Document K6X1R77OgY5Xboaxqy35VJB8K

3048 ff ARG 112 REVISED DRAFT JIAZARD ASSESSMEONTF PERFLUOROOCTANOIC ACID ANDITSSALTS ROBUST SUMMARIES. 2= 9 a 102 000001 0 EPIDEMIOLOGIC DATA TDEoSnTsSUBSTANCE "Title: Identification of Fluorochemicals in Human Sera. 1. American Red Cross Adult Blood dentin: PFOA and 6athe Tuorohemicals Remarks: This is. inal repr, The preliminary report wasdatedJune 25, 2001. METHOD Study desig: Crosssional ManufacturingPracesing Use: NA CViryopwotlhoeasds taesktesd:inT6ordeegtioenrsmiofnhleeveUlSs.ofPFOA i he serum of America Red Study period: 2000 Setting: NIA ota population: Serum pooled fom 6 ARC blod bank in various geographic regions inthe ndUS: HLaosrAonugenl,es,MCDA.; Minneapolis/St. Paul, MN; Charlotte, NC; Boston, MA; Portland, OR, Subject selection criteria: Unknown otal ofsublet in sud: 645 donor, age 20-6 years Comparisonpopulation: NA Participation rate: N/A Subject description: The only demographic fctors known wer ge, gender and E alt efe fects studeinedcaLesvelwseso:f7PMEaGoSr.ocPheFmOiScAalAs,inMh5u7m0anM3b5l6o.odOsSuA,.iPncFlSu.ding Date callconmethods: Esch bod bank wes requested o provide approximately 10 103 000002 samples per 10-year age intervals (20-29, 30-39, etc) for each sex. cDhertaoimlastoognradpahtya/ecloelcletcrtoisopnr:ayBtlaoonddesmermaassasmsppleecstwroemreetarnya(lyHzPeLdCu/siEnSgMhSiMghS-)praensdsuervealliuqautiedd Versus an extracted curve from a human plasma matrix (sce report for more details) Exposure period: Unknown--PFOA serum levels used as surrogate for exposure. TDheescrreipwteiroen/1d0eloirnmeoatrieonsuobjfeecxtspofsourrbeotghromuaplse/seaatnedgofreimeasl:es3i3n2eamcahleagdeoncoartse,go3r1y3(f2e0m-a2l9e, 3do0n-o3r9s,. etc.) except the 60-69 age group where there were fewer. Measuredorestimated exposure: N/A Exposure levels: N/A SAtarteilsitaibciallitymeatshsoesdssm:ent was done. Geomefric means, 95% confidence intervals ofthe geometric wmeearnesc.alrcaunlgaet,edi.nteCreqnutarratlilteernadnegnec,yraanwdcduimsutlraitbuitvieon9o0fthpeercdeanttailbey, aanged,fgreenqdueern,caynddisltorciabtuitioonnws,ere plroecsaetniotnesd.adBjouosttsetdrfaopra1n0a-lyyesairs awgaesidnotnerevatlos,caglecnudleart,e amnedanthesierriunmtePraFcOtiSonvatleuremss.foMruelatcihva6riable regression analyses. A reliability assessment was also done for the chemical analyses. fTlhueosroecohmeemtirciaclmveaalunesda<taLwLeOreQctahlecumliadtpeodiunntdbeerttwheeeansszeurmoptainodntthheatLfLoOr Qindwiavsidausasligsneerdu.m However. PFOA had a lot of subjects with LLOQs. Owterheernomteitnhcolduodleodgiincatlheiannfaolrymsaistiboenc:auSseevtehne sseurbajescatmspwleersef>r7om0 tyheearpsreolldi.minary report RESULTS "DTehsecrreisbueltrsoefsutlhtse: reliability analysis indicate that there was a strong correlation between the split samples (+= 9) for PFOA. TPhFiOsAladcikdonfoltomgeneotrtmhaelcirtiytemraiyafoberdauleotgo-ntohermgarleadtiesrtrpiebructeinontabgaeosefd sounbjtehceStshawpiitrhov-aWliulesk lteessst.than the LLOQ (1.92). "1T.9h.e sc52o.m3etprpibc. meArainthomfetPiFcOmAeoafnaslwesruebjneocttsprwoavsid4e.d.6 ppMbal(e9s5h%adC1hi4,g.h3e-r g4e.8o)m.etTrihcemreaangneswtahasn ifmepmoarlteasn[t4p9repdpibct(or9o5f%aCd1u,lt4.s6er--5u.m3f)lu.or4.o2 cphpebmi(c9a5l%coCn1c,en3t.r9a-ti4o.n5s)., respectively]. Age was not an 104 104 000003 "fTuhoergoecohmeemtirciaclmveaalunesda<taLwLeOrQe,catlhceulmaitpeodinutndbeertwtheeenaszseurmopatnidonthtehaLt LfoOrQinwdiavsidausasligsneedr.umThere w1e0r%e oqrui9te0%@offetwhsiusbrjaecntgsewbietthwePeFnOzAerLo LanOdQth(e<2L.L1OpQpb)t.heIfretshpeescetivvaelruaesngweoerfegaesosmuemtreidctmoebaens. btheecmaimdepo4i.n0t0b4e.t8wepepbn.zeTrhoeasnedvtahleue<sLwLerOeG;notthesruebfsotraen,titahlelymiddifpfoeirnetntbtehtawneetnhozseercoaalcnudlattheed using <LLOQ was used. `SaWmhpelnesstrfartiofmieCdhbarylogtetoeg,raNpChi(c6.l3ocpaptbi,onr,atnhgee:hi<ghLeLstOgQeo(m2e.t1r)~ic2m9e)aanndfotrhPe FloOwAeswtafsroinmtPhoertland (l3o.c6atpiponbwrearneg:e:Lo<sLALnOgeQle(s2,.41.)-1 p16p.b7).(<TLhLeOoQth(e2r.1P)F-O3A4.1g)e;omMientnreiacpmoleiasn/sSta.ndParual,ng4.e5 s by ppb (TSheLLcuOmQul(a1t.i9)ve~9200)%; wBoesrteonh,ig5h4stppfobr(C1h.a5rl-ot1t3.e9)(;13H.3a)g,erMsitnnoewanp,ol4i.s2/Sptp.b P(auLl L(9.O9)Q, Bo(2s.1)t-on52(.93.)7.), and Los Angeles (9.2). Hagerstown and Portland were lower (7.6 and 6.8, respectively). Tlohceatrieosnusltasdjfursotmeda bfoorot1s0t-ryaepaarnaalgyesiisn,tedrvoanles,togecnadlecru,laatnedmtehaeinrsientreurmacPtiFoOn Atervmasl,uersesfuolrtecdacihn 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 PEHS (= 32) PprFedOiActo(rnaotufrPalFOloSg),inaadjmuusltteidvafroiraabglee,mgoednedle.r,Aagned tahnedirgeinntdeerracwtieorne, nwoatssaigsniigfniicfainctanptre(dpic<to0rs00i1n) this model. Study strengths and weaknesses: Blood donors cannot be considered representativeofthe `general populationof the US. Research sponsors: 3M Medical Department, Corporate Occupational Medicine Creopnosritsetdenincyotohferressaumltpsl:esGoefoemledterrilcy mineSaenatPtlFeOaAndlecvheillsdrreenpoirntveadriinoutshilsosctautidoynsa.re similar to those CNOANCLUSIONS REFERENCE Ofllsueonr.ocGhWem,icBaulrsriisn,hJuMm,aLnunsderbae.rgI., JAKm.erHiacnasnenR,eKdJC,rMoasnsdaedlu,ltJHb,loZoodbedlo,noLrRs.. IFdiennatlifriepcoartti.on of February 25, 2002 Last updated on: 4/15/02 105 105 000004 EPIDEMIOLOGIC DATA Title: Identification of Fluorochemicals in Human Sera. Ill. Pediatric Participants in 2 Group A Streptococci Clinical Trial Investigation TEST SUBSTANCE Identity: PFOA and 6 other fluorochemicals Remarks: The results reported are final. METHOD Study design: Cross-sectional. Manufacturing/Processing/Use: N/A sHaymppolteheosfcihsitledsrteedn:toTporodveitdeermainmeortehesspeecriufmiccuonncdeenrtsrtaatnidoinnsgooffsethleecdtiestdrifbluutoirooncohfetmhiecsales in a compounds in children. Study period: Child sera samples were collected from January 1994 to March 1995. The sera samples were analyzed in Spring 1999. Setting: N/A Total population: Not reported Subject selection criteria: The sera Minnesota Department of Pediatrics. samples were provided to They were obtained from 3M by a large the University of clinical trial on Group A streptococcal infections children presented with in children. The children were residentsof23 states in signs and symptoms of acute-onset pharyngitis. Allof the the US. These children had positive throat cultures at the inital visit. Total# of subjects in study: n = 599 children, age 2-12 years Comparison population: N/A Participation rate: NA Subject description: 299 male children, 300 female children from 23 states and the District of Columbia. 106 106 00005 Health effects studied: PFOA serum levels in blood, as well as 6 other fluorochemicals. Dchartoamactoolglercatpihoyn/emleetchtordossp:raByltoaonddseemramsaasmspslpeescwterormeectorlyle(cHtPedLCus/iEnSgMhSigMhS-)pr.esSseurrae wlieqrueidfrozen at 20 degrees C prior to the request for analysis. Exposure period: N/A Description/delineationofexposure groups/categories: Blood sera samples were collected from children 2 ~ 12 years old. Measured or estimated exposure: N/A Exposure levels: N/A Swtearteisctailccaullmateetdh.odCsen:trAarlitthemnedteinccymeaanndsd,isrtarnigbeust,iogneoofmtethreidcamtaeabnysaagen,d g9e5nd%erc,onlfoicdateinocne ainndterthveailrs respective interaction terms. A reliability assessment was also done. fTuhoeraoccohmeemtirciaclmveaalunesda<taLwLeOreQctahlecumliadtpeodiunntdbeerttwheeeanszseurmoptainodntthheatLfLoOr Qindwiavsidausaslisgneerdu.m However, PFOA had a lotof subjects with LLOQs. Other methodological information: N/A RESULTS Describe results: Trahnegegewoamset<riLcLmOeQan(1o.f9)PtFoO5A6.1foprpabl.l oMfatlhee cphairltidcriepnanhtasdwsaisgn4if.i9capnptbly((9p5<%.0C11),h4i.g7he--r5g.1e)o.meTthreic mean PFOA levels than females: 5.2 ppb and 4.7 ppb, respectively. AWhgeenwaansalsiygzneidfiacsanatlcyon(tpi<nu0o5us) negatively variable in assismopclieatreedgrweistshioPnFmOodAelisn. both males and females "fTlhueorgoecohmeemtirciaclmveaalunesda<taLwLeOreQctahlecumliaptoeidnutnbdeetrwteheenazsesruompatnidotnhtehLatLfOorQinwdaisviadsusailgnseed.rumThere w1e0r%e oqrui9te0%a foeftwhsiusbrjaecntgsewbietthwePeFnOzAerLoLaOndQsth(e<L1.L9OpQpb)t.hIe fretshpeescetivvaelruaesngweoerfegaesosmuemteridctomebaens btheecmaimdepo4.i3nttb04e.t9wepepbn.7eTrhoeasnedvtahleue<sLwLeOrQe;notthesruebfsotraen,titahlelymiddipffoeirnetntbtehtawneetnhozsercoaalcnudlattheed using <LLOQ was used. 107 107 000006 P48F).OSAadnjdusPtFedOAforweagree, hgiegnhdleyr,coarnrdeltahteeidr (irnt=er7a0c)t.ionP, FPOFAOAanrdePmaFiHnSedwaerseiganlisfoiccaonrtrperleadtiecdt(orr=of PFOS in a multivariable regression modelofPFOS (p < 0001), 9In59b%ooctosntfriadpeanncaelylsiemsit, othfe1m1.e0apnpobf.thWeh9en5%antaollyezreadncbeyliamgiet,ftohrePyFouOnAgewsatsch1i0l.d1rpenpb(awgieth2 ayneaursp)per ghraoduptsh.e hAigghees4twraasngtehe(1n.e9x-t 3h4i.g2hepsptgbr)oaunpd (cruamnuglea,ti2.v0e~9056%.1vaplpube; (9107.%7 vpaplbu)eo,f1a0.n1yoppfb)t.he age Study Tevels isntrUe.Sn.gtchhsiladrnedn.weaVkenreyslsietsle: deTshcersieptdiavteaianrfeorcmraotssi-osncaatbioountalthdeatsaubujseecdtstiosdaevtaeirlambilnee. PFOA To 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 collected on PFOS serum levels in children. CONCLUSIONS NA REFERENCE Olsen, GW, Burris, JM, Lundberg, JK, Hansen, KJ, Mandel, JH, Zobel, LR. Identification of fluorochenticals in seraofchildren in the United States. Interim Report. June 25, 2001. OTHER Last updated on: 5/07/02 108 108 000007 EPIDEMIOLOGIC DATA TCihtalne:gesIdeinntTifhiocuagtihotnoSftuFdly,uoSreoacthtleem,icWaalsshiinngHtuomnan Sera. 11. Elderly Participants of the Adult TEST SUBSTANCE Identity: PFOA and 6 other fluorochemicals Remarks: The results reported are final METHOD Study design: Cross-sectional. Manufacturing/Processing/Use: N/A Hsaymppolteheosfiesldteersltyedp:erTsoondsettoerpmrionveidtehea smeorruem scpoencciefinctruantdieornssotafnsdeilnegcotfedthfeludoisrtorcihbeumtiiconalosfitnhease compounds in this age group. Study period: 9129/2000 Setting: N/A Total population: 238 serum samples from elderly adult donors from the Adult Changes in Thought study. Senurbojlelcmtenstelpehctaisoeon fcrtihtiesricao:mmDuonniotrys-wbearseed65p-ro9s6peycetairvseolcdo.hoSrutbsjteucdtys owferdeemiednetntiiafiaendddunroirnmgalan a(gHiMnOg)c.onEdluicgtiebdlecionldlaibvoirdautailvsewlyerbeetthwoeseenwtihtehUn. oofknWaoswhnihnigsttoornyaonfdneGurroouppsyHcehaialttrhiCcodoipseeraasteiovre dementia. Total #of subjects in study: 238 Comparison population: N/A Participation rate: NIA `Subject subjects description: had resided in 238 the adults--1 18 Seattle area males, 120 females. for 53.3 years, males The 50.2 mean age years. was 76 years. Female Health effects studied: PFOA serum levels in blood, as well as 6 other fluorochemicals. 109 109 000008 cDhartoamactoolglrecatpihoyn/emleetchtordossp:raByltoaonddseemramsaasmsplspeescwtreormeectorlyle(cHtPedLCus/iEnSgMhSiMghS-)p.ressure liquid Exposure period: NIA (Dens=er9i3p)t,i8o5n+1/0d9eli6neayteiaorns (onf =ex2p4o).sure groups/categories: 65-75 years (b= 121), 75+ 10 85 years Measuredorestimated exposure: NIA Exposure levels: N/A Swtearteisctailccaullamteedt.hodCse:ntrAarlittehmnedteinccymeaanndsd,irstarnigbeust,iogneoofmtethreidcamtaeabnysaagne,d g9e5nd%erc,onlfoicdateinocne ainndterthveailrs respective interaction terms. A reliability assessment was also done. Other methodological information: N/A RESULTS DTehsecrreilbieabirleistuylatsn:alysis indicated moderately strong correlation for th split samples with PFOA = "ATnhaelreyzweadsiandweepaekndceonrtrleylaotfiaogneb,etthweereenwaegreeannodsyieganrisf'icraenstiadsesnocceiaitnitohnes Sbceattwleeenaryeeaa(rrs=re0s.i2)d,ed in SceoartrtelleataenddwiPtFhOAP.HSPF(OrS= a3n6d).PFOA were highly correlated (r = 75). PFOA was less highly hPaFtOtAhiws aascknootflnoogrnmoarlmitayllmyadyisbteridbuutedtobathseedgroantethrepSehracpeinrtoag-eWiolfskutbejste. ctTshweiatuhthPoFrOs Aposvtaulluaetse< LArLiOtQh.metiTchemegaenomsewtreirce mnoetanproovfiPdeFdO. AfTohrearlalnsgaemwpaless1.4was~ 41.62.7pppbpb.(95Bo%otCs1,tr3a.p9a-na4.l5y)s.es pcornofviiddeendctehelimmietaonfo1f1.t3hep9pb5.% tolerance limit for PEOA was 9.7 ppb with un upper 95% Sletvuedlys isntrelednegrltyh.s aVnedryweliatktlneedsessecsr:iptTihveesienfdoartmaaatrieoncraobsos-ustetchteiosnuabljedcattsa uissaevdaitloadbleet.erTmhineesPubFjOecAts ochnalryaccthearriazcitnegriszeerPuFmOPAFOleAvellesvienlsthien Stehaetetlldeerrleyg.ion. 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. no 1o 000C09 CONCLUSIONS PFOA levels in these Seattle residents are similar to those found in adults and children in the us. REFERENCE Olsen. GW, Burrs, JM, LundberJgK,, Hansen, KJ, Mandel, JI, Zobel, LR. February 25, 2002. Identificationoffluorochemvicals in human Thought study, Seattle, Washington. Final sera. 11. Report. Elderly participantsofthe Adult Changes 3M Company, Medical Department. in Last updated on: 4/24/02 m nm 000020 PHARMACOKINETIC STUDY Titles The sex-related difference in perfluorooctanoate excretion in the rat TEST SUBSTANCE Identity: Perfluorooctanoic acid (PFOA); also referred to as {1-**C/Perfluorooctanoie acid (ammonium salt, APFO) Remarks: Purity was not specified METHOD Methodguideline followed: Guideline not noted Test type: Mammalian Excretion Speciesistrainfcell type or ine: Holtzman rats Sex: Male and female Age and body weight range of animals used: Not noted `Number of animals/sex/doses Tes`tCognrtoruopl:g4romupasl7esf,emafleemsa.les Routeof administration: Oral gavage Vehicle: Distilled water Doses: 2 mgof nonionic fluorine a APFO in a volume of2 mL Excretion routes, body fluids, and tissues monitored and/or sampled during study: Blood and urine Statistical methods used: See methods. M24ethhouordsraeftmearrgkasv:agAentirmeaaltsmewnetrweitphlaAcPedFOi.n inTdhievibdluaolodmewtaasboallilcowceagdetsoacnlodtsaancdriftihceesdebryumcacrodlilaecctpeudncatftuerre cIenncttraibfoulgiacticoang.esTwhaesvroelcuormdeeod.ftThheeuiroinnieccfolluloerctiidoencso,nitnecnltoudfintghethseevroulmuamnedoufriwnateerwasusdeedtteormriinnseedtahtepH e51x0t.racTthieontotteaclhnfilquuoer.ine content of the serum and urine was determined by the oxygen-bomb reverse FfoorrccolnetairnaunocuesstiundfiuessioonfoAfP$F%Omaanndniitnoulliinntihseotroatnsicwesarleinaeneasntdhetthiezefdemaonrdalthaertfeerymowraals vceainnnuwlaastecdanfnorulated dIrnatrwaivnegnobulsooddosseasmoplfesA.PTFhOe aunrdinianruylibnlawdedreerwgaivsenatlosoccaacnhnualnaitmeadl taondo.btfaoinllsoiwailnagco4ll5e-cmtiinonesqoufiluirbirnaet.ion p`eardimoidn.isbtleroeoddaannddaudrdiinteiosnaamlpclleesarwaenrceectoelsltesctweedr.e pWehrefnorcmoeldletcotitoesntstwheerceffceocmtpsoleftperdo,bpernocbiedneocnidthweaosrganic acid transport system. n n2 0000114. i{hnethaertecruimalulcaatninvuelaetxicornetwiaosn sntoutdyn,edtehde.rasThweerreatpsrweepraereddoasseddeisvcwriitbhedafmoirxhteurecloefarraadnicoel(asbtesleedxcAePptFOthaatnd unlabeled APFO. RESULTS Detailed results: T24uoHroiunres(aafsteArPaFdOmi)niisnturraitnieonanodfthheaddaosm,eafnemsaelreurmatnsoenxicorneitcefd7lu6or+ine2.l7evpeelrcoefn0t.3o5ftphpemd.oseofnonionic I17n mpalpems,n9on2i.o4ni3.5cflpueorrciennetowfasthien othsecseorfumn.onionic fluorine (as APFO) was excreted. A level of44.0 APFO was bound toa similar extent n the plasma ofmale and female rats (97.5% bound). Icnimfienmaalteiso,n AocPcFurOswbaysamnaarckteidvelyscreerdeutcoeryd mbeycphraonbiesnme,ciwdhi(cfhrio5m.in8hi1bi0ted0.1bmylp/rmoibnen1c0e0idg), indicating that a"TfheerApProFbOennceuild.i cTlheesrAaPncFeOirantuiloiwnascl1e4a.r5anfcoe rfaetmiaolwearsats0..2T2hfeoamiaosw,asanddecdreecarseeadse0d 00.406.1i2naffelmearles probenceid. CONCLUSIONS "iTshoemexaclareuestthfeordrsoimcop1n4a.5crtlub1dy0e.da0nt.ha4actatitfvhece shteihcegrheatdAimPoiFnnOim/seitcrnhauatlniioinnsomcf.lperaTrohabneecnedeerccaitrideoasisunpfipoermttahsleetAshPipsFrOcoiovnnicudleludisnieovcnil.deeaTrnahcneecetlhoavatetAroPFiOn. a'bAsPoFrOptthiaonnionfuliAnPcFleOarianncbeosthinsebxoetsh. sTehxiesssfeecrretaodrmyinmiescthraatniiosnomfisprloacbkeinnegciord iinnadcitciavteedinpamratliaelstaunbdular accounts for the greater oxictyof APFiOn male ats. eHxacnrheitjairovnii,h Hh. eRr.a.OpPhraoucge,edainndgsLo.fStihnegeSr.oci1e9t8y2.orTEhxepeserxi-mreenltaatledBdiioflfoegryenacnedinMepdeircfilnuoersoo1c7t1a:n50o-a5t5e. ns 000012 IE PHARMACOKINETIC STUDY Title: Elimination and ToxicityofPerfluorooctanoic Acid During Subchronic Administration in the Wistar Rat TEST SUBSTANCE Identity: Perfluorooctanic acid (PFOA) Remarks: Purity was not specificd METHOD Method/guideline followed: No specific guideline was listed Test type: 28-Day subchronic toxicityandelimination study `Speciesistrainfcell typeor ine: Wistar rat Sex: Female and male Age and body weight range of animals used: Newlyweaned Numberofanimals/sex/dose: 6animals/scx/dose: Routeof administration: Oral gavage Vehicle: 0.9% NaCl solution Doses: 0,3, 10,30 mgkgiday pEexrciroedt.itohnearnoiumteasl,sbwoedryefwleuiidgsh,eadnodncteisasuweesemkonaintdo2r4edhoaunrd/uorrinseawmapslecdolldcuertiedngonstsutduyd:yDduaryisng7 athneds2t8.udy Tblhoeodbeahnadvitoirssaunedsafmeepdleasndwewraetecrolcloencsteudmpftrioomncownetrreolobasnedrv3e0dmreegkulgarrlayt.s.At the endofthe study period. wStearteistthiecaplrimnectihpaoldsstautsiestdi:calSptruodceendtu'ret-steusst,dPefaorrstohne epvraolduuacttiomnomofenthtecfoirnrdeilnagtsion and Fisher's exact test Msaeltinheosdolruetimoanrskwsa:sPaFlOwAaytsrea0.5tmmeln/t|0o0cgcuarnriemdalovweerig2h8t.coPnsFeOcuAticvoe ndacyse.nTthreaiatdnmibilnooinsotsderaenddvuorliunemesoafmtphlees were analyzed bygas chromatography. RESULTS DPeFtOaiAle(dmere/s2u4lthsrsffrkog)mwDaasy 7lo:werOtnhatnhethseevdeanitlhy ddoasyeofintahlelstthurdeye gpreroiuopds,otfhemamleesa.n uArisntaartyisetixccarleltyion of Sitgenaitf.icaInnttdhiefffeermeanlceeafnriommaltsh,endoanleyofdotsheewtahsrefogurnodupisn ealxlcrtherteeedgsriognuipfsiocafnmtlaylelesrsatPs F(PO<A0.i0n5thaendurPi<n0e.o0n01. day 7 than they were administered. The mean urinary PFOA concentrationofthe female rats in the lowest ns 14 000013 dose group was significantly higher (P<0.01) than that ofthe male animals. In the group receiving the highest daily dose ofPFOA, the urinary PFOA concentration was significantlyhigher (P<0.05) in the `male animals; however, this can be explained by the significantlylower (P<0.05) mean urinary volume of the male rats. Detailed results from Day 28: By test day 28, the males seemed to have also reached the steady sate, with the exception ofthe 10 mg/kg group which showed a significantly lower (P<0,05) excretion of APtFaOcAhthdaonsethleevaedlm,itnhiestmeeraend dPaFilOyAdocsoe.ncentrations in the plasma ofthe male rats were significantly higher than those ofthe female animals (P<0,001 for the two highest dose groups and P<0.01 for the TAowdeesttaidleodsestgartiosutpi)c.al analysisoforgan weights did not reveal any differences. The weightsof th liver relative to body weights of male rat showed a significant positive dose response (P<0.001, Pearson). A p(oPs<s0i.b0l5e,ePxepalrasnoant)i;onhowwaesvetrh,e stihgendiiffifceanrtendcoeseb-ertewleaetendtdheeccroenatsreolinmtahleesboadnydwethieghltoswefsotu-nddosiengtrhoeumpalweass mInotrheeohbivgiho-udsostehagnrobueptwfeeemnalaens,yoofntehoerdmoosreed mgirlodupisnf(lP<a0m.m0a1t.ortyesfto)c.i were observed in four livers, which was not significantly different from control females with only one small chronic focus (Fisher's exact test). Metabolites measured: None CONCLUSIONS "1T0hetimmeeasnhiugrhienrartyhaenxcirnettihoenmsaulgegeasntimsatlhsa.t Tthheeasveexr-argeelarteendaldicflfeearreanncceeionfpPlaFsOmAa PinFtOhAe fceomnacleentartastiiosnasbaoruet best explained by active bular secretion in the female kidney. The steady state was achieved by 7 days inthe female animals only. By the 28" day, both males and females excreted roughly the same amount of PFOA in 24 hours as their daily dose. REFERENCE Hanijarvi, H. M. Ylinen, A. Kojo, and V. Kosma. 1987. Elimination and toxicityofperfluorooctanoic acid during subchronic administration in the Wistar rat. Pharmacology and Toxicology; 61:66-65. us 000014 ns PHARMACOKINETIC STUDY Titles A Proposed Species Difference in the Renal Excretion of Perfluorooctanoic Acid in the Beagle Dog and Rat TEST SUBSTANCE Identity: Perfluorooctanoic Acid (PFOA) Remarks: No information on supplier, lot number, or puityof substance tested was given. METHOD Methodguideline followed: NA Test ype: Invivo Speciesistrain/cell type or line: Beagle dogs Sex: male/female Age and body weight range of animals used: Not stated NGruomubper1:of6.a(n3immaalless/saenxd/d3osfee:males) given 30 mg/kg PFOA with continuous infusion of 5% mannitol GSorlouutipon2: at412.7 mmailmeisn.andPr2obfeemnaelceisd)wgaisvetnhe3n0amdgm/inkigstPeFreOdAaton3l0ymagn/dkkgepitntrinavmeentoausbloyl.ic cages. Route of administration: Intravenous Vehicle: Notstated Doses: 30 mykg- see above (under Number ofanimals/sex/dose) Excretion routes, body fluids, and tissues monitored and/or sampled during study: Group 1: urine aGnrdoubplo2o: d bslaomopdlessamples `rSetdautcisttiiocnalofmePtFhOoAdscluesaerda:ncPeaiinreedacShtuddoegntbsefto-rteestanudseadftteordaedtmeinrimsitnreatstiaotnisotficaplrosbiegnnciefiidc.ance of the ne 16 000015 Method Group 1: remarks: Dogs were anaesthetized with methoxyflurane. Catheters were fixed in both ureters after laparototomy and eystotomy. Urine was collected at 10 min intervals for 60 min. (Dosing and other `methods described above.) Group2: Dogs were kepl inmetabolic cagesaftr the injection. Hal-iveswere determfiornceacdh aPnFiOmaAl csoenpcareantterlayt.ions were analyzed witha GLC-method. RESULTS Detailed results: Probenecid effectively and statistically significantly reduced PFOA clearance in each dog (P PFOA < 0.05 for cach dog). plasma half-lives (males): 473 and 541 hours PFOA plasma half-lives (females): 202 and 305 hours Metabolites measured: None. It appears that only PFOA was measured. CONCLUSIONS Bfeecmaaluesseohfavtheeanstaacttisitviecaslecsriegtniiofnicmaenccehoafntihsem rfeodruPctFiOoAn.ofPPlFasOmAa chlaelaf-rlainvcees bwyerperolboenngeecridi,n mmaalleess tahnadn females. "PTFheOaAiutshosrismiallasro icnobmoptahrespetchieesc.leaHroawnceeverrat,esthweitachtitvheosteubinulaatrss,encorettiinogntrhaattetohfe PglFoOmAulainr tfhielsraattioanndradtoeg.of are quite different FFERENCE rHeannahliejxacrrevtiHi,o.n,oMf.peYrifliunoernoTo,.ctHanaoiacraacindaeinndntT,h.e Nevalainen. beagle dog 1988. and rat IAnp;rBoepyonseend,spAe.Cc.ieasnddifHfAer.enScoellienvtehled (Eds). NewDevelopmentisn Biosciences: Their ImplicationsforLaborAnaimtalSocirencye. Martinus NijholTPublishers. Dordrecht, Netherlands. n 000016 ig PHARMACOKINETIC STUDY "RTailse: Tissue Distribution, Metabolism, and Elimination ofPerfluorooctanoie Acid in Male and Female TEST SUBSTANCE Identity: [1"C]Perfluorooctancicacid (PFOA, 99% pure, specific activity 5.44 mCi/mmol) Remarks: Synthesized and purified accordintog methods described previously METHOD Method guideline followed: NA Test type: Invivo Speciesstrain/cell type or ine: Sprague-Dawley ats Sex: males and females `Age and"Abgoed=yswiexiwgehetkrsangeof animals used: WWeeiigghhtt ((mfaelmeasl)es=) =17103-01-91555grgarmasms `3N2ummableers oafndan1i6maflesmiasleexs/dfoosret:iss4uoeflciamcihnatsixonfoerxpiesrsiumeednitsstribution experiments: Route ofadministration: inzaperioncal Vehicle: Propylene glycolivat(e1r:1 vi) Doses: 4 mgs Eivxecrr,etbiioen, rfeocuetses(, obotdyiflsuidsa,blaen0d imsestuabeoslmizoenietnodroegdenaonuds/ofratsyamacpildesdorduwreirnegtsartguedty:tisusruiense,foprlPasFmOa,A oicity) Statistical methods used Not stated Method remarks: none 1s 000017 ns RESULTS Males: lTiivesrs,uepldaissmtari,bKuitidonne-ys,Pehrecaernttedsotsees,onfatp(eerpigdirdaymmablasfiast(pfardo),m ghaisghtersotcntemliouwsesm?u)scilne.monTihteorleidveroragnadnsplwaass:ma wademrienitshteraptriiomna.]ryTthisesuhcisgohfcdoinsctreinbturtaitoino.n i[nSleieveTrawbales e1xoaftmhineesdtufduyrtfhoerr pinermceantlabgeyesasnbyitnimseitafter nsionngrleecipracsusl"ating liver perfusion technique 11%of the PFOA infused was extracted by the liver in a Eurliinmeiannadtfieoc--nesUarfienre2a8nddafyescewsawser3e6.b4ot%hamnadj3o5r.r1ou%treesospfecetliivmeilnya.tioTnh.e aCpupmaurleanttihvaelexfcreetfioornowhfoPleF-OboAdyin eliminationof PFOA was 15days (360 hours). Halflives Organ Liver KiPldansemya Heart Gastrocnemius Fat BTleostoids Hmrs2 D1a3ys 221566 9940 296 104 208 92 192 80 22162 8980 Females: pTliasssmuae. diksitdrniebyust,iolniver,Poevracreienst.doTsheeolnivaerp,eprlgarsamam,baasnidsK(ifdrnoemyshiwgehreesttthoe lporwiemsatr)yiin smsouneistoofrdeidstorrigbautnisonw.as: [See Tabl2eofthe study for percentages by time after administation.] dEalyimwiansat9i1o%n,- wUhreirneewasasthethaemmoaujnotrirnoufteeceosfewlaismniengaltiigoinb.le.CumTuhleaatpipvaereenxtcrheatlifo-nloiffe fPoFrOwAholine-ubroidneyaftr | eliminationof PFOA was < | day. Halfives Organ Hrs PlLaivsemr a 3289 Kidney 32 Blood 3% Mmeettaabboolliizteeds. mSepaescuifriecd:metDaebfolluiotreisnwateiroennooftPdiFsOcuAssweda.s measured to determine whetheirtwas ne 000018 19 CONCLUSIONS slfieemmiaxnlaedcilofinfmehrailetneividnesIu.rsisnHatorhywaencvl1ei%rm.iontathtehorenoPwfFaPOFnsoOdAaoppswaarbseynottbisdseirfoviuerdte,.nceesSueinlcoibnnildgi,airinydeeixrfcereeettnietonwpheorbsloiest-thbenomcdeeyosr and ccPooFmmOppAoouuinnnddmaaelxpecprereaatrtessdwtioansbreniotthnedaounncdly0btigesrehatsetofroarcgmeaatffiodorinoomffeorefPnPFt,FaOOlArAtpiebidotfchomnesjuotgaxateabs wfTeohrlimrda4,tittohneebopanrlsyeyent was not r1e9s92p.onsniobtliengfothr sepxosdsiifbrleenicneks.be(tTwheenauttehsotrosstaelrsoonediasncdushsitbhituinopnuobfliPsFhOeAd.reesxuclrtsetoifoVnasnden Heuvel eo FERENCE dVmeaytnadsbeoonlinHsemu.vealn,d Jc.lP.imiKnuastliiokniso,fpBe.r1.f,luVoarnocRatfaenlogihceamc,idM.iLn.maalned aPnetdeorsomn,eREr.ts.1991B.ioTcihsesmu.e dTisiiebuntion, 10 000019 wn PHARMACOKINETIC STUDY Title: Renal Excretion of Perfluorooctanoic Acid in Male Rats: Inhibitory EffectofTestosterone TESTSUBSTANCE Identity: [CJ-Perfluorooctanoic acid (PFOA, 99% pure, specifi activity 5.44 mCimmol) Remarks: Synthesized according to methods described previously METHOD Method/guidelinefollowed: NA Test type: Invivo Speciesistrain/cell type or line: Sprague-Dawley rats Sex: males and females AAggee=asnidxbwoedeyksweight range of animals used: `WWeeiigghhtt (males)= 170-195 grams (females)= 130-155 grams Number ofanimals/sex/dose: 4/sex/dose Route of administration: intraperitoncally (ip) Vehicle: Propylene glycol/wate(1r:1 vv) Doses: 4 m/ke implantation) (administered as [1"'CIPFOA one week after vehicle, 1 Tbeta-cstradioolr, testosterone. UErxicnree,tipolnasrmoau,tefesc,esb,odliyvefrlutiidss,e,ankdidtniesysuteisssmuoenitored and/or sampled during study: Statistical of variance methods used: Differences (ANOVA). Duncan's test between treatment groups were determined was performed to compare individual mean by one-way analysis values when ANOVA showed differences. (Levelofsignificance tested was p<0.05.) 121 000020 121 cMaesttrhaotedd,roevmaarrikesc:tomTiozetde,stodrifsfhearmenocpeesriantecdl;imeisntartoigoennoofrPtFesOtoAstbeerotnweeewnasmaaldemisniasntderfeedm,ales, ras were iEnsctirsoigoennp(oasste|rTiboertao-ctshterasdciaoplu)lacca)p.suleswere inserted subeutancously into castrated males (through an T(tehsrtoousgtheraonneinccaipssiuolnesmawdeerepoisntseerritoerdtsoubtchuetsacnaepouluascl)y. in castrated males or ovariectomized females Girmpoluapnstoefdswhiatmh-topienrgatoendlymaanledssaenrdvefdemaaslceso,ntcraosltraftoerdthmealiemsp,laanntdatoivoanriperoccteodmuirzee,d females were IPnFOcaAs.tra7tehdoumraslaeftraetrs,PpFrOobAenaedcmiidnwiasstardamtiinroisant,serweedre(aatn6a5esmtghe/tkigzeidp.w)it3h0mNiemnbpurtiaolrt(o50admmgin/iksetriapt)i.on of RESULTS Males: Tis(su%eDPoFsOeA"CC-oPncFeOnAtrRa)t*i*ons* [Tv TKideye Thr am] [castratedivehicle [0.112003 [castrated 1Toeta-cstradiol |0.02 + 0.001 0.087003 0.020.004 0.0+00.0602 t"rSeiagtnmifeinctagntroduipfsfe(rsehnacneys/vienhiicvleer,,caksitdrnaetye,davnedhipcllaes,mcaasctornacteendt!|raPthieotna-seosftrPadFioOlA, cwaesrtreaotebdsetersvteodstaemroonneg).. In lciavsetrraanteddkeisdtnoesytse,roPnFeOgrAoucpo.nceInntprlaatsimoan,wPasFOhiAghweastsihnigthheessth(aamnvdeshiimcilleargirnocuopn,caenntdr2atnidonh)igihnestthein the csahsatmr/avteehdicTloeetaan-desctarsatdriaotledg/rtoeustposstweerroenevgerroyuplso.w. Plasma PFOA concentrations in castrated/vehicle and #* Source: Table 1,pg. 33 Urinary Elimipation c`asshtarma/tveedh/ivcelheicle >1 time greater than castrated Tocta-cstradiol | s=ha| mtsiemheigcrleaeter than Castrtedtestosterone ssihmaiml/avrehoischlae nvehicle pFeecraclenetxcofretPiFonO:A dThoissewaclsimeisnsatetdhainn fuercineasryoevxecrr4etdiaoyn,s wRaesgasridmilleasrsoinfsrheaant/vmeehnitclger,ocuap,strtahteecdumvuelhaitclieve strated Theta-estradiol groups. Excretion was higher in thecastratedtestosterone group. sEhffaencvteohfiacdlmei,nbiustterreidnugcepdroPbFeOneAciedl:imiTnhaitsiohnadinncoastefrfaetcetdognrouurpisn.aryThPeFrOeAweerleimnionadtiifofneriennces in plasma concentrationsof PFOA amongtreatment groups afierprobenecid. 12 000ra1 2 HHiysatloipnaethdorloopgliect faonramlyastiisondi(dantoetstrfeovreaPlFfOorAmabtiinodninogfthoyamlailnee-sdpreocpilfeitcspirnotteheinmaallpehak2iud-ngelyo.bulin). oFFemPaFlOesA: wTeirsesuoebsceorncveendtraamtoionngs:treNaotmseingtngifriocuapnst d(isfhfaemr/evnecheisclien,liovvearr,ikcicdtnoemyi,zeadn/dvephliacsime,a concentrations 7ov0a%ricofcthomeizPeFd/OeAstodsotseeroinneu). rUirini4nnadrayyese.limFineactailone:xcrNetoiosni:gninfoisciagnntidfiifcfaenrtednicfefse:raelnlcreast;saellliemxicnraetteeddaJbeossu.t than 0.5%of the dose. Metabolites measured: None CONCLUSIONS pTrhoebseenercesiudltrsesduugcgeedstPFthOatAteelsitomsitneartoinoen pirnceatsrteratamteendtmianlhiebirtastetlhiamtinhaatdioinnocrfeaPsFeOdAPFinOAtheurmianlaer.y Also, excretion. Testosterone isa key determinantofthe sex difference in PFOA elimination i rat. Remarks: none REFERENCE VpearnfdleuonroHoecutvaenlo,icJ.aPc,idDaivnimsa,lJe.rWa.t,s:SoImnhmiebristo,ryRe.f,faencdtoPfetteersstoons,tRerEo.neJ1..992B.iocRheenma.l excretion Toxicol. of 7(1)31-36, 123 000022 123 PHARMACOKINETIC STUDY "RTaiithse: Covalent Binding of Perfluorinated Fay Acids to Proteins in the Plasma, Liver, and Testes of TEST SUBSTANCE Identity: [1-"*CJPerfluorooctanoic acid ([1-"CIPFOA) Remarks: 99% pure, specific activity = $1.7 mCifmmol METHOD Methodiguideline followed: Not specificd Test type: Invivo `Speciesistrain/eell type or line: (Indianapolis, IN) RavHarlan Sprague-Dawley, obtained from Harlan Sprague-Dawley Sex: Male Age and body weight range of animals used: Six-wecks, 170-195 grams Numberofanimals/sex/dose: Not specified Routeof administration: Intraperitoneal (ip) Vehicle: Propyleneglycol/water (1:1, viv: | mike) Doses: 9.4 umole. tEexsctresetion routes, body fluids, and tissues monitored and/or sampled during study: Liver, plasma, "`STthaetilsetaisctalsimgneitfhicoadnst duisfefde:reDnciefsfetreestncweassfursoemdtcoontcroomlpwaerree idnedtievridmuianledmebaynosnweh-ewraey analysisofvariance. analysisofvariance. indicated differences. The levelof significance for all analyses was P < 0.05. Met"hToesdt raneimmaarlkssa:nd test substances ([119-8"7C)J.PeHrefmlougorlooobcitnan(o2icx acid was synthesized crystallized, dialyzed and and puriasdfesicreibded by lyophilized), fatty acid IL. free Reich bovine et al serum Calobmupmainn,ya(nStd. alLloutiisss,ueMOc)u.ltuRreeamgeednitagaranddessuoplpvleenmtesnwtesrweeorbeiaoibnteadinferdofmrAolmdSriigchmaChCehmeimciaclal aCofmoupra-nbyow(lMMiillwlaiu-kQeew,atWeIr).purWiafticeartipounrisfyiscatteimonanwdasa performed by 0.25 Am filer passing distilled (Millipore Corp, water through Milford, MA). Rats controlled were room individually housed in (approximately 21C), suspended A 12-hour stainless-steel cagesin light and 12-hour dark a temperaturephotoperiod was `maintained. Food (Purina Rat Chow No. S012, Ralston Purina Co, St. Louis, MO) and water were 124 124 000023 pberfoovriedeidnaitdilatiiboinotfumthtehreoxupgehroimuetntth.e study. An acclimation period ofa least -week was allowed `Cova{l1e-nCt]bPeriflnuoodrfoioPcFntaOgnAoictoapcriodte(i[n1s-i"nCvIiPvFoOA) was administered to rats in propylene glycoliwater a(1n:e1s,thIetviz1edmwiikteh)Naetmabudtoasleo(f590.m4 gA,moi.l) iips.sAutesdweesrigenaqtueidcktliymersepmoovsetd-,trfartemeezen,claatmspewder,e.and cbsetrnootruregidfhutagtaut7pi0otnoC..1M0aB%clroTooCmdoAwlaeascnudrlepaurmtoboivnnediicinenagfowlraisg10hdlemytinehuretpmeaisrn.iendTizooenrdtenimseosevudeelehaoanmnyodgupennlbaaotsuemnsad,wpwaehsrifselehupoararirantaeeidedby uacsiidn,gs3ammpLloesfwcehrye awcaesthaeted.wWitahsh3imngLowfasmceotnhtainnouledt,hiefrne(c3e1s)sa6ryt,imuenstilanndo tahdednit3iomnoalrePtFiOmAesdpreortieviendp"reCcicpoiutlatdebaenedxtprlaaccteeddifanromshtahkeipnrgotweaitn.erObnaethmoilvleirlnitiegrhtofat| 3N7NCatOoHsowluabsilaidzdeetdhetoprtohteein wpsrcaeiscnitppiiletlraatfteio.ornmTechodeuansctcianomgrp.dlwiehnigwla(es0aOtn.hoHet.nhenLreouatwlrriaqyluioczttedwalaws(i1t9uh5s1e|)d.MfPoarFcpOcrAtoi-tcdeaeicnriaidnvaaelndydsrias|d.imoTLahctweiavpsirtouytseieindnfalaolnraslalymisqpiulsieds wwaistahquaPnatciktaarteddDuPsiMng 1a-2P-a3cksoafrtdwLairqeupirdogSrcianmt.ilRlaatdiioonacAtniavliytzyeirn whiytdhroqluyesnactehscworarsecdteitoenrpmeirnfeodrimned Hionic-Fluor scintillation cockiail. Binding was expressed as pmol PFOA equiv/mg protein. `Cova"lCe-ntlabbeliednPodFfOiPAFnwOagAs atoddheedmoogltoubbiens caonndtaailnbiunmgianlibnumviitnroor hemoglobin in 1.0 mLof phosphate abudfdfeedritno g1 imvLaeo2f,p4h,o8s,phoart1e0b0ufAfMers0olubtriionn.g tIhfemeretahcitoinoinnmeioxrtucryestuipnteow2ermeL.prAelslente,xptehreiymewnetrse. wPreorteeidnonweasusprienciagpiftiantaeldvwoiltuhm1e0o%f bTuCfAf.erToof2remmLo.vTehaenytifmreeeofunibnocuubnadtipoenrfwuaosri|nhatoeudr aatci3d7,C. spaumnplaets2w5e0r0reewvaolsuhteidonwsitmhin5utmeLfofoarcemtionnuete5staimfeesr. eSaacmhpalceestowneerweavsohrtsetxeep.dTfohre|acmeitnounteewaansd wtraasnscfoenrtreidnuoeffd.ifPrnoetceeisnssaarympulnetislwneoreadtdhietniownaalshPeFdOwAit(hasdmeit.eorfmientehdeb2ry aldidqiutidiosncailnttiilmleasti,onWashing c1oNuntNiangO)Hcoatul3d7beC eixntaraschtaekdifnrgowmatteher pbraottheionv.erTnhigehtp.rotBeiinndpinogwdwearsweaxsprheysdsreodlayszepdmowlithPF|OmAL of <auivimg of protein. Sele"cTthieonloivfert,arpgleatsmtais,sauensdftoerstthsewaenraelysseilsecotfePdFaOsAa-rbgientditinsgsuteos pfroorttehiensanalysisof PFOA-binding to oprrottheeiynsarbeectaaurgseettohregyanasrefiorthpeerrfmlauojroirntaitsesdueascoidftdoixsitcriitbyut(iloinverfoarnPdFtOesAts)i.n rats Iver and plasma) RESULTS Deta`iCloevdalreenstulbtisn:dingofPFOA to target tissues in ats wTehreecpoovaolleendtbbeicnaduisnegndoattaifmoer-dPeFpeOnAdefnotr ccahcahngteisssiuneh(2ehaobusro,lu1tdeaay,nadnredla4tidvaeycsonacfetnetrtarteiaotnmsenotf) ctoivsaleen1tl=y b9oduanyds)prsohteoiwnewdetrheatobtsheerrveewd.asTlheetidsisfufeecrleinmcienaintitoinsshuaelc-oinfceenftorraPtiFoOnsAof(PavFerOagAe.in the rangeof 2 hours 10-4 days. In PFOA-trated rats, the absolute concentrationof covalently bound 125 000024 123 hPaFdOtAhewhaisghseisgtnirfeilcaatnitvleychoingcheenrtrianttihoen polfaPsFmOaA-thdaenriinvetdherlaidviero.acOtFivithtey ctoisvsauleesntelxyambionuendd,ttoheprtoetsetiens. wHAhopimpcrohogxepinrmioaztteeeidlnsyanw0de.r4seu%bomjofedtcithfeeidettdeosftSoeDsllSPo-FwPiOnAAgGiEcnoanvucitevonortraaaddtmiiioongnirsawtparhasyticwooinvtaohlfefnPltuFloyOrAobg,oruatnpidhs.ys.ueTsoDwudecertet.eortmhienesmall ademtoeucntteod fwchoevnal5e0nt4lyprbootuenidn w"aCsfsoeupnadrawtietdhionntShDesSe-tPisAsuGeEs,annodrtahdeioXa-crtaiyvefpiriotweiansbaenxdpossewderoe the gel for up 10 2 months at 70C. CovalTehnetcobvianldeinntgobfinPdiFnOgoAftPo FheOmAogtloohbeimnoagnldobailnbuwmaisndiinmviintirsohed by the additionofcysteine with no effctofmethionine in parallel incubations. Metabolites measured: [1-'C)Perfluorooctanoic acid CONCLUSIONS bDiensdpsitteo tphreotmeeitnasbionlitcheinpclratsnems,solfitvehr,eapnedrftleusotreisniantaecdovfaatlyeanctidmsa,ntnheer.resAulltthsoiungdhicPatFeOdA-thdaetrPiFveOdA rthaediaoamcotuinvittoyfcroaudlidoabcetifvoiutyndascsoovcailaetnetdlywiatshsoacniyatgedivweinthprportoetieniwnafsolnlootwicnngoutghehotrogabneisceeexntractions, ffoolllloowwiinngg SthDeSa-ddPiAtiGoEnoafutcoyrsatdeiiongeratpohtyh.e Tinhceubiantivointr,obcuotvnaloetntthebiandddiintgioonof fPFmOetAhiwoansinreedtuoctehde tihnactubpartoitoeni.nTshuulsfh,ytdhreylabgirloituyposfmcayystbeienientvoolivnehdib;istuPlfFhOydAryclovgarloeunptsmbianydibneg otfheprsiotteesionfs scuogvgaelsetnted attachment of PFOA. REFERENCE aVcainddsetno pHreoutveeiln,s1i.nP.t,heKupsllaiskmias,, Bl.iLv,eraannddPteetsetressoonf,rRa.sE..Ch19e92m.-BCioolv.alIennetrabcitn,din2g:o3f17p.e3r2f8l.uorinated fatty 126 000025 126 PHARMACOKINETIC STUDY ATimtmleo:nCihuolmes['t"yCrJaPmeirnfelu-oErnohoacntcaenodaFteecoarlPEoltiamsisniatuimon[o`CflPCearrflbuoorn1o-4ocitnanReasiuslaffotnearteAdministration of TEST SUBSTANCE Identity: Ammonium['"Clperfluorooctanoate (["CJ-APFO) Remarks: (/*CJ-APFO: specific activity= 0.51 uClimg, radiochemical purity >98% METHOD Methodguideline followed: NA Test type: in vivo Species/strainfeell type or line: rat, Charles River CD. Sex: male Age and body weight range of animals used: 12 weeks, 300 - 342 grams. Nuofmanimb als/e sexidr ose: 5 Routeof administration: intravenous Vehicle: 0.9% NaCl mDoesaens,:anSiimnagllse dnootsetsrawteerdewaidtmhincihsotleersetdyraasmfionlel~ows:13.5anmigm/alksgtmreeaatned(cwointthroclhoglreosutpy)ramine =13.3 mg/kg. Eplxacsrmeat,iornedrobultoeosd,cbeolld,yafnlduidlsiv,eranwderteismsouneistmoorneidtaonrde/dorasnadm/polresdadmuprliendg dthueristnugdys.tudy: Urine, feces. u`Ssteadtisttoiccavlalmueattheosdigsniufsiecda:nceDoaftadiwfefreereenxcperebsestewdeeans tmweoangsro&upsstaantdaarsdidgenviifaitciaonncse.lTevheel sotufpde<nt0'.s05-.est was aMceetshsod0rweamtaerrkfso:r 2R4athsouwresrperihoorus10edaidminiinsdtivriadtuiaolnosfttaihnelesess-tstseueblstmaentcaeb.olCiasrmbocnaygle-slaabnedlefdas[t"edCwJiAtPhFfOree pwraespaorbetdaibnyeddifsrsoomlv3iMn.g tChheotleesstsyurbasmtiannecewains0o.b9t%aiNneadClfr(otmheM[e'aCdJJAoPhFnsOons.oluTthieodnocsoinntgaisnoeldut2i.1onmsgw/emr). Cholestyramine (dried and ground resin Z-620) was mixed, 4% by weight, with Purina Lab Chow. The rthaedidoo-sfianbeglseodltuetsitosnuwbastsaandcmeiwniassteardemdintiosteearcehdoaf a10sriantsg.leFiivnetrraavtesnwoeusrdeogsieve(nla4te%ralchtoaillevsetiyn)r.amTinweoinmLfeeodf (raaddiloimbeittruimc;retshueltosthoenrarnatsabwseorleutgeibvaesnisn,otrhmealradPiuor-ilnaabeLlaebd Cdhooswe.s wIenroerndoetr atodjaulsltoewdfaorcionmdpiavriidsuoanlobfodthye waeniigmhatlss.) aTnhde a1v3e.5ramgge/dkogse(scoanstraodlmainniimsatlesr)e.dUtroienaecahngdrofeucpeswesraemp1l3e.s3 wmaer/ekeco(lclhcoelteesdtaytraimntienrev-atlrsefaotred individual rats 14 days after administration ofthe test substance. At thi time, the ais were anesthetized 127 7 000026 wsrs esEson anoremEeormmmeiepmcdo emm roftsofpnatolfrGa1bsr1cfd4ad,nwschlirioineced44ddh.ie0a Te Red Blood CE RL Cells After a Single Intravenous Dose of ["CJAPFO so Er eens Remarks:Thor concussed edi wince 128 000027 PHARMACOKINETIC STUDY Title: Metabolic Handling of Perfluorooctanoic Acid in Rats TEST SUBSTANCE Identity: Perfluorooctanoic Acid (PFOA) Remarks: Mining and PMearnfulfuaocrotoucrtianngoiCcoamcpiadn(ya,mSitx. tuParueol,fMliNncaSrS1a0n1d. bIrtsanpcurhietdy iwsaosmenrost) iwnadiscastuepdp.lied by Minnesota METHOD Method/guideline followed: Not specified HTeusmtatnypsee:ruFmleuionrivdietrdoeterminations and ultrafilration studies were uilized--Rat in vivo and in vitro: Speciesistrain/cell type or line: Holtzman rat; Human serum Sex: Rat-female; Human-not specified Angotespaencdifibeod:dyHwuemiagnhtsrcarnumg-eoagfeaannidmawlesiguhsteodf: sRoautrscewweaisghneodtssppperciofxiiemdately 250 grams, ageofrats was Nscurmubme-trwoofalainqiumoatlss;/Hseuxm/adnoses:eruFml-utohrricdee adleitqeuromtsination--not specified; Ulrafiltration studies--Rats Routeof administration: Rats were dosed via stomach intubation Vehicle: Rats were dosed with an aqueous solutionofperfluorooctanoic acid wDeosrees:fedRaatlsowwefrleuodroisdeed(<w0i.t5h p2pmmg) dnioctn;ioHniucmaflnuosreirnuema-s0,pe7rf,luoorro1o5c0t0anuogicnoanciido;niacddfiltuioornianlely(,asfour rats perfluorooctanoic acid) uErxicnre,etainodn freocuetsesw,erbeodaynafllyuziedds,faorndfltuiosrsiudeesdemtoenrimtionraetidonasnda/nodruslatrmapfilletrdatdiounrisntugdisetsu;dyH:umRaant--sseerruumm, was a`Sntaaltiyszteicdalfomreutlthroadfislturasteido:n studies Means were statistically comparedby calculating Student's t-value. A P-value OF <0.025 was chosen as indicating significance. Method remarks: `Fnlounoiroindiecdeftlueorrmiinne.ataisopnesr--fRluaoirsoowctearneoiacdmaicniid,sbteyrsetdo2mamcihoifantnubaatqiuoeno.uTshesoalnuitmiaonlscownetraienpinlgac2edmign of 2i4n,diovrid5u2a.l5mheotuarsb.oliInc acdadgietsioann,dfofuerd rraattscwheorwe (pPluarcienda)inamnedtatabpowlaictecrag(e1sppamndffeld ua looarwdfilludiobreiitdu)em(<f0or.54p.p5m8,.) d`ciotntaenntdodfitshtiellfeedcwesataenrdffoarcailpiteartieoddothfe9a6nalhyousriss. foTrhinsonrieasnuilctefdluinorainseu.bsAtafnteiwalcrdyesctralesaosfe tinhyfmonoilc wfleuroeriaddeded 129 129 000028 cctaoxrtpdhrieaicrmiepnnuetnclctopear.iodnTh,retshblorioidniweatasnbdaalcfltoecwreidsw0gerroclvootthaldnudreitnhegnstdehertuchmoelwlneacestsitcoonlplesroeiioddd.saAentslhaewecnedsmosf haee fmcetby Sbctaaogsreeesld,inafenaddazthea,euTwnhiieghvntosloyuafmsehdse.offUercwienisenw,eecorrllc,eoirod3nnesdd,.fwchAiccshwailincklsundosewdonwvqasurnacnnetoeodfmeddiatsidleodd enmtsttiddteo hofeneciecfscwueaossrisdademetpralmeip,nHwedi5 ctwhiptwHhe5rt.0hhwnlitohhrtodmhsoagfeonrni-zesepdcli0ci3icirsolcdecketoadSteu.smyTo. eTahfenoiseoofMtraeavnid awneste emHremea msop.oy "xpTreharcctioaorlncfaeuocirhdinnaie1e6c.o0ntFCein(lthtooefnsrmeilu.do,feiuinnsep,refaldnudarwcoaetoecsranwwoaatssedaaecdeirddmsi1n0neohdtekwxidhyaeneineobrdsgesrpbteoese ccaosnntnon opSfortlahlmosofamwlpelienrspa)arp0ei3rdp6uwl5epraeTnpdoifrpddedrwaoipt.htoUutpthde0ip0e.nl3gemnalt.nhdoefprouxiymgeenodfborpimrn.ieoLsfaorpcgoiorvttoeir.tesrHsp.h10r6 .3a-soptmyoaf SOrericioogvnehrRyemssoeaadmripclhfe,isInfwcoe)rtwtsahcsaaandidyersdoooutfgthhheeohfxeeyegnseinmebhoptrmo1pc5hrmeoL.0oftnogl snoinicasroefnp1inm acotfsL muresPo(nrttoet. cpUaeliiflauifobtraaoitooitnoanwnsiotluehdiamecisdx--)tTuwharese paodfido9e5fd%ttwosoiosn9ae0-dsmiLq5.5u4oaltciqaaurnodtbso1o5dfi0o0hxiuudmgea.wnaSsseeavrduedmnedwtyfso.hafetoaefcodmno.ni7Ae.e4srbyo3rovie (1ss ncwliLrdaoffainledhaethiesopnirkueemndaiisniieinugdswwuiatsrhrcmoDanivatefadliXfnoMrpSdee0raamrremomibonracaianonene.oifwehtcceihnrteatsasiners mnmolciecioulmretsaeo5ad0on.p0oe0r0oaroconTm.eerTeoc Sl(dafomispelldeiTcosheatmhwbaesorcwrlalseetfolddu.esihAerdmniwlintahieo9ni5%dtiy,w)a5s%4i.3chaoorbuporrnehpdairroeddreo,empirepnsosoultreiedse3sd.cwriumtofnoitisseoanset,deafPdooo1t5nyorre piecrlhuo9r0o0octaonficoamcidnbiy sMtaormaicnhhiandtubbaetcionadadneddom 75 mL of ulered (4174) ene come RESULTS [r-- 7pEem8pu0loo:ryoio1nc0gtStahEneMooYcx%ycgwieadnswbaaobsmabcirnreedavesorersdepe0rxf9tur4arco+toioc1ni.a5en%cohwiihcqenuaceid1,5fomrThieetorrfmeTicInovSaetAriRyoonbfuofTftfaetrrleiunrrdionmeof,watreerc,owvearsy uSdiusvbdiidraiasncgitnbhgy ftchoietreoirndie8c0rTaourpo5rii4nds%iedfeTtohhem botaxhnygkotelaonlbTotmohbr.piTrnhodeecqeueramniteinmtepyldoofFyinenogniaocnh0iicn.gM7io4rhieTnohvwsyagssoacnpboe omaiattradllt adnedte1m3inmel tohfroetdailsiflulerdidweatceornate3ntorfihde efercaesphwaasd0.b1l3a.n0k.o0f20.040u.g3. 