrdoauiglhyopuhtotthoepetersitoidngopfer1i6odh.ours light and hours dark with a 15 minute transition ("pT2uh0me0hw0oasmtiecrgmLc(hceeoxmnptiorssotulrr)yea)pn,adrtae7mm1ep0te-er7ra2st0umremeah=sou2sr0ei.de4md-u2(r0i2.n0g70C0thm(ecgos/nttLuodley)xpioanscnuldrued2)e0,d.:3p-cH2o0n=.d8u8c.t2Ci:v8(i.3t30y0(rc0oanmntgareo.l=)e6ax1np0do-s86u.21r.0e8).2, and 4(dis8sehscooolunvrdesdhiogxhyegse)nco=n8c.e1-n9t.a1imogn/wLas(cuonsterdolb)ecaanusde t8.h1e9.h1miggh/esLt c(o2n0c0e0nmtrga/tiLoenxpreossuulrtee)d.inTfhoeal20m0o0rmtga/Ll.by Remarks: Wate hardness, during the study, was no indicated. RESULTS Doseofeach endpoint (as mg/L): 284 hhoouurr CEC5S00== 11729000 ((713505-02-020007)0)mmgg//LL 48 hour NOEC = 730 mg/L. Remarks: none Wascontrol responsesatisfactory (vesinofunkaown): yes Statistical results, as appropriate: none CONCLUSIONS 2T0h7e0FmCg-/1L0.15T4h8eh4o8hurouECrNS0owOabssedrevteerdmEifnfeedcttoCbonece1n2t0r0atmigo/nL(wNiOtEhC8)9w5a%sc7o3n0fimdge/nLc.e intervalof 730mSeuebtmsitttheerrs'ierieamafrokrsq:uaFliotrydeasttainrge.liabHiolwiteyv,ehre,tshtudsytuadyslaascsksiginnefdoarmKaltiimoinsocnhpruatritnygooftf2h.eTfheet sstuubdsytance and actual measurements oftheamount oftest substance i soon. Reviewers' remarks: none REFEREWaNrCdE, T, Nevius, ,andR. Boeri. 1996. Acute toxicityofFC-1015 to Daphnid, Daphnia MmaNg,na. TR. Wilbury Laberatorics, Inc. Labrequest number P1624. 3M Company, St. Paul, OTHER OGeNneLrYalNrOemMaIrkNs:ALThTeESmaTjoCrHcEoMncIeCrAn LforCtOyNinCgEtNoTdRetAeTrmIiOnNetSh wevraleiudsietdy.forOtPiPsTtersetcisomthmaetnds cthhaetmmiecaalsucroendcetensrtacihoenmiocawlhciocnhce0ntrtahteitosnts boreguasndis,mssoatrheatexopnoesecda.n sIcficutrsatdeleytedremtiennemdintehtthtehetest. vnaolmuiensaclacnonbceenatnrdatmiuosnts rbeeaodnjluys,tefdoedcoxwanmwpalred5b0y%o50f%the. Imfaenaasluyrteicdaclonmceeansturrateimoennst,sthoef tsooxmiceitsyort Tad been fumished, we could calculate chemical recovery ate, and ake into sccount hydrolysis, 33s 000232 -------------------- evoxlpaotisluirtye,caonncdentthreartiponhsy.sicochemical processes that might ower the actual tet organism Pteusrti.tyTonfstohmeeteessttsmaittearpipaleaarlesd tishatm1a0j0or%cteosntccehnemaincdalwwasasnoutsesdu,fffiocrieontthleyrschaarcahcetmeirciazledofinlethsisser wpuarsituys(eadpipnrooxtihmrateesltys,8f5o%)10waOsbvuisoedu.s sWaatteed,reaassoolnv.enItn(icsto,pr3opManionlt)hoirr sa ucmommbairnyaotfiocnacohfb(ostth Tstaagtre:ee"Dwaittah tmhaisycnoontcaecnc.uraItnealdydirteilaotne,ifttohxisicwaosfthe"ttyepsitcsaal"mpTlSeCwAitshetchtaitonof4threevtiesetw,suIbwstoaunlcde." e`meecatsutrheemseensttsuodfiets,hepteensdticnhgemriecceailptinotfhaddtietstiomneadliiunmf.ormation on purty and studies on analytical APPENDIX `mCheemicaal suremofdeiluntiontwatser Parameter Detection Limit: Met`aAllsuminum BAorrsoennic CChardommiiuumm CCoobpapletr LTeroand NMiecrkeeulry ZSiilnveer NChlioreide FlTuootarlidoreganic carbon TOortgaalnopchhoisoprhionreouPessticides OrTgaonxoapphhoesnpehorous Pesticides DiTmEePthoate PCMBosnocrotophos 00011 mmgg 00050m02gLmgt. 001mg 00.00305mmplL 003 mglL 0.005 mg0l0L003 mg. 003mg 002m0g.02 mg/L 0I.0m5 gmg NIL 0I.1mmgg 003 mg/L 205gg 0.5 ug/L2080 20081 2005gg 36 0002233 -- ------ E-- E ------------ Ecotoxicity Study ACUTE TOXICITY `TEST SUBSTANCE TO AQUATIC INVERTEBRATES (DAPHNIA MAGNA) Identity: `2s PFOA aPemrmfolunoiruoomctsaalnto,iAcmamciod,niaummmopneirfulmuosraloto;cmtaanyatael,soPbFeO,referred to FpeCn-t1a1d6e,caFfCl-uo1r2o6-,,FaCm-m1o69n,iuormsFaCl-t1,4C3A.S(O#ct3a8n2o5i-c2a6c-i1d), Remarks: The 3M FC-143, referred to production by the test llaofbonruamtobreyrawsaNs2840237-.4.ThTehteesTt Rs.ample is n`Woitlsbuufrfyicsiteundtlyyncuhmarbaecrteirsiz$e9d5,-TaHl.thTouhgehpcuurrirteynotfitnhfeorsmaamtpilone was indicates it is a mixtureof96.5- 100% test substance and M03E.T5H%ODC6, C7, and C9 perfluoro analogue compounds. Method: U.S. EPA-TSCA Guideline 797.1300 TGeLsPt:tyYpees: Acute static Year Completed: 1995 SSpuepcpileise:r:DOabpthaniinaedmafrgonmacultures maintained by T.R. Wilbury Laboratories Inc, Marblehead, MA `Organisms, Hampton, from NHL an original culture from Aquatic Research Analytical monitoring: DO, `Exposure period: 48-hours conductivity, pH, and temperature. ``STteasttiostrigcaalnmiestmhaogdes:: < 24-hours Interpreted by standard statstial techniques. `Computer ECS0s. methods (Stephan, 1983) were used to calculate LC505 and TDielsuttcioonndwiattieorn:s Deionized water adjusted toa hardness of 160-180 mg/L as CaCO DHialrudtnieosns:wa1t6e4r mchge/mLisatsrCya:CO3 Alkalinity: 106 mg/L as CaCO} RTeOsCi:du<al1c.h0lmogri/nLe: <0.1 mg/L PLihgohttoipnegr:ioCdooolf-1w6h-ihtoeurfsluloirgehst,cent-hbouulrbss with dark wainthinate1n5simtyinoufte 110 flc. transition period. sSttoocckksaolnudtitoenstwsaosluptrieopnasrepdreipnadrialtuitoinon: wAat1e,r.00A0fmiegr/Lmixpirnigm,artyh.e pprreipmaarrey tshteoctkestwacosncpernotproarttiioonnsa.llNyodiilnustoeldubwliethmadtielruitailonwwaastenrotteod during the test tEexstpososluurtieonv.esTsehles:ap3p0r0oxmiLmagtleasdsepbtehaokfetressctonstoaliuntiinogn 250 was mL of 9 cm. Number of replicates: 2 `Numberof daphnids per replicate: 10 Numberof concentrations: five plusa negative control 337 SE ---------- ere E------------------ 000234 WBatye chaemlistcroymdmuerpinpgyothnetsrt)udys: SCo1n8t7amctLranBgeo(m5a poeys) 540-560 umhos/em (control exposure) D7H10r-a7n2g0e (p 0-4m 8 hh o(u1s,o )000s mg// Lexpc osum re) 80-83 (control exposure) um 8.(10 ,000m8 g/Le. xpos2 ure) R119E.91S4U2L70T,2S503C ((c0on0t0rolmeaxrposeuxrep) o) NoEolmmisennatlvciotnconatI nedat9o5ns9.cBoannkdcenotne1v3,0a,220,360,600, 00 gL. Show C30 730600 1000 mu 24-hour EC50 = 780 (600 - 1,000) mg/L. 24-hour LCS0 = >1,000 mg/L (C.L. not calculable) 48-hour LCS0 = 720 (600 ~ 1,000) mg/L. 4F8l-mheonurtNvOtEusCb=e3d60omsg/mL.ins concn. Cumlatisepert immobilization includes mrt T er -- o T--o-- t To-- o ---- Bff oe o f--ot Tiso --| foe TT w w] Nbotie:tAini 1000 mg g, lls dapbnidswere immobilized a 4 hows and dea ConCLOSIONS TbSTehioe72tnm0estemasgu/w5biLstthhwaaion5tcwhea5E489C-5chS%oouocnrortLneefCinSd0tenfpmcoereiDanathtperhvonalioeafFm6a0gd0n.a w1ra,0s0d0ematge/rLm.hieanTeh1de5t.otest FShoouubrmnMiotoiabrsseSrvEoedCSoeofmfpecatncyonEcennrtroamtmioenn(tNlOELCa)bowraesr3,600m.g/LB.ox 33531, St. Rei: Kim DATA QUALITY skin2 they cramer Th sd aks aynpomoessecat 338 000235 -------------- REFERENCES `MTAhi,s sattutdhye wreaqsuecsotnodfutchteed3aMt TC.oR.mpWainlyb,urLyabLaRbeoqruateosrtiensu,mIbnce.r, MNa2r8b0l3e-h4ead, OTHER `General remarks: ONLY NOMINAL The major concern TEST CHEMICAL for trying to determine CONCENTRATIONS the validity were used. for this test s that OPPT recommends cthhaetmmiecaalsucroendcetnetsrtacthieomnitcoalwhciocnhcetnotrtahteitoensst obreguasneids,mssoatrheatexopnoesecda.n aIcciftuiratdeeltyedremtienremdintheatthtehetest v`naolmuiensaclacnonbceenatnrdatmiuosnts baereadonjluys,tefdordeoxwanmwpalred5b0y%o50f%.theImfaenaasluyrteidcaclonmceeansturrateimoennst,stohfestooxmiecitsyort hvoaldatbileietny,faunrdnoisthheedr,pwhyesciocuolcdhecamliccuallatpercohceemsisceaslthraetcmoivgerhyt rlaotwese,ratnhde tacatkuealintteostacocroguanntishmydrolysis, `exposure concentrations. 339 000236 ------------------------------------------------------cc--c------ ee Ecotoxicity Study TEST ACUTE SUBSTANCE TOXICITY TO AQUATIC INVERTEBRATES (DAPHNIA MAGNA) Identity: Perfluorooctanoic acid, tetrabutylammonium referred to as PFOA tetrabutylammonium salt, salt; mayalsobe: cteotmrpaobnuetnytloafmmLon-i1u34m92p.erf(lOucotraonoocitcanaocaitde,,opernatasdeacmaafjluoorro-, tReetmraarbkust:ylTahmemo3niMumprsoadltu,ctCiAoSn l#ot9n5u6m58b-e5r3-w0a)s 2327 The `TR. test sample i referred to by the testing Wilbury study number is $40-TH. The laboratory as L-13492. The 3M Environmental Laboratory RcheaqruaecstterNizuemdb,earltihsoNu2g3h3c2u.rrTenhteipnufroirtmyoatfitohneisnadimcpalteews aitsisnoastolsuutfifiocnieonftly 44.9% tetrabutylammonium isopropanol perfluorooctanoate, 27.9% water, and 27.2% tTehstesfuoblsltoawnicneg isnuwmamtaerrysoalpuptliioens woitthheintceostmpslaemtpelley acshaaramcitxetruirzeeodfthe ocfontcheenttersattsiaomnpsolfeiwmiptuhritthiaetso.ftDahteatemsat ysunbsottaanccceu.rately relate toxicity METHOD MTeestthotydp:e:U.ASc.utEePsAt-atTicSCA Guideline 797.1300 GYeLaPr:CYoemspleted: 1995 Specles: Daphnia magna ISnucp,plMiaerrb:leOhbetaadi,neMd AfrofmrocmulatnuroersigmianianltcauilnteudrebfyrTo.mR.AqWuialtbiucrRyesLaebaorrcahtories `Organisms, Hampton, NH. Analytical monitoring: `monitored daly. DO, conductivity, pH, and temperature were. Exposure period: 48-hours S`Tteasttisotricgaalnmiestmhaogdes::<L2C4S-5h0ouarnsd ECS0 values calculated, when possible, by probit analysis, moving average method or binomial probability interpolation using the computer softwareof CE. Stephan. with nonlinear `Test conditions Dilution mg/L as water: Deionized CaCO3IL water adjusted to a hardness of 160-180 DBiAluCtKionTwOatMeArIcNh.eLmiigshttriyn:gN:oCtoogilv-ewnh.ite fluorescent bulbs with an intensity of 20 fl-c. Photoperiod of 16-hours wansition period. light, -hours dark with a 15 minute sSotlouctkioannwdatsesptrespoalruetdiionnsdiplruetpiaornatwaitoenr:. AAf1t0er0mmigx/iLngp,ritmhaerpyrismtaorcyk stetsotcckowncaesntprraotpioornts.ionNaolliyndsiolluutbelde wmiattherdiiallutwiaosn wnaotteerd tdourpirenpgatrhee the: tEexstp, osure vessels: 300 mL glass beakers containing 250 mL of test solution. The approximate depthoftest solution was 9 cm. 340 a---------- EESSSSS---- 000237 eae `The vessels were loosely covered during the test. Numberof daphnids per replicate: 10 a 8.58.7mg/L (control exposure) `6p2H0r--a6n4g0e (pm0h4os8/hcomur(s1)00 mg/L exposure conc.) 8.48.6 (control exposure) 8.5 -8.6 (100 mg/L exposure conc.) ft20.5 - 20.7C 20.5 - 20.6C (control exposure) (100 mg/L exposure conc.) =i D 48-hour EC50 = 34 (30 - 39) mg/L. [Comrol To To 1 [TTo e 1 ss feo To Two | aE TE 000238 `Paul, Minnesota, 55133 DReAliTabAilQitUyA: LKlIiTmYisch ranking 2. The study lacks analytical measurement oftest substance concentrations in the tes solutions and sample purity is nRoEtFsEufRfiEcNieCntElSy characterized. `MTAhi,s sattutdhye wreaqsucesotnodfutchteed3aMt TC.oR.mpWainlyb,urLyaLbabRoerqauteosrtiens,umIbnce.r, MNa2r3b3l2e,head, O19T9H5.ER `General remarks: ONLY NOMINAL Themajor concernfortrying to determine TEST CHEMICAL CONCENTRATIONS the validity were used. for thi test i that OPPT recommends that measured test chemical concentrations chemical concentration to which to the test be used, so that one can organisms are exposed. aIcfciutriastdeeltyedremtienremditnheatthtehetest nvaolmuiensalcacnonbceenatnrdatmiuosnts baereaodnjluys,tfeodrdeoxwanmwpalred5b0y%o5f0t%h.eImfaenaasluyrteicdaclonmceeansturrateimoennst,sothfe tsooxmiecitsyort had been `olalty, furnished, and other wpheysciocuolcdhceamliccuallatpercohceemsiscesalthraetcmoivegrhyt rlaotwese,ratnhde tacatkueailntteostacocroguanntishmydrolysis, exposure concentrations. sPuormiteyotfesttshiet atepsptemaarteedritahlatal1s0o0i%s atemsatjcohremciocnaclerwnasanudsewda,sonrototshuefrfiscaiecnhtelymicchaalroacftelreiszseedr piunrtihtiys test. In (otahpeprrotxesitmsa,tfeolryn8o5o%b)viwoauss ussteadt.ed Wraeatseorn,. a Isnolfvacetn,t3(iMsoipnrtohpeainrosl)umomraarcyoomfbicnaacthiotneostfsbaotte:h "wDaastuasmeadyinnot aadcdciutriaotne,lifytrheilsatwe taoxsaic"ittyyopifctalh" TteSstCsAamspeclteiownith4 trheavtioefw,hIewoteusltdsruebjsetcatncteh.e"se1satgurdeices,wiptehndthiinsgcroencceeimpt. ofIn additional medium. information on purity and studies on analytical measurementsofthe test chemical in the test 342 eteeee~ereeeeee ------------ 000239 Ecotoxicity Study ACUTE TOXICITY TEST SUBSTANCE TO AQUATIC INVERTEBRATES (DAPHNIA MAGNA) Identity: Perfluorooctanoic acid, tetrabutylammonium referred to as PFOA tetrabutylammonium salt, salt; may also be: ctoemtrpaobnuetnytlaomfmLo-n1i3u4m92p.er(fOlcutoarnooociicaancoiadt,e,peNn2tad0e3c-a2flouroraos-a, major tetrabutylammonium salt, CAS `Remarks: The 3M production l#ot9n56u5m8b-e5r3-w0a)s 2. The TR. test samplei referred to by the testing Wilbury study number is 889-TH. The laboratory as purityofthe N2803-2. The sample was not ssoulffuitciioennotfly4c4h.a9ra%ctteertizreadb,utalytlhaomumgohnicuurmrepnetrfilnufoorromoacttiaonnoaitned,ic2a7t.es9%itis waater, `and 27.2% isopropanol. tTehsetfsoulblsotwainncge sinuamnmairsoyparpopplaineosll10wattheertessotlustaiomnpwliatesh ainmcioxmtpluerteoelfy the characterized concentrationsof relate toxicityof the test sample wimiptuhritthiaetso.ftDhateafemsat ysunbosttaanccceu.rately METHOD TMeestthotydp:e:U.ASc.utEePsAta-tiTc:SCA Guideline 797.1300 GLP: Yes Year Completed: 199. SSpuepcpileise:r:DOabpthaniinaedmafgrnoma cultures maintained by TR. Wilbury Laboratories Inc, Marblehead, MA Organisms, Hampton, from NH. an original culture from Aquatic Research, Analytical monitoring: monitored daily. DO, conductivity, pH, and temperature were Exposure Period: 48-hours Test organism age: < 24-hours `Sptraotbiisttaincaallymsiest,hmoodvs:inLgCaSv0ereangde EmCeSth0ovdoalrubeisncoamlciuallatperdo,bawbhielintypowsistihblneo,nb-lyinear interpolation using `Test conditions the computer softwareof C.E. Stephan. Dilution water: Deionized water adjusted toahardnessof 160-150 mDigl/uLtiaosnCwaaCtOerILc.hemistry: Hardness: Not noted pAlHk:alNionittny:otNeodt noted PLhiogthotpienrg:ioCdooofl-1w6h-ihtoeurfsluloirgehts,cent-hbouulrbssdwairtkhwainthinate1n5simtyinoufte110 fi. transition period. Stock and test solutions preparation Solution was prepared in dilution water. AAf2t0er0 mmigxi/nLg,prtihmeaprryismtaorcyk stetsotcckowncaesntprraotpioorntsi.onNaolliyndsiolluutbeldewmiattherdiialluwtiaosnnwoatteerd tdourpirnegpatrhee the test. 343 ----------------Sees ---------------- 000240 `Exposure vessels: 300 mi glass beakers containing 250 mL of 87-9.0 mg/L (100 mg/L exposureconc.) Conductivity range (0 -- 48 hours) 670-720 umhos/em (100 mg/L exposure cone.) pH range (0 - 48 hours) 8.3-8.5 (control exposure) fsNominal concentrations: Blank control, 13, 22, 36, 60, 100 mg/L. 24-hour EC50 = 72 (63-83) mg/L. FEE a `48-hour EC50 = 62 (36- 100) mg/L 48-hour LC50 = 93 (74 -->100) mg/L. 48-hour NOEC = 13 mg/L [Comrot To To 1 TT [2 To 0s 1] Be To Is-- 1 feo TsT o as] Loo TeT s heo] 36, and 60 mg/L (noted as "less active than control daphnids), but were 344 000241 CONCLUSIONS "bTehe93tesmtgs/uLbswtiatnhcae 4985-%hocuornfLiCdSe0nceforinDtaerpvhanlioaf m74ag-n>a10w0asmgd/eLt.erTmhienetdestto substance 48-hour ECS0 for Daphnia magna was determined to be 62 mg/L with a 95% confidence intervalof 36 ~ 100 mg/L. The test smgu/bLs.tance 48-hour no observed effect concentration (NOEC) was 13 Submitter: 3M Company, Environmental Laboratory, P.O. Box 33331, St. DPaAulT,AMiQnnUeAsLotIaT,Y35133 oRfeltieasbtisluitbys:taKnlciemicosnccherntarnaktiinogns2. iTnhtehestteusdtysollauctkisoannsalayntdicsaalmmpelaespuurreitmyenist not sufficiently characterized. `RThEiFs EstRuEdyNCwaEsSconducted at T.R. Wilbury Laboratories, Inc., Marblehead, MA, 1996, at the requestof the 3M Company, Lab Request Number N2803-2, OTHERGeneral remarks: The major concem for tryingtodetermine the validity for this test i that OthNatLmYeaNsuOrMeId NteAstLchTeEmSicTalCHcoEncMeIntCrAatLioCnsObNeCuEsNedT,RoATthIatOoNnSe wcearneacucseudr.ateOlPyPdeTterremcionmemtehnedtsest chemical concentration to which to the test organisms are exposed.If tis determined that the `vnaolmuiensaclacnonbceeantnrdatmiuosnts baereadonjluys,tefdordeoxwanmwpalred0by%o5f0t%h.eImfaenaasluyrteicdaclonmceeansturrateimoennst,stohfestooxmiecitsyort vhoaldatbileietny,afunrdnoisthheedr, we could calculate chemical recovery physicochemical processes that might rates, and lower the take into account hydrolysis, actual test organism exposure concentrations. `Pusroimteyotfesttsheit atepsptemaarteedritahaltal1s0oi0s%atemsatjcohrecmoinccaelrwnaasndusewda,sfonrototshuefrfiscaiecnhtelymicchaalroacftelreiszseedr piunrtihtiys test. In o(tahpeprrotxesitmsa,tfeolryn8o5o%b)viwoausssutsaetde.drWeaatseorn,.a Isnolfvacetn,t 3(Misionptrhoepainrosl)umomraarcyoomfbienaacthiotneostfbsaotte:h "wDaastausmeadyinnot aadcdciutriaotne,lifytrheilsatwe taoxsaic"ittyyopifctahl"eTteSstCsAamspelcteiwonith4rtehvaitoefw,thIewtoeustldsurbesjteacntcteh.e"se1satgurdieees,wiptehndthiinsgcroencceeirpnt.ofIn additional medium. information on purity and studies on analytical measurementsofthe test chemical in the test 345 000242 TOXICITY TO FISH `Title: Acute Toxicity to Fish TEST SUBSTANCE IAdmemntointyi:uPmerpfelrufolruooorcotoacntoaincoaatcei,d,PaFmOm,oFnCi-1u1m6,salFtC;-1m2a6y, aFlCs-o1b6e9,roefrerFrCe-d14to3.as(POcFtOaAnoaicmmacoidn,ium salt, pentadecafluoro-, ammonium salt, CASRN 3825-26-1) Rwaesmanroktss:uffTichieen3tlMy pchraordaucctterlioztendu,mtbheorugwhacsur8r3.enTthienftoerstmastaimopnliendwiacsatFeCs-i1t 4is3.a mTihxetuprueriotfyo9f6.t5he-- s1a0m0pl%e:test substance and 0 3.5% Cg, C; and Cs perfluoro analog compounds. METHODS Method/guideline followed: Not sated Test type: Static GLP (Y/N): No Year study performed: 1974 Species: Fathead minnow (Pimephalespromelas) Average weight = 1.6 g Average length = 2 inches `Supplier: Not stated Concentrations used: 0, 10, 20, 30, 40, 50 mg/L. nominal Exposure period: 96 hours Analytical monitoring: The test substance concentrations were not measured. Statistical determined methods: There graphically. were no statistical methods given by the study authors; theLC was T~eOsnteCroenpldiictaitoenwsa:s performed. ~Dissolved oxygen range (24-96 hours)= 4.7 -pH range (24-96 hours) = 7.0- 7.1 (control) - 5.7 and 6.4 mg/L (control) and 4.0 - 49 - 6.5 (50 mg/L exposure) mg/L (50 mg/L) "Temperature range = 70 - 72 degrees Fahrenheit ~Water hardness was not indicated. "Dilution water was carbon-filtered city water from St. Paul, MN. Remarks: Further details on the test conditions and procedures were not provided. 346 000243 RESULTS Doseofeach endpoint (as mg/L): concentrations, 96 hour LCs = 70 mg/L (C.1. not calculated) based on nominal Remarks: Observed mortalityofthe controls was 10% at both 72 and 96 hours. `mortality with the exceptionof 20% mortality in the 50 mg/L group. There was no other `Was control response satisfactory (ves/no/unknown): unknown,seeRemarks above Statistical resultass, appropriate: obtain a calculated LCs value. Percent survival versus concentration (mg/L) was plotted to CONCLUSIONS `The study authors concluded calculated) based on nominal that the acute LCs concentrations. to fathead minnow was equal to 70 mg/L (C.1. not mSuebtmhiotdtoelro'gsy.RTehmearLkCss:o wRaelsiaebxitlriatpyol-atKeldimfirsocmharnaninksiunfgfi3.cieTnhterneumwbaesroinfsdufaftiacipeonitndtso.cuTmheentgaetnieornaolftprhe-etest health and ageoffish were not noted. Sample purity was not `analytical confirmationoftest substance concentrations. properly characterized and i lacks tRheeviweatweerr'hsarRdenmeassrkwsa:s nTohtegipvHen.leTveelsstidnugrisnhgoutlhed theasvtepebreieonddwoenree wwiitthhitnwtohereaplcicceapttesa.blTehreanugem;bheorweovfer, `organisms per dose and the loading rate were not indicated. REFERENCE 3M Company. [No title given]. Lab Request number 2340. St. Paul, MN. OTHER Rreepmoartrkwsa:s aTvhaiilsasbluem.maThreyrewfaosreb,atsheedcoonntaenstusomfmtahriysrseupmormtaarnyd, oinnlryefleirmeintceed tdoattahetapbrloetso.coNlos adentdairleseudlts of the study, are limited. `The major concern for trying to determine CHEMICAL CONCENTRATIONS were the validity for this testis used. OPPT recommends that that ONLY NOMINAL TEST measured test chemical cthoencteensttroatriongs abeanurseeide,xspsoomstehsda.t oInfiet ciasndeatcceurrmaitneelyd dtehattetrhmeinnotmhienatelstcocnhceemnitcraalticoonnsceanrteroantliyo,nftoorwexhaimcphleto: I5fa0n%aolyfttihcealmmeeaassuurreedmceonntcseontfrsatoimones,sotrhtehtaodxibcieteynvfaulruneisshceadn, bweeacnodulmduscatlcbuelaatdejucshteemdicdaolwnrwecaorvderbyyr5at0es%, `aancdtuatlakteestinotrogaacnciosumntexhpyodrsoulryesicso,ncveonlattrialtiitoyn,sa.ndAsotihteirs physicochemical we are operating processes that in the dark on might lower thi issue. the. 347 0N0244 ---------------------------------------------- TOXICITY TO FISH Title: Acute Toxicity to Fish `TEST SUBSTANCE Identity: Perfluorooctanoic acid; may also be referred to as PFOA, FC-26, or FX-1001. (Octanoie acid, pentadecafluoro-, CASRN 335-671) Remarks: sufficiently 3chMarpacrtoedruiczteido,ntlhootunguhmcbuerrre2n6t9.inTfohremaetsitosnaimnpdliecawteassitFCis-2a6m.ixTthureeopufri9t6y.o5f-t1h0e0s%atmepslte was not substance and 0-3.5% Ce, Cs, and Cs perfluoro homologue compounds METHODS Method/guideline followed: Notstated Test type: Static GLP (Y/N): No Yearstudy performed: 1974 Species:`AFvaeirhacgaedlmenigntnho=w(2Piinmcehepshalespromelas) Average weight = 1.5 g Supplier: Not stated Concentrations used: 0, 50, 125, 250, 375, 500mg/L nominal Exposure period: 96 hours Analytical monitoring: Nominal concentrations were not measured `dSettaetirsmtiincaeldmgertaphhoidcsal:ly.There were no statistical methods given by the study authors; theLCsowas. TOenset Croenpldiictaitoenwsa:s performed. "Temperature 69-70 degrees Fahrenheit "Dissolved between oxygen 3.8 and range (24-96 hours) 5.2 mg/L for the 375 wmags/Lbettewsteeexnp4o.s7uraen.d 5.7 mg/L for the control exposure and Water hardness was not given. pH range (24-96 hours) was 7.0 07.2forthecontrolexposureand6.0 0 6.7for the 375 mg/L exposure. 348 000245 -------------------------------------------- Remarks: No further details were provided on the test conditions or methods. RESULTS Doseofeach endpoint (as concentrations mg/L): 96-hour LCs = 440 mg/L (C.L not calculated) based on nominal Rsuermvaivraklsw:asFor10co0n%ceantt2r4athioounrss,obf0utt0o %37a5t m4g8/-L9,6 shuoruvrisv.al was 100%. For the S00mg/L concentration, `Was control response satisfactory (yes/no/unknown): Yes Statistical results, as appropriate: obtainan LCs Concentration (mg/L) versus percent survival was graphed to CONCLUSIONS iSnufbomrimtatteiro'nsoRnetmhaermkest:hodReollioagbyil.itSyam-pKlleimpiusrcihtyrwanaksinngotofp3r.opTerhliys cshtaurdayctlearcikzsedd.ocTuemsetnctoantcieonniraantdions were not characterized. Conditionofthe fish prtio soturdy initiation is not known. sRteuvdiyewpeerri'osdRweamsarnoktsg:iveTne.stiTnhgesnhouumlbdehroavfeorbgeaennipsemrsfopremreddoisne tawnod rtehpelilcoaatdeis.ngWaatteerwhearrednnoetssindduirciatnegd.the REFERENCE 3M Company. [No ite given. Lab Request Number 2485. St. Paul, MN, OTHER Remarks: This this summary, in sruefmemraerncyewtaosthbeaspreodtoocnolassaunmdmraersyultrseopfotrthseubsmtuidtyt,edarbeyli3mMit,edt.herefore, the contents of C"THheEmMaIjoCrAcLonCcOeNnCfEorNtTrRyiAngTtIoOdNetSerwmeirnee the validity for thi tet is used. OPPT recommends that that ONLY NOMINAL TEST measured test chemical tchoentceesnt torragatniiobsnmessuasreed,exspoostehda.t oInfeitcaindaectceurrmatienleyddtehtatertmhienneotmhienatelstcocnhceemnitcraalticoonnsceanrteroantliyo,nftoorwehxiacmhplteo I5fa0n%aolfytitchaelmmeeaassuurreedmceonntcseontfrsatoimones,sotrthhtaodxibceietyn values can furnished, be and must be adjusted downward by we could calculate chemical recovery 50% rates, ``aacntduatlakteesitnotrogaacnciosumntexhpyodrsoulryesicso,ncveonlattrialtiitoyn,sa.ndAsotihteirspWheysairceoocpheermaitcianlg pirnotcheessdeasrkthoant mtihigshitssouew.er the. 349 000246 r-- E ------------------------------------------------ce --ct-- a TOXICITY TO FISH Tite: Acute Toxicity to Fish TEST SUBSTANCE IAdmemntointyi:uPmerpfelrufolruooorcoioacntoainccaatcei,d,PaFOm,moEnCi-1u1m6,salFtC;-m1a26y,bFe Cre-f1er6r9eod,rtoFCa-s1P43F.O(AOcatmamnooinciaucimd,salt, pentadecafluoro-, ammonium salt, CASRN 3825-261) wRaesmanroktss:uffTihcieen3tlMy pchraordaucctteiroinzeldo,ttnhuomubgehrcuwrarsen8t3.inTfhoermtaetstiosnaminpdliecawtaessiFtCi-1a43m.ixTthureeopufri9t6yo.f5t-1h0e0s%amtepslte. substance and 03.5% Cs Cs, and Cs perfluoro analogue compounds. METHODS Methodguideline followed: Not sated Test type: Static GLP (Y/N): No Year study performed: 1978 Species: Bluegill sunfish (Lepomis machrochirus) `AAvveerraaggee lweeniggthht==04.c2m0 `Supplier: Not stated Concentrations used: 0, 135, 150, 240, 320, 420 mg/L nominal Exposure period: 96 hours Analytical monitoring: Concentratiwoenres not measured. Stadstical methods: No stated T"DeisltutCioonn:dictairobnosn-:filtered well water, Dilution water chemistry: dtiesmspoelrvaetduroexy=g1e9n d=eg9r.e1epspCme.lsius. pH=79 ~"OExnpeorseuprleicavtees.sels were tanks containing 16 litersoftest solution 2"L0oafdiishngperratreep=li0c.a2t5e g/L 350 000247 "Water chemistry during study (24-96 hours): dpiHssroalnvgeed =ox7y.g9e(nco=nt5ro3l-),679.8m-g8/.0L((4c2o0ntmrgol/,L 5ex.p1o7s.u3rem)g/L (420 mg/L exposure) test temperature = 18-19 degroes Celsius Water hardness was not stated `Remarks: No further details were provided on the test methods or conditions. RESULTS Doseof each endpoint (as mg/L): 96-hour LCS0> 420 mg/L based on nominal concentrations 4R2e0mamrgk/sL:grNouopsmobrtoatlhitcioenssiosctceudorrfedonien tihnectownetnrtoylsfoisrh d1e3a5d-2at4072mgh/ouLrgsroups. Mortalities in the320and `Was control response satisfactory (yesinofunknown): Yes Statistical resultsas, appropriate: Not sated. CONCLUSIONS Sfoulblmoiwtetde.rN'soRienmfoarrmkast:ioRneolinabsitloictky o-rKtlesitmisoslcuhtiroannkpirnegpa3r.atTieosntsinwgaascpkrsoviindefdo.rmaAtvieornaogen ftihsehmweetihgohdt is `ssuubspsetcat.nceSacmonpcleentpruartiitoynsw.as not properly characterized and it lacks analytical confirmationof test Reviewer's Remarks: not indicated. Only one replicate was performed. Waterhardness during the study period was. REFERENCE 3M Company. [No itl given]. Lab Request number 3844. St. Paul, MN. OTHER Remarks: This this summary, in summary reference wtaosthbeaspreodtoocnolassaunmdmraersyultrsepoofrtthseubsmtuidtyt,edarbeyli3mMi,tetd.herefore, the contents of C`THheEmMaIjoCrAcLonCcOerNnCfEorNtTrRyiAngTtIoOdNetSerwmeirneeutsheedv.alOidPiPtyTfrorecthoimsmteesntdiss tthhaatt OmeNaLsuYreNdOtMesIt NchAeLmicTaElST cthoencteensttroartgiaonnsisbmesuasreed,exspoostehda.t onIfeitcaisndaectceurrmaitenleyddtehtatertmhienneotmhienatelstcconhceemnitcraalticoonnsceanrteroantliyo,n ftoorwehxiacmhpltoe 5Ifa0n%aolyfttihcealmmeeaassuurreedmceonntcseontfrastoimoens,sotrhtehtaodxibceiteynvfaulruneisshceadn, bweeacnodulmduscatlbcuelaadtjeucshteemdidcaolwnrewcaorvderbyyr5at0es%, and take into account hydrolysis, volatility, and actual test organism exposure concentrations. other physicochemical processes that might lower the 351 000248 eee------------------------------------------ TOXICITY TO FISH Title: Acute Toxicity o Fish TESTSUBSTANCE AIdmemntointyi:uPmerpfelrufrlouoorcotoacntoainccaatcei,d,PaFmO,moFnCi-1u1m6,salFtC;-m1a26y,aFlCo-1b6e9r,eoferrFreCd-1t4o3a.s P(OFcOtaAnoaimcmaocindi,um sal, pentadecaluoro-, ammonium salt, CASRN 3825-26-1) Rsaemmpalrekwsa:sTnhoet s3ufMfipcrioedntulcyticohanrlaoctteurmizbeed,rhwoausg8h3.cuTrrheentteintfsoarmmpatlieonwaisndFiCc-a1te4s3.t iThameipxutruiryeoofft9h6e.5 -- 100% test substance and 0 3.5% Ce, Cy, and Cs perforo analogue compounds. METHODS Method/guideline followed: Not stated Test type: Static GLP (YIN): No ear study performed: 1978 Species:"BAlveureaggielllesnugntfhis=h3.