0T.h053mopdgi.fied provers wee TiSonhlautbrileosenulbt1suTeahrbeeaidcnoaentdtpoilin pt7he4erwpilrmovevaniidtledrtvwoihnidscuehdnpyehoTftutohhreeobowicndaiinncrgioafatpiieodnrfwmlaueeraodomdcetedan1ib0coauancsdidtyoion srelrcuemsare given pleirunorsoooluctiiaonnowiaessclia.FVeiasbuallely.alToeftahdedihioonioonfipeMrofuroircoc(taanpeelremcerdootcoshnoorme sseokm)iamsndaoctuhmes 130 000029 130 wnraohtnisic4oh.n5ieclheofvulaurtoeardfintteehebtehnieonnagidombnioinucinsfdtlrutaootrisioneneruotfmoalceo2vn-eslmtsietausdeonhstiesghoafnadsno1nno6itopnbpiemci,nfgrleuuslourlratifelndtaeeis,rnaapbtelerl.leTausStoer9rou9oem%tohanafortivhceesatcaeidddd,fehrdaodm a `slenevorenulismonwaiecnrdfelnu0oo.tr0iu3nle2ralafenvldeilr0a.ibn0l7eex.pcpePmsr,sioorfre1stpo3eictnpitpvuebmlayta.inodWnoivtfhipienrr4ft.u5auolrhalooooulcrfsttlahaniyfostiewrcatashceibdao,dumtnihndeitsiootnrciaoctmiaponnoodnfennotnthiseoninicthfeluorine (Pp2eP0r)0t.-lfuooTlrhdoe)ocintnoanntihooeincniocancifidlo,unoitrchienfelnuolonerivieonlneiiclnevftelhlueosirnicnrtehueminSdetehrceurmse,casrteuhdemitrooons1ie.c2 1fa0lnu1od3r.i6d0ep.3pl5me.vp elDreasep pmtiatienhem otdhuervsleraaygnedloi2wn4c(rhe0ao.su0er3.s, rhsteoasutpriessc.ttiitcvahelellyym.ediaTfnhfeelreelvneetvleflorfoobmnsotenhriavotenodifcattfhl2eu4ourhnioddueorsisendwtahaesnissmetailrlsu.ampThpharrdooxduiegmcahrtoeeualtsyetdsheetvoeen0nt.i0tr8iem9pe6psmht,hoeuarbsva,asletulheeintfehoanltievcwealf,lsuBonryoitd9e:6 level ofthe serum remained very low. "Table 1. Fluoride Content of Sertuhem,AdSdeirtuiomnUolftrPaefrlfrlautoerso,oactnadnoBiucffAecriedd"Isotonic Saline Before and After `Specimen p [ Ulmfiiai| e Bullered Saline | Perfiuorooctanoic aci[d Tonic (oH 7.4) added | To2u1l | ionic | Toul | [AllgAulioquott t"T| NPeerwfluorooctanoie aTcid0014 | ooa 0080 added Paedrdlelduarooctanoic acid | 001% 63 0025 0.086 "Fluoride co2ntents TCommlenn we[reExrpeeporritmeednatsalpspemruanmd 1002 [ on | ~ 1wer0e 0the1me3an_of|t_wo 1de3te2rmin|ations0, 016 T |_0.03 | ""PPoooolleedd sseerruumm ffrroommrantosr4m.a5l rhao.urs afcr administration oaf 2-mg doseofnonionic fluorine as perfluorooctanoie acid. TnohneiuorniincefwlauosriannealfyrzoemdthfeorsneornuiomnithcearnedsuilotnsiacrfelsuohroiwnensiinnTceatbhlee2i.nAvlitvohoduagtahsthheouwrienade frrapoimdtrheemuonvdaolsoefd a7n4i9mjalgsorco3nt7a%inoefdtnhoe dfeltueocrtinaeblienntohneiaodnmiicnfilsutoerriende,wdoistehiwna4s.5rehcoouvresreadfeinrtrheeceuirivnien.g Tthheedqousaen,tiatnyaovferage of naodniboeniecn felxucorreitneediinnththeeuurriinnee.inBcertewaseeedn12046a1%o9nf6hthodeuradsomifntihseteerxepdedroismeenattal pheoruirosd.antdhebqyua2n4tihtoyurosf76% `innocnrieoansiecd fflruoormin0ejfgo/uhnodurininthteheuruinndeoisnecdreaansiemdatlos t9o%.16Thseg/rahtoeuorfe,xc4.5rheotuirosnoafftenrorneicoeniivcinfglutohreindeostehuosf pinetrefrlvuaolroforcotman5o2i.e5 atcoid9. 6Thhouersr.ateTohfe nroantioonfiecxcflrueotriionne oefxcfroetniofnluroarpiiddelyndetchereuarsiende tfoortpheghuonudorsoevdearntihmeals, bsfaaotswieasdrtidocanalnlayi2ng4cr-reheaaotsueerrdtuhriaoinnnietchcafotllulooeftrcithdieoene,nxocwnraedstoisfoeonduniandnit(mh0aebldse.os1e.7d3aynigmaFlrhso,uri.oniAcltfhlouourgihdetheexrcerewtaisonartteendweanscynot 131 0060030 3 ee |[ee NTaobnlieon2i. cUr(AisnaPreyrfElxucorreotoicotnanooficonAicicd)antdoNRoantisonic Fluoride Following Administrationof 2 2-mg Dose of "Time (hr) Tonic" (ugh) | Nemome hr `Accumulative % of [Basing Bs T1 T ipmse o n| | 0[0 deems| 37ie0 Bo e 523 T osesos | esos TT eee| ieea0 | eiess 76e27 18208 | Tsriz | wisar | bp"eoEixnct.retTihoen baatseeslifnoervfao1lune7awnadsnboansieodniocnfalu2o4r-ihdoeuwreurreincealcscoullelaetcietdisoans ig| excretehwdr faromrthee preced|ing ime ""TMheeanjoniSc EflMuoride excretion rate for the 96-hour period is not givensince these animals were fed low Auoride diet. nanonandin9on6ei-ffchoorfutlru1op0reiarnciecoordusencwtoevfreorereadtnheairnleytmzhaeediunrfiionnregnaonnnoidnoinfoeincciecsfolfufolruaionnriei.nmea,Tlhsfeeacpefestreccoe5ln2lt.ea5cgtaeeonddff9rt6ohemhoadudormsisendiissastnheirmoeawdlnsdioonsveTearobf5l2e.53,efAexfccierese.rt$eA2dn.i5andhtdohiuetrisfo,encaaelsm8ea1an.dn5uo%rifwnae4s.150p%o8rf6t%eh.seiBeanydtnmh9ite6nihusortuienrres,e,dwhdhooiwsceehvoefbrnr,ooutnhgiehotqnutiahcntfitlottuyaoolrfiqnuneaonwntiaiostnyrioecfcofnlvouenorireiodnneiicnextfchlreueotreidne ainndthfeecfeesces had increased to 14.3% and the entire dose ofnonionic fluorine had been excreted in the urine. aTfatebrl53e2..5Paenrdce9n6tahgoeuorfs the Administered DoseofNonionic Fluorine Recovered in the Urine and Feces [l[5i2m5e % TUr8i1n5e530 [803226 [[4Foseesi0 TTosle0s3s| Lassal"7 Tissers| Metabolites measured: lonic and nonionic fluorine CONCLUSIONS t"roTehtneuornnnuoelndtirotanofiibclaisfeelrluaibonlreeinlceeovlmeelpvseolnbeyinn5tt2sh.e5isnhctorhureusms.ewrAaulsmt,hiontuchrgeeheanspteeidrrfe2l0du0oo-srfoeoolocdftaannfooeniireoanadicmicidnfilissutorrraiapntieidolwnyaoasfbrsteohcreobdveoedsreea,dndbiunbttohuend euxrcirneetainodn ifnetcehseaufrtienre9w6ahsousri.gnNiefiictahnetrlythaeltieorneidcbfylutohreidaedmleivneilstirnattihoensoefrupemrnfolruotrhoeocrtaaenoofietaocnidc. fAlulotrhidoeu.gh epxecrrfeltueodroioncttaactnooircianc,ipdoshsaisblnyo.tabceoennjiudgeantteifdiefdorimn.the urine, the available data Suggest that it has been REFERENCE 32 000021 132 `BOipolhaMuegd,,RH16.3a:n1d9-L2.3 Singer. 1950. Metabolic HandlingofPerfuorooctanoie Acid in Rats. Proc Soc Exp 133 000032 133 PHARMACOKINETIC STUDY "ite: Stimulation by oestradiolofthe urinary excretionofperfluorooctancic acid in the male rat TEST SUBSTANCE Identity: Periluorooaccitda(nPFoOiA)c; 98%pure. Remarks: The test concentrationof25 substance mg/ml. was dissolved in a mixtureof propylene glycol-water (1:1) ata METHOD Methodiguideline followed: NA Test type: in vivo, Speciesisrain/cell type or line:rat Wistar Sex: male and female rAagnegean1d50b-1o5d0yg,weight range ofanimals used: age not specified, male bw range 170-300g, female by iNnutrmabpeerritoonfeaanliimnajlesc/tsieonxo/fdoPseF:OAD:os6efd weimthavel6himecallsee:s,6, males and 6 10 castrated females: Dosed with single males, 10 castrated males treated with oestradiol, and 10 intact males treated with oestradiol Route of administration: intraperitoneal injection Vehicle: propylene glycol-water (1:1) Doses: 50 me/ke. single injection Excretion routes, body fluids, and tissues monitored and/or sampled during study: urine, serum Sftoartuinsptiaciarledmedtathaod(dsifufseerde:nceosneb-ewtawyeeannamleyasnissooffvatrwioagnrcoeu(pdsi)fferences between groups), Student's ttest Method remarks: Rats and tap waatd leibinrum. were housed in Twenty males metabolic cages were castrated a itnhgeraogueposfo2f85.daTyhseaynwdearfetfeeSd standard rat weeks they chow were used in the test. subcutaneously Halfof the operated every sccond day for and the 1140dainytsactbemfaolreestwheerteestd. osUerdinweitwhas50c0olgl/ecktgedoiensttrhaedicoalgevsaldeurartieng sthaemp9l6eshowuerrsaeftuelrtaraislienrgeldedtoosdeeotferPmiFnOeA.thepBrlootoedinsbaimnpdliensgowefrePcFoOllAecitnedsberyucma.rdTihaec PpuFncOtAurec.ontSeentrsumof `ucrionnej,ugsaetreudmf,oarnmdsoufltrPaFfiOltAratiensuwreirnee wmeeraesusreepdarwaittehd agansd cahsrsoamyaetdogfrorapPhFy.OATchoencferneteraatniioonn.ic and passible 134 000033 134 RESULTS 5sDte%itma(ui1ll2aet6do)rroyefsetuflhfteesc:dtoosCena,tsthwrehaeturiroeinansanriydneaaxcdctmriemntaiilsoetnsroaeftxicPorFneOtoAef.docosDniualrdiyinogl+ t40h%etih(se1-tm6a)2l.4ehArofaursrsh,haoedamoesesitgrnraiadftiisocleannnteerstteedr7s2,+ bP1oF9t%Oh Aianniadnc6tur8ainn+ed 1fc4aa9ss%tterarattt2ehd4anmhailnrteeasscptewcmrtaielveealsyb)(l.50oT:heex1c3cr%aestatetraP2tF4ehdO)Am,albiuetsurnwiointtehaoisuntfiasoltesaatsrrafdaeimmoaolluernsetaostrmaoeeenfsttorreamxdaittosrl a(a6]1ted smaelreusmdoufrnitnagctthemawlhesolwatsecso(ntPsi<de0.r0a1b)l.y hAitghtheere(n17d-o4f0 hteictses)tt(h9a6nhinthhee scconrcuemnotfraottihoenrogfroPuFpeO.A in she (FPem<a0l.e0s5)anadfenrtatcrteamtmaelnets. trPeaFtOedAwmitahyPcFnhOaAnceexctrheetuerdisnleivghotlyummeoreexcurertiende.than control animals up to 72 diUelsttarenarifmoiinlntieccdatfoionnrmta.hnedOsavanemspryls9ei8ss%toafokftehnPdFuuOrrAiinnwegas1sa2mbpholauetnsedrintddooispciarntogee.dintshatiPtFheOAseirsunmotofmfeetmaabloelsizaenddainndtaicstsmecerested in Metabolites measured: none CONCLUSIONS No conclusions were given. REFERENCE eVxicirneetni.onM.p,erHfanThuiojraorovc.tHa.n,oifaackiodnianhtoh,e mJ.aalnedratP.. PPheaurrmaac1o9l8o9g.yS&tiTmuolxaitcioolnobgyy o65e:st2ra7d4i-o2l1o7fthe urinary 135 000034 135 PHARMACOKINETIC STUDY Tile Disposition of peeorooctanoie acid nthe rat afc single and subchronic administration TEST SUBSTANCE entity: Perfuoroocane acid (PFOA) fom Aldeh-Cheni: puiy was no indicted Remarks: T62h)e0per9so%ptysiNueabnCsei1asnshoccleuowtliaowsnadftiorsrsmnolitvxaeagdrasnvca(g1s:1adfmionimsvtarapteiroinoannedl administtion. METHOD Method/guideine followed: NA Test type: in vivo Speciesstraincell type or line: Wistar Sex: male and feral Age and body wight angeof animals sed: a) newl1y0wweecaknsbewdnontotspsepciefieedd Number ofanimalssexdose 4) 215 Route of administration: 3)iWnrrmaegsapveangieoncal Vehicle: 2)0.p9ro%pyNlaeCnel gshoyeonntwater 1:1) Doses: 05))3,$010m, aend 3s0inmggle/idnafeyc,uond,aivloylduomsee-s f0o.r2258mcLo/n1se0c0u;tive days lEixvcerr,etkiidonneyr,ouutens,, bSopdleyn.uiodva,ryn. desttiis,sauensdmaodniiptosoerekdoaendor sampled during study: serum, brn, nSftraaotmissttehimecaisliqmugeaatirhoionod(ssnuiaesr.drgTrshsiioonl)ogafihcal biancla.laotfiRonOshAiipnbettheweseenruimmaenadnodecronscesnsatownasoef estoesd NwMerrtehgodiedvcearnpeimataaprtikwosan:ttehTeahbnrdaaignniuwmlaaaslrswoaetmrpeclhehodowuasanedddtiahtie2hn1.Ce, Twihisetshuseacsrdwaaemkraepessraimcopdalelfdloemdpbepysnse.opd0ero7oamme.onThsey Scornocmenittroataipohnys.of PFOA inthe srum. tissues, ad id exacts were desmind sng spar gas 136 000035 - RESULTS moDateithnaelilyies1ds0uretehsseualsnteasr:luymz3,e)dbAuwttaellrivethrhi,rgekheieddrnoeisnye,mlaaenvldeslsltuihnnagntthfiesesgmuaaelvseasagle(sopst<huad0dy..0h5t)i.hgeh lTceohvneecledsnitosrtfartiPibFountOsiA.onioAnftsPhieFgnsOiefAricuwamnatan(dp < li0siv.g0en5ri)f(ip=coasnitt0ic.vo9er9r6ce)ol.rartkeiiloadntniewoyans(wafso=u0on.bd9s3ie3nr)vm,ealdsepsbl.eeetnwHeo(ewn=evteh0er.,9d9ot5sh)ee, saapnnlddeletunh,negtceos(ntric'se,=nat0nr.ad9tb5ir9os)nioonffcfPoenFmcaOelneAtsr.faotuNinoodnssiiomfitlhPaeFr OA corrslated positively with the concentration i the serum (r= 0.969, 0.971, and 0.976, respectively). h5i)gAhfetrerinimntarlaepsertihtaonneianl fienjmeaclteisond,utrhiengcotnhceenwthroalteiotness.ofPPFFOOAAwiansthmeaisnelryumdiasntdriobtuhteedr itosstuheessaesrsaa,yebdutwere PvtiF0eOr,Awa.kcikadbsno.euyat,bos1up0lt%eeo3n.f,5ta%hneodftdbohrsaeeindwotasisessfuweoasusnadlssiiolhnl atehdfe hsiiengrthuh mcoosnfecferneutmmraalotefimsoa,nlsce.so.mTpwaeIrnlevodemtaholoeausbr,osutathfet4e0Pr %FadOmiAninmilaseltveresla.stiinoAnftiohefer hosafelrtfuhlmei,fceofinovcfeerPn,tFarnOadtAikoiinnodntfeheyPldFieOecrAreoaifnseftdehmeiaslancersdudimsucrwoiennrtgeihn2ue4oufhsiarsfntadswhei1eo0nk5,whianisdnicfeasettmiianmlgaetsdeiadstni0dnbcmteaplhe6as0s,e,sr.ewshpTeichlteeivihenallymf.a-lliTevhseseit owwbeasrseerfvfoeoudun.nddtPoiFnbOtehAe2s1wp0alesh.ennoaItnsfmoaiulnnetdsh,eianitmvhoerrae(sfsleamiyanleoeafstrhe=lea7tl3iipohindasnhfirdpacmbtaeilotenwosef=etnh1te7i0mliehv)ea.r,ndInSPtihFmieOlAkairdclnoeenvyce,elnshtorafaltPivFoenOswAaosf M1e4t5ahboalnidte1s30mehasweurreedf:ounnodnfeo females and males, respectively. No conclusions were given. a4Y6fl-it5nr3e.sni.nMg.le aKnodjos.ubAc.hrHoannihcijaddrmviini,sHt.r,aatinodn.P. BPuelulertai.n o1f9E9n0.virDoisnpmoesnittiaolnoCofnptearmfilnuaotroioocnt&anaTioeviacciodloignyth44e:at 137 000036 137 EPIDEMIOLOGIC DATA Title: Mortality Among Employees ofa Perfluorooctanoic Acid Production Plant TESTSUBSTANCE entity: Perluoroctanic acd (PFOA) (cRh2ee8mm.aircbkaelsnsz:eansTeh,weealscboehsotrots)wawsereexpaolssoedusfeodPoFrOpArodduurciendgtptrohdeucptlaino.n oTfhtehewcohrekmeircasl.werMeaenxypoostehderfchtehmeisceals METHOD Study design: Retrospective cohort mortality study `MaaapnnpdluifpcraaoctctieuosnrssinPagFnOdAPc.rooncsPeusFmsOeiArngp/irsUousdseue:cdtsTashienarcseluurwdfiaanscgtnapnolta,sitnaifncoidrzmeiarsti,isolunusbcirdnictiahnetss,tlauwrdegytetoinnnugmmbeagteehrnootdsfs,uuanssdedremtuo]lmsiafniuefrasc.ture (HMyipnontehseostias)tmeasntuefd:actTuoridnegteframciilnietywwhaesthaesrsomcoiraatleidtwyitfhroomccaunpyatciaounsse]axtptohseu3rMe oCotPtFaOgAe.Grove Study period: The study population worked at the plant from Jan I, 1947 to De 31, 1983 Setting: Minnesota 3M plant that produced PFOA and other chemicals, dtToeotctaelaalwsepodor,pkouelfdawtiihnoitnch:eh C31h45e83m7miacelamelpslDoaiyvniedseis1o1np.faerm3iac9li8epsa(t3we4od8rimknaeltdhcesinsattnuhddey$C0(h2ef7me8im8caamllael)Deiosvfiastnihdoens7e4e9mfpelmoayleese)s,we1r3e39 of this SubDjeecct31s,el1e9c8t3i.on criterias All workers employed for at leas months atth plan between Jan 1, 1947 `dspeCeaoctmihpfiarcartieMssi.onnnWepsooomptuealnaatwtiesorne:orcIonwmoSpmaMreRendawnoeanrllyeyseowsit:thavUta.hiSel.abUgl.eeS.n.erpaIonlpupprlooapptuoilroatntiiobonenacladuehsaaetzhacrrdaeste.sa;naaMlniysdnensce:asloentnoadnap-roCppreuerlmiaiotdei.aonl ivision workers at the plant. rdPeeacarodtr)idcswi.aparsetosiuboltntairinangteied:nf0oS9rix91.w0o80r%%kpeoarfrsttihecemippialntdoiiyoveniddautdaluesr(,i3na3gn7dt7h3di5se4ai3tn)h.ecewrOteifrfeitcheaixstecpslouwpdeuelrdaetbioobentc,aaivvnisetadlthfseoryt9hs9a.d(5ti%invcoeofmotprhloestee Who died. Spaegurebsjaoetncndteeladterhseccwroairdpsst.iSo6nM4:afIonnrdmiavagildeuasatlaesnmdepml5po5l.y4omyfeoendtdfweuamrsailn2eg7s.t3heysetaurdsyfporermiaoldewsearnedi2d7.e6ntifyieeadrsthfroroufgehmacloesm.paMneyan Health effects studied Mortality 138 000037 138 ee oD1ba9t8ta2ai.nceaodnldlferfcotrimoomcnotmhmeeptNahanotydisopn:earlVsoiDnaenlaetlshtraIetncuodsrewdssa.fsorDobe1ta9at7ih9n-ec1ed9r8tf9irf.oicmaWtteohserwkSeohrciiesatolobrStieaecisunareindtdyforAtodhmmeirtnheiemstspralatoteiyoheenadlfatorhs1w9e4r7edepartmentsfo those employees presumedfobedeceased Exposure periods The potential exposure period was from Jan. 1, 1947 fo Dec. 31, 1983, wCDheeesrcmeriiccpoantlsiioDdnie/vrdieesdliioennxeopafottsiohened optlfoanPetxF.pOoAEs.muprleEomgypreoleuospyswe/cshatwewhgooorrknieecdvse:irnPwtoFhreOkACehdpermionidctuahcletiCDohinvewimasiiscoarnelfsotDriivacittselidoenattoort|hwmeoornktehd there forfess than | month were considered not exposed fo PFOA. mMeeaassuurreoedfmoornetshtsimoafteCdheemxipcoaslurDei:viCsiuomnuleamtpilvoeyemxepnotsure to PFOA was estimated usin the surogate Exposure levels: Not measured. Employees were considered either exposed o not exposed. Srwatetaretesiswcteailcrcaeullamavteaietldhaobaldnesd.:coSTtmhapetaiSrfeiMcddR0StfUao.nrSd.maaraldneidszeMwdienMrnoereststaorltaitatiyfwihRedaitcfioordse3a(taShtMeRrnaStc)ey,s pfaeodrrjiumosedtnse.d(1f0Fo,orr1a5wg,o,amnseednx,,20aonyndoluyrrassc)aet,aend b3eptewreieondsoexfpdousreadtioonnounfeexpmopsledoywomrek(en5rt,s s10i,nagndst2a0ifyeeadrs)S.MRCa.use-specific mortality rates were compared cnRamerlpdalitooiyvvmeaesrcniutslk,aaryneddairs9eoa5fsf%erssc,otannpfdildooetynhcmeereinsnettle.ercvtaaenldsdcwdaeuurrsaeetseiosuntsoiifnmgaptpleroofpoyordrmteeiaontnthalswhefarrzoeamraidnlclmlocudadueesldess4,(cScoAavSna)c.reira,Atgese iat tfhierst womfioadtpehrlg.ordauTphchitecaaelprpamnraoblpyerstiiwsseotefnnleesoxgpoofvsteurhsreuesprnfodopolrlotogiwo-nfuaoplltlhioamwz-eaurrpedliaamtseis.ounmsphtiiposnasndwamsodteesltsedthwaintegstserdathiefisdigmnoidfeiclasnce OAtnhoesrolmoegtihsodcooldoegdictaheldienaftohrmcearttiiofnic:ates for underlying causeofdeath for the workers according 10 ICD cDdumartpaaltoicyoonmseonftteedminpiltnohceylmuCedhenedmtiyicanartloheDfiCfvhiiressmitiosnc,maplclaoDliyevnmidesanortny,.eaagLeoefnagtftsihstotfcemcmpmplploloyoymmyeemnnettn,,tadanutdrhaaiegotnplaoatfnf,reslmtepnelgmotphylmooefynmte,natnd swpeerceifaincaclayuzseesd.to determine whether they had a effcct on numbers of deaths fom al causes and from "DTehsecorinbyeerleesvualttse;d (Faolrthaolugfhemnaotlesiegmnpilfoicyaenets),StMheRSwMasRfofroryamllphcoaupsaeiseatncdcfaonracle.caanndcewrasswbeurseeldesosntohnalny|3 dsoeitaghtnehirsf.iecmapWnltholeyyneleoeswxeoprfosttuhhraeneplesaxtnaptte.ucstewda,sbcaosnesdiodneretdh,e SUSM,Rraftoers.alflorcabuostehshoef dCehaetmhicaanld fDoirvialsliocnanwcoerrksewresraend the 139 000028 139 IU.nS.maalnedwotrhekeMrisn,ntehseotSaMdResatwherraetesc.losWehteon| lfaotremncoystanodftdhueractaiuosneosoffemdpelaothymwehnetnwceormepcaornesdidteorbodo,ththtehree wdeeartehnroateesl.evtahteedSMSMRRsf.or Wprhosetnateemcpalnocyeerefodreawtohrskeinrsthien CthheemCihceamlicDailviDsiivoinswieonrewacsom2p.a0r3e(d9t5o%MCi1nne6s3o+ta 459) The was SMR bascd for on prostate 4deaths c(a1n.c97erfexoprecwtoedr)k.ersThienrtehewaCsheamliscaaolsDtaitviisstiicoanllwyassig2n.i0f3ic(an9t5a%ssCoIci5at5io-n4.w5i9t)h. This. length o`fproepmoprltiooynmalenhtazianrdthmeoCdheelmsi,ctahle Dreilvaitsiivoenraisnkdfpororast1at-eyecaarnicnecrremaosretailniteym.plBoaysmeednotn the results of in the Chemical Division was 1.13 Chemical Division (95% C1 1.01 for 10years wthoe1n.2c7)o.mpIatroesdeto10t.h3e.3ot(h9e5r%emCp1lo1y.0e2es-1i0n.6t)hefoprlawnto,rkTerhse employed SMR for in the workers not employed in the Chemical Division was less than expected for prostate cancer (58). Study strengths: Vital status was determined for 100% of the cohort, SChteumdiycwaelaDkinveisssieosn:emTphleoryeeweass maaypohteanvteiablefeonremxipscolsaesdsitfoicPaFtOioAn.ofIenxapdodsiutrioen,beecxapuosseurmeasnwyoerfetnhoet non- mmiesacsluarsesidf;ictahteiroenfowroeucladtebgioarsietshoefeefxfepcotseusrteimwaeterse tvoewrayrbdrtohaed n(uelvl.er Wvos.rkneervesrweexrpeoasleds)o.expTohsiesdextpooostuhreer cihsekmaicmaolnsginthteheChweormkipclaalceD.iviTshieonauatnhdornsonal-sCohenomtiecatlhatDitvhiesrieoanrweodrikfefrersenacnedstihnatthtehidsicsotruilbdutcioonnfoofaungdetahte reesspuelctisaolflythfeorsftuedmya.lesThienraellwcearteegaolrsioess.maTlhlencuomhboerrtsonefeddesattohsbeinfomlalnoyweodfftohre categories many years for males and to come in order to develop an accurate picture ofthe mortality experienceofthe employeesofthis plan. Research sponsors: Corporation National Institute for Occupational Safety and Health Grant and the 3M Consistency of results: Currently there are no other mortality studies on PFOA workers. CONCLUSIONS `oAblstehrovuegdh, atnheasressouclitastimounstbebteweinetnerepmrpetleodycmaerncttulilny.theCoCnhteimniuceadl fDoilvlioswiounpaonfdtphirsossttautdeycoarncoetrhewrasstudies. with direet exposure measurements might help to confirm the association. REEERENCE Gpirloldiulacntdi.onF.pDl.anta.ndJOMaMn.del3,5(19.)5:. 915909-39.54.Mortality among employees ofa perfluorooctanoic acid OTHER "tThhriosusgthud1y99i7.thIet sheacsonnodtuypedtabteeoenfstuhbemmiotrtteadlittoyEsPtAu.dy. Another update is expected to cover the years 140 000039 140 a --------------E--E---------------- ci EPIDEMIOLOGIC DATA. Title: Mortality Studyof Workers Employed at the 3M Cottage Grove Facility Identity: Perfluoroctanoicacid (PFOA) and other fluorochemicals Remarks: 950-954. This study is an updateofthe study published by Gilliland and Mandel, Occup Med 1993, METHOD Study design: Retrospective cohort mortality study. `Mcaonmupfoaucntdusrisnign/cePr1o9c4e7.ssiAngp/rUismea:ryTphreod3uMct Cottage Grove, from this plan iMs Nampmloanntihuamspeprrfolduuocreodocptearfnlouaotrein(aAtPeFdO), a ppoetrefnltuosryonotchteatniocastuer(faPcFtOaAn)t.used in industrial applications. APFO rapidly dissociatiens biologic media to rHeylpaotetdhetsoitshetemsotretda:litTyoedxepteerrimeinnceeowfheetmhpelrooyceceuspaotfitohneal3eMxpfosaurceiitnolCPoiFtOttAagyaenGdrootvhee,rMfilnunoersoocthae,micals is wStausdfyolpleorwieodd:thTrhoueghstDuedcy.po3p1u,l1a9t9i7o.n wCourrrkeendtlayt tehmeplploaynetdfowroartkleerasstwe1 ryeeaarsssiignnceedJaDne. c1,311,94179.97Tahsetchoeihrort last date of employment. Setting: 3M plant in Cottage Grove, Minnesota that produced PFOA and other chemicals. o"Tnoetayleapro.puEliagthitoyn:per6c6e7n8towfortkheercsohwoerrtewiadesnimfaileed,. Of these workers, 3992 worked at the plant for at least ``cSouhbojretcwtasselfeoctliloonwecdrittherrioau:ghAlDlecw.or3k1,er1s99e7m.plCouyrerdenattlytheemCpoltotyaegde Gwrorokveersplwanetrefoarsastiglenaesdt 1 year. Dec 31, The 1997 as their last dateof employment. MCoormtpalairtiysroenfeproepnucleartaitosn:frIonmS7MrRegiaonnaallysceosu,ntMiiensnewseorteaalpsoopuulatsitooenrdudelaethourtatleasrgfeorvwahriiatteisonwsebraesuesdedo.n regional mortality reporting differences Participation rate: Death certificates were obtained for 97% (n = 590)of the cohort who were deceased. fSoulbljoewc-tupdewscarsip$t6i.o6n:yea8rs0,%an(dn =th3e1m8e3a)nofnuthmebeemrpolfoyyeeaerss iwnotrhkeecdohaotrttheweprlaentmawlea.s The 12.1. mean age at The number of person-years at follow-up was 108198, There were 607 deaths identified in the cohort. Health effects studied: Mortality 141 000040 141 Dyeaatraecmopllleocytmieonntmewtehroedasb:strAacrteevditeoworfecoermdptlhoeyewoerwkoerrsk'hniastmoer,y SreScNo,rd3soMfiadnenytiefmicpaltoiyoneenuwmibtehra,t dlaetaseto1f `biermthp,loaynmdendtatiensofforwmoatrikonhiasntdoryv.eriTfhyoisthceorhdoartta.wasThleinNkaetditoonarlecDoeradtshfrIondmetxhewaosrisgienaarlchceodhofrotr taoluopfdtahtee the workers. the Social DSiesccurreiptaynDcieeasthwiItnhdetx.heAorigliincaelnsceodhonrotsowleogriestrecsoodleveddtahenddedaetahtchesrtbieffiocraete1s9o79IwCeDre. verified in Exposure period: The potential exposure period was from Jan. 1, 1947 to Dec. 31, 1997. bDaessecdriopntijoonb/dheilsitnoreyatiinofnoromfateixopn.osuTrheosgerogurposu/pcsatweegroer:iesde:fiWniotrekePrFsOwAeexrpeopsluacreed(jiontbos 3wheexproescuerlel groups `pgreonbearbatlieonP,FdOryAinegx.psohsiuprpein(ogtahenrdcphaecmkiacgailndgiovifsPioFnOjAoboscwchurerreedetxhproosuugrheoutto PthFeOhiAstwoarsyopfotshseiblpelabnu)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. Exposure levels: Not measured. (1685), or not exposed (1815). Employees were considered exposed (492 workers), probably exposed SutsaitnigsttihcealPmCeLtihfoedTsa:blSetaAnndaalrydsiizseSdyMsotretmalsiotfytwRaarteiodse(vSeMloRpse)d abnydN9I5OS%Hc.onfTihdiesncperoignrtearmvaclosmwpeurteesdeargiev,ed `egsetnidmeart,eadnbdyramcuel-tsippelcyiifnigc SMRs using standard the age, gender, race, lie and table methods. calendar period Tthabeuelaxtpeedctpeedrsnounm-ybeearrosfofdefaotlhlsowaruep to tuhseedcoarsrreesfpeornednicnegdcataau.sc-specific mortality reference rates. Mortality ratesfor white Minnesotans were. Other methodological information: Deseribe exposure results: 607 group, 267 in deaths were identified the probable exposure in the cohort. 46ofthese group, and 294 in the not deaths were in exposed group. the PFOA The authors also setxrpaotisfeidedgbroyupasm.in1i8m2uwmooforne(-k1y7eedaeraretxhspso)suwreeretodePfFinOitAeliynebxoptohstehde fdoerfaitnilteealsty-1cxypeoasreadnadnd16p7r3obwaobrlkyers (219 deaths) had probable exposure for at east one year. hWihgehenrfalolreamlplloofytehees cwaeurseescoofmdpeaartehdatnotahlyezesda.teNmoonretoalfittyheraStMesR.sSwMeRrse wsetarteislteiscasltlyhasnign1iofricoanntyatslpigh=tly05 wTehreehoibgsheersvteSdM(3R.r8e3peoxrpteecdtewda)sfor bladder cancer (SMR = 1.31, 95% C1 = 0.42 - 3.05). Five deaths tAhefelwarSgMeRisntewsetrineee(SlMRe=fvo1.r6ae7)m.tpl1oefyreodemspiannctrheeadteifcinciatencPeFrO(ASMeRxp=os1u.r3e4)g,roaunp:d12frdoematphrsofstraotme ccaanncceerr of (diSeMfRro=mc1e.r30e)b.roIvnasadcduiltaiorn,diseemapsleoy(5eedseaitnhtsheobdsefeirnvietde P1F.9O4Aexepxepcotsedu;re9g5r%ouCpIw=er0e.824.-5 t6i.m0e3s).more likely to I(nStMhRe p=r2o.b7a5b.le95e2x%poCsIur=e0g.r0o7up,153.3S):MpRanwcreeraetinoctacbalnec:erc(aSncMeRro=f1t.h2e4,te9st5is%aCnId =ot0h.e4r5ma~l2e.7g0e)nitaanldorgans 142 000041 142 ombasleirgvneadn.trmesepelctaivneoo.fmtThaheesSkiMnR(fSoMRpro=st1a.4t2e,c9an5c%erC1bn=i0s.1g7ro5u.p11w)a.s 0O.n86ly 1, 6, 5a. n2cadses were oThoerreiwnearerynoorngoatnasb.leFeoxurcecasssesinweSrMeRosbsienrtvheednaonnd-eoxnpyos1e.d89grwoeupr, eexxcpeepcttefdor(c9a5n%cCe1oft0h.e5blad4d.e4r0and xc"TohhpeoroetxsceOsngsrloiyunp|p:rdoes1at0tashtedwicafasincrcuelrptodroetaettdhsirthhpaet wdteahfseisnoeitbresesxeulrptvsoiinsntehgerhofeiurpsetxwspthousdiuyr5ewacwsaetnerogtoorbaisseessrtwvreeordne mintotedhiipseruodppdudabteleeed ahPnFedOaAp.ltacsTetdhudeyh.neemHwondweltvio2enrag,rtaooulnposof,ftwehhxeiplcoersmutprhleeosgiefmeusrtpihlnearcntidetefhmiepnlegdrooytuehpeeswheserrlmeliscraaelmuampilonadendt1enmhtpahlveonysoeonsm-eeoxfeptoxhsepeordssreodbnssy rTahpeonreudmfboerpofryosetaartesctahnactetrhese employees worked a he lan andor were exposedt PFOA waco wTuohrrekbeeerxacsenwsashloymzowretedarbleaitseyempdinloocneyreuedmbrbionevjaroscobuflwyaiertahdrisdsoecffaisnpeiltneooPtyeFmdOeiAnn teemxapplotsouhyreepefsaoni.nmtohTerherdeehfeinnoifteShceeaxprosdsuberuethgroo1u0epywosaussin dd(eSfeiMnRiit~e ePx1F5p.oO0sA3u,re9ex.5po%TsuhCree1.S-MW3R.h0we2ansh436e.99e1()d.3ea5Tt%hhsCe1wte-hree13rf2u9ro.tchce3r0u.ra2e4d)lifnoreymibppyllcozouyymeeuseelsastwwiiditvthehopgsroattrehraet| (hyimc&c.soofurs of jdWoiebsiesgahostreethdhaaoncsctowrhidtighnengeyoreaalerxpspooopufsludaretefiiocnnai.tteeAgPordFyoO)s.eA.wreoexrspkpaeosrnussrweilwheir2eo73y.ne3astrismwoefhsptomonsrtueorHbeseeilrnvep1rddowibiaetbohlfeycPeeaRrscOboArfoevxepsoosnetdr hrheiepgohreltriegidhntiwneoexrmckepeslrsosyiwenietbhisaehdridughem eactxaptnohcsruDreiencjatothuber,choAhalonratbtha5emgaaenpwelhraoanll,epasonhpdouulllaadtdibdoeenrn(ocStaeIndRc.erPmF4o.Or31At,9etx5yp%owsCus1re4s tw0ie.m9re9es nu1so4e0wd6)ba.teihnTgihrmepaelnaudfneatactathsuarweeedrlaeatsrDetepcooarmtteiuerrdn.,lasMnodruoanplocolfyimteehremhpirosocdcbuuecrtneiodoncnoctruihreinshgipgirhnocdeuxecpeo19ds9u94r,e grboyu-pp.rodPucEtO.AI h1asabeeen lSSttiuumddyitshaatttrhetnheegCinhoestwiaewgreeaekGxnrepososvseesep:lcaa1nttesigodnriifeefishcauelrtem0xocporosemupraacecruceraattteehg,eorrtiehesesurlswtesroeSfimtlohdelaiffriieerasd.tncdAhMasnhecoceoungtdhhatmtehoexrpaoaustluhroers wemxiepsroceslsusursbei-fdccaiatvreiigdooenrdioeicsncthuoarPetEdw.OeAr-Wecixdtephfooiunsetedd.megarIstouusrphesodualnxddbpheeooifsidlm.tplhiaasntdinmitphelisausyetocuejuethdmegacithneeemdirceiainlatbphiellanynoonefm:pshleoyees Sietxunpdyoh.sewdo"rThkgipsrloaiucpe.i.mpNoSerctvavenrettnhcbeeelcneasdusesaeatlhtoccfcottuhilefdidgceraaettashtlswywecethraennocgoenotsahiedieearndeadal0nydspetrhfoeobrraebftlohryechwoaeuvreseehomaofdtdeiexnaptochshuterhdea1ih0aPhdeFOA Wrmeaeglralrdunisngdbceorcerbotrfhocevaarsseecfsue.lraernTchdeeirpseocpaauslteatoi(ovena.rs acTnhheermiricaelasupsorfdeidsdeeanttohticnchheaenrgpelatnt.co1dinogd),orgi1ocnaolnfmiorheayresiuletss Research sponsors: UniveofrMisnniestotya aCsontsriosntgenicnythoifs ruepdsautse:d cTohhoertx.ceOsnslyin 1prdoesattahtewacasncreeprodretaetdhnstthhaet dwaestoebseprovseduri ethgerofursptwshtiuldey wawseroet 143 000042 14 ee acosabssceugrmoveredidsi whetarhveeepmrsoaobmaiebldeexpeioxspnuoerseuhrteeogPlrFsotOupAs..tdyIT.thieHdnoifewiwecuvdletirn0aatilnitooernhporeeftpctxlhpoeossyurereeseusltfnsuttshiehncrredtegheirnoexeupotwsheurncehemical wprleearmnaetieenxmeppdolsioneydheeetsonoPfoFn-OheAxpfwosastsedsntaturdoryuepap.nordTtpehdleafcuoermdpbtrehroemsoefnyaeonacrsegrrhoautpsd,esheiemphleoyFeels wploarnkedpalohysopnesntt anor coxcLusions GaFdiodvliletoniwohnuaelpordfeeawatolhrsskoiefnrcslmuuodrieadsliinatnythuaitsrCoanoratclayhsgeiens,iGctrlosveiinnlbeoetdhssmnalicloanntluimnabuene.drhnAudlmtahtnoseu,gchothtohhretrre5 nw6ear1elemsoarssewe olthyamnom2u0e0n. hOFepivaerr,ialnad ipnatnecrreestataiec cbalnacded,er ance, prostate cancer cerebrovascular disease, cancer and orden of REFERENCE oFAfilneMaxliamnRedeseporort,ta.3.H.DivAispiroinl o2f6,E2n00v1i.roMnormtealnittayanldstOucdcyuopfwatoiroknealrsHeeamlpthl,oySecdhoaoltahfe 3PuMblCiotHteagaetGhroUvneivferct.y omer AiTnhdiitshiesoctnouahdloyrdctiof(faoesrrsopmfpeoomsmbeetdhre0s 1w9e9mr3oenmtiohnrsct)la.uldietIdyna(sdtrdu=idtyi1oi6n,9httahhethciSxhspooousnlredshrceaaqcuvigrobeersein1csyienwacerlrouedfemdexonpntoshsuepreecsitffoircsidnc.lusiItonis not lea why these employees wer nt included in he 199 study 144 000043 144 EPIDEMIOLOGIC STUDY 1"0TiPtheerflAunorEopocitdaenmoiioeloAgciicdInvestigationofReproductive Hormones in Men with Occupational Exposure Identity: Perfluorooctanoic Acid (PFOA) tRheemsiasrtkhsat:toTthailssperaupmeofrugratnhiecr euxoarmiinneesmathye boebsaesrovcatiiaotnediwniitahlyrerperpoodrutcetdivbeyhGoirllmiolnaendichnahnigsesdocintoPrFalOA production workers METHOD Shtourdmyondeessiignns:erTuwmoofcrmoasls-eseecmtpiolnoaylesstuadties,PwFiOlAzipnrgogdeuncetriaoln mfeacdiilictay.l surveillance and analysisofclever iMnavnoulfvaedcatufroiunrg-sPiraogceepsrsoicnesgs/:Usies:olaPtiFnOg Aanwdacsonpvreordtuicnegdtahtetchheempilacnatlb0y.0asnaelltescturroc,hecmoincvaelrtpironcgesthses,lwuhircyh th0eadrsyalitncgakaere,a.dyPiFnOgA.thacpaoktee,ntansdynptahcektaigcisnugr.faTchtaentgreiastuessctdikinliinhdousotdrifoal aepxppliocsautrieon0s. PFOA occurred in aHcyipnoart.heasnidsLteeysdteidg:ceSllinacdeePnoFmOaAs hianslabbeoernatsohroywannitmoarlessualntdinindcorseea-sreedlasteerduimnccrsetarsaedsioilnlheevpealtsi,cR, pOanAcrmeaatyic dsehcorweaasseidmitleasrtocsftTecrotneinsheurmumanlsovwesi,th regard t reproductive hormones,pariclary increased stradiol or Setting; PFOA production plant (presumed to be 3M plant in Cattags Grove, MN) p"Trootdaulc#tioofnswuobrjkeecrtss winersetucdyo:mm1o9n93t-o1b1o1thpcroohdourcttiyoenarsw.orkers, 1995-80 production workers. Sixty-cight Cpopmmpa1r-i<s1o0pnpgmr,ou1p0/-p<o3p0ulpaptmi.ona:ndE2m3p0lopyepems iwneorrededrivtioddedetienrtmoifnoeurfasenreufmfePctFeOxAistleevdelatctahteeghoirgiheess,t0-<1 Serum levels. Participation rate: Not specifi. Subject description: Characteristicsof subjects were not described. Health effects studied: Potential changes in: serum cortisol, dehydroepiandrosterone sulfate (DHEAS). ebtsietsnrtdaodisintogel,rloonfebo,ullltiiccnlien(-isSztHiiBmnuGgl)ahtoinrgmhoonrm(oLnHe),(FprSoHl)ac,ti1n7,a-thhyydroriodx-yspirmougleasttienrgohneorm(1o7n-eHP()T,SHf)re,eatnedstsoesxterhoonre,motontael Deiagthat.clwleiegchito,namnedtphoudlsm:onaMreydifcuancltisounr;vesiallnadnacredcobnisoicshteemdiocfala nmeddiucrailnalqyuseisstitoensntsa;irPe,FOmeAadseutreermmeinnattoiofn: and several hormone assays. 145 0coe' 4 145 Details was no uopnpedratlaimciotollfedcettieonc:tiTonheinup19p9e5r. liAmittohfedremtoescptriaoynomafsPsFsOpeActirnop1h9o9t3owmeatsry80aspspamy,wwahseruesaesd tthoere. duestiengrmainfelusoerresucmenPcFeOpAolalreivzealtsioinn 1im9m9u3naonadss1a9y9.5. RaEdlieoveinmmhuonromaosnseasyswe(rReIAa)sswayeerde. usCeordtfiosrolDwHaEsAaSs,sayed estradiol, FSH, and p1r7o-lHacPtianndwetrotealastseastyoesdteursoinneg. Farmeiecrtoepsatrotsitcelreoneenwzaysmedeitmemrumnionaesdsuasyi.ngTcSqHuilwiabsriduemtediramliysniesd. LH, using cahcrhoemmaitlougmrianpehsiccesnacmepliemmpuurniofimceattiiocn.aBssoauyn.dStHeBstGostwearsonaessweasssecdavlicaulaatredaadsitootiaml mteusntoosatesarfsotnaeeyrless free testosterone. The same assays were used for both 1993 and 1995 analyses. Exposure period: Not specified. dDievsicdreidptiinotno/fdoeulrinseeartuimonPoFfOeAxploesveulrceatgergoourpiseis:ea0te<g1orpiepsm:, F1o-r<1t0heppstmr,ati1f0ie-d<a3n0alpypse,s,aenmdp2l3o0yepepsmweinre woridtehrsteorduemtePrFmOinAe liefvaenlsefaftec1t0 epxpismteodr agtretahteehripgahretsitcispeartuedm ilnevbelost.h ySeeavrse.nty-five percentof the employees Measured or estimated exposure: N/A `Sctoaetfilsitciiceantls,meatnhdoodrsd:inaSriympmlueltainvdarsitarbalteifriecgdraensasliyosnesw,eranealuysseidsotfo evvaarliuaantceea(ssAoNcOiaVtAio)n,s Pearson between correlation PFOA and ach were hdiovrimdoende.inwtiotfhouardjsuesrtummenPtFfOorApolteevenlticaaltecgoonrfioeus:nd0i-n<g1 vparpima,ble1s-.<1F0oprpsmtr,at1if0i-e<d3a0naplpyms,esa,nedm2p3l0oypepesm in obroddeyr mtaosdsetienrdmeixne(BiMfIa)n,eaflfeccothoelxiusstee,daantdthceighairgehtteestusseerwuemreleevexlas.miFnoerdmausltbiovtahricaattecegvoarliucaaltiaonnd, PcoFnOtAi.naogues, vsaqruiaarbel,esa.ndRseqguraersesiroonotmotrdaenlssfowrmearteiofnist.tedTwhiethpoPssFiOblAe ennotnelriendeaarsaasscoocnitaitniuoonuosfevsatrriaadbiloel,usfirnege ltiensetaors,terone, and and bbyoucnodmptaesrtionsgtepraorneamweatsereveasltuiamtaetde.s,uNsoinlnigneiandridcoatsoer-raensdpocnosnetirneuloautisonvasrhiiapbslewse.reSteexpawmiisneedseblyectmioodnel it procedures were also used. Study results were analyzed using SAS. Other methodological information: No additional comments. RESULTS DPeFsOcAribmeearseusurletmse:ntTshewerarngheoigfhlsyecrourmrePlaFteOdAawmaosng0 the8068ppemmplinoy1e9e9s3 wanhdo 0pa--rt[i1c5ippatpemd iinn t1h9e95s.tudSyerum during both years. PFOA was not highly consumption, BMI, or correlated cigarettes. wiMtohstanoyfotfhteheemhploorymeoenseshaodr wPiFthOAthesefroulmlolweivneglscolveasrsitahtaesn: 1a0gep,pma.lcoIhnol 1993, only 12 approximately employees 10 ppm to had serum level>s 10 over 114 ppm. There ppm, were and only 415eimnpl1o99y5e.esHionwtehvee3r0,ptphemsePlFeOveAlsgrraonugpedin from e1i9t9h3eraonfdtohnelhyigSheinst1c9a9t5e.gorTiheesr,efoTrhee, miteiasnliakgeeloyfthatthetheemrpelwoayesensotinetnhoeughihghpeoswteerxptoosduerteecctadtiefgfoerryenwcaess itnhe dliofwfeesrtenitn fbrootmh t1h9e9o3thaenrdca1t9e9g5or(i3e3s.,3 ByMeaIrswaansds3li8g.h2tlyyeahrisg,herresipnectthievehliy)g.hesAtlPthFoOuAghcantoetgsoirgyn.ificantly 146 000045 146 Estradiol 1995. all ewmasplhoigyheleyscowrirtehlaPteFdOwAitlhevBelMsI>(130= 41, ppm p< had 001 in BMIs >129983,,aaltnhdourg=h 30, this pef<f.ec0t1wians 1n9o9t5).obsIenrved in 1993. `roups: hoEwstervaedri,olthleevdeilfsfienretnhce,e 3w0asppnomtgrstoautipstiincablolythsiygenairfiscwanetr.e T1h0e%auhtihgohresr ptohsatnulthaeteotthhaetr tPheFOstAudy may nsoctruhmavPeFbOeAenlseevneslistwiveereenloiukeglhy tboedleotwecttheanobassesrovcaibaltieoenffbeecttwleeevnelPs FsuOgAgeasntdedcsitnraadniiomlalbesctauudsieesm(e5a5suprpemd PsuFgOgeAstinthtahtetChDe hiragth).erOenstlryad3ioelmlpelvoeylseeisn tihethhisghsetsutdyexhpaodsuPrFeOcAatsegeorruymcloeuvledlsstuhgigsehsitgah.thTrheeshyolaldso. relationship between PFOA and estradiol. FnergeaetitveesatsosstoecrioanteiownasbehtiwgheleyncPorFrOelAatseedrwuimthleavgeelsinanbdotthes1to9s9t3eraonned. 19T9h5e.reTwhaeraeunthoorstsatdiisdtincoaltlyrespiogrntiaficant ttersetnodsstenrootneed, fwoarsPhFiOghAesatnidnctihtehe3r0bpopumndPoFrOfAreegrteosutpositnerboonte.h 1H9o9w3eavnedr,191975-.HPI,na1p99r5e,cuPrsFoOrAofwas stihgenaiuftichaonrtslystaasrseotchiaattethdiswiatshso1ci7a-tHiPoniwnarsegbraessesidoonnmothdeelrsosualdtjsuostfeodnfeorepmopslsoiybleeec(odnaftoaunwdeerres.notHporwoevviedre,d in the report). SHEG. There were no significant associations between PFOA and cortisol, DHEAS, FSH, LH, and Sthteudreysuslttrsoenfgtthhiss astnuddyw.eaFkinrsets,saelst:hoTuhgehrtehearree wseevreera2l sdteusdiyygneairssse(s19th9a3t asnhdou1l9d95b)e,nhoetedpowphuleantieovnasluwaetrien.g neomtplionydeepeesndwehnot.paSritxitcyi-pcaitgedhtienmtphleosyteuedsy pinar1ti9c9i5p,attehdusinrebdoutchinyegartsh.e pSoewceorndo,ftthheerestwuedyr.e 3T1hefreewewrere also vseecrtyiofneawl edemspilgonyeofesthiensctiuthdeyrdyoeeasrnwoitthalsleorwufmorPaFnOalAysliosveolfstegmrpeoatrearlithtaynof10anppams.socTiahtiirodn,.thSeicnrcoesst.he ha: laicfecoomfmPoFdaOtAioisnsteovetrhaeleyfefeacrtss, otfhePsFuOthAo.rsFsouugrgtehs,totnhlaytoitneisspaomsspilbelewatshattatkheenrefomracyacbhe hsoormmeobnieolfoogriceaalch of thtaeksetnuidnya ysehaorsr.t tIinmeorpdeerriotdo sghetoumlodrheaavcecubreaetneumseeadsuforreamecnhtspafrotricsipoamnte.oftFihnealhlyo,rmtohenrees,mapyoohlaevdebbloeoedn Some measurement errorof someof the confounding variables. Research sponsors: 3M Company Cwoornkseirssteanncdyionfcrreesausletds:estArandieoalrlainerdsdteucdryearseepdortteesdtaosntearsosnoecilaetvieolns.beHtowweeevnerto,tatl siedriufmficourlgtantoiccofmlupoarrienetihne results of this study to the previous study because serum PFOA in workers was measured in this study. CONCLUSIONS eInmptlwooycerosssw-esreectniootnaalpsptaurdeinetsiinnr1e9la9t3ioanndto1t9h9i5r,mseigansiufriecadntsehrourmmoPnFalOAchalenvgeelss aasmhoandgbteheenmparleeviporuosdluyction o`mbuscehrvleodweinr ltahbaonratthoorsye alneivmeallssr.epoHrotweedvteorc,auitssehoefufledctbseinnoltaebdortahattorPyFaOniAmaslse,rum levels in workers were REFERENCE OOlcsceunp,atGiWon.aletEaxl.pos1u99r8e. tAonPeErpfiludoermoioocltoagniocicInAvceisd.tigJaOtEioMn.of40R(e7p)r:o6d1u4c-t6i2v2e Hormanes in Men with 47 000046 147 FE EPIDEMIOLOGIC STUDY "pTeirtlfel:uoAronoecptiadneomicioalcoigdipcroidnuvcetstiiognatwioornkoefrpslasma cholecystokinin and hepatic function in Identity: Perfluorooctanoic acid (PFOA) Remarks: METHOD Study design: 1995. and 1997 3 cross-sectional analyses based on workers' medical surveillance data collected in 1993, Manufacturing/Processing/Use: electrochemical process involving The substance converting the is a synthetic surfactant chemical toa salt slurry that and itshepnro1d0ucesadvlticaakae.4-siage. (HyCpCoKt)helseiveslsteasntdeds:erTuomdPetFeOrAminleevwelhseitnhfelaruoprooscihteimviecaaslspocrioadtuicotnioenxiwstosrkbeertsw,eaenndptloadsemtaecrhmoilneecywshteotkhienrin PFOA may modulate hepatic responses to obesity and alcohol, Study period: Medical exams were performed in 1993, 1995, and 1997 Setting: PFOA production plan, Cottage Grove, MN Total population: Not specified `wSausbjveocltunstealreyc.tion criteria: None specified, although participation in medical surveillance at the plant 7T4o.tarles#poecftisvueblyj.ectTshienrestwuedrye: 68 pTahrteicniupmanbtesrisnocfopmarmtoicnipfaonrts19in9319a9n3d, 11999955, a2n0din19c9o7mwmeorne f1o1r1,19890,3 aanndd 1997. and 17 in common for all three years Comparison population: N/A Participation rate: approx. 