(0 Lcepmomismachrochirus) `Average weight= 12g `Supplier: Not stated `Concentrations used: 0, 420, 560, 750, 1000,1350 mg/L nominal Exposure period: 96 hours Analytical monitoring: Concentrations were not measured. Statistical methods: Not sated TDeisltutCioonndiwtaitoenss:ource: carbon-filered well water "~DOinleutrieopnliwcaattee,r2c0hefmiisshtpreyr:rteepmlpiecartaeture = 19 degrees C, dissolved oxygen = 9.9'ppm, pH = 7.6 ""TLeosatdipnegrrfaotreme=di1n5tagnLks containing 16 ters est solution "WDaitsseorlcvheedmiosxtyrgyendurrainnggete=st5:6(24to-69.65 hmogu/rLs):(contro) and 4.9 to 5.9 mg/L (750 mg/L exposure) pH range = 7.8 (contro) and 7.6 to 7.8 (750 mg/L exposure) 352 000249 ---------------------------- "WTaetmeprerhaatrudrnees=s 19 to 20 degrees not given C Remarks: No further details were provided on the testing methods or conditions. RESULTS Doseof each endpoint (as mg/L): 96-hour LCSO = 569 ma/L, based on nominal concentrations tRheema10r0k0s:andTh1e35905m%gc/oLnfciodnecnecnetrianttieornvaglrowuapss.500 -636 mg/L. 100% morality occurred by 48 hours in c`oWnatsroclongtrrouopl.response satisfactory (yes/no/unknown): One out of twenty fish died at 48 hous in the `Statisticalresults,as appropriate: Not sated CONCLUSIONS `foSlulbomwietdt.erN'soRienmfoarrmkast:ionReolniasbtiolciktyor-- tKelsitmsioslhutriaonnkpirnegpa3.ratTieosntsinwgalsapcrkosviindefdo.rmaStaimonploenptuhreitmyetwhaosdnot properly characterized and the study lacks analytical confirmationoftest substance concentrations. Rnoetvigeivweenr.'s Remarks: Only one replicate was performed and water hardness during the test period was. REFERENCE 3M Company. [No itl given). Lab Request number 3844. St. Paul, MN. OTHER tRheismasrukmsm:aryT,hiisnsruefmemraerncyewtaosthbeaspreodtoocnolassaunmdmraersyultrseopfotrthseubsmtuidtyt,edarbeyli3mMi,tetd.herefore, the contents of C`THheEmMaIjoCrAcLonCcOeNmCfEorNtTrRyiAngTtIoOdNetSerwmeirneeutsheed.valOidPiPtyTfrorecthoimsmteesntdiss tthhaatt mOeNaLsuYreNdOtMesIt cNhAemLicTaElST concentrations be the test organisms used, so that are exposed. one can I it i accurately determined dtehtatertmhienneotmhienatelstcocnhceemnitcraalticoonnsceanrteroantliyo,nfotorewxhaimchplteo I5f0an%aolfytitchealmmeeaassuurreedmceonntcseontfrsatoimoens,sotrhtehtaodxibceiteynvfaulmuiesshceadn, wbeeacnodulmduscatlcbuelaatdejucshteemdicdaolwnrwecaorvderbyyr5at0es%,. `aacntduatlakteesitnotrogaacnciosumntexhpyodrsoulryesicso,ncveonlattrialtiitoyn,sa.nd other physicochemical processes that might lower the 353 ---------- EE 000250 -------------- ee------EE ---------------------------- Title: Chronic Toriciy to Fish TOXICITY TO FISH TEST SUBSTANCE Isadletn,taitmym:onPeirufmlupoerrofolcutoarnoooicctaanciods,tea,mPmFoOn,iFuCm-1a1l6l;, mFCa-y1a2l6s,oFbeCref-ero1rerd6FtoaC9-s14,37.5.0(3O,cPtFaOneA aacmidm,onium peniadecafluoro-, ammonium sal, CAS # 3825.26.1) Rreefmerasrtkos:it aTsh"e783.0M3.proTdhuectpiuorntlyotofntuhmebsearmwpalse w3a.s TnhoteseutfcsianmtpllyecwhaasraFctCe-r1i4z3e.d,Tthheouegshticnugrrleanbtoratory pienfftouromraotiaonnalinodgiuceatceosmiptobuenidnsg.a mixture F96.5% - 100% est substance and 0 3.5% Ce, Cr, and Cy METHODS `prMeestehnotde/dguiind"ePlrionpeofsoeldlorweecdo:mTmheendmeedthboidooalssoagyypfroorctehdeueregfoarnedgfgyanedxpforsyusrteagcelsosoeflyfrfeoslhlwoawteedrtfhiasth," US. EPA, 1972. "Test type: Flow-through GLP (YAN): No Year study performed: 1975 Species:PrFea-tthreeaatdmemnitn:nEogwg(sPiwmeerpehpallaecsepdrionmael6a0s)mg/L malachite green solution for 15 sconds to eliminate possible fungus growth. "Test fish age: Eggs within 48-hours after fertilization Supplier: U.S. Environmental Protection Agency's Environmental Research Laboratory in Duluth, MN. Concentrations ested: Blankcontol, 62, 125,25, 50, 100mg/L. Exposure periods 30 days post bach AWneaelkyltyicsaalmmpolneistwoerriengt:akTeenmfpreoramtcuarceh, adqiusasorlivuemdfooxydgeetnercmoinncaetnitornaotifona,mamnodnpiHumweprerefmluoonriotoocrteadnodaitley. c31o,19n78centrattoiont.heA3llMsCaompmlpeasnyt.aken during the test were stored in polyethylene boule and shipped on May aStnaatliysstiiscoaflvmaertihaondcse:(SMteeealnesaonfd Tmoeraiscu,re1d96b0i,olcoogmipclaletpealryamreatnedrosmrizoemd dbulpolcikcadteesiagqnu,arPi-a0.w0eS)r,e sDuabtjaecftoerd to apnearlcyesnist.age survival and percentage hatch were transformed 0 re sin square root ofpercentage prior to 3s4 000251 TDeisltutcioonndwiattieornss:ource and contaminants: Wellwaterpumped to 3 concete reservoir where it was aerated Dieluftoironfwlaotweirngch0emtihseterxyp(o0s-u3r0edsayyss)t:em through aged PVC pipe atoltaallihiatrydn=es2s6=-3321.m3g8/mL La5 CaasCCOa;CO, PSpHec=i7fi0c-c7on.d4uctance = 149 170 Omhoslem Sutsoecd.kTanhd deisltustorlduetiloinveprreedpafriavteinono:minAalmocdoinfcieendt,raptrioopnosrtaiomnmaolndiiluumteprewriftlhuor0o.o5ct0adniclautteiornanagcitnogrfwoasm 100 s1y0s6.t2emmwga/sLuasneddctoontdreollivweart6.e6omLdupolfiacantoemtienstalaqauarmiamAa4 lpeerrlguloarsosoMcatraniooatttebsottolcektcooxnicceannttradteiloinveorfy F2r0y.4emxp/osmurienvedsissetlilylpede:waGtleastso ttehsetmaiqxuianrgiucmhammebaesruorfintghe30d.i5l%u3e0r.5x30.5 cm ith a 17.5 om high Egg cups: Acrylic tubes (3 cm O.sDt.a,nd7piepme ldroanign),wwiatthe4r0vmoelsuhmNeoifte16sicrrese.n on one end. An egg cup rosocciklelrataertmheaepgpagrcautpuss,iansthdeesecsrtibweadtebry Mount (1968), was used0 gently Diluer: Delivered 0.50 lesofwaetsetrwraetpelratcoemceancthianqueoarfiaupmp1ro9s5itnaitmeslpye1r0dhyo,ursy.ielding a 90% est Feeding: Fry werefd ivebrine shrimp naupli three tines daily on weekdays and vice daily on Numofbrepleicatres: Two repliwccaeatceehkse.engdgTshcteuphr.reowuegrhoeu5t0theeggesxfpoorsutrheepaetricohda.bily testand 40 from "Water chemDiissisyoldvuerdinogxyegsen: >95% saturation PTeHm:p7er0at-u7re3: 25 + 1 degrees Celsius, maintained by water bath `Rweemrearpkress:erAvtedheint1er0m%inbautfifoenreodftfhoermeaslitntwhheiflreytfhreofmrythferocomntthrolotahnedrttheeshaiqguhacroinacweentrreatfiroonze(n.10T0enmg/L) hfoirsmoaplaitnh-oplroegsiecravleedxfamyin(5atfiroonmoeafchtrraenpslviecrastee)sfecrtoimonthoefctohnetrnoalreasndantdhecehpihgahlicconecxetnetnrsaitoinoonfutnhdeerewreantl alimnem.oTnhieurmempaeirfnliunogroporcetsaenrovsetdefcroynacenndtrfartoizoenns.fry were analyzed at a later date (by 3M Company) for RESULTS Doseofcach endpaint (1s mg/L): 30-day NOAE>L 100 mg/L CNoonmceinntarlation Fach % |TSSouviDvawl%|sPMeoan slengtth|hMueawn wecigh| ht (mg/L) i(n= mSDm) inmg Control 5 595 555 2021009) @7s Ce osTo 1 a 200) | 5 | 355 0No2s2 [IT TwTwTm[ LK eg i= I R a r Ea. `Was control response satisfactory (ves/no/unknown): Yes TTA CONCLUSIONS I RELTS am --e------------ 356 000253 REFERENCE `fTahteheeafdfemctisonnfocwon(tPiimneopuhsaleexspopsruormeeltaos)7.8.01397o8.n haRcetpcohratbi#lBiWty-o7f8-e6g-g1s75a.nd gRersoewatrhcahnrdepsourrtvisvuablmoifttfeyd toof3M Company, St. Paul, MN by EG&G Bionomics Aquatic Toxicology Laboratory, Wareham, MA. OTHER `NGOenMeIraNlArLemTaErkSsT:CTHhEeMmIaCjoArLcoCnOcNeCnEfNorTtRryAiTngItOoNdSetewremrieneustehde. vOalPiPdiTyrfeocrothmimsetnesdtssthtahtatmeOaNsLurYed test wchheimcihcatol tchoencteesnttroartgiaonnissbmes uasreede,xspoostehda.t oInfiictaindaectceurrmaitneeldy tdheatterthmeinneomtihenatlestcocnhceemnircaatlicoonnscaernetroantliyo,nftoor `beyxa5m0p%le. 5I0f%aonaflytthiecamlemaesausruerdecmoennctenstorfatsioomnse, stohret thoaxdicbietyenvafluurensischaend,beweancdoumludstcablceualdajtuesctheedmdicoawlnward `rmeicgohvterlyowreartetsh,eaancdtutaalketeisnttooragcacnoiusnmt ehxypdorosluyrseisc,onvcoelnattirlaittiyo,nsa.nd Aosthietripshwyesiacroecohpeemriaclailngprionctehsesedsartkhaotn this issue. 357 000254 -------------------------------------------------------------------------------------- FISH ECOTOXICITY Titles 96-hour acute state toxicity to fathead minnow -- FX-1001 TEST SUBSTANCE Ipdeennttaidteyc:aflPueorrfol-u,orCoActSan#o3ic35a-c6id7,-1al)so referred to as PFOA, FC-26, or FX-1001. (Octanoic acid, `noRtemcaormkpsl:eteTlhyec3haMrapcrtoerdiuzcetdi,onalltohtomuugmhbienrfowramsatniootn noted. The indicated it test was saammipxlteuwreaosfF9X-51-09081.percItesntputreistty was substance and 1-5 percent perfluorochemical inerts. METHODS Method/guideline followed: Not noted Test type: Static GLP (Y/N): No Year study performed: 1985 `Species:avPeirmaegpehlaelnegsthpr=om4e.l1acs,m; average weight = 0.50 g; age not noted Supplier: Dale Fatiigof Brady, NB Concentrations used: 0, 690, 750, 810, 870, 930 mg/L (nominal values). Exposure period: 96 hours Analytical monitoring: No measurements were taken. Also, there was no information on detection limitsof the chemoriimpcuriatiles inthe sample. Statistical methods: Probit analysis 358 0N02S5 `Test Conditions: -Fish were pretreated with -Dilution water chemistry: 25.0 mg/L tetracycline HCI, months prior to study to fight diseases Carbon filtered well water DO 9.5 ppm TpeHmp7819C ~ Water chemistry during the test: Dissolved oxygen range (24-96 hours): 7.37.7 mg/L (control) 6.1-6.7 mg/L (870 mg/L)* `pH range (24-96 hours): 7.5 7.7 (control) 7.5- 7.5 (870 mg/Ly* #870 mg/L test group (second highest concentration) data given because total mortality occurred in the highesttest concentration by 48 hours. Test temperature (24-96 hours): 1920C - Stock solution was prepared by dissolving 45 g test substance (neutralized with NaOH to pH. 7.5) in 3 liters water. Test solutions were prepared by transferring stock solution aliquots to make - Loadin5lgirtaetre:s at the selected 0.50g fish/L. test concentrations, - Stabilityofthe test chemical solutions was not noted - Exposure vessels were glass beakers with 2 24 cm inside diameter and a 26 cm depth, and "Two repcloinctaatiensewde$relittearksentesatt solution. each dose, with 5 fish per replicate Remarks: Water hardness was not presented. The pH values are acceptable according to the OPPTS. `harmonized guidelines. RESULTS Doseofeach endpoint (as mg/L): 96-hour LCS0: 843 mg/L (C.L: 811-878), based on nominal concentrations. Remarks: - 930 mg/L was the lowest test substance concentration causing 100% mortality (seen at 48 - There whaousrns)o mortality in controls - Surfacingofthe fish occurred at dosesof $10, 870, and 930 mg/L `Was control response satisfactory (yes/no/unknown): Yes, based on zero mortality. Statistical results, as appropriate: No p-values were reported. 359 000256 CONCLUSIONS `The test sample 96-hour LCS0 for fathead minnow was determined tobe843 mg/L with a 95% C.L. of 811-878 mg/L. Submitter remarks: The data quality ranking was a Klimisch ranking o2f because testing met criteria. forquality testing. However, sample purity was not properly characterized and it lacked analytical `confirmationoftest substance concentrations. Reviewerremarks: none REFERENCE 3M Company. 1985. 96-hour acute satic toxicity to fathead min~nFX-o100w1. Environmental Laboratory, St. Paul, MN. Lab Request Number C1006. February 2. OTHER General remarks: This summary was based on a summary report and only limited data tables. No detailed report was available. Therefore, the contentsofthis summary, in reference to the `protocols and resultsofthe study, are limited. "The major concern for rying to determine the validity for this testis that ONLY NOMINAL `TEST CHEMICAL CONCENTRATIONS were used. OPPT recommends that measured test chemical concentrations be used, so that one can accurately determine the test chemical concentration to which to the test organisms are exposed. Ifitis determined that the nominal concentrations are only, for example 50%of the measured concentrations, the toxicity values can be and must be adjusted downward by 50%.If analytical measurementsof some sort had been furnished, we could calculate chemical recovery rates, and take into account hydrolysis, volatility, and other physicochemical processes that might lower the actual test organism exposure: concentrations, 360 000257 FISH ECOTOXICITY Title: Acute Toriciy to Fish TEST SUBSTANCE pIedrefnltuitoyr:cocPtearnfolautoer,ooFcCt-a1n1o6i,c FacCi-d1,2a6m,mFonCiu-mo1sral6F;Ca-9l1s4o,3r.ef(eOrecdtatnoaisaPcFidO,Apeantmamdmeocnafiluurorsoa-l,,aammmmoonniiuumm sal, CAS#3825.26-1) sRoelmd.arkIss: pTuhriet3wMasprnoodtuccotmlpoltentuelmybecrhaursacetderwiazsed3,90a.lthTohueghteitnfsoarmmpalteiownaisndFiCc-at1e2d6,tawawshi&temipxotwudreeroyf7693% test substance and 7-22% C6, C7, and C9 perfluoro analogue compounds. METHODS Method/guideline followed: Notstated Test type: Static GLP (VN): No Year study performed: 1987 Species: PimephAaveersapgreomleelnagsth = 3.5 om `Average weigh=t 030g Supplier: Dale FatofBrady, NB Concentrations tested: 0, 100, 150, 320, 560, and 1000mg/L Exposure period: 96 hours Analytical monitoring: Non because nominal concentrations were used Statistical methods: Prob analysis Test conditions: ""DDiilluuttiioonn wwaatteer schoeumricsetcrayr:bon-flered well water TDeOmopoff2931pCpm pHor7S "Test solutions were prepared by direct weights addition 361 000258 "StEaxbpiolsiutryeovftehsseelesswtecrheem4icLiatlersoPlyurteixongslwasassbneoatkenrostecdontaining 3 liters test solution "Two replicates were used "-LSoiaxdiisnhg praetrerweaplsic0a.t6egwLe.re used. "Water chemiDsOtryradnugrein(g24f-es9t6: hours): 65667.646mmggl/LL ((c3o2n0trmogll)L) PH range (24-96 hours): 777.9 control) Temp (24-96 hours: 20C 77:80 (G20 mg/L) *This group was used because total mortality occurred at higher doses wRietmhairnkasc:ceNptoabolteherrandgeetasilasccoonrdteisntgctoondOiPtiPoTnSs wHearremogniviezne,dingculiduedliinngesw.ater hardness. The pH values are: RESULTS Doseof each endpoint (as ma/L (95% CI: 244-370), mg/L): The 96-hour LCSO for fathead minnow was determined to be 301 Remarks: -- LSuorwfeasctintgeostfsfuibsshtawnacseocbosnecrevnterdaattio1n8c0aaunsdin3g2010m0g%/mLo(rbaoltihtryepwlaicsat5e6s0) mg/L - No morality was observedi the controls ``mWoarstacliotnytrol response satisfactory (vesimo/unknown): Yes, based onth fact that thre was no Statistical results,as appropriate: Not presented CONCLUSIONS wRoausnddeitnegrmtihneerdetsoulbse03.020smiggn/iLfiwciantthfaig9u5re%s,ctohnefitedsetnscaemipnlteerv9a6l-ohfo2ur40L-C3S7O0fmogr/fLa.thead minnow qSuuablmiittytteerssti"ngr.emHaorwkesv:erD,atthaeqsuaamliptlyewpausrigtiyvweans nKoltipmriospcehrlryanckhianrgaoctfe2r.izeTdesatnidngitmleatcktehdeacnrailteyrtiiacaflor confirmationofthe test substance concentrations. Reviewers' remarks: none REFERENCE 3M Company. 