70% Swuabsjeprcotviddeesdc.ription: Workers who engaged in the production of PFOA. No other information Health effects studied: and CCK levels. The effectsofserum PFOA levels on hepatic responses to obesity and alcohol, sDuartvaeiclollalnecceteioxnammsetwhhoidcsh:coPnlsainsttwedorokefarsquveosltuinotnanraiilryep,aprtuilcmiopnataerdyifnubnicetninoina,lhmeiegdhitc,aland weight `rmeeparsoudruecmteinvtesh,obrimoocnheemaiscsaayls.and urinalysis testing. PFOA determinatiaond, some male 148 000047 148 pDretoaviildsedonindaantoathceorllreocbtuisotn:suHmomramroyne(Odlasteanweefrl.e, on1l9y98c)o.llected in 1993 and 1995. These results are s`Sleurtuammyb!ioocxahleomaicceatlictetstrsanisnaclmuidneads:e (aSlkGaOlTi)ne,pshcorsupmhagtlaustea,mgylampmyrauvgilcuttarmayn!satmriannassfeer(asSeGP(TG)G,T)t,otaslebriulmirubin, dtirriegclytcbeirliidreusb,inb,locohdoluersetaronli,trloogwe-nde(nBsUiNt)y,licproepartoitnienien,s a(nLDdLg)l,uchosieg.h-dHeenmsiattyolilpoogpyrotetsetisnisn(clHuDdLe)d,: hematocrit, hemoglobin, rd blood cells, platelets, and white blood ces thPelramsmoaspCrCaKy-(31399w3aasnmdea1s9u9r5e)danbdyeldeicretcrtosrpardaiyoi(m1m9u9n7o)ashsiagyh.perSfeorrummanPcFeOlAiquwiadscdhertoemramtiongerdabphyy mass spectrometry methods. Exposure period: Not specified. dDievsicdreidptiinotno/fdoeulrinseeartuimonPoFfOeAxploesvuelrecatgergoourpises/:ca0t-e<g1orpiepsm:, F1o-r<1t0heppstmr,ati1f0ie-d<3a0naplpysme,s,aendmp2l3o0yepepsrmweinre order to determineifan effect existed at thehighest serum levels, Measured or estimated exposure: N/A Exposure levels: N/A oStradtiinsatriycamlulmteitvhaoridast:e rSeigmrpeslseioanndwistthraatidfjiuesdtamneanltysfeosr,pPoetaenrtsioanl ccoornrfeolautnidoinncgacvfalriicaibelnetss, ANOVA, and Other methodological information: RESULTS 6D.e4scprpimbe(rraesnuglets0:.1T-h8e1.m3epapnm)P.FOTAhesmcreuamn lCevCeKl ivnaelmupelwoaysee2s8.p5arptgi/cmiplat(irnagngien 8t.h8e -19869.77sptgu/dmyl)p,eriTohde.was hhiigghheesrtinCtChKeseva2luceastewgeorreiersetphoarnteidntinhethceat2eegoxrpioessugrreecaatetregtohraines1l0ospsptmha(np 10 pm. =.06). WThheenmaedajnusstewderfeor50% s`pioCgtCneKinftiaicanaldnctPodFnifOfofAue;nrdehenorcwesse,vimenurls,teitrvhuaermsieacbdhlaeetmairsewtgerrryeesvsaniolotuneimsnocfdloeruldpesadritinincdtiiphcaeantrtesepadworitwt.ehaThkihgenhregeCaCwtieKvreeoarnsoPsoFsctOiaatAtisitloiencvaebllelsytween compared to participants with low CCK or PFOA levels. oSrerwiutmh PaFnyOAhemlaevteollsogwiecrael noortcchoenmsiisstternytlpyaraasmseotceirast,edanwidtnhoanneyovfartihaebvlaesl,uessucfhorassuaclhcophaorlamoertceirgsarweertee. usc, hsteaptaitsiticcarlelsypsoingsneisfitcoanotbeastiatynyaonfdtohreaPlcFohOoAl. levels. There was no evidence that PFOA levels modify iSntduidcaytesttrheantgtthhescaronsds-wseecatkinoensaslesst:ud1y1 fsohromualtddboeensontoetdpthaet rCCamdKiirweatcstoannlaylysmiesasoufraendoibnse1r99v7e.d aTshsoecaiauttihoonrs with than trheespneuctmbteo rtoifmep.artAidcdiiptiaonntaslliny,1t99h3e.numberofparticipants in 1995 and 1997 was significantly lower 149 000048 149 Research sponsors; 3M Company mCnooddnusCliaOsttKeesnlcheyevopeafetriecsruessp:onsTehseralceohsoolufahsnids osbteusdiytyaarnidnctohnasitshternet1wi.thpcosiatisvefCinodmiengisvtohnatBePnFsOoAn PFOA "PTFhOAfolalnodwiCnCgeKxpvlaalnuaetsions may indwihyctiassttaey filed fo ind posits sociation between HisSpaomseibblieocthheamtihcealhleypitnohcurmciannosgenic cfc ofperoxisome prfifrstors inrodents do no act he "(TChCeKrasneiucmemapltsoPwrFesOrmeAaoylvbbeeldisofbfsarteeernivtgerdhbeei wtvdoworeskneeearcshsdamannadmyohhusvmoaenfbset.he Ts0eh0reuomlrocw,ltodstehetfeomsuotnndaknieeyafvfmeocrgtt.erbswEffrcatrsein "TThheeprirtnoamplraviyeamnteoenttabnoeifamCanlCaKpmrooidprehies0iicunmidtoadtoetneionpratnpecrrotemaotdtiicoacnfpcofaspraneocfrnePatFtiOccAacnacnecrheiirmmhaenustmarnveesrssilacinar cl malignancies induced by carcininroasg,aerns rein mars. iTheaevtersP.eFsnOioArsddloeovenhloetyobsssuegggrevstetdhtnhaepthireseetidsyaconmfsnohsedopciauatestiicoponxabieiitywseapetnotnhPseFePOsEAOlAebvleeelvsselatsndoanbidencrsrveeeassdeshainepelcasmta CCK REFERENCE SaOlesptetn.cGfVun.ciieotanla.nd19s9c8.rum3MpeFriTnoarlaRoespoarntc:ieAnsepdidveemiloliongpiroiducntiovn weorkosefrstplaSist.magPcahao,le3tcysitCokooimninpn,r 150 0060049 bs0 EPIDEMIOLOGIC STUDY OTictcluep:atSieornuamlyPeErxflpuoosreodocMteannoie Acid and Hepatic Enzymes, Lipoproteins, and Cholesterol: a Study of mIedeanstuirtye:d dTuoetatlostehreucmosftlouofrainnealwyazsinugscthdeasaampsluersr,ogate for PFOA exposure. Serum PFOA was not tHRhoeawmneavtrehkres,g:ewnheeOrranilgtiphnoeapilurllsyat,circoumnm.plloeTyvhecelerseswfowererere,eatncoaotlanlyszisededer,ruetmdhef"slueuno"erxuipnnoeesxwepados"seubdsa"esdwcodtorokcnelartsshseihfiayjdwoPobrFdkOeesArcsrilipentvteiolosnesxh;piogsheurre wroups METHOD Study design: Cross-sectional study Manufacturing/Processing/Use: This plant produces PFOA, aswellss several other specialty chemicals aHnydpoltihpiedsimsettaebsotleids:m.ToTdheetseeremfifneeitfswhoarvkeebrsenexopbosseerdvetdo PinFrOoAdeentxspeerxipeonsceedd (c0haPnFgOeAs.in hepatic enzymes. Setting: PFOA production plant- 3M Chemolite plant in Cottage Grove, MN "Total # of subjienscttudsy: 115 wSuhbojewcetreseelemcptliooynecdridtuerriian:g tPhaertpiecriipoadnotsfw1e9r8e5-r1e9c8r9u.ited fromall employees at the PFOA production plant Cinommpeaarnivsaolnuegsrooftuph/epobpiuolchaetmiiocnasl Aelnldpsouibnjtecstwseproetecntoimaplalryewde.re exposed to PFOA. Therefore, differences. Participation rate: Presumedtobe > 80% pSeurbjdeacytadnedsc1ri7p%tidornasnkMe1-a3nozs.geal=oh39o.l2A;dmye:a7n4bpoedrycemnatsssmoikneddex. = 26.9; 76% drank less than | oz. alcohol lHiepaolptrohteeifnfse,ctasnsdtuchdoileeds:terPools,siibnlcelucdfiencgt:sosferoutmalgsleurtaummy!flouxoarlionescoentcletvrelasnsoafmhienpaasteic enzymes, e(hSoGleOsTe)r.ols,clrouwm-dgelnustiatmyy!lippyorpruovtiecintsra(nLsDaLm)i,naasned(hSiGgPhT-)d,engsiatmymliapoeplruotteaimnysl(trHaDnsLf)erase (GGT), hDeaitgahtcoalnldecwteiiognhtm,etahnodddso:naPtaerdtibcliopoadntssacmopmlpelsetbeydvaenmiepduinccatlurhei.story questionnaire, were measured for Exposure period: Unknown. ist 151 000050 sbDaeessrecudrmiopfntliujooornbi/nddeeelslicernvieelpasttii2oo0nns-;5o0fhoetwixempveoessruh,irgtehhegorrsoetuhwpaosnr/kcteahrtosesgepolrreieveseslus:mreeWdpootrroktheeardvsienwletirhteetlgpoelrnaecnreoadlPipnFotOpouAleaxetpixoopsnou,srueTrcheaehtraeegdfoortroietc,asl rwoorukpesrosfwteortealclsaesrsuifmiefdluionrtiongerloeuveplss:by<1totpalpms,cr1u-m3 fplpumo.ri>ne3l-ev1e0ls.ppmE,mp>l1oy0e+e1s5 wpeprme,palnadce>d into on 15 ppm. of sMuerarsoguarteedmeoarseusrteimfoartePdFeOxApoesxuproes:ureE.xposures were estimated. Total serumfluorine was used as mStualttiisvtairciaaltemeretghroedsss:ionStwreartiefiuesdeadnatloyesviasl,uAatNeOaVssAo,ciaPteiaornssobnectowrereelnatPiFonOcAoeaffnidcibeinotcsh,eamnidcallineenadrpoins, mFoarssstirantdiefxie(dBaMnIa)l,ysaelsc,ohAoNlOusVe,Aapnrdocteodbuarcecso uwseereweurseedintcolausdseedssindtihfeferreegnrceesssiinonmemaondevlasluaess.potAegnet,iablody m`coodnefolunfdterwsa.s Nimupmrboevredofcciogmapraertetdeswsitmhoktheedpmeodrdelayuswiansg cuasteedgoirnictahle vmaordiaeblleass.acontinuous variable if RESULTS ADepspcrroixbiemarteeslulytsh: aTohflethfreanwgoeorkferthse feslelriunmtfoluthoeri>ne1v-al3upepsmwacaste0g0ory2,6wphiplme (2m3ehaand3s.3erpupmm)l.evels < 1 ppm and 11 had levels > 10 ppm. c`Thhoelreestwereorle, nLoDLsi,gnainfdicHanDtL.difPfeFrOenAcewsabse,thwoeweenvecrat,eagsosroiceisawthedenwiatnhalHyDzLed luesvienlsgiunnimvoadreirataeteandarliynkseerss.forIn cthhoelmeusltteirvoalroiratLeDanLalayfstiesr,atdhjeursetwiangsnfoortaalcosihgonlifciocnasnutmapstsioocni,ataigoen,bBeMtIw,eeanndtotcailgasreertutemsfmloukoriinnge.anTd.here SwGePrTe.noanstdatGiGstTi.callIynscirgenaisfeiscainntSdGifOfTereanncdesSaGmPoTngoctchuerrceatdewgiortiheisnocfrteoatsailngsetortualm fluorine for SGOT, scrum fluorine levels in coobnessieswtoenrtkewirtsh(hBeMpaIt=ic 3di5sokrgd/emrs).. NNoocwloinrikcearlscarseepsoortfeldihveepradtyisfduinscetaisoendassoiciaateodrgwsiitgnhnPs,FooOrAssyemxpeptosoumsrse.. were found in these workers. Studystrengths and information provided owneatkhneeesmspelso:yePeFsO(Acg.walesngntohtomfeaesmuprloeydmdeinrteicetlxypoasnudreth)e.reiTshenoauetxhpoorssusrteate that no. adverse clinical is not lear that tohuetrceohmaessbreeelnatfedoltloowP-FuOp Aofefxopromseurreemhpalvoeyebeese.n observed in [n addition, their employes; however, the standard deviations it irneptohreteredsuflotrs.theMalinveyr peanrztiycmiepsantwserine tvheerysthuidgyhwfeorremeamnpylooyfetdhienexpproosduurceticoantoegforcioesm,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 Aassmoacyiamteodduwliatthemtahrekeefdfehcetpoaftiaclccohhaonlguesseinanhduombaenssitays ohnadhebpeaetincolbispeidrvaendd ixnernoodbeinottsi.c metabolism. 152 000051 152 REFERENCE 5aGn6ld8.achnoldes.teroF.Dl. : anAdsJt.uS.dyMoafnodcec.upa1t9i9o6n.alSleyerxupmopseerdflumoerno.octAamn.oiJcacoiduaonfrd InhndeupasattircileanlzMyemdeisci,nlei,pop2r0o:te5i6n0s., 153 000052 153 EPIDEMIOLOGIC DATA ETimtplleo:yeAens,Ep1i9d9e3m-i1o9l9o5gic Analysis of Episodesof Care of3M Decatur Chemical and Film Plant TEST SUBSTANCE entity: POSF-based chemical used at the Decatur plant Remarks: Episodesof care analyse ae not often used in occupational epidemiologic studi. METHOD Studydesign: Epoifcsarecoompdarieson uMapprnooutfefcahtcievteufcirhliemnmpiglcPaanrltosc,anepdseirtnhfego/rcUmhasenemci:ecacTlhhepelma3intcM.alD,Tehcaaentd3urfm,lauAjolorraobepalrsmotadoumpcelarngstr.obuPepegsraTniunpotrroohdaucccthtaeinmoeinscuaillnfpo1ln9a6y1n!.t faurIoet riis dmeade p(rPoOdSuEc)tiiontohefamavajroiestuyolffonpaetreflfulouroirnoactheedraimciadlemsa,naulfcaochotlusr,edacartylDaeccsa,tuarndantdhe1rwudoroacshtehremipcraecluprosolrymveorhse wHiytphotlhoengs-itsertme,stheidgshTeoxpuosseureepiosodPeOsSoFf-bcaarssedmeptrhoodduoctlioognyaa ta hesc3rVeenfacfiolritmyorinbiDdeictaytuoru.tcAolmaebsaramssociated awSnetdruedDyaencpaeelrmyibzoeedrd: f31oE,rpiw1so9or9dk5eesrosfatcatrheeepxlpaentriwehncaeeorf e65e2mcphleomyiecdalfoemaptleoaystes| ayncdar6b5e9twfielemnpJlaannuaermypl1.oy1e9e9s5 Setting: 3M plant in Decatur, Alabama "TThoetatlotpaolpwuolartkieorn:pop1u3l1a1tiwonorwkesrsnwoterreepoerltiegdi.ble fo the cohort at east 1 year ofemployment atthe plan), eS1u9mb9pj3leacontydsseDlhcei.crteid3o,1n.tce9rri9mt5ie.nraitaeE:dp,iAsloolrddweiosoerdkfedcruasrrieenmgwpetlrhoeeyseltdiumadiytetpdheertioDodte.hceaitrHuoDrwepeclavtaeunrr,fmorreecaotorffdesaoatmfp1elmyoepyalmroeybneteesefoeornn Jan. 1, iMnecdliucdaerde,inltohneg-etpeirsmoddeissaobficlaitryeofro whtohatchpolsoeyHeMeO coverage were not i the database and would not be Wc`oCoromkmpppalararecidestoeonxcppaoocsphuurloetahtteoir.oPnO:ESmCFphlefomlyuieoceraolccohamenpmdiacrfaiillsmopnrpolgdaruncotueipomsnp.wleoryGeeredsoefuwiAepnr+eedaaalnclacclohyrezdmeiidncgsaetloppatlrhaanettilyepomatpenlndotyitaehleens and al aiflnilltmchhepelcmahinectmacilmcppalllaonpytlcaeensmtpaellniodgyiabellsefwfiomtrhtphlheaingcthoheolmrupto.lrooyGcerheeosmuipwcaBh:l weaxollprocksheuedrmeiescxacclloumpslipavanertleyedminphlhoeyfeeisjmorwphlcoaontuw.notrGekrrepdoarsusoCpli.enly 1t0hethfeilsmtupldaynto.nsGetrocuopmpDa:readltpolatnhterwojrokbecrosunwtietrhpahritgshifnltuhorofchmcmipclaalnexposurefo a east 10 years prior Participation rate: 97% of Decatur employees were eligible for participation in the study. 154 154 000053 oiSnuftbthjheeecfctihledmmeispcclaraniltp)p.tliaoTnnth:eem8m2pe9la%onyoefateghseehwacadmswpol4r5o.yk1ceeidsnontinhletyhcehinecmotihhceoarclthpewlmeairncetamlaanpldlea4n8(t.S6a30niindathtsehiemfiicllhamermppileacrna.clenpStliaaxngtteyaopnffedircl$e5mn5t wploarnkterwsorhkaedrshihgahdewxoproskuerdeejxocblsu.sively in the film plant. Seventy-six percent of the chemical plant ePHneFdaOolSct,rhicneeefrftdeaicistnosresdpteiursdsoidieendsv:ooflMvociranbrgiedtiwhteeyrt.ehycrBooanissdeigddleoarnneddanaainpmdraiollriipd.iadtmaTehatenaydboeilpniicsdlmue,dmgeiados:ltorlgoiiivncetrsetasuntdidincabsllaoddnidsePorrFdcOearAnsceoarfn.dthe liver and biliary tract, and reproductive disorders. wDaastausceoldlteoctpironovmiedtaheocdosm:prTehheenCsliinviecaglroCuapriengGroofaulplsviespitiss(oidneopaftciaernet asnofdtowuatrpeadtieevnetl,opperdocbeyduIrncgse,nix, Inc. 4ra0nec0ciodlrildsarcbyayssesesrevaoircrcehcsio,nngadinbtdaicopnkrsew.sacrrTdihpeatinsodonffdtorwruawgraserducsoiedndeticiomnetshfteorrduictathgsenaohsneiaeslp,tihtsrcoeldaaetiommfesnctraeracenoadrrdomsuatnnhaadtgtaerhmeeerinentldoaetxfe-dcmlotiorgcitbhlteehan doifsaeafsaeceo-rtoc-ofnadcietieonncoounntteher oirndaepxharercomrad.cyTrheecoirndfdeoxr raedceolridnecaotnisinsgtdsorufge.ither procedure codes indicative. JEaxn.po1s.u1r9e93pe1r0iDoedc:.T3h1e, e1p9i95s.odesofcare that were included inthe study were those experienced between pDoetsecnrtiiapltiwoonr/kdpellainceeaetxipoonsoufrees:xpowsourrkeergsrowuhpso/ewaetreegoermipesl:oyeWdorskoleerlsy winertehepclhaecemdicianltoogrrfoiulpmsplaacnctosr,dtihnogseto Mwuhaorohcahdemhiigchalexepxopossuurreej.obs, and those who worked at east 10 years in jobs with high potential for Measured or estimated exposure: estimated basedon job history information. dEexspcroisputrioen.levels: Not measured. Employees were placed into exposure categoriesbasedon job. oSbtasteirsvteicdaltomeextpheocdtse:d eApirsiosdkesroatfiocearpeisfoodrecohfceamirceal(RplRaEnPtCe)mpplroovyiedsedcothmepeasrteidmattoetohfe roibsskebrevtewdeteon the ethxepefcitlemdaenpdicshoedmeiscoafclaprlaentameonmg fpilmlwplaaosntcaeylmcpuelloaytseeeds.froTmheheeaxlptehctceldainmusmdbaetarooffetphies3odMesmaonfucfaarcetufroirnbgoth sptorpuucltautreiso,nainnatdhjeusU.tSe.d rBaeticoawuassectahleccuhleamtiecdaalnadncdofmiplamrpeldanttoctohheourtnsadhjaudstseldigrhitslkyrdaitfof.ereInntmaogsetacnadsegse,ntdheer rriisskk rraattiiooss were comparable. Therefore, 95% confidence intervals were only calculated for the unadhusted eOptihseordemoeftchaordeolcooguilcdarlepirnefsoernmtaatnioynasnd1taslhoiuncliddbenetncoatseeds.thpartevfarloemntancaespsi,deamnido/loorgmiicscplearssspiefciteidvec,asaens (thbeotshofftawasrepoussietdi,veanadnditifaspeosnesgiabtlievet)h.at 2Indiafdfdeirteinotn,ditaygpnesosaensdmacyounbtesoafsesipginseoddetsootfhecasraememacpyisdoidfef.er by `eCnedrptoaiinntsoerfvaicnesc,pissuocdheamsaaybvparroyceadmuornesgasnodftpwraersecrpirpotgiroanmssm.ayThneotclbienircealpofrlteexdibfiolrittyhoefeptihseoadle.gorAiltshom, mtahey differ depending on the software program, 155 000054 15s (nDweehosipcclrhaisbimenscorlefusudltethdse:cmaanTlcheeeroroefnplrtyohdeiunmcctarilevaeesresedypsirtsoedkmuocfatniedvpeifssooyrsdttehesemo)fv.oerrTtahhleelrcceoantwdeaigtsoiroyannosfioncfcaranecapsereirdosrraiinsndktoebfreeesnptiigwsneorgdereosfwoftrohrsthe cTovmnecprrlaeolalyseecedasnrciwesikrtohcfatethpeeigsohriogydhefesosrtinanldlo4nglc-ootnmigpmeaes,trichsxiopgnohs-gucrxropueposss.tuorefTuheoemrporlcioshkyeemreaitsciaoallwssao(swRgaRrseEafPteeCpsot-rtine1.dh6,feo9rg5mr%aoluCep1or-fep1r.od2u2c.t1i)v.e ocFaobrnscemerarvlseed(rRfeoRprrEroPedpuCrcot0di.uv7ce,tciav9ne5cce%arnsCcIaenr=ds t1i.hn1ec-sh4ue5bm8-)i<.caatleItgposlrhayontuolfedmpbrpeolsntooaytteeedceatsnhcae(t1.r8 .ethxepFeiccvotenefdei)pd,ieosnfocwdeesihontfeircv4aawcrleefrhsweevreperryoswtiadtee pcfalinancndetirnsmg.oritsOailnmieptyoersttapundtyi.boescHfaopouwrseoevsdteaarnet,ectchaxenuccpeidrnaewptraeosssofttoabshtseeercsvatenudcdeyirndmifodirltnmaoptllicatnyotwneafmsipoltbhosieysrefvie(end3sdi.in4gn.tehxpeeCcotetdt)a.ge TGhriosve 2s"Tr.h09eu,rpe05(w%aRsRCI'Ea=nPCi1n.cr71e5.a.8s,2e)9d.5ri%sMkCoo1sft=epo1fit.s2ho-ed3e.cs0p)ifosarondndeestohpwelealrosenmgas-tottrfeirbtmuhteeamgbpalsletotryoomibenententsi,tginnhaiclgohltoreancxitpcoipnsoutlrhyepesgh.riogShuipemxi(lpRaoRrsEurPeC = numbers ofepisodes were reported in film and chemical plant employees. caoInbnscteehrervee(nd1t.i(5r0e.e9xcpoeehxcoptreetcd,t)eo.dn)l,Byobt1ohtphioscicnoudtrehroeefdchicenamrfieiclwamlapspllaranentpto.ermtTpehldeoryfoeerelwsi.vaesrOcnaglrnyecae2trecra(rs0ie.ss6koeofxfcpielrocrwtheeords)iusarniondftarh|yefforlriebvtleradwdeerre osfinaefmepecitseiomodpnelsosiynreeecpsho.ertmeidIct.sadlipflfainctuclmtptloodyereasw,abnuyt ctohnecylwuseiroensmoasbtoluytdtuhees{e0orbesceurrvraitnigonesp,isgoidveesnofthcearsemably ntuhember I1C0h=esmeci1kc.ac2la5r.pel5a)fno.tr deEimisgpohlrtdoeeyerensosefpitinshtoehdeebsihliiogafchryaertxrepaocwtseutrrheea,nolbtoshneeigrr-vtceeodruminnteecmrhpeplmaoiryctmailenpttlhaegnrtfoieulmmpppwlleoarynetee(2sR%aEntdCim.1e4simn2o.f6ri,em.9l5ik%ely caplacasunettse wocochrcokulercrresey.dsiiTtnhscehaesnmudbi-cchcaoallteeplglioatrnhitieaessmitpshlwaoiytiehnsfc.lhuroennicce otrhiusnosbpseecrivfaiteidocnhowleercyestciptiisso.deMsoosftcohfoletlhietohbiasseirsvewdith dRiiasbketreast,iohsoypferelpiipsioddeemsioaf, acanrd otfohrerenedoncridneodoicsonrrudteririst,niownheailcdhisionrcdleurdse,dwseurbe-cnaottegeolreiveastoefdtihnytrhoeid discase, ticnhoemtphpeaanr9ci5rse%oansc,gorncoyfusipidsie.insc,Ceaorninldtieltroivwoalenrsfouwrrhitinhcaehrhywitegrrhaeecxniponotfseiucdtrieeo,nnisl.foindg-ateprrmioermpbultoywmheincth egxrcoluupdeidnctlhuedemdu:lldhiyspoortdehressiosf eStpudiysstorefdncgeatrshessaofntdwawree.aknTehseserses:ulStseeof"othtihserstmuedtyhosdhooluolgdiocnallybinefuosrmeadtifoonr"hsyepcottihoensifsogreinmeirtaattiioonns of drAeelpmtoohrgotreudag.phhntiohcesdeibpsuietsaosddieeffioenfrcceiandtreneecxedp;eosstiuhgrenersea,floltroh,weehrdiasfrepoamarraadnmieyrteceltirmccioatmantpniaoortnisbsetooniotnhtfiesrwpdoreresiktgeendr.sinwEaipntihysosoidtmehiselorafrmcaannreer,areThe odTfahdteiasaacnraaesleyd.isfifsIincwuaaldtsdi0ltiimioinntt,eedmrpatrone6yboyeefcatarshu.seiAaslkslaorr,agtteihoResRwfiEolrDiezCaptimisaoonydoefsnoohtefacnleatcrehescshaaarrdielvsyeeirrnvydiicwceiasdtmeeachyiognrhfeifrdlieescnkotcefloicinantlcerimvdeaeldnsi,cceal cpartacetgiocreizpeatdteurnnds.er lIanrdgievridouralssmamlaleyrbdeisceoausnetceldasmsirfiecattihoanns.onEcpeisiondtehsoe fdactaarbeasmeabyecianucsleudtehtehyecsaanmbeo 156 000055 156 idinsdaibviliidtuya.l several times. Notall employees were included in the database, such as those on long-term Research sponsors: 3M Company `Consistency of results: No other morbidity studies have been conducted on fluorocheicals. "CTOhiNsCstLuUdySIshOoNulSd only be uscd for hypothesis generation regarding workers employed at the Decatur plant who are employed injobs with high exposure to POSF-based fluorochemicals ORlEseFn,ERGEWN.CBEurlew, MM, Hocking, BB, Skratt, JC, Burris, JM, Mandel, JH. An epidemiologic analysis o1f8e,p2i0s0o1des of careof 3M Decatur chemical and film plant employees, 1993-1998. Final Report. May 157 000056 157 TPietrlfel:uoAroCorcotsasn-osaetceti(oPnFaOlAa)nailnysriesloatfiosnetroumclipneircfallucohreomoicsttarnye,sutlhfyornoaitdeh(oPrFmOoSn)e,anhdematology, and uNruionraolycshiesmirecsaulltmsefdriocmalmasulreveainldlafnecmeaplreoegmrpalmoyee participoafntthse 2000 Antwerp and Decatur TEST SUBSTANCE Identity: PFOS, PFOA Remarks: METHOL Study design: cross-sectional `Mmaannuuffaaccttuurreinpger/fPlruoocreososcitannge/sUuslef:onyFlaciflliutoireisdeinprDoedcuacttusr., ATlheasbeamfaluaonrdocAhnetmwiecralps, cBaenlgmietuambwolhiizceh in the body to PFOS. aHnydpohtohremsoinsaltepsaterda:meTteorsproofvivdoeluannteaegrgreemgpaltoeyeaneaslyisnirseloafttihoen 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. "cThoetmailcpaolpupllaanttioanre:a 3w4e0reAneltiwgeibrlpe efomrplinocyleuessioannidn 500 the sDuercveaitlulranecme.ployees working in the Subject selection criteria Voluntary participation in medical surveillance program in Y200. "Total # Decatur oefmpsulbojyeecetss (i2n1s5tumdayl:e a2n5d5 4A8ntfwemearlpe).employees (206 male and 49 female) and 263 Comparison population: N/A P`Daerciactiupraptliaonntrwahteo: w7er5e%eolfigeimbplelopayreteisciaptattehde.An7t3we%orpfptlhaenptaartnidci5p0at%ionfg Athnetweemrpplomyaelees eamiptlhoeyees paanrdti7ci5p%aroifngthAenDtewceartpufrememaplleoeymepelsoyweeerse ewnegreageendgaingperdoidnupcrtoidouncatcitiovnitaicest.iviOtneslyco1m2p%arofedth1e0 63% of the Decatur female employes. Ssiugbnjiefcictandtelsycryioputnigoenr: tMhaanleDeAcnattwuerrmpaelempelmopyleoeyseehsa,dhlaodwelrowPeFrOBSMaIn,d wPoFrOkAedlefveewlesr, were 158 000057 Is8 `pyheoasrsp,hahtaadseh,igGhGerT,seAlfS-Tre,poArLteTd daanidlytrciognlsycuemrpitdeiovnaolufeaslcaonhdolh,ighhaedr tlootwalerbimleiraunbianlakanldinHeDL vfaelmuaelse.s.Comparable results were observed for Antwerp female employees vs. Decatur bHaesaeldthonefPfeFcOtsS/stPuFdOieAd:levTeols:detheermmaitnoeliofgyth(ehreemwaetorceridti,ffheermeoncgelsobiinnt,heRBfoClsl,owWiBngCspa,rapmleatteelrest caomuinnto)t.racnlsinfiecraalsec,heamliasntirnieesamailnkoatlriannesfpehroasspeh,attoatsael,agndamdimraecgtlbuitlairmuyb!int,rabnlsofoedrausre,eaasnpiatrrtoagteen, cirgelaytcienriined,esg)l,ucaonsde,thcyhrooleisdtehroorlm,olnoewsd(etnhsyirtoyidlisptoipmruoltaetiinnsg, hhiogrhmodneens,istyerluimpoptrhoytreoixnisn,e,anfdree thyroxine, serum triiodothyronine, thyroid hormone binding ratio, and free thyroxine), Dsaamtpalecso.llmeecatisounremmeetnhtosdso:f hMeeigdhitc,awleqiugehstt,ioannndaibrleo,owdoprrkesshuirset,oruyrqiuneaslytsiiosnn(aDiercea,tbulrooondlys)e,ra paunldmsotnaanrdayrfduncclitniiocnaltecsthse.misVtarlyueasndusheedmfaotrorleofgeyretnecstes,ratnhgyreosidwehroermnootnperomveiadseudr,ement, and pDaerttaiiclispaontns.datTahecodlalteactwieornesTshelef-srietpeo-rstpede.cifQiucewstoiroknnhaiistroercyoqnuteesnt,iodnensaiigrne,waadmsinaidsmtirnaitsitoenr,ecdict.o al wUreirnealnyostisprwoavsidoendlyinasthsiesssreepdorfto.r DDeactaatuornebmlpoloodyceoelslevcitaiosnta(nadmaorudntu,rientce.)mincortosptriocvkidaenda.lysis which tested forurineglucose, albumin, and RBCs. TweSrHe,dferteeerTm4inaenddbTa3ywcelroeneddetcenrzmyimneeddboynoirmimmumnuoncohaesmsialyu.minFToImewtarsiccaalscsualy.ateTd4byanmdulTtiHpBlyRing T4and THBR. SPeFrOaSs,atmhpeleexstrwaecrtes ewxetrreacatlesdouasnianlgyzaendifoonr-pPaFiHriSn.g ePxFtOraScAtiAo,n pPrFoOceSdAu,rea.ndInMa5d3di6tion to PFOA and t(apenrdfelmuomraosocstsapneecstulrfoomneatmriydaoancdeetvaatleu)autseidnvgehrisguhs-apnreesxsturraectleidquciudrcvherformoamtoagrhaupmhaynesleecrturmosmparraiyx, All serum values for PFOS and PFOA were above the LLOQ. Exposure period: Unknown. PFOS/PFOA serum levels indicate exposure. 159 000058 159 lDoecsactriiopntiasonw/edlelliansebaytisoenroufmePxFpoOsSurdiestgrriobuuptiso/nc,atpergoodruicetsi:on Wsotartkuesr(sprwoedruectsitornatvisf.iendobny-pprloadnutction workers), and gender. DMeecaantusre(rnum= P21F5O)Swelerveel0s.9f6oraanldl e1m.p4l0opypeme,s rpeasrpteicciipvaetliyn.g iLnetvheilsssatumdoynagt pArnotdwuecrtipo(nne=mp2l0o6y)eeasn.d awnedre1.h6i3ghperp.m At at Antwerp, Decatur. the mean PFOS levelof male production employees was 1.16 ppm Mean PFOA respectively. lLeevveelslsfoarmaollngempprloodyuecetsiowneermep1l.o0y3eaensdw1e.r90 hpigphmer.at AAnttAwnetrwperapn,d tDheecamteuarn, PFOA level of male production employees was 1.28 ppm and 2.34 ppm at Decatur. Measured exposure. or estimated exposure: Serum PEOS and PFOA levels were used to estimate aStnaatliysstiisocaflvmaertihanocdes.:anDedsmcurlitpitviavreisaiblmeplreegarnedsssitornatwifeireed aunsaeldysteos,evPaelauratseonascsoorcriealtaitoinosn cboeetfwfeiceinents, FPoFrOsStraatnidfiePdFaOnAalyasneds,caecmhplhoeymeaetsolwoegriceadliavniddecdliinnitcoalqucahretmiliesstroyf ttehsitrasndertuhmyrPoiFdOhSodrimstorniebutaisosna,y. cPootnesnutmipalticoonn,fociugnadrietntgefuascct,oryseacrosnswiodrekreedd iant tchiethaenrapllyasnet,s ainncdltuydpede: ofajgoeb,.BMI, alcohol NMautlutriavlarlioagblterarnesgfroersmsaitoinomnsoodfetlshewedreepefnitdteendtwivtarhiaPbFleOsSw/ePrFeOpAerafnoarlmyezde,d wahs ecnonnteicneusosuasryv,artioables. normalize variables and to enhance model fit. SAS was used to analyze the data. RESULTS Describe results: aAbnotvew)e.rpTahnedrefDoercea,tuurnievmaprilaotyeeaensalwyesreesdwieffreereinntitiinalsleyvsetrraaltiwfiaeydsby(seleoc"aStuibonjeacntddtehsecnritphtoisoen" daneapleynsdeisngweorneprraotdiufciteidonbystgateuns.derThaenrdefporroed,ucthteioPnFsOtaStusv.aluTehseyin wteherequpalratcileedsianrteo dqiufafretrielnets for ampaplreopprrioadtuectfioornP,FnOoAn.-production, and female employees. In addition, these analyses are not Antwerp `WThheenmesatrnatPifFieOdSbylevperlodfuocrtailolnemstpaltousy,eetsheamtetahns wplaasnt1w.1a6sp0p.9m6fpopr mpr(ordauncgteio0n.0e4mp-l6o.y2e4epspma)n.d 0.42 wpapsm0f.o1r3npopnm-.production employees. The mean for female cmployecs. Mean PFOA serum levels wer 1.03 ppm for all male employees at the Antwerp plant. Male 160 060059 ie (p0r.o3d4ucptpimo)n.emTphleosyeeveasluheasdwheirgheesrigmneiafincasnetrlyumdliefvfeerlesnt(1b.e2t8wpeepnm)pltanhtasn. noFne-mparloeduecmtpiloonyeemepslhoaydeeas (m1u.c23h plpomw)e.r mFeeawnerPoFfOthAesAenrtuwmevraplufeemaatltehsewAonrtkweedrpatpplranotdu(c0t.i0o7npjpobms)tthhaanntahtethfeemDaelceatur plant employees at Decatur. (Mmaelaen,pr0o.d2u9ctpipomn;ermapnlgoey,e0e.s04wer0e.4p1lapcpemd)i,ntQo2th(emefaonl,lo0w.i5n8g pqupamr;tirlaesngbeas0e.4d1on- 0P.F7O8Spplme)v,els0:3Q1 (mean 1.18 ppm; range 0.79 ~ 1.66 ppm), Q4 (mean, 2.61 ppm; range, 1.67 - 6.24 ppm). PIn Pma(lreanpgreod1u.c7t6i-o6n.e2m4plpopyme)esan(nd =the15l0)o,wetshte whaigshe0s.t29qupaprtmil(ermanegaen0s.0c4ru--m0P.4F1OpSpmle)v.el Pwraosdu2c.t6i1on Aemnptlwoeyrepesthianntehmephlioghyeesst qiunatrhteilleowweerset qsuiagrntiifliec.anTtlhye(opn<ly.d05i)ffoelrdeenrceanidn cwloinrikcealdcmhoermiestyreiaerss aftor spirgondiufcitciaontn (wpor<.05k) derisffweasreinncBeUsN.amoWnhgenmacloemppraordeudctbiyonqeumpaloroyetfesiserlwueemrePobOseSrvdeidstfroirbutthioynr,oindo s(TaSmIe.hTel4d. rfrueee fTo4r,nTo3n,-pTrHoBduRc,tiFoTnIe)moprlfooyreheesm(anto=l5o6g).y (HCT, HGB, RBC, WBC, platelets). The aFnorda4l"lqufaermtaillee.emTphlyoryoeieds,anBdUhNemwaatsolsoiggnyifriecsaunlttlsywdeirfefenroetntsi(ghniigfhiecra)ntbleytwdiefefnereIn*tqbuaerttwieleenanadny3of the quartiles for females. Decatur `WThheenmesatrnatPifFieOdSblyevperlodfuocrtailolnemstpaltousy,eetsheamtetahins wplaasnt1w.6a3sp1p.m40fporpmpr(ordauncgteio0n.1e1m-plo10y.e0e6spapnmd).0.73 wpapsm0f.o9r3npopnm-.pro7d5uc%toifonmeamlpeloeymepelso.yeTehsewomrekaendfionr pfreomdaulceteiomnpljoobysee(sn = 161) and 63%of female employees worked in production jobs. p"TrhoedumcetaionnPeFmOplAoyseeersumhaldevheligfhoerramllemaanleseermupmloleyveeelss tathatnhemaDelceantounr-pplraondtucwtaison1.e9m0pplpomy.eesMa(l2.e34 Fpepmmalaendem0p.5l9oypepems,hraedspaecmtiuvcelhy)h.ighTehresmeeavnalPueFsOwAerseersiugmnivfailcuaentalty tdhieffDeerecnattubretplwaenetn(p1l.a2n3tsppm) wthoarnkeatdtahtepArnotduwcetriponpljaonbst.(0.07 ppm). There were many more females a theDecatur plant who (Mmaelaen.pr0o.d5u5ctpipomn;ermapnlgoey,e0e.s11we~r0e.p75lapcpemd)i,ntQo2th(emefaonl,low1.i0n1g pqupamr;tirleasngbeas0e.d76on1P.3F0Opplme)ve,lsQ:3QI (mean 1.74 ppm; range 1.32 ~2.29 ppm), Q4 (mean, 3.22 ppm; range, 2.31 - 10.06 ppm). dWihffeenremnacleebeptrowdeuecntitohne qwuoarrktielresswwearseipnlaAcLeTd i(nhtioghqeuasrttqiuleasr,titlheeodinflfyerseingtniffriocmanatll(3p <oth0e5r)s). 161 000060 161 NTHoBsRi.gniFfTiIc)a,nthdeimfafteorelnocgeys(bHeCtTw,eeHnGqBua,rtRiBleCs,weWrBeCo,bspelartveeldetsf)o,rotrhyurroiindal(yTsiSsH,(aTl4b,umfirne,e Tbl4o,oTd,3, sugar), sFiogrniffeimcaanltedeimfpfleroeyneceess (abmoothngprqoudaurtcitlieosnfaonrddenmoong-rparpohdiucctsi,otnhyermopildo,yheeemsa)t,otlhoegrye,woerreurninoalysis except for mean quartile, but the 4p"lawtealsetncoot.unt where the third quartile was significantly lower than the 1 `foWrhehenparetsiucltcsliwniecrael acnhaelmyizsetdrybytesntusmabnedrloifveremepnlzoyymeeesanwdhobilhiardubvianltueesstsa,btohvereetwhaesreafehriegnhceerrange ptoetraclelnitvaegrepoafnemlatlheanDetchaetoutrheprroqduaurcttiileosn. woMroksetrsnoitnatbhleehwiegrheestthPe FreOsSultqsuafrotrilAeLfTorwAhLeTr,e G8G%To,fand evamlpuleosyaebeosvien tthheerleofweersetnceexproasnguer,ewghrioluept(hQe1p)earncdent2a8g%esifnorthteothailghleivsetrepxapnoeslu(rwehgircohuipnc(lQu4d)eshad arelskpaelcitnievpehlyo.sphTahtiasster,enAdSTw,asALnoTt,eGviGdTe,ntainndDteoctaaltuarndnodni-rpcertodbuiclitriuobnine)mwpelroeye1es8%(aalntdho3u5gh%.the n wpoapsuloantliyon54h),adian Ddeicffaetruerntfesmearluems,oPrFiOnS aqnuayrtoiftlehedisAtnritbwuteiropn. employees. Therefore, Htohweyevcearn,noctacbhe subdirectly compared. Analyses combining employees from both plans pWrhoedunctcilionnicaanldchneomni-sptrroydurcetsiuoltns)o(fnal=l4m2a1l)eaenmdpplloayceeedsifntroomquabrottihlepsla(nnts= w1e0r5epceormqbuiarnteilde)(,bomtehan v0a5l)uehsigfhoerrtriingtlhyece4ri"deqsu,aratliklaeli(nmeepahnosPpFhOatSaslee,vetlot2a.l69b,ilriarunbgien,1a.6n9d AL10T.0w6eprpems)igtnhiafniciannttlhye(fpir<st (AmnetawnerPpFpOrSodluecvteilo0n.e2m7pplpomy,eersanwgeere0.e0v4e-nl0y.4d2isptprmib)u.tedI asmhoonulgdtbhee nquoatretdiltehsatwhtihelenuthmibsewrasofnot the case quartile. for In Decatur employees. addition, overall the The highest number employees in the 1* qoufarDteicleatwuerreemspllioghyteleysyowuansgeirn,thhea4d"a lower BMI, and worked fewer years than employees in the other quartiles. `TTHhyBrRoidwaressuslitgsniffoircathnitslysalomweegrr(opu<p 0in5d)icianteQd4thtahtanT3QI.wasInsifgenmifailceanetmlpylhoiygeheesr (cpom<b.i0n5e)danfodr both pbillainrtusb(inn s=ig9n7i)f,icaalnktallyinleopwheorsipnhaQt4astehaanndinGQG1.T wMeorset soifgntihfeicDaenctaltyuhrigfheemral(epe<mp0l3o)yaeneds twootarlked in pQraodwuacsti9o2n9j%obfsemwahlieleprmoodsutcotifotnhewoArnketrwserapndfealmlaolfestwheomrkweodriknednoant-pthreodDuecctaitounrjopblsa.nt Therefore, "fTohreaclkoamlbiinenepdhopslpahnattadastea, wAeSrTe,aAnLalTy,zeGdGTfo,r eamnpdltooytaelesivwehropahneald. vaFlouresmaalbeoveemptlheoyreeefesrfeonrcealrlaonfge tahbeosvee mtehaesurrefeesr,etnhcee lreavnegles ifonrcrAeLasTedanfdro6m%Q1for10GQG4T., IwnhiQlIe, 142%%owftahsereepmoprltoeydfeoers had Q4 values for both of these tests. For total liver pan, 14%ofthe employees had values above the reference range in 162 000Cs1 162 Q1 as compared t0 23% in Q4. The numbers of female employees with values above the reference range was very small (n = 8) PFOSand PFOAanalyses `aTnhaelaybsoevsewderaetacownedruectneodt. adTjhuesrteedwafosr paotpeonsttiiavlecsoingfnoiufnicdaenrts;(pth=er0ef4o)rea,ssmouclitaitviaorniabbeltewereegnrePsFsiOoSn achnodlecshtoelreols.terWolheanndbaoltsho aPOpoSsitainvedsPiFgnOifAicwaentre(pi=ncl0u5d)edasisnoctihaetmioondeble,twneeietnhePrFwOerAeasntdatistically significant at p=05. PFOS was not significant with HDL although PFOA was negatively aasnsdocPiFatOeAd w(ipt=h.0H0D2)L. (pW=he0n4).botThriwgelryecelreifdteisnwtehreemopdoesilt,ivPeFlyOaAssroecmiaatiendedwistihgnPifFiOcaSnt(p(p==0012)). aTsostoacliaotrigoannsicwefrlueoroibnseer(vTeOdF)wiwtahsPhOiSgh,lyPsFiOgnAi,fiocranTtOfoFr rinigrleylcaetrioindetso (aplk=al0i0n0e9p)h.ospNhoatsaisgen,ifGicGaTnt. AST or total bilirubin. A significant (p= 02) positive association was observed for TOF and ALT. A positive significant (p = 04) association between T3 and PFOS was observed. Plant alloscoatsiiognniwfiacsanth.igh(lIyn stihgeniufniicvaanrtia(tpe-<an0a0ly0s1e)s,inAtnhtewmeordpele.mplBoMyIe,escihgaardethtiegsh/edraym.eaalncoTho3l/ldevaeylswetrhaen Decatur employees overall. However, for each plant (individually) T3 values increased by quartile as PFOS serum levels increased, although the differences were not statistically significant] THBR,aswell as the other thyroid hormones, were not significant in the regression analyses. Mostof the thyroid hormones, including TSH, T4, THBR, and FTI, were not spiogsniitfiivcealnytlayssaoscsioactieadte(dp=wit.h04,PE0O1S,,anPdFO0A0,4,orreTsOpeFc.tivHeolyw)evweirth, TP3F.OS, PFOA and TOF were Study strengths and weaknesses: Cross-sectional design, voluntary paricipation, the Decatur and Antwerp populations were significantly different in certain demographic and clinical cthhaenmiPsFtrOySresseurltusmalsevweellsl, ahsowienvPerF,OSemapnldoyPeFeOsAwesreeraunmalleyvzeelds,bPyFPOFAOSselreuvmelsl,evteoltsalwoerrgeanhiicgher fluorine serum levels were higher than both PFOS and PFOA levels and it is unclear how this is affecting the analyses, plant populations cannot be compared because quartiles are different for each subgroup, only one measurement at a certain point in time was collected for each test, and other perfluorinated chemicals in addition to PFOA and PFOA are present in the plants Research sponsors: 3M Consistency of results: These results are somewhat consistent with thoseof the 1995 and 1997 cross-sectional medical surveillance data, in that all ofthem conclude that there were no sDiegcnaitfuicrawntorakbenrosr.malNiotideescliinnheeimnatcoholloegsitcearlolanldevcellisnwicaasl cohbesmeirsvterdyapsaPraFmOeStesrseroufmthleevAelnstwinecrrpeaosred. "The hormone data collected in 1995 was different from that collected in 2000 and therefore. cannot be compared. A longitudinal analysis of these data did not reveal any significant changes in hepatic or lipid clinical chemistry values; however, there were many limitations to the study. 163 000062 163 CThOeNaCuLthUoSrsIcOoNnScluded that these data continue to suggest that Antwerp and Decatur sfeurourmocchheomliesetcelroplr,odliupcotpiroonteainnsd,noorn-hpepraotdiuccteinoznyemmepslhoayeteasredoconnostishtaenvtewsiitghniftiocxainctolcohgaincagles in findings in laboratory animals. However, the study weaknesses should be considered ROlEsFenERGEWN,CBEurles MM, Buris JM, Mandel JH. October 11, 2001. A cross-sectional analysis of serum perfluorooctanesulfonate (PFOS) and perfluorooctanote (PFOA) in relation o clinical pcFahirnetamilicsirteprpaoynr,tts.thoyf3rtoMhiedM2he0do0ircm0aoAlnneDt,ewpheaerrmptaamtenondl.oDgeycaatnudrufrlinuaolryoscihsemreiscualltsmefdriocmamlasluervaenidllfaenmcealperoegmrpalmo.yee Last updated: 429/02 164 000063 104 EPIDEMIOLOGIC DATA "PTeirtlfel:uoArooLcotnagniotautdein(aPlFAOnAa)lyLseivseolfsSienrRuemlatPieornfltuoorLoiopcitdaanensdulHfeopnaattiec(CPliFnOiSca)laCnhdemistry Test RMeesduilctaslfSruormveMialllaencEempPlrooygereamParticipantsofthe 1994/95, 1997, and 2000 Fluorochemical TEST SUBSTANCE Identity: PFOS, PFOA Remarks: ETHOD Study design: longitudinal `Manufacturing/Processing/Use: 3M Decatur, Alabama plant and Antwerp, Belgium plant Hisyrpeoltahteedsitso ctheastnegde:s Tinocdleintiecramlicnheewmihsettrhyeranodccluippaitdiroensaulltesxipnoesmurpelotyoefelsuoorf2oc3heMmifcaclislitoivces.r time Study plants period: Therewere 1994/95,1997,and 3 ime 2000. periods during which medical surveillance took place at the Setting: 3M plants in Decatur, Alabama and Antwerp, Belgium. "sTaomtpallipnogpupelraitoidso.n: 175 male employees participated in 2000 and at least oneofthe other Subject selection criteria; Employees participated voluntarily. Comparison population: n/a aPanrdti1c7i5papatritoincirpaattee:d i1n0260/0107.5 (2641%%)ppaarrttiicciippaatteeddininal1l9394s/a9m5p,l1i1n0g/p1e7r5io(d6s3(%n)=pa4r1t,icAinptatweedripn2109,97, DAenctawteurrp2304),, 3De7c%atiunr13959)4/in951a9n9d7 2an0d0020(0n0=. 65, Antwerp 45, Decatur 20), and 39% (n = 69, Spluabnjtse.ctIdnegsecnreirpatli,onA:ntMwaelrep memaplleoeymepelsovyoeleusntweeerreedsitgonipfairctainctilpyatyeoiunngbeiro,mohnaidtolroiwnegroBfMfeIrsedaantdtahe ehmigphleorydeaeislyalcsoonhsaudmpltoiwoenromfeaalcnoahloklalrienpeorptheodspthhaatnaDseecaantdurtrmiaglleyceemripdleoyveaelsu.es Aanndtwheirgphemratloetal bilirubin and HDL values than the Decatur male employees. 165 000064 165 Health results aerfefeacftfsecstteuddibeyd:PFTOoS daentderPmFinOeAwhleevtehlesr workers" lipid and hepatic clinical chemistry hDiagthadceonlslietcytiloinpomperottheoidnss:(HCDlLin,icmagl/dclh)e.mitsrtirgilyecserainddeshe(mmagt/doll,ogaylkcaollilneectpehdo--s--pchhaotlaessete(rIoUl/L()m.g/dl), gamaimnomtaragnlsuftearmays!e t(rAaLnsTf,erIaUs/eL)(,GGotTa,lIaUn/dL)d,iraescptarbtialtieruabminin(omtgr/adns)f.erDaesmeo(gArSaTp,hiIcU/dLa)t,aacloalnlienceted via questionnaire. dDeestiaginl,s aodnmidnaitsatrcaotliloenc,teitocn.:anDdetabillosodoncodlalteactcioolnlemcettiohnodmsetwheordesniontcplruodviindgedq.uestionnaire content, tPeFtOrSabauntdylPaFmmOoAnimuemthtoodfsono-fpaaniarlwyistihs PdiFfOfSereadndsliPgFhtOlAy ciancthhyeesarc.rumI.n 1994/95, the method used The ion-pairs were then epxetrrfaocrtmeadnwciethlicqtuhiydlcahcreotmaatetoagnrdapthh-etahbestrrmaocstpiroanyprmoadsusctspweactsrotmheetnrya.nalIynze1d99u7s,intghehisgehr-um samples wtheereneagnaatliyvez-eidonbymolidqeu.id Icnhr20o0m0a,tosreerraaspahmyp/lmeassswesrpeecetxrtormaecttreyd, uussiinngg asneljeocnt-epdaifroinngmoenxittroacrtiinogn in procedure. was used. THhieghs-apmeprlfeosrwmearneceevlailquuiadtecdhrvoemrastuosgarnapehxyt/realcetcedtrcousrpvreayfrtoamndaehmummaasnsssepreucmtrmoamtertixr.y Exposure period: Unknown. PFOS, PFOA levels measured in blood serum. sDtersactirfiipetdiionnt/odesluibnpeoaptuiloantoiofnsexAp,osB,uraengdroC.ups"/Ae"atweagsorcioemsp:riTsheedogfrtohuepseomfpelmopyleoeysewehsowere p1a9r9t4i/c9ip5aatenddi2n0a0l0l,3aynedar"sCo"fscuornvteaiilnleadncteh,os"eBw"hcoonptaaritniecdipattheodseinem1p9l9o7yaeneds w20h0o0.participated in Mseerausmu.reNdooarmbeisetnitmaetxepdoseuxrpeosduatrae:arePFavOaSilaabnlde.PFOA levels were measured in workers" blood Exposure levels: AMnetawnerPpFOS levels in DMeaclaetsur 199495 187 ppm 1997 142 ppm 262 ppm 185 ppm 2000 116 ppm 1.67 ppm 199495 1997 2000 Viean PFOA levels in Males Antwerp Decatur 1.08 ppm 154 ppm 1.90 ppm 1.41 ppm 1.43 ppm L83 ppm 166 000065 166 Smtiaxtiesdtimcoadlemletushiondgs:SASr.epeRaetsetdrimcetaesdumreasxiinmcuomrpolriakteilnighotohdeersatinmdaotmessoubfjveactrieafnfceectpafirtatmeedtteor-sa were computed. covariance Adjusted structure. regression models were Covariates included in tbhueilmtobdyelinwterrodeuacgien,g aBlMl Ic,ovnaruimabteesroafnadlctoehstoilnigc.the drinks per day, and cigarettes smoked per day. ODtechaetrurm)etwhhoodoplaortgiicciaplateidnfionrtmhaeti2o0n0:0 Asurtvoetiallloafnc1e7y5emaralaelseomppalrotyiceiepsat(e1d00inAanttlweaesrtpoannedpr7e5vious ofplpuoorrtoucnhietmyictaolumneddeirctaalkesuarvleonigliltaundcienaelxaamssseisnscmeen1t9.94/95. Therefore, this provided an RESULTS Describe results: PFOS results dWehcerenasmienagninsethreumpaPrtFiOciSpalnetvselisn wmeedrieccalomspuarrveeidllbayncseurivnebioltlahncpleayntesa.r,WPhFeOnStlheevedlastahawveerebeen aannadl2y0z0e0d),byAnthtewe3rspubacnodhoDretcsat(uthroesmepwlhoyoepeasrtiinciepaacthedofint2heo3r smuobroehmoerdtiscahladexloawmesrbmeetawneesner1u9m95 PEOS levels in 2000 than at theiryearof entry. `DeWchaetnuarneamlpylzoeydeuessi,ngthmeirexewdasmondoealssmouclitaitviaorniabbeltewreeegnrePssFiOoSn aanndd csoemrbuimnichnogleAsntterwoelroprand wPiFgOlyScearniddecshainngmeasleovpearrttiicmiepainntsHoDvLe,r atlimkea.linTehpehroeswphearteasael,soGnGoTs,igAnSifTi.caAntLTas,sotcotiaaltiboinlsirbubeitnw,een and direct bilirubin. PFOA results eWmhpelnoymeeeasnpasretricuimpaPtiFnOgAinlmeevedliscawlerseurcvoemilplaarnecde abtytsheurAvneitlwlearncpepyleaanrt,iPncFrOeaAseldevbeelstwienetnhe1994/95 asnedru1m99le7vealnsddethcerneadseecdrebaestewdeselnig1ht9l9y4/b9e5twaenedn11999977aannddt2h0e0n0.incArteatsheed Dbeectawteuernpl1a9n9t7, PanFdO2A000. `meWdhiecnaltheexdaamtaswbeerteweaennal1y9z9e5d abnydpl2a0n0t0)a,ndthtehree 3wesruebcnoohcoorntsi(sttheonstecwhhaongpeasrtaiccriopsastesdubicno2hoorrtmsoarte. the Antwerp plant. increase. However, among the 3 Decatur subcohort, mean PFOA levels tended to. When analyzed using mixed model multivariable regression and combining Antwerp and sDeecrautmucrheolmepsltoeyreoels(,pt=her0e00w8a)s aansdtattrisitgilcaylcleyrsiidg(enpisfi=ca0nt00p2o)siotviveer atsismeo.ciaWtihoennbeatnwaeleyznePd FbOy Aplaanntd ainndpaarltsiocublayr,sutbhceo2h1orAt,nttwheesrepaesmspoclioayteioensswwheorepalritmiictiepdatteodthine aAlnl t3wseurrpveeimllpalnoceyeyesar(ps =(p 0=0500)1a)n.d, However, the association between PFOA and triglycerides wasalso statistically significant (p = 167 00906 167 w0a2s) nfootrasusbiggrniofuipcaBnt(aesmspolcoiayteieosnwbhetowpeaerntiPciFpOatAedainndbtiroimgolnycietroirdiensgaimno1n9g94D/e9c5ataunrdw2o0r0k0e)r.s,There pThhoesrpehawtearsee,noGGsiTg,nifAiScTan,tAaLssTo,citaottiaolnbsilbiertubwiene,naPndFOdiArecatndbilcihraubnigne.s over time in HDL, alkaline Total Organic Fluorine (TOF) results sDWeehrceauntmucarhneoalmlepyslztoeeydreouelssi(,npgt=hmeir0ex0e7w)dasamnoaddsettlratiigmslutylictceiarlviladyreissaib(glnpei=friec.ga0rn0te8s)psooisvoientriavtneidmaecs.soomcHbioiawnteiivonnegrbA,entttwhweeeeirnnpteTarOnadFctiaonnd e{meprmlowyietehsitmhean(yDeeacrast)uwraesmpnlootyseiegsni.ficant. This association was more consistent for Antwerp Study 1. 2. satrveenrgytshmsaallndnuwmebaekrnoesfseesm:ploSyteuedsy different labs were used cach year plairmtiitcaitpiaotnesdiinclaullde3tshteufdoylpleorwiiondgs (only 24%, n for analysis and different analytical techniques = 41) for 3. cPoFuOldS and PFOA not analyze female employees due to small numbers 4. 5. aPPnRFiOOmaSSlsalnevdelPsFiOn AemspelrouymeelsevaerlesdiencermepaslionygeeosvearretibmeelowhwitlheoPseFcOaAuslienvgelesffaercetsinincrleaabsoirnagtory 6. mDeecaantusrerum PFOS and PFOA levels were significantly lower in Antwerp employees than 87... mthoerree aArnetsweevrepralemcpolnosiyseteesntthdainffDeerecnacteusrbpeatrtwieceinpatthiengAinntwtheirspstaunddyD(e5c7a%tvursm4a3l%e) apnodpudliaftfieornesnc(eegs. isntacthiesmtiicsatlrlyypsriogfniilfeisc)ant differences in BMI, age, consumption ofalcohol, 9. oesntly | measurement at certain point in time was collected for each clinical chemistry 10. 11. aoltlheparrpteircfilpuaontrsinwaeterde cvhoelmuintceaelrssare present in the plants Research sponsors: 3M pCroonbsaibsltyenncoyt of be rreespuelattesd:, This is the first longitudinal analysisofthe surveillance data and will tTwhihetehaputothsheiotrhisyvperoealpsiosproticditeahmtaitiaotnheifbsfeeetcfwtfeeocebtnsheParsFveOndoAtinabnerdeondseoenbrtssuem(racvnhedodlneaosttt3eorMbo'slsearCnvodetdttraiinggeplryGicrmeaortivedese)sf.aicsiInlniottaydcwdoihntesiirosent.ent tPhEeOmAossterreucmenltevdealtsai(n2w0o00r)kehrasvaerncomtubcehenhisguhbemritttheadn taot tEhPeADefcoratruervoierw:Antwerp plant. However, CONCLUSIONS 168 000067 ies PE nAotlosnhgoitwudsiinganlifaincaalnytscihsaonvgeers,acsoinxs-iysetaerntpewriitohdtoofxi1c7o5loAgnictawledraptaa,ondfDleicpiadtuorr hmeaplaetiecmpcllionyiceaels did cohbesmeirsvterdybveatlwueeesnasPsFocOiAataedndwicthholPesFtOeSr.ol Aanpdotsriitgilvyecesrtiadtiesst.icaWlhlyesniganniaflicyaznetdabsysopcliaanttioanndwaaslso by Asunbtcwoehrorpt,emtphleoseyeaesssowcihaotipoanrstiwceirpeatleidmiinteadllto3 tshuervAenitllwaenrcpe yeemaprsl.oyTeehsealnidm,itaintipoanrstidciuslcaur,sstehdea2b1ove should be considered when interpreting these result. ORlEseFnE,RGE.WN.C.EBurlew, M.M, Burris, LM., Mandel, 1H. A Longitudinal Analysis of Serum aPenrdflHueopraotoicctCalniensiuclaflonCahteemi(sPtFrOyS)TeasntdRePseurlftlsuofrrooomctMaanolaeteEm(pPlFoOyAe)e LPeavretlicsiipnanRtesolafttiohne t1o09Li4p/i0d5, 1997. 2001 and 2000 Fluorochemical Medical Surveillance Program. 3M Final Report. October 11, OTHER Last updated on: 5/7/02 169 000068 169 GENETICTOXICITY STUDIES TCihleem:icaAlnTA2s9s4y2oCfoCCell Transformation and Cotxiiy in C34 107 4Clonal Cell Line for the Tes TEST SUBSTANCE entity: T:2942 Coc Remarks: Whit powder dissolved in DMSO; compostion and pity not indicated METHOD Method/Guideline followed No guideline number specifi Test types Cytotoxicity and eel ansformaton Test system: Mouse embryo oblast Gr No Year study performed: 1950 SpeciesStraiaicllypelel line: Cellsofthe C3H 107-172 clone Metabolic activation: None Concentrations ested: 01,10, 10,50, 100,200 gin, Statistical methods usd None: crRooenmwtaiornlkgsa:inndTEhaDegMlteeSsBtOumsaasal.tMseaodlviweuanmst dc(oiBnMstEoo)ll..sdBPeirnnizoDorlMiaSpthOyraepnnedrsaf<no2rd0mda5in-cocefptaohfxeyhseotlruatenifsoonsrwemaarstaivdoedntedsaafoypt.ohdscoioleansge arTahnesfawoperpmrraotxoiibomtnaaitpneeodintiveinhteooLfftDohrSemOeocsfyttcocthioexmeiicciattly.yoTsehsowadaasnscshfoeosmetniaso1nixpesremeyesdwsiabdpeoprsfaforoimeh(de1mssse)hscotmheesen laPsorsteesnasipmllein(ctahotafisocenel2a)nadnPtshrtaocsrum1lawteoasnwpienrretfhoerrmceeodlfoinvnyeimroyde3eld(eapycsh.oarT1 ah14e1ndcsdt1e7stdehroemyi.mnaatPlioeenssofwr1ae)rmemaadnseh3emdp,oiononsn, a(pr1no1dc0es1s0is.end3da0da3t810140digdga/symsaLtf)orswcrioetrmheobvfuaotlratdorfihaennseefoerepmtaotnisioundb:sstaPanhcaepsoest2iwveasco1n0verperIfnoprmsetd 3mrpohtpcodes RESULTS Overall transformation results: Negative 17 000069 1m Cytotoxic concentration: approximate LD= 50 gL. Statistical resus: None CONCLUSIONS hfoecrsaswsaaysmneotehvoiddsence ofransformation observ at any ofthe dose eves ested ster the colony or REFERENCE GClaornya,l VC.oF.lianned RfoLr.iNheToenx.Ch1e9m81i.calAnT-A2s5s4a3yoCofc.Cel3lMTrCaonmspfoarnmya.tiSot.n aPond CAytotoxicity in C3H 10.5 m 000070 m Tiles Mutagenicity Test on T6564 nan Fi Morse irom Asay TEST SUBSTANCE deni: T6564 Remarks: ls, colores ids composiion and pry ot cists METHOD Methou Guideline followed Procol No.5, Edition 17, mie for 3 Corporsion Test ype: vivo mouse micronucleus assay Lp: ves Vear studyperformed 1995 SpeciuStain: Mouse CHLCD-IE(CRIBR Sex Male and fale No. animals/sex/dose: Five (micronucleus assay), Three (range-finding studies) Vehicte if wed: Deionized ter Route of administration: Ors eve DDDooossseses:SSeeletctoionn SSttuudyy:T11001000,11551200.,220012,0,2255430,03m01g0sme Micronucius Asay: 495,995, 1990 meg Frequencyoftreatment: Once Statistical methods vd: Analysisof rian; Dunn's st oiaRfnelitmneaghsrddkeostisho:eenrTiSazhlegedceniwwioaaansrl,sbtouawdndeydey.k3stw.JheeiogmDshotiasieofnmtgchaowemaaoon,liameiacalntsiegwddacsoywcs2il2no.wg4pash-osss28s.po3thilammanitdoefoder11If5oe55r0m0a0m0lggEakn,des.3we1e0dA-3los1n.eipmirmfoeeor,ms, hasAninadileomyssailassnc.dwansrd(etNsecCsocdErr)eiwdfeiiftlochedMamatiy.c-2Gr4Or,ou4nnn,evhlaaonlasddda7sn2ohldhuetoEipuoClnrEya3en6hpdorrGndiaiotonnisiscsmlyiawonbrdrebroownoeetseMd(cR.COyE)T0ahesmSovrdrmoarcihtvdcoamdeofor n 000071 ie Effect on mitotic index or PCEINCE ratio by dose level and sex: Negative Genotoxie effects (unconfirmed, dose-response, equivocal): Negative Statistical results: Negative: hRoewmeavrekrs.:onAellmaalneimfarlosminastehceomnidcarroynudcolseeusgreosutpgwraosupfaopupnedadreeaddn2o2rmhaolurismmaeftdeiradtoesliynga.ftAerlldootshiengr;animals appeared normal. The to the vehicle control positive control induced significant increases in micronucleated PCE as compared sIingtnhseodfotsoexisceilteyctiinotnhsetdudoisees,setlheecrteiwonarsetumdoiretsalwietrieeshauntchheed15p1o0s,tur1e5,20h,yaponadct3i0v0itmyg,/akngddroosueghlevhealisr. cColaitn.ical "The test article did erythrocytes and is ncootnsiindedruecdaenesgiagntiifviecainnttihencmaosueseinmimcircormoinclueluis in bone assay. marrow polychromatic REFERENCE M17u7r5,0-0H.4551.9963.MMCuotrapgoernaitciiotny, toen Ts-65t64 St.Paul, MN, in an invivo mouse micronucleus assay. Study number 173 000C72 m3 T(iCtHeO:)MCueltlasg:enwiictihtay TCeosntfiornmTa-t6or5y64AsMseaaysuwriitnhgMCuhltriopmloesHoamravlestAsberrations in Chinese Hamster Ovary TEST SUBSTANCE Identity: T-6564, also referred tao s L-13167 and FC-1015-X. lRieqmuiadrks: The specific gravity ofthe est substance was 1.22 gn. Substance was a clear colorless METHOD `Method/Guideline followed: Protocol No. 437C, Ed4iwatsmoodifined for 3M Corporation Test type: In vitro cytogenetics Test system: Chinese hamster ovary calls in culture Gey ear study performed: 1996 SWMpooeldcfaifle.s/cUSnhtirrvoaemirnos/isctoeymloelf-tnCyuaplmeibefeeorlrnlwialai,sneS:2a1.nCFhriannecsiescho.amsCteelrl olvinaeryhacdelasnipaevremraagnecnctyccleleltliimneeosfup1p2lied1b4yhDoru,rs,. NTyApDePofarme1t.5abmoleimc acatnidvaitsoicointruicseadc:idAarto2c.l7ormg1/2m5.4 inducedra iver $9 homogenate, 15.0 uml, plus CRaonngceefnitnrdaitnigons tested: 0(b.o1t6h9.w0i.t5h08a,nd1.w6i9t,h5o.u0t8,act1i6.v9a,ti5o0n.)3, 169, 508, 1690, 5080 pg/ml InitiaWlitshtuoduyt activation: 62.5,125, 250, 500, 1000, 1500, 2000 pgm ConfWiirtmhataocrtyivasttiuodn:y 250, 500, 1000, 2000, 3000, and 4000 pgm! WWiitthhoouuttaaccttiivvaattiioonn//2d0d..12 hhoouurrss:: 5100,0,120000,,20400,0,460000,,60800,0,80100,001,00102,0a0ngd/1m2l00 pgm! With actvation20.1 + 44.2 rs: S00, 1000, 1500, 2000, 2250, 2500, 2750, and 3000 ug/ml Test conditions: Nh4ou.um2rbshbeoerfouofracseesaltylr.:eaTthImneentcthuelbtymsuareieendmisetndugidiaucbmsou(ubtsoe1td.h2wwaxis1th0MacncCadollwysi'tsfhoorSuatthceauclt1ti7uv.ra8ehtiomouen)rd,aicsuesmlalyssuwapenprdlee0mc.eu8lntxtuer1de0dwifctoerhllasnbufotourritetn2hte4s and antibiotics, 174 00073 = Nem1g0ea.d0tiiuulvmmeio.Cnloyn.ItnrtoShloelsv:aecIntntitvcahotenitonrnoonslauscdciioicnsvt,tainioenngeadatsoisnvaleyysa,ntnhdeegssaootllvivevenencttocnfotonrrtortlohlseswtweesertreaerctutihlcleteu,Sraestsmeewriilateshdtceheioloslnseiaisnnedtdhcweualtteurreat nomactivation studics but also included the $9 activation mix aPcotsiivtaitvieonCosntturdoiless: MitomyciCn was used for nonacivaton studies. Cyclophosphamide ws used in the Otpornseliayttimcveeenltlcsognwrtiotouhlps2c1ualn+tdur|neecsgeawntetirrveoemaaennraedlsyszwoedle.vreentancaolnytzreodl. grOonuepshuwnedrreeadnacleyllzsedf.romAtealecahstre2p5liccealtles cruoltmurtehoef dIonnthee main study (afer range-finding study was completed), both inital and confirmatory sudics were Sonftuamctbiesestriscwoailfthmceealtlbhseowdristrhuasaetbideinr:rcoaaFtnicisshohnesrr'wasitmEhxeaictntcrTgeerasostuinp(gSwodikohasletahwneedrceoRnoatblrsololfdg1or9no8cu1.p).wTaeLsisnsucsaweredrtteroeccnoontsmeipxdtaserroeefdtihfneocrpbeeearscienngt significant a ap valueof< 0.01 RESULTS Overall results: (1)Without activation -- cInointciealntrraaltionnsetgeasttievde)(no significant increases in lls with chromosomal aberrations observed at a2b0e.r1r-ahtoiuornscoonbfsierrmvaetdorayt csotnucdeynt--ranteigoantsivtees(tend.o)significant increases in cells with chromosomal 4ab.e2r-rhatoiuornscoonffpiorlmyaptlooriydystwuedry-e onbesgeartvievde a(tnocosnigcneinfaictainotnisnctreesatsecds)in cells with chromosomal 2) With activation cIonintciealntrraaltionnsegteasttievde)(no significant increases in lls with chromosomal aberrations observed at a2b0e.r1r-ahtoiuornscownafsiorbmsaetrorvyedsattud2y5-0p0osgi/tmi.v)e (a significant increase in cells with chromosomal 4ab.e2r-mhatoiuornscownafsirombasteorrvyedsutt2~7u5p0osdgi/tmiylv.e (Aslisgon,iaficsaignntifiinccarnetasiencirneeceslelsinwiptohlycphlroiodmyoswoamsaolbserved in cultures dosed with 2250, 2500, and 2750 g/m.) 175 0coca 375 aGucget/nimvolat)toiioinnctheeffpercetsse:ncPeoosfitaicvteivraetsiuolnt. foProscihtriovemofsorompaollyapbleorirdaytiaonndseantdtowroedcuopnlciecnattriaotnioinnsth(e25p0r0esaenndce2o7f50 CdwoyestreoedtsowexieitnchicnSo0tn8hce0enmutagri/anmtiisot(nubsdo:ythwIewnriteth:heraanndgew-iftihnoduitngascttiuvadtyi,onc).ompTlehteelcoywteosttoxdiocsietsy awtawshoibcshercvyteodtoinxicculetfufreecsts WithoutIniatcitailv-at0io0n ug/ml 4240..21--bhrr ccoonnffiirrmmaattoorryy~- 640000 upgg//mmll With acItniitviaatlio~n2000 pg/ml 4204..1-2h:r ccoonnffiirrmmaattoorryy-- 22205000 igg//mmll rStaattiesrtincaulmbreesruslotsf:chTrwoomocsooncmeanltraabetriroantiionnst.he main study (2500 and 2750 ug/ml) showed significantly dsRteeattmeiasrtrmiikcansle:swihSgtenaittfhiisectriacncaclhers(oii.mg.n,oisfopimc<aanl0c.ea0b1wearwrsaajstuiuodsngseeddweruarsteihnesgrigtanhirafunilcpeant<tha0at.t0w5p.a)s< s0Nt.r0oi5c,tienrftohramnatuisounalwlaysuasveadiltaobjluedtgoe I1n2t5h,e25i0ni,ti1al00t0i,alanwidth1o5u0t0agc/timv,atiorne,spmeicttoivreclyinwdheexnrecdoumcptiaornesdwweirteh2s5ol%v,en3t0c%o,ntro7l%s,. and 96% at doses of Cinhirtaolmotrsiaolmwailthabaecrtriavtaitoionns,waermietaotniaclyizneddexfrreodmuccutlitounreosfd2o%sewdawsisthcen12a5t,225500,u5g0/0m,lawnhden10c0o0mgp/arme.d wIinththe s2o0l0v0enptg/cmonlt,rols. Chromosomal aberrations were analyzed from cultures dosed with 250, S00, 1000, and aItndtohsee2s0o.f1-8h0o0u.r1c0o0n0f,iramnadto1r2y0t0riualgw/imtl,horuetspaeccttiivvaetliyonw,hmeintoctiocmpianrdeexdrweidtuhctsioolnvsenwtecroent7ro3l%s,. 8C4h%r,oamnodso9m5a%l `aberrations were analyzed from cultures dosed with 200, 40, 600, and 800 g/ml 9102t%heat44d.o2s-ehsooufr5c0o.nf4i0r0m.a6t0o0r,yatnradl8w0i0thuogu/tmalctwihvaetniocno,mmpiatorteidc wiintdhexsorlevdeunctticoonntsrowlesr.e C1h2r%o,m6o1s%o,ma6l39%, and aberrations were analyzed from cultures dosed with 100, 200, 400, and 600 g/m. anntdh3e02%0.a1t-dhoosuerscoonffi10r0m0a,to1r5y00r,ia2l0w0i0t,h2a2c5t0i,vaatinodn,25mi0t0otuigc/miln,derxesrpeedcutcitvieolnyswwheerne c1o3m%pa3r8e%d,wi1t5h%s,ol1v1e%r, onnigrols. Chromosomal aberrations were analyzed from cultures dosed with 1500, 2000, 2250, and 2500 i5n3t%heat44d.o2s-ehsooufr c10o0n0f,ir2m2a5t0o,ry25r0i0al,awnidth2a7c5ti0vaptigonm, mwihtoetniccoinmdpeaxrereddwucittihSonoslvweenrtec1on4t%r,ols1.7%C,h5r6o%m,osaonmdal aberrations were analyzed from cultures dosed with 2000, 2250, 2500, and 2750 g/ml. `"aTnhaelayuztehdosrespadreastcerliybebetcheaufsoellsoowmiengddoesveilaetvieolnss sfhroowmetdheipnrcorteoacsoeld -enednodroerdeudpulpilciactaitoinonanadndsopmoelysphlooiwdeydwere increased polyploidy. 176 0090C'7S 17 Id 000076 1 CONCLUSIONS "hTahmesatuetrhoorvsarsytacteelltshaetxTpe-c6t56a4tawasisngcloensdiodseereledvneleg(awtiitvheafcotriviantdiuocn)intghacthirnodmuocseodmsailgnaibfeircraanttitoonxsiciintyC.hincse tRheemhairgkhess:t Sciognnciefnitcraanttitoonxsictietsytewd.asThoebsseertvweodcoinnctehnetr20a.t1ioannsdw4e4r.e2 ahlscoonpfoisrimtiavteorfyortrcihalrsowmiotshoamcatlivation at ahboewrervaetiro.ns. Thesignificance of positive response in the presence of excessive toxicity is questionable, OMvuarryiH,(.CHO19)96C.ellMs:utawgietnhiacCiotnyfTirmeaotnoTsr-y6A5ts6s4ayMewaistuhrMiunlgtiCphlreoHmaorsvoemsta.l AFbienrarlaRteipoonrsti.n CChoirnneisneg Hamster Hazleton Inc. CHV Study No.: 17750-0-437CO. September 16. 178 0060077 178 RTeivteer:seMuMtaagtenoincitAyssTeasytwwitihtaTC-o6n5f6i4rmianttohneySAalsmsoynella-Escherichia ColiMammalisn-microsome TEST SUBSTANCE entity: T6564 alorefed08s L-13167 and FCI01S.X SRuebmsatrakncse: The substance was ler, colorless uid. No ober information was provided on he fst METHOD bMaestehdoodnGAumideeslitnae.fo(1l9l7o5w)edandCGHrVeePnroatnodcoMlu4ri0e9lR,(1E97i6i) on4. Experimental methods nd mites were C"ToenstfitmyapetsorSyalAmvonyella Escherichia ColiMammalianmicrosome Reverse Mutation Assay witha. Test system: Salmonella typhimurium and Escherichia col sins Gury Year study performed: 1996 SpeciesStrain/cellypelel line: oSaflBmiooncehlelmaisttyrpyh,iUmnuirvieurmsistyionfCsalTiAfSoSr,niTa,ALBOeDrk,elTeAy1.S3S, and TAIS37 rom Dr. Bruce Ames, Department SEtsacthoenr.icShcioatlcaonid.ssn W207 from National Collcion of Indust! Bactrs, Torey Research NMeatHa.boPlOiUcNaactHiPvaOti.ong:luAcrooscelo-rph1o2s5p4h-ianed,ucKeCdLraMtElCiv,er $9 homogenate, pus NADP, 0, RCaonngceefnitnrdaitnigon-s ested: Main sud10ydoses from 667 0 5000 plate 100,333, 1000, 3330, S000 pg ple (ith an without activation) Test conditions: Numberofcells: Densityoftester strain cultures were > 0.5 x 10 bacteria per ml, h$Nee9grmamitixi.cvaelP(owvseeihrtiiecvleues)ceocndtordmorelopsle:sn:dTihTneghseoesnewtewhreerSeuispclndatbebodithfnoiratltlsheseptrresesnaceinanbdoatbhsienntcheeopfrsehseen8c9e manid:sfbsoenncetof 1m 000078 hid During system the was rdaentgeer-mfiinndeidngusstiundSyg., tthyephgirmouwrtihuimnhsitrbaiitnorTyAeLf0fDe.ct (Cyctyottooxtiocixtiycowifatsyhd)eetteesrtmiarnteidctleobtoethae test edyetcorteoansieciitnytwheasnuombsbeerrvoefd rienvetrhetraantngce-ofilndoipnnegrisptlueadyts.e or thinning ofthe background bacterial lawn. No During the main study, both initial and confirmatory studies were conducted. dhTeahpdeetanoudbtsehooransc"tchocermipsttaerrnaiiianefdtoebsarteaypd)osdiiontsimeveeraetnessptroenrveseserutlftaonrwtasinspcer(r0eappslriaontgdeucccooenmcapetanlrtereaadsttiwaoi2nts-hootfrhet3hv-eefhotilesdctlieanrcctoircneltaers.oel.(thTehaemoiunncrte.ase Statistical methods used: None indicated Remarks: RESULTS pOovseirtailvel irnecsruletass:es In in tmhuemibneitrisal oafssreavyeartnadntcsonpfeirrpmlaattoerbyoatshswayi,thalalnddatwaitwheoruet acceptable activation. and In there the were no. cinonSf.itrympahtiormyuraisusmays,trhaoinweTvAe1rSa,37noinn-tdhoeseabrseesnpcoenosfiveS9S-mfioxl.d iTnhcisrsetarsaiinn nwuamsbreertoesfterdevaenrdtaanltlsdwaaaswoebrseerved acceptable and no positive increases in numbers of revertants per plate were observed. Gnoetnoctoonfxiircmeefdfeucptso:n rAetSe-sftionlgd.increase in revertants occurred in one strain (see Overall Result), but was Cmyationtsotxuidcy.concentration: No eytotoicity observed in the range-finding test, and none was noted in the Statistical results: NA Remarks: oSfitnchee tdhoeseporseistipvoensreescpuornvseeasnedenwawsitnhot. retpyepahtiabmluer,iuthmeTtAesLtSa3ge7nto,ccTu-r6r5e6d4atisocloynsoindeerdeodsneeagtattihveebiengithninsing CONCLUSIONS Tthheenauumtbhoerrsocfornecvleurtdaentthsatpeurndpleartetohefcaonnyditteisotners sotfratihnes,stcuidthye,rTi-n6t5h6e4adbisdenncoet ocfaupsreesaepnocseitoifvethien9creamsixe.in REEERENCE mLiawclroors.omT.eE.Rev1e9r96s.e MMuuttaatgieonnicAistsyaTywesittwhiathCoTn-f6i5r6m4ationrtyheAsSsaalym.oneClolmai~ngEsHcahzelreitcohniaInCc.oliFiMnaamlmRaelpioartnCHV Study No: 17750-0-409R. September 13 180 180 000079 TLiytmlep:hoMcuyttaegsenWiictihtyaTCeosntfoinrmTa-t6o3r4y2A,sMseaaysuWriitnhgMCuhltriopmloesHoamravlestAsberrations in Human Whole Blood TESTSUBSTANCE Identity: T-6342; clear, colorless liquid. No other information was given on solubility or purity. Remarks: METHOD Method/Guideline followed: Protocol No.: 449C0, Edition No.: 2, Modified for 3M Corporation Test types i vitro mutagenicity assay Test system: Human whole blood lymphocytes GLP: Yes Year study performed: 1996. `Species/Strain/cell-type/cell line: Human/whole blood lymphocytes hMoemtoagbeolniacteasctfirvoamtiloinv:erWsiotfhraatnsdpwriettrheoauttedmewtiatbholAircocalcotriva1t2i5o4n fforrotmhethneonSs9pescuipfeircnaitnadnutctfiroanctoifon of metabolizing enzymes. Concentrations tested: Range Initial finding assay--0.167,0.500, 1.67, 5.00, rial (without activation)--127, 253, 505, 16.7, 50.0, 167. 500, 1670. 5000 1010, 1510, 2010, 2510 pg/mL; pg/mL; Initial ial (with activation) Confirmatorytrial (replicate c--ul2t5u3r,es5,0w5i,th1o0u1t0,ac1t5i1v0a,ti2o0n1,02,2.2151h0o,ur30a1s0s,a4y0)--1102g5,/m2L50;, 500, 900, 1200, 1600. 2000 pg/mL; Confirmatory trial (replicate 1200, 1600, 2000 pg/mL; cultures, without activation, 46.0 hour assay)--62.5, 125, 250, 500, 900, Confirmatory tial 1000, 1500, 2000, (replicate cultures, 2500, 3000 pg/mL with activation, 22.1 hour assay and 46.0 hour assay) --250, 500, SFtiasthiesrt'iscaElxamcettTheosdts(Tuhsaekdu:r eSttaatli.stic1a9l8a5n)altyosciosmeparme thpe paeClrocecnhotraagnyeo-Afrcemeiltlsadgweitthestabfeorrraltiineoanrs t(raenndd, ainfd atprpelaitceadbcleel.lsthweitpherrceesunlttasgeforfomcevlelhsicwliethcomntorroles.thTaensotnaertaibcelrersaitginoni)f.icpaonlcyepwloaisdye.staanbdliesnhdeodrwehdueprleicpa<0t.i0o1n. in All factors as stated previously were based upon scientific judgement. taken into account and the final evaluationof the test article was. 181 000080 181 Remarks: ExpeHruimmeanntavleDneosuisgbnlood from asingle, normal, healthy male donor was drawn into sterile, HfienpdairnigniazsesdayV)acourta0i.n6emrsL.oCfulbtluoroeds/1w0e.r0emiLntciutlctdurweit(hch0r.o3mmois.oomfabllaoboedr/rSatmiio.nscauslstuaryes)(dines1e5rmaLng.e. acennattrimfousgpehteurbeeos.fTahbeoucetll$s%wCerOeiinnaciurb.aTtehdeatcualptpurroexmiemadtieulmy 3us7edCwoansaRsPloMpIe,1w6i4t0h (lRooHs.e caps, in raBniogsec:ifeinncdeisn)gsauspspalye:mLeontteNod.:wiTt0h610524%,fectharlobmoovsionmeasleraubemr(raFtBiSo;nsBaisoscahy)e,me1d%. LphoyttsoEhSem3a3g1e,lduotsienin CQ(uPHaHVlAi.-tMyL:oB;itoGli2ob0gc)ioc)wa.lasps)e.tnihacenidlslo2ilnvme(nM1t0o0Lf-cughnlioutitsciamemLi_fn;oerQ(utQhauilsailtaiystsyBayiB.oilooTlgohigeciactalelssts))a.arntdiDcelsierowcnpaitzsoeddmwiysacstionelrv(e1(d0Pi0rnuepga/remdlat cdoenitornoilz.eddewiaotniezreadt waactoen,cewnetrraetdioonsoefd w5i0t0hmadao/smiLn.gTvhoelutemset aorft1ic%le s(o1l0utuilomnsLa)ndftohethvieshaiscslye. Negative and Solvent Controls mInedtihuemn.onSaocltvievnatticoonnatsrsoalyssw,enreegactuilvteurceontthraotlscownetraeinceudltduerieosntihzaetdcwoanttaeirnaetdhoenlhyigcheellsstand culture s`coolnvceennttrcaotnitornolusswederien ttehsetscaulmteuraessd(e1sc%riobred10i.n0tphueL/nmoLn)a.ctIinvatthieoancatsisvaaytsi,onbaustsawyist,htthheen$e9gaatcitvievaatnidon mix included. Positive Control Agents "0T7h-e7p,osSiitgimvae,cLoontttro4l0aHg2en5t0s8,)whfoircthhewenroenaucstevdatiniotnhesearsiseasysa,ndwecryeclmoipthoomsypchianmCid(eM(MCPC:;CCAASSH# S06a0be5r3r5a-t1i9o-n2s, aSsisgamyas,, Ltorte#e4co3nHc0e2n6tr9a)tiinontsheofmeMtMabColi(c0.a0c8tiavnadti0o.n1s0ergis/,m.In tihneitciahlraonmdoscoonmfailrmatory ctwhiralos;mo0s.o1m,al0.2,aabenrdra0t.i3onus.g/OLn,eotfhitrhdetrdioshs)ealnedveClsPw(a2s0,a3n0a,layzneddi5n0cgacmh)of wtheeraebeursreadtitooniansdsuacyes. Both MMC and CP were dissolved in water Range finding Assays I2dnatyhessepraisosraytso,tcruelattmuernets.were initiated wit0h.3 mLofblood/$ mi. culture and were incubated for Assay Without Metabolic Activation "`TwhaeshIeydmpfhrooemyttheescwelelrsewiintchupbhaotsepdhwaitteh-btuhfefteersetdasrtailcilneefaonrd1f9r.e5shhocuormspalte~t3e7mCe.diTuhmectoenstaairtniicnlge was `TaCtoerl.cemid (final concentration= 0.1 g/mL) was added. The cultures were harvested 20 hours `Assay With Metabolic Activation Ipnretsheinscaesosfay,a tahte lliyvmerph$o9cyretaecstiwoenrmeiixntcuurbea(t$ed9<w1i5thltihmei,tesNtAarDtiPcle= f1.o5r3mhgoumrs,atan<d37isoCciitnritcheacid olrivd2ee7rro0mfgma/avmlo)ei.dSppTorhsasegiubSel9-eDfiarnawaclctteiiyovnart(aitMoso,nlowcfhcsiuhlcoahrrthTalodixvibecdeoanlnodgpyrh,eivgiIhnoclu.ys,lLryeoatcrtteai0tv6ee6d7iwn)ittewhramsAerddoiecartlieovsredp1r2fo5r4do.umcIetndheby. `iehxep$os9uerenzpeyrmieods. tAhfrtoeurghthbeienxdipnogsutroespeerruimodp,rhoteeicnesl,lsthweermeedwiausmhedditdwinoctehwaivtehFbBufSfedruerdinsgalitnhee. 182 182 000081 mCCeooalmppehlaeamtsiecdRcPe(Mlin.Ialclctounrceentmradtioin =w0a.s1 dgdmd0whheiecuhltwuaress,dwheidchowrrheefintcub2.atehdvfoer 1to6s. ehosurs AsaMmyiettEoatvpihacassiiensodnreexsewnatsinan1a0l0y0zceodnsfereoumivtheclssurviving dose levels by analyzing the number of ChrnTonemghaotesicovhmeracolomnAotrbsoeolrmsa,atlpiooanbseArirsastciaooynn--tWrsoialty.hsa,nadnredspWlliivtcnhato,uCctolMnutoeotlsb.owTlrhieeAcsbtreiadvatatitiooennalsadyossrevee aennddored cWIoeinvlflisharma2a2n.t0doorfyuormraosnh.earoCefhsrttohemmopesosminaitlh acbonernirtaoltliorndsioanwsaenrde waniahly2ze.d1o4md t46h.0chuowessasrerudpmnessdetc Ab1oC5rultmtiuLorencseAnwstesrairfyungWeitbiheouste2TMdeawdtyoasbodplaiycsraAftcoetiitrvecasottlimonerrntnwaitthio0.n6,cmlLsofwwehreolre eloogd/1i0.0tmeLccpulturceiisnt ippltraehcdebdeutfbmfierneeoaddnstcalocinhnceee,nctCklrolamt.piloTentsweooRrhPopuMprIsrco16Ir1T,0AmtIehdCeicu1am9l.,3wcaornndeta4ih3ni3nagho0ur.r1s.svaTngdhenea.iuesdCriteocscwhdeorwe mweaane wmbairdtmehi.ouotTnhsmee.silaTibadlbeilscewea|crcteivsaottaiionnnedaSsnu$mi5m4aGsriyemostafhSoleuatomnenft oehheedanuallsysoifs oofecahrhomeestmunsassy AbeC1r5aimlLnlscAewsnstearriyfuWngiethbMaecss.2btdToawlyocsedpAacrytiidovfrateiosncaulmuersnnwaitthio0n.6,tmhl.coflwhoelewbserlonacdbm/ia1.sct0tl-a.3er70eodCin fcoxorpmpoSlsoeuterpsRerPiinMoIhd,et1p6h4r0 lmslesedwioneurfmce. heweOanst-ehseteandtrth igic/nmlwLdi.thhCeboul5fc9faeemreaidcdilowneasmdaineud d.he0Aecfthe heweerrsee-rsheoeudnduwnigththe mTaty22s.0 hoursof incubation. The meaphisecls were harvested and predor yopenee Ha"rwTvihelsehtclhPylrpoosctueosdnpuiercnesKiCoInw(a0s0c75ntMi)ffgoerd=,10thesminuutep. eAfrwemansafdigtscaaatrdoendn, annddteh ocnlssowfeteereKstoedhe 5el1l,s0w)e.reAwiadesdh3siiedmedsswewirth prrespahrepdreopamrehdehaartvievsete(dscsllc methanolie ser si. SlidSweliPildhrees5p%waerGraieetpmiraseonapndasrSoelsduitbiiyonndgfroorptihnegatnhahalrovyefsmstietdiocsultuirnedsexonanldeharofmdoss.emTihsessbiedneastwornse sind Sides ers aedieanddcover ppd. AboiCareltlimsowodenarAlenussmeylbseectread4nf6dorwAegsroaeydanEmvaoallryupa.thiooOnlnonehudyndornleydccelllss,wpiot sheen,umbreormocfaccheentprsomsqepuruarlet0sot 4 dose Teoeftlh est article, th negativecontol, thesolvent ono and pois ome] 183 000082 18 cc2u5hclretolumrleossswowemerarele aaannbaearllryyazzteiedodnfsf.oorrCctehhlerlodmiwfoifsteohremsnaetlrtrayabpteeirsrooanftsicowhnesrroefmrrooesmcootmrhadoelsde.abcMeuirltrtoauttriiecosniwsni(dtEehvxa~wn2sa5,s%1a9cs6es2le)ls.ssewAdittbheyast amtainbtauolltyaiztciendce.glltsTh.heeCynhurwmoebmreaertnioodftm,ainthdoowtieisvcoeccrhe,rlocsmo/an1ts0ii0dd0egraceepdlsl,isnifhothebesreearvtvaieloudwa,atiwsoeenrxoepfrnetoshtseeedadbiianlsitthypeoerfractwehendtatateagseaanortdficwleerteo tihnedurceesuclthsrowmeroesotmaabullaatbeedrrations. Percent polyploidy and endoreduplication were analyzed and RESULTS Overall results: positive,negative, ambiguous: Negative Genotoxic effects (unconfirmed, dose-response, equivoca--l with/without activation): Negative Cytotoxic concentration: RangHee-mfoilnydsinigsAwsassaoybWsietrhvoeudtprMieotratboolwiacshAcitnivtahteicounltures dosed with S000 ug/ml. Reductions of d3o5s%e,d6w%i.th308.%5,001,51%.,67,185%.,005,71%6,.7,an5d001,0106%70w,earnedo5bs0e0r0vged/imn.the mitotic indicesofthe cultures. RangHee-mfoilnydsinigsAwsassaoybWsiertvheMdeptraiboorltiocwAacsthiviatitohne cultures dosed with 5000 g/mL. Reductionsof%, 5S0%0..41%6,701,%a,ndanSd001000g%/wme,reaosbcsoermvpeadreidn mwiittohtticheinsdoilcveesnotfcotnhtercoullctuurleused.osed with 1.67, 50.0, Chroimniotsiaol mTarilalA--beHrermaotlioynsiAssswaaysWoibtsheoruvtedMeptraiboroltiocwAacsthivianttihoen Reductionsof 38%, 18%, 18%, 50%, 35%, and 95% in the cmiutlottuircesidndoisceeds,waisthco2m5p1a0rge/dmwLit.h the saonldve2n0t1c0onptgr/omlLc.ulrteusrpeesc,tiwveelrye.observed in the cultures treated with 127, 253, 505, 1010, 1510, t`hCecounlftiumreastdoorsyedTrialw--itIhnt1h6e0022a.n1d-h2o0u0r0cgon/fmiLrm,ataonrdyatsriiagl,htheemvoildyesnicseowafshoebmsoelryvseids pwraisorevtoidweansthatof h9a3rv%esitnotfhethmeitcouilcturiensdidceoss,edascwiotmhp1a6r0e0d gw/itmhL.theResdoluvcetnitoncsoonfto2l%c,ul1tu4r%e,s,6w4e%r,e7o4b%s,cr9v3e%d,fnantdhe `ccuolntfuriersmadtoosryedtrwiailt,hhe1m2o5,lySs0i0s,w9a0s0,ob1s20e0r,ve1d6p0r0i,oarntdo w20a0s0h pofg/tmheL,curletsupreecstdiovesleyd.wIintthhe14660,00-anhdo.ur te2h0e0ms0olgv/ermnetLsp.ceocntRtievrdeoullyc.ctuilotnusroesf, w59e9r%e,o9b3s9e%,rv9e8d%i,natnhde c9u8lt%urienstdhoesmeidtowtiitchi9n0d0ic,es1,20a0s,co16m0p0a,raenddw2it0h00 ChroInmiotisalomTarliaAlb--eHrreamtoiloynsAissswaaysWoibtsherMveetdabporliiorctAoctwiavsahtiionnthe cultures dosed with 2010, 2510, 3010, awnidth40401100gg//mmLL.. NHoemcoelllysswiesrweavsisoibbsleerpvreidorptroiotrheoatdhdeitaidodnitoifoCnooflcCeomlicdemitodthetocutlhteucruelstudroessed dosed with 3010 ug/mL. Reductions of 15%, 20%, 15%, 43%, 77%, and 95% in the mitotic 184 0060CS3 184 indices, as 253.505, 1c0o10m,pa1r5e1d0,w2i0th10t,heansdol2v5en1t0 cpognt/rmoLl,curletsupreecst,ivweleyr.e observed in the cultures treated with a`CnodnpfriiromrattoorhyarTvreisatl-o--fItnhethecu2l2t.u1re-shoduorsceodnwfiitrhma2t0o0r0y,t2ri5a0l,0,heamnodly3s0i0s0wpags/moLb.serRveedducptriioonrstoofwa1s5h%, c5u%l,tur6e9s%,, we82r%e,ob9s7e%r,veadnidn 1th0e0c%ulitnutrhees mitotic treated wiindtihce5s0,0,as1c0o00m,pa1r5e00d,w2i0t0h0t,he25s0o0l,veanntdco3n0t0r0ol agn/dmpLr,iorretsopehcatrivveelsyt.ofInthtehecu4l6t.u0r-ehsoduorsceodnfwiirtmha2t0o0r0y,t2ia5l0,0h,eamnodly3s0i0s0wga/smoLbs.erRveedducptriioonrstoofw1a5s%h, o8b0s%e,rv1e0d0i%n,tahnedcu1lt0u0r%esintrtahteemditwoittihc 1i5n0d0ic.es2,00a0s,c2o5m0p0a,raenddw3it0h00thges/olmv,enrtescpoencttriovlelcyu.ltures, were: Swtiatthiosutticmaeltraebsoullitcs:acTtihveatieosnt. substance did not significantly increase chromosomal aberrations with or Remarks: ChroImnoitsiaomTailaAlb--erNroatsiiognniAfiscsaanyt Without increase Metabolic Activation in calswith chromosomal aberrations, polyploidy. or endoreduplication was observed atthe concentrations analyzed (253, 505, 1010, 1510 g/mL) c`hCroomnofsoimralmTaarbietarlroa--rtinyonst,hepo2l2y.p1l-ohioduyr. coornefnidromraetdourpylitrciaatl,ionnowsaigsniofbisceanrtveidncartetahsee cinocneclelnstwraittihons anianlcryezaesed i(n1c2e5l,lsw25i0t.h5c00h,roamndos9o0m0alpga/bmeLr)r.atiIonntsh,ep4o6l.y0p-lohioduyr, coornfeinrdmoarteodruypltirciaalt,ionno significant was observed at the for cionnduccetnitornaotifocnhsraonmaolyszoemdal(1a2b5e,r2r5at0i,o5n0s0w,aasnds9h0o0wng/bmyLt)h.e iTnhceresaesnesditfivrietqyuoefnctyhoecfealbercrualttiuorens in the cells exposed to MMC, the positive control agent. Chromosomal Initial Trial A--beNroratsiiognnsifAicsasnatyinWcirtehasMeeitnacbelollsicwiAtchticvahtrioomnosomal aberrations, polyploidy, or `endoreduplication g/mL). was observed at the concenizations analyzed (505, 1010, 1510, and 2010 `cChornofmiorsmaotmoarly aTbriearlra--tiIonnst.hepo2l2y.p1l-ohioduyr, coronefnidromraetdourpylitciaalt,ionno wsaigsniofbiscaenrtviencartetahsee cionncceelnltsrwaittihons analyzed (250. 500, only 52 metaphases w1e0r00e.aavanidla1b5l0e0foprg/amnaLl)y.siIsn itnheon4e6.o0f-thhoeurcuclotnufriersmdaotsoerdy trial, with due to toxicity, 2000 g/mL. No. significant increase in cells with chromosomal observed at the concentrations analyzed (500, aberrations, 1000, 1500, polyploidy, or endoreduplication 2000 pg/mL), except foar weak was. winacsreialsleusitnraetneddobryedtuhepliinactrieoasneadt i2n0c0i0degnc/emoLf.celTlhsewsiutchcecshsrfuolmoasctoimvaaltiaobneorfratthieonmsetianbtohleiccusltyusrtese.m treated with cyclophosphamide, the positive control agent. CONCLUSIONS Tblhoeodteshtuamrtainclel,yTm-p6h3o4c2y,tewsacselclosnwsiitdheraenddnweigtahtoiuvte mfoertaibnodluiccinagctcihvartoimono.soTmhaelsaebreersrualttisonwserienvceurlitfuireeddinwhole. independently conducted confirmatory trials. 185 000084 185 a MuBrlolo,d LHyemmaplhaotchyat.es19W96i.thMuataCgoennfiicrmiattyoTreystAsosnaTy-W6i3t42h,MMuletaispulreinHgarvCehsrtos.moCsoommiangl-AHbaezrerlattoino,nsInien. W(hCoHlVe). Vienna, VA. CHV Study No.: 17073-0-49C0. 186 186 000085 "(TCitHleO:)MCuetlalgseWniictiathyCToensftiornmaTt-o6r3y42A,ssMaeyasWuirtihngMuClhtripolmeoHsaormvaelstAsberrations in Chinese Hamster Ovary TEST SUBSTANCE Identity: T-6342 C: clear, colorlessliquid. cRoenmcaenrtkrsa:tioTn-6o3f44298w0asugs/olmuLblien icnulsttuerrielem,eddeiiounmizreedmawianteedr >c4o.m9pl8e0tge/lLy. (stohleubtlesetastuabsptHaonfce at7.5a). METHOD Method/Guideline followed: Protocol No. 4370, Edition No. 4, Modified for 3M Corporation Test type: Invitro mutagenicity assay. Test system: Chinese hamster ovary (CHO) cells GLP: Yes Vear study performed: 1996 o`Srpiegciineasl/lSytorbaiian/ieneeldl-ftryopme/tcheellllaibnoer:atCorhyionfesDer.haSm.stWeolrfofv,aUrnyivceelrlssi(tyCoHfOC-alWiBfoLr)nifa,roSmana pFerarnmcainsecon.t Tcehlelcienlel,s iusmeedoinft1h2i-s1s4thudoyurhsawdibteheanmroedclaolnecdhrtoommoaisnotmaeinnukamrbyeortoypfic21.staTbihleityC.HTOhiscelcllslwleirnee ghardowann ainveMrcaCgoeyc'yscleSa culture medium, which was penicillin and streptomycin, supplemented with 10% at approximately 37C, fetal in an bovine serum (FBS), atmosphereofabout 1% 5% L-glutamine, CO in air and 1% `Metabolic activation: With and without rat liver $-9 Concentrations tested: RaInnitgiael rfainldi(nwgitahsoustaya--c0t.i1v6a6t,io0n.)4--9182,5,1.26560,,4.59080,, 1765.06.,4190.050,, 116560,04,9280,01066p0g,/m4L9;80 pg/mL; Initial rial (with acivation)--250, 500, 1250, 2500, 3750, 5000 pg/mL; Confirmatory trial (withoutactivation)--125, 249, 498, 746, 995, 1490. 1990 pg/mL; Confirmatory trial (with activation) --249, 498, 1250, 2490, 3730, 4970 g/mL. Repeat tial (without activation) 250, 500, 1250, 2490, 3740, 4980 g/mL Statistical and RohIF, methods used: The 1981)was employed Ftioscheorm'psaErxeacthteTpeesrtcweintthaagenaodfjcuesltsmewintth for multiple aberrations comparisons (Sokal in cach treatment `roup with the resuls from the solvent controls. A linear rend test ofincreasing number ofcals with easbtearbrlaitsihoends wwihtehreinpc<r0e.a0s1ing dose (Armitage,1971) was also performed. Test article significance was Remarks: ExpeIrnitmheentcahlroDemsoisgonmal aberrations assays, replicate cultures were used at cach dose level and for negative and solvent control. Single cultures were used for cach of two doses of the positive 187 000086 Iw cawonrndterwolia.tnhaTl2hy0ez.e0ad-beafrnordamt4it4oh.ne1s-cahusouarryeshsawrrevearsettecidoneadsu3citdeodtsheweicetvohenalfi2ae0nm.ad0t-ohonoyumrvihoaasr,nveCsohtniieomomfeestienertmphe)ossthcrialcriemsl doves. NegaImtneidvtiehueamo,nndaSScotvlvveeanntt:iocCnoonnsttraroyollsss,wenreegactuilvteurceosnctoonltawineirneg ctuhletSuerievsetnhtatfocronttheaiensetdrnillyeeolsthaengd hcuelteure cthoencseantmreataisodneusscerdibien eisntthculntuorneasc.tiInvthieonacatsisvaaytsi,onbuatsswaiytsh,htehe$5 cttivieaonndSmoilxveinntcchoedm.et were Posit0Ti7hv-ee7,pCooSsniittgirmvoael,AcLgooentntttosl25aHgOen6t1sS,)fwhoircthhewenroensuctsievaitiotnhseeaiscssayasn,dweryeclmoipthoomsypchianmC(idMeM(CCP;;CCAASSHY $06awb0ie5lr5r;-a1t09i.-o52n0,saSansidsgamy1.a0s,g. /LwomotL#c6,o7nFctOeh1nit5rrd3a)itiaion)ntshaoenfdmMeCtMPabCo(5l.i(0c0.aa0nc8dtiavn10a.d0t0ig.on1/0smeglri)Le w,Inotrinhiwtceahldraonmdoissnodounmciiemt.matory cahherroamtoisoonmsaalyasb.erBaottiohnMsMnItCheanCdHCOP cweellrseOdinsesoolfvtehdeidnowsaetelrevels was analysed in eve ofthe RangeTn hiensienagssAasyss,aytshe els were culured or approximately (=) 24 hours prior to treatment by as1ccchodineitvaneid=gnsw0i.st3huxam1m01a9rc(ye1ol0lfsmt2h5Lerm)aflmdaoesskinnigSnctoohfe$cdaumclLheosoffochcoemsprolalneudtteieo-nMcnaCdnidonyhg'esassSsoaalyvceunAltltlucrodenotmsreiodnlgiuuwmln,saTrabwles dosed with 10 uLinLofserif deionized water Assa"`yTwhaWesihctelhdoufuertosmMweeharebeocilenillccsuAbwcaitttihevpdahtwoiisotpnhhatthe.ebsutffaerreidlsafloirne17a.8dhoeurhs acto3m7plt.e Tmheediteusmt acrotnictlaenwiansg CHaorlvceesmtiedd2(.0fhinoaulrsonacteenrtation 0.1 g/mL.) was added. Th cultures were the eypinized and AssaoIynfaWthiaitsthaiMsveeatr,ab$to9hleirecCaHcAtcOitoineveamltiisxotwnuerree(eSx9po1s5edutlomt,heNteAstDarPt~icl1e.5fmog3r/hmouLrsanad ~s3o7cCiinctihde pr2e5s.ence mmavagol/iemdSLp)por.sasgTiuhbeeleD$ia9nwaflcatecityviatoriantosn(o,MwfohlseihccouhrlthaarvdTeobdxeieacnnodlporhgeiyvg,iohnuysclr,yeaeLcotsittvheed0i3nw6ti3et)rhmweAdarioacdtleeosrrper1d2o5d5ru.coeImdn otbhdyeenvreetry$9of cpMencrziCoyodm.ye'sAs tf3harromtuehgedhiebuxipmnodswiuanrsgeoapdedsrecidroudtmotpthhreoctcleiusnr,wseth,rewmwheaidscihheuwdmetdrwediccneutwibatehvedbuFffofBeSre1dd6u.sr8iahnego,ttshCe oeixmpposruere CmSteoatlianepehndaiassdedceo(sflrisniablTechdoenfccoeurnltttrhuartneioownnesrc=ei0vr.1ayptsoginn/iamznLegd,ewhhiarenvdheiwsntagesdaa,sdsidyee.dd,faonrdthSidlesst w2.e0rhopurrospanceolalnegct AssaMoyiftmEoevttailacupiahntadiseoexnswparsesaennatliyze1d00f0rocmontsheechuitgihvesstcfilve suviing dose evs by analyzing the umber 188 060s? 134 Abcration Assay Without Metabolic Activation a`ceCflutllrstuc(r=ue4ls4uw.re0erheioniuinrittaiisaostaenyd)fbpoyetsrch7e5diinenimtg'aalpaflpnarsdokcxoiinnmtfaoitoe1lm0yamt1Lo.r2oyfxic1a0omlpceltlehltesec20Ml.c0lCowhyeo'uesriSasanscmaeyu)dbiauanmd.02O83n9exd1C0ay atWshiselahsyo)hlveheontuetrsstc.oanArttlrioclldeocsautilntpguerwdeaewstaeasmcdihoniseeevddeddwwoisitethsh1f0or1a%bom(u1Lt0ou1f7L.si7tmr(L3).0ddohseoiounnsgizsofesedaaw)cahtaens.tdoTc4k1h8sc(ou44tu1iennoudr aC`wnedorealiwra-cdsrheieeddmwswaliiisdtedhslabwucefe,rfdeerbemudacdskeal.ointTe,ohCtholemdpcellseswt.eerAMpecpCrsooixyin'msdatSnealmy3e%2dihGuomiw,soctonsrtoaluittnihionncglfos0.1r gtmhamrLes.nhairpvesstoerd ciFhBnScr.uobmaAotfsetodemraathl~e3a3b7e-rhCafotuoirro3enxsp.hooFsuourrrsethnptehertihoidpr,rtherseielncecolelonsfwdehareyeafwefsaetsrahrcetiduclrteweiicnteMiwciaCtthoiybuosftneh$.raemcduelsdtaiulriuenmse awwintdshothuet Cuaprltilonggwenehcreircleasfnteadl=y2ws.ii0ts.hhocuormsploeftiencMucbaCtoiyon'.s TShaemmeedtiaupmh.asOenec-ltesntwhemeLha.rveCstaedlaneddprewpaorseaddfdoerd Aberration Assays With Metaboli Activation lCautllestru(rc4eu4so.1wreehroenuriinaaistoisnaaty,e)dbhpyeersce7e5udrcimen'gsfahlpaaptsrkwoeixnritmeoat1r0mealtyLe1d.o2ufnx1cdo0emrpltceeeltlecsoMn(d2ci0t.Ci0oohnyosuor5f2amsmesetadaybi)oualmni.cd Os0n.e8etxdae1iy0n cwinarcMehcsCiionocycu'kbsastoSeladutmaiteond3ia7undmtwhifetohsoroultvheoFnuBtrSsc.oinnAtlrtlohledpcousrlietnsugrnwecaewsoaafsctdhhoiseevedetdwiawtrihtit1lh0e La1n%mdt(.h1e0o8Lf9isremera)iceidoodnseiimnoignxitsuerde heatelelcru.wlteAurreerrmeefthededi3wui-mthhoduucrroiemnxpgploetsthueraMesctpCe~o2r.y0io'hdsotuSahrsmceoldfsiuinmwc.aubrOatnwi-oants.hnetTdhhtgimcenet.awpihCtahoslebeusfeefmleirsdewdesrwaeaishnaardnvdedesdtsetdeo and prepared for cytogencic analysis. HarvPiernsictolruPdroteohdceadnuhraaesrsvsesstmoefntthoeftcuhletupreersc,evnitsucaolnofblsuecrnvcatoifontsheofceollxmioinylawyereer mwaitdhei,n TthhesceuotbseervPaatcikosns T"iTnhhteeerccpuuhalrseeesscelwflseoarmndtlhsweedrcoeasleeuraaattneeedd.wfoiirntdhtihn0eg.0pa7rs5essMaeyncKweeCorfhtytrpoyoprtsioicnniioczdesdoofudrtsotcnl0.csTofhlloctautmlioangrtinwtheearmwesfeixded swiitehdraendabssiodleustewemreethparnpoa:rgeda.cial acti acid (1, vv) Txative and washed several times belone SideSWliPilrdheeps5a%wreatGriieoenpmrasenapdasrSoetldauitbinyoinndgfroophpeinantahleyshiasrvoefsmtietdotcuilctuirnedseonancdlecahnrsolimdoess,omTahleasbleirdersatwieonrs sAltland Slides wee i-dried an cover sipped using Depexc mounting medio AnahllelyssmoiowfdsesrA]beensruermlabetceitorends2f1oan+dg1oA(ossdraamynogrEe-pvha2oa0lt.oig2oy)nawnrdeolanyaleyzlesd.wiOtnhethheunndurmebdecreollfs,catproosrnseir,s fcqruosml cCualcthurreesplwicraeteacnualltuyrzeedatfordtohsdliefvferlesnotfethsesotfcarhtriocimcoasnodmaflroambtehrratnieognasti(vEevannds,s10o63)p, Actoemaos 1s 000CSS 18 mC2ie5tlolctesilwlcsictwehellrasbe/e1ar0rn0aa0tliycozenlesldsw:fetorhreechrtaertcoioomrdowesado.smeaMxliptraobetesircsreiadtnidaoesnxswpfaersrocmaesnostneaesgosefeodftbhmyeiatponotsaiilctyizcvieelnlgcso,tnhCterhornloumcmuabltteiurdreosaf.nd hisoowcehvreorm.atciodnsgiadpesr,edifionbsteherveevda,luwaetrieonnootfetdheinabtihleitryoawftdhateataesntdawrteircelettaobuilnadteudc.e Tchheroymwoesroemanolt. aberrations. Percent polyploidy was analyzed from the ~44.0-hour assay. SULTS Overall results: positive, negative, ambiguous: Positive siGnuebntshotetaopnxrcieecsweenafcsfeepcaotnssidt(aiuvbnescefononrcfelioarfsmteaodng,eSdn9oiscmeea-tcrtaeibvsoipltoiyncsfaoecr,thieviqaguthilioyvnotsciyasc--tlemtw.rietaThth/meweinttteshsootfuesdthsaoucrbtstitvdaautnricaoetnwi)o:ansT(ha3elshtooeupsrtoses)ditbiovteh, for polyploidy for the highly toxic treatments. iTCnhycitrsoetasosexecisticioncnoconhncrleyonmtdoreasstocirmoiabnle:sabtehrercayttiooxniscoictcyuorrbesde.rved at concentrations at which statistically significant ChroInmiotisaolmTaelalAb--eTrhraetitoencsatAmsesntaywiWtihth37M5e0taubgoilmiLc. Awcatsivoantliyonslightly toxic, but the S000 ug/ml aatrnneddaoatmnbelonyutt9w47a5ms%ethriaegpdhhulacystetisooxniwcef,orrceatauhnseairlneygpzlaaibbcolauteetfc9ruo5lmt%urtreh.eedFcuulclottaiutorinengiwnidtmehoandgorcleeaaltyleserratncodxoindcfeiltbuyrei(ns5cw0ye0rf0eoruagob/numenld)c.aunltt,ure CFoonrftihmem2a0tohroyuTrrialharv--est, the confluencyofthe cultures treated with 4970 ug/L was reduced by i(anb2o0muihttoou7tri0ch%airnavdneedsxt)t,hetmhietroetwicasinadpepxrowxaismarteedluycead3b0y%4r3e%d.ucFtoironthien ccuolntfulrueentcryaatendd wainth153%73r0eduugc/timoln Aber2ra0tihoounr AhsasravyesstW--itAho3u0t%MerteadbuocltiiconiAcnticvoantfiloune;n3e-yHoocucrurTrreedatimnetnhte cultures treated with 2490 cuogu/lmdl.beTehxeamnienxetdh.igher dose, 3740 ug/L, was so toxic that only a small numberofmetaphases 43474h0ouurghiarmvLeasntd--tAhe 52459%0ruedgu/ctLiotnreinatmmoennotlraeyseulrtecdonifnlaue3n0c%y orcecduucrtrieodn.inTthhee cmuilttoutriecsitnrdeeaxtewdawsith significantly reduced (7%) for thehighdose (3740 ugimL.). StatiCshtircoamlorseosumlatls:Aberration Assays With Metabolic Activation cIunilttiuarleTsrdiaolse--dSiwgintihfi3c7a5nt0 ianncdreSa0s0es0 ign/cmeLl.with chromosomal aberrations were observed in the aCboenrfriartmiaotnsor(ysimtrpalle--aFnodrctohmepl2e0xh)owuarshaorbvessetr,vaedfsiogrntifhiecacnutltiunrcersedaoseseindcawliltshw4i9th70chgr/ommo.somal wAalst,honuegvehrtthheel4es9s7,0ngot/emdLthattretahtempeenrtcweantsp(o0l0yptloxoiicdocelyliselidncsruefafsiecidensitgnmieftiacapnhtalys.es for analysis, it 190 000689 19 ChroAmosisgonmifailcaAnbteirnrcarteiaosne AinsstahyesnWuimtbheoruotfMceltlasbwoiltichAcchtriovamtoisoon;ma3l-HaboeurrraTtrieoantsmweants obscrved in the ocublsteurrveesddoisntehdewciutlhtu3r7e4s0dogs/emd.wit(7h.53%7)4.0Ag/smigLn.ifiTchaentmiintcorteiacsienidnexpewracesntsipgonlifyipclaonitdlyy rweadsucalesdo. (57%) for the 3740 g/mL. dose. RemaRrankgse:-finding Assay Without Metabolic Activation wInasth<e 5cu%ltcuornefltureeanttedanwditthhe49cu8l0tugr/emcoLn,sinsotevdisoinbllyeomfidteobtricislalnsdwdeeraedocbeslelr,vefldo;athiengcoerllatmtoancohleda.yeAr s1e6v6e0rejrmed.uctiTohneincetlhlemnounmoblaeyroerfvliosoikbelde umnihteoatlicthcyelalnsdwathse odbesgerreveeodfincotnhfelcuuelntcuyrewdaossereddwuictehd bcuolututre1d5o%s;edflwoaittihng49d8eagd/cmelLl,s abnudt doetbhreirswiwseerethneocteudl.turFelowaatsinsgidmeiblraristwoatsheanlesgoaotbisveercvoendtoiln,the aMnitdotciocmpiandriecdestowetrheesaonlavleynztecdonftrroolm. thAetc1u6lt6u0regs/dmoLs,edthweitmhit1o6t.i6c, i49n.d8e,x