1987. St. Paul, MN. Lab Request Number E128201, completed on May 1 362 000259 OTHER GNeondeertaalilreedmraerpokrst:waTshiasvasiulmabmlae.ryThwearsefboarsee,dtohen caosntuemnmtsaorfytrheipsorstumamndaroyn,lyinlirmeifteerdendcaetatotatbhlees. protocols and resultsofthe study, are limited. `The major concern for trying to determine the validity for ths test is that ONLY NOMINAL ``cThEeSmTicCalHcEoMncIeCntAraLtiCoOnsNbCeEuNseTdR,AsTo IthOatNoSnewecraen used. OPPT recommends that measured accurately determine the test chemical test `concentration to which to the test organisms are exposed. Ifit is determined that the nominal `cboenacnendtmrautsitonbse aardejuonsltye,d fdoorwenxwaamrpdleby505%0%of.Ithfeanmaelaystuircaeld mceonacseunrtermateinotnsso,ftsheomtoexiscoirtty hvaadlubeesecnan furnished, we could calculate chemical recovery rates, and take into account hydrolysis, volatility, `and other physicochemical concentrations. processes that might lower the actual test organism exposure: 363 NO260 TOXICITY TO FISH Title: Static Acute ToxicityofFX-1003 to the Fathead Minnow, Pimephales promelas TESTSUBSTANCE I`daemnmtoitnyi:umPeprefrlfulourooroocotcatannooiactaec,idP,FaOm,mFoCn-1i1u6m, sFaClt-;1m2a6,yFaCl-so16b9e,rFefCe-r1r4e3d,tooraassPaFmOaAjoarmcmoomnpiounemnstaoltf, FX1003. (Octanoic acid, pentadecafluoro-, ammonium salt, CASRN 3825-26-1) RFeXm-a1r0k0s3: waTsheno3tMsufpfriocdiuecnttliyocnhlaortanctuemrbizeerd;wahsow2e3v2e7r.,TahveaitleasbtlseaimnpfloermwaatsioFnX-i1nd0i0c3a.teTdheit pwuarsitay of asonldut1io-n2of%<C4s5a%ndamCm;opnerifulumorpoe-rfalnuaolroogoucteacnooamtpeo,un5d0s%. water, <3% inert perfluorinated compound METHODS Method/guidelinefollowed: OECD 203 Test type: Static GLP (YN): Yes ear study performed: 1990 Supnedceiresf:lowP-ritohrrotuogthesctoinndgi,tjiuovnesniilneafnaatlhlegaldamssinanquoawrsiuwme.reFiaschclwiemraeteadccfloirm6a3teddatyostihne 1ta0r0ge%t dtielstution water dtiesmepaesreataunrdew(e2r3efr2eeCo)ffaoprp1a4rednatyssibcekfneosrse,tiesntjuirniietsi,atainodn.aDbunroirmnagliatcicelsimaatitoesnt, ifniisthiatwieonr.e Fniosthtrweearteefdefdora `vcaolmumeesrocfitahleffisihshfwooedr,eo3.8nocrmctawniedce0.d4a5ilgyr,faomrsth(weedac)crleismpaetcitoivnelpye.riod. The average length and weight R`eSsueppalricehr:OrTghaenifsimshs,usHeadmipnttohne,tNoxHi.citTyhteestspwoenrseorp,u3rcMh,apsreodvfirdoemd athceotmemsetrscuibsatlanscuep.plier (Aquatic Ccoonncceentnrtartaitoniso:ns0t.e1s,te1d,:10A, 1s0c0r,eeannidng10to0x0icmigt/yLt.esFtowratshpeedreffionrimteidvewtiotxhictihtey ftoesltl,ofwiivnegnfoimviennaolminal concentrations and one blank used in the definitive toxicity dilution test and water control were used. Two replicatesofeach the nominal concentrations tested were: 0, 150, concentration were. 250, 400, 600, and 1000 mg/L. Both tests were performed under satic conditions Exposure period: 96 hours rAencaolrydteidcadlaimloyniintoeraicnhgt:esDticshsaolmvbeedrotxhyatgecno,ntpaHi,necdonldiuvectfiisvhi.tyC,onacnednttreamtpieornastourfetwheerteesmtesausbusrteandcaenwdere not `measured during the test. 364 000261 oSftatthiesttiocxailcimteyttheostdsc:oulNdonn-oltibneeairntienrtperrepotleadtbioyn,stmaonvdiarndgsatvateirsatgicea,l atnedc/honriqpuroebsidtuaenatloys1i0s;0h%oswuervveirva,lraetsutlhtes highest tested concentration. Test conditions: teTshtessucbrseteannicnegutaedsewrassimpielarrfocromndeidtiuosnisnganotmhionsaeolfctohnecedenftirnaittiiovnes (te0s.t1., 1.0, 10, 100, and 1000 mg/L) ofthe WfraotmerwuesleldaftoErnavcicrloimSaytsitoenmosftinheHtaemspttoorng,anNiHs.msW,aatnedrfwoarsalaldjtouxsitceidty0teasthiangr,dwneassswoelf$l8 wmagte/rLcaosllCeactCeOd; anantdursatlorweedllinwtaatnekrs,uswehderaestiht ewadsilauetriaotnedw.atAerchfoermithcealtocxhiacritayctteersitzwataisonpoefrfaorremperde;setnhteaftoilvleoswaimngplveaolfuetshe owregraendoeptheorsmpihnoerdo:uspHpe=sti7c.i4d,ecso,nadnudctPiCviBtsyw=er1e50b0eulmohwosth/eeml.eveOlrogfandeotcehcltoiroinn,eorpensotticpirdeesse,nt. The est cvme)s.selSstawbielrietyo19f.6thLe gtleastsssuabqsutaarnicaethwaatsconnottaiinndeidcat1e5d.LNoftoessttoscoklsuotliuotnio(napwparsoxpirmeaptaerewdataesrtdesetpmtahtweraisal17was anodmdiendadlirceocntcleynotradtiiloutnisownewraeteursecdonitnatihneeddeifnintihteivteestesvte:ss0e,ls15w0i,th2o5u0t,t4h0e0,us6e00o,faansdolv1e0n0t0. mTgh/eL.foTlwloewnitnyg dfiesthewremirneerdatnodboemlaypparnodxiemqautalellyy d0i.s3t0rigbLu.tedTessmtovnegssetlwsowreerpleicraatnedsoofmlcyaachmatnrgeaetdmeinnt.a wTahteerlobaadtihngdurraitengwtahse 9ph6o-thoopuerrfieosdt wSatastiacutcoomnadtiitciaolnlsywmearientmaaiinnetdaiwnietdhtchoroolu-gwhhoiutte tfhleuosrteusdcye.ntAli1g6h-tshotuhratipgrhotvaindded8a-hloiughrtdark cinotnecnesnittryoatfio3n5s aEbsovme"a.ccAeeptraabtlieonlewvaelss.emFipslhowyeerdeafnottef4e8dhdouurrisngtothmeaitnestta.iTnhdeisfsoolllvoewdinogxywgaetner chemistry r1a3n0g0es-(106-009p6 homurs)hwe(r1oe0d0e0tsmegr/miL'n.eedx:peoscuonrmdeu)c;tpiHvirtayn=ge12=007.~4--15008.4ucmohntorso/leemxp(ocsounrtero)l,e=xp7o.s8u~re),3.2=1000 9m.g2/mLge/xLpo(scuornet)r;olteexmppoesruarteu)r,e =ra6ng.e2=.211.(01-00202mCg/(cLonetxrpoolsuarned).10T0h0e mpgH/aLnedxphoasrudrnee)s;swdeisrseowlivetdhiOns=the6.1 accepted ranges (6.0 < pH <8.5; 40<hardness<180 mg/L) for the duration of the study. Remarks: No additional comments RESULTS Doseofeach endSpcroeiennti(nagstemsgt:/L): `96-hour LCS0 > 1000 mg/L, 96-hour NOEC> 1000 mg/L Definit9i6v-ehoteusrt:LCS0> 1000 mg/L, 96-hour NOEC > 1000 mg/L `Reexmpaosrukrse:anAdllalteostthveersseesltserxepmoasiunreedscilnetahretshreoruegnhionugtttehset atensdt.i1n0t0he%dseufrivniitviavleotcecsutrred in the control Was control response satisfactory (yes/nojunknown): Yes SSattaitsitsitciaclalmeretshuoldtssdauseatpopr1o0p0ri%atsuer:vival aRtestuhlethsiogfhtehset tteosxtiecditcyonecsetntcroautlidonn.ot be interpreted by standard 365 000262 CThOeN9C6L-hUoSuIrOLNCSS0 and96-hourNOEC were determined to be >1000 mg/L. s`Saumbpmliettpeurrsi'tyrweamsarnkost:prKolpiemrilsycchharraanctkeirni2zg.edTaenstdinthgemeteesttsltahcekecdriatnearliyatifcoarlqcuoalniftiyrmtaesttiiongn.ofHoewsetvseurb,stance concentrations. Reviewers' remarks: The conclusions appear to be supported by the data. REFERENCE EnviroSystems, Inc. 1990. Static Acute ToxicityofFX-1003 o the Fathead Minnow, Pimepliales ~promelas. Hampton, NH. Study number was 9014-3, OTHER `The General remarks: major concen for trying to determine the validity for this test is that ONLY NOMINAL TEST cCoHncEeMniIrCatAiLonsCbOeNuCsEedN,TsRo AthTatIoOnNeScawneracecuusreadt.elyOPdePtTerrmeicneomtmheentedsst that measured test chemical chemical concentration to which to t5h0e%toesfttohregamneiassmusreardeceoxnpcoesnetdr.atiIofnist,isthdeettoexrimciinteydvatlhuatesthceannobmeinaanld cmounsctenbteraatdijounssteadredoonwlny,wafrordebxyam5p0le%. I`fanadnatlaykteicinatlomaecacsouurnetmheyndtrsoolyfssiso,mveolsaotritlithya,dabnedenotfhuermipshhyesdi,cowcehecmoiucladlcaplrcoucleastseeschtehmaticmailghrtelcoowveerrythraetes, actual tet organism exposure concentrations. 366 000263 TOXICITY TO FISH "Title: Acute ticityofN2803-3 to the Fathead Minnow, Pmephalespromelas TEST SUBSTANCE peennttiadteyc:aflPuoerrof-l,cCroAoSctRaNno3i35a-c6id7;-1m)ay also be refered o as PFOA, FC-26, or FX-1001. (Octanoi acd, Rsaemmpalre,ksF:C-2T6h,ew3aMs prreofdeurcetdiotonblyottmhumlabbeorwataosry26a9s.NT2h8e03e-s3t.sTuhbesapnurcietywofsthewhsiatmepploewwdaers.noTthe test ssuufbfsitcainecntelyancdha0ra-ct3e.r5iz%edC;e,hCorw,evaenrd,Ca;vapielrafbllueorion-fohrommaotlioonguinedciocamtpeoduintdwsa.sTahmeitxetsurseoubfst9a6n.c5e-(*1a0-0% est mriexcteuirveedw)aswarsecfoembrir0needsdwtihteh"iassotpersotpeadn"olsuibnsatan5c0e:.50 ratio prio o use. The substance resulting rom tis METHODS Method/guideline followed: US. EPA-TSCA Guideline 797.1400 Test type: Static GLP (VIN): Yes Year study performed: 1996 Stapnekc.ieDsu:rinJguvaecncilliemaftaitohne,adthmeiinsnhowwserweernoetatcrcelaitmeadtfeodrudnidsecarsf,lTohw-etfhirsouhgwherceondfrieteioonfaspipnare2n7t0 sLicfkinbeesrsg,lass Dinujruirinegs,thaend14a-bdnoarympaelriitoidesbeaftotersettientitniaotni.onMo,rttahleiatcycdluirmiatnigotnhetefmipnaelra4t8urheourrasnogfeacwcalsi2m1a.t0ioCn --wa2s2.<33%C5 aexncdepthtedduirsisnoglvtehd 4ox8yhgoeunrscoinmcmeendtriaattiloyn wpraesceatdilnagstth8e.0esm.g/LT.heDauvreirnaggeacoctlailmalteinognt,hiasnhdwweertewfeeidghdatiloyf,the test organisms were 33.4 mm and 0.35 rams, respectively. Sspuopnpsloire,r:3MJ,uvseunpiplleiefditthehadtemstisnunboswtasncwee.re procured from Aquatic Biosystems, Fort Collin, CO. The `wCeornecuesnetdr:ati0,on0s0t5e,s0te.d5:,F5o.r0,h5e0,satantdic5s0c0remengi.ng Fteosr,tthhesftoatlilcodweifnignintoimveintaeslt,ctohncefnotrlaltoiwoinnsg,naosm-irnecaslived, icosnocpernotpraantoilo,nns,omai-ntaelstcdon,cewnetrreatuisodn:s o0,f13(0d,i2t2i0o,n3w6at,e6r0c0o,natnrdo)1a0n0d05m0g0/mL FLoritshoepsrotpainotleswtewriethused. Exposure period: 96 hours rAencaolrydteidcadlaimloyniintoeraicnhgt:estDicshsaomlbveerd. oTxhyegetne,mppeHr,attuermepeirnaotunreet,esatnvdescsoenldwucatsivriteycowredreed amtealesausrtehdouarnldy during the test. Concentrationsofthe test substance were not measured during th study. 367 000264 Sptoastsiisbtliec,aulsmientghpordosbi:t a1n.aClsyosvisa,lumeosvwienrgeacvaelrcaulgaetmedetbhyodn,ono-rlibnienaormiianlerpprooblaabtiolinty(.Stephan, 1983), when "Test conditions: Fwaotretrhceosntattrico,sc0r.e0e5n,i0ng.5te0st,, 5n.0,om0i,naalndco5n0c0enmtgra/tLi.onTshoefstchereetneitngsutbessttawnaces,paesr-froecremievdeudn,dweerrseim0i(ldairlution conditions as those ofthe definitive test. `coWlalteecrtuedsead fTo.rR.acWcillibmautriyonLaobfotrhaetotreisetsoirngaMnairsbmlse,haeandd,foMAa.llWtoaxtiecriwtyatsestaidnjgu,swteadstdoaehiaonridzneedswsaotfer40 - 48 mpags/sLedasthCraoCugOhyaapnadrtsioclreedfilienr,poullyteratvhiyolleentestearnlksz.erI,nathnedtaacntkisv,attehdewcaatrbeornw,aIsn aecrhaetmeidcaanldcchoarnatcitneuroiuzsaltyion ocofantraempirneasnetnstawteirvee siatmhpelreobefldoiwlutthionlewvaelteorfd,eitreocntwiaons,doertencottepdraetse0n.t0.3 Tmhge/Lt.estOtshuebrstmaentcael,sasa-nrdecpeoitveendt,iawlas c1o0m0b%inteesdt wsuibtshtiasnocperodpuarnionlg ithneao$s0i:c5i0tyattesot.prTihoertetusseu.bsTtiasnc5e0w:a50s maisxstuumreedwtaoshtahveenacopnusriitdyeroefd1t000b%e aaqcutairvieai,nwgrheidcihenctoanntadi0nedbe15taLbloefteusndtesrolsuttoiroange(aapnpdrtoexsitmiantgecownadtietriodnesp.thThweastes1t8vcems)s.elTswweenrtey2f0aLthgelaadss `Ampipnronporwisatweeraemionudnisscorfimtiensattesluybsatnadnceequwaelrley daidsdteridbduitreedctalmy otonltuwtoorneplwiactaetresionfcthaecehsttrveeastsmeelnstt.o foarnmd1ul0a0t0etmhge/Lm.eTdihae. eTshtevteesssteclosnwceernetrlaotioosnesl,ycaosv-eesrteedda,nfdorrtahneddoemfilnyiatrirveantgesetdwienre:wa0t,er1b30,h220d,ur3i6n0g,t6h0e0, 9au6t-ohmoautritcesatl.yAma1i6n-thaoiunredliwghitthancdoo8l--hwohuirtedaTrukorpehsocteonpterliiogdh,tswtihtaht pr1o5v-imdiendutelitgrhatnsiinttieonnsipteyrioofd3,1was faococtecpatnadbllees.leAveclrsa.tMioenaswuarseidniwtaitaeterdcahfetmeis7i2ryhoduurrsintgotmhaintteastinprdoivsisdoeldvetdhoxfyoglleonwicnogncreanntgreasti(o0ns a9b6ovheo.urs): D1i1s0s-o3l7v0edpm0h;o=s/6e.4m (c8o.n7trmogl/aLnd(c2o2nt0romlge/xLpoesxuproes)u,re=);5.p2H-=9.70.m1g7/.L6(2(c2o0ntmrgo/lLexepxopsousruer)e,);=C3o.n0duc7t.i4v(it2y20= mtestLsoleuxtpioosnusrfeo)r tTheemp3e6r0a,t6u0r0e,=an2d1.180-0022m.g6/LC e(xcpoonstuorleacnodnc2e2n0trmagt/ioLnsexwpeorsuerei)n.thTehreanpgHe ovaf3l.u0es-oft4.h3eat t<epsHt<i8n.i5ti)a.tioHna.rTdhneesses wloaws pwiHthvianlutehsewaeccreeploaubtlseidreatngheafcocretpotxaibclietyrastnugdeiefsor(a4q0u-ati1c30tomxgic/iLt,y asstuCdaiCesO()6..0 FscorretenhinsgaatndtdoexfiicniittyivteesotxpiecriftoyrtmeesdswwiitthhiNso2p8r0o3pa-n3o.l0, (adsiilmuitliaornwpartoetroccoolnwtrso)faolnldo5w0ed0ams tLhatifsoorprthoepanol (inntoemnisnitaylwcoansce2n8trfaotoitocna)ndwlecsr.e used. Test vessels were randomly arranged ina water bath and the light Remarks: No additional comments RESULTS Dose of cTaecsht esnubdsptoainncte(caosncmegn/tLra)tiionnt,haes-deesftiendi,tiavnedteassts:ociated 95% confidence limits: 4284--hhoouurr LLCCiino == 228800 ((222200 360) mg/L 360) mglL 7926--hhoouurr LLCCis== 228800 ((2222-00 336600))mmg/LL 96-hourNOEC = 220 mg/L 368 0oNe26S `Test subs2t4a-nhcoeurcoLnCcsengt=rat1i4o0n,(1a1s0-r-ec1e8i0v)edm,g/aLn.d associated 95% confidence limits: 4782--hhoouurr LLCCsso=o= 11440(0(11101-0-118800))mmgg//LL.. 96-hour 96-hour LNCOsEpC= 1=4101(01m10g-/1L80)mg/L. cRoenmtraorlk,s9:0%Fosrurtvhievaslcraete0n.i0n5g mtegs/t,L,the10f0ol%loswuirnvgivsaulravtiv0a.l50r,at5e.s0,wearned o5b0semrgv/eLd,: a1n0d00%%susruvrivviavlalinatthSe00 `smtgu/dLy.. F1o0r0t%hesudrevfiivnailtiovcectuerstr,endoinintshoelcuobnltermoalteexripaolsuwraesaonbdsetrhevseed in anyofthe test fathead minnows vessels did not during exhibit the any swuabsleotbhsaelrevfefedctwsi.thFiinsh24inhtohuers13i0n athned326200, 6m0g0/,Laenxdpo1s0u0r0emcgo/ncLenetxrpaotsiuornes caopnpceeanrteradtnioornmsa;l.theTroetfaolrem,orthtea.lity lmogw/eLsticsoonpcreonptarnaotli,onno, wmhoritcahlictayuosredsu1bl0e0t%halmoerftfaelcittsy,wewraeso3b6s0ermvge/dL;.thDeur9i6n-hgotuhre LtCoxeigcivtayltueestwwaisth>550000 mg/L. `Was control response satisfactory (yes/nofunknown): Yes `Statistical results, as appropriate: No additional comments CThOeNaCsL-tUesStIedO9N6S-hour LC was determined to be 280 mg/L, with a 95% confidence intervalof 220 - 360 `bmags/eLd. oTnhethaes-ttesetstseudbs9t6a-nhcoeurasnor-ecoebievrevde,d-wfafscedte-tceornmciennetdrattoiboen 1(4N0OmEgC/)L,wawsit2h2a0 9m5g/%L.coTnhfeid9e6n-cheoiunrteLrCv:aol, Of 110 180 mg/L. The 96-hour NOEC for the test substance, as-received, was 110 mg/L. Scounbcmeintttreartsi"onrseimnatrhkest:estKlsoilmuitsicohnsraannkdisnagm3.plTehpeursittuydywalsacnkoetdsaunfafliyctiiecnatllymcehaasruarcteemreinztedo.ftAedsdittsiuobnsatlalnyc,e. tthheerperaopcpeedaurreedctoondbuecateddisbcyretphaenlcaybboreattwoereyntothperespaamrpelethperetepsatrsaotliuotniodnisr.ecTthieonasbgsievnecneotofpthaertlaablormaotrotrayliatnydat intermediate doses resulted in a study may not accurately reflect sharp dose-response curve. As a the true toxicityofthe solution. result, the LCso values determined in this The low pH values observed in the high concentrations tested may have had an adverse effect on survival. Reviewers' remarks: The conclusions appear to be supported by the daa. RTERFEWiRlEbNurCyELaboratories, Inc. 