w16a6s, e4s9s8e,ntainadlly176c0ro,ug/ml However, ng/mL. litle or no reduction in mitotic index was observed a the next lower doseof 495 Range-finding Assay An unhealthy cell With Metabolic monolayer was Activation observed in the culture dosed with 4980 g/mL. The cell o`fmvoinsoilbalyeermictoontfilcucenecse owcacsurrrede(abbdoyutau6p3p%rc)o.xiAemtattedhleyne8x5tl%oawnedrdaosseevoerfe 1r6ed6u0cptigo/nmLin,tthheenumber smoonmoelwahyaetrrceodnufcleuden(caebowuats2t7h%e).same as the solvent control and the mitotic index was only ChIrnoimtoiaslomTarliaAlb-e--rNroatsiiognniAfiscsaanytsinWcirtehaosuest iMnetcealbloslwiicthAccthivraotmioosnomal aberrations were observed for dtheeadcucletlulrseasnadnadleybrziesd,(s7e5v0e,re10l0o0ss, o1fv5i0s0,ibalnedm2it0o0t0icpgce/lmlL,).anUdnhaebaolutth2y5c%ellremdouncotliaoynerins,celflloating umnohnelalatyheyrceclolnfmlouneonlcaeyewresr,efolboastcirnvgeddeiandtchellcsulatnudredsebdroisse,darweidtuhct1i5o0n0 ianndth2e0n0u0mgb/ermoLf.viSsliibglhetly cmuilttoutriecscdeolls,edanwditahbo1u0t0015g%/mrLe.ducAttiotnheinlocewlelsmtoannoallayyzeedr cdoosnefolufe7n5ce0wpegr/emoLb,stehrevceedllinmothneolayers ``aanpdpeaabroeudttaob1e5a%lmroedsutcntioornmial,twhietdhoegnrleye aofcsolingfhltueedncuec.tioSenvienrethreenduucmtbieornsofinvmiisitbolteicmiitnodteixc,cells 2re0l0a0t,ive15t0o0t,he10s0o0l,veanntdco7n5t0roplg/cumlLt.urreess,poecctciuvrerlye)d,at all dose levels (95%, 86%, 67%, and $7% at a`bCeornrfaitrimoantsorwyerTeriaolbsFerovredfthoer2a0n-yhooufrthhaervceusltt,urneos asinganliyfziecadnt(7i4n6c,re9a9s5e,s1i4n9c0e,lasnwdit1h99c0hruogm/mols)o.maAl m9i5to%tircediuncdteixonwains moibtsoetricveidndatex74w6asgombs.erveTdheatce1l9l9m0onpogl/amyLe;rwchoenrfelause,nace2w5a%srreedduuccteidonbiyn about 2T20o50%cmoaemttpea1np9sh9aa0tsuee.sg/f1o1Lr7tmahinesdtdaoopnshleay.se8Fso3rwmeterhteeap4sh4ca.o1sr-eehsdocuforruohlmadrtvbheeestsr,cepoclrhiercdaotmfeorcsoumolmtouanrlee,aobifentrhorradtreieropntlsoiscwcaetorereecualantautrloetysaz,leodf cfhrromomtohseocmualtluraebserdroastieodnswiwtehr2e49o,bs4e9r8v,ed7f4o6r, aanndyo9f9t5hpeg/cumlLt.ureNsoansiaglnyizfeidc.anPteirnccernetaspeoslyipnlcoeildlys wwiatsh 191 0GGC90 nl soacbfoo1ru9et9d04a0ta%ntdhrise1dh4ua9cr0tviegosn/tsmtliin.memwoaennordlanlyeotehsrailgcnoiTnfrfielcaautnetmnecinentcarwneidatsh7es999%w5errgeed/uncmott.ieodn.waiTsnhemsiettvowetroieclhyiignthdoeexsxi.tc,aAprtpels7ui4le6tdidngosiens mregd/umcLt,iohnoiwnevmietro,titchintdoexxic,ictyomwpaasremductho tlheessso(lavbeonuttc1on5t%rorledcuulcttuiroesn),in confluency and [8% ChroInmitoisalomTarliaAlbeCrrhartoimoonsAosmsaalysabWeirtrhatMieontsabwoelriecaAncatliyvzaetdionfrom the cultures dosed with 1250, 2500, a3inn7cd5r0e5,a0sa0en0sdipSng0/c0mel0Ll.spgwT/ihmteLh.tcrhienraotthmmeoensptroemwsaietlnhcae3boe7fr5tr0ahtgeio/rnamstLwleiwvreaerso$bs9sliemgrehvtteaydbotilonixictch,aecbtcuiutvlatttuhireoensS0dsy0oss0teeudmg.w/iSLti.hgn3i7f5i0c.ant atanrneddaaotmbneolnuytt9w47a5ms%ethriaegpdhhulacystetiosoxniwcef,orcreatauhsneiarnlegyplzaiabcboalutetfc9ruol5tm%urterh.eedcFuulclottaiutorinengiwnidtmehoandgorcleeaaltyleserratncodxoindcfeilbtyru.iesnHcowyweerfoverearob.nuentdchauelntture mitotic index was reduced by only 13%, compared to the solvent control cultures Catoboxenirfcriawttmeiaaotntsomre(ynsTtirmirpaelldeu--acFneddorctohtemhpecl2oen0xf)lhuoweuanrcsyhoabrbvyseesartbv,oeuadtsfoi7g0nit%fhieacncaduntlctiunracersuedaaosses4eei3dncd%weilltrshedw4ui9ct7thi0ocnuhgirinomtmLho.esmoTihmtiaosltic 4ri4end.deu1xc-.thioTouhnreihnatrrtveheaesttmm,ietnnototiwsciitgihnnid3efxi7.c3a0nTthgei/nrcemrwLeaascseasunsoinecdcleaalsbltsoouwgtietn3hi0cc%ahcrrtoeidvmiuotcsytoiomobnasleirnavbteehderracatotni3fo7nl3su0cwngecr/yemaLonb.dseF1ro8vre%tdhe froariamneynotfwtahse c1u0l0tutroexsican1a0lyyizeeldd s(u4f9f8i,ci1e2n5t0m,e2t4a9p0h.as3e7s30forugan/aLl)ys.isA,litthwoausg,hntehveer4t9he7l0esps.igno.ted that tthoeripceiryceenvtidpenotl.ypTlohiedscueclclessisnfcurleaacsteidvastiginoinfibcyanttlhye.meAttab3o7l3i0c gsy/smtLe,mwtahserielwluasstrlaitetdeobrymtohte l0arge eixncproesaesde oin cpyecrcleonpthocselplhsamwiidteh.chromosomal aberrations (at 20 hours harvest) in the cultures ChroFmorostohema2l0-AhboeurrrahtairvoenstA,ssnaoyssigWniitfhiocaunttMientcarebaosleisciAnctceilvlastiwoint;h3c-hHrooumrosTormeaatlmaebnetrrations were otrhbeadstuecortnvileoydnasiinmnatchloenlcfulnluteunruceys awomnafasmlbeoybtzsaeeedprhv(ae2rds5.0e,sH5co0ow0ue,lvde1b2re5,0,etxh2ae4mn9ien0xetpd.hgimgFh)oer.stthAdetos42e44,-9h30o7u4pr0gh/pamrgLv/e,mstL,,3w0a%s so toxic: csinhnrtho.emocusAlotmusarielgsnaidbfoeiscraernadttwiiiotnnhcsrew3ae7sr4ee0iangnta/hlemynzLuedm(7bf.er5ro%om)f.tcAheelslciusglnwtiiufrtiehcsadcnohtsrieondmcorwesiaotsmheail5n0a0pb,eerr1cr2ea5nt0ti,opn2os4l9yw0pa,lsoaiondbdyse3wr7av4se0d asflrseoamtombesntetrrervaeetsdmuelintntedtrheiensucalubtloetduurtien3sa0dbo%osuertedd5uwc5itt%ihorn3.e7du4Tc0htegiom/nitmiont.imcoRneiolnaldteaixyveewratcsootanhlfeslouseoslnivgcneyinfatinccdaonnttthlreyol2rs4e,d9tu0hceye3d/74m0L. (57%)forthe high dose. CONCLUSIONS "stTyrhseetaettmme.setnPtasorotliyfcplsleh,ooiTrd6ty3dw4uar2as,twailoasnso (ieegnv.daulcu3eahtdoeufdroasrt)bhbeeohitinhgghci tllyhasettoopxgirecensitercnectaeotmcaeunnldttsua.rbesdeCncHeOocfealnls$f9ormehtiagbhollyictoaxcitcivation REFERENCE 192 0060091 192 (HMuaCrmHis,tVerHeVOmivaealnarntayh,a(,VCAH,1O99C)6,HCeVlMSlustt:awugieytnihcNiCotyoTn1es7ft0i7om5n-aT0-t68A3o74c02rs,.yMewaistuhrMinuglClhsroHmoosmoemsa.l CAbeorrmatimones irn Cchinese 193 000092 1% TLiytmlep:hoMcuyttaegsenWiictihtyaTCeosntfoinmmTa-t6o3r4y2,AsMseaaysuWriitnhgMCuhltriopmleosHaormvlesAtsberratioinns Human Whole Blood entity: T-6342; clear, colorless liquid, Remarks: No other information was given about purity or solubility METHOD MethodGuideline followed: Protocol No.: 449C0, Edition No.: 2, Modified for 3M Corporation Test types Invitro mutagenicity assay "Test systems Human whole blood lymphocytes GLP: Yes Yearstudy performed: 1996 Species/Strain/cell-type/cell line: Human/shole blood lymphocytes vMaettsapbroeltriecataecdtiwviatthioAnr:ocWliotrh1a2n5d4wfiotrhothuetnmoent-asbpoelciicfiacctiinvdautcitoinofnorofmm$et9asbuopleirzniantganetnzfyrmacetsi.onof ivers of RCoanncgeen-tfrnadtiinognasstseasyte--d0.167, 0.500, 1.67, 5.00, 167, 50.0, 167, 500, 1670, 5000 pg/mL; ital ital ial tial w(wiitthhoauctatcitviavtaitoino)n)-- 2--5132,75,052,531,01005,,1511001,0,2011501,0,2521001,0,3021501,04p01g0mp:g/mL; C1o60n0f,ir2m0a0t0orpygt/rmiaLl;(replicate cultures, without ativaion, 22.1 hourassay)--123, 250, 500, 900, 1200, C1o2n00f,ir1m6a0t0o,ry20t0i0ag(rienpl.ica cultures, without activation, 46.0 hourassay)--62.5, 125, 250, 500, 900, `1C00o0n.fi1m5a0t0o,ry20i0a0,l 2(r5e0p0l,ic3a0te00culgtumres., with activation, 2.1 hour assay and 46.0 our assay)--250, 500, FStiasthiesrt'iscaElxamcettTheosdts(uTsheadk:urScttatailst,ic1al9a8n5al)0ysciosmeparme thpapeClrocecnhotraagnyeofArcemeiltasdgewitthesatbfeorrraltiincoanrsr(aenndd, aifnd Aatplrplaltifeacdcatbcolerels,lsatshweisttpahetrercedespunlrtteasvgiefoorufosmlcyveelwhseircwelietthacokmnetonrroilenst.tohaaTnecscotonuaenrttaibcaelnredrsaitthgienonif)fi,incapalonlecyvepawllouaiasdtyie,osntoaanbfdltihesenhdeodtreswethduteprilelicpea<0tw.i0ao1ns. in based upon scientific judgement. RemaErxpkesr:imental Design fhHieunpmdairaningniavzseesdnaoyVu)ascourbtla0oi.on6dermsf,LoCrfaulbtslouiornoegdmls/e1w,0en.ro0ermmiian.lit,ciuahtleeuadrlwteih(tyhcmh0ar.lo3emmodsoLonmoofarlbwlaaobsoedrd/rrSaatmwiionn.sicnuaolstsusaryeesi)(td,iens1e rmanlg.e194 000093 194 caenntartimfousgpehteurbeeos.fTahbeouctel$l%s wCeOre;iinncauibr.atTehdeatcualptpurroexmimeadtieulmy u3s7edCowansaRlPoMpeI,1w6i4t0h OloRosHe caps, in rBainogsec-ifeinncdeisn)gsauspspaly:emLeontteNdo.wiTt0h601254%, fcehtarlobmoovsionmeasleraubemrr(aFtBiSo;nsBaisoscahy)e,me1d%, pLhoytttohEeSm3a3g1a,lduotsienin `C(QHPuaHVlA,it-yLMo;BitGoli2ob0ge)ioc)wa,lassp)e,ntihacenidsllo2ilnvme(nM1t0o0Lfc-ughnloiutitsca/emmiLfn;oerQ(tuQhauilasilatisytsyaByi.BoiloTolhgoigeciactalelssst))a.arntDdicelsietorwneaipzsteoddmiyswcsaitonelrv(e1(d0Pir0neupgariemd+Lat dcoenitornoli,zeddeiwoantiezreadtawatceorn,cewnetrraetdioosneodfwSi0t0h madgo/msLi.ngTvhoeltuemsteaorfti1cl%e s(o1l0utuiLoinsmLa)ndotrhethvisehaiscclaey. NegaItnivteheannodnaSocltvveanttioCnonatsrsoalyss, negative controls were cultures that contained only cells and culture. mcoendcieunmt.ratSioolnveunstedcoinntrtoelstscwuelrteurceusl(tu1r%esotrha1t0.c0onutLa/imnLe)d.deIinotnhiezeacdtwivaatteironatatshseayhsi,ghtehsetnegative and smoilxveinntclcuodnetrdols were thesameas described in the nonactivation assays, but with the $9 activation PositTihvee Control positive Agents control agents, which were used in the assays, ere mitomycin C (MMC; CASH S0- 0670-575,-1S9i-g2m,a,SiLgmoat, 4L0oHt254038H)02fo6r9t)heinnothneacmievtaatbioolincsearciteisvaatnidoncsyecrileos.phIonspthheamcihdreom(CoPs;omCaAlS# arbiearlr:at0i.o1n.s0.a2s,saaynsd, t0.h3repegc/omnLce,ntthriartdiotrnisalo)faMndMCCP((02.00,83a0,ndan0d.1500gg/mLL,)inwteirael uansdedctoonfiinrdmucaet.ory cBhorthomMosMoCmaalnadbeCrPratwieornse.diOsnscolovfetdhiendwoasteer.levels was analyzed in cachof the aberration assays. RangIen.fthiensdeinagssAasyss,aycsultures were initiated with 0.3 mLofblood! mi. culture and were incubated for 2 days prior to treatment. `Assa`yThWeiItyhmopuhtoeMyetteabsowleirceAcitnicvuabtaiotne:d with the test article for 19.5 hours at ~37C. The test article was Cwoalshceedmifdrom(ftihneallclosncwenittrhapthioosnp=ha0t.e1-bpugf/fmeLr)edwsaasliandedaedn.d fTrheeshcuclotmuprleestweermeedainudmhacrovnteasitneidng2..0 hours late. `AssIanythWiistahssMaeyt,atbhoelilcymApchtoicvayttieosnwere incubated with the test article for3 hours at <37C in the. pr2es7enmcge/omLf)a.atThleivSer9$f9rarcetaicotnio(nMomliexctuulraer(T5o9x-i1co5llogiyn,i,InNc.A, DLoPt#=061.657m)gw/amsL,dearnidveidsofcriotrmicthaecid otrivdeerrotfomaavloeidSpporsasgiubel-eDianwaclteiyvartaitos,nowfhischhorhtaldivbedenandphroivgiholuyslryeatcrtaitveedinwtietrhmAerdioactleosrp1r2o54d.ucIend by. `tehxep$os9uerenzpeyrmieods. tAhfrtoeurghthbeienxdipnogsu(r0espeerruimodp,rtotheeicnesl,lsthweemreedwiausmheddidtwnioctehwaivtehFbBufSfedruerdinsgaltihnee. `CCoolmepclmetiedRP(fMiInalcuclotnucreentmreadtiiounm~w0a.s1 agdde/d jtoemwthheiLecuhltwuaress,adwdheidchfowretrhee ilansctu2b.a0tehdoufrorst1o8c.o5llhoeucrts. metaphase cells. 195 000C94 195 pMArseissaeiyntEivinanld1ue0ax0ta0ioosnmasneaclyuzveed fcreolm.the survivingdose levels by analyzing the umber of metaphases ChroImcnootsnhoetmoSelh.rAopbmoaessromiianlcoAanbstesroarlay,t--iaWonnidtsshyoasnl,dvWicotnhtoroults.MueTthrebeoslbcewraAaceitiosvneastdiosanscwhedsosseonedsolceadndwifnor neg5ative ue poHCashrrhvoiesmvtoescioommneatloinlatbdheoersanetsilonswriealrenadnailtyzhed22r.1o-m35thd 4c6ul0t-uvreusteresdt11.sdosrteveecl oanntForerEeeohe CCuhltrcuoremenostsrwoiefmrueegeAibnteuirbteaestd.iTo2nwdoAaydssasypysrWfoitltohrocwuteuslMmteetsanbitolwiincthAc0it.ci6vlmattLlioownfeirwehooleesnleoow,di/1h0f.hm6L51clureeoin p15ocmnlm.ermined CCooounmrcpselnetatrtaeet,RiotPnhMseIfcoor1lsa6p4wpermroeexdihimauartmve,elsycteo1d9i.a3nndainsndrg4d3r.0.1e3gdh/omsurLisd..esCTowhleecrecemmiladdr,e wwTihseepsaacdcehsdeaadcrwks ointbootehhe ce5l Tuo Grieemmesnatsoslcuhtieodnuloerofheheaanbyeasioofncshrsomyoswoimtahloubtermmeattiaonbso. Tsatlaeti|ocn osmov a oe cCCuohlirtioufrmueosgsewomebeersA.nearTtawetoidod2nydsAasyassfatyperWicoiruthleMseianbimotleiioncn,wAcitthhiv0ac.t6liomunLe.sofwewrhtaliencbulboaotde/d10a.t0<m3L7Cculftour3re hino1s5 mmL.h upWramesshleendcCeiocofethlewtietoshtwabearrstmeaiddcdialenseddadlttiohnteeh$a9nrdceautchreteicsoelnldsumriwixentrgurete.hreeAfeafdtrwi2tt.hh0ecohhmopwoelertoexfpRionEcsMuubrYaeti1op6n9r.0omTdhtefrmo.easlOhereenseth heeldluwleereofhtahrevesstbeedaaondnspraespaaryedwfiyotthoegteanpciacaacntavlaydsiosn.. Tale | ontins a summary of omement The cll suspensioMn)wfaors+c1o0nmuiinguteeds,. tAhfetserucpeentmraitfwuagsnatHdaiainrosvdcneasrrdteemPdo,rvoaacnleddouftrhethle KsC.wehree tceelsltsewdewriethwhyapatos3nitcipmKeCsIw(t0h.075 ffircosmhltyhepraerpsaroetdeidxcalisv (absolute mcthanallaial sce eid, 31, vo). Aeried shies wen proarcd iGidemssawesroeluptiroenpaorredtbhye sdnrloypsiisnogSfitmdheiheParirevpeasirtnaedtdeixocnunladtnudrcehSsroionmnolsgonmasliadbeosraTtihonfs.idAes wsehrisesstwaeinnedtwvietthi5os% and over sipped mCaoldlaslwneremseele4ct6ewdefroer gsnoaldyzmeod.rApOhbnoeleroahgoyannnsddAonacllylys,ailsplasonswdsiiAtbslhaeeyfnEouvmamlbuceaartcoihofnrceertomenrcesueqtuasl4f ohnee aalnenvaaelllyszyoe.fdftfohero cttehhsert odaimrfoiesrloe,mnattlhteyspnheeesgroattfiicvoehnrscoofmnootsmroomthalhole,seasbcoelruvrleantetisocnoswnti(rtohBlu,2na6snd%1p0co62sl)is.tivwAeittclhoSmoel2v5eeasiersmowror: hmiieStrooahttiricoomneals1i.d0Cea0lpl0ss.wciitlfhsobasbtcheevmerrdai,toinowsewrawesernxoeptreredecosredhedde,a FMpairldctcesmadangedevwoefarmesiaatcleossscelbeyTChayhnaeassltomhorgntdwmaemvbee,rof 196 000095 1% pcoonlsyipdleorieddy anndtheenedvoarleudautpiloincaotitofhn waebrileitaynaolfyhzeedeasntdarthticlrees1u0ltisndwuecreecahbruolmaotse.omal aberrations. Percent Overall results: positive,negative, ambiguous: Negative Genotoxic effects (unconfirmed, dose-response, equivocal - withvithout activation): Negative. Cytotoxic concentration: RangH3ee5-%mfi,onl6dy%isn,sg3Aw8sa%ss,aoy1b5Ws%ie,trhv1eo8du%tp,rMie$ot7ra%tb,oolwaiancsdhA1cit0ni0tv%ahtewiecounrletuorbessedrovseedidnwitthhe Smi0t0o0tigc/imndLi.ceRseodfucttheiocnusltoufres dosed with 0.500, 1.67, 5.00, 16.7, 500, 1670, and 5000 gin. RangH5e7e-%mf,oi4ln%yds,inigs1%Aw,sasasanoydbWs1ie0rt0vh%eMdwepetrarbieoooltbioscewrAacvstehidviaintnitmohinetoctuilctuirnedsicdeossoefdtwhiethcu5lt0u0r0esgd/omsLe.d wRietdhuc1t.i67o,ns5o0f.0$,%, 500, 1670, and S000 ign, as compared with the solvent control culure. Chromosoinmitiaall TArbeirarla--tHieomnoAlsyssaiysswWaisthoobusterMveetdabporiloirc1A0ctwiavsahtiionnthe cultures dosed with 2510 pg/mL. sRoeldvuecntticoonnstroof3l8cu%l,tur1e8s,%,we1r8e%,ob5s0er%v,ed55i%n,thaendcu9lt5ur%esinttrheatemditwoittihc i1n2d7i,ce2s5,3a,53c0o3,mp1a0r1e0,d w1i5t10h,the and 2010 g/mL, respectively. `tChoenfciurltmuarteosrydoTsreidalw--itIhn 1th6e002a2n.1d-h2o0u0r0cuongf/iLrm.ataonrdyarisalli,ghhteemvoildyesnicsewoafsheombosleyrsviesd pwraisoetvoidweansthatof 9Ha3r%vesitn othfetmhietcoutlitcurinedsidceoss,eadswciotmhp1a6r0e0dgw/imthL.theResdoluvcetnitoncsonotfro2l%c,ul1t4u9r%e,s,6w4e%r,e7o4b%s,er9v3e%d,i anthde ccoulntfuirremsadtoorsyedtrwiailt,hhe1m2o5l,y5s0i0s,w9a0s0,ob1s2e00r,ve1d60p0,raniodwo2a0sr0h0 gof/tmhLe,curletsupreecstidvoeslye.d Iwnitthhe14660.00-ahnodur t2h0e0s0olgv/enmt .conRterdoulcctuilotnusroe,fw5e9r%e,o9b3s%e,rv9e8d%i,n atnhed c9u8lt%urientshdeosmeidtowtiitchi9n0d0,ic1e2s0as,0,co16m0p0a,raenddw2it0h00 sgl. respectively. ChroInmitoisalomTarlalA--beHrermaotlioynsiAsswsaayssobWistchrvMeedtapbroiloirctoAcwtaisvhatiinonth cultures dosed with 2010, 2510, 3010, a`wnidth44001100gg//mmLL.. NHoemcoelllysswiesrweavsisaibbsleerpvreidoptroiotrh0e adthdeitaidodniotifoCnoolfcCeomliedemitodthetocutlhteucruelstudroessed dinodsiecdesw,iatshc3o0m1p0arge/dmLwi.thRetdheucStoilovnesntocfon1t5r%o,l 2cu0l%tu,res1,5%w,e4r3e%o,bs7e7r%v,edainndt9h5e %culitnutrhees mtirteoattiecd with 253,505, 1010, 1510, 2010, and 2510 j/mL, respectively. `aCnodnpfriimoarttooryhaTrvreisatlo--fInthtehecu2l2t.u1r-ehsoduorsceodnwfiitrhma2t0o0r0y,r2ia5l0,0,heamnodly3s0i0s0wgas/mob.serRveedducptiroinostroofwa1s5h%, 197 0060C28 197 $am9lL,t6,e9,%r,ewse8pr2ee%c,tcih9vse7lr%yv,eIadnntidhe1h40e60.c%0u-lihtouutrhrecesomenfniietrmdeatwioinrtdyhiei$s0,l,a1ec0mo0em"play1ri5e0sd0ww3ai0ts0ha0h,bes5es0oel0dvetpntracsonwmtraolsh ao5nb0ds%c.prr1ivo0dr0n00,tHhaaenrdvcesu1t0ro0ef%sthicenatchtueerdmewisitidho1si5e0nd0c,wi3,t0h002c,0o03m05p0a205r0ea0d,dw40intd0h0010mh0sLpe./ntmpoeRmeee,smeotr oonr,, Sbtoatuistticmaeltraebvoallitcs:acTthveareisotn susan did no significantly nese chromosomal sbertions with or Remarks: ChronnmdiooslrodmTuarplilaAibceNirooantsiwoiansgAosabssaneyrsvceWrdiatahsotsuhteinMcocenetlcleasnltwiriacthiAcocnhsrtoaimnootsynosmcadl(s5h3r,raSi0o5ns1,0po0lyp1lo0idya, so e Ccanhoarnlofymizeemsdao(tm1ea2ly5T,br2e5im0sa,t--0ino0n.hs3ep0o2l19yp0-l0hooigdu/yrm.Loc)o.nnfdiIorrmheadteuopr4yl6i.rc0iaahtlo,iuonrnocwsoeignsnfiofiimcatwnot yin1careiasce onecsleslnwtsinthms hfionercirCneodanusccetininoacntliofsocnhwsritaohnmaoclshyrozoemdmaol(s1oa2me5a,rl2a5tS0bi,eo5Tn0i0wo,anassn.dSp5h0ao0wlmbayL.ThnoTeSoperdsdsrocpihnetayeioonsfnehsr mmuemsne st ithe cals expose 10 MMC. the ose cont apt ChroTnmdoosnrosmdaTurlipailAcbNaotoriotnisoiwgannsiAfaiscbsasnyrtssicWdnitaehshMeentcaobcnooclleisnctwrAiactthtiiohanrtsoiaomnemsopmsal(s0b5e,ra1t0i7o0n,s1p5o0l0yploivdoyn,r em, Caaocnnnhafrylioyrm27mo6asdmtoeo(mtr2aa5yl0p.Thsrab5sie0ear,sla--rw1Io0enn0rs0t,,hpweaaon2iyd2l.p11lb-5olh0io0couypr,rocgaormnncf.niydrmbsIarntenoddrhpoeyln4ctr6aioatOfli,.otnnhhoeowsciiogsunnirhfliemceaanvtteeiondndcrerwsatshedci3n0co0e0llsps weait.hsKio Soiinbgcncrierfaiiscedaniatntiehnncedroercaeosdneucpinlnti<caatItiioownnistaha2c0lh0r0oyumogs(am0lm0.a,lT1sh0h0rca.i1eo5n0cs0.e0p0oc0tpmhleattro.nofxhepomoensnuweoastte wraesslt wsithdcycblyopthhoesipnhcarmeiasdeed.itnhcipdeoncseoifsceolnltsrowlitahgecnhromosomal ahora eco 198 000097 9s "biTlnhodeoedpteeshntduaemnartnliyc,loynmTdp-uh6co3t4c2ey,dtewcsaocsneflciosrnmwsaiittdoherryaendadlnwesig.tahtoiuvte fmoertaibnodluiccinagcicvhtrioomno.soTmhaelseabreersrattsiownesrienscuclurred whole REFERENCE VBMliuoeroind,a,LHyeVmmApa.hatoChcHay.tYesS1t9W9u6id.tyhMNuoat:Caogen1nf7ir0cm7ia3t-ty0oT-re4ys4tA9sos0na.Ty-6W3i4t2h,MMuelasiupreinHgarCsehsrtosm.oCsoommianlg AHbaesreshtioonn.sIien. W(hCaHlVe. 199 000098 ws `GENETIC TOXICITY (IN VIVO) "Tiles Mutagenicityteston T-6342 in an in vivo mouse micronucleus assay tdentit: T6342 Rinedmicaartekds.: [tis aclear, colorless liquid. The purity and chemical identity ofthe tes substance were not METHOD bMyetHheodddlGeutiadle.li(n1e98f3o)l.loPwreodt:ocoTlhiNso.st4ud3y5,wEadsitcioonndu1c7t(endourseifnegremnocdeifgiicvaetni)o,nmsoodfitfhieedprfoorce3dMureCsomsauagtgiesotne.d Test type: Mouse micronucleus assay GLP: Yes Year study performed: 1995 SpeciesStrain: MouseCrLCD-IB(ICRIBR Sex: Male and female No. animalssevidose: 15 for treatment group, for control groups Vehicle (ifused): Deionized water Routeof administration: Oral gavage Doses: 1250, 2500, and 5000 mek; Doses selected on the basis ofa previous study. Frequency of treatment: Single dose ihStehatterirsotugincetanlreaomnuesstf)hoprormdoespdoru(tssiehodne:snTovhfaercieaalnnsaclewysistiwhseormfeitchhreoondmuaetolaegwapeesrnpaeonorirfumoarsrlam.n)ekdItfutrshaiennsAgfoNArONmeVOdVA(Awwhae(sWnisvniaegrrni,iafni1cc9ae7ns1t)weorne st(iiPgm<ne0i.fa0in5c)da.nstaelxyDducinofnmfbeirtnetan'ttsivofnrc.osm (thDeunnengaet,iv1e95c5on;tr1o9l6.4)Anwaalsysuessedwetoredepteerrfmoirnmeewdhsiecphardaotseleygfroorupcsa,chfhaanrye,ewtere aaRpnepdmrSaorxfikemsma:atleeTlsyh)e2w4ae.nri4em,arlaosnrdw7oe2mrlehyoduaorsssseiadgfnwteirdthdtootshcieancgahpfdoporospeerxhitararatcveteaisomtnoutoinftmtheoegfrbotohuepn.efemTtaersnruobawsn.tiamTnaeclensaa(nn5dimmeaaullteshsa(an5inmzdead5ls cdfoeenimtoarnloeilsz)egdrwoewuartpeesr.awsrsTiehgneeeudptoh0sainttiihzveeecdcooanntftreroroll2ga4rnohiuompusar.ls.s TwAheefenredgotashteeidvbeowcniotenhtmr$ao0rlrmnowikawlasscyowclellrocepihedodos,spheawmwiiatdshes(tpChrPee)av.dehoiBcnoluoet, 200 000099 200 Osmlinicedreostn,hudocrulesedai.nadannPddCtEshsteappineoerldyacwnihitrmhaolmMaawiyec-reGerrsyuctonhrwreodac.lydtTesho(elPuCtfEiro)enqtauoennndcoGyriomefomcmshiarc.ormoaTntuhicelcesclaritdyeedrsocwcoeylrtseews(acosNrCeeExdp)froeorsesledrataiso. pferrecqeunetncmyiocfromniuccrlocnautceldeielilnstbhiassesdtaoinn tiheaobotuatl 0P.C0-E0-4p%r.esent inthescored optic field. The norms] RESULTS Effect on mitotic index or PCE/NCE ratio by dose level and sex: I= Positive control [Males 54410577 |Females | | 20500211000323 || Males | 00654111000076 || Females 00669311001015 | ny; 1250 mekg: |_ [2h |" o28r005 |0001000| owoioow | 0751017 0061000 | 00002211000022 |00366108 08 |1 | 00 07d4o0 1r0o00e8 6 | 2500 meg: [20h "0121004| 0.041000 | 0691007 | 0641005 | S000 mee: [38h 002002 0061002 | 0471007 | 00.66541100.0071 0.101004 | 0801008 | 0191009 [38h 0150.09 | 0.061002 | "Significantly different from the cores0p.o1n7d1in0g05vehi|cle co0nt.r0o3l1(0p0<30.05) 0610.00 | 0631006 Genotoxic effets (unconfirmed, dose-response, equivoal: Negative Sotbasteirsvteidc.al results No significant increases in micronscleatedpolychromatic erythrocytes were `Rreomuapraktst:heD7u2choourtohxairivteys,ttghreoPuCpEw/eNreCEsigrnaitifoiscaonftltyhelomwaelresthaanndthfeemvaelheisclfercoomntthoelSa0n0i0mamlgsfkg dose 201 00100 2o! CONCLUSIONS `The test material, T-6342, did not polychromatic erythrocytes under induce a significant increase in the conditionsofthisassay and micronuclei in bone marrow is considered negative in the mouse: `micronucleusassay. MInuc.rVl,ieHn.na1,9V9i5r.ginMiau. t3aMgCoertpenorsaittoicnonTi.-6St3t4.y2Pauinla,nMiNn.vivo mousemicronuclasesuasy.CorningHazleton 202 000101 202 `GENETIC TOXICITY (IN VITRO) "Hiutmea:nELvyalmupahtoicoyntoefsthe Ability ofT-7524 to Induce Chromosome Aberrations in Cultured Peripheral TEST SUBSTANCE entity: T-7524 Rpuerimtay;rktsh:e reTmhaeisnpiencgif2ic%grwaavsitIy-omftethheylt-e2s0tpsyurbrsotlaindcienownea.s 1.23. Substance was brown past of98% METHOD 8MI7en0td.hu5os37d.5G;uJiadpealnicnsee fMoillnoiwetd:ofOHEeaClDthGauniddeWleilnfea4r7e3a;nEdEJCapDainreescetiMvieni6s7t/rSy48of/EIEnCte;rnOaPtiPoTnaSlGTuriaddeelianned Test type: In vito cytogenetics Test system: Cultured human lymphocytes GL: v Year study performed: 2000 SpeciesStrainicll-typelell ins cells obained rom healthy adult male volunteers sWTpiyescptieaarlofrraomseo,tmoabbutonaldiiencredsatcfatrniodvmaartCdihoalnarbuloseresadtR:oirvryerac,olnSidviuetrlimoeinsc,,roaGseordmmeaaslcnryei.nbzedyAmnieinsmtahrleosuSttwiaennerdleayrhpdorueOsppeaedrreaadttiNfnrgOoTmPrOaodXcueldtiunmraaelse a(nSdOPm)in.ceRdaatsndwesrupeerinnajtcatnetdwianstruaspeerdtofnoeraallcytwiitohnAroclor 1254 induced in com afl. Livers were wished Concentrations tested: WithoutFi9rs+t Experiment: 1000, 3330 and 5000 ug/ml S3e33c,o4n2d0,E5xp6e0r,i7m5e0n,t:1030303,,1536000., 1a0n0d0,18103000g,i1n5,00, 2400, and 3330 g/m. With $9Expe(1r8i%mvevn)t-1: 1000, 3333 and S000 pg/ Experiment 2.1000, 3333, and S000 ug ml 203 000102 203 Test conditions: cRualntguree-Fmienddiiunmg,wTietsth:anLdywmipthhoocuyttSe9curletsupreecsti(v0e.l4ymalndbl0o.o1dmolfa(9hmegal/tmhly)pmhaylteodhoaneomragpglluust$inmiin)orw4e.r8eml acublsteunrceedoffor$948-mhioxurosr afnord3thherienafttheerperxepsoesnceed otof sSe9lemcitxe.d dAofsteesro3fhTrs-,7t5h2e4ceflolrs3exb,po2s4ehd, taonTd-47852h4iwnetrhee rtiimnes)e.d oTnhceecweiltlsh t$rmealteodffHorB2S4Sharnadndin4c8ubharteidn aibnsSenmclecouflt$u9re-mmiexdwieurme fnoortarniontsheedra2ft0e-r22irhea(t2m4enht fbiuxtatwieorne fixed immediately after 24 h and 48 rangeofdose levelswaschosen for h. Based on the the cyotgenetic resultsof assay. dose range-finding test, an appropriate Experiment 1: of T-7524 for 3 Lymphocytes were cultured for hours with and without $9-mix. 48 hours and then exposed Afte3r hrs, the cells were in duplicate to selected rinsed with 5 ml HBSS doses and incubated in the dose range ml culture medium finding test and the for another 20-22 hr (24 h fixation time). first cytogenetic assay, appropriate dose Based on the mitotic index levels were selected for the of `sorecmoonrde:cytthoegmeinteottiiccaisnsdaeyxo- fthtehehiglhoewsetstdodsoeseletveesltetdeswtaedsianphpirboitxeidmattheelmyittohteicsaimnedeaxsbtyheaspoplrvoexnitmacotnetlryol5.0% E75x2p4erfiomre2n4th2a:ndCe4l8lshwienrethceualbtusreendcefoorf4S89h-mainxdotrhefroe3arftherienxtphoesperdesinendcuepolifcaSt9e-mtioxs.eleAcftteedr d3oshetsroefatTm-ent, cfeolrl4s4i-n4t6heh p(r4e8sehncfiexoafti$on9-timmiex).weTrheercienlslesdtorenacteedwiftohr 2$4mhlaHnBdS4S8 ahnwditihnocuutbaSt9ed-miinx$wmelrecunlotturreinmseeddiafutmer treatment but were harvested immediately after 24h and 48 h fixation time. sCphirndolmeoisnhoimbietoprrceoplacrhaitciionne:(0D.5uruign/gmlthmeeldaistum3)h.ofThceurletaufrtee,rcetlhle dcievlliscionuwaslawretrreesucteendrtrbiyefaudgdseidtifoonro$fmtihen at 1300 rpm and the supernatant treatment with hypotonic 0.56% was removed. Cells in the remaining cell (w/v) potassium chloride solution at 37C. pellet After were swollen by 5 min hypotonic treatment, the cellswere fixed with 3 changesofmethanol; acetic acid fixative (3:1 v/v). 0SlFi9de6%pr(evp/avr)acttihoann:ol/Feitxheedr caenldlsclweearneeddrwoippteahd toinssuccl.eaTnehdesslliiddeess twheatrewemraerkiemdmewristehdthfeorN2O4TbOr Xin satu1:d1y mix identification number then stained for 10-30 and group number. minwith 5% (v/v) GTiwemossalisdoelsutwieorneipnrteapparweadt/ecru.ltuSrlei.desSlwiedrees were then rsientsteod dirnytaapn-d water and set MicroMount to dry. The and mounted dry slides were with coverslip. cleared by dipping in xylene before they were embedded in mMiettoatpihcasiensdepxersc1o0r0i0ngce:llsT.heAtmilteoatsitc3ianndaelxoysfabclaechcocnucletnutrreawtiaosnsdewteerremiunseedd;btyhecohuingthiesntg cthoencneuntmrbaetrioonfs atonatlhyezseodlvweenrtecotnhtorsoel.cuTlhtueremsitwohteicreintdheexmoiftotthiec lionwdeesxtwdaosseinlheivbeiltaendaalpypzreodxiwmaastealbyo5u0t%heosrammoereasctohmepared mcihtrootimcosiondmeexoabfertrhaetisoonlsv.ent. Cultures treated with an intermediate dose were also examined for Cofocuhnrtoimnogscohmreomaboesroramteioanbsearnrdatsicoonrsed:. To prevent bias, slides were Anadhesive label with the randomly coded prior to examination NOTOX study ID number and code wbyaslisgthutcmkiocvreorsctohepymafrorkecdhrsolimdeo.soAmtelaebaesrt1ra0ti0omnse.tIapfhtahseencuhmrboemroofsaobmeersrparnetacdeslplesr(cgualptsuerxecwleurdeede)wxaemriene2d5 owrermeoranealiynzSedO.meNtaupmhbaesresso,fncoelmlosrweimtehtaabpehrarsateisownseraendexnaumminbeedr.sofOanbleyrrmaettiaopnhsawseersewictahlc4ul6atcehdr.omosomes 204 204 000103 suLTs Glesnotwoitxhiechefrfoemctoss:omTe-75e2r4adtiidonnso induce siatistialy abioogiealysignificant increase in numbers of CVyitootouxic concentrations: 234hhr necatammeenntt;2244bhrffiixxaattiioonn:2m4o0t0oxaincdd3o5se3:0hgigmhetstdosetested S000gm, 3h estment 48 nation:1300and 1800 int Wits3he treatment: 24 he vation no oxi dose: highest dose ested S000 gn, hr estment 48 brfixation: no onc dose:Highest dose(oted S000 rm. concLusions iWm nhceansteoe esfitnebdthawerir ntthuoomunbte.ro9Hfoswcnehdvreworim,tohws2ho4emnecgsoabnpetsrianatruixooucnsslarutad1m0de00nhu,egTu752wm4h,enoibfnssdaupecesrewdaeriestntautidelewidlthnsiingenhiefticoal ChHoirmstoiomrnioocsauloscmoernaetbsreoirlmrreaantntigonBosefcsahnues.elxtabioisracntorrgey.agsTaehpiosscaeiruncrwreiedatshaeinwthatsh iohdtisltsoercidecoaslatceo1an0tn0r0.egnu/elediofthigea8phpeoeutuodrrmhe laboratory and no increas occured with 48 Coninuous reament he nErase Bot contin ty cBaosendodntiohetfatibhoovsenurdes.sult, T-7524 i notclastogenic in humanlymphocytes unde the experimental Remarks: none REFERENCE PNeOriTpOhXer.al H20u0m0.anEvLaylmupahtoicoyntoesf.theNAObTiOlyXPofre7e52N4umobeInrd2uc9e2C0h6r3omHosromteoAbgeretinTohnbsNoienCstuhcrrihendd.s 205 000104 25 "Title: CHO/HGPRT FORWARD MUTATION ASSAY - ISO (T-6889.7) `Test Substance: Ammonium Perfluorooctanoate (FL-143) Identity: CAS#: 3825-26-1: T6889.7 Remarks: >lgimL. The chemical was a white, crystalline, solid; Lot# 332: at pH 4 -- 7; it was soluble at METHOD: Method/Guideline followed: for GenoBtiooxliocgiitcyalCaErvcailnuoagteinoincoiftyMaenddicRaelprDoedvuiccteisv--e Part 3: Tests toxicity, OECD Guideline ANSO/AAMUISO #476 109933: 1993 Hsie, 1981 Test type: In vitro gene mutation in mammalian cell in culture `Test system: Chinese hamster ovary (CHO) cells GLP: Y Year study performed: 2002 Species/Strain/cell-type/cell line: CHO-KIline of CHO cells Metabolic acid. activation: Aroclor 1254 induced rat liver S9 homogenate plus NADP and isocitric Concentrations tested: 1:128, 1:256, and 1:512 Test article was dilutiofotnhse S dissolved in culture medium mg/mL solution were tested ata top doseof $ mg/mL. both with and without activation. PSthaatrimsatcicoallogmiectahloCdaslcuusleadt:ioSntsatPisrtoicceadluprreo;gAraNm,OVTaAllaarniddaN,eRw.Sm.ana-nKdeRu.lB.s Murray's Test for Confirmation. Remarks: tested. The There were no significant negative control for both protocol deviations. Duplicatesof each the activation and non-activation assays concentration was culture were dmeemdeituhmy;lbtehnezapotshirtaicveenceonftorrolthweaascteitvhatyilomnetahsasnaye.suCluflotxuirdees for the non-activation assay and were exposed to chemical for 17 hours wfoarsthheedn2onX-aacntdivsautpipoln-eamsesnatyedanwditfhorcSomhpoluertseinmetdheiuamct.ivFaotritoyn-eaissgahyt. hoAuftresraenxdpo6s4u%rea,ftceerllesxwpeosruere the and cells from plateda | the non-activation x 10cells per 100 and mm activation dish. The caeslslasyswerreesppeacstisveedlyevweerrye4t8r-y7p2sihnoiuzerds, counted. to maintain `exponential growth during phenotypic expression fo6r days. Following phenotypic expression 206 000105 206 cells were grown in hypoxanthine-free Ham's F-12 medium with 10 uM 6-thioguanine, fetal bcoolvoinnieessetroudmevaenldopa.ntCilboiontiincgs aetffaicdieennsciytywaofs2dexte1r0m/i1n0e0d matmthePestraimdeisthimfeorby9dpalyatsintgo acelllloswinmutant csweoilltehocntGyiiveefmosmrame.adtiiOounnml.ywAicttohltoohunetiee6nstdhowiifottghhu5aen0iionnec.umboBarotetihocnesepltelsriwooefdr,ceupllctaouturenestsewdwe.erreefiinxceudbiantemdetfhoarn9odlayansdtsotaalilnoedw Overall results: positive, negative, ambiguous: Negative GNeegnaottiovxeicboetfhfewcittsh(aunndcowniftihromuteda,ctdiovastei-orne.sponse, equivocal - with/without activation): C5y0t%otcoexllicsucrovnicvaelntartaatidoinlu:tiBoontohfw1i1t1h28antdo 8wi0t%hoourtgmreetaatberolaitcadaicltuivtaitoinonofcy1t:o5t1o2x.icTihteysreandgoseedsfrom were chosen for treatment and are adequate. Statistieal results: Negative ceRoxelpmoencaitrceksdsiin:ntdTriechaaetteitdnecgsutatlhtarutretchsvedstedstthnsooystesitinendmutcwheeascaosbnatetrhsoalivcicanulglltpuyrrosepi.egrnPlioyfs.iictainvte ianncdreneagsaitnivteheconnutmroblesrroefacmtuetdaan5t CONCLUSIONS REFERENCE (CHOI) ell in culture: his i correct as stated CSMoairdnphnouer,saotDti.aon25,050B12e4d4C-f1oH0rO0d/0,.HMGAP,RTToxFicOoRnWFAinRalDReMpUorTtA: T0I1-O7N01A9S-SG1ASYub-mi1tStOed(Tt6o:.838M9,.7S)t.ToPxaiulcon 207 000106 207 ACUTE TOXICITY Title: An Acute Inhalation Toxicity Study ofT-2305 CoC in the Rat TEST SUBSTANCE Identity: Ammonium Perfluorooctanoate; CASH: 3825-26-1 Remarks: Fine white powder, ceived from 3M Company; composition and purity not indicated. METHOD Method/guideline followed: Guideline number not stated. GLP: No earstudy performed: 1979 Species/Strain: RavSprague-Dawley (21110 264 grams) Sex (Males/females/both): Both No. of animals/sex/dose: S/sex/group Routeof Administration: Inhalation dReelmiaverrkesd:ianThteotnaolmvionlaulmteeostfc9o6n0cenltirtaetsoiofndwraysair1.8.6Thmeg/tLes,t wmiattheraiaoltawlasofsi1c7v.e9d0 agnrdampsaocfketdesitnmtaottehreial dlusit-nladeeonfraairWwriagshptasdussetd-fientcod tmheech32a.n3islmit.er gTlhaessfelxopworsautreoefchdarmybaeirr whaosus1i6nglittheerste/smtinauntie.malTsheforreasnulting ad`eunxrdpiodnsaguirlteyhepteehrxeripcooadsfoutrfeero,fnoucrpoh1on4urdr.aeymTsohvpearalionfrirmtooamlsastchwreiefcrihceea.mobbesre,rvheodurfloyr afobrn4orhmoaulrssiagfntsratre1m5o-vmailnuftreomintteesrtvaclhsamber, RESULTS Numberofdeaths at each dose level (by sex): There were no deaths. dReecmraeraskesd:acDtuivriitnyg, ltahbeoerxepdobsrueraethpienrgi,odg,astphiensg,tucdlyoasendimeayless,exmhuicboiiteddneaxscaalsdsiisvcehalragcer,imaantdioinrraengdulsaarlivation, eabxrnecoaegtsehnsiiintvgae.llafAucfrrtie(m9ra/t1ri0e)om,novd(ra1y/l1r0fa)rl,oeamsn(td6h/eb1o0e)dx,yportesrduermmeaotrceshrai(ma1bl/e1ar0r),owureenrddentahosebaseleydreivssec(dh5/ai1nr0gt)eh,e(e1ax0tc/se.1s0s)Ei,xvcyeeesslasllioivwveaststiaaolininvi(an4t/gio1o0nf),,the 208 000107' 208 a---- ------ A ------------ ymlaeatlcelrrioimwaaltsitooabnisnaeinrngdveobdfoadtrhyeoutanrnedomgtoehrnesitehayalefdsuaarbt(at6th/ee1d0tb)wyoatnhhdoeudorrnypeo-rsahtloeuesrx(pp5oo/s1su0tr)-eewxoepbroseserusvrtaieltlioobsnsc.eernvRaaettditohnenaasaannleddthihsoecurhreaprwogasets-(n10o/r1e0d) m(`3eo/xi1ps0ot)s,uarlmeeusocbo(si1e/rdv1a0nt)aiswoanle.rdeiDsoucbrhsiaenrrggvetehd(e1i0n1/41t0-h )d,ayrdarso.ybsreaWrleveisagt(hi8ot/n1g0p)ae,irndisorday,prpeeexdacrmeeassdtienvroeir]mlaaalc.rroiumNnaetdcitorhnoep(s6n/oy1s0fe)in(a2dn/i1dn0g)ss,aslavhnaodtwieodn Hung discolorationin $10 rats (a higher than normal incidence). CONCLUSIONS 1118w.6asmuc/oLn.clfourdoednefhrooumr.thIemsmteuddiyarteesuelftfsectthsaotftthreetaetsmt esnutbswtearneceexiscensostifvaetallatcorirmaattsiaotn,a snaolmiviantailone,xdpeocsrueraeseodf nyaacetslialvliotwdy.isstcLahaianbriognrege,odfdbrtryheeraatlahenison,-gdg,erngyiatsrapelidnfgmu,ar,tcealronisdaildnagrryoofruatlnhedse.tehyTeehsne,ospmeeurcasoinsidtdemnonciaessoatflaldlaiecsrscihamalarotgniego,nwi,irsrtaehlgvulaluatnrigobdnrie,sacmtohuliconorgia,tdion seen at necropsy indicate that the material may havea prolonged or residual effect at 14 days, FERENCE MBiNo.fdyPnroajmeicctsNoIn.c.781-977195.4.An Acute Inhalation StudyofT-2305 CoC in the Rat. 3M Company, St. Paul, 209 000108 209 ACUTE TOXICITY ite: Acute OralToxicity (LD) Study in Rats TEST SUBSTANCE Identity: Ammonium Perfluorooctanoate; CAS#: 3825-26-1 Remarks: Whit powder, 31 Lot No. 340; compasiion and puiy no indicted METHOD Method/guideline followed: Guideline numnbtseistred GLP (VN: No Year study performed: 1975 SpecesStrain:Rat CharlesRiver CD Sex (Males femalesboth): both Number of animalsisex/dose: Sisex/dose Vehicles 40% scctonc/60% com oil Route of Administration: Oral gavage R21e5m0armkse:kTihneafvsotlumamteeroifal10wamsiagdm.iniTshteerreadtsatwetihghfeodll1o8wi0n-g21d8osatlesvtelusd:y 0n0ti,a2i1o5n,. 4A6n4,im1a0l0s0,wearned dabasleyrvtehdeorreamtorftaolraittyotaanldofp1h4armdeaoyst.osBiocdsyigwnesigdhurtisnwgetrheerfecsordfoeudrihmomuerdsisatfeelrydopsriinog.foatd2o4sihnoguarnsdanatd7 oafntdhe141d4aydsa.yAonbismearvlastitohantpdeirieodd.on study were subjected 0 gross necropsy as wet all survivors at the end RESULTS cTohrenefaollloopawciintgy,lhiypcothseirgmnsicwetoreouocbshe,ravnedd:depasthi.,Sipglnosreobcsteirovne,dhayponseccriovpisyy,odfaecnriemaasleds lwihmibchtownee,reaia sftooumnadcdhes:adoor rstsoamcraicfhiscefdimlaerdiwbiutnhdliincdiuidnecd:lud1i)ncgondgaersktrieodno,rirteidnguda.n srteodmfaocihsincotnhtealiunnignsg: d2a) rdirsetdended pinatretsitciunleastefimlaletdewriit:hsrteodmiacdh:s waintdh4h)yppaelrdinsiccoolrortaitcikoennocfdthmeuciovsear) rreodssianiiofngthaergoluannddutlhaeromsuecoasnad: 3) mmouuctohs.a,Anhiydmraolmseitrhaatofsturhveiveerduosdaanyd 1m4ohtaidlethcioclkoernaetidosntooftmhacehkmidcnoesyss.,Shygpnerwemeirce golbasnedruvleadrastaolmach 210 000109 218 tterremaitnmaelntsalcerveilfsi.ceTreatment did not appear to have an effect upon weight oftheanimals that survived to Numberofdeaths at each dose level (by sex): 100 mkg: 1/5 males, 0S females 215 mg/ke: 0/5males, 0S females 464 myke: 2S males, IS females 1000 mghkg: 3/5 males, 55 females 2150 mgkg: 5/5 males, $5 females Remarks: CONCLUSIONS LD (male rats) = 680 mg/kg, with 399 -- 1157 mg/kg 95% confidence limit LDLD ((fceommablieneradtss)e=xe4s)30= mye, with 295 540 mg/kg,with - 626 389- mg/kg 95% 749 mg/kg confidence limit 95% confidence limit REFERENCE FInltueomraatdiFonlaulorRoecsheearicchalanFdC-D1e4v3elAocpumteenOtrCaolrTpooxriactiitoyn.(SLDpxocn)soSrteuddybyin3RMatsC.om1p97a8n.y.Study No. 137-091, 21 000110 21 ACUTE TOXICITY Title: Acute Oral Toxicity StudyofT-6669 in Rats (OECD Guidelines) TEST SUBSTANCE Identity: Ammonium Perfluoroocianoate; CAS: 3825-26-1 Remarks: Purity not stated METHOD Methodguideline followed: OECD Guidelines GLP (VIN): ear study performed: 1997 `Species/Strain: albino ratsofCrlCD (SD)BR strain Sex (Males/females/both): both Numberofanimals/sex/dose: S/sex/dose Vehicle: disilled water Route of Administration: gavage mRemlarbkosd:y Dweoisgehsto.fT2h5e0 raantds w5e0i0gmhegdk2g08w-e2r6e9tgestaendd. wAelrled8o-s1e2lweveeelkssweolrde.aCdlmiinniicsatleorbesdearsvavtoilounmsewseroef 10 cchoencdkusctweedrae c1o,n2d5u,ctaenddt4whoiuardcsaaeyft(emtoesmtimnagtearniadlaafdtmeimnoisotnr)atfioorn1a3nddaycascahnddaoynftorhe1m4odranysi.ngMoofrDtaalyity14. Body were swuebijgehcttosfwaenreadbberteevrimaitneeddgornosDsanyescr0o,ps7y..and 14 or at death if survival exceeded 1 day. All animals 212 000111 212 RESULTS LDSO: Males: > 500 mgrkg Females: between 250 and 500 mg/ke. Numberofdeaths at cach dose level (by sex): 250 mgkg -- none: S00 mgkg 2/5 males and 55 females. Rmemkarkasp:peaArleldanniomramlasledxuhriibnigtetdhebostduydyweeixgchetptgafonr tthwrooufgehmoaluetsththeasttuedxyh.ibiAtleldarndi-msatlasinteredatfeadceast a2n50dloar wtheetaunriomgaelnsittarleaatreedawwiitthhiSn0204mhogur's woeftree:st rmeadte-rsiaailncaddmfiancies,tryaetliloonw.-sCtlaiinniecdalorsiwgents uorfotgoexniictiatly aorbesa,erved in Ireylpaotaecdtilveistiyo,nshoubnscehrevdedpoastunreec,rospasgyg,earletdhoguagih, aatnd25e0xcmegs/skivgeosnaelvfaetimoanl.e hTahderlearwgeerpeelnvoisteesstin-mbaotctrhial aKricdanesysi.n thAetg5l0an0dumlga/rkgm,ucoonseaomafltehheadstaocmaancnhi,abanldisasedecriognhtdlfaenmka,loenheafdeamaclleeahrafdlumidulitnitphlee dlaurmkenborfowtnhe bilateral homsofthe uterus CoNCLUSIONS None were specified beyond the results, REFERENCE G6l1a0z0a1,76S0M.. Ja1n9u9a7.ry A1c0.uteSpOornasloTroexdibciyt3yMS,tuSd.yoPfaulT,-6M6i6nn9eisnotRaat.s. Corning Hazleton Inc. CHW. OTHER 213 009112 23 ACUTE - SKIN IRRITATION Tite: Primary Skin ition Study --Rabbis TEST SUBSTANCE entity: T1395 Remarks: 10 other entfing informationwasgiven, METHOD Note pHoftest materia: Not specified MAdemtihnoidsGtutiidoenlinaend September 1973 foElnlfoowresde:menSitmiRleagrul1ateisonts.in FSeecdtriaoln 1R5e0g0i4o1r,HaVzola.rd3o5usNoS.ubs1t8a7n.ceps. a2n7d0A1r9t1cle3s7, Test Types invivo Speciesstrainell ype: albino rabbis Sex (malesfemales/both): No pecied Nuofmanibmalsseexidrose: 6 ol "droyaatndodsae:r aDpopsiscaoiofn 0o.f5w3 awtreerpalatcheednodnafnhieaetxpieraimenntan sbradd sic. ies were examined whi Vebicte: Not specified uLetntghtehrsowfaismneo tiensdticmaatitoenrsihaouits winhectohnetrac1ht wSiitehwainsimwaaslhieedl.; RWeaadpipnignsgwsorweeraesoremmaodveedaa7feeho2ur4s,hours Grading scales Scores for yh an cha formation aswell as cde formation ver presented `eRrneamunarr(kp0sa5t:c2heSfsixeanltdinamnaoteirrmaipbaelbriwvsisohudslamcthueediirohm]aaiwbaclasidpwpereaddpyrpeoodfmiatroecuindbyatcekpsrseahpneadr1ef0dah1ness,p6atsnh,ed bitahvenendatcgotevesirneodpflwaoicnehe A+eecornd2o4d ahcocuorrsdianngd 752 shtoaunrdsarthdizecdoveeraiengsheerDsreemomreetdhoadnd the degree of atthe and sds wae 214 000113 2 14 RESULTS In all cases it is reported the primary skin detected. No clinical signs were reported. iritation scores were 0, indicating no reddening or swelling Primary irritation score: zero Remarks: There was no indication of reliability and no QA/QC. CONCLUSIONS Based on the results, the substwaanscnoet classifiedas a primary iritant. Gabricl, Karl. Summary of: Primary Skin Submitted to 3M Company, 3M Center, St. IPratualt,iMonN.Study ~Rabbits. Performed by: Bioscarch. OTHER Gdeetnaeirleadl remarks: report was aTvhaiilsabslue.mmTahreyrewfaorseb,atsheedcoonntaenstusommfatrhiys report and summary, only limited in reference data tables. No to the protocols and results of the study, are fimited. 215 000114 215 ACUTE - EYE IRRITATION "Title: Primary Eye Iitation Study - Rabbits TEST SUBSTANCE Identity: T-1395 Remarks: no other identifying information was given. METHOD Note pHof test material: Not specified MAedtmihnoisdtGruatiidoenliannedfoEnlfloorwceedm:eSnitmiRelgaurltaotitoensst,iFneSdeecrtailonRe1g5i0st0e.r4,2 V-olH.az38a,rdNoou.sS1u8b7s,tpa. n2c7e0s1a9n+d, 2Ar7ticles, September 1973. Test Type: in vivo Speciesistrain/cell type or line: adult albino rabbits Sex (males/femalesboth): Not specified Numberof animals/sex/dose: 6/single dose Total dose: 0.1 grampereye. L5seencgotnhdosfitni3meantiemsatlmsa;t3e0risaelcoisndins cionn3taacntimwailtsh animalcll: Observation period: 1 hr, 24 br, 48 hr, 72 hr, and 5 and 7 days `Raendmaafrtkers:30 Tsheecotnesdtsmiante3riaanlimwaalss wwaitshhe2d00frcocom ftwhaeteeyre.s in 3 No oatnhiemrailnsfaorfmeatr5iosnecoonntdhse with 200 methods ccofwater was given. RESULTS Corrosive: Not specified. 216 216 000115 Irritation score: fcoinejrunctsieev:acAlwlarseco4r,esanfdoriCno|mreaabbai,ndthIerisscwoerreweazesr2o,sth(frooruagllhoruabtbittsh)e.obIsnertvwaotiroanbbpietsr,iosdc.ores for CAfoinejrun3c0tisevc:aewAelrlesc4oraets1f-o4r8Chorsm,eaandainndcrIerassweedr(e0z6eratos72(fohrasllanrdababtitSs)a.ndIn7odnaeys.rabbIint,| srcaobbriets,ftohre score. was 4 throughout period. the observation period and in I rabbi the score was 6 throughaut the observation "ITrroiotlatiuosnedBytoHaaszsaerssdosucsorSeu:bsStcaoncreisn.gwasdone according to the Ilustated Guide for Grading Eve Description of lesions: None Remarks: None CONCLUSIONS The only conclusion provided in study was that the test substance was not an ocular irritant wRietmhaorutksa:ddi`tTihoinsacloinncfloursmiaotnioisnsounsptehcet sdcuoeritnogtmheetphoosdit,itvheesrceoirsesioowbsaeyrvteodpdruorviindge tahne isntufdoyr.medHojwuedvgemre,nt abou the results REFERENCE G`aSburbimcilt,teKdartlo.3SMuCmommapraynyof,: 3PMriCmeanrtyerE,ySet.IrPraiutla,tiMonNS.tudy -- Rabbits. Performed by: Bioscarch. OTHER `deGteanielreadlrrepeomratrwkass: aTvhaiilsabslue.mmTahreyrewfaorseb,atsheedcoonntaenstusmomftahriysrseupmormtarayn,d oinnlryefleirmeintceedtdoattaheabplreost.ocoNlos and results ofthe study. are limited. 27 000116 27 ACUTE - EYE IRRITATION Title: Primary Eye Iriation-Rabbit TEST SUBSTANCE Identity: 3M identified the test substance as T-1395. Remarks: The test substance was not further characterized. METHOI Note pH of test material: Not specified EmManetfteohrroicadle/mGaeurneitdtehRloesgieunledaetfsiocolrnlisob,weedFde:idnerSTaehlcetRimeogenitsh1toe5dr0,s0.Veo4ml2.p-lH3oa8yz,aeNrdod.oinus1t8hS7eu,tbepss.tt2ain7ng0c,1ee9sv,aaln2ud7atASireotpintc,l1aes9n,7d,Agdrmaidniinsgtroafttihoen taenstd Test Types in vivo Speciesistraincel type o line: AlbinorabbitNot specified Sex (males/females/both): Not specified Number of animals/sex/dose: single dose: Total dose: 0.1 gram n"Toesttrceoantdeidtainodnss:erTvhede atsesctosnutrbosltsa.ncTehewatsestinssutiblslteadnicneowathsenroitghwtaesyheesodfftrhoem ttehsettarneiamtaeldse;yetsh.e left eyes were fLoelnlgotwhinogfatdimimneistetsrtatmiaotneorfiatlheisteisntcsounbtstaacntcew.ith animalicell: The exposed eye was not washed Observation period: 1,24, 48, 4nd 72 hours post-cxposure; S and 7days post-exposure. o`uStcloirniendg mine"tHhlousdtruasteedd:GuInitdeerpfroertaGtriaondoifngthEeyeresIurlittsatwiaonsBmyadHeazianradcocuosrdSaunbcsetawintchest"he grading system Remarks: Healthy young adult animals were used in ths study. RESULTS Corrosive: Not specified sIurbrsittaatnicoen, s6c/o6rae:nimNaolsoveexrhailblitieidaitsioinristcaotrieonwascsorgievseno.fInadnidvi4d/u6alalnyi,m1alhsouerxhaifbeirteadppcloincjautnicotnivoafcthireritteasttion 28 000117 218 c4soc8norhteoisunruosefadf1te0or;dtihasedpmlriaenymiasiitrrniatitanitgioontnwoooffatthnhiemfaierslitsssaeunxbhdsitcbaionctneej.duncIcoitntijavutanico(tniirsvicaaotriieiostnaatsncidoorniesns:cciodr5eenascneodoff62i-r6ar,nitdraet8s.ipoe6nc/t6hiavaednliym)alusp to adaennciirmmeaaallsssetedxbhhryiobduigatheyodua7tcooftnhtejhsueundcssti.uvday,caittwahtiicohntsicmoer2e/o6fa2n.iNmaolscoemxehaiblitierditiaitisoiniwtaatsioobnssecrovreeds oinfanaynodf1h/e6 o"Tuotollinuesdeidnt"oHlaussstersastesdcoGruei:deInftoerrpGrreatadtiinogn oEfyteheImrietsautlitosnwBaysHmaazdaerdionuasccSuobrsdtaanncceesw"i,th he grading system Descriptionof lesions: Not specified Remarks: None CoNCLUSIONS cRoenmsairdekrse:d tBhaesteedstosnubtshtearnecseultotbsoefathpisrismtaurdyyoacnudlatrhersioaunrc;e |usacgrdefeorwiitnhtetrhpirsetcionngcltuhseiroensults, the authors REFERENCE 3M Company. 1976. Primary Eye Imitation Study-Rabbits. OTHER rReefmearernkcse:oTthhiespsruotmomcaolrsyawnasrbeassuelds oofntahseumstmudayr,yarreepmoirtt: etherefore, the contents ofthis summary, in 219 000118 210 ACUTE - SKIN IRRITATION "Title: Primary Skin Irritation Test with T-3371 in Albino Rabbits TEST SUBSTANCE Identity: Riker Laboratories, Inc. identified the test substasaTn-3c37e1 Remarks: The test substance was not further characterized. METHOD Note pHoftest material: Not specified Method/Guidelinefollowed: ICAO Test Type: in vivo Species/strain/eell type: Rabbit/New Zealand White Albino Sex (males/females/both): Female Number of animals/sex/dose: 3/exposure period Total dose: 0.5 gram Vehicle: None Lengthoftime test material is in contact with animalicel: 3 minutes, 1 hour, or 4 hours aTnedstfcloannkdsiotfioenas:chOrnabebitd.ayFoprrioeractho raapbpbliitc,attiwoon toefstthseitetesstwesruebsstealneccet,ed.theThhairtewstassistehsavweedrefrlaotmeratlhetobatchke midline of the test sites and back and occluded waiptphro2x-iimnacthelsyqu1a0recegnatiumzeeteprastcahpaerst.. The The pteasttchsesuwberse wsteacasuarnpepdlciweeidthtogacuazceh owfrtahpe: then, the exposure trunk period. oAfftcearchthaeneixmpaolsuwraespewrriaodp,peadl wwirtahppiimnpgesrwvieoruesreplmaosvtiecd sahnedettihneg for tes the sites dwuerraetieoxnaomfintchde for imeversible damage and scored for erythema and edema. g`rGardaidnigngscsaclaeloe:f T0h-e4.auTtehsotrssiptresewseenrteeadlsseopaorbatseerivreidtaftoironthsecoprreessefnorceeroyrtahbesmeancaenodfecdheemmai,caclacbhubma,seedscohanr,a necrosis, and epithelial sloughing. rRoeommasrkwsi:th Afnoiodmaalnsd wwearteerhoofufsereeddaidn sltiabnitduamr.d wirc-mesh cages in temperature and humidity controlled 220 000119 220 pHRroesouudrlutccsoe:ndtafTochlelpeotrweiisontdg.sauMlblosdtteahrnrecaeetceponrrtyoatcdhteunpcneraiioaednvsd.ereAsdniebmelan,dtpiaosssiunweteldwlaamassagncoehtefmaoiclchlaiolcwvibenudgrd,auee3s-ctmohiantruh.teea,enxdt1-rneehmcoeruorsi,iisaantediro4enTollowing each contact period. Primary irritation score: Not reported Remarks: CONCLUSIONS, re"Terhpyeotrhcthe1em0maieacvanalldupdarteeodmquu,caleicdthyermroivfcetahrlesbislutemud,tyiesassncuhdearvd,aalmaidnaidgteyneo0cfrttohshies.sckoIinnncalodufesqifuoeanmtaeleinaflobrimnaotiroanbwbiass; pinrcelsuednitnegdmiondheerate REFERENCE LParbiomraartyorSikeisn, ITnre.iaStt.onPaTuels,tMwiintnhesTo-ta3.371ExpinerAilmbeinnto R1a0b8b8i3s.580190873.9 Safety Evaluation Laboratory, Riker 2 000120 2 ACUTE TOXICITY "Title: Acute Oral Toxicity Study-Rats `TESTSUBSTANCE Identity: 3M identified the test substanceasT-1585. Remarks: The test substance was not further characterized. METHOD Method/guideline followed: Not specified GLP (VN): No Year study performed: 1976 Species/Strain: RaSherman-Wistar, 200-300 grams Sex (Males/females/both): Male and female. Number of animals/sex/dose: /sexsingle dose Vehicle: 50% water Routeof Administration: Oral tTheeststcoomnadicthiobnys:meEaancshoafanismyarliwnagesawnedidgohseidnganndeeddoles.edTbhye ddiorscaegtea-dlmeivneilswtraasti1o,n0o0f0 tmhiektegstasnudbstthaenceestinto sthuebsatannceiwwaesmrdeoaaslelldowasseda 50% food wiv and swuspaenasdieolnibiirntuwmatefro.r Following the 14-day oadbmsienrivsattriaotnipoenroifotdh,deurteisntgsuwbhstiacnhcet,ime the rats were abserved for signs oftoxicity and mortaliies. Remarks: The test animals were deprived of ood (not water) for 24 hours prior to dosing. RESULTS LD: <1,000 mgkg Numberofdeaths at each dose level (by sex): 1,000 mg/kg-3/S males, 45 females Rsuebmsatarnkcse:; t6he0r%efoofrem,atlheesL(D3S/50) wanads 8de0t%eorfmifneemdaltoesbe(4</51),d0i0e0dmfg/oklgl.owiSniggnasdmoifnitsotxricaittiyonionfcltuhdeedteasnt eroded m m 000121 iantseuircvmiuvcionsgaaannidmawlserxhibiittheedtnnuomicbhearnnogfeangnimiastlss, wnhdichiaexlhbiobidtyedwheisgehstigns, was not speed. The Remarks: The authors concluded the LDia to be-< 1000 mk: ares with is conclusion. RAcEuFtEeROrEaNlCTE oxiinRcatis-1t58y5. 1976, 3MCompany, OTHER hRiesmasrukmsm:arTyh.isinsruemfemraerncyewoatshbeapsreodtooncoalssaunmdmraryeresopofrttshsstuudybarbmcyi3iMt;ettdheerefdor, thecontentsof m 000122 = ee ACEYUEIRRTITATEION Tits Primary Be nation Su-Rdaiss TEST SUBSTANCE dentiey: T1555 Remarks: Noother specificationsreanding thetest substance ers need METHOD Nopitofteest material: Not specified EMneftohroedcGmueindeRleignuelatfioolnlso.weFde:drSaelctRieonge1r50,0.V6o2. 3H.azaNor.dou1s87S.u3bs7ta0n1ce9s sSnedmmAretiscle3s3,.A1d9r7miistiaonnd Test Type inivo Specestrainceylple oline: RabbivAlbino Sex malesfmatesbothy: No pci Number ofanimalssexidose: single dose Total dos: 0.15 Lengthof ime test materia is in contact with animal: 7days Observation period: 1h, 24h, 45,721, 5 and 74 HSaczoarnidnognmseStuhbosdtaunsceds:" Used grading systemoutlined in"lustted GuideforGrading Eye Ion by ycReersmaewrrkrvsed:scTohreecdeofsootlcs.uobmsTehalenacpess(t0c.t1my5)awnuadswraaerdns.m1ii0nai,iarnceldhdec1dootmhmurinhgheet pyeednn.ocfActacchhbcerhamboboits,bwnidolsthertwieested Corrosive: Notspeciid Ir&ritCaotinoonnestcioa:l dCiosrcnheaarlgeop3acitysnd rca = 4 fs 2: Conjunctival igs = 2Conjunctival chemonis ool used to mses sores "sted Gidefr Grading Ee rion By Hazardous Subsiances" Description ofsions: None 24 000123 = eRrfeefmemcaatisr.nkesd:thTehseamseortehsrofuogrhaldatyhe7. sbObniltysawesruemmthaersyaambelfeoorfesaccohrceastweagosrygiavennd,owbistehrvnaotidoens,crTihpteiosncoorfeshe CONCLUSIONS Tprheesetnesttedsuibnstthaencreeipsortpotriemvaarlyuaoctutlhaerqiuiatlaintty oafndthreqsutiurdeysacnaduttihoenavarlyildiatbyeloifntgh.eIcnoandcelquusaitoensi.nformation is REFERENCE BPaiuols,caMrcNh., Inc. 1976. Primary Eye Imitation Stud-y Rabbits. Philadelphia, PA. 3M Company. St. 25 000124 25 ACUTE TOXICITY Title: Acute Dermal Toxicity Study of T-6342 in Rabbits TEST SUBSTANCE. Identity: T-6342;aclear, colorless liquid. Remarks: None METHOD 4M0e4thfoodr/DGeurimdaelliTnoxeicfiotyl.lowOeEd:CDOGEuCidDeliGnueisdedloinneotTPb2e0g7i1n.witMholsetttelriskaelnyd tdhoisnsothou0ladsbheiOghEaCsD4 nGuumibdeerlsi.ne GLP: Yes ear study performed: 1995 Species/strain: Rabbits/Hra(NZW)SPF Sex (males/females/both): Both Numberofanimals/sex/dose: 5 males, femalesisngle dose Total dose: 2000 mg/kg Vehicle: None Routeofadministration: Dermal sRuebmsatrankcse:waTsheaprpalbibeidtstohathde tihnetahcatisrkicnl.ippTehdefarroeamotfheaiprpbliaccaktsiobnefwoarse ctohevearpepdrowpirtihataegaamuozuenptatocfhtahnedfeasnt cooclcllaurssivaenddredsrseisnsgi.ngsCowlelraersrwemeorveedu.scdTthoertesetsrasiintetshewearneimawlass.heAd fwriththteap24wahtoeurraenxdpodsiusrpeospaebrlieodp,aptehre tfeoswtelmsa.terCilailniacdamlinoibssterravtaitoinonasndantdwimcoertdaaliiltyytchhereecakfstewrefroer m14addeaysa.t apBpordoyxiwmeaitgehltys 1w,e2r.e5,adentder4mihnoeudrsbeaffoerre test material minutes after was applied, removal of at the Day test m7ataenrdiaol nanDdayon14D. aTyshe3.in7i,ta1l0,dearnmdal14i.rrAitlatitohne reading end of was made the study, 30 the animals were euthanized and subjected to necropsy. 26 26 000125 Number ofdeaths at cach dose level (by sex): none. eRxecmeaprtikosn:ofAlolneanimmaalles tahpaptealrosetdwneoirgmhatldaunrdinegxhtihbeitfeidrstbowdeyekw.eigDhetrgmaailnsimtihtraotuigonhocuotnstihestsedudo,f Swliitghhtthteo vmiosdieblreatleesieornysthweemrae,obesdcermvae,d aatndnecartoopnsiya., aTnhdesdleirghmtaldeLsSquOamiantiroanb,biscowriaascegoruesanteersst,haann2d00f0ismugri/nkgg.. | No np"TerhcoerdodupecsreymdawsleirgLheDtSnotOtoeomdf.odTe-r6a3t4e2dwearsmaglreraatteriotnha.n 2N0o00clmingi/ckalgsiingmnsaldeurainndg ftehemaslteudryabobritvsi.siTblheelteessitosnusbasttance REFERENCE PGrlojaecztSaI.D:19H9W5.I A5c0u80t0e3d7e4r.ma3lMtoCxiocmitpyanstyu.dySot.fPTa-u6l3,4M2N.in rabbits. Coming Hazelton, Inc. Madison, WI. 2 000126 27 SKIN SENSITIZATION DATA Titles Assessmentof Contact Hypersensitivity to T-7524 in the Albino Guinca Pig (MaximisatiToesnt-) TEST SUBSTANCE Identity: T-7524 pRaesmtea,rwkist:haPusrpietcyifwiacsgr9av8i%ty tohefre1.2m3.aining 2% was |-methyl.2-pyrrolidinone. Subswtaasanbrcowen METHOD `MCeotmhmoids/sgiuoindeDliirencetifvoell9o6w/eSd4:/EEC;C OmEeCthDoGdusidfeolritnhee Nduetmebremrin4a0t6i;onMoaftgonxuiscsitoyn,aansdlKasltiagmmeannde1d97b0.y Study duration: about 90 days GLP (YIN): Y ear study performed: 2001 Species/strain: Guinea pig:DunkinHartley strain Sex: Females Number of animals per dose group: 10/treatment groups S/control group Routeof administration: Intradermal and epidermal administration Range-finding study: C1o%n,ce2n%t,ra5t%i,on1s0:%S,ta2r0t%i,ng50a%n,d subsequent and 100%, acnodncdeonstersatlioownesrwtehraen t1ak%einfnfereodmetdh.e fTohlelroewiwnagssenroi.es: indication about whichdoses were usedforinductionor challenge. Vehicle not indicated. Vehicle: not indicated wIanrduecatsisoenssmeedtahto2d4: anIndi4ra8dehromuarls injections of four concentrationswere used. Dermal reactions CDhearlmlaelnrgeeacmteitonhsodw:areepaisdseersmsaeld a2p4plaincdat4i8onhwouarssadfotneeruexspiosn4ugret.est substance concentrations. 228 000127 2 Main study: duction (concenteation nd method: s14t wDsbawsytma1in:xctTsuhrareoo5f%nFjcrceotunnidoc'nsewCnoetmrp,lmeaatndedoAadtjuvcalnitppweidhscwaaputlearr region A:hWeavhmiiltrweasofn1t0%ndeitaesudbsiance with Freund's Adan bDeatywe7e:nTiennjepcteirocnenitess:odhusm-pdroodveoekye-dsumfitled(iSnDflSa)mwmaastoarpyprleiaecdtiiodn:ermaly to lipped ara aDraeya a8:ndFhiefltdy perlcaencteewtithsuMsicirnocpeorcsonacee.nrTahteondweassinapgplwiaesd epmidoevmeadlalyrot4h5eSDSrested Induction vice: Not ndicicd Challenge concentration and metho): lDiapypeId:arAk.iyVepheirccleentwacsonnconntitocnio.fth cst substance was appl spdormaly othe Challenge vehicle: Not indicted Postobservaton period: Sites were assess 24 and 48 hours ae induction snd chllengs phases Geforrraeddiignnrgagedrseodau.steRsuebTashlteasnscwoeeusrraecneedovfaplrtuehaptaeerdatesiocnwc.aosrodti1ninEdiCctcedt, sbutfborocaissiocanioannnddchabllleinngegeraecqtuiornesments Stata methods wed: None pRheeersmcyaeinrctkisnf:moamtAihcsracleodmlephaoyduyendah.e.cpkoosfihive ccosnttotl.dSidntrenaocttiinondsicwteedr)iwnadsidctosnoufsiennatlpahtaion te of 100 RESULTS TBoodsyewreeisgphotnssaenedfbeocdtsywbeyidghotsglaevnelwseNroimmoraalibeytowcecenurcedoannsd osndsyesstteed troourpsi was bserved. icIronendsiumcceltn.ito.nLiaDgnuhdrticynhgsalclohlaeslnlsgeeinngseci,onrgneosw:saksiDnusrreiennagcattiinohdneuscwteietorne,scukisidineanfntcsaef-tevrewssehearlslkceinangen16icnser(a3b4yetadhnedgr41o50up%hsoSnuDsdSpost Challenge. The sain did not hamper scoring fhe sin reactions. Sensitization: A sensitization te of percent ws2d9temined. 000128 2 Remarks: nore. coNCLUSIONS There wasno evidence that T7526 caused skin hprsensiviy in guinea pigs [-- REFERENCE (NMOaTOxXi.mi2s0a01t.TieoAxsn)s.esNsOmeTnOt XofPCroonjetcatctnuHympbeerrse2n2si0t2i7v.ityHtoeT-t75a24ginethnTe hbAelNboeitnsohecGrulihanne,das Pig 230 000129 ue REPEAT DOSE DATA ide: S Daily Dose Oral ToxicityStudywith T-6669 in Rats CenAtSiRtNy:38T2h5e.2e6s.t1material was perluoroocianoie acid, ammonium salt,T-6669 (EC-143), Lot No. 235. Remarks: Its described as a white powder that is 93-97% smmonium perfluorooetanoste. METHOD dMaettehdoDdegcueimdbeelri2n0,fo1l9l9o6wiendclTudheedsitnutdhyewraespocrtonductedinaccordawnitchae company protocol TPG755 Study duration: 20 deys GLP (VIN): Year study performed: 1997 Speciesistrain: RaCrl:CS(SDIBR VAFPlus) Sex: Male Number of animals per dose group: 10 Routeofadministration: Oral gavage cDoonsseescutteisvteeddaaynsd frequency: 0,5.0, 14.0, or 42.0 mg g/day. Doses were administered once daily for Posttreatment observation period: 15 days t(StWeaistntiesr(t.iDcua1nl9n7me1er)t,,h1Lo9ed6vs4e)nues'esd:TeMstet(hLoedvsenaer,e o1u96l0i)n,edanidntDhuenrneepto'rtsmnudliipnlcelucdoemApaNrOisVoAn aiRndeitmliiaabtriiktounsm;:,thIReneapvroedterovscioaoltsimsotonastfiersdowwmaettihegehrtpwsraobsteocutoswlee,dentshe2t1ah0neiavmneadhlis2c5lwe0egai.nghdeTtdhheebedantoiswmeeaevlnso3lw0ue3mreaenwpdarso3v9Si5dmgeaidktfeo.sotdudTayhned water dcaoansgieemaaaldnsmdiwneeixrsaetmroiabtnsieeodrnfvoaenddctldwiiancliecyalhesdriaegyanfsfioebrre.fmoorrBteoalddioytswyienaigngdahnmsdowraetirbpuepnrdmoiextai.smuartEeeadlcdyhaai1nl,.i2m.a5Bllawooandsd4srahemompuolrvesesadwffeerrroecmacfhs a6cno.li9lme.acl1t5ead.nndodnweD2i0a.gyhseOd-.n2 DpTarhyeed6oi,sgiehv,tetlahatoneuiragmlahlltsohbepeeoprrfogtrhooecuoplivwteearrteweassatchcratoifltilhceeecdtp,erdaendfdooshmeesciaimcvphelraewnisamsacloe,llmwevectieegdhdeodfn,rDoamanydea-c1h, 31 000130 231 OnnyDsaye20o,ehpeuemmipinCgoNaniimadlsswasetsyc,eifcTedhadehrieemrsriwsenur awlasecdoinld wlereheanncdwteieghded RESULTS NOAEL dos and fc: resstehrclhoiwneswta4s2ddomseeei6idtnebaibsyegdhhsoentthdodee usetodp,.icAINS]OofC<5Eo0omLngs, 5L0OAmEkL.(dboasseeadnodneHifgh:er heGprateiecprlhony2]mCeok.vtihdshigsheeisntdiyssposirs. AdLOyFL of lToxiicarsegsnpwoenresoebserbeyddonsealvgeroAsl.animals sive 0 chu sre, No estmentltcd c5o0ntme): igher bpp! Conoxide sity (24 1UG compared 3 1UG for P14a.l0mmioyysCosingnoifxiicdaanstleyaievidyd(3m9 aL1nGocdoympwairehdt13sinsTUdGionr sdosoinmgpaid her epic: a42.m0imeegCosnignaixfidcuanetlaytrveiduyce(d33m1e0a1bcodoymwpeaigrht s5in1s0d1ifgo sdoosminegsprid, igor hepatic Satiatsiistciclayl rnesualt:nThecoomwpearrmedeao cboondtyolwe(i1gh.t0ga0i)nsfor he ida igh dos groupswere odRoersmaianlrgkrmsei:aonTdhootduhygeyhwetsihhgohmwiegdd-icaonnvdewherirygeh-ndoolsseygnewvTietahgnrsoyhupdsticirttebeydeeorveenrbadndy Bwrweeeicgogmhapitlnetdeu.riTnhthe 5iTh0ns a7dutmihoorcwfthapeedntroaixhidaostombmnaeisperdnoolnfmrsalainoeinn,CaeHlLrlCcDdoAseSDsvIBilRnVhsAteRev,leshsoefnpo lsoitS]eCcvoeolnnsof1aexc-idi6u6seo6aysi.lio ,hann pcRhaealmnaigroeksys]i:sCnToohtnelaaneudtyhaorinsddecisicivagitniyav.teeodHftoahweeivoecr,foecfnty,mvehlrnbdeetdsioonnonsmLisOgAibEisLsaawtrasisneeresrsamneidsniiendhhebesyeetvnhescseuofosfthe MHaedinsoan.oW,Si.. 1L9a97b.ora5toDrayilPyroDjoest dOennsifTcotosni: SCHyW w4i3t2h5.-6176.603i.n SRatt.s.PaCuo,mMinNg Hato, ne. m 000121 x> REPEAT DOSE DATA Title: 28-Day Oral Toxicity Study with FC-143 in Albino Mice; IBT NO. $532-10655 TESTSUBSTANCE pIedrefnltuitoyr:oacFtlaunooartaed,PFFlOu,orFoCc-h1e1m6i,caFlC-F1C2-61,43F,Ca-l1s6o9r,efFeCr-r1e4d3t,ooarsaPsFaOmAajaomrmcoonmipuonmesnatlt,ofaFmXm-o1n0i0u3m (octanoic acid, pentadecafluoro-, T-1742CoC, Lot No. 269. ammonium salt, CASRN 3825-26-1), Remarks: The purity ofthe est substance was not indicated. METHOD Method/guideline followed: Not stated Study duration: 28 days GLP (YIN): N ear study performed: 1977 `Species/strain: Charles River CDalbino mice Sex: male and female Numofbaneimarls perdose group: 10 (5 malesand 5 females) Route of administrations Diet - Purina rat chow Doses tested and frequency: 0,30, 100, 300, 1000, 3000, 10000, 30000 ppm Post-observation period: None Statistical methods used: body weight ratios among A test groups, was but used to the type compare mean oftest was not body weights, noted. liver weights, and liver to Rmeeamsaurrkesm:entDasiwleyroebstearkvean.tioGnrsosfsorpbaethhaovlioogriaclerxeaamcitnioantsioonr wmoarstaclointdieusctweedreatmfaidnea,l Weekly sacrifice obnodalyl wsuerivgihvting nmeiucter.al11buwfafsersetdatfeodrtmhaaltin"aforrepfruetsuernethatiisvteopsaetthoofloogrigcanexsaamnidnaottihoenr."tisHsuoewsewvears,roermgoavnesdexanadmipnreedsewrevrede innot `scpeocnidfuicetd.ed oLnivleirvewresigfhrtosm aalnldslaicvreirfitcoebdomdiycew.eSigahmtplreatsioosf were calculated. livers and blood Microscopic examination was were sent to 3M for analysis, but the results,ifthe analyses were completed, are not included. 233 0001352 233 RESULTS NOAEL (dose and effect): none; effects at all doses nwLeeOcirgAohsEtiLsr:at(cidyoots:soepblaoandsdymiwceefifveagcchtut)o:lleo3ss0s;)pbiplme d(uhcetpaptroocleiflelrualtaironh;ypiencrrreoapsheyd:lhiveepratwoecieglhltu,lairncdreegaesneedraitvirontabndo/doyr "Toxic responseleffects by dose level: p31r00o0lpippfmper:ma:ti[osinen;echrLeepOaasAteEodcLel]livleurlawreihgyphetrtcryoanpohsyi;sc;yhteoppaltaoscmeilclulliapriddevgaecnueorlaetsi;onboadnyd/woerignhetcrloossiss bile duct d3u0c0tppprmo:lifemruastciounl:arbowdeyakwneeisgsh;trlooussghed fur; cyanosis: hepatocellular degeneration andlor necrosis; bile h1e0p0a0topcpeml:lulmarushcyupleratrrwopehayk:necsyst;oprloausgmhiecdvfaurc;uoclyeasno(sbiesf;orheepdaetaotcheblyludlaaryde9g)eneration and/or necrosis; 310000000pppmp:m: mmuusscculualrarwewaekankensess;s;cocuogughheeddfufrur(b(ebfeofroerededaetahthdudruirnigngwweeeekk1)1) 30000 ppm: muscular wesknes: roughed fur (before death during week 1) Statistieal results: `The following parameters (A) Body weight loss were significantly diferent from controls (at a level ofatleast p< 0.05): 13000 ppppmm:: mfaelmealseastawteweekesk14-4; females at weeks 2-4 1300000ppppmm:: mmaalleess aatndwefeekmsalIe.s4;atfwemeaelkes1 a(tawneimeaklssd1i-3d afte week 1) (B3)0Apbpsmo:lumtalleisvearnwdeifgehmtalienscrease: N1o0t0rpeppmo:rtemdaalteosthaenrddfoesmeaslebsecause micedied before day 28. (3)0Rpelpamt:ivfeemliavleersweight increase: N1o0t0rpeppomr:temdaalteosther doses because mice died before day 25. cRoenmsaurmkesd:aBlbooduygwheifgohotd wwaasstseuwpparseaslsseodsneena.dose-related manner; increased amounts of food ere 3100000pppp:m aalnldmhiicgeheerx:ceapltl m1amlaelseadnidefdewmiathlisndi2e6ddawyistohifntetshteinfg.i9rdsayts of testing. 3s0hoawnedd1e0n0laprpgmemteenstt garnodu/posr: diosnccolaonraitmiaolndoifd1 ionremaocrhegrloivuepr. loNbouleosthineadlleaatnhismaolccsusrarecdr.ificGerdosasheprat2h8adlaogg.y 234 009133 234 No conclusions were given by the study authors. RlRoeeslmsaeatsirvkiensa:mnidcAelalbfsemodilcu3et0e,el1di0v0Ae,rPowFreiO3g0hl0tospspwwmee.rieghAitn.dcorRseeea-dsrueecdltaiitnoenmdsipciaenttbfeeordndy3w0awspeipsgmehnorgiamniotnhrweeedAreePpFrfeOosl.sleodGwrebodosbdsyy wweeiigghhtts. dcpiahstachnooglleoosrgaiwtcieaorlneeoxofabms1ieonrravtemidooinrnotflhikvielrdinvleeorbysessa.omroHointsghteoarpllaotArhgPoaFlnosObgeitcsrieedaxteaesmdilaninvaeitrmisaolniosnfionatclllduiAdsicPunFsgsOeendt.lraeraTgtreeedmaemtnimtceneatnrdrelevoleraatleedd adicfcfoumspeacnyiteopdlbaysmfioccaelnltoarmguelmtiefnotcoalfchyetpoaptlocaystmeisc tvharcouuoglheo.utDtehgeenlievreart(ipoanniaonbduloarr nheycpreorstirsoopfhyh)epatocytes and focal bie duct proliferation was also noted inmice within al groups. REFERENCE RCherpiosrtto,pIhedru,srBi.aalnBdiMoa-rTieasst,LAa.bJ.orat1o9r7i7.es,2I8n-.DaSytuOdryalNoT.osi8c5i3t2y-1S0t6u5d5y,w3itMh RFeCf-e1r4e3ncienNAol.biTn-o1M7i4c3eC,aCFi.naLlot 269. 2s 000134 25 REPEAT DOSE DATA "Title: 25-Day Oral Toxicity Study with FC-143 in Albino Rats TEST SUBSTANCE (pIodecertnfatlinutocyir:cooacFctiladun,ooaprteaend,taPdFFelcOua,olrlFouCoc-rh1oe-1m,6i,caamFlCm-Fo1Cn2-i61u,43mF,Cs-aal1st6,o9C,reAfFSeCrR-r1eN4d33t,8a2o5sr.a2Ps6F-a1O)mA,ajaomrmcoonmipuonmesnatlt,ofamFXm.on10i0u3m T-1742C0C, Lot No. 269. Remarks: Purity of he test substancewas not indicated METHOD Method/guideline followed: Not stated Study duration: 28 days. GLP (VN:N ear study performed: 1977 Species/strain: Charles River CD albino ras Sex: male and female Number of animals per dose group: 10(5 males and 5 females) Routeofadministration: Diet - Purinarat chow Doses tested and frequency: 0, 30, 100, 300, 1000, 3000, 10000, 30000 ppm Post-obscrvation period: None bStoadtyiswtieciaglhtmertathioosdsamuosendg:grAoutpesst,wbaustuhsedtytpoeocfotmepatrewamsenaontbsopedcyifwieedi.ghs, liver weights, and Iver to r`Racetoimnoassruwmkepstr:ieodnAenwtieemrramelidsneewtdeerratemitonebersmdcirwnevaelekdslaydc.arilfyiLcifevo.errGcwlrieonisigcshailpsas,tihbgonolsdooygfitwcoeaxiligcehixttasym,.iannaBdtoidloiynvewwreawisegihcgtohnatdnutdoctfbeoododdyonwelilght `scuormvpilveitnegsreasi.@ o[ftistisstsauteesdatnhadtotrhgeasntsuwdeyriencelxuadmeidneadc,ombputlehtee esxpeacmiifniactliiosntsofnogtrossusppplaitedh.oloLgiyvearnsdwAeare iTwinevcielgrushdeaednddtobldoeotderwmiene rseelnatttiove3oVrgfaonrwaenailgyhstist,hebnutstthainreedsfuolrs,hiisfttohpeaathnoalloygsiecs ewxearmeincaotmipolne.teSd,amaprleensotof 236 000135 236 RESULTS NOAEL (dose and effect): none; effets observed at lowest cst dose LOAEL (dose and effet: 30 pm (inressd iver weight and hepatoeyt hypertrophy) 1"ofT.to3ex0sit0cinprgeo.smpToshnhesoreweleewdfeersceisngboyhpdrroeesmdeautecuveredelb:doeadAtylhlswaoeniigothmhaegragicnislv.iennicBa1ol0ds0yi00gwneooir fg3h0o0gx0ai0ipcnsyaanimnoitnehdg oawtnihtirhmiasnlout0hpes3.1ir0so00pweepe,ky aosamtsomnofrgedealiwl emearlse1i0ga0nn0id.fifceanm3ta0ll0ye0r1epsdptum.caenidmTairlnesda.uomsTeehn-etdesppareitmneaddreynmtsorimpoahnnonlecorog:nisciRscethedaduncogefedsfonootadhtleoiimkueetrifwweoareseavssiyotdreopelesaamrico m5enu0ll0ai0rfgopecomamelnttod(ihfyfpueseroepnhlyar)goefmehnetpoaftohcpyactsoacmyoensgwamsamc a ameosntggarnouipmses0,i30,e4tngdro1u00ppey30,so1d000, and sSttaattiissttiiccaalllyrseisgnuisf:icaDnitfafter1e0n0c0esanidn b3o0d0y0 `male ai 300ppm and n female at 1000 wpepimg.htAbbestowleuetne nd 3000 pom. vth rcownetirgohltasnwdecreatimgennitegarnotuypsiwnecrveensd Relative Iver weightwas sin canty for increased for males at 3000 pom. aRbneeismimadaerlssksif:veedrG3.r0o0sTsphopmam.tahoiIlnnogafinfciacmltalewsxaafsmdfdo1ci0adl0n0oftopmpeumsloilfcmraaclraetcmyhetenotpflraTesclmatitcewaenseflfmaerucgtlesimieonncKtaiodf0nehyuespftaocetyhieecnrsroseraogmanonssnt cfaeoFsnhtteraponaliosmcaoylntsleys.bAebcsTaohulesuetsevoefvribrtoydw/yediwegeghittgcshotifnrsmeaduulceetsioiatnnvi1on0l0hv0eeamnehnidtgh3oe0fr0td0hepospmlaeamsriemonnaso.twassigmnoirefipcraomdoifmfereedntstmhe The authors gave no conclusion. Rwieinmgahtrtkdgsa:i1ns0Awl0le0aprnimmraeoldsucihenidgthihneert1ih0n.g0dr0oo0usapensdree3lca0it0ved0i0nmgapnp1n0me0rg0rooupmsordisepdobme.foRredthueceedndfooofdthteafkies wwaeesk.obBsoedyr eRTfeiflseacattmisvowenatlsirveemrloawrteeedgpchrhtoasnnowgueenrsceewdienricenremoabasseledrevinsetdmaainnlitsmhaelsdliv3e0rspapmmonogr mlolrAsPaFndOetentesd nfiodt3s0.0 pThotrsemovree. of M2R6ee9tp,roriStce,kp.itnMeid.musbaternrida2lM0Ba,i1ro9iT7es7s,t A.LJ ab19o7r7a.to2r8i,.DaIny.OrSatludTyoxNioc.it5y53S2tu-d1y06w5i4t,h3FMC-R1e4f3erinenAclebiNno.o Ra1t,HF2iCnaCl, Lot 7 000136 7 REPEAT DOSE DATA "Title: Ninety-Dey Subacute Rhesus Morey Toxicity Sud poIecdretnfatuniootriyoc:ocatcFadln,uoosprteean,disaPdFFeOuc,oarlFouCca-rh1-e1,6m,iaamFlCm-oF1nC2-i61,u4m3F,Cs-aal1lt6,s9oC,rAeFfSeCRrrN-ed31t5oo23r5as3-a2sP,6aF11Om)Aoarmmcoomnpiounmenstato,f aFmXm.o1n0i0u3m MReNm.arTkhse:IotTnhe utestmsoubfbsFtCea-n1cr4e3ususdediinhhsisstsutduydwy swaosbt3a40i,neTdefrtoesmttshuebsstpoannscoerw,a3sM,a wChoimtpepanoy,doSst. Paul, METHOD Method guideline followed: Not sited Study duration: 90-day GLP (VIN): No Yearstudy performed: 1978 Speciesisteain: Rhesus monkey Sex: Male and female Number of animals per dose group: Two pe se per group Routeof administration: Oral gavage Doses tested and frequency: 0 control group), 3, 10, 30, and 100 mg/kg/day7, daysiveek,for90 days Postobservation period: None oSotymaotsiogs.etincTcahliemyeesatinhsdowdteshreueaspcepodrm:oppraAirlaetdsetbaetyistaticn(alfoaarnealoqlfuyyvaslaessroiciaounmnscpeeaq(uraoelndevt-awhrairaynaccileamss)esniafstidcgeartsoicuorpni,sbeBwdairtbthyltSehttesecloonattnrdoolTrgorroiucp, (1960) using Dunnet's malple comparison ables o judge significanceofdifferences cwRaeegrmeeasruaksncsdd:mianTietnhntiasmiasntleueddyti.hneTashutesemmmopoennrkkaeteuyyrsse,(weh2urm.ei6hdio03tuy.s,9e0daknigdn)daiivgnihdduca1ol0lnyfterimonalhleaednhegenisnvugisownimmrreeinmteesyhPsa,r(-i2nsgq9u5Mco3esn.sk8ey0ypkCg:)how mswuoabnssitkfaednycstevianidcgmciondoiadsythraeaantlditohfnr,weesthrheasspetllaeecfstveewdterrfieonrfatidhaen3stucmdyeo.swnTehcdok.utaectcWoacmttopemlerpewotdaeusnpdah,vyassiiucasabplleenxdaaemddiinianut0mo.n,5,%POMrnieoltryho1c3eslt, vdwooalssuemsae.wdermTehiebnassiaemdsebutyvpgoeoalnruvhmaeeegodebfoad0t.sa5w%ferieMgqehutlesnlcooybcaoeifln7edwdaaywseg/eikwvleeyen.ktfT0ohtreh9em0voednhakiycesl.yesAcwolnedtrrooosloebsgsreowurepv,redisntidweiivcniediudnaaclilodynusoltyyant 38 000137 28 ``gceonnedruacltpehdyisnictahleacpopnteraorlanpceer,iobdehaanvdiomro,natnhdlyphdaurrmiancgotthoexsitcudsyi.gnsB.loGoednearnadluprhiynseicsaalmpelxeasmiwnearteioonbstawienreed for aAnfatleyrscisomfprloemtiaollnomfotnhkeeytsestonscubesdtuarnicnegatdhmeinciosnttrraotliopnerpieordi,odt,heanllasguarivniv1ianngdm3onmkoenytshswearfeeransetsutdhyetnifzteadtion. awdirtehnSaelsr.nyslplaenen,(pPihteunitcayreyl.ikdiidnneeyHsC,I)l,steexs/soavnargiueis,naantdaendbrd,ainnecwreorpseicwde.igAhtedn;ecrreopprseys,entthaetihveearfts,svucesr.were cwoalslewceteidghiendbuaffifeerrefdixnaetuitorn.alH1i0st%opfaotrmhaolliong.yEwyaesspweerrfeorfmiexeddoinn tRhuessfeolllloswfiinxgatoivreg.anTshefrtohmyraollidm/opnarkaetyhsyroinid tchoerocnoanrtryovleassnedlst)r,edautmoednetngurmo,upls:euad,rejneajlus,nuamo,rtca,ecbuomn,e,coblraoinn,,reccstoupmh,agkuisd,neeyyse,s,figvaerl,lblluandgd,ers,inh,eart (with pmaenscernetaesr,icprlosytmapthefnutoedreu,s,rerirbojpuhnacrtyinognea(lbolnyemmpahrrnoowde),, msaalmivmaaryryglgalnadn,d,lunmebravres(pwiintahl mcuosrcd,lep)i,tusiptlaereyn,, sitdeonmtaicfhy.intgetsattetsooo,vaarnids,antyhytriosisdu,esp(asr)atwhiytrhoildes,iotnhsy.muHsi,sttroapcahtehao,ltoognysiwl,atsonpgeuref,orumreidnaoryn btlhaedfdeorl,lovwaignignao,rgans aflrlobmlaaldldemro,nkheeayrst i(nwitthhe ccoonrtornoalraynvdestsreelast)m,ednutogdreonuupsm:,aldereun,alsj,ejsuorntusm,,bcoenec,umb,racion,lone,sorepchtaugmu,sk,iedyneesy,s, lmiuvsecr,lel)u,ngs.pslkeienn,, pmaenscernetaesr,icprlosytmapteh/untoedreu,s,rertbsojpuhnacrtyinogne(ablolnyemmpahrrnoowd)e,, smaalimvmaaryrgylagnlda,ndl,unmebravres(pwiintahl cord, pivtaugiintaa,ry.isdtenotmiafcyihn,g tteatsttoeo/,oavnadriasn,ytthiysrsouieds,(sp)arwaitthhyrloeisdio,nst.hymus, trached, tonsil, tongue, urinary bladder, RESULTS NfrOotAhyEeLme(sdiossewearnedoecfcfaescito):na0ll(ycoobntsreorlv)eadnadt3bomtkh gof/tdhaesye--dSoosafgetoloelve,lsm,oderate to marked diarrhea, and aLdOreAnaElsL, (bdoonseemaanrdroewf,fescptl:een3,0amngd/kley/mdpahy--nColdiesn,icaanldsdieganthsso.f toxicity, adverse histologic changes in the "lTevoexlis,c rTehsrpeoenmsoen/ekeecytssibnythdeo3s0e mlegv/ekl:g/Tdhaeyrdeowsaagsengoromuopr,taalnitdyaalltt4hemo0n,k3e,yasndin1t0hmeg1/0k0g/mdgakygd/odsaaygedosage `aroup. died during this study. d3omsagg/eklgev/eld,ay Soft stool andor moderate to marked diarthea, frothy emesis were noted a this p1a0lemga/nkdgs/wdolalye--nTfhaecefodlulroiwnignwgeseykmp7,toamnds wblearceknsottoeodlsidnuornicngmwoenekeky1:2.anorexia during week 4, t3h0esmeyk3gm/odnakye--ysThwreeree manoonrekxeiyc.s dAileld4dmuroinnkgewyeseiksth7i,s1g2r,oaunpds1h3oowfedthselisgthutdy.to Fmordoemrawteee,kan4,d sofotmheetifmaecse saenvdergeu,mdsecwreeraesendotacetdiviintayl. I4n madodnikteioyns,.sOwtohlelrensyfamcpei, ocmyss,obasnedrvveudlvian, as wel as some/all pallor stmooolnsk,edyeshyidnrcaltuidoend,tphteosfiosollfowitnhge:eyeemleisdiss,,anatdaxlioas,sobflabckod weight. The surviving male had dpleactreleeatss.edPnruomtbhreormsboifnertyitmheraocnydtaecst,idvaetcerdeapsreodthhreommobgilonbtiinm,edweecrreeaaslesod ihnecmraetaoscerdi.t,Thaensdeiinnccrreeaasseeds walekraelaipnpeaprheonstphaata| smeolnetvhelbsuattwoenreemmouncthh m(3o6r5evmsa5r9k7edinatthtehrceoentmroonlt)hsw.hicThhepreerwsiasstedadienctrheeaosneein surviving male (360 vs 851 1U/ in the controla)t 3 months. SGOT levels were rediiced at one. 239 000138 239 mt(h4oe6ntcvohsnt3(r1o5l9)I.vUsS2iG9nP[tThUe/wcaoinsntterhloeelvcgaortnoteurdpo)al.t) a1Cnmhdoolnientshtthe(er4oo4lnveisnsatuhrcevoionvtnrieonlgsumvraavlliueveianogtf3m1am5lo1enUt/wh1a)ssa(en8ld8eavvtast34ed5mo(1n2t/4h10s.ivns aD1u6cr5oinmtnrggo/lt1h0lee0pvaemltlh)o.olfoTgoi8t.c21aall/ps1rto0utd0eiiemsnl,aatnnhddeaftlootblaullmoawilinnbgiunmcitohnmispwoaaunsinm2da.-l0r0ewlvestreeadcrseodynumtcopeltdo:lmetvsoetlawleorpfre4o.ot5eb2isnegrw/v1ae0sd05im.nl5.3 vs myIpayolmcepehlalnnudoldaferesimtayloefmothnekebyosn:e mmaarrrkoewd,lainpiddmdoedpelertaitoenaotfrotphehyadorfenlaylmsp,hloiigdhtftololimcoldeseorfatthee splecn and t1h0e0smtuedyk.g/Indaadydi--tiAolnl,mtohenkmeoynskefyrsominthtehis10g0romugpksgh/odwaeyddtohseasgaemleevseilgdniseodfdtuorxiincgitwye4e5ktshe2 - 5 of damcootsinavkigeteyy.gsrpdrooousspter(daatn3ioo0rne,mxgbi/aok,dgyf/rdwoaetyhi.yghHctomewlsoeisvsse,,rap,nadlthebfosadciyeg,ntsporaeflmebtlgoixunimgcs)i,tayspowpboeslaelrreevndeefdaarcileineartnhiedn1et0yhe0esm,Sgtd/uekdcgyr/etdahasayendwas ocdebopsmlepertoviueondnodifnrettlhhaeete3ad0drsmeynemaklpgst,/odsmlasiyghwtdeortsoeamgoobedsgeerrroavutepe.d hiDnyupmroaiclneegllatunhledarpfiaetymohaofllteohgmiecoabnlokensyetusdm:iaemrsra,ortwkh,eedafnodldiofmfwuoisndege.rpaitde atrophyof lymphoid follcls of the spleen and lymph nods Stthaet3is0timcga/lkrge/sdulatys:doTshaegreelewveerledsutraitnisgtwiceaellky s1i3gnoiffitchaensttdudeyc.reTasheesfienmbaoldesmwoeriigkehytsofforththee m30almegm/kogn/kdeayys at Sdtaotsiasgteicallevleysliagnndiftihceanmtovnakreiyatsioofnstihes1e0x0-gmrgo/ukpg/mdeaayndwoesiagghetsleovfelawfeerweoarlgraenasdyocdceuardreadt tbheitswteiemn.the careobsnsptoerlcoutltievaenaldnyd)e,xrdpeleeacrtriiemvaeenshteeadalratgbrswooeulipugst.hetTbfrhoaerinfsetwametaiilsgethistcaiflnolyrthsfeiegm1na0ilfmeigcs/ankintg/tvhaderaiy1at0diomonsgsa/gkwegedrgearoytuhpedo(fspoal<gleo0w.gi0rn5og,:uppd<e(cp0r<,e0a10s,.e0d1), avanrdiaitnicornesasweedrereolfatuivnekpniotuwintabriyolwoegiigchatl fsoirgnmiafliecsanicnetahned3wmegr/ekngo/tdaayccdoomspaagneigerdobuyp m(por<ph0.o0l5o),giTchese alerations. gRreomuaprk(1s1:7Fvo5ll8o9wmian/g1o0n0emmloinntthheoftcornetartolm)e.ntT,hgeluacuotsheorwsaosfstihgenifreipcoarnttlaytrclbeuvtaetetdhisinttohae s3inmggl/ekhgi/gdhayvaluc f1o1r2,ma1l0e5.#a7n3d6612w0hmogh/a1d00a vmla.lueGloufc1o3s1e. lTevheelsotinhetrheth1r0eeanmdon3k0eymgs/ikngt/hdeay3 gmrgo/ukpas/dwaeyregr1o0u4pahnadd 1l2e5vels of m81g./9160.08m8l,,arneds6p6eimvee/l{y.00afmtierionntehemoconntthroolf,t3r,ea1t0meanntd. 3A0Lmtgh/rkeeg/mdoanythgsrooufpstrrceastpemcetni,vegllyu,coSseGPleTvewlsaswere e"Tlheevraetewderinetnhoet1r0e.aatnmden3t0rmelaaktged/dcahayngdeosseingruoruinpaslyastis| msotundtihe,s batutanwyerteimceompperairoadblsteudtioedc.ontrol at 3 months. CONCLUSIONS "mTahrertoewst,ssupblsetean,ncaendcaluysemdphclnionidceasl,saingdnsdoefattohxsiciintmy,alaedvaenrdsefehmiasltoelorghiecsucshamnognekseiynstwheheandeandamlisn,ibstoenreed at dosage evelsof 30 and 100 mg/ke/day. Remarks: The test substance was not sufficiently characterized. REFERENCE 240 000139 kad M3oMnCkoemypTaonxyi.ciItnyteSrtnuadtyi.onLaalboRreastcoarrychstaunddyDneuvmebleorpm1e3n7t-0C90o.rporation. 1975. Ninety-Day Subacute Rhesus 241 000140 El TCiytlne:om2o6l-gWuescMkonCakpesyusl.e Toxicity Study with Ammonium Perfluorooctanoate (APEO) in TEST SUBSTANCE entity: Ammonium Perfluoroctanoate (APFOY: Perlluorooctanoate (PFOA) Remarks: APFO a 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: Y Yearstudy performed: 1998/1999 Speciesstran: Cynomolgus monkeys Sex: Males Numberofanimalsperdose group: 6 animals group or groups 1, 3,and 4; 4 aimalsgroup for group 2. Route ofadministration: Oral capsule mDgoskegs/dteasytefdoarn2d6fwreeeqkusency of administration: 0 mg/kg/day3, mg/kg/day, 10 meke/ or 3020 Postobservation period: 3 wesks SAtNatCisOtiVcaAl,mectohvoadiastues-ead:djuLseevdenmeea'nes,s5o%rtvwaor-itaanicleedhopmroobgaebnieliittyy:evAeN.OVA, Dunn's cst dtRoeexsmiiacgirtnkyas.t:eWdhDteohseni3dn0og7so2if0nagmnewn/akasgl/rsdeasiyun.mtehed3o0nmDga/ykg2/2d,aayndiosmeagrroecuepiwveads2s0tmogp/pekdg/fdraoymadnadyshi1s1g-r2o1upbewcaasuse of eoAxnraimsmiianglnasstoiwfoepnrsoeowoerbrsheeeradvloetnhdeotbrweiafcbeonrodarnimliayltfiboeorhnmaoovriftoarrl;itcfyooaadndcuomanomnsrduiedmbupurnrniidntoigtnywwaaensedkawsses2re6sesaeenxddaqm4u0ai.lnietaBdtoiadvteyllyew.aestiOgophnhtctehdaadtliamliyc sawtneadrrteuorrfietncreoersadatemmdpelnwetassaknwldeyraetbecsfopolerlceeicfttieheddsfitonartrtecrlovifantlirsceadalutrhmieenmngatt,tooclnaotgmDyea,nyctl1ianonifdctarlreecachotvememerinys.ttayBn,ldoaonwddeesukarlmiynpalhleeysrseiwasfebteerrf.oarseBoltohtoeadken fs"oeTrphaehroafrtoemllolyon;weiadndegrteoenrragmlainn(s2a)t,wieobrrnaseinw,eeipgihdeiddaytmsicsh(e2d)u. lkeiddnaenyd (u2n)sclihveedr,ulpeadncsraecarsi,ficeessi;s p(a2i)r,edanorgtahnysrowiedr(e2)wweiitghhed parathyroid. Organ to body weight percentages and organtobrain weigh ratios were calculated. 202 000141 22 dmTuhaoerdofewnuo(m,alcctllspuseodusrfwawi(ce2eor)id.sfecstlnhyoelphcdagmiegstduasilfoniysdes)stog[papalrtbehsaledordvgeeyrd:,ihneaDadrartve,indasluo(mn2'),,sjscourjntusin,uvbm,r(iK3,i).ncefeycoeumm3,c,soaletohsno,pnonneliver, h{Tuonmrg.caimnecsdaennidc(rba2iuc.bllsrcyiam.aptrihpcnlnoecdrsv,,em,SasmetmmiaunarlywviThaenbos,n2epi)ar,nscrkosealleswt,ealpStmoiumsacrclhe.p(eogssht,e(.s3k)riempc.orsnpeienaldlecponnr.dB(ossoosmnsitte, Solution, thymus thyroid (2) withparuhy roaches and rary bladder {rBhelacotoowvde,arsryfisanocerriPafnFidcOeAfdeciconenscmeownretirrbauctnoildolnccotanenddailtydisuoersni.nAgnnWieamadcldksow2nea:rndoblneoovotedfrayw2tawesdckboelsfcotrteehdcrlerlaocltmorntdsh.unSnammtprleeastmCweonetmnmds occoolmmlreyicftuecdgsewdaiwntidhtohsuihtnispaipnecbdoos10gruolafncf,oorlmaeaiinlotnay.inseedrautmowoasmhaermvpersatteduraen,danodradloatwed10soCctoo. 