1996. Acute toxicity of N2803-3 to the Fathead Minnow, Pimephales promelas. Marblehead, MA. Study number $91-TH. OTHER `General remarks:The major concen ONLY NOMINAL TEST CHEMICAL for trying to determinethe validity CONCENTRATIONS were used. for this test is that OPPT recommends that measured test chemical concentrations chemical concentration to which to the test be used, so that one can organisms are exposed. accurately determine the test Ifit is determined that the nvaolmuiensalcacnonbceenatnrdatmiuosnts baereaodnjluys,tefdordeoxwanmwpalred5b0y%o5f0t%h.eImfeaansaluyrteidcaclonmceeansturrateimoennst,sothfstooxmiecitsyort had been furnished, we could calculate chemical recovery rates, and take into account hydrolysis, 369 000266 veoxlpaotisluirtey,caonncdeonttrhaetriopnhsy.sicochemical processes that might lower the actual test organism `tePsutr.ityTonfstohmeetteessttmsaittearpipaelaarlesdo itshaatm1a0j0or%cteosntccehremaincdalwwasasnoutsesdu,fffiocrieontthleyrschaarcahcetmeirciazleodfinletshisser pwuarsituys(eadppinrooxtihmeartteelsyt,8f5%o)nwoaosbvuiseodu.s tWaatteedr,feaassoonl.venItn (fiacsto,p3roMpainnolt)hoerrasucommmbairnyaotfioenaocfhbtoetsth sTtaagtre:ee"Dwaittha mthaiys cnoontcearcnc.uraItnealdydirteiloant,eitftoxhiicsitywoafstahe"ttyepsticsaalmpTlSeCwAitshetchtaitoonft4 hrevtieestw,suIbwstoaunlcde." rmeejaescturtehemseentsstudoiftesh,epetensdticnhgemriecceailptinoftahdedtietsitomneadliiunmf.ormation on purity and studies on analytical 370 000267 ------------------------ FISH ECOTOXICITY Tide: Acute toxicity ofFC-1015 othe fathead mina, Pimephalespromelas TESTSUBSTANCE IAdmemntointyi:umPeprfelrvfolruooorsoioatnaoniocataec,id,PFaOm,mFoCn-i1u1m6,saFlCt;-1m2a6y, aFlCs-o1b6e9,reFfCer-r1e4d3toofasasPtFhOeAmaajmormocnomipuomnesanlt,of FC-1015. (Octanoic acd, pentadecafhuor, ammoniumsalt,CAS #3825-26-1) Rinefmoarrmaktsi:onTihneditceasttessaitmpislea 3is0F%C-s1t0r1a5ig.htIcsarpbuornitcyhawiansvneortsisounfofifciFeCnt-l1y4c3hairnac3t0er%izweadt,ert.hoTuhghe 3cuMrrepnrtoduct Tfoetstnsubustanmcwea.bsD"aeHtaOrGweEre20u5s.e"dDatotcaommapyarenottoxaiccciutryatoeltfyhreblartaenctohxeidc/isttyorafgthhtectheasitnsaammpmloenwiiutmh tha of the apemrmfolunoiruoomctpaenrofautoerhooocmtoalnoogatmeixitnuFrCe-i1n0F15C.-143 vs. what i supposed o be the 100% straight carbon chain METHODS Method/guideline followed: USEPA-TSCA 1983.797.1400 Test type: siatic GLP (VN): N Year study performed: 1996 Sepiegchiets:ofPi0m3e6pgh(awlete)s.promelas. The fish werejuveniles with a average lengthof35mmand average Supplier: Aquatic Biosystems Creopnlciecanttersaattieoancshucsoendc:en0t,ra5t3i0o,n8w3e0r,e1p3e3r0f,o2r1m0e0d,. and 3300 mg/L. The concentrations were nominal. Two Exposure period: 96 hours Analytical monitoring: none. Statistical methods: LCS0 values were calculated using the Stephan compute program, 1983 "TepsatrtCiocnuldaitteifoinlse:r, uThleavdiiolulttioSnewaitzeer,usaenddwaacstidveaitoendiczaerdbowna.teTrhaedjduisltuetdiofnorwahtaerrdncehsesmiasntdrypawsassedmteharsouurgehd aTsigfhtoilnlgo,wsc:oohla-rwdhnietsesT=uo44remsgc/eLn alsigChtasCatO,30aflkoatl-icnaitnydi=es29w-e30emus/edL. asACdaaiClOy,phaontdopTerOiCod<of| m16g/hLo.urFsolright atensdt s$olhuotuirosnsdawrekrweictrheaste1d3 bmyinduitreecttrianndsiitviiodnuaplerwieoidghwtasadmdiatiinotnsa.ineAdftrhraou1g4hoduatytahcectleismtaitngiopnerpieordi.odT,htehe fish were exposed, at a loadingof 0.24g fs, in 20 L glass aquaria conaining 15 ters tet Solution t an Serer 000268 ewe FE ---------------- ainn eaapcphrorexpilmicaattee.depth of 18 cm. Two replicates were tested at each concentration. Twenty fish were used s`Tmhheowsa/tcerm c(hceomntirsotlr)yapnadra3m0e0t-e3r2s0muemashuorse/demdu(r2in1g00thmegs/tLudeyxpionsculrued)e,d:pcHon=du7c.t3i-v7i.t9y(rcaonntgreol=) a18n0d-71.920-7.7 d(i2s1s0o0lvmegd/oLxyexgpeonsu=r5e.)8,9e.m2pemrga/tLur(eco=nt2r2o.l0)-a2n2d.45.7C-9(.c2onmtrgo/lL) a(n2d10201.m5g-/22L.5expCos(u2re1)0.0Tmhge/L2e1x0p0osmugr/eL)., and h(osuercso.ndThhieghpesHt)racnognecewnatrsatwiiotnhiwnatsheusacecdebpetcabalueseratnhgee.higMheeasstucroenmceennttrsaotfiodnilruetsiuolntwedatinertcothaelmmiosrttrayliwteyraet. 72 also performed (see 20.03 mg/L. Appendix for parameters and detection limits). The only chemical detected was iron Remarks: Water hardness,duringthe study, was not indicated. RESULTS Dose of each endpoint (as mg/L): 9966 bhrr LNOCEC=S=24807300 m(g2/1L0.0-3330) mg/L Remarks: none `Was control response satisfactory (yes/no/unknown): yes Statresiultss,atsapiprcopraiatle: none CONCLUSIONS `The test sample 96 hour LCS0 for confidence intervalof 2100-3330 mfga/tLhe.ad minnow was determined to be 2470 mg/L with a 95% `tShuebcmriittetreirafs'orrqeumaalirtkys:teFsotirngd.atHaorweelivaebril,itsya,mtphleestpuurdiytwywasasansostigpnreoapderKllyimcihasrcahcrtaetriinzgedoaf2n.d Testing it lacks meets `analytical confirmationoftest substance concentrations. OReNvLieYweNrOs'MrIeNmAarLksT:ESTTheCmHaEjoMrIcCoAncLerCnOfNorCtErNyiTnRg AtoTdIeOteNrSminweerteheusveadl.idiOtyPfPoTr trheiscotemsmteisndthsat `tchahtemmiecaalsucroendcetnetsrtacthieomnitcoalwhciocnhcetnotrtahteitoensst oberguasendi,ssaoatrheatexopnoesecda.n aIcfcituriastdeeltyedremtienremdintheatthtehetest v`naolmuiensaclacnonbceeantnrdatmiuosnts baereadonjluys,tefdordeoxwanmwpalred5b0y%o5f0t%h.eImfeaansaluyrteidcaclonmceeansturrateimoennst,sothfestooxmiecitsyort hvoaldatibleietny,faunmdiosthheedr, wpheysciocuolcdhceamliccuallatpercohceemsiscesalthraetcomviegrhyt roatesw,tahneedactatrkuealintteosatcocroguanntishymdrolysis, exposure concentrations. Puryof test. In the test materia als some tests it appeared is a that major 100% concern and was not sufficiently characterized in this test chemical was used, for others a chemical oflesser wpuarsituys(eadpipnrooxtihmeartteelstys,8f5o%r)10waosbvuisoedu.s sWtaatteedr,reaassoonl.venItn (faicsto,p3roMpainnolt)heoirr asucmommbairnyaotficonaocfhbfaetsth Tstaagtre:ee"Dwaittah athiys cnoontcearcnc.uraItnealdydirteiloant, itfoxtihciistwyoafs tah "ttyepsitcsala"mpTlSeCwAitshetchtaitoonf4threvtieesw,su[bwstoaunlcde." 32 000269 ee meeeacsturtehemseentsstoudfiets,hepteensdticnhgemriecceailptionftahddtietstiomneadliiunmf.ormation on purity and studies on analytical REFERENCE pWraormde,laTs.., NTevRi.usW,iJl.baunrdy RL.abBooreartio.rie1s9,96T.n.AcLuatbeRtoexqiuceistytonfuFmCb-e1r0P11562t4o.the3fMatChoemapdamniyn,noSwt.,PPaiulm,epMhNa.les OTHER General remarks: none APPENDIX `mCheemicaal suremofdeilutniontwatser Parameter: Detection Limit: MetAallsuminum B`Aorrseonnic CChardommiiuumm CCoobpapletr LTeroand MNeirckceulry ZSiilnvcer CNhilotreide FlTuootarlidoreganic carbon OTortgaalnopchholsoprhionreoPuessticides `OrTgoasnaopphhoesnpehorous Pesticides DTiEmPetPhoate: PCBMsonocrotophos 00.011mmgg. 05 mal 00..00100m2 mgg/L. 00..00305mmgg//LL 0.005 mg0l.0L3 mL 00..00300m3gm/gL/L. 002m0g.02 mg/L. 0m.g05/mLg NL 01.m1gmlgLlL 0.03 mg/L. 05uugg 0.5 ug/L. 22001g 0250uugeL 373 00270 ATECSUTTESUTBOSXTIACINTCYETO FISH (FATHEAD MINNOW) 4I5dePntFiOtyA: aPmefmlounoriouomctsaalnta,iAcmacmiod,naimummopneirfulmuosraolto;ctmaanoystael,soPbFeO,refered to pFeCn-t1a1d6e,caFfCl-u1o2r6o,-FamCmo-nio1urm6FCsa-9l1,4,3C.ASOc#ta3n8o25i.c2a6c.i1d), RFCe-m1a4r3k,sr:efTehreed3Mbpyrtohduecteisotn llaotbouramtboreyraws aNs2840237-.4.ThTeheestTRs.amplies. nWoitlbsuurfyfscteundtyyncuhmarbaecrteirsiz8e9d5,TaHl.thoTuhgehpcuruitryoefitnhfeorsmaamtpiloen wis i3n.d5i%caCte6s,iCt7i,s aanmdixCt9urpeoefru9c6r.o5 -an1a0l0o%guteesctosmupbosutnadnsc,e and 0 MMeEthToHd:ODU.S. EPA-TSCA Guideline 797.1400 TGyLpPe:: YAecsute static YSpeeaciresc:omPpilmeetpehd:ale1s99p5romelas SAunpapllyiteirc:alAqmuoantiitcorBiinogs:ysDtOem,sc,oFnodrtucCtoliivnistp,yHC,Oand temperature EStxaptoisstuircaelpmeertihood:ds9:6-LhCouSr0svalues calculated, when possible, by probit ainnatleyrspiosl,atmioonviunsginavtehreacgeommpetuhtoedsoorftbwianroemioaflCpEr.obaSbtielpihtayn.with non-linear TLeesntgtfhishanadge:weNigohtn:otAedv.erage length = 28.6 cm ALvoaedriangge:we0i.1g3htg-L0.19g (wet) PTersettrceoantdmiteinotn:s:None mDilLutiaosnCWaateCr:ODeionized water adjusted t0 a hardnessof 40-48 DLiilguhttiionng:waCotoelr-cwhheimtiesftlruyo:reNsoctenntobtueldls witha intensityof30 ec. Pwhaontsoipteorniopedrioofd.16-hour igh, -hours dark witha 15 minute Sditroecctklayntdo ttheetdisloultuitoinonwsatperreipnartahteitoenst:vTeessstelssu.bstanceadded CStoanbcileinttyroafttihoenedsotsicnhgemriactea:lOsnolcuetions: No insoluble material wEaxsponsoutrede dveusrsienlsg:th2e0tLesg.lass aquaria containing approximately 15 LNoufmbteesrtosoflruetpiloni,cawtaetse:r2depth approximately18 cm NNuummbbeerr ooffficosnhcepnetrraretpiloincsa:tei:v10plus anegative control WDiastseorlvcehdeomixsytgreyn druarnigneg(0th9e s6tuhdoyu:rs): 67.72-88.55 mmgg//LL ((c1o,n0t0r0olmexLposeuxrpeo)sure) 374 0Ne271 ee `1C4o0nduc1t8i0viutmyhorasn/gcem((0co-n9tr6olhoeuxrpso)sure) P28H0r-a3n8g0e (m0h-o9s6/ehomur(s1),000 mg/L exposure) 77437-.75 6((co1ntro,ml gex0poseux0rpeo)su0re) 2Te2s.t0-t2e2mp.e6raCt(ucroentrroalngeexp(o0su-r9e6) hours) R21E:S8U-2L2.5TCS (1000 mg/L exposure) ENloemmiennatlvcaolnuceenatnradt9io5n%s:cBonfciodnetnocle,i1nt6e0r,va2l5:0, 40, 630, 100 mg/L h24o-huourr LLCCSS00 ==>7910,(060030m1g,/0L0(0C)L.mngo/tLcalculable) 9762--hhoouurr LLCSC0=S=7760400 ((666300-~813000)0m)gm/gL/L. E96l-ehmoeunrtNvaOlEueCs =ba4s0ed0omng/nLominal concentrations wStearteisdteictaelrmEivnaelduabtyiobinnoofmiMaolrtianltiertpyo:laTthioen.48Praonbdit7w2a-shouusreLdCt5o0cavlacluuleaste Bthieol9o6g-ihcoaulroLbCsSe0r.vations after 96-hours: Fish inthe control and the 160, d2i5s0c,oalonrdat4i0o0n amngd/Lereaxtpiocssuwriemcmonicnegnotrfawtioonsfiasphpweaasreodbnsoerrmvaeld. aDtatrhek24-hour observation period in the 1,000 mg/L exposure concentration. Cumulative percent mortality: TeNosmtinal mCsone, [Conwol To "To foo "To"To so "To To foo To "To [oo To "To [ooo 5 Te0 bows | h[9o%urs "To To] To To | To To 1 To To | To To | Too Joo `LMoowretsaltitcyonocfceonnttrraotliosn: Ncaounseing 100% mortality: None 375 000272 FE C"TOheNtCesLtUsSamIpOlNeS96-hour LCS0 for fathead minnow was determined fo be n7o40obmsge/rLvewditefhfaec9ts5c%onccoennftirdaetnicoen i(nNteOrEvaCl)ofwa6s6040~083m0g/mLg./L. The 96-hour `PSauubl,miMtitnern:es3otMa,Co5m5p1a3n3y, Environmental Laboratory, P.0. Box 33331, St. DReAliTabAilQitUyA: LKlIiTmYisch ranking = 2. The study lacks analytical s`maemapsluerepmuernityoifstneosttssuufbfsitcainenctelycocnhcaernatcrteartiizoends.in the est solutions and R"TEhiFsEstRuEdNy CwaEsSconducted at T-R. Wilbury Laboratories, Inc., Marblecad, MOAT,HEatRth request of the 3M Company, Lab Request number N2503-4 `OGNenLeYralNOreMmIarNkAsL: TTEheSTmaCjHorEcMoIncCeArLn fCorOtNrCyiEnNg TtoRdAeTteIrOmiNnSe twheervealuisdeidt.y fOoPr PthTsrteecsotmimtehnatds cthhaetmmiecaalsucroencdetnetsrtacthieomnitcoalwhciocnhcefnotrtahteitoensst obreguasneids,m5s0atrehtexopnoesecda.n aIcfciutriatdeeltyedremtienremdintheatt hthetest vnoamlinsaclacnonbceenatnrdatmiuosnts baereandjluys,tefdordeoxwanmwpalred5b0y%o5f0t%h.e Imfeaansaulyrteidcaclomnceeansturraetimoennst,sothfestooxmiecitsyort vhaodlabieletn,faunrdniosthheedr,phwyesciocuolcdhecamliccualaltpercohceemsisecsalthraetcmoivgerhytrlaotwse,ratnhde aackteualintteostacocroguanntishmydrolysis, exposure concentations. 376 600273 ACUTE TOXICITY TO FISH (FATHEAD MINNOW) TEST SUBSTANCE rIedfeenrtrietdy:toPearsfPluFoOroAoctteatnroaibcuatcyidl,amemtornaibuumtsyallet,mmonium salt; may also be `tceotmrpaobnuetnytloafmmLo-1n3i4u9m2p.er(fOlcutoraonoocitcanacoiadt,e,peNn2ia0de3c-a2f,luooraros-,amajor tReetmraarbkust:ylTahmemo3nMiupmrsoadlu,ctCiAonSlo9t5n6u5m8b-e5r3-w0a)s 2. The test sample is rneufmebrreerdi0s $b3y9-thTeH.teTsthieng3lMaboErnavtiorroynamsenLt-a1l34L9a2b.orTahteorTyRR.eqWuielsbturNyumsbtuedryis: 'aNl2t3h3o2u.ghThcuerrpeunrtitiyonffotrhmeatsiaonmpilndeiwcaatsesnoittissuafiscoileunttiloynocfha4r4ac.t9e%rized, tetrabutyammonium perfluorooctanoate, 27.9% water, and 27.2% isopropanol Tthesetfsoulblsotwainncge isnuamnmairsoyparpopplainesoltwoattheertseostlustaimopnlweiatsh ianmcioxmtpulerteoelfythe rcehlaartaecttoexriiczietydocfontcheetnetrsatstiaomnpsloef iwmiptuhritthiaetso.fDtahteatemsat ysunbosttaanccceu.rately MMeEthToHd:ODU.S. EPA-TSCA Guideline 797.1400 Type: Acute static GLP: Yes SYpeeaciresc:omPpilmeetpehda:le1s99p5romelas `Supplier: Aquatic Biosystems, Fort Collins, CO Analytical monitoring: DO, conductivity, pH and temperature were `Emxopnoistourreed pdaeirliyo.d: 96-hours S`atnaatliysstiisc,amlomveitnhgodasv:erLagCeS0mevtahlouedsocralbciunloamtiead,lpwrhobeanbiploistsiybwlie,thbynopnr-olbiintear interpolation using the computer softwareofC.E. Stephan. TLeesntgtfihshanagde:weNiogthtnootefdf.ish in control: Average length = 32.8 mm Average weight= 0.28 LProeatdrienagt:me0n.t1:9 gNofniseh/L. BACK TO MAIN TDeisluttcioonndiWtaitoenrs:: Deionized water adjusted to 2 hardnessof40 -48 mg/L as CaCO LDiilguhttiionng:waCotoelr-cwhheimtiesftlruyo:reNsoctenntobtuedl.bs with an intensityof28 fc. Photoperiodof16-hours light, -hours dark with 1 minute Atrearnastiitioonn:pIenriiotdi.ated afer the 72-hour DO measurements. `Stock and test solutions preparation: Tes substance was added directly 10 the dilution water in the test vessels on a weight/volume basis. No insoluble material was noted during the 377 000274 -------------------------------------------------- tCeosntcentrations dosing rate: Once ELxopfosteusrtesovleustsieolns,:w2a0tLer gdleapstshaaqpuparroixaicmoanttealiyni1n8gcsmp.prVoexsismealtsewlyer1e5 lNouomsebleyrcoofvreerpeldicduartiensg: 2the tet. NNuummbbeerr ooff fciosnhcepnetrraretpiloincsa:tef:iv1e0plus a negative control `sWaamtpelreochfedmiilsuttrioyndwuartienrg):the study (from a representative AHlakradlniensitsy::4348mmgg//LLaassCCaaCCOO33 PDiHsTsolved oxygen range (0-96 hours): 5611--8898mmgL/L((1c,o0n0t0romlg/exLpeoxsuproes)ure) Nhootuer:s aration was supplied o test vessels at 72C1o7n0duc1t8i0vimthyorsa/ngeem((0co-n9tr6olhoeuxrpso)sure) 2P0H0r-a2n1g0e (p0mb-o9s6heomur(s1),000 mg/L exposure) 7723--7798 ((c1o,n0t0r0olmgex/pLoseuxrpeo)sure) 2T2e.s1t-t2e2m.p2eraCt(ucroentrroalngeexp(os0u9re6) hours) 2B1A9C-K22T.O2MCA(I1,N000 mg/L exposure) RNoEmSiUnLaTlSconcentrations: Blank control, 130, 220, 360, 600,1,000mL. E2dlcehmoeunrtLvCaSl0ue=a1n,d00905(%6c0o-0nf>i1d,e0n0c0e) imngt/erLval: 4782--hhoouurr LLCCSS00 == 894900 ((660000 - >>11,,000000)) mmgg//LL 9966--hhoouurr LNCOSE0C==69000(m60g0/L- >1,000) mg/L. REleemmaernkts:vaTlueesstibnagswedasonconnodmuicntaeldcoonntchenetrmaitxitounrse. as describedin the Test SnoutbstthaenfcleuoRreomcahrekmiscafilelcdo.mTphoenveanltuealsornee.ported apply to that mixture and CNoummiunlaaltiv|e pe2r4c-ent morta[l48i-ty: [7 TeCsonte, hows [hours | hours [Como TT o 071 To0 Go To To To To 1] 378 000275 Po"-- To "T To To o] Boo To"To--"TT o o| [eo To To To To | [ooo 750 Teo 70 J70 | LMoorwteasltitcyonocfecnotnrtartoilosn:cNaounsei:ng 100% mortality: None "CTOheNtCesLtUsSubIsOtaNnSce 96-hour LCS0 for fathead minnow was determined to bteest8s9u0bsmtga/nLcew9it6h-haou9r5n%ocoobnsfeirdveendceefifnetcetrvcaolncoefn6t0r0at-io>n1,(0N0O0EmCg)/Lw.asTh6e00 mBgALC.K TO MAIN P`Sauublm,itMtienrn:es3otMa,Co5m5p13a3ny, Environmental Laboratory, P.O. Box 33331, St. DReAliTabAilQitUyA: LKlIiTmYisch ranking 2. The study lacks analytical measurement onfottessutffsiucbisetnatlnycechcaornaccetnetrriazteido.ns in the test solutions and sample purity is R"TEhiFsEstRuEdyNCwaEsSconducted at T.R. Wilbury Laboratories, Inc., Marblehead, M19A95,,at th request ofthe 3M Company, Lab Request number N2332, OTHER`General remarks: Themajorconcern or trying to determine the validity for this test is that tOhNatLmYeaNsuOrMeId NteAstLchTeEmSicTalCHcoEncMeIntCrAatLioCnsObNeCuEsNedT,R5A0 TthIatOoNnSe wcearneacucseudr.ateOlyPPdeTtreremcionmemtehnedtsest nchoemmiincaallccoonncceennttrraattiioonns taorewhonilcyh, tfoortheexaemstploerg5a0n%iosfsthreemeexapsouserde.d cIoniceintdreattieornmsi,netdhetthoaxtitchitey hvaaldubeseecnanfubreniasnhdedm,uwset cboeualddjcuasltceudldatoewcmhweamridcablyr5ec0o%ve.ryIfraantael,ytaincdaltmaekasinutroeamcecnotusntofhsyodrmoelyssoirst, evxoploasiulrte,caonndceontthreartipohnyss.icochemical processes hat might lower the actual test organism PSuormietyteosfttshiet atepsptemaarteedritahlata1l0s0i%s temsatjcohremciocnaclerwnasanudsewda,sfnorotohsuefrfsicaiecnhtelymicchaalroacftleersiszeerd piunrtiitys test. Tn (otahpeprrotxesitmsa,tfeolryno5o%b)viwoaussussteadt.ed Wraeatseorn,. Isnolfvaectn,t3iMsopirnotphaeinrols)umormaarcyoomfbienaacthiotneostfsbtaotte:h"wDaastuasmeadyinnot aacdcduirtaiotne,liyf rtehliastweatsoxiaci"ttyypoifctahle" TesStCsAamspeclteiownih4 trehvaioefw,heweousldsurbesjtecatntchee.s"es|taugdrieees,wiptehndthiinsgcroencceeirpnt.ofIn amdeddiituiomn.al information on purity and studies on analytical measurementsofthe test chemical i the test 379 000276 ACUTE TOXICITY TO FISH (FATHEAD MINNOW) TEST SUBSTANCE Identity: Perfluorooctanoic acid, tetrabutylemmonium salt; may also be referred to as PFOA tetrabutylammonium salt, tetrabutylammonium perfluorooctanoate, N2803-2,oras amajor `tceotmrpaobnuetnytloafmLm-o1n3i4u9m2s.alt(,OCctAaSno#c95ac6i5d8,-p5e3n-t0a)decafluoro-, Remarks: The 3M production lot number was 2. The test sample is referred to by the testing laboratory as N2803-2. The T.R. Wilbury study number is 888-TH. The purityofthe sample was not sufficiently characterized, although current information indicates it is solution of 44.9% tetrabutylammonium perfluorooctanoate, 27.9% water, and 27.2% isopropanol. Thefollowing summary applies to the test sample as a mixtureof the test substance in an isopropanol/water solution with incompletely characterized concentrationsof impurities. Data may not accurately relate toxicityof the test sample with thatofthe test substance. METHOD Method: U.S. EPA-TSCA Guideline 797.1400 Type: Acute static GLP: Yes Year completed: 1995 Species: Pimephales promelas Supplier: Aquatic Biosystems, Fort Collins, CO Analytical monitoring: DO, conductivity, pH and temperature were monitored daily. Exposure period: 96-hours Statistical methods: LCS0 values calculated, when possible, by probit `analysis, moving average method or binomial probability with non-linear interpolation using the computer softwareof C.E. Stephan. Test fish age: Not noted. Length and weightoffish in control: Average length = 34.9 mm Average weight = 036g Loading: 0.24 g fish/L Pretreatment: None Test conditions: Dilution Water: Deionized water adjusted to & hardnessof 40-48 mg/L as CaCO Dilution water chemistry: Not noted. Lighting: Cool-white fluorescent bulbs with an intensityof25 fu. Photopeiod of 16-hours light, 8 -hours dark witah 15 minute: transition period. Aeration: Initiated after the 72-hour DO measurements. `Stock and test solutions preparation: Test substance was. `added directly to the dilution water in the test vessels on a. weight/volume basis. Concentrations dosing rate: Once. Exposure vessels: 20 L glass aquaria containing approximately 15 Loftest solution, water depth approximately 18cm. Vessels were loosely covered during the test. 380 @No277 NNuummbbeerroofffreipslhicpaetresr:ep2licate: 10 N`Wuamtberercohefmciosntcreyntdruartiinognst:heisvteudpyu:sanegative control 6Di3ss8o.lv6edmoxLyg(ecnonrtaronlgeex(p0o9su6re)hours): 4No6te-:8a4ermatgi/oLn (w1a,s00s0upmpgl/ieLdeoxptoessutrvee)ssels at 72`oCuornsductivity range (0-96 hours) 114700--115800 pummhhooss//ccmm ((c1o,n0t0r0olmgex/pLoseuxrpeo)sure) 7p.H4r7a.n7ge(c(o0nt-r9ol6ehxopuorssu)re) 7 Test te5 mp(e1r,a0- t0u0rmegr7 anegxepo7 (s0u-re9)6 hours) 22116.6-~22119C.( 9C 1(cont,romlge/0xLp.ose0uxrpeo)s0ure) RNoEmSiUnLalTSconcentrations: Blank control, 160, 250, 400, 630,1,000mg/L. E24l-ehmoeunrtLvCaSl0ue=a>n1d,09050%mgc/onLfi(dCIenncoet icnatlecruvlaalb:le) 4782--hhoouurr LLCCSS00 == 9>17,00(0603m0-g/>L1,(0C0l0)nomtgc/alLculable) 9966--hhoouurr NLCOSE0C==966030(m83g0/L- >1,000) mg/L Element values were based on nominal concentrations `RSeumbastraknsc:e RTeemstairnkgswfaiseldc.onTdhuectvaelduoens rtehpeomritxetduarpeplasydteostchraitmbiedxtiunrtehaenTedst nCoutmu10lathteivfelupoerorccheenmticmaolrtcaolimtpyo:nent lone. TeNsomtinal [h2o4ws [[4h8ows |[hBours | h[o9u%rs Cone, [Conor To "To "To To 1 [eo To To To To [s Too --"To o To [T a0 o Too To | [eo "To "To To To | LMoorwteasltitcyoonfcecnotnrtartoilosn: cNaounseing 100% mortality: None CONCLUSIONS 381 000278 b"eTh9e6t0esmtgs/ubLswtiantche a969-5h%ocuornLfCidSe0ncfoer ifanthteeadromfvi8an3nl0o-w>w1a,s00de0tmegr/mLi.neTdhteo test substance 96-hour no observed effect concentration (NOEC) was 630 mSugbLm.itter: 3M Company, Environmental Laboratory, P.O. Box 33331, St. DPaAulT,AMiQnnUeAsLotIaT,Y55133 oRfeleisabtisluitbys:taKnlciemciosncchenrtarnaktiinogns2. iTnhtehestetsutdysollauctkisonasnaalnydtiscaalmpmleeaspuurrietmyeinst nRoEtFsEufRfiEcNieCntElSy characterized. "MTAhi,s sattutdhyewraeqsuecsotnodfutctheed3aMt TCRo.mpWainlyb,urLyaLbabRoerqauteosrtiensu,mIbnec,r MNa2r8b0l3e-h2e,ad, 1995, OTHER`General remarks: The major concern for trying to determine the validity for this test is that OthNatLmYeaNsuOrMeIdNteAstLchTeEmSicTalCHcoEncMeIntCrAatLioCnsObNeCuEseNdT,RsAoTthIatOoNnSe wcearneacucsuerda.teOlPyPdeTterremcionmemtehnedtsest cnhoemmiincaallccoonncceennttrraattiioonns taorewhonilcyh,ofortheexatemsptloerg5a0n%iosfmsthareemeexapossuerde.d cIofnicteinstdraettieornmsi,ntehdetthoaxtitcihtey vhaaldubeseecnanfubreniasnhdedm,uwset bcoeualddjcuasltceudldatoewcnhweamridcablyr5ec0ov%.eryIfraatneasl,ytaincdaltamkeeasinutroeamcecnotusontfhsyodrmoelyssoirst, veoxlpaotisluirtey,caonncdenottrhaetriopnhsy.sicochemical processes that might lower the actual test organism sPuormietyotefsttshietaptepsetamarteedritahaltal1s0o0i%s &tmesatjcohreaciocnaclerwnasanudsewda,sfonrototshuefrfsicaicehntelmyicchaalroacftelreiszseedr in thi purity test. In o(tahpeprroexsitmsa,tfeolryn8o5o%b)viwoauss ussteadte.d Wreaasont. eIsnorlfvaec,tn,t3(iMsoipnrtohpeainrosl)uomrmaarcyoomfbienaacthiotnesotfbstoatt:h "wDaastausmeadyinnot `aadcdciutriaotne,ilytrheilsawteatsoxiacittyypoifctahle" TteSstCsAamspeclteiownith4 trhaetovftihIeweotweuslt,dsurbestcatncteh.e"se satgurdieees,wiptehntdhiinsgcroencceeinpt.ofTn ``amdeddiitiuomn.al information on purity and studies on analytical measurementsofthe test chemical in the test 32 NOo279 TOXICITY TO MICROORGANISMS Titles Microtox Toxicity Test TEST SUBSTANCE Ipdeernftliutoyr:oocPtearnfolautoer,ooFcCt-a1n1o6i,c FacCi-d1,2e6m,mFonCiu-m o1sartF6;Ca-9l14o,3r.efe(rOrcetdatnooiacs aPcFidO,Apeantmamdoecnaifluumorsoa-l,, aammmmoonniiuumm salt, CASH 3825-26-1) tRsempaurriktsy:waTshneot3Msufpfriocdieuncttliyonchlaortacntuemrbizeerd,waalst3h9o0u.ghTihnefotremsattsiaomnpilnediwcaasteFdCi-t1w2a6s,aa mwihxittuerepoowfd7e5r-y93solid. percent test substance and 7-22 percent CS, C6, and C7 perfluoro analogue compounds. METHOD Method/guideline followed: Beckman's Microtox "BASIC" Procedure Test type: Static GLP (/N): No ear study performed: 1987 Speciesistrain: Photobacterium phosphoreum Supplier:Notnoted. `Concentrations tested: 0,420, 560, 750, and 1000 mg/L as nominal concentrations. Exposure period: 30 minutes Analytical monitoring: No measurementsofthe test substance were taken throughout the test, Statistical methods: Not noted T"Deisltliceontndwiatsio2ns%: NaCl Microbic's Reagent "Deionized water pH - A 2000 mg/L stock swoalsut6i.o5n was prepared by dissolving 200 mg test solution in 100 mL diluent, --TMeesdtisaolwuatsionnostwreerneepwreedpared using aliquotsofthe stock solution. Stabilityofthe test chemical solutions was not noted. "~ETxwpoosruerpleicvaetsesselwserweerteakceunv.etes. Remarks: none RESULTS 383 000280 EE... Doseofeach endpoint (as mg/L): 5 minute EC20= 810 mg/L Sminute ECS0 = >1000mg/L 5 minute EC80 => 1000 mg/L. 15 min EC20 = 520 mg/L 15 min ECS0 =>1000 mg/L. 15 min EC80 =>1000 mg/L. 30 min EC20 = 420 mg/L 30 min ECS=0 870 (810-930) mg/L 30 minEC80=> 1000 mg/L. `Was control response satisfactory (yes/no/unknown): unknown Statisticalresults,as appropriate: Not noted Remarks: none CONCLUSIONS "The 30-minute ECS0 was determined to be $70 mg/L with 95% confidence intervalsof 810 to 930 mg/L `Submitters' remarks: A Klimisch data quality ranking of2 was given. Testing meets all criteria for quality testing, but lacks analytical confirmationoftest substance concentrations. Characterizationofthe test sampleisalso lacking. Reviewers' remarks: none REFERENCE 3M Company. [No title given.] Lab Request Number E1282. St. Paul, MN. OTHER General remarks: This summary was based on a summary report and only limited data tables. No detailed report was available. Therefore, the contentsofthis summary, in reference to the protocols and resultsofthe study, are limited. 384 000281 `TOXICITY TO MICROORGANISMS DATA "Title: Microbies Microtox) Toxicity Test TESTSUBSTANCE I1d2e6n,tFitCy-:16P9,FOFACa-mm1oo4nia3us,masmaaltjoarsocormepfoenreedntfoofasFaX-m1m0o0n3i(uomctpearnfoliuoarcoiod,ctpaennotsatdee,cPafFlOu,crFoC--,1a1m6m,oFnCi-um sal, CASRN 3825-26-1),a stated in the submiter's summary. Remarks: The 3M production lot number was 2327; the tes substance was FX-1003. The purity ofthe test substance was not sufficiently characterized, though current information indicated it was a solution of< 43% ammonium perfluorooctanoate, 50% water, < 3% inert perfluorinated compound, and 1 ~2% Cs and C7 perfluoro-anslogue compounds. METHOD Method/guideline followed: Microbics MicrotoxTM "BASIC" Procedure Test type: Static GLP (YN): No Year study performed: 1990 Speciesistrainisupplier: Photobacteriumphosphoreun/3M Doses (concentrations) tested: 0 (blank control), 125, 250, 500, and 1000 mg/L Exposure period: 30 minutes Analytical monitoring: Concentrationsofthe test substance were not measured during the sudy. uTseisntgcaolnidqiutoitosnosf:thTewsotorcekplsioclautteisoonf,eaa2c0h0of0tmhge/LfosuorlutetsitoncopnrceepnairzeadtiionnMsialnldipbolraenMkiclolntir-oQl wweatreer.pr2ep%ared NH:aSC0l,;Mifcorroobisem'ostiRceaadgjeunsttmweanstsu,s2e00asmtgheNdaiClulenwt.asTahddiedtatol 1p0Hmiofofsa6.8mwpalse.adjTuhsetefdintaol psoHlu6t.i7onwsitwherdielute oclregaarnaisnmds,coilnorrleefses.reCnucveettotetshewmeeroanusleigdaht gtehneereaxtpeodsbuyrethveescsoenlst.roPleorrcgeanntiosfmlsi,gwhtalsosussebdyttohaesdeosssedthe toxicity ofthe test substance. SptraotviisdteicdalfomreMtihcordso:toExC, and ECo values were calculated using a statistical linear-regression program Remarks: The test conditions and procedureswere notfutherdescribed. 385 0N0282 RESULTS Doseof each endpoint S-min (calculatedbystatistical ECco >1000 mg/L. linear-regression program): 3105--mmiinn ECCyoo >>11000000mmgg//LL `Was control response satisfactory (ves/nofunknown): Unknown `Statistical results, as appropriate: Not specified ofSutbemsittt-esru'bsstraenmcarekcso:ncTeensttriantgiomnest. Aalllsoc,rittheerriea fwoarsqauallaictkyotfescthianrg,acbtuetrilzaactkieodnaonftalhyetitceaslt csoanmfpilrem.ation Reviewer's remarks: Unable to determi%ne mortality of the controls. C`TOheNaCuLthUoSrsIcOoNncSlude the FX-1003 30-minute ECsoforPhotobacteriumphoshphoreunt o be >1,000 mg/L (nominal concentration). `thSeubtmeistttseurb'sstarnecmearinksw:ateKrlismoilsuctiho-nrawniktihnign2c.omTphleetsetluydychsaurmacmtaerryizaepdpcloinecsetnotrtahteitoensstofsaimmppulreitaiseas.miDxattuare of may not accurately relate toxicityofthe test sample with thatofthe est substance. Reviewer's remarks: None R3EMFEEnRviErNonCmEental Laboratory. 1990. Microbics Microtox() Toxicity Test. St. Paul, Minnesota. Lab request number G2882. OTHER rReepmoratrkwse:s aTvahiilsabsluem.mTahreryefwoarse,btahseedcoonnteaatssumofmthairsy sruepmomratrayn,dilnirmeifteedrernacew tdoatth.eNporodteotcaoillseadnd resultsofthe study, are limited. 