3S0uCmaphwuecked shaWhcoorllfeclb,oadidlviawdnaeodsdpcionloltolaeascdptpeursdoifxnrgiompmaottatehslesyviucemqnualcEasDviTzaeAodfsaasemafpchhleemsiicmoofasslgcuraltuabmntt(.hcosSlcachmceptdleudelsewidwtehavoneudtsusnosercahegesduuil1oegnd)1.30 wahC.espaWcrhoionnliaer5fbauimgoeoaddniawcnaodsagscuealplnalrtca.tteeOddneft-oohmapltfhewaansaiaannmdssa1fildrnebtsldeooicndotnoutorllv, rou aandsepmoionlaelds.aTrh orsesmtiungssohvue Thpasaand rd bloodel sone lt Fproolzeendaannddeay inetos3M ftoorpocsysoitbblees.tuArllesaamnpylses.were stored Foren 60C KC un ped WoAtelltlecacsett:onmotfLohrPoufFruiOrneiAnaenddeatnfeerdemasinwaeetsirtosns.cooAlfnilmefaetlcseoswvweeermrieegcnhoottllsfetcoetreedddabet1fheo0rsaCcmoletloet3cit0ieonaC. ubUlrnoiondeswhoiarpspseccdounmlcgteoodne 1030 for analysis d"ATrhyneeSoeam6npl3-eMwfafsoorvwaerniagsmlhyaesmadip,sllTeaswhasfcroozelnlinelifquoimd nciatcrohgeann.imsatloraetdb1ot~h6s0eCed10e-dS0anCdasncdhsehdiuppleeddospacerinficcoe acaTtcihhviratinygihamnalalaltfyeosraelsc.leRolebpeprroeffsetfnhrteaalttiiivvoeenrwseaavmsaplulcaeotlsilooencftseidivenfrg,opmirgoahltcifhaenradantiiJmoafnlc1alt,ince0loapatspyaatfiorgreepnnlm(wiFetrCoeNyC]Ao.CloeAcoonxiodamse aTAlinluiesdvrannliatabrologenebniatnudsptoredamti--)6wUsC ctoolleScOtedC uabon shispcpheedduoltehdeanUd snchievduoelfeDrdussdceiisfiosg,biTassihraen in "StThhe1epd0reecsAitnsuiodnyLityomteaenpanelcry.izoewd,hbelcrooenldetcfhtryontweDesrateoyssats3nr5ao.ynes6e6wd,asf9om4,aakdnsedoas1f8et3rraotnendrmirneaclovesarcyriDfiacye.s A2l2i0qu3o4ts8 afpna3s7swrfeom eTRnoowzsyaomrse:nocNfonOocoAednEctLroant(siduoomnspsta(i.nco.dn,sfmsfpiialrltylaeviean:cmrie1am0soemdanrsi/giyscaeayk.r.dadelasag:nti:annedyapmmoiosnedoievvriayn:1sTwmraeerikoegdrhtbrlefadowesshoysrdnrsmooegrfeoonms: andcrcting Kinase ad a mildly increased sem bile cid concemtraion IY 060112 23 `1Lc0oOnfAcoeEondLtrca(otdinoossnuesmap(int.id.oenaf;sfpemacrittlladetlveeyla)im:nicn3ro0etarmsagen/dskftger/ridagalsyyec,,eradiledaaentsih;n;emhoyadpmeoirancaotttiervaitntosym;feawrreakiseg,dhstionrlbcoirstseo;alsfedesewhinoydrsrenoroguefmneaceesnse:z,ylamonewdor creatine kinase) anad mildly increased serum bile acid concentration "T0oxfiocodrecsopnosnusmepbtyiodno;semilledvlely:i3n0c/r2ea0smegd/tkrgi/gdlyacye:riddeeast;ha;nhdypmoialcdilvyittoy,mowdeeirgahttellyossd,ecfreewasoerdnaobsfoecleust,elow or `nmoeinuletdrtloyeprhiminilcnracetoaesudendi,nsometorarulimpbrbuoinltdeeiacncoicndodnicctoeinnoctnernatanrtaditoiononnsesn,dfoarlwbhumoimntcroenactemnetrnattiwoans. sTtowpopeadnibmeaclasusienotfhistodxoiscietygrhoaudp, SbSttaaadttiiyssttwiiecciaallglhrytesscuilhgtnasin:fgiSectasanttfiosirtniGccarrlelaoysuesspi4ignnwiefmireceaansntigalnboisfwoielcruatnbetoldfyiyvleworewweiergihtgthhadtnuarcinondngtmrWoeleasendkuirv2iefnrog-roWG-ebeakrdsy4o7w,aen9iiugamhnatdlps2;4.mean sspaiecgrrnciifefinictcea,angtelsyiinnacnriemaaselds ifnraonmiamlalldsosinetghreou1p0smgat/ktge/rdmainyadosascerigfricoeu.p.MNeoaneflfievcetrstwoebrreainnwoteeidghattrweacsovery Remarks: `"gTrwooupanwiemraelss,acorniefimceadlinfmroormitbhuen3d0c/o2n0dmitgi/okngd/udraiyngdotsheegstruoduyp. aTnhdeomnaelmeailnethferom the 3 mg/kg/day dose. dw3ee0ai7tg2h.h0tmTalhokeses,gan/eidmwaayolrdfonsroeomgfetrchoeeusp,3 lwmoagws/kosgra/cnrdoiafyifcodeooddsoecnognrDsoauuympp2wt9.aioTsnhsiaascnrdaifntiihcmeeadelnoetnxihrDeibabiyotde1dy37w.saiTgsnhsciosolfadhnyitpomoatalhcetsithvooiuwtcyeh,dbefore clinical 0 food sciognnssumopftliiomni.ted use and paralysis ofthe hind limbs, ataxia and hypoactive behavior, few feces and wtMhaaeslyenslootsgtirvweeesniug3mh0etdmdguu/rnkilngg/Ddwaaeyye2fk2r.o1 mWofhDeatrynesattr1mee-an1t1t.mehnBatadswceladisniorcnealstuhsmeiesgedn,ssiotgfhnesf,deotwsreefeawctemasesnatlnodwwaelsroewsdtfotopoop2de0dcoomnngs/kuDgma/pydtai1yo1;natanhndids 2grtooulperwataesd tthhiesnddoesseiglneavteledfotrheth3e0:r2e0mamign/ikngg/2d3aywedoeskesogfroturpe.atOmefntth.e Trreemaatimneinntgoafnitmharelesmianltehsisggirvoeunp,30o/n2l0.y "imTngh/tekhaegns/eidmaaanyliswmaaalspspheaialnriceelddudtoeondrDtehacioynvsear4pp3fer(aorWmaeneccokem,p7)of,ue6nw6do-(rrWeneloeaftkeecde10se),f,fleaocntwdso8wr1int(ohiWfneoe3okdwec1oe2)nkssrueamsfpptetecirtoicnvee,slsaya.ntdiColwnienoiifgchatl sliosgsn.s treatment, wDMauersainrnegbswouedmeykedw2ea,itg2thh0tismcgch/haaknnggg/eedsawwyeaorsnestDnaoattiysatb2il1cya,lllmyoewsaeingrnidbfuoirdciaynntgw,eWiTegrehektastcmh|eanantngdewsa2swfeosrrteompaspilegendsiofrineccaDenaitvlyiynl1g1o3wa0enrdmgtw/hhkagne/ndaiy. TcoonwterrolfsordutrheinmgalWeesekinst7he.930a:n2d02m4.gO/vedraalyl mdoesaengbrooudpy. weight changes through Week 27 were notably e"Trhoeurpe wthaast wanasinccornesaisdeedreidntcoidbeencetorefatlmoewntorrenlaotefd.ood consumption for animals in the 30.20 mg/kg/day dose. Thhoerrmeonwee.reorntoesctoonsstiesrtoennet tohratclweearrleysdcoesne-irnelaantyedtreeaftmefnotengerscoturtponoesv,eersttriamdei.oIln,egsetnreiroall,,tthhyyrrooiiddshtoirmumloantcisn.g 244 000143 244 T`wreiroeddoetchryeraosneidnebergeimnaniinnegdodneDpraeyss3e5ditnharnoiumgahlDsaiy t1h8e31i0notrhe303.02/200mgm/gk/gk/gdadoysdeogsreougpr.oupTso.tal thyroxin ownasthdyercorxeiansewdasbemgoisntnipnrgoonnouDnacyed3a5tiDnaayni3m5alisn aadnmiimnailsstaedrmeidni1s0toerre3d071200mmgg//kkgg/dAaPyFaOndpDerayda6y.6 Tinhe effect aonbismearlvsedademitihneirstienrtehde3l0as7t230 mmgo/nktgh/sdaoyf.doTsheirnegafotredru,rtihnegetfhfeecrtebceovgearnytpohdaismeionfisthheanedxpreerciomveerny.wNaoschanges in chlocestokinin concentrations were seen overtime in cither dose group. tTrweaotmmeanlteswafsrosmtotphpee3d0b/e2c0amugs/eokgf/pdoaoyrdhoesaeltghr,ohupa,d tmhoedoenreatseactroimfiacrekdeodniDnacryea2s0edansderounmeefnorzywmhe.om ccroenacteinnteraktiinoansse)(iacn.daaspmairltdatleyaimnicnroetarsaendsfseerrausme,bialleanaicnied acmoincneonttrraantsifoenr.ase, sorbitol dehydrogenase, and uArti3nalmyskisg./Adtay30/or201m0gm/gk/ek/gd/adyayt,heArePwFeOrehasdlingohtefifneccrtesasoens hinemtaritgollyocgeyri,decocaognucleanttiroant,icolnisniacnadl cmihledmitsory, or Tmowdoeraantiemadlescrienasthees 3i0n/a2b0somlgu/tkenge/udtaryopdhoislecgoruonutp htoatdalmparrokteedinlcyoninccernetarsaetdiosneraunmdeanlzbyummienaccotnicvietnetsraatnidon `mildly increased serum bile acid concentrations "rTehceorveewryaspenrioode.vidence ofpersistent or delayed toxic effoencclinticsal pathology test results during the oErnhteasntceseodfcterleaptreodliafneirmaatliosn. was equivoeal in the liversoftreated monkeys; t was not seen in the pancreas. s"aTchreirfeicwee,riencnloudtirnegatlimveenr,tealdaretneadl,mascprleoesnc,oppainccroefamsi,carnosdceosptisc.cThhaenrgeesweinreannyootrrgeaantsmeantt-trheelatteerdmienfaflets on ltievremrinwaeligbhotdcyhwaeniggehstsseoernoan atebrsmoilnuatle soafcrreilfaitcievweeorregarnevweerisigbhltesoaverretciomvee,ryThsearcreinfiocetriendaitcmaetnitnrgeltahtaedthe macroscopicormicroscopic findinags recovery sacrifice. eOsfopthheagtewaol maanldesgasstarcircifliecseidoninsathmatorwiebruenidndciocnadtiitvieoonf, athneimnajlueryftrhoamt otchceu3r0r7e2d0dmugr/inkgg/ddoasyindgosaendgrliovuepr had lmeaskiogn/sdtahyatdwoesreegprroeuspuwmaesd ntoobtededtueerm1i0nteh.e test material. The causeofdeath in the male from the 3 Ngrionuepshun1,d2r,ed3 aonrdy4saenvdenselnitvetr,o 3seMra,fourriannealaynsdisfdeucresinsgamtpheletsrewaetrmeenctolplheacsteeodffrthoemsmtoudnyk.eOyfstihnetr9e4a7tment rseacmopvleersy, 2ph0a2sweoerfethseersutmu,dy1,9awteortaelloifve9r6, 2s7a2mpwleersefurroimneGarnodup2s721awnedre3fweceersesspeenctimtoen3s.MDfuorrianngaltyhseis. OF athnedseu,ri3n2ewsearmeplseesruwmersepaencailmyezends4,atw3eMre; lfievcearl, s2a8mwpelrees wuerirneesahnidpp2e8dwteorCeenfterceesAsnpaelcyitmiecnasl.LaSbeorruamt,orliievserfor analysis. Samples were analyzed for PFOA. eStehryal, alciveetra,tea.ndExutrriancetswewrereeexatnraalcytzeedduussiinnggahnifgohn--ppearifroirngmarnecaegelnitquainddchmreotmhyalt-otgerra-pbhuyt-yellcetchterros(pMraByE/)tanordem amnadsslisvpeercwterroemeqturaynt(iHtaPtLeCd-bEySe/xMteSr/nMalS)caliinbtrhaetimounlt(iwpiltehoruetspaonnsinetemronnailtsotrainndgarmdodree.ferPeFncOe)A, lwehvielles tihneseurraine a`asnsaalyyssiswewraesbpeelrofwortmheeldobwyerilnitmeimtalofcaqluiabnrtaittiaotni(owni(thLOaQn)inftoerrntahlesctoamndpaorudnrdefoefreinnctee)r.estA;llinblsaonmkes iinnstthanecelisv.er 25 000144 245 hoMoernobkclehaynekmusriwicneearlvaaisbnouuvsneeedxhfpeoosLesOdaGnmdoafnorrkdseizryassieaornnadaaunnrddinOveCesa,smpmalpebse,osBeiencrauasnerditTnheerrenwwaarsyessendodouogssernsoueasmseplss oofi. tamenrtdahcacontloelled.ctweTidt.hh Techoecmbooilnneudm,esxtrwraeecrtssdcweturedrcowviptuo3hrgsssichesdoa10naoemdfoolTldorwyedspboyvacsndderhteoamchtosancesopwseishsaesntgiaenool Sicuadtlogvtootlceulsmeteaanotdsaf2rdthmLbu.atmTwohauesntsuaosmfdplPoeFlsOywAetroiemahanerailtoyosnehdsewaislntcgseSenceroFqhraey ALHCSO.prToHPcFeOSamretx MSLiaavmetprliessasmpwpielkeeesssawpmeiprkleeedsspiwitkeherdcspitr.erpeamvreoeldnkofferpyormoacxnodinotmrraoltaesblamiypls3e5se0 otnfsero,anldivrceironanmdsaeimnpnltewowiftah5sc0ab5cho0b0dacrh. sSe pproima6t0mcg/lmLy. These eels approximate (he background ves 1 sev. po sed nc of the Group | (0 mg/kg/day) monkeys. LHPooFwwOeAvleewrvae,lssthofeofsuePnFdleOvi eAlhsweewreserreo,fstivegnneirdfeitrceaicnttnleydalniondwteherec tsheaonafhaliovrse,dfuornuinindemal1nsdh:fscHleosswo3fmtehmeaGnrgtoupw/1 ppaommeagssa,yi)a, AfferlsottmhaonruigamhilPsdFiaOnciAremwaasssedwdeietteehcstdeidonsicbtauhtneldsyerrehusimgs,heeidrveho,vaurnhmeasssndsduereinnegnssohtfeccnoontnt,trroolSla.enirPmvaFlsnO, evoelssseimptinsmes3of ai36m.1l.gndimn GfercioenusGpire2o.uapnd2$a1n5im+al7s a.ndg1i5n9.7 +in2G39r2ogu4md.uriinngGWres4oa2nu0im3a7plsThonsDvaayn0e10o5o3.5 c3o14 for aLWneeveDeklasy26i,9natInhnedtuShri1nf6eec5ewse,1r3eP.7F7,3.O51A0+l9e-3v87e.l15,,w2o2ar1nd&61s192:5t2,a4ann7hd.e090Hu9gk-g2o0rfe9sqpgea/stmniLvt.elayinsiGn rtnohueispes ws2,n3o, mapnrdoon4gmsrsPeppecsiely S72t54o23p:6pe4.d1534P5,E,O14A5340e+.e3l16s092ina3bn0oddth510ur36in+e7.2n30.d367ueugg4sggdilunrGirn1poguIWpesle2k.3t26tanAwdsereegsmphcbprovvliyeditopceonmcWpeeapsk seoonntriwanrge anGWiremoeuakplss32d6su:ar3mi4pn,lgeesW.eeTlehkeirn22e.hiesPnFoFceOcsxpaolpfapntesahirsocn0oTmobrotpahrmeihfmcgarhlesnoiwvaellryse o0oxf2Pc7r9Fc.tOe0dA.ins7ta4nv nignsshnodem0es6oo3f -hn0ee3s7oe2noin liough it bviously exceed n bah rine ond foes trough es sPIFsuOmdAiilfnevfGeurlsooudpsrea3rawucmaomamylpsfoarrdemedccr1oe0nac0sl.ue0s7ia3ov8nes0o.m0ue0t2d5cu6roimnpgarhraeetciaovvoeenrlpyolvuslnsdliinhnvegyorWreeaanckdhes4d0a1m.1s8i0n.ce82t7hegrimsto.y oSiscnorenutlmiymatephippseernaioetdob,etHiWmieegcpkhoei2nr7t.tafhvoaarniwlhhaibsceehfdionactiohfmopiavrevri.sroTnhaiansdndebnreoctaaducseindobseiiCnogmospftatrere. muatnottwosnapsshbele3ne0cn30cre i27msgcrdumosangdrovueprhaed vsasppetdhbeyCrWoeucpk 1a2animnalstins msay,hve ffeed Fneh i he mals 0 nck imDguerhielnrgtdthohaseneatgrheoyuppaerrwieaoasds3st0oof2p0speamdmdekurni,ndgaiytr.acptTpmieesanrtsm,ahyoanbevDebeyelsca4ai3ts,160d.omnngd/nk$fg1or/rd1eicsnpsseercutmms, reTihneioearnmdSefv0ecees arc 246 000145 246 2aa7vf,afiiPlcatFbelOdeAPfFolreOvtAehlesleliivnveeltrsh,elilnievvtieeslrssauriensefGr15or.3m4aon4iumrp3a.c0l2,sh1iig4nh.eG0r+rao7t.uW55p4e,.eakHnod2w7e4vt2eh.ran,8+ti6hn3.e3tyhfeaorocrnGeinrcoGourmpopusapr2sa,t23ia,venadnsda3m.4pAlte Wtheaet kis lrievsepresctfirveolmy.GrTohuepP3FaOnAimalelvselaricn0t.h1e1c4on+tr0o.l04l4i1veraantdWteheeklev2e7lsisin0.t1h7e7co+nt0r.o0l73a0r.e BbeyloWwectkhe4f0i,tlseveolfs in the detection. IePnvFdeiOvlAidiulnaelvtehalensuiirmniansleevararulemuseashreoawrsenhpoirnwenTsaeibnnlteeTsdabi3lneasTnad1bla3enAsda11n,Ad2:,l3le,evvaeenllsdisni4ntrthehesepfelecictveiesvrealaryre.e ssVhhaoolwwunensiininnTTTaaabbbllleeesss421aaAnn,dd2442a,A;3 and 4A are group average+s the standard deviation associated that group at cach time period. 247 000146 247 eo ereeewe; weor wr Grou1p 00 105700M 10571aM |0635|0399|<1.0Q|<16Q| 0.191 10.157102% 170.128 T<L0Q |0.105 |0207| |0.0994| 0355 0.15 | 023s |<100 | 0.244| mekg/day Control [105715M [7105718M_| |<LOQ| 0.0889 0.0785 [<1.0Q_|<LOQ| 0347 [100[<10Q| 0.0919 | 0.120 | 0.064| 0.0981[<L0O| 0.0950 0.139 | 0.15 [<r| 00.650| [iosJ07572250M_M| 1701040909|T 00..111647 T<110000T1<110000 0.28|0.130 | |0110 | 0.0869| 0182[<t00 | 0193| 0.105 [<|10.0 38| i a lcd 3 ol mekgday [| Control 1 Tos70oM TosTiaM |ot04o7iTT0o2s00[ TT T 1 T T1 T T 17 T 1 10STI3M tos71sM_| 170.101 00045 0.093 | 0.0680 0206T0206T0200T0161|0135 |0104| 014 00719 1toossipsoMM_ [oLsoooseTToosnesTT17--711--1 1[TT --1 megday [TOSTON ote [osdTomsrTiMMiT n[ i_w Te1r 7-- | e rT 000147 ET PFOA Concenruions inhTSaebu1a(mk)ofTred Anis oaGvmreog?|| dmvGnoetHibth|| dtvoGmomoeeeytryssd|| 3A0v%Gmmrepboea7msisny [wes Siog |wirems|oesas| ieeomo | [weiteomoum nesseeanswiossi--] Wei oamsom |reszis isis | steric] [[wvei7 esseTTooommTisrIoemoumserTnne 2 msioamTw ns] ARL0e0YusNrLs eSiaoxfmpmQpuraeniistatirono arsetsh sandand dovaion asocaed vith ot group SDaaisasamts tSoDworim on Sof oe averge fond sample conn. he mses ied ample covey PFOA Concnrions ntheTaLev (5) of Trt Annals [-- OAovGmgrehogsda)y || nmvGoekp3eesdp| | A10vSmeeekEgidsedy || 3h02Tu0ameerk?esiy [Timvepeoinr--T -- w--T ----w -- --T ----wTw wee dooTW JorsmnIw] LNRY0e0sNLoe xSoiafpmiudnani1skigornou averages he sndarddvition sociated witht group, fDoarttaifireed saaccmuprlaetere0cowvietrhyinwanse9S0D% woiftthheanavSeDraogfe2f6or%tified sample recovery. Th average 249 000148 POAConceatons ntheTLse nd)of Ted Airs -- oeTmTeen || AsommTby|| ntaTmseytnty || 0mmTmeeTeheue [mepom---- -- -------- ---------------- |Weska TT <T0Q 1 3sese1 | ooizid| owize | [--Weka 70153:0337| Sa9:462 | 190=9i6 | da0ziel | [Weeks 100161000040| 476206| 206a73.0 | isosto | [Weck2 T001a1=000648| 4ss=18% | 2014027 | iisein_| [Weskin 1ousesoos| 377503| Tse-ars | aise] [Week20 100201400130 | 521=963 | i44xi3s | aa0as00 | [Week2e To0268000265| S16:137 | 109s | 192-270 | |Weeh28 1"oiissoid2 TNS os2eoom | Ns | |Weex3o Tero TNS os6rsoais | Ns | WeekdTE00 TNS ori4z0068 | Ns | Weeks Tio TNS omizooss| ns | [--Week3s 1 100 TNS |"ooaszoo0i02 | Ns | 0L 0We-einkr iatoof gTaTniio=n100 NSTooasazooiol | Ns | Rul eda op veraes Besaiddein sc vith ht gr TDatoa aire saaccmuprlaeteretsoowvietyhinwaosne$9S%D woiftthheinavDeroagte f1or.tified sample recovery. The average 20 000149 PRON Concent nnTFacs (4) fT Ais [a | tb r |aie,e [ois| | A[ veragAe' SD|IAverage +3D| AvEerageL+ SD| AIveCrage SD [erm -- ee ey boironss oi TITRA | ToTEReT 0084 pris sou Wes 36:40 0b0on1e0s3 + Doosers s 1N N00S rien mioofpQunte3inigdroonu vgs he saad deviation sited ih trop Ds ie segura 10 Wilh ome SD of th verge ford sample recovery, The average fortified sample recovery was 117% with an SD of 22% Reference "(TAhDoFmOfo)rdi,n CPJym(2o0m0o1l)u2s6-MWoenekekyCsa.psSutluedyTopxiecritiyoSdtubdyy CwiotvhaAncmemoLanbioruamtoPreiresf nc. Mado luorooctanoate Wisconsin 53704-2592 for APME Ad-hoe APFO Toxicology Working Group. Study No. Covance 6329-231, Completion Date December 18, 2001, 463 pp. 251 000150 REPEAT DOSE DATA Title: Ninety Day Subacute Rat Toxicity Study TEST SUBSTANCE (pIoedcretfnaltnuiootiryco:oacFctiladun,oorapateden,tFaPlduFeocOra,oflcFuhCoe-rm1oi1-c,6a,lamFFCmC--o11n42i36.u,mFACsla-ls1to6,9Cr,eAfFSeCrR-e1Nd43t3o,8a2os5r-Pa2sF6-aO1Am)aajomrmcoonmipuomnesanltt,ofaFmXmo.1n0i0u3m iRnedimcaartekds.: White powder, 3M stock no. 98-0211-0008.0 Lot 340; purityof the test substance was not METHOD Method/guideline followed: No guideline number stated Study duration: 90 days GLP (VIN): No ear study performed: 1977-7 `Species/strain: Charles River CD rat Sex: Male and female Numberofanimals per dose group: S animals/sex/group Route of administrations Dietary Doses tested and frequency: 0, 10,30, 100, 300, and 1,000ppm Post-treatmentobservation period: None t``Shgteraotauippsptwrioacapslripmaeetrtefhoto-rtdmessetdu(sbfoeyrda:cnqauSlatyalstiiossrotifucanlvcaaarnuiaaalnyvcseairs(iocanonemc-pewa)aryui)sn,ignBagrreDtsluuelmttntse'tsotftt'hessemfatolrreihaotmmeoncgtoemngperaiortuipyossofwnvitaahrbiltaehnsectceoosnjtaurndodgle significance of differences. wmRiaetlmheasSr0wk0ass:go2fI2nf2ite-i2eal5d4aaggtewoaenfadkthtlehyetiiennstitetraivanalilsmw.aelisTghhwteaostftrnehoaettegdfieavmneainlm;eashloswwawesever1re5,1ot-bh1sec7mr9evge.adnTthiwneiitctieealsdtabciohledymyfiocwraeclilgiwhnaitcosaflmtsihixegends of bctoiolxoilccehicettmyeidsatnprrdyi.ofrourtroimnosartlauylsdiiytsy,i.naintIidnatdsiieovnriudaumnadslaabmtpol|deyas.nwdeFi3ogomhtodsnctwohensrseuomfrpettcrioeorantdmewedanwtseterokelccyvo.arldueBadlt.eooAhdtema9an0tdodularoyisgn,ye,tsheamapnliemsalwsere rpweaarirfneowsraimcterhdifcoiencrevtdihcaeanlfdoclnolcrocdw,riolnpugsmiocbrdagrafsnoprsinmfaalrcocrmoorsracdto,sppfiercroiampnhdtehrmeailcconrneotrsovcelo,,pie1cy0e0se,.xa3pm0ii0tnu,aitatianrodyn,.1t,h0Hy0ir0sotipodppwmaitthdhoolpsoaegryagtrwhoayursposi:d, adrenals, lung. heart with coronary vessels, aorta, spleen, mesenteric lymph node, thymus, bone with 252 000151 mKiadrnceoysw,(usrtienramruym)b,lasdadleirv,arfyesgtlsa,ndo,vasrmiaelsl, ipnrtoessttaitnee,su(tderuuosd,esmkuimn,(jmeajmunmuamr,ylgelaun)d),coalnoyn,tipsasnuccr(esa)sw,itlihvegrr,oss lleisvieornss.amLpilveesrsfrformoamllradtsosfergormoutphse 1w0earnedf3r0ozpenpamnddosseentgrooutphsewseproensaolrsofoerxaanmailynseids.microscopically and RESULTS NMaOleAs:EL30 ppm Females: 300 ppm LMaOleAsE:L100ppm (decrease in food consumption, liver lesions) Females: 1,000 ppm (liver lesions, increased liver weight) TRheemsaerkdesa:thOs nweerfeemnaoltecionnstihdeer1e0d0.taonbdeontreeaftemmeanlte rienlattehde. 30A0llpoptmhegrraonuipmdailesdsduurrviivnegdcounltlielctsicohnoedfulbeldood. sacrifice. "inThtehree cwoanstraolsiggrnoiufpi)c.antFroeodducctoinosnuimnptmieoannwbaosdyrewdeuicgehdtiinnmmaalleessiinntthhee110,00,0300p0pamndgr1o0u0p0 (p3p6r2m ggrvousp4s6,6b&ut the differences were not statistically significant. eMnadloefstihnethtere3a0t,me1n0t0,pe3r0io0d.andTh1e,0v0a0lpuepsmwegrreou7p.s95h,ad7.s0i5g,ni7f.i1c6a,n6t.l7y2r,eadnudce6d.9n4uminbetrhseocfontrryotlh,r3o0c,yt1e0s0,at30th0e adonsde1g0r0o0uppsp,mbugtrowueprse,srteastpisetcitciavlellyys.igMnaifliecsanhtaad rtehedu3c0e0dplepumkogcryotuepvoanlluye:s cleoumkpoacryteedvtaoltuheescwoenrterol1s0.i6n4,all 8si.m8i8l,ar9.p3h3e,n9o.m3e5n7,.o6n3,waansdse8e.n06wiinththheecmoongtlroolb,in10v,a3l0u,cs10w0h,ic3h00wearned1r,e0d0u0cpedpma aglroduopsse, lreevseplesctbiuvtelwy.ereA stihgenciofnitcraonlt,at10t,he301,01p00p,m3d0o0seanldev1el00o0nlyp.pmHgermoougplso,brienspevcatliuveeslyw.erTehe1r6.e2,wa1s4.7n,o 1s5i.m0i,la1r5.e4f,fec1t49u,po1n3.t1hein hematological parameters of female ats in the study Mwearleesstaattitshteic3a0l,ly1s0i0g,ni3f0i0c,anatnadt a1l,l0b0u0tptphme d10o0sepplemveldsosheadlevienl.creRaespeodrgtleudcgolsuecolesveellsev(emlgs/w1e0r0eml1)21,wh1i2c0,h l1e3v6e,ls13w4e,re14e3leavnadte1d3i5nmmga/l1e0s0a mtihefo1r0t0h,e300,0,10a,n3d011,0000,03p0p0madnodse1,l0e0v0elps;pmmegarnouvpasl,uersesaptec9t0ivdelayy.s wBe.rUeN. t2h0e.4c,on2t3r.o9lsa.ndAl3k5a.l1inmeg/p1h0os0pmhiatfaosretwheastherleeevadtoesde ignromuaplse,sriensptehceti1v0e0l,y,30c0o,mapnadre1d,0to001p6p.2mmggr/o1u0ps0;mtihefor cloenvterloslsw.erFee1m4a7l,es20s4hoanwded2n1o2siImUilfaorrcthhaentgherseeignrboiuopcsh,ermeiscpaelctmievaeslyu,recmoemnptasr.ed (0 104 1U for the Nfeeimtahleers mfraolmsalnlorgrfoeumpaslesshoswheodweadhaingyhetrrefartemqeunetncryeolafteodcccuhlatngbelsooidn iunritnhaelyusriisnepatrhaamnedtiedrsmaalletsh.ough "eTnhlearogneldylgirvoesrss nwehcircohpssyhoowbesdervvaatriyoinngwdaesgrneoetseodfisnumraflaecseadtistchoelo1r,a0t0io0np.pNmeidtohseer lfeevemla,leTshefsreomantihmea1l,s0h00ad ppm dose level nor males or females from the lower dose levels showed such effects. 253 000152 Bpmoaptlmhegarrabtossuopliunsttaehneadn1id0n0r.oenl3ae0ti0fveeamnaidlvee1rn0w0t0heep1m,wi00ge0rrogepusppismgh,ngiTrfhotieucpsa.snstlCleoysmiiponnocsurcneoadns-seridlsitanetdmeaodlflefisovceiarnllte1hs0eimo3un0sl,iof3co0cc0ualra,neddvei1rn,y0a0ll0light res1s0oemsmlebilgihintnsghtyalnpiceperostfztuohsepcshieynloeifsnihtoehnpesactwyoetcroyetpelasacscimnoomcfpheaennpiaettdorcbiyytlietnsocorambeniauddszeloodcancaaarmsloiournneagtlilooynfsinyoefslitlnhouewsioasifhdfaeblcrtioendwinlnigpviceeglTmeoe.bnutTtahse 11 lienvceildence and severity ofth lesionswas more pronounced among male rts a he 1.000 ppm dciry CONCLUSIONS "slTiehgseniiotfneissctainnstumbraseltdeausncctaeitor1ne0s0iun,ltt3he0ed0inanunamdbse1irg0no0i0ffpiecprayn.tthrreodcuyctteisonininmamleeasnatbo0d,y 1w0e0i,g3h0t0in4nmdal1e0s0a0tpp10m0,0 apnpdm,Tea r FlGoulodreandthFallu,orEoDch.emJiecaslsuFpCR.-.14G3e.il,3NM.JCeofmpfaenyr.saoSntdnuR,d.y Anor.cco1.37-018997.8, Ninety daysubacute toxicity study: 254 000153 REPEAT DOSE DATA "Tite: 1(3C-AWSeeNok.Di3e8t2ar5y-T2o6x-i1cii)ntyMaSlteudRyatwsith T-5180, Ammonium Perfluorooctanoate TEST SUBSTANCE lIidgehnttliytyc:oloTr-e5d15p0o,wdAerm.monium perfluorooctanoate (APFO), CAS No. 3825-26-1, Lot No. 115. Itsa Remarks: Purityofthe test substance was not indicated. METHOD ``MceotmphloidangcueidweiltihnHeafzolleltoownedW:iscGounisdienl,inIenc8.2-(1HW(Iso)urpcreotnooctolspTePci9f3ie2d1).daTthedeNstouvdeymwbaesrc3o0n,d1u9c9t0e.d in Study duration: 13 weeks GLP (VIN): ear study performed: 1993 Species/strain: RaSprague-Dawley, Crl:CDRBR Sex: Male Number of animals per dose group: 35 in cach group, except pair-fed controls, which had 45 animals. Routeof administration: Dietary amDneoisamenaslcstoepmsetpreodguranondudpcofwnreseruqeumsepantcciryoi:nfiac0ted(wpaeiter4k-,f7e[,3daoanndfd 1n0.3o05n,wpe0ae.ik4rs7-.,fe1dT.4hc4oe,ntrarenomdlas4i).,n9i71n,gm1e01k,0g3a/0n,dioamyal)1sp0f0eedrpagpdrmolui(pbaipt(upamrl,ogxFirimofauttpoeson except pair-fed controls) were sacrificed after 13 weeksoftreatment and weekswithout treatment, Post-treatment observation period: wecks Shteatteirstoigceanlcmiyetohfovdasriuasnecde:atLpev<en0.e0'5s,ttersatnwsafsorumsaetdiotnostweestrefoursveadritaonscteabhiolmiozegetnheeivtayr.ianIcne.casAeNs OofVA was u`pMseoerddfiofrimeaedndaTlouynkzeetyhb-eoKhdroyammweeoriggehesttnsw,oacuosursmuuslteardtainfvsoefrobproamiderdywdiwaseteai.gchotmIfpgtaahrieinsA,oNnfsoOobVdeActownwesaeusnmspgirtgoinuiopfnsi,.cacnltOi,nnieGc-aalwmaceyhseAmaiNnsdtOryHV,oAwewlals. (Bheooxrdcmyepotwneepigavhiatlrsue,esdc,mcoournltgaratonliswv)eeiubgsoihndsgs,twohereigSgahnAt-Stgoap-irbnoosdg,yraawnmediafgcohcotopdredcriocnnegsnuttomapgHteWsi,oInamnvedatlhouoredgssa.nw-etrGoer-boarunaapilncyowzmeepidgafhrotirsraoaltnlisogsrw.oeurpes 1ev0a1l.u1a0t.ed30a.t athned5.0%1t00wop-ptmaAiPlFedOpwreorbeabciloimtpyalreevedl.toItnhethceonatnraollysainsiomfatlhseindatthae, naonnipmaailrs-fiendggrroouupps,ewxhpiolseed the data from the pir-fed control animals were compared to animals exposed to 100 ppm APFO, 255 000154 aRAptepsmrtaouprdrkiysa:itneitaMiamalotieuonnr.tattoshfewteahnreiemtuaesltessdwutbeosrtceahanarcpaepcrtwoeaxrsiimztaehttoehrleoyueg4fh1flecydtasmyoisfxoetldhdewaientsdhtwrseouidbegsnhttaendcche1o8o1wnbttoeefs2ot2ri9ecu5lp.arroTpvhhiyesdiionligotgay.d nidiobctittacruoynmtc1ao0inntcihenengtarntaihtmeailfoesns.otfsCtuobhnsettartnoesclteg.sruobAulslptasdonicfeet;psatwihere-rrfeeeafdaisaesrna,dywenedoenwkpelaeyikral-nyealdfyorsraettsshewweefrirseetpmfeaoriufnrotwraemieneekddsoon(n0tdhaeetbcaeosmnamtlirndoielestdihcet and one test diet, selected sequentially. d"daaTtthaarowwueegrrheeoucrtoelctloheercdtseetddudodyna,iatlhyneifmfoairrlspstaidwrae-yrf,eedwoegberskoelurypvsetdhaentrdweaiwfcieeeerdk,aliaylnydfoforonrnsotinhgpenadsioarfy-ofteofxdingcericotruyop.sp.syI.nSdieFvrioudoumdaslcaobmnopsdluyemswpetiigohnt tcaeonsldtloesscuttbeecrduontfear,nocmlouut1es0inaaidnziiipmnoagslheso/trgimrsoosnuueepswa,tereaeancdchotleslscethcmetadetudelrfeirdaolsmccoaantcechntar.wnieiAmratelfanaenincardlocyfpzrseeoydz,fesnoarfmoeprsltperosasdoifilblil,veeotrto,aslttemsatteesr,ilaulngs, raaennsiiimndaduliesc/aagntraolrooyufspipsae.treoAaxcishescsotcmihoeendpourflolleiidvfeesrraactrwiioafnsi.coe,bFttiahfietneleeindveafrnrwiomamaasllalssgasrnaoiyumeapdlwsfoearrtetchnaeeclchervsoecplhsoeifcddupalafeldemirst4aoc.ryi]f7i,Cceao.nAdFoo1xr3i5dwaeseekass `ofexracmaintamteinotn,s aisnwcleuldleads t1he0 aenxitmeamlasl/gsrurofuapceaot fthteheenbdoodfyt,halel 8or-iwfeicceks,retchoevcerraynipaelricoadv.ityT.htehemaexctreorsncaolpic saprunordsftapacetelesv,ioccfotcaahgveuiltbairteasiinnagnagdnldavinssdcp,eirnuaar.letchTorhrad)e,rbtrhaeeinn,awselaiivlgehrce,advl.iutnygOsar,ngtdaesnpt-aeros,a-nbaaonsddaylacswcieneiusgssheotsr,ypaesrnecdxentohtreaggatehnsosraa(ncsidecm,oirangabaldno-vmteiosn-icalle,, blersaiionnsw,eibgrahitn,raitvieors,wleurnegsc,altceusltaetse,da.ndTahcecefsoslolroywisnegxwoerrgaense.xamEilencetdromnicnrrocsrcoospciocaplylywa(swhaelsnopurseesdenfto): evaluate tissues from the brain, iver, lungs, tests, and accessory sex organs. RESULTS NOAEL(doseand effect): 1.0 ppm LOAEL (dose and effect: 10 ppm "4Tdoxuicctroessepvoenrseelneefcfkecstosrebsy, dboutseallleovtelh:erOanniemaalnsimsaurvaitvtehde u1n0ti0lpspcmheddousleedlesvacerlifwiaces.saNcroifcilciendicdaulrsiinggnsweoefk toxicity were observed in any groups during treatment of recovery. i1n0cprepamse--d ahbisgohleutrehaenpdatrieclaptailvmeitliovye]rCweoiAghotsx,idaansdehaectpiavtiotcye,ldleulcarreahsyepdermteraonphbyody weight gains, 3in0crpepamsehd iabgsholeurtehaenpdatrieclaptailvmeitliovye]rCweoiAghtosx,idaansde haectpiavtiotcye,ldleuclarreahsyepdermteraonpbhoydyweight gains, hh1ei0pg0ahteporpchemelpl--autlialcrohwpyaeplrembrittorodoyyp]hwCye,oigAahntodsxeialdneadvsaectueamdctuielvsaitttriya,vdieionlbcorldeeyavsewlesdeiagbhstolguatiensa,nldorweelratfioveodficvoenswuemipgthitos,n, s`Sictguanmtiiufslitacitacinavtlelrybeolseudslystswf:eoioHgdihtgthhagandiotnshseecanonominpmpaaailrrse-dcfxethdoicbtoihntotesrdeoocflostnahstieswteneoennktplsayi1sri-agfnnedidf2i.gcraonAutnpli.ymlaTolhwseeryatbadloosdsoyecwloeenivsegluhsimosefda3n0d and 100 ppm exhibited higher hepatic palmitoy] CoA oxidase activities that were statistically significant at 256 000155 ihwnaettchkewsaas.nism8,alaasnodif1t4lh.e Ashinigignhmiafdliocssaenitdgarto1wu0eppctpkhma5n.htaAhdebstporaalniustrieeendatnlcydonhetilrgothliesvraehtevwpeaeterikcwspe4ia.gl7hm.tisatnwodeCr13o.sAignoixfiidcaasnetlaycthivgithy rdReeeppmoearntrdekedsndt:uarTnihdnogruetvgreehrastsimtbaelteni.ts,tiTncnaolclrdyiefasfsieegrndeinfaicbcesaownltaustiensacenerdneaeasaetiinvtheheeplaSt-viwcepweaeklimgrihettcosoyv)aenrCdy ohpeerpoiaxotido.dcaesTelhueatcsteifhvfiyetpiteeswtarweoeprdieoyse. pwHrioogghrreerosbissnieotrnhvoeefdanhiienmpaaatlnosicmoeaflllstuhlfeaehrdihg1y0hp,de3or0st,erogprh1oy0ud0pipdtphnamonsttaahbpespopelaauirtret-oeadbnedcoarnfetflreaoctltisevdeaibvyweetrehkweselie4gn,hg7tt,shoawfnedrwee1a3s.thmaeTnnhthe.canTthye acafshseaorncgiteahsteeordbeswceoirvhevrepydepraerorexiiossduo,gmgweehspitricovhleifioenrdfaaitcitoaents.et mtTahhtaeetrrtehie)wfaesfefencotsoewvneirdienetnrrcaeecveeolrflsuiilbnalrcer.meeaAtsnaeidbmoialvliessrmiwnaentidhgehmthasioygfhbdaeonsiemaglrsoup eattxhhewienbeoinktpesdai|c-oafnnsedids2t.ceonnOttvlreyorlasliglgr,noiunfpi.ocasniTtghlneyifyliocaawlnsetorcdboonidsyfuwmfeeridgisehintgnmsniecafaniecdnanctfulomyoudlalcteoisnvsefuombopodtdityohnWaebiteghthewtnegoenanpinanoisnrhp-aafoindr-tcfhoeondersoalonsfd phaeihriegdh gdroosuepasnwimaaslsnotaepdp.esrTehdoutoghbethcelreevawtaesd antowsetaetkist5.ically significant ference, the cardio levels in CONCLUSIONS. "`(TwNhhOeeEnsLtfu)eddywaaadsutf1h.ob0rpicponm0clruadtesdftohrataheeansto1b3wseerevkesdwaadsve1r0s0e pefpfmetanedvetlha(tNhOeAnEoLsYeforvtehde teefstfestubtsotavnce mhRyaepmyearbtrerkoscpo:hnys,Iindaeanrndeidsmiaagldnsvieffriecsdaen,1tl0iy,n3ci0ln,ucdraiennagdsei1dn0ch0reeppaapstmei,dc taphbaeslmoriletpuootyr]tanCddeosrAcerlioabtxeiisvdeatsrlieevaaetcrmtiewveniittgirehestl.sa.teOdhenpitahvteorcbeealfslfiueslcoatrsftthheatse findings. the LOAEL was 10 ppm and the NOAEL was 1.0 pom PNoa.laz3z5o2l6o-,1)M.in 1m99e3. at1s3.-WHeaezkledtioentaWriystcooxnisciinty, sItnu.dyMwaidtihso5n1,8W0I., a3mMmoCnoimpuamnyp.erfSutorPoaouclt,anMoNs.te (CAS 257 000156 REPEAT DOSE DATA Title: Two Year Oral (Diet)Toxicity/Carcinogenicity Studyof Fluorochemical FC-143 in Rats TEST SUBSTANCE p(Ioedcretfnaltnuiotoiyrc:oaoccFitiadun,oopareiancdt,aPdFeFlcOua,oflrFuoCoc-rh1oe-1m,6i,caamFlCm-Fo1Cn2-i61,u43mF,Csa-all1ts6,o9Cr,eAfFSeCr-Rr1eN4d3t3,o5o2ar5sa-sP26Fa-O1m)Aajaomrmcoonmipuonmesnatl,ofamFm1on0i0um adRepetpmeracotrxakibmsla:etceThlhayenogtneeesstywseeuarbrsetfafrnooucmned,.thaewTshhtiaetrtecoopfmoptwhodseirst,tiuowdnya,sanaadnndapluayrtizttehydoefptreitrohmreiontaetsttihosenusbotsfattrthanoefctedhoweseirsnetgundpoyetr,iioandf.dteircNaot.ed in the main bodyofthe study report, METHOD Method/guideline followed: Guideline number not stated Study duration: Two years GLP (VIN): Yes. earstudyperformed: 1981 - 1983 Species/strain: Sprague-Dawley ra [Crl:COBS* CD(SD)BR] Sex: Male/Female Nlouwm-bdoesreogfroaunpimcaolnstapienreddo0sergatrsosuexp,: The control and high-dose groups contained 65 rats/sex and the Routeof administration: Dict Doses tested and frequency: LowH-idgohs-ed:ose1:.3 1m4g./2kmgy/dkagy/d(amayle(sm)a,le1s.)6, m1a6k.1g/mdga/ykg(/fdeamyal(efse)males) Post-treatment observation period: None `2tShrti0asuttipesst1ti0cwatlahsemecnotonthtorsiodglsngiufrsioecuadpn:utsBaaitrnatgllpaehtat'=wot-e0ts.ta0if0lo1er,dhtDohumenondgeaettnta'ewsiteteryseotffauvrtathrheieraanalcnpeahwlayaz--se0du.sb0e3ydsctioogmnapinafarilciyanzngecectahleecvhetlst,rtedaattead. If yRiehearmroauirgnhkcoslu:utdTetdehset1dSaonsaiitmnsagslepsexrwifeordr.oem3Wb9oe0tehk4lt1hydpcahoyynsstoircfoalalagenexdawmhhiiengnaht-tidrooensasetmigernnoctulpubsde.egdAanlp.allpaAanntiimoiannltsferrwiemarnteyerommbaisnseasrteviseodnprdaeatsioelnnyte paweenardkflpoyhr.amremdEaycaetotetohxexaimocinneoa-btysieeoarnrvsapteuirsoiinonsdg.. inBCdloiidrneyicctwaeloippghahttthhsoaallomngoysfcdeoeeptdeycroamnnidns/auotmripotsnhiistonilnawcmelpurdebeirdoehmceiomcrardtoeosdlcwooegpyey,kwlceylrionericbale (serum) chemist and urinalysis. Tests wereconductedon samples obtained at 3, 6, 12, 18, and 24 258 000157 ``cmwhohenitmthisbslftoroopdamcreralamlnedctooemurnsnityi,nscheleluemdcoetgdeldooatbanilinm,baihllesimroauftbeoineaicstha,dlaospnerdaogtrcdoiiunfp,f.earleHbntueimmaialnt,wohbliltooegoidbleuosrodsecnilinltcrlcouogdueenndt.(toBtCUallNi)ree,dnltauncdose, aUMlrekitanalebiontleeisptchseoixsnapcmhliauntdaaetsdieop(nHAs,P)is,pnevcclriesfaietcdignceroalpvlhieotcstypiaohlnobkouifmniuanrsi,eneg(lCauPncKdo)sfe.e,cabasilplasirratumabptilene,sa.omcicnPuooltstrtabmnlsooforedtreaamsnedexKaeantdmoisnaaetslioonnss. were pawneedrrfeuotcreomrleuldsecowtneaeldraenrdaencoiobmrsadelersdvafenrddommtihc1er5owsrecaiongpdhiiocsmalloylftyshefelreoacmdtretedhneaastlesg/alsnaeinxmd/asgl,rso.burpa.n,Satemsptlee,sheoafrmt,aKniydndeifyfsreinvtroseplseens SGFueerwnveeirvrdaaellar,tahtsseusrw:veirvealsereantesinohrigthh-edFoCse-1m4a3-ltsraatneddfreamtaslweesrtehgaooidtdhuericonngtrtohles.ful two yearsofthe study. Neoplastic effects: Percent Neoplastic Lesions in Males |Jem Te we] Adrenal Pheochromocytoma, benign TaTxT ------ 1 |LPihveeorchromocytoma.mali.--| 0 | 5|p | |Hepatocellularcareinoma |____6[3] 10 [ATdeestnesoEmpiadi-- dymis TT Sy 1 36 [aw | [Levdigeeladenoma |0]4]a [CedCelclelal dcaerncionmomsa Source: Table 19 T ToT 0 | "Significantly different (p 0.08) from controls 259 000158 Percent Neoplastic Lesions in Females Adrenal Tw[Tew Ww) PPhheeoocchhrroommooccyyttoommaa,.bmeanliiggn Liver [74 0T -- Tp e 51 |Hepatocellular carcinoma | 0 [5] 7 `Adenocarcinoma `Adenoma Carcinoma Fibroadenoma. PLiytmaphangiosarcoma. [Adenoma [sr [oo i 0 Te o Te m ae TT Tw] 7 [Ceeelladenoma [CeSeoulrclee:arTcabilneo1m9a 5 10 0 |] 0 "Significantly different (p <0.05) from controls fStraotmistciocnatlroalnsa;lypsi<s0o.f05n)e:oplastic effects (ic, percent that was statistically significantly different MFeammamleasry(16g.l1anmdyfei)br:oadenomas LMeayldeisg(c14e.l2 marke): adenomas in testis Nonneoplastic effects: NOAEL (dose and effec): none LOAEL (dose and effect): t1h.e3 smtyu/dkyg/audtahyor(smailmpsl)ic-dbaanseadssuopcoiantisoanliovfartyhigslalensdiosniawliadteahnitssus(pneoctteedthat aouvtibrruesawkoasfsnaoltocdoancfriyromaedde)nitis viral infection; however, the presence of a1t.a6ximay,kagc/ldinaiyca(lfseimgan)l.es)-basedupon ovarian tubular hyperplasia (and 260 000159 Percent Non-neoplastic Lesions in Males fo TT Gwe [te Em [NoSidnuuasroihdyaplecrcptalsaissia Heart I|4E[ E E 5S I 32 LiMvyeorcarditis,chronic [mT 3% 7 34 Cystoid degeneration Hepatocealltlbausolphailr, | [ 74 -- 1 T 5]r ------s--e------ [Hyperplastienodule [0|p [Megaloeytosis 10|,----7 6 80% [Portalmononucleareellinfil.| [NeTeunrgosis 7 764 |0 e7 Tgp 10 ] [AlveHeomolrarhragmeacrophages 1e 0Tmy Tn ae] Perivas. mono. infil. [oe 7 [Vascularmineralization | 86 | 86 14% 94 IPneumonia nterstivial |3 | or jg------]| [Tubularawophy -- TT [NVascularmin | 0| 6 2 i8* [CoPalnlcrbeyasperlia [3 J 5----T5] [_ASacliivanray ragtloapndhy [3 J 20 2 ] |SSpilleaednenits. chrome | 3[am 3 ] ] [CHemo`Ssouirdcee:roTsaibsle 20 13] 8 a "Significantly different (p <0.05) rom controls 21 000160 Percent Noa-ncoplasic Lesions in Females [ Adrenal GwaTiw] ig [[NSiomdwusoatrdfaycepnesiisna[ 1m 6Tf 3 1 w= | eHHeyppseorr cpellsuilrcanlto.bdT aesagh,_| EE 16| r ----i-- g] 55 1 [T MN eosye tossws|E o 0 SF I ] e ---- ] 4-- Tong [[CCPheormvoanstmaogneo inf1 ag----1 [Vascular mineralization Tas Te EEry 5 | [Pneumonia mesial | 14] 6 ig] IVache E -- IN -- ------ r Tot e E -- --E ---- -- etSm or [Cosihpeion [0[3[7] Mme TT u T] Bem Tw TT | T Spleen T -- 1] ChieSomurocse:igToabolses0----T----% Fa "Sinica diffrent (p<0.05) romconirls 262 000161 iLinsdticoaftesdta;tipst<ic0a.l0l5y)d:ifferent non-neoplastic effects (increased compared with controls, unless MaClherson(i1c.3smioa/lakdee)n:its (salivary gland) IPnetreirvstaistciuallaprnmeounmoo.niianfi(l.lu(nugn)g) Hemosiderosis (sploen)* MaClyessto(i1d4.d2egmegn/ekrga)t:ion (liver) PMoergtaallomcoytnoosniuscl(eliavrerc)el infitzation (iver) HAlevmeoorlrahramgaecr(loupnhga)ges (lung) CVharsocnuilacrsimailnaedreanliitziast(isoanli(veasrtysg/leapnidd)idymis) perivascularmono. infil. (lung) FeVmaaslceusla(r1.m6inmegr/aklgi)z:ation (lung) CThurbounliacr hmyypoecraprldaistiias"(ovary) HPeermiovsaisdceurloasrimso(nsop,leinefinl). (lung) FeMmeaglaelsoc(y1t6.o1simsg/(klgiv)e:r) "HTeumbousliardehryopseirspl(asspiiaee(no)v"ary) "Decreased incidence relative to controls Genetic toxicity studies (study type and results): None Remarks: ~fDemoaslee-sr.elated decreased in mean body weights in excess of 10% was observed in high-dose males and t"hMreoaunghfoeuetdtchoensstuumdpytwiohnen(acsogmrpaamrsedd itoemualbewc)onwtarsolinfcereedacsoendsiunmapltioofn.theOvFeCr-al1l4,3thtereavtaerdiamtaiolnesswere hrielgaht-eddosioetmhaelveasriraetlioantiinvtoebocdoyntwreolisghftoratmhoenfgirsgtryouepasr.oftAchteuasludm.ean feed consumption was decreased in A~Dosseta-triesltaictaeldlyoscicgunrirfeincacneotf(apt<a0.x0i5a)idnecfreemaasleesinwraesdbthleooodnlyceclllipniacraalmesitgenrsobwsaersvendo.ted in the high-dose: mAalsetsataisstcicoamllpyarsiegdnitfoictahnetc(opn<tr0o.l0s5.) increase in relative liver and kidney weights was found in high-dose males and an increase inrelative kidney weights was found in high-dose females. 263 000162 HUfeirmsiatnloaeprayctohnfotilrnoodgliinacgansldinFecfCfl-eu1cdt4es3d-witenrrcaertencaodstegedrdioiuncpistdhaeetnlc1ie2ve,arno1d8f.hsaienvgedhr-i2dt4oysmoeofanmtlahblsue.msiTanhnedasnfedemfoiacnlcdeuilsntgslowoerdeimnoalrlcmale and pbReratotwnseoeguinnvcteehnde tifhnresmttaealstnedsatstieheaclnoeniednxpfmeeormniatelhnescsoefadttahthseeusstpteuerdcmyit:neadhtooiwuoetnbvorefera,tkhheoefsstpuidrayel.soednacceryoofadevniirutss w(aSsDAno)tvciroanlfiinnfeecdtion CONCLUSIONS "The"Tsrteuadtymreenstulrteslaarteedscuhmamnagreiszewderaes ffoolulnodwsm:ore commonly in males than in femalesofcach ofthe two fstretemuaadtlmse.ndtemgroonusptsr,awthiinacghhwiegrheersreutepntpionoborfyeFtaCre-li1ed4r3pbhyarmmaalceoskitnheatnic B"Tahseetdesotnmadteecrrieaalsewsasincboondsiydweiernietdgthheotbmgaealicenas,racinindncormgeaeansmimicnailrniyvtehgrelaarnnadd, ktiinuddmhuoecryisnwgienitfgeehsmttasiluealsna,dr/tLoesyidciigyceilnl tmheors hiL5eO3mAa0t0EopLlpogfmiorc(ammlaallaeen:dr1ah4te.sp2iatmig1c./3ksgym/sgtd/eakmygs/,dftaehymeaiLlfeOs:a1Al6iE.v1Larmyfgog/rlkmagna/ddlaesyia)a.nlda[dfTeehnmieatlseisrats tbhaeseidncuipdoenn.cestohefaLtOaxAiEaL(afcolrifniecmaallsegrna)tsainsd1.o6fomvga/rkiga/ndatuybuiflairncreases in Thedotseset-idceulpaerndLeenytdiigncceclalsaeshdyeipnneornpmelaoaps(lipaa-s<(i0mc.a0a5yndabenhorineg-vhenredsooipsblela)es)taiancrdelvebasasiscoenudslawurpeomrnie]n.earalfoilzlaotwiso:nofthe testes (t9h<y0r.o0i5daCt-choilglhadodsee)nomaisn low-dose males. ltmuhanymgromliaedsrCiy-ocngesllilannmhdyapfleierbsprlo(apasdi<ea0n.io0nm5ahsiatgihhn-idfgoehsmedaolfseeesm)a(lpe<s0.03 at high dose) = osavlairviaarnytgulbaunldarsihaylpaedrepnlitaissiaininmafleemsal(eps<(0p.<005.a0t5laotwlaonwdahnidghhidgohsdeso)ses) tivmeergwaeliogchytosainsd ilnetvhaetifoinvesrooffsmearluemseannzdyfmeemaalcetsiv(ip<tes0i.n0d5icaattiivgehofdoisve)ewtiotxihciitnycreases in reve +hicgyhstdooisde)degeneration and portal mononuclear cell infiltration in the liverofmales (p <0.05 at ofRefesFmp3ao4rn4skesr:a0ts;Ithneefvlatuleesuntactseiouobfnstopafontc2ee9ndtsiiaclotticrocnlateariro.nlfeaScattligoordnoauicnprsmyaoalated3edSnipifrtfasrgevuniert-uDslaa(bwoSlrDeaytAoVrr)aiessisawtaibtcohotahmnmddoowsnietsvhioornaulttihvneifeacltion (iRnfaeoc,ticotan.,fou1n9d88n).o consistent influence ofira infection on body weight, survival,o tumor prevalence REFERENCE F31l6M.uoCr1oo98mc7hp.eamniyc/aRliFkCe-r1L4a3boirnatRoartsi.es,ExInpce.riTmweontYNeoa.r0O2r8al1C(RDOi0eI)2T.oxiSct.itPya/ul,CarMcNi.nogSenEicHi.ty1S0t8u7d-y03o9f4, Oct. 264 06090163 Rwaeoi,ghGtNa.ndEsdurmvoivnadlsoofFnis,Jc.hearnd34H4asreams.anTo1xKi.colIongfilsute,n8ce1o6f6,vir1a9l88i,nfections on tumor incidences, body 265 000164 REPEAT DOSE STUDIES Title: Mechanismsof Extrahepatic Tumor Induction by Peroxisome Prolifeators 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 (VIN): Unknown Vear study performed: 2001 (publication date) Speciesistrain: Crl: CD BR rats from Charles River Breeding Laboratories (Raleigh, NC). Sex: Males Number of animals per dose group: 156 Routeof administration: dict Doses tested and frequency: 0, 300 ppm Post-observation period: None Satmaotinsgtigcarloumpestwhaosdssiugsniefdi:canOtn,ep-awiarwyisaenacloysmipsaroifsvoanrsiawnceer.e mWahdeenwciotrhrDesupnonnedtitn'gtFe-stt.estTfhoerBdaifrftelreetn'cetsest ffoorr ehqoumaolgemneediitaynosfavnadriMaanncne-WwahsitanlesoypUertfeosrtmfeodr.paNiornwpiaseracmoemtprariicsponrso,cedures included Kruskal-Wallis test aR1n.ea3ml.ay6rz.9ke.ds:f1o2r,H1toe5rs,tmo1os8nt,earalonndaen,2a1elsytmsrioasnditwohals,salcfuotcneirdnuiicnzititenidgatihinoonor1m0forntaethse,.sftBoulldlyoi.coldeSwsctairsmuumcloawltaliesntgpehrdoerpfmarrooenmdet,ahneadntadiflrpovrzeoeilnancaatnibdnoutthen concentrations. All samples were analyzed simultancously in duplicate. Rerpaeitmdsoivwdeeydrm)ie,deeprso,ustaatctcee,hsasaaonrdtynilnsitveieexrrzigwmletaerniedmdew(epAieSgrhGie)odd,usni(t1wi,t3h, 6f,l9u,id,12c,oa15g,u1l8at,ianngdg2l1andm/osnetmhi)n.al Tveesstiecsl,e (with fluid 266 000165 eAlLa2n4d/smeomnitnhasl, vseusrivcilveisngwirtahtsfwlueirderneemcorvoepds,iepdr.ostBartaei,n,ephiedairtd,ymliivdeers,,spalenedn,tesktiedsnweaysr,e AweSiGghutneitd,actonaegcurloaptsiyn.g lLeisvieorn,s.testes, epididymides, pancreas, and organs with gross lesions were examined microscopically for Six rats/group scored. were selected for evaluationsof cell proliferation. For each tissue type, 1000 cells were Six and rats/group were selected Leydig cell peroxisomes fwoarsevmaelausatuiroenod fatpaelrloixnitesroimmetpirmoelipfoeirnattsi.on.f-ofx-iodxaitdiaotnioanctaicvtiitvyitwyafsrom liver determined using the method of Lazarow (1981). RESULTS Toxic responses and effects: ddBeuoccdryteoawsreeeiddguihcnte,tdhfe*ofCood8odcgoerfnofsuiucpimevpnetcryis'ou.nst,hOaennadddasyluir7bv1iit4vouamlf:ctohnFetrrtooelmstg,erssotuurpdv.aivyaTslheintdoteh6ce3r0Ce,a8sbegodrdobyuopwdeywiagwshetiignwhcatrsewasasiesgdnpirfiicmaanrtillyy compared discussed with the control group in a separate article.) (statistical significance not indicated). [Hematological changes were Liver: 0.05) wRehleanticvoemlpivaerrewdeiwgihtthsonaenodrhempoatriec cfo-notxriodlagtrioounpsa.ctiCvi8typwreordeucseidgnaifsitcaatnitstliycailnlcyrseiagsneidfiactaanltl times (p increase (p< 0.05) in incidenceofhepatocellular adenomas (10/76, 13% vs. 2/80, 3% in controls). `iTnecsitidse:ncTeesstosfweLeiygdhitgscewlelrheypsteartpilsatisciaallaynsdigandiefincoamnatlsy wienrcereaalsseod s(tpat<i0st.i0ca5l)laytsi2g4nimfoicnatnhtslyiinnCcSr-etarseeadt(edp<rats. 0.05); the incidence of Leydig cell tumors was 8/76(11%) as compared to 0/80 (0%) in controls. Pancreas: 18. and 21 mPoanntchrse.atiIcncaicdiennacreocefllapcrionlairfecrealtliohnypwearslpsatsaitaisatincdalalydesingonmiafiscawnatslysiingcnirfeiacsaendtl(yp < 0.05) at increased 15, in C8 craotmsb(ipn<ed0.i05n)c.ideCnacrecoifnoacmianawracselolbasedrevneodmainaonnde cCa8r-ctirenaotmeadwraats(8n/o7t6st(a1t1is%t)icwalhleyrseiagnsiftihcaatntof)t.hTehecontrol was 0/80 (0%). Serum at 1.3, 6h,o9r,maonnde12memaosnutrhesmecnotmsp:areSdertuo mcoensttrroaldigorloucposn.cenTthrearteiownesrweerneo csoingsniifsitceannttldyifefleerveantceeds (p in < 0.05) scrum testosterone, FSH, prolactin, or LH concentrations in the treated rats when compared to the controls Statistical results: Statisticallysignificant results are reported above, wRheemtahrekrst:heAmafmulml arranygegolfanodrgtaunmsoarnsdobtsiesrsvueesdwiansthneoctaerlxiaemrimnueldtih-idsotsoleosgitcuadlyly(.3MT,he1r9e8f7o)rew,aist iisnudnuckendoiwnn this study. 