386 000283 `TOXICITY TO MICROORGANISMS Title: Microbics Microtox Toxicity Test of FC-143 TESTSUBSTANCE IAdmemntointyi:umPeprefrlfulourooroocotcatnaoniocataec,idP,FaOm,mFoCn-i1u1m6,saFlCt;-1m2a6y, aFlCs-o1b6e9,reofrerFrCe-d14o3.as (POFcOtaAnoaimemaocindi,um salt, pentadecafiuoro-, ammonium salt, CAS # 3825-26-1) Rinefmoarrmaktsi:onTihneditceasttesaimtipslae misixFtCu-r14eo3.f 9I6t.s5pu~ri1t0y0w%astenstotsusbufsftiacniceentalnydch0a3ra.ct5er%izCeyd,, Ct5h,ouagnhd cCuyrrpeenrtfluoro `analog compounds. The 3M product lot number was 427. METHOD `Method guideline followed: Microbics Microtox "BASIC" Procedure Type (tet type): static GLP (YIN): N Year study performed: 1996 Speciesistrain: Photobacterium phosphoreum Supplier: Microbics r`eCpolnicceanttesroaftieoancshtewsetreed:te0s,te1d2a5f,a25c0h, c5o0n0c,enatnrdat1i0on0.0 mg/L. The concentrations were nominal. Two Exposure periods 30 minutes Analytical monitoring: none MStiactriosttoicxal.methods: ECS0 values were calculated by a statistical linea regression program provided for `PTHesotfctohnedisttioocnks:solAutpiroinmwaarsy t2h0e0n0amdgju/sLtesdtofcrkomso.lu8tito0n7w.a6suspirnegpa1r.e0dNinNMaiOlHl.iporAenMoislmloii-iQc"adwjautsert.meTnthe wApapsemaaradnecueosfintges2t00somlugtiNoansClwadsisnsootlevdedasin"c1l0eamrLansdtoccoklosrolleustsio.n". AlTlheteswtastoelruthiaorndsnewsesrewamsadnoetbryeported. proportional dilutions. The tes Vessels. Two replicates at each temperature was not noted. of four concentrations were Cuveties (3 mL) were tested, along with two used as the controls. exposure Remarks: indicated. The numberofmicrobes per replicate and the growth phaseofthe microbes were not RESULTS 387 000284 Doseofeach endpoint (as mg/L): minute ECS0 1000 mg/L 3105 minute minute ECS0 ECS0 = = 800 730 (790 (630 -- - 820) 850) mg/L mg/L. `Was control response satisfactory (ves/no/anknown): unknown `Statisticalresults,as appropriate: none Remarks: none CONCLUSIONS `9T5he%FcCo-n1f4id3e3nc0emiinntuetrvealEoCfS603f0ortPoh8o5t0obmagc/tLe.rium phosphoreu was determined to be 730 mg/L with a `Smuebemtistatlelrcsri'terreimaafrorksq:ualFiotyr dteasttainrge,libaubitliltayc,ksthaensaltyutdiycawlacsonafsisrimganteidoanoKfltiemsitscshubrsatnaknicnegcoon2fce.ntTreasttioinnsg. `There is alsao lackofcharacterizationofth test sample. Reviewers' remarks: none REFERENCE 3M Environmental Laboratory. Lab Requestnumber P1626. St. 1996. Paul, MMiincnreosboitcas. Microtox Toxicity Testof FC-143. OTHER dGeetnaeilreadlrRepeomratrwkass:avTahiilsabsleu.mmTaherryefwoarse,btahseedcoonnteanstsuomfmtahrisy sruepmomratrayn,dionnrleyfelriemnicteedtdoatthaetparbloetso.coNlsoand resultsofthe study, are limited. 388 000285 TOXICITY TO MICROORGANISMS itl: Microbes Microox Toricity Test of FC-118 TESTSUBSTANCE AIdmemntointyi:umPeprefrlfulourcotoocotcatnaonioeataeci,d,PFaOm,mFoCn-i1u1m6,saFlC;-1m2a6y, aFlC-o1b6e9,reFfCe-r1e4d3,tooraassPFthOeAmaajmomrocnoimupmonseln,t of FC-118. (Octanoic acid, pentadecafluoro-, ammonium sal, CAS # 3825.26-1) Rinefmoarrmaktsi:onTihneditceasttesatmsple20is%FFC-C1-1184.3 ilns8p0ur%itwyatwear.s nTohesu3ffMicpiernotdluyctchlaortacntuemrbizeerd,atshonuogthncoutrerde.ntData may not accurately relate oxiiy ofthe est sample with that ofte test substance METHOD Methodiguideline followed: Microbics Microtox "BASIC" Procedure Type (test type): sate GLP (VN: N ear study performed: 1996 Speciesstrain: Photobacteriumphosphoreun Supplier: Microbics DoTsweosre(pcloincacteenstrwaetrieontses)teudsaetdca0c,h6c2o5n,ce1n2t5r0at,i2o5n.00, and 5000 mg/L.Theconcentrations were nominal. Exposure period: 30 mines Analytical monitoring: none SftoartMiisctircoatlomxe.thods: ECS0 values calculated by stitial linea regression program provided o"TfetshteCosnodciktisoonlsut:ioAnpwraisma6.r0y(1n0oga/dLjussttomceknts)olauntdioannwoassmoptriepcaardejduisntMmielnltiwpaorsemMaidlelu-sQinTMgw2a0te0r.mgThNeaCpli tdeisstoslovleutdioinns1w0emreLmsatdocekbsyolputrioopno.rtiAopnpaeladrialuntcieoonsf. teTshtesotleusttitoenmspwearastnuorteewdaassn"oltenaorteadn.d cCoulvoerlteesss.("3 AmlLl) cwoenrteoulscd asth exposure vessels. Two replicates were (sted at cach concentration, as wel a the iRnedmicaartekds.: The numberofmicrobes per replicate andth growth phase ofthe microbes were not RESULTS 389 000286 Dose of each endpoint (as mg/L): 5 m1i5numtienuEtCeSE0C=S044=6033(64002(030~9409-503)64m1g)/Lmg/L. 30 minute EC50 = 3150 (2910 - 3420) mg/L `Wascontrolresponse satisfactory(ves/no/unknown): unknown Statistical results, as appropriate: none Remarks: none CONCLUSIONS `The 95% FcCo-n1fi1d8en3c0emiinntuetrvealEoCfSO2f9o1r0-P3h4o2t0obmagc/tLe.rium phosphoreun was determined to be 3150 mg/L with a a`lSlucbrmiittetriearsf'orrqeumaalritkys:teFsotirngd,atbautrlealciakbsilaintayl,yttihceasltcuodnyfwiramsataisosniogfnetdeastKsluibmsitsacnhceractoinncgoenftr2a.tioTness.tinTghemreeetiss alsoa lackof characterization of th test sample. Reviewers' remarks: none REFERENCE 3M Environmental Laboratory. 1996. number P1626. St.Paul, Minnesota. Microbics Microtox Toxicity Testof FC-118. Lab Request OTHER d`eGteanielreadlrReepomratrwkass:avTahiilsabsleu.mmTaherryefwoarse,btahseedcoonnteantssuomfmtahrisy sreupmomratrayn,dionnrleyfelriemnicteedtdoatthaetparbolteso.colNsoand resultsofthe study, are limited. 390 0N0287 `TOXICITY TO MICROORGANISMS "Title: Microbics Microtox Toxicity TestofFC-1015-X TEST SUBSTANCE IAdmemntointyi:umPeprefrlfulourooroocotcatnaoniocaatcei,dP,FaOm,mFoCn-i1u16m,saFlCt;-1m2a6y,alFsC-ob16e9,reFfCer-r1e4d3t,ooarsaPsFthOeAmaajmomrocnoimupmonsaeltt, of FC-1015 or FC-1015-X. (Octanoic acid, pentadecafluoro-, ammonium salt, CAS # 3825-26-1) Remarks: The test sample information indicates itis a is FC-1015-X. Tis purity was not sufficiently 30% straight carbon chain versionof FC-143 characterized, in 80% water, though current The 3M product sluotbsntuanmcbee.r wDaatsanwoetrneotuesd.ed Dtaotcaommpaayrenottoxaiccciutryaotfetlyherelbartaenctohxeidc"itsytroafitghhtectheastinsaammpmloenwiituhmthat ofthe test perfulorooctanoate homolog mixture in FC-143 vs. FC-1015-X. METHOD `Method/guideline followed: Microbics Microtox "BASIC" Procedure: Type (test type): static GLP (YIN: N Year study performed: 1996 Speciesistrain: Photobacterium phosphoreum Supplier: Microbics `DTowsvoesre(pcloincacteenstwraetrieontess)tuedseadt:a0c,h4c1o6n,ce8n3t2r,at1i6o6n5.,and 3330mg/L. Theconcentrationswere nominal. Exposure period: 30 minutes Analytical monitoring: none Statistical methods: for Microtox. ECS0 values calculated by statistical linear regression program provided `PTHeostfCothnedisttioocnkss:oAlutiporniwmaarsy66..96a6n0dga/nL ostsomcoktiscolaudtjiuosntwmaenstpwraepsamreaddeinuMsiilnlgip2o0r0e mMiglNlaiC-lQTMdiwsastoelrv.edThine 10 wmeLrestmoacdkesoblyutiporno.porAtpipoenaarladnilcuetoifontse.stTshoelutteisotntsewmpaesrnatoutreed as "clearand colorless." was not noted. Cuvettes All test solutions (3 mL) were used as the exposure vessels. Two replicates were tested at each concentration, as well as two controls. iRnedmicaartekds.: The numberof microbes per replicate and the growth phaseofthe microbes were not RESULTS 391 ------------ eee 000288 SSS------a-------------------- Dosesofeach endpoint (as mg/L): S m1i5nmuitneuEtCeSE0CS=023=0109(6200(7107-3025-6202)1m0g)/mLg/L 30minuteEC50 = 1950 (1-271606)mg0/L `Was control response satisfactory (ves/no/unknown): unknown Statisticalresults,as appropriate: none Remarks: none CONCLUSIONS 2`T9he5F%Cc-o1n0f1i5d-enXce30inmtienruvatleoEfC1S7060f-or21P6h0omtogb/aLc.teriumphosphoreum was determined to be 1950 mg/L with a`lSlucbrmiittetreiarfso'rRqeumalairtykst:estFiongr,dbautta lraelcikasbialniatlyy,ttihcealstcuodnyfiwramastaisosnoigfnteedstasKulbismtiasncchercaotnicnegnotr2fat.ioTness.tiTnhgermeeeitss alsoa lackofcharacterization ofthe test sample. Reviewers' Remarks: none REFERENCE `3nMumEbnevriPr1o6n2m6e.ntSatl. LPaabuolr,atMoirnyn.eso1t9a9.6. Microbics Microtox Toxicity Test ofFC-1015-X. Lab Request OTHER dGeetnaeirleadlrRepeomratrwkass:avTahiilasblseu.mmTaherryefwoarse,bathseedcoonnteantssuomftmhairsy sruepmomratrayn,di onrleyfelriemnicteedtodatthae tparboletso,coNlsoand results of this study, are limited. 392 GNO289 ee `TOXICITY TO BACTERIA Title; Activated Sludge Respiration Inhibition TEST SUBSTANCE IAdmemntointyi:uPmerpfelrufolruooorcotoacntoaincoaatcei,d,PaFmOm,oFnCi-1u1m6,salFtC;-m1a26y,aFlsCo-1b6e9r,efoerrFrCed-1t4o3a.s (POFctOaAnoaimcmaocindi, um salt, pentadecafluoro-, ammonium salt, CAS # 3825-26-1) sRuebmsatarnkcse:waTshneo3tMsupfrfiocdiuecnttilyonlchoatrnacutmebriezredw,atsho37u.ghTchuerrteenstt sinfaormawmtaisopnFiCln-d1i4cea3t.esThitewpuraiatmyioxfts tuhreeof96.5 -- 100% test substance and 0 -- 3.5% Ce, C, and Cs perfluoro analogue compounds. METHODS Method/guideline followed: Protocol reference EAR, 11/8/79 Test type: Not noted. GLP (VIN): No ear study performed: 1950 Test organism: Activated shudge mixed liquor Source: Metro Wastewater Treatment Plant, St. Paul,MN. Concentrations tested: Blank control, 1000 mg/L Exposure period: Seven minutes Analytical monitoring: None Statistical methods: Graphed dissolved oxygen versus time in minutes. "mTLestwictohndDitLionwsat:erN.ot noted other than the stock solution was prepared with 0.6 g FC-143 diluted to 100 Remarks: No further details on testing methods were provided by the submiter. RESULTS 393 0N0290 `Dmogs/eLowfietahcahcoenntdapcotitnitme(aos fm7g/mLin)u:teNs.o acute inhibitory effect on activated sludge respiration rate at 1000 Remarks: Results baosnnoemindal concentrations. `Was control response satisfactory (yes/nofunknown): unknown Statistical results as appropriate: Not noted CONCLUSIONS Limited contact time ofactivated sludge. estimates that ammonium perfluorooctanoate is not expected to inhibit the activity Submitters" remarks: not an agency approved Klimisch method. ranking There is 3l.acTkoefstcihnagralcatcekrsirzeactoirodnoofftmheethtoedstoslaomgpylueseadn.d tTehstesmoelutthioodnswnaost analyzed for test substance concentrations. Reviewers' remarks: No ECS0 or other effect level was given. REFERENCE 3M Company. [No ite given. Lab request number 56255. St. Paul, MN, OTHER `NGoendeertaalilreedmraerpokrst:waTshiasvasiulambmlea.ryTwhearsefboarsec,dtohenaconstuemnmtsaorfytrheipsosrtumamnadroyn,lyinlirmeifteerdendcaetatoabthlee. s protocols and resultsofthe study, are limited. 394 -- -------- -------- -------- -- ---------------------- 600293 TOXICITY TO BACTERIA Title: Activated Sludge Respiration Inhibition Test TEST SUBSTANCE `Ipdeernftliutoyr:ooc_tPaenrofaltueo,rFooCc-t1a1n6o,icFaCc-id1,26a,mFmoCni-umo1sralF6tC;-a91ls4,o3.ref(eOrcrteadntooiacsaPciFd,OpAenatmadmeocnafiluumorsoa-l,t,aAmmmmoonniuimum salt, CAS# 3825-26-1) Remarks: "The purity The was 3M production lot numberis not completely characterized, 390. The although test sample information was FC-126, a white powdery solid. suggested it was a mixtureof 78-93 percent test substance and 7-22 percent CS, C6, and C7 perfluoro analogue compounds. METHODS Method/guideline followed: OECD 209 Test type: Static GLP (Y/N): No `Year study performed: 1987 `Test Organism: Activated sludge mixed liquor was used the same day it was collected. Source: Metro Wastewater Treatment Plant, St. Paul, MN. `Ccoonnctreonltsr-a0timogn/sLte-swteerd:e u0s,e1d0,0a,s1w8e0l,l3a2s0,a r5e6f0e,raenncde 1s0u0bs0t0anmcge/.)L test material solution. (Two blank Exposure period: 30 minutes; 3 hours Analytical monitoring: It was not stated whether the concentrations were monitored throughout the test. Statistical methods: Not stated. Test conditions: - Dilution water was aerated, distilled, deionized water with a pHof6.7 --SSuysnptehentdiecdssoelwiadgsewwearsep2r.e7pagr/eLd according to OECD Guideline #209 - Test solutions distilled water, 1w6ermeLprseynptahreetdicbyseawdadgiengfeiendd,ivainddua2l0w0emigLhtisntoocusloulmut.ioTnhsecponHtoaifntihneg 284 mL solutions was adjusted to 7.0 using 1 N NeOH. solutionof3,5-diochlorophenol, The reference solutions were created using 500 mg/L stock 395 000292 -copnHceonfttrhaetiaocntwiavast7e.d4sl(uindigteialm)iaxnedd8l.i1q(ufoirnwaa)s 7.8 (initial) and 8.0 (final); pHofthe 1000 mg/L test + Temper~atEuxrpeoosfutrheevetsessetlwtayspe20w-a2s1 nCot(fdoerscbroitbhed3.0 min and 3 h), ~~NRuesmpbireartoifonreipnlhiicbaittieosnnwoatsstdaetetde,remxicneepdtbtyhamtetawsuorbilnagnkdciosnstorlovlesdwoexryegeunsecdo.nsumption. Remarks: Hardnessofthe dilution water was not presented. RESULTS Doseofeach endpoint (as mg/L): At3 hrs: ECS0 (for respiration inhibAitti3on0) m=i>n: 10E0C0Sm0g/(Lo.r respiration inhibition) = > 1000 mg/L Remarks-:A reference substance was used, but no results were presened. ~ Noneof the doses resulted in 100 percent inhibition. ``pWearscecntonrtersoplirrateisopnornasteesianthiibsiftaicotnoroycc(uvrerse/dn.o/Aulsnok,ntohwn)d:iffCeornetnrcoelbreetswpeoennsethaepptewaorceodnatdreolqsuawtaes; 2le.s2psetrhcanen|t actac3h0omtihenru.tes and 0.8 percent at 3 hour; his meets th guideline criterionofbeing within 1S percent of Statistical results, as appropriate: none CONCLUSIONS "mTgh/eLauatfhtorr3s shaotuertshoaft tehxeptoessutrmea.terial induced 38 percent inhibition in respiration rate at 1000 `mSeuebtmsitttheercsr'itrereimaafrokrsq:ualTihteyateustthiongr.s sHtaotweetvhear,ththeKlsitmuidysclhadcaktead qcuhaalriatcyterrainzkaitniognwoaftsh2e, aensdt tsuhbtstthancsetudy pcuormiptoyuanndd. analytical confirmationofconcentrations. Also, no results were presented for the reference Reviewers' remarks: REFERENCE 3ReMquCeosmtpNaunmyb.erAcEt1i2v8a2t.ed SStl.uPdaguel,ReMsNpi.ration Inhibition Test. Environmental Laboratory; Lab OTHER NGeondeertaalilreedmraerpkorst:waTshiasvasiulambmlea.ryThwearsebfaosre,dtohn caosntuemnmtsaorfytrheipsorstumamndaroyn,lyinlirmeifteerdendcaetatotatbhlees protocols and results of the study, are limited. 396 ------------------------ i------E-------- @No29a3 TOXICITY TO BACTERIA Title; Activated Sludge Respiration Inhibition TEST SUBSTANCE IAdmemntointyi:uPmerpfelrufolruooorcotoacntoaincaatcei,d,PaFmOm,oFnCi-1u1m6,salFtC;-m1a26y,aFlsCo-1b6e9r,efFeCr-r1e4d3(,0oarsaPsFaOmAajaomrmcoonmipuomnesnaltto,f FX1003. (Octanoi acid, pentadecaluoro-, ammonium salf, CASRN 3825.26-1) suRbesmtaarnkcse:waTshneo3tMsupffriocdiuecnttilyonchlaortancteurizmedw,batsh2eo3u2gr7h.avTahielatbelset isnfoarmawtmiaosnpFiXn-ld1ic0a0et3e.d Tithweapsuarsiotuy toiftohneoftest C<;45pe%rfalmuomroo-nianuamlopgeureflcuoormopoocutnadnsoa.teT,h5e0te%stwsautbers,ta<n3c9e%wianserta pleerafrluloirqiuinda.teTdhceormepfoeruenndceansudbs1t-a2n%ceC;usaendd. for this study, 3,5-dichlorophenol, was Aldrich red label, lot numberD7-060-0. METHODS Method/guidelinefollowed: OECD 209 Test type: Static GLP (YN: No Year study performed: 1990 ``TTehsettoesrtgoarngiasnmi:smMsiwxeerdeluisqeudoroancttihveatdeadysolbuidaigneedw.asTchoellceocntdeidtifornomofMtehtroorWgaansitsemwsatwearsTnroetatspmeecnitfiPelda.nt. `Supplier: Metro Wastewater Treatment Plant C(3o0ncmeinnturtaetsiaonnds3tehsotuerds:).0T(wbloanrekpcliocnattreoslofatnhde1b0l0a0nkmgco/nLtrFoXl-a1n0d0o3nweerreepluisceatdefoofr e1a0c0h0emxgp/oLsuFsXe-p1e0r0io3d w`ceorneceunstreadtifoonr eoafc1h0emxgp/oLs.urOenpeerrieopdl.icAateroeffetrhencreecfoenrternocle,c3o,n5t-rdoilchwlaosroupsheednoflo,rwaacshienxcplousdeudreatpeariod. Nominal concentrations ofthe est substance and reference control were used during thi study. Exposure period: 30-minutes and 3-hours rAensapliyrtaitciaonl imonnihtoiribnagsi:dteDtiiesrsomolinvnee,ddobxyygoexnygceonncceonntsruamtpitoinosnw.ere monitored inorderto determine. Statistical methods: Notspecified w"Taesstccroenadtietdiboynsa:mTahses aidndoictuilounmtoco&ntsoaliunteidon3.c2ong/tLa.ionfinmgi2x8e4dmliLquMoirlsluipsopreendMeidllsiol-iQds.wTatheer,te1t6smubLstance: 397 NO294% frsiynenatlnhepctHiecofssoelwhueatgiaeocnfvwoaedts,edacnSedeu2d0g0immniLgxeindoSgc0uil0uomm.wiTahsetotce7sktsnssodulbu7.s1ttiraonnecoefs3ve.asr5s-vpheraorThpehseiirasollTpefhowfmitihhelwa1tae0rn0:d0A "mThLe mtpesetrsaolturionrawnags wa3s. 2T0he i21alCduprHinofgtthhee rsfyee.ncTeosolputlioen1s0mfg/hL 3S.a-dkiechoornopthaenndl,onwe as7. arecphliceatxeopofseaecphercioondceCntOramtiionntosf FnXd-130h0o3w(s1)0.00 mg/L) and 3,5-dichlorophenol (10 mg/L), were used for Remark: No additonalcoments RESULTS Dose of each endpoint (as mg/L): 30-m`3i-nhuotuer CEC5S00 >>11000000 mmgg//LL. aRepmyartkost:htTemsititnrgewaasndconntdutcetetdtonstuhbenmcixst,ureofthe described cst substance, Th values reporid Was control response stfacory(sesnoankao: Yes Statistica revolt, as appropriates No addon comments `CONCL"mUThSLeI.FOXN-S1003 hour ECS0foactivated she respon iin was determined 0 be >1000 SSaanumabplmylteii.tceaTlrshc'onerfseitmimanargrkirso:nooKfiiedntisswcuahbssrtnaaonntkceFilncog2y.ncdTeoencsrutamiteningotmend.e.Tshlelee1 aackfoorfqhaalriaycteenstziangonbuotfatkesfs aRveaviileawbleerst'o dremearnks:eT3h6e6csonhcoludsiyon.s sppe to be supported by th data, however, mid data were RSReMEaFvEEnevsRiEraomNnbCmeeEnrtaGl26La8b2oratory. 199. Activated Shdge Respirtion ain. t. Pl, Minnesoa Lab OTHER rdGeioneesrdaalrreaepnomdratrewksas:stTavhoaiislfbhseluem.smdTahr,yrsawoassrB,sdehed.coontntssorftyhssspuomrmtaary iinierdendcue bltshe. No 398 000295 TOXICITY TO BACTERIA Title: Activated Shudge Respiration Inibiion Test TEST SUBSTANCE sIadletn,tAitmym:oPneirfulmuopreorofcltoarnoooicetaacniods,taemPmFoOn,iFuCm-1sa1l6t;, mFaC-y1a2l6s,o FbCe-r1e6f5e,rFeCd-014a3s,PoEraOsAatmearjaobructoymlpaomnmenntiuomf GC-1015 or FC-1015-X. (Octanoic acid, pentadecafluoro-, ammonium salt, CAS # 3825-26-1) iRnefmoarrmaktsi:onTihnedicteasttessiatmiplsae w3a0s%FsCt-ra1i0g1h5t-cXh.ainIVvserpsuirontyofwaFsC-n1o4t3suifni8c0in%tlwaytecrh.araTchteeri3zMed,prtohdouucgthlcoutrrent `naummmboenriwuamsp"erHfOluGoEro2o0c5t.a"noDaaethaowmeorleougsueedm0ixtcuormepainreFCt-he14t3oxwiciitthy wohfattheisbsruanpcphoesde!ds(i0rabisghtthceh1ai0n0% right carbon chain ammonium perfluorooctanoate in FC-1015-X. METHODS `Method/guideline followed: OECD Test #209 Testtype: sate GLP (VIN): 10 Year study performed: 1996 "Test Organism: activated shdge SiunptpliPearu:l,TMhNe.activated shudge mixed liquor was collected rom the Mero Wastewater Treatment Plant `wCeornecaelnstoraetsiteodn.s eTshteedc:on4c2e0n,tr5a4t0i,on1s6w6e0,raenndom3in3a2l0.me/L. Two blank controls anad reference substance Exposure periods 30 minutes and3 hows Analytical monitoring: none Statistical methods: none "rTeefsetrecnocnedistuibosntsa:nceT,he3-ddiiholonrowpahteenrauls, wawsasprMeiplalriepdorbeyMdiilssloil-viQngwa5t0er0.mgAisnto1c0kmsoLluItiNonNAofOtHh,e diluted ov1ef0s.ts3h0eelm.rLe,fetrheenncebsrooluugthitontowathsempeoainsturoefdintcoibpeien7.t2p.reTchipeitteasttiosnubwsittahnc1eNwHa;sSaOdydaendddidrielcuttleydttooh1eL.teTsthe pH. Synthetic sewage per OECD guidelines (Test #209) was used. 399 000296 A`Tthethteeemnpderoafttuhreetreastn,geTdSfSro=m 19.1 to 1.3 g/L. 22.1 The C. Initially, initial pH = 7.8, total suspended solids were while the fipnH =a7.l9. measured at 3.22 gL. The waterhardness was not indicated. `The element basis was respiration inhibition as determined by oxygen consumption. Remarks: Authors reported that values were corrected to 20C for calculations. RESULTS Dose of each endpoint (as mg/L): 30 min ECS0 > 3320 mg/L 3hEC5023320 mg/L. Remarks: Testing remarks field. The was conducted values reported on the apply mixtureofthe to that mixture test and substance as described not th test substance. in A trheefetreestncseubstance substance of 3,5-dichlorophenol was used, but ECS0 values were not reported. `Was control response satisfactory (ves/nofunknown): unknown Statistical results,asappropriate: none CONCLUSIONS `The FC-1015-X 3 hour ECS0 for activated sludge respiration inhibition was determined to be ereater than 3320 mg/L. q`uSaulbimtiyttteesrtsi'ngr,ebmuatrklasc:ksTahnealsyttiucdaylwcaosnfaisrsmiagtnieodnaofKltiesmtissucbhstraannckeincgonocef2n.traTteisotnisn.g mTeheetrse asllacrliatcekrioaffor characterizationofthe est sample. Reviewers' remarks: none REFERENCE 3M Company Environmental Laboratory. 1996. Lab Request N2169. St. Paul, MN. OTHER N`Goendeertaalilreedmraerpokrst:waTshiasvasiulambmlae.ryThwearsefboarsec,dtohneaconstuemnmtsaorfythriepsosrtumamnadroyn,lynlirmeifteerdendcaetatoabtlhees. protocols and resultsofthe study, are limited. 400 000297 TMEISCTROSBUIBCSSTAMNICCEROTOX TOXICITY TEST rIdeefnetrietyd:t0PearsfPluFoOroAoctteatnroiacbuatcyidl,amemtornaibuuntsyallat,mmonium salt; mayalsobe tectormapbounteyantmomfonL-i1u34m92p.er(fOlcutoarnooocitcanacoiadt,e,peNn2t8a0de3c-a2i,luooaros-,amajor Rteetmraarbkust:ylTahmemo3nMiupmrsoadlu,ctCiAonSo#t9n5u6m58b-e5r3w-a0s)2. The test sample is rweafserneotd stuofbfiycitehntltyescthianrgacltaebroirzaetdo,ryalatshLo-u1g3h49c2ur.reTnhteinpfuorirtmyatoifotnheinsdiacmaptlees it `iwsaatesro,launtdio2n7o.2f#%4 i9so%prtoepraanbolu.tyammonium perfluorooctanoate, 27.9% Tehstefsoulblsotwainncge isnuamnmairsoyparpopplaineosl1wattheeressotlustaimopnlweitahs ainmcioxmtpulerteoelfythe crhealraatcttoexriiczietdyocfotncheenttersattsiaomnspolfeiwmptuhritthiaetos.fDtahteatmesasyunbsottaanccceu.rately MMeEtThHodO:D:Microbics' Microtox "BASIC" Procedure. GYeLaPr:CNoompleted: 1995 S`Apneacliyetsi:caPlhomtoonibtaocrtienrgi:umppHh,olsipghhtooruetupnut RSteaptliisctaitceals:me2thods: ECS0 values calculated by satistial linear Treegsrtesosrigoannpirsomgrsoaumrpcreo:vMiidcerdofboircMsiCcorropotroaxtion, Carlsbad, CA TDeisluttCioonndwiattieorn:s:Millipore Mill-Q TM water. SSotlouctkioannwdastepstrespoalruetdioinnpMrielplairpoarteioMni:lAlip-riQmawartyer2.00T0hemgp/HLofsttohcek satnodckansoolsumtiooincwaadsjutshtemneandtjuwsatsedmfardoemu4s.i7ng10260.07NusaiCnlgd0i.s1sNolvNead OinH "1c0lemaLr asntdocckolsoorlluetsiosn".. AApIpetaesrtasnocleutoiftoensstwesroelumtiaodnes wbaysprnooptoerdti1o5nal iElxuptoisounsre vessel: 4 mL glas cuvettes NNuummbbeerrooffrceopnlciecnattreast:iTonwso: Four plus blank control. RElEeSmUeLntTSBasis: Percent light loss. ENloemmiennatl vcaolnuceenatnrdat9io5n%s:cBolnafnikdecnocnetrionlt,er1v2a5l,:250, 500, 1000mg/L S1-5m-imniuntueteECCS500==633000((257-096-63053)0)mem/gL/.L 3E0l-emmiennuttveaEluCeSs0b=as2ed60on(2n2o0m-in3a0l0)comngc/enLtrations. RSuebmsatraknsce: RTeemstairnkgswfaiseldc.onTdhuecvtaeldueosnraempoirxtteudreapapldyetsocrtihbaetdmiixnttuhreeTaenstd CnoOtNtCheLfUlSuoIrOocNhSemical component alone. 401 000298 "The test sample 30-minute ECS0 for Photobacteriumphosphoreun was determined to be 260 mg/L with a 95% Confidence Intervalof220-300 mSugbLm.itter: 3M Company, Environmental Laboratory, P.O. Box 33331, St. PDaAulT,AMiQnUneAsLotIaT,Y55133 Rteesltiianbgi,libtuyt:lKalckismiasnaclhytriacnaklincgon2f.iTremsattiinogn moefettesstlslubcsrtitaenrciea cfoorncqeunatlriattyions RinEtFheERteEstNsColEuStions and sample purity is not sufficiently characterized. "LTahbiosrsattuodryy,wSatsPcaounl,duMcNt,edLbaybtRheeq3ueMstConmupmabneyr,NE2n1v6i9r,on1m9e9n5tal OTHER 402 000299 Title: Bioconcentration test of Perfluoroalkylcarboxylic acid (C=7-13) [This test is performed. using Perfluorooctanoic acid (Test substance number k-1519)] incarp TIdEeSntTitSy:UBK-S1T51A9N.CEPerfluorooctane sulfonic acid, potassium salt. Lot number A37626B. Remarks: Test substance number K-1519. The test substance is a white powder. Purity determined to be 98%. The test substance was treated as 100% purity. MMeEtThHodO/Dgu:ideline followed: Method for Testing the Degree ofAccumulationof Chemical `1S9u7b4s,taRnecveisseindFOicsthoBboedry8", 1s9ti9p8u,laKtaendpiongtyheo"NToe.st5,MPeltahnondinfgoranNdeCwooCrhdeimniactailonSuBbusretaaun,ce" July 13, Environmental Agency; No 615, Pharmaceutical Affairs Bureau, Ministryof Health and Welfare: and No. 392, Basic Industries Bureau, Ministry of Intemational Trade and Industry, Japan), and Bioconcentration: Flow-through Fish test Guideline 305, June 14, 1996)" in the. `OECD Guidelines for Testing of Chemicals. Type: Flow-through system GLP (Y/N): Yes Year: December 18, 2000 `SSuppepcliiese:r:CaFrupl(uCoykparkiennusyacbarepgiaow)a fishermen's cooperative association Length and weight at test termination: Mean lengih = 6.8-8.6 Mean weight = No weight recorded Loading: 2 and 20 ug/L respectively FAniaslhyAtgieca:lYmeoanriltionrgifnigsh: High-performance liquid chromatography-Mass spectrometry PrTeetsrteawtamteenrt::Aliquotoftest water for level 1 and level 2 were one and two mi respectively for HPTLesCt-mFiasshs: sFpieschtrwoemreetrtya.ken from each test tank and pretreated for HPLC-Mass Spectrometry. Measurementof body weight and length, chopped into pieces, making sample fine, taking out 1 5 grams. Treated with acetonitrile (20 mL), homogenized, washed, and centrifuged. Residue Supernatant Filtration and sampled for LC-MS analysis Numberof concentrations: Two plusa negative control Test concentration: (mean measured): Negative control, 5 and 50 ug/L. UDepptuarkaetpieorniopde:ri2o8d:daNyost stated. Test cDoinlduittiioonnsw:ater: Groundwater from the premisesof Kurume Laboratory Dilutio`nSpweactifeirccchoenmdiusctrtya:nce: Not recorded Hardness: 111 mg/L Alkalinity: 96.1 403 0Ne300 pH: 78 Dissolved Oxygen: <6 Temperature: 24.3 10 25.6C Stock and test solution preparation: Based on preliminary test results for the 96 hour LCS0 value and analytical detection limit, test concentrationsofthe test substance were decided as follows. The control wassetas ablank test. Level I was 5 ug/L and Level2 was 50 ug/L. The fest substance was dissolved with ion-exchanged water to prepare 500 mg/L stock solution. Diluter flow rate: 2 mL/min for stock solution and 800 mL/min for dilution water; 1155 litersday for test water were supplied. Exposure Vessels: 100 lierglass tank Numberofreplicates: None NumLbeevreolff1iasnhdp2e:r2v8essel: Contol: 8 Diet: Nippon Formula Feed Mfg. Co, Ld. `Water chemistry ranges during the study: C INepComwol JSOugL _ Tsugl | lp: (76-78 [76-78 76-78 | : PLhiogthotpienrtieonsdi:tyA:rtAirftiicfiiaclialliglhitgohtfowfhiwtheitfelufolrueosrceesnctelnatmlpam(p14 hrs./day) Collectionoftissue samples: Analysisoftest fish was performed six times at each level in durationofexposure. Four fish were taken out at each sampling time and divided into two groups, and then both were analyzed individually. Analysisof control fish was performed before the experimental starting and after the experimental completion. Four fish were taken out at each sampling time and divided into two groups, and then both were analyzed individually. The fish were sampled for there lipid content by fixing theme in chloroform-methanol extraction with gravimetric analysis Statistical methods: Calculationoflipid content was as follows: Lipid content (%) = (T-To)'S x W1h00ere To = Weightofvessel (2) T== WWeeiigghhttoofffsianmespalmeoplfegtraakviemnetourticfoarnaalnyasliyssi(scoonftaliipniidngcovnetesnste.l) (g) Two fish were employed to measure the lipid content becauseof insufficient size. `Confirmationofthe steady-state was reached. It was evaluated that a steady-state had been reached when there successive analysisofBCEs made on samples taken at intervalsof at least 48 hours were within 20%ofeach other. When BCFs were aless than 100, it was evaluated that a steady-state had been reached afer 28 days even if BCF were over 20%ofeach other. 404 nolo -- Bioconcentration factors (BCF): Level 1 (5 ug/L) apparent steady-state BCF Time to reach 50% clearance: TTT [owtTass Taeo [ael Jas6 [483 [a6l |azi+oior] =wwPFOA CAConcentration in Tissue of Carp Exposed to 5 and 50 ug/L: Test organism mortality: Negative control: None documented. Analysisof PFOA in the test water and carp was performed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. The test waterofeach level was. analyzed once before first analysisoftest fish and at the same time as the analysisofthe test fish. Steady state was reached when three successive analyses of BCFs made on samples taken at was evaluated thata steady-state had been reached after 28 days. == `CTohnecemnetarnatcioonncoefnttersattisounobsfttahnecetiensttseustbswtaatnecreaitnatsestteawdayt-esrtaattea steady state were 94% of `nominated concentrations. The measured lipid contentsinthetestfish were 3.10% before initiationofexposure and 2.82% (CONCLUSIONS In this study, PFOA BCF ranged from 31 for level 1 and 5.1.9.1 for level 2 in the tissuesofcarp. ---- " `Test concentrations of5 and 50 ug/L were used. The fish were exposed for 28 days. eeN0302