267 000166 CONCLUSIONS tu"(GTmehosetrissstbuadnyydCdp8eamniocsnresaaisrre)astuielnttChoaDftaCrsa8tus,s. taDipaneteradoxfiirnscoormematehsiepsriosnltisueedryrautaomlrse,ostsirunagddgiueocsletsctohhneacpteanttthiercaaitsniwdouencltlioansofexLteryahdeipgatcieclltumors Remarks: none. RLaEsFtEMRodEiNfCieEd: 703/01 eBxitergaelh,epLa.tBi.,c tHuumrotr,iMn.dEu,ctFironambey,peS.rR.o,xOis'oCmoennproorl,ifJe.aCt.orasnidn Jm.aC.leCoCoDk.rat2s.001T.oxiMceoclhogainciaslmSscioefnces. pret 60: (31pM0e.8r7f-Fh0iun3oa0rl4o,orceOptcoa.rntano1e6af,"m1mT9ow87no.iyuemar ocraarlbo(xdyilcat)tet)oxiincirtatys.anVdol.car1c-i4n,oAgeMn/iRciItKyEsRtudEyxop.fNfol.uo0r2oc8h1eCmriocoa1l2:FCS-E1H43O- 268 000167 DEVELOPMENTAL TOXICITY Title: Oral Teratology Study of T-2998CoC in Rats TEST SUBSTANCE. Identity: Ammonium Perfluorooctanoate (APFO) or T-2998CoC (FC-143) Remarks: Purityofthe test substance was not indicated. METHOD MUiesstes"uh)e.od diTnGhJueainsduteaulrdyiy,new1a9fs6ol6clo(on"wdGeuudci:dteeTldhianecepcsroforocdreiRdnuegrp1er0ocdthuoecmt1pi9ol7ni8SGwtioutdohidetshLefaobgroenrSeaartfaoelrtyyreEPrvcaaoclmtumiaectneidoRaneotgiufolDnarstouiogfnssthfaeonrFdHDSuaAmfeatny Evaluation Laboratory's Standard Operating Procedures. GLP (VIN): Yes ear study performed: 1951 Species/Strain: RavSprague Dawley-derived CD. Number of animals per dose: 22 Routeof administration: Oral gavage aDnodsi1n5g0rmegg/ikmge/nd:ayFAivPeFgOroiunpswoatfe2rb2ytigmaev-amgaeteodnSgperstaagtuieo-nDdaawylse(yGrDat)s6w-e1r5e. adAmicnoinssttearnetdd0o,se0.v05o,lu1m.5e, o5,f mig was administered. Doses: 0.0.05, 15,5, and 150 mg/kg/day o`Sftarteissotripcatliomnestitheos,dsnuseu d:ofDm iumnpnleabtntt'asteiotensstr iftoersdaanmdannudmbpuepr owfeciogrhtpso,ranulmubteear;oCfhfietsuqsueasr,enfuormber percent abnormalities. wrRehsieuclthms foiavfae--rgDarenkotguaepsislfioanfnd2id2ngdtiissmtcueud-syms,aatanenyduSspippgernraigfduiocesa-enDtalepwvrleoeltyoofcrao1tls50pweamrgre/akagmd/medinatiyesawtrneadsrsedsdee0tvi,faotr0i.to05hn,es1:d.e5f,Bia5n.sietaidnvdeons1t5tu0hdey in 6`-m1y5.kg/DdoasyesAPweFrOeiandjduissttieldleadcwcaotredrinbgytgoabvoadgyewoenigghets.tatDiaonmsdawyesr(eGmDo)nitored on GID 3-20 for clinical ussaimcgbrnisefoirfceotdfoxocinocriGtpyoD.ra2I0nfdubtieyvai,cdeunrauvlmicbbaoeldrdyiosfwvleioicagabhtltiesoanwnaednrdenotrnhe-ecvooirvadaberlideesof,netuGutsrDeis,,3,ann6ud,m9bc,oenr1t2e,onft15rs,ewsaeonrrdpet2ie0ox.nasmAiintenisem,daalnfsodrwnteuhremeber AoFpipmrpolxainmtaatteiloynosniete-st.hiFredtoufsetshewefreteuwseesigwheerde afnixdedseixneBdouainnd-=ssubsjoelcutteidotnoanexdteerxnaamlignreodssfonrecvriospcseyra.l 269 009168 Susoimnogramlaiizaircisn rbeydfrc-hand sectioning. The remaining fuss were subjected to skeletal examination RESULTS mIekle/sdy.pTheaNndOAeEcLt)frdmeavtecrlnaaplmaenndadoecxloipmen1t5a0.mgThpeaNyO.AEheLhifgohemsattedmoasle toesxteid.c is 5 NoIengesfyoofdbeeavseenldodopnmeesnatttia)sltit-coaxmlilacyittesyirgwnneairlfiecaaannhdtsdrreevdveuedcltoaiptomnaesnitnadrl:aThmea0rrAbody mweaitgehrtn,alttaxoic,iayndisd1e5at0h, HSeioghnh-iodnorsmeessagperoodnusupecetofofencstsinbmyeadonsme lcem-mvbaotdeerynwaleli:ghStigonnsoGfDma5.tse1rnalartoxicity consistedof stistcaly 150 mg/day. ataxia and death, all a the ddeoveelopemsebnotanlsetolxfiecictty wbeyredossceeneavelan-ydedvoeselofpmaenntal: Nossa significant signs of Statistica resus: blooadhbwlIaefho wtheeSrresoaibgsntesrvoeefdmolantegimeastltatoixoenidcdiuyyiso(n5a,so1s6D,uanedtd15so. ne cs pa 05)iinnfomremaatniomnatwears aas o; bserveAd sattihseihciaglhleystsidgonisfeidcagnrtoiuncroefa1s5e0(Cmhip-sa quare, 0.08 in one stemcbrac missing Remarks- Additional information to adequately assess the data: SrCoomonoymretmGtaa2aralemai1no5xoitswitetery cthohinagsnhi-csdtooensdteoofglsr,sotuailptcohafolu1gl5hy0hmseiggdniifdficta.pnteeec dwucteior n in meabnodmyatweeringahltboondyGwDei2g0hts tt0.aaffesct ahmesv.ariNeonsoaotrhlersreperofofcdeccuutcrstiiwnveegrtornarceytpcaoornttth.aechtAiogfhdhdeosirsouopsessw dwuirsitnicgcaglelsytE astiigonnifdoiicbadsnetn,roveOadrphipneerar eSbrseaoameenrmroeensatorn0erlEisgiheelai:nicnicodieduennccereibnuittsuowsekeserlewttiahtlhavotrhnethmoignshit-ndygpseterrayewaes orbseervped at thtehheiagthh-deotsheree re onssoopfe mentar aml ipanaotcefandmea,eslNtoolrsmsyiitgdohnsentisiiscintcasln,udimefpdrlhenenicmieeosannbeimnvseesrncopr mopnsy s prc ronfeem.tahle0erfUesefDtoorutSesalwwweaaersniednnodtoetacedodnfsfeiotrduesoretseh,derto and trheroeforreynoot ncoansisduelrceuds,10wbcaetsrriecabetemdeadnrtiireentteoyedosfstoarnoam y pn o EchaEngesselcotcgiaholsin.ziendgLotiekcehhweniisqeu,e 270 ee -- -- re ------ 209169 CONCLUSIONS Comment on authors conclusiaonds whether you agree: Conclusions are summarized above and this reviewer agrees. REFERENCE GExopretrniemreE.n.t#1096818.1OTrRaOl T10e,raDteocloegmybeSrtud19y81ofT-2998CoC inRats. Riker LaboratorIince.,sS,t. Paul, MN, m 409170 DEVELOPMENTAL TOXICITY Title: Oral Teratology Studyof T-3141CoC in Rabbits TEST SUBSTANCE Identity: Ammonium Perfluorooctanoate (APFO) or T-3141CoC (FC-143). R3the1ism4a1arnCakolsyCs:ihsa,AsctachnoeraCdnxianlagycsitidoswtwahiesths9it7nu.dsy6p%eacuaitfnhidocra9st,8io.tn4sh%,aonifsaltsyhatebilcteaelsartnesdpuobirssttrae(npAcrpeepspeenrnteda-itsxiuvdIeoyVf)adncedopmmoomnsesrttcsritaautldeydm.attheartiaTl-, By respectively. METHOD MiestsuheoddinGuJainduealriyn,e19f6o6l:loAwGeudi:deTlhienepsrofcoerdRuerperocdoumcptliioens wStiutdhitchsefgoernScarfaeltyreEcvoamlmuaetnidoantoifonDsroufgsthfeorFHDuAman Use@ Type of study: Developmental Toxicity GLP (VIN): Yes ear study performed: 1981 `Species/Strain: New Zealand White/Minikin rabbits Numberof animals per dose: 15 Routeofadministration: Oral gavage D50osmian/gkgr/edgaiymeAnsPFFOouirngdriostuiplsleodfwa1t8eprrbegyngaantvaNgeewonZegaelstaantdioWnhdiatyesr(abGbDi)ts6w1e8r.e aAdmcionnissttaenrteddo0s,e1v.5o,l5u,maend of 1 mig was administered. Doses: 0, 1.5,5, and 50 mg/day Srteastoirspttiicoanlsmiteets,hondusmbuesreodf: iDmupnlannctiatt=ionesistesfoarnddanmumabnedrpoufpcowreipgohrtas,luntueam;bCehri-osfqfueatruseetse,stnwuimtbherYaotfes correction for percent abnormalities. Rreesumlatsrkosfa- aDentgaei-lfiannddindgissctuusdys,aannyuspipgenrifdiocsanetlperveoltoofcoSl0pmagr/akmge/tdearyswaansdsdetevfioarttihoensd:efBiansiteidveosnttuhdey in `wmhgi/ckhg/fdoauyrAgrPoFuOpisnofdi1s8tiplrleedgwnaantteNbeywgZaevaalgaendonWhgiestteatriaobnbidtasywse(reGDa)dm6i-n18i.stePrreedg0n,an1c.5y, 5w,aasnedst5a0blished in afoclhlosweexdubayllayrtmiafitcuirael finesmeamlienbaytiio.nv.wiitnhjec0t.i5onmooffpiptoiotlaeryd sluetmeeninzicnogllheoctremdofnreoimnmoarldeerr0abbiintd:ucheeovdualyatoifon, insemination was designateda day 0ofgestation. A constant dose volume of | mI was administered. m 309171 coInnodnGitvDiednu3a.el2x9baomfdoiyrneawdbenifogorhrmttashlewcenlruienmibmceaelraossifugrncseo.drpoOonrnaGGDluDt3e2,a9,6,,l9tv,heea1nd2o,dc1sd5,ewae1dr8,efaectnuudtshe2sa9,n.iezsTeohdrepatndidoosntshsewaeonrvdaeriiomebpssl,eansrttveaertduisodanainldy Assuitrbsv.liovoaFldectshuaesmcepksl.weePwruaepsestxwaaekmerinenfesrduobfmsoersqiugxreodnsotselsyabepnurotirohmraanflioiztdeiodessainnagdndaenxpdalmatcihenedendionnfaoGr3Dv7is1c3eriaanlncduabn2ad9t;osrkaeflieovtreaarl2sa4abmnhpoolmuemrawlaisis. itankfeonrmfartioomntwheassaumnaevaaniilmaballesaotnthGeDi2m9.ofAlthlissamvpilces.were sen o the sponsor for analysis, This RESULTS edNsoOtsaeAbltEiessLhtee(ddd,sofisonerceamnasdtigeenmfsoaflfecodtxe)ivecmltaoytpewmreannsatlianladtinocdaxtidecdei.vteylAwoepNrmeOensAteEaelnL:aftAoarlNldOedvoAesEelsoL,pmwoeintft5h0asltmatgt/iiskctgii/ctadylaysc,iogutnlihdfinhcoiatgnhcbeeesattthe highest dose aLtOanAyEdLos(edolseveela.ndTheeffeLcOt)A-EmLatfeorrndaelvealnodpmdeenvtealloposmiecnittayl:isN5o0 msgig/nksg/odfmaayt,ebrnaasldtoonxidcoistey-wreelraeteodbserved increases ina skeletal variation, with statistical significancea th high-dose group. s"iTgnoiefirceanstpotnrsaenlsieefnftecrtesdubcytidoonsseinlebvoeldyBwmeaitgehrtngali:n oSnigGnIso)f6-m9atwehrennalctoomxpiacirteydcotonsciosntterdoolfs;stbaotidsytiwceaillgyht gains retumed to contol levels on GD12-29. dToosxei-crerleatsepdonisncerleeaescetisnabyskdeolseteallevvaerliBadteiovne,leoxptrmaenritbaslo:r 1S3ignisbo,fdweivthelsotaptmisetnitcaallsitogxniicfiitcyanccoenstishteedhogfh dose groupof S0 my/kg/day. Statistical results: MPa<t0e.m05a)lbdeattaw:eeStnatgiessttiactailloyn dsiagyni6f-i9cawnterredoubcsteirovnsedininmtehaenhibgohdeystwediogshetd-ggarionuspo(DfunSn0etmtg=/skgt/edsta,y. After gestation 9 mean body weight gains were comparable to control animals for all doscd-groups. (FDeutnanletdta-tsa: eDsotse,-t0e.l0at5e)daitnctrheeahsiegshi-nd.ossekeglretoaulpv(a3ri8a%tioatn,5e0xtmrga/krgib/sdaoyr,1330%riba,twSitmhesktgaitidsatiyc,al2s0ig%niaftic1a.n5ce rmiebksg-/spduaryr,edaoncdcu1r6re%daitn 0thmeg'mkigd/-ddaoys)e.grAouspatosftiemagl/ykgs/idganyi.ficant increase (Dunneti= fest, 0.05) in 13 Remarks - Additional information to adequately assess the data: GSIiDgn6so9fwmahteenrncaolmptaoxriecdittyo ccoonnstirsotlesd;boofdsytatwisetiigchatllygasiignnirfeitcuanrtmerdatnoscionnttrroeldulcetveilosnsoninGbDod12y.2w0e.ight gain on tcAoodnmgtiaenvniatsgsteroafettrirhooernso.dofcNsA.oPcFSliOixniddcuearlaitonhrgsogotechsceturarttrireoednatddmuierdnitnn.ogrtetlahapetpseetdaursdiy0g;nhasofwwfeecrvteehrr,eepoforivtvaeerodi.festohe rsiexdpreoadtuhctsivweertreacatttributed ffNoeormtashilegensniufdimecbaaendtroodrfifrlfeievsreoerfnepctteuissoewnse,aranenddniofmtepetladlabnwteeatitwgiehoetnsn.sictoLenist,krecowolisrspaeo,rnathtlerureceaatw,eedtrgheerocnuoopnssciegfpnotiriftoihcneanintnucdimidbfeefnecrre,eonfcamebasolrertesipooanrntrdeatde, m 000172 vuoarnrriteahtmeiao2rn4k,ahbeolxuetrr.amTorirhbtesalooirntly1yi3snicigibndo,efnwcdietehocfslttoahtpimsfteeictnautlseassi.ogxnGiircfoiisctasynccnoeencasriostpthseeydohaifngdh-sddkooessleeetgaelrlvoaiutspecd(er3ian8lc%reaextaamsSi0innmatagisokknegsl/edweaelyr,e si3in0gcn%riefaaiscSeanimncueo1kf3g"t/hrdiiasbyse,-fsf2peu0crt%reisaduon1cc5ceurmrtaegidkngisnditanhyce,imnaindbd-odt1hos6teh%egarhtoi0guhpm-oea'fnkSdgimldgoa/wyk-)gd./odsAaeys:gtrahotouiwpstsei,vceahlril,sy tsehieegncbitifoilcooacgnitecmaled at the same rae and was not statisticallysignificantlydiffrent fom controls. CONCLUSIONS dc`oeCnvocemllmuosepimnoetnnstoaonlfattuohxteihcaiuottyrh.sorcWsohtnihcllteutsithieoisnfsaignadrniendegdowtfhheeatxthtrehaerrbyiiboosul,ogoaigcra1el3e:siiTgbhn,iisfirceatvhniicseeowpeafrratdincoucalshaernrosettduadigynrceaierdweninotcthe3ohfseign of tiahnnecarrteeofamosireceawliistvehavrsaitlaauttaiistotenidscaslisssdiigfpnioicsfusilictbaln1eceianasdeistcshae,tihtoihnogehfeisndtceivddeoelnsocdpegmorefontu1ap3l*, itionixitnchiettysh.ies nsctuedyosfmhaotweerdnaadlotsoex-ircietlya.taendd REFERENCE CGoormtpnaenr.y.E.GRi.keE.rG.LabLoarmaptroericehst,,IMncT, StC.asPea.ul,19M8N2.. OErxaplertirmaetnotloNgoy.s0tu6d8yoITfBOT3-9381,4F1eCboruCianryrab1b9i8t2s.. 3M m4 000173 DEVELOPMENTAL TOXICITY Title: The Embryo-Fetal Toxicity and Teratogenic Potential ofAmmonium Perfluorooctanoate in the Rat TEST SUBSTANCE aoIrdmeamnstoiantiym:aujmAorpmecmrofomlnupioorunoemocntptzeonrfofalFtueoX,r-o1ao0mc0tma3on(noaiCtuAemS(RApeNPrFf3Ol8)u2o,5r-opc2ea6np-tra1yd)leactaef,luPoFrOo,ocFtCa-n1o1i6c,acFiCd-a12m6m,oFnCi-u1m69s,alFt,C-143, SRSeLm4a4)r.ksI:t pTuhreittyeswtassub>s9t5a%nc;e,thAePcFonOta[mCiFna(nCtFs:p)rCesOeOnNtHw,eJre, [wCaFs,o(bCiaFi:n)eCdOfOrNoHmL3]Man(Sdt.PPFaOulA, MN isomers. No itnhheibtietmopre.rcaatrurireersw,aostroadedixtcieveeds 2w5e0reCpr(eusnenptu.bliDsehgerdadDautiPoonntofdaAtaP).FO was considered insignificant unfoss METHOD MethodGuideline followed: Not specified GLP (Y/N): Not specified Year study performed: 1984 Species/Strain: RaSprague-Dawley derived, Crl:CD (SD)BR strain. rNautmsgbreourptorfaaln.imTawlos padedritdioosnea:l,Fpoarirt-hfeedignhraoluaptsio(n6pdoarmtsi/ognorofutph)e, swteurdey,atdwdoedtitaolEsxwpietrhim1e2nmtat1 e(diefreatmoalloegy), aexnpdatswuroegproorutpison(o6fdtahmes/sgtruodyu,p)25wearned a1d2demdatteodEfxepremarliemreatns2tat(cdaacmhseaxlplooswuerde tcoonlicteenrt).raFtoironthweegraeviangcel-uded in Experiment I(tcratology) and Experiment 2 (dams allowedtoliter), respectively. Routeofadministration: Inhalation and oral D12ospirneggnraengtiSmpernag(iusct-Dalalwwlietyhruantsitps)e: gFrooruptheexpinohsaeldattioonApPoFrtOiobnoyfwhtohlees-tbuodyd,ytvhaeptowrointhiaallastcioonns0i.s0t,ed0.o1f, f1e1d00. athned 1205.amngd/2m56'mgh/omur's/gdraoyu,pso,nwGerDe6a-d1d5e;dttwooeaadcdhittiraoinl.algIrnotuhpesor(a6ldpaormtsiopneorfgtrhoeups)tutdhya,t 2w5eraendpai1r2`ASPpFraOguien-cDoawmleoiylrbaytgfaovratghee ofinrsGt aDnd6-s15c,cond trials, respectively, were administered 0 and 100 mg/kg/day Doses: 10and 25Fomrgi/nmh'algartioounpse:xpfoosruorreasl:ex0p,o0s.u1r,es1:, 100,aanndd12005mmgg//kmg'/,dawyi.th two additional groups pair-fed to the Setvaatliusattiicoanl (mSettaphloedssanusdeHd:ascTmhaenl,it1e9r7w4a;sHuasseedmaasntahendexHpoegrainm,en1t9a7l5)u,niTthfeorsithgenipfuircapnocseeooffdsitfafteisrteinccaels in tprhoebianbicliidteyncteesotfp(rSieeggnela,nc1y95,6)c.linAictalwosi-gwnasy. aannadlymsaitseronfavlardieaantchewawassdeusteedmitoneddetbceytudsieffoefhreenceFsisinhefro-cedxact `cotnesstumtphteisotnataismtiocnalgsbirgencidfiincagnlcoeotsfadinfdfbeertenwceeesnbgerotuwpese.nDtuhenncoenttr'olteastnd(SAtePelFOangdrToourprsei,n 1m9a6t0e)rnwaalsbuosdcyd 275 000174 sdwieegitngeihfritmc,ianniten.dbbToyhdeyJowpnreceiksghehentecregoeai'fns,ctoaesnntcde(inJnotnrfcaekiehdoenec-rorene,slut1me9pd5t4ri)e.osnTphownehsesenisgntfiohrfeihocneanec-ienwhoaafydlaiatfnifaoelnrypesoinrscoteifsovnioanrfiinatcnhiecdesenwucaedsowfas FisMsianhniecnrt-u'WrsahleixatalncteterypartUoibotanesbsitblei(ttMywaetneensntatwnhaedscWaohpnipttlrnioeelydg,r(oH1ua9p4s7ea)mn.adWnthhaeenndAPmHooFerOle,gtr1h9oa7un4p)7.w5aT%shtedeelsteevoerclmcoiufnrersdeidgbnyiinfaitpchpaelnidccaeattas,ieoltneohceftedthe sweavserp[al r0.e05p.rVoadriuabciilnidtiycaebsouwtermeeacnalscuwlaasteedxpfroresssoemdeasresstualntsdafrrdoem Erxropfeotrhirememne2tan(d(aSmE)s.aIlnloawddeidtitoonf.ice), tcReoernmastiaosrltkoegdsyo-pfoaDrnettiaioinnlhoaafltnahtdieodnsitsaucndudys,saniannowryahlsiicpghonrittfihioecna,dnactmapscrhowtweoircteohlstapwcraoirtfraiimcaleedteoorrnesGxpaIenrd2imd1eenvwtihsai.tlieo"niTsnh:tehfTeihrssetecisotanulddywtrdaiesgs,ithtgeh.ne AdpoaPrmtFsiOownobeyrfetwhhaeolllsoetw-uedbdyo,tdoytvhleaiptttoweroanitrndihaatllshaetcioponunspis1st0we.ed0roe,fs0.a1,1c2r1,ip1f0ri,ecgeadnnaondnt2dS5apyrmag3g/5umpe'o-s6Dta-hwpaloretyuumr.ratssFopoe/nrrGdtghrDeaoui6ynp-h1,ea5lx,aptoiIsonnetdheto aoarddammliinnpiiossrtttreiaortneidoonf0,tafhneedmsat1lu0ed0sy,wmge2/r5keaemn/addtae1y2dASoPpnrFaaOnguaiens--cnDoeaemwdleoeidyl bbrayastigsafaovrnadgtheweohfnernsGttDahne6dn-1su5em,cboeFnrodorftrbmioaatlsht,errdoeustfpeoesmctaoilfveeslyw,erweere. obfrerda.nkt.heyFiwnealrley,ratnwkoedadwdiittihoinnalbrgereoduipnsg dsaiyxsdabymsbopdeyr wgreoiugph)t tahnadt wasesriegnpaeidr-tofegdr1o0uptsheb1y0raotnadti2o5n ming/ormd'er groups, were added10 each trail. Foobrsetrhveedtedaatiollyofgoyrpaobrntoimomnoalftchliensitcualdysig(nrs.alOonne)G,Ida2m1,stwheerdeawmesigwheerde osancrGifDi1ce,db6,y9,ce1r3v,ic1a6l,dainsdlo2c1ataionnd laianvnidemeaanlxdawmdaiesnaeeddvaflfeoutrautsaeendsy., rgeTrshooserspotavibaonrnoisremsaa,nldiuttieimrepusls,aalnintvadetrciowonentiseignthtesss. wwPeeurrpeserx(elacimovirednaeendddafdnoedratdthh)eewnreerpuerocdomuuocntfbticevodee,rspwtoearrtiuagshuoetfdeesaa.cndh es`ygeerxsoe.udp afnetduseexsawmeirneedexfaormiexnteedrnfaolr,vviisscceerraall,alatnedrastkieolnestaals awletlelraatisonmsa.crToh-aenhdeamdiscorfoaslclopciocntervoallauantdiohniogfht-dhoese atFnroarlintodiniavleiutdwupoa,tlociaGngeDw.h2i1c.`hThetThdweaodtcadomafsypsawrbeteruferoiratelilotonhweweeadtxspoenlcoittteeded,daanthydoedfpeprsaoircgtenudarutiretediowDna,asycat|chheposdsaatmmpeawarastsuthmhaot(uPfPso)er,d in al`ElDaacdmhasmpswueprwweearwseeissagucbhrseiefdiqcaueendn.dtlePyxuawpmesiinwgeehdreedfocaroncudlnitinenidcs,aplewcsetiieggdnhsfeodor,naaDdnvadeyrsesxe1a,cml7i,inni1ec4da,lafsonridgen2xs2toePnmPa.DlaOaylnste4Dr,aat7iy,on21s34., PP apDonardyti23o25n PaPPnP.adTnohdneDeeaxyyaesmsio2nf7etdafhneodrp3vu1ipssPcewPreafrloeraatnlhdseosgekaexvlaaemtgiaelnpeaodlrtteorinaotnDioaonfytss.he15staunddy.17PuPpPsfworertehesianchrailfaitceidonon RESULTS NOAEL (dose and effect-) maternal and developmental: dNeOvAIneEhlLaloaptfimoorend:nevFteoolxroicptiimtaeylntiosanl1e0-tomtxgihce/imNt'yOiAs EF1o0Lrmtfgioa/rlmm.tatweorn--atlhetoxNicOiAtyEiLs |fomrg/mamt'e;rntahle NtoOxiAciEtLy ifsor1mg/m's the 276 000175 Oral: portion A NOAEL of the study ucsoeudldonnloyt obneeddeotseermlievneel,d for either maternal or developmental toxicity since this LOAEL (dose and effect)~ maternal and developmental: Inhalation: F(ocornsriisatlionngoe-fwethte aLbOdAomEeLnsf,orcmhartoemrondaalcrtyooxircrihteyai,s c1h0rommgo/rmh'i,nobrarsheeda,onatnreadatgmeennetr-arleluantekdepctlianpicpaelarsaingcnes), aisn2d5simggni'fi,canbtasreedducotniornesduicntifoonosd consumption in mean fetal baonddybwoediyghwtesigahntd; athsetaLtiOstAicEaLllyfosrigdneifvieclaonptmiennctraelasteodxicity incidence of fetuses with partially osified stemebrac. cLFooOnrsAitEsitaLlinfgtoworofd--ewvetethleaoLbpdmOoeAnmEteanLls,ftoocrxhimrcaiottmyeodmisaac2lr5ytoomxrgir/chmiet'ay,,ibsch1r0oammoognr/s hmsi'ani,oserbtraihcseaedladl,oyannsdtirgaengiaeftimnceeanrntat-lrreeuldnauktceetdpitoclnaispnpiicenaalpruasipngcnbesos.dtyhe weight portOiroanlo:fAthLe OsAtEudLycuosuelddonnloyt obneeddeotesremlienveeld. for either maternal or developmental toxicity since this `Toxic responsc/effects by dose level - maternal: Inhalation `consAutm1pt0iaonndan2d5bmogd/ym'w,eirgehatt;maetnt2-5remlga/tme'd,clsitnatiicsatlicsailglnyssoigfnimfaitcearnntalintcorxeiacsietsy,iannldivreerdwuecitgihotnss;ilneftohoardgy and death, Onl A100 mg/kg/day, Consumption, reductions in tbhoedoynwleyidghotsgtaeisntse,da: ndcdlienaitchasl.signsof toxicity, reductions in food "Toxic response/effects by dose level - developmental: AL2S mgm, reductions increases in the incidence in mean fetal and pup body weights and statisicaly of fetuses with partially ossified sterncbrac. significant Onl A100 mgkg/day, the only dose tested, no signsofdevelopmental toxicity ware observed. Statistical results: Inhalation - maternal Aasts1i0gnaedn)d. 2s5ignmigf/imc'a:nt trreedautcmteinotn.sreilnatfeododclcionincsaulmspitginosonf(m21a.8t+ema0l.4t6oxvisci2ty3(.+no4st0a.t3i8sitniccaolnstirgonlsi)f,icaanndce sPi<g02n.5i0f5mi)cg;an'lte:rtehdasrutgcaytiis(o4incsoauiltnyobsfoidg1ny2i)fwaiecniadgnhtdteianwtcihrteh(a3ssetoasuttiisntoimfcea1la2nsdigalinmvisefr)icwaenicgehtats 2(5twmog-/taiinl'e(dDMunannent-t'Wshietstn,ey0<U0t.e05s)t:, Inhalation - developmental 277 009176 sAtaLtiSstimcagl/lyms,igrneidfuiccatnitonisncirneamseeasn(pfe=ta0l.(0p4=b0y.t0h0e2)twaon-dtapiluepdbMoadnyn-wWehiigthnsey(,p U~ 0te.s0t2)),inatnhde incidence offetuses with partially ossified sterebrac. Oral:maternal significaAnc1e0as0simgene/dk)g,/draeyd,uctthieonosnliyn dfooosde tceosntesdu:mpctliioninca(lnosisgtnastoisftitcoalxisciigtnyif(incoanstcaetiasstsiicaglned), reductions in body weights gains (p< 0.05), and deaths (3 out of 12 dams), Oral developmental No the sptaartaimsteitcearllsy mseiagnsiufriecda.nt differences were noted between trated and control groups for any of Remarks ~Additional information to adequately assess the data: InhalationExposure "Trial One: mTrge/amt'meanntd.rceolnastiesdtceldionficwaeltsiagbnsdoofmemnast,emcharlomtooxdiaccirtyyofrorrhteraa,lcohnreom(oterrhaitnoolrorghye)ao,ccugrerneedraatl u1n0k.aenpdt 25 s`aipTgphneeiaefrioacunatcnteol,yfar1ne2dddulaceemtdhsaardtgiyebdoitndhufro1iu0nrgadntadrme2sa5tamtmegtn/htmea'tc;a2dh5oowmfteghv/eemr'e,x(npooonssGuirgDenifp1ie2c,rain1ot3d,d(aihfnifdgehr1-e7cn)oc.neFcseownoetdrraectoinnoosntuegmdrpobtueiptownoenwleyan)s, `tcroenacteendtarantdiopnasi.r-wfiotdhgsrtoautpisst.icaSligsniigfniicfainctanrceeduatcttihoenhsiignh-bcoodnycewnetirgahttiowneornely.asoLoibkesweirsvee,dstaattihsetsiec.ally csiognndiiftiicoannstoifntchreassetsudiyn.maeNanOAliEveLr waenidgLhtOsAwEerLefsoeremnaattertnhaelhtiogxhi-cciotnycoenft|raatnidon1g0rmougp/.m',Unrdeesprectthievely, was indicated. mbNgoo/dmey'f.wfeeitAgshdwtesetraweielroedbesmseiirgcvnreiodfsiccooannptitlhcyevdmiesaccirenretaaelsneaadnndcineeotyfheeper2x5eagmmnigan/namtc'iyoognrrootfuhtpehaiennfcdeitidunesntechseeodcifodnrtenrsooollrprgteivroeonauslp.apnaMyiert-arfneeadtf2em5te.anlt. tirehnlecarsteteaudsdeeydf.feiacntNcsi:OdAehnoEcweLeovaffenerdtiuLnsOtehAseEwciLotnhtfroporalrdtgeirvaoellulypopotsmhseaitnftiwaealdstsoptxaeiimcrei-btfyreadoef25w1a0msgaon/bdmse,2r5vaemsdtg.a/timUs,tnidcraeelrslypsteihcegtnicvioefnlidyci,atnwitaonss of indicated. "Trial Two: dCelsincirciabledsifgonrsorfiamlaotnee.rnaMlattoexmicailtybsoedeynwaetig10htangadi2n5dmurgi/nmg'trweeartemesnitmialta2r5inmtgy/pme'anwdasinlceissdetnhcaenacsontthroosles, ntarolettaehtdomufegonhrttaahntey2do5iffmtfgeh/reme'nm.ceeaswNuaorsconmtohetenrtsttsraoetiafstrtmieecpanrltlo.ydruescliagttnieivdfeicepafenftre.fcotrIsnmwaaendrcdeei.trieoUpnno,rd2teerodu,tthnoeofrc1ow2neddriaetmiasonnysdaoidefvdtehdreusresinteguf.fdeyca,ts NOAEL and LOAEL for matemal toxicity of and 10 mg/m', respectively, were indicated. 278 000177 cwSoeinigtgnihsntoufoedndevtDoealryoepmPmaiPennt(l6ao.l1wetgroxttihca2itn5ycmiognn/ttrmhoi'lssgv,sr.aol6u.t8phocg uognihsnitschotnetddrioolffssf)t.aetriesOntnicwaDalaslyynsosti4gsnatinaftdiics2atn2itcaPrlPle,ydupSciutgpinoibnfosicdiaynntpwe(uiDpgahbytos4dy `PsePi:xgnaim9fii.ncaa7tni1ton2ef5offecmttghse/wmeey'rese5..r1eUp0no.rd3teeirdn tcfhooelnclrooonwldisin;tgiDeoaxntyseo2rn2fatlPhPee:xsa4tm9ui.dny0,agtaaitoNnO2o5AfmEtghLe/map'nudpvssL.oO5r0Aw.Ei1tLhinfocoporhntdtrehovalels)lm.oopsmcNeoonptiacl toxicity of 10 and 25 mg/m'. respectively, were indicated. ulExposure Trial One: i0TnhhiacloeantoiuGotnDoefx1p22)o5.sudCrlaei.mnsicFadoliocsddigdcnuosrniosnfugmmrpacttaietommnaelannttdooxbfioc1di0tyy0wimnegit/ghkehgsdAawmPesrFeOthradetuddruiiccnedgdgwieensrtteartesiaiotnemdi(aolnnatieormdatelhasotshceoomsnepeaGnrDewdi1t11h;0 ctmoranaittrnoetldesn.aanndNceocooanftdprvroelergsgneraosnuicpgsnyswooerfrietnocnxiiodcteientdycefowoefrrfreeetnsaooltrwpeeidiogfnhostr.s,anoLyoikfeitnwhitsehee,riennpocriosddieugncnctiefisivoceafnptamrdaailmffefoetrerermnsacseosuncbsheat0nswdeen variations; nor were there any effects noted following microscopic examinationofthe eyes. Trial Twos eSfifmeicltasroonbsreerpvraotdiuocntsivfeorpcelrifnoicramlasnicgensorweinraennyootfedthfeoftethaeldoabmscsrvaatiinontrsiawleornee.notLeidk.ewise, no adverse. CONCLUSIONS sCuoppmormteednbotyntahuetdhaotar.'s conclusions and whether you agree: Theauthor'sconclusions appear 0 be REFERENCE TPerroavtiodgeenfiuclPcoitteanttiioanlooffsAtmudmyonrievuimePweerdf:luSotraopolecst,anRoEa.tee(tPaF.OA19)8i4. TthheeREatm.brFyuon-dFaemteanltTaolxiacnidtyApapnldied `MTeodviicciolnoeg,y.Ne4w:a4r2k9,-44D0E. 1T9h7i11studywasperformed at Haskell Laboratory for Toxicology and Industrial 2719 000178 REPRODUCTIVE TOXICITY STUDIES "RTiEtlPe:ROODRUACLT(IGOANVSAGTEU)DYTWOOF-AGMEMNEORNAITUIMONPE(ORNFELULOITRTOEORCPTEARNGOEANTEER(AATPOFION))IN RATS ARGUS RESEARCH LABORATORIES STUDY NUMBER: T-6389.6, 2002. TEST SUBSTANCE Identity: Ammonium Perfluorooctanoste, CAS No. 3825-26-1 SwRoeelrmueatirsotknossro:edfTtrhehfeerittgeeessrttatsseuudbb,ssttpaarnnoccteeecwwtaeesdrefrrpeocreemiplvaiergdehdtonweINenokfvolreymmaabtteitorhne7g,esa2tr0id0n0ignafgancdihlseittyopruaerndidtaytp,rreeonpoatmriettdeymfpsoetrrrmaeutnlugarttehi.omnds `composition of the test artic s on fle with the Sponsor METHOD `EMnevtirhoondmGeunitdaellPirnoetefcotliloonwAegde(nicy, (OEEPCA)Dw4e1r4e,uestecd):sTahbearsesquoirretmheentsstoudfytdheesiUg.nS.. "Typeof study (one-generation, Owo-generation, tc): Tuo-generation reproductive ticity GLP (Y/N): The study was conducted in compliance with the Good Laboratory Practice (GLP) r(eOgEuClDa)ti.onsTohfetrheeweU.rSe. nEoPdAeviaantdiotnhse OfrrgoamntihzeatGiLonPfroerguElcaotnioonmsicthCato-aOffpeecrtaetditohneaqnudaliDteyvoerlopment cinotnedgurcittyooffthtihse ssttuuddyy.haQvuaelbietyenAsdsoucruamnecneteUdn.it findings derived from the inspections during the Year study performed: 2001 SpeciesStrain: Sprague Davey ras Sex (males/femalesboth): Both Number of animals per doses 0 Routeofadministration: Gavage PmDaoRtsOiiSnnggbwyraegsgaicvmoaengfneir(fimosretds,iaxlawnwdeiettkhrseuapntirmtieso)nr:t ofFtainhvdee dgFurOroiufnpegsmoamfaltei3nr0gat.astcsTorpnetraitnsmuexendtpteohrfrodtuohgseheFoguOrtmogauetpsetwaertaritoesn,caodpnmatiritnunirusiettdeirounen.dtil and lactation. Doses: 0. 1,3, 10, nd 30 my/kgday. Perneemraattionngaetxspwoesrueregipveerniotdetfosrubmsatlaenscefeomnacleedsai(lPy,anbedgiFn1n,iinfgaaptparpopprroixaitmea:telMyalseiawnedekfsemoafleagPe 280 000179 `(amtalleeassatn7d0fdeamyaslebsefwoerreecgoihveanbidotsaatgieaosnod)ncceondtaiinluy,inbgeguinntnilintgheatdawyeabneifnogre(saapcprriofixciem.atFe1lyge7n0erdaatyison before cohabitatiaond) continuing until the day before sacrifice. cStoantsiustmipctailomnedtahtoa,dsduruasteido:nsCoofngteisntuaotuisodnaatnad(dbeoldiyvewreyi,gfhitttse,r abvoedryagweesigfhotr pcuhapnbgeosd,yfweeeidghts and Bpaerrtcleenttt'msaTleestfoetfusHeosmoorgpeunpesitaynodf Vmoarrtialaintcy,eaanndd cAunmaullyastiisvoefsVuarvriivaanlc)ew(erAeNOanVaAl)yzewdheusning (appp=ro0p.r0i5)a,teD(u.nc.n,eBta'rstleTtets'tsTweasstuwsaeds tnootidseingtniiffyictahnetstoartips>t0ic.a0l01s)i.gniIffictahencAeoNftOhVeAinwdaisvisdiuganlificant cgraosuepss.wheIrf ethteheAKNrOusVkaAl-wWaasllniostTaepsptrowparisatseta,tiis.t.i.cpal<l0y.s0i0g1n,ifitchaentKr(ups<ka0l.-0W3a),lliDsunTens'ts wMaesthuosedd.ofIn tMhuelrteipwleerCeogmrpeaatreirstohnasnw7a5s%usteesd,tFoiisdheenrt'isfyExtahcetstTaetsitstiwcaalssuisgendi.ficAlalncoetohefrtnheatiunrdailvdideulailvegrryoudpast.a If diensvcorlivbiend.g discrete data were evaluated using Kruskal-Wallis Test procedures previously Remarks - Detail and discuss any significant protocol parameters and deviations: FO Generation BThoedyFOweaingihmtaslsofwFer0emaelxeamriantsedwetrweicreecdoarildyedfowrecelkilniycadlursiingngs,thaebodrotsiaognes,pprereimoadtuanrdedtehleinveornietsh,e adnady doefbs. asancdriftihceen. oBnogdeystwaetiigonhtdsaoyfsF(OGDf)em0a,le7.a1t0s, w1e4,re18r,e2c1o,radneddw2e5ak(ilfnyecdeursisnagryt)heapnrde-oannldacctoahtaibointdaatyiosn(pLeDr)io1d,s5, d8u1r1i,n1g5t,heatnrdea2t2me(ntterpmeirniaold,bowdhiylweeiignhFt)O.feFmoaoled rcaotns,suvmalputeisonwevraelureescoinrdFeOd wmaeleeklaytsduwreirneg trheecorded weekly precohabitation period, on GDS 0, 7, 10, 14, 18, 21, and 25 and on LDs 1,5, 8,11, and 15, sEcshteroduuslecdyccloihnagbiwtaastieovnapleuraitoedd adnaidlcyobnytienxuaimnignuanttiiolncoofnvfiargmiantailoncoytfomlaotgiynbgegbiynntihengpr2e1sednacyesobfesfpoerermthein a evsatgrionuasl csymcelaerwoarscaosnsfeisrsmeadt.ion ofa copulatory plug. On the dayofscheduled sacrifice, the stageofthe oWniethmianlcearcaht dpoersafgeemaglreourpat,. cTohneseccouhtaibvietaotridoenrpwearsioudsceodns(0isatsesdigonfapamreanxtailmguemnoerfat1i4ondaaytss. tFoecmoahalbeitraattison, iwnidtihviedvuiadlenhcoueosifnsg.perPamreintnaalvafgeimnaallesmweearreoervacloupautleadtofroyr pllenuggtwheofrgeedsetsaitginoant,edferatsilG ity i0nDadned, gaessstiagtnieodnto ainnddexl.ittneurmdbureirngantdhesepxosotfopfafrstpumripnegripoedr, lltitre,r sniuzembaenrdovfiiabmiplliatyn,tavtiaiboinlistiytisn,dgeexn,elraacltactoinodnitiinodenoxf.tpherecednatm survival. and sex ratio. Maternal behavior of the da wasm recos rded on LDs 1,5, , 15, and 22. mFaOlgeenraetrsa,tii.oc.n, aanfiemraclosmwpelerteisoancroiffitcheedcboyhacbairtabtoinodnipoexriidoed;asapnhdyxLiDati2o2nf(odrafyem1a0l6etroat1s1),0noefctrhoepssiteudd,yafnodr weexlalmaisneidnftoemraglroesxsamliensiaotnis.on Gorfotsisssnueescraonpdsyoriganncsl.udeIdndeixvaimdiunaaltoirognanosfewxteerrenawlesiugrhfeadceasndanodrgoarni-fitcoe-sb, o4dsy twheyimguhst,anlidveorr,gaadnr-etnoa-lbrgalianndwse,ipigthutirtaatriyo,suwteerruescwailtcuhloatveiddufcotrstahnebdraciernv,ixk,idenfetyse,pisdpildeyenm,isov(awrhieosl,etaensdcs, cflauuidd)a.),Tiigshstuecspirdeitdayimneids,inprnoesuttartael abnufdfseermeidna1l0%vesfiocrlmeasl,i(niftohr pcoosasgiubllaetihinsgtgolloagnidcsalanedvawliutathiaonndiwnciltuhdoeudtthe 281 009180 prsiietgluheitctteaerpdyi,draiatddsyrmepinesar,lsegalxnadnfdprrsoo,mstvtaathgeei.ncao,nHtiurstotelorluaosng,idcwhaiiltghehxodavoimdsiunaeagttesi,gorncoeuwrpvasis.x pAaelnrldfgoorvroamsresidelsoe,sniroitngihsstswuteeesrstefisre,oxsmaemm1ii0nneradal.nvdeosmicllyes, histologically. All FO generation ats that did or appeared moribund were also examined. aHfotirsstwothlhioacgihecxeahslitberixotauemsdicnryaectdliuioccneiodyfofterrhtiseliptreyerbpmryonducumicbttheiervr,efomiorllgiianlngtsyt.oinmotrahtme,olrocpwoh-nocaleniodvgeym.iwsdei-rrd,eoosareldteegrlreiod.vueprsSpwheeaarslmtchpoynmodbfuefcsrtp.erdinign: or timeomstptililacinuttlyaa.rtaisonpndersmmioatrtspiwhdeocrloeongcreyencwtorerardteeidoenvisanlwFueaOrtgeeedenvienarlatuthaietolenedfftiencmaatulhdeearlaeettsp.itdesiRtdiasyt.smitTshohatefinFduOmgnbeoentredraeanltdiiovdneisrmtarlifbetuetrriatwosne,roef ps`aeeclxrvaiimfciinvceeiddstcoeonracGownDafsi2rp5meartfnhodereamebxdsa.emnicnFeeeodmfafilomerplpraartnestgawntiaitnohcnoyustsittaaesct.uos.nAfUigtrreomrsieosdfnmeaacptrpioanprgseyndtaoltfyte htnheoanttphdroierdgancniaocnt,tdarebaldtisovmweieanrrea.iltaenrd were sacrificed on an estimated day 25of gestation. Amfeatmlsaeclsheaenadtdusl,3edbflseoamcoardliefsisacemf,oprlaefttsheer(c1co0onmtmrpaollleegtsrioaounnopdf)t1w0heerfeecmoachloaleblsietccaattecidhoanfnopdrertfihroeodz1e0inn afFnoOdr mf3au0tlumerger/aaktnsga/laydnsaidys.odnoTsLheDegr2mo2eutiphnso;FdO3s. nseocttaipopnecairetsobtehatalviavielrasbalempaltetshewefriemoalfsocthoellreepcotretd.,but no other details were provided and theresultsdid EL Generation e`PTxuhppeecbFtoIeddgyelnwaeecritaagtthiitoosnnwbpeeurhpeasvriienocreoaarcndhdedlgiortontesrsLweDexrtee1m,c5ao,lun8p,they1ds5i.ocanancldea2dn2a.oimlyaO.lniePLsh)yDswie1c2ra,lealrsliegcFnoIsrd(geiednnceflrouardtiitnohgne vpmauarpliseatcpiauocnphssdfwareyo.rme eLlexDsaimo|niswneeardnedfeofrvoartlhtuehaetpercdeasufesoneocevfoitdfaelansittphap.tluessA.lalt PbFiIutphgs.etnheParutadptsiifodonurbnaetdfsdowreeeardeexaowmneiaLnnDaetid2oonn0oL.f2Dt2he2w2elribteaerseexfdaormoipnnueopdbsvifeaorbrvigelirdtoysson `rowih and viabilityof these pups gAfiruvoewuped)aosnwaiegnregeg(srLeoluDepcs2t.2e)d,AtftowrloecaFosInttgtiewnnoueermdaaetlvieaolnpuuapptuisposan,npderretsswueloxtifpnegmeailnie6t0epr0upptseortpagelrrroalutitspte((r3,600w0hmreaanlseppoaesnrsdisb6el0xe),fawesemsarilegenseeplduepc1st0edtp,heer pHFeu1apdgseapnteerrtahsteeixloenpveeplruopifstetnrhoetwefsrreolenetceatlxe-adpmarfiioncretcdaolnfstouritnguurreoedsasonbldesseeirxovnaasm.tiinoNanteifcoorrnospoesfxytuhailenmccralotusudsre-aasdtcicsotininogwnleeerdcerbsorasacsir-nisffeiccotedia.opnopTafrheitnchtee wphoyesdisrgiohbceleedphhaainlsdyt.otlhoeTgihbcreaalibnre,aviasnlp,ulaestepinol,ne.eannAadlntldhrytemhmuyasmiunfsirnofgmrpotumhpeosntwhereeorefestdehilsetcchatrereddeepdsuewplisetcphteoerudtspeufxuprsptehpreerrfiestxteeaxrmiwpneearrteiiotrnee.traiwenreed.for ctThohenertiFenlsuipgneegcnieuirnavtiteliFotnOhergaedtnaseywrebaetrfieoonrgeisviseraencsitfahineceds.adamFmes1.dgoesDnaeogrseaatglieeovsnelwfoeefrmtaehlgeeriatvteessntwosenurbcseetdaeanxicaleym,iannbedegdiinnftonhrienaggseaaotmfweveamaganininnnaeglraansd rppreaetapecunhtceiyda,lsbesexegpuaiarnlantmiianotgnu,roanbteidgoainyn.n2iA8npgotaosbtnlpedaaorfyrtua3m9nd(pLooDsmtpu2a6n)ri.ttsuFwm1a(sgLeInuDesr3e9ad)t.itoonBaosmsdaiylgenweaFitIgshgtwesenerwreearetiveoarnleurcaaottresddteofdocrwoahhagebenitorafattison, s`iobnleinmgasl,earnatapleerrmfaetmeaalsesriag.nmIefrntanwdaosmmaades. TsheicgohoacnboihmtaabteiitoanntpiteornioredscuolntseidsitnedthoefapaimrainxgiomfuFm1ogfen1e4radtaiyosn., 282 009181 pBeordiyodwaenigdhotnsotfhetdheayFo1fgseancreirfaitcieo.n BmaoldeyrwaetsigwhetrseorftehcoerdFe1dgweeneekraltyidonurfienmgatlheerpaotsstwweeraenirencgorded nweeceekslsyardyu)rianngd tohne LpoDsStw1e5a,n8i,ng1p1e,r1i5odantod c2o2h.abFitoaotdiocno,nasnudmpotnioDnGsva0l,ue7s, 10, for 14, the F118,g2e1nearnatdi2o5n (i `mgaelneerraattisonwefreemarleecorratdsedwewreeekrlecyodrudreidnwgetehkeldyosduargiengpetrhieodp.osFtowoedancionngsupmerpitoidontovcaolhuaebsitfaotritohne, oFIn mGaDtser0n.a7l,fo10o,d 1o4n, o1r8,ab21ouatnLdD2515a,ndfooond LcoDnssu1m,p5,ti8o,n11vaalnudes1w5.ereBencoatutsaebupluaptsedbeagftienrtLoDco1n5,sume 3rAatfte,smcbahlleoedosudfloesdratmshpaeclreicsfoin(cte1r,0olamfagtlerreosucpoa)mnpwdlee1rt0eiofcneoomllafeltcehtseedccaaocnhhdabffiortroatztheienon1f0oprearfniudotdu3r0ienammngaa/llkyegsi/rsdt,asyuatdnoodsnoenygrLtoDhuep2ss:eri3unmmfaealmneaasllyeasneds tcfoholerlrteehcpetoerFdt.O, bguetnenroatoitohnerwederteaiplsrweesreepnirtovetihddedreaponrdt.th Threesumlettshdoiddsnsoecatpiopneairtosbtehatavlaiivlearbsleamapltehsewteimree oafio pbFio2rsttghepsnaaernrtadutmigorpnoersilsoidat.letresDraewtaeirodnesp.euxpEasamcoihbnseiedrtvarefdewraasdetelhveiasvleeurtaytiteeodsifdwoerenrtvieifayrbietlmhietoyvneautdmlbefaersrotmatntwdhiecseeesxcotaficphnugdpabsoyx,.ofsttAihlnleobgi2re2tnh-isd,tayyllive distance was measured for al live 2 generation pups on LDs 1 and 22 tpNeasOrteeAndt.EalLTmh(aedloeNsseOcAaonEudlLdefnfoofrtctFb)Oe-pdaefrtoeernrtFmaOil,nfe1edm,Sailanencsed=tFr12e0a(tm1mgse/naktpgp/rredolapayrt.eidaAteec)N:tOsAAEwNeLOrAefoEsrLhnefaoFtltahlmeadlFoeOssessould not be edfseetmteaeldmeisn=ed10simnckeetgedaatym.enTtheelNatOdAeEffLecftosrwtehreeFs2egnenaetraaltliodnosoefsfstpersitendg.=Th3e0 mNgO/kAgE/dLayf:ortFhIe hgiegnheersattidoonse KcLioOdnnsAeiEydeLwree(iddgtohostesb-eatno|d-mcger/fmkifgne/acdlta)by,ofdtoyheFwOle,oiwgFehlst,taadnnoddsetFot2besr(taaeisdn,awbpeapisrgeohdptroirnaattsieio)g.:niTfThicehaenLtLOiOAnAcErEeLaLsfeofsroriFnOFtOphaepraevrneetnartlaalfnedmmaalleess is `tisgeercnmoeinrnsaatilidoebnroemddayl0weesbieigsh3ct0oanmsngid/dke0gr/ebddaaiy0,nbebwaesi1egmdhgto/nkragst/iidogsaniyof,biscbaeanrstveedrdeodanutcsttiihgoennihsfiigicnhaenkstitdddneoecsyre.ewaesTiehgsheitnLabOnodAdEyKiLwdefciogyrhwFt1esiagnhdtoodwboeosidegy.hrtweseliatgnehddt rigneaditunhsce,tiraaotnnidsosiinnolbtieovrdmeyirn,waekliigbdhontedsyy,awnaednidgbhsotpdsl;yeeawnnediwgeshiitgghngtiasfi-inctsaon-otbbrcsaheiarnnvgweeedisigphnrtsia,btsaoonladnubdtasd1uevrdeironangncsdoiShgpanlbieifteianctai,on ammnaetdrukrdeautdriiaonyng,,tdbheaecsrteediasoeenssdtioanstiibsnotgdicypaelwrlieyoidsg.ihgtnTihafenicdLanbOtoAdinLycLrweeafisogrehstFIignagpienonssc,trwuateniadonndienfcgermmeaoarlsteeassliiintsyca,obndsseoilldaueytrseeifdnotosodexbueal30 tdceeostnteesrdmuimnpedt:iouannld,lerobtsheercvoenddaittihoenhoifgthheestsdtuodsye,ensotetdr.eaAtmeLnOtAeElaLtfeodrcftfhectFs2wgeerneeroabtsieornvceoduaktdaonty dboeses. "Toxic responselefects by dose level - parentalFl: 253 009182 oTbosecrveefdfeicntsthienhFiOghg-ednoesreatgiroonupa.niSmiaglnsi:fiFcOanmtarleedsu;ctStiaotnisstiincablolydysiwgeniifgihctanatnidncbroedaysewseiingchltingiacianl wseirgen.s were pmreegrp/oikrogtd/esddaatfyotrdhoemso3es0tgmorgofu/tpkhsge./ddAaobyssadogolesuetpeegrrfiooouodpd,acnwodhnicslouenmtpsiitngiunoiifnnigvcauannlttuielisntcwereremraiesneaasltsiinoonroseiflganttiihfveiecsafntotuolddyy rcieondntushcueemd3p.tdi1uo0r,ninavgnadltuh3ee0sse oswifegrnteihfeoilbceasfnettravrneeddduricintghittohneesp3ii,dni1t0de.yrmaminidndeasl3,0blomedfgty/ckwageu/iddgaahytespwiiwdteihrdieynmsitehseo,nsseactsava3i,mnae1l0p,veeraisnoiddcsl3.e0sAm(twgi/ntkehgc/radonapdys.yw,itAshtbaostuoitsltufiltcueaildlw)ye,ights wpmrgeo/isktggah/tdsea.wype.irteuTitshaiergyna,ibflsieocfltaunattneldywireinigcghrhtetaasodefrtdehniaenlstl,hievsepr1l,we3ea,ns,ansadingdn1i0tfhimcygam/nutkslgy/wdieanrcyeredaaolssseoedsgiirngonuaiplfsi,dcoabsnuett-lygSrirogeundpisuf.icceadnKtailtdy3n0ey rsdieegcdnruiecfaeiscdafendotrlisynotihmnecer3eo0arsmgegad/nisknga/atldltahryeeaghrtioegudhp.gdrooAsuleplsg.ororugOpar,ngaawnnediwgsehiitgg-nhtiotf--itcoea-rnbtmrliaynianilnwcberoeidagyshetwderfiaotgrihotostawhneerdreorrasgtiiagonnssiwfaeimrceao.nntlgyall totrhfeetahlteeefdtadgarrneodunparsli.gchotrIktniecdxrneewayse.erdeatnohdbisctekhrenverseasdtiaionnsdtohfperto1hm0e.isaenneodnrcg3ea0onmfwgte/hikeggh/zsdo-antyao-dgtolesoremmeigrnruoalulposbs.aodayFnOdwevfieagmchautloelasan:tdiToohnfoetfwheteihlgeohtctesllosf Kidney weightto-brainweight were significantly reduced at thehighestdoseof30 mg/kg/day. s`iTgoniifiecfafnetcttsreiantmtehnet-FrIelgaetneedraetfifoenctasnaima3l,s:10,FaIndma3l0esm;gN/ekcgr/odsacyorpaincgeixnagmfirnoamtitoann raervceaasliendtshteatliastteircaalllaynd smiegdniifaincalnot,bedsosoef-trheelaftievderdteocrmeoadseersantetteormsliingahlt bdioldaytiwoeniogfhtthsewpeerleviosbosferovneed.orTbhoethabksiodlnuetyes.weiStgahttissotifcatlhley trliihgvyhemtruaksinddwnaessypslaelwesenowrseeirgseniisgfniiigcfnaiincftailnyctaldnyetdclerycedraeescaersdeeiadnsietndhetaht1ea0l3.l0antmrdeg3a/t0kegdm/ggd/rakoyugp/dsdo.asyeTdghroeosueapbg.sroolTuuphtsee.awTbeshioegluhatsbeosowfleuitlhgeehtwleeofifttgahhntedo/for "tThheeprraotsitoastoeftbrhaeinweaingdhtlsefofadtrheensaelmgilnaanldvweseircelessi,gnwiiftihcaanntdlywdietchroeuatsfelduiidn, tlhieve3a0nmdg/lkefgt/adnadyrdiogshatgkeidgnroeuyps,fo sttihhgeenltieefirfcmaeinnsiatllsy,biowndictryhewaaesneiddghawttist3hwmoegurt/ektsghi/egdntaiufyniiaccanandtallhybiguihgneicrnr.eeaaTshaeenddriantthiaelolsortifrgtehtahteteedswtgeirsiogtuhoptsts.heoTftheterhmrianlteaiflotsbeopoftiddhyiedwyewmieigishg,th,tesfwteorfe w`1ae0urmdegai/nekcpgri/eddaiasdyeydmaianstd,|hrimiggghhektrge./pidTdhaieydayrnmatidishosiaognfhdtehrb,reawiwinetithgohsttthoaetfitstetirhcmeailsnseailmginbnioafdliycvaewnsecieicglahetst1 wwaientrdhe fs1l0iugimndigft/iokcgta/hnetdlabyyr.aiinncTrhweeeaisrgeadhttiaots ogfrtohueps,ivaenrdwtehieghrta-titoos-obfrtaihnewleeiftghatndwrrieghtsikgindifniecyanwteliyghitnsc-rteoa-sberdaiinntwheeig|hmtgw/ekrge/dsaiygnainfidchaingtlhyerindcorseaasgeed all treated groups. The ratiosofthe spleen weight-to-brain weight were significantly decreased at | in m1g0a/nkgd/d3a0ymagn/kdgh/idgahye.r,Tahnedrtahteiorsaotfitoshoefltehfeatnhdymruisghwetiegshtets-twoe-ibgrhati-ntow-ebirgahitn wweerigehstigwneirfeicainntclryeadseecdreianstehdea3t ltmeagsntfidkssgodnolafyyh)iaagnnhdd-dh3oi0sgehmegar/nkidgmo/asdlaasgye.(cgyrTtoruoeppsal.tasmTmehincetsrheeylpraeattreitdorsomwpihecyrroeasnscdiogpnviiacfciuccoahlnaatntlgiyeoisnnwocerfertaheseeocdbslaetsro1v0efdmtgih/nektaghd/erdeaandyarle(nrcaiolgrhttex) oafbnesmdaelirenvste:hdeSitnlaithvieisrgtoihcf-adalolnsyiesmiaagnlnisimftairlcaasnt(te4di.n7wcivrteeharss3eu,ss1i50n.,4tahinencdao3vnte0rrmoalggse)k.ngu/mdStbaaeytris(stohiefcpaaeltsloytcrseoiluglsnuilsfatiracgahenystppederetrcrr2oe1pahsyde)as.yisnFwlbeordey ddwaueyriisgonhgtfsapgraeenc)do,hbaaobndidytadwtuieroiingnhg(trgegecasoitrnadtseidwoneoranentdohbelsadcetraavytieocdno.hianbDhieitcgarthie-oadnsoesbseegaiannnia,mbaswlohsleuontneFdf1aoyogsdenc5e0ornaastnuidomnp5t7riaptosonswwteewrreeaen9oi2bn-sg1e,0r6ved during during precohabitation and during gestation and lactation in animals treated with 30 mg/kgday. 284 000183 TTooxsiic reeffsepcotnssienleFfIecgtesncbryatdioosnemleavleelp-uopfsfscpornisnigst(eFdIo/fFs2i)g:nificant reductiinopnusp body 3iwne0cirmgegha/tskegos/ndiaanypr.eeraOltimnteeenrtra-btaeslwiaastseindmotdrheieabt3uh0snmd(g7s/aakcmrgiimdfaialcysedgootnarld)aoowyneudr3e9ayprpseopsot1r,wte5e,adnaiinnndgF8Ianomfdallaaencsotatithineotnrh.weaSiisggnfhiofudinocdasnedtegaroduapnof cBdoaohydayb1i0wt7eatipigoohsnttswaenaadnnddiunbrgoi,dnygbuwttheetihgeehnttmiargjeaoidrniostsyiwonafgreptehsretiaFtoiIdstimincaaalllelytasrtiesgantwieefdirgceraonfutopluysn.rdeSddteuaactedisdtoipncraidloalryystsoi2.g-4n4nidfpidocsuatrnwtienragendiuncgt.ions pi1no5s:bt2ow2de,ay3n6iw-ne4gi3.g,ht5Bs7o-wd6e4yr,ewaeonibdsge6hr4v.ge7ad0inapstows1et0wreaeannadlisn3og0.smiggSn/tikaftgii/csadtniatcylayldluryreiidgnungciedfdaiycisnant8,h-e1d5o3,s0e2-m2rg:e2/l9ka,tge/2dd9a.ry3e6dgu,rc4ot3iu-op5n0so,niandnabdyosd5y01-.85,7 pcweeorinigsohudtmp(gtdaaiiyonsns w1v-ea7lr0ueepsoobswsteewrreevaensdiingfgnoi)rf,itcwhahenitellneytirrreeelddautocisveaedgfaeotop1de0rciaoondnds(u3dma0pytmsigo1/-nk1gv1/a3dlapuyoessdtuwwreeiarnneginstighg)en.iefniAtcbiarsneotllpyurtoiecnocfhroaeaobsidetda.tion roSetbsaspteeircsttviievcdaellilyny).hsiiggTnhoi-xfdiioccsaenetfafdneeicltmsaaylissn ivFne1rssgeuexsnueacrloanmtcaiutorunrreafntetimoacnloen(ttprhuoeplassv(ce5or2na.sg2iesdtdaeaydysooofffpsarigegepnuivtfeiicraaslnutsser4pe8ad.ru5actdtiiaoonyn)soswfienargpeeu,p body htwiregeihagethsmttenodtno-arseepleaortfe3ldi0tmeomrrgt/bakalgsi/itdsyaiy(n.6tahnSetiam3ta0ilsmstigct/aoktlaglly/)dswaiagygnsirfooibcusaepntrovdneedcdraienyasFsIe1s,f5ie,nmaablonedsdyowonefiplgoahsctttaswtieaoannn.dibnAgonddyaiynwsceri2eg.ah8steagfiantihnes JwDaeeccrtreaetoaiosbnesseirnivnaenadibmisnaolhlsiugtthr-fadotooesddewcaiontnihsmua3ml0pstmoigno/kndga/wydesarye8.,ob1S5st,eart2iv2se,tdiadcnuadlrliy2n9sgidpgonaisyftsiwcea1an-nt8i,dne1gl,a5yasnpdiondssuterwxieunaagnlilmnacagttaautnirodant.diuorni(ntghe davaeyrsoagfeadgaeyovfervsaugsi3n4a.l9pdaatyesnocyf)agwee,rereosbpsecetrivveeldy)i.n high-dose animals versus concurrent controls (36.6 Statistical results: wiFnaOrtgeheenrheeripagotrhit-oedndosfmeoarglrmeoouaspnt.imoaSflisgt:nhiefdSitcoaastnaitsgteriecpdaelulrcyitoisdoingasnni(dfpicc=oan0nt.t0ii5nnucoirnepga=sue0ns.ti0(lp1t<)e0ri.mn0ib1no)atdiiynocnwoleifingicthahtleassnitdgundbsyowdienyrtewheeoib3s,geh1r0vg,eaadinnd. dr3ue0lraimtneigvketghf/eodsoaedypceodronissoeudsmgpratotuitpohsne. v3a0Albumsegos/lkwuget/redefaooybodsdoecsroevnegsdruomiunpptt,iheownh3i,vlae10l,suieagsnnidwfei3rc0eanmatgli/snokcgsr/iegdanasieyfsiwc(iaptnshtil0ny.0tr5heodosurecepsdeam(0pe,0<1)0i.0n1) s3p.eermi1io0nd,asa.lnvdAets3i0ncelmcegrs/o(kpwgsiy/t,dhasyat.antdiAswtbiisctoahlloluuyttesifwglenuiiidfg)ih,ctapsnrtoosrfteatdthueec,tlpieifottnusaitn(adpry=r,i0gl.het0ft1c)apniindditrdeiyrgmmhiitndaaedlsr,ebnolaedltys,cswapeuiidcgahet.espaiwndeidrdeytmhsieysem,nusat 0ww.ae0sr5esoiarglnspio=fis0ci.ag0nn1itfl)iyciiannnttchlreyearIs,eed3d,u(caben=dd0(1.p00<1m)0.gi0n/5adlolradpyo<sed0-o.gs0r1eo)ugparsto.u3p0sK,migdb/nkuegy/sdiwagenyii.fgihcTtashntewleyarbdeseocslirugetnaeisfweiedcia(gnpht=lty0o.ifn0ct5rhoeearvspeeed.r(p< si0i.ng0cn1ri)eifainsceadtnht(elpy3sr00e.dm0ug5c/ekodgrf/pod<rasy0o.g0mr1oe)upoi.nrgaalAlnllstroaatrtgteahdne gwhreioigughphsdt.o-soOe-rtggeraromnuipwn,eaialgnhbdto-sdtiyog-nwibefriiacgiahnnttwlaeynidignrhcarteriaaotssieowdsefwroeerorsetihgenirfoicragnatnlsy among all treated groups. (wFPeOi=gg0he.tn0se-5rtaootr-i{open=rmf0ie.nm0aa1ll)aebtoatndhiymeawlhesii:gghhTetshtaendwdoesoiefgohtfthse3o0lfetmhhgKekigde/nfdteayya.nwdeirgihgth-ttok-ibdrnaeiyn, waenidghthtewreartieossiogfnitfhiecsaentolrygraenduced 285 000184 iHFnIctrgeeabnsaeesrsiastiinwotanrseoafotfbmsspeernirtnv-gre:edlaiMtnaetldhaedse;3a0tShimsggni(/7fkigac/nadniatmyarlegsdruooctutpai)oownnsedr(apey<sr0e.1p,0o15r),teaindndpinuopFf1bloamdcatylaetwsieoinng.hhtieeonniafipeearnt dahneioagthdhdeoornswdeaagsyrsof2uo-pu4ondfpod3se0tawdmeeao/nnkiend/gad.yayB.1o0d7Oypnoewsetaiwgtehatwnsaisnagnm,dobrbuiotbdutynhedwemsiaajgcorhritifgitcayeiodnfsotnwheedraFeyIs3tma9atlipseotsirctaawtlselyawneirnegfaonudnd otsbriegsanetirefvdiecgdarnoatutlpys1r.0eadSnutdcaet3id0stpirmcigao/lrlkytgo/sidagannydifddiucurarniitnnggredcdaouhycastbi5iot1na5st,i(op2n=2:a02n.9d0,5d2uo0rr-i3np6g=,t04h.3e0-1e5)n0i,irnaebnoddod5sy0i-wn5egi7pgephrotissotdwweeirnaenaillng B0o1rdopyu=p0wo.en0i1gd)h,atydsogsa1ei--n8rs,elw1ae5t-re2ed2,arle3sd6ou-cs4ti3ig,onin5fs7i-ci6na4nb,tolaydnyrdewd6eu4ic-ge7hd0t(pgpois=nt0ws.e0aw5neoirnregp.ozbsS0ea.ri0v1se)tdiicfnoatrlhyehe3si0egnnmtiigfriKecgad/nodtsa(ayog.e0.05 p(peoprs=it0ow.de0a(1n)dianaygts).110-wa1h1ni3dlep3or0seltmawgte/iavknegin/fgdo)ao.dy cdAuorbnissnuogmlputthteiofeonnotvidarelcuopenrsseucwmoephraetsbiiioganntivifaoilncuaepnsetrwlieyordien(cdrsaieygasnsie1fd-i7c(0apn<tl0y.r05edourcpesd vs0ee.0pr1as)ru.astS4it8oa.nt5)swidecaarylesloyofbssiaeggrneiv,feridecsaipnnetchtdiiegvlheal-yyds)o.s(epF=aen0m.ia0m1la)eliss;nvsesiregsnxuiusfailccoamnnacttuurrreradetunictotnicoo(nntsthreo(alpsv<e(r05.a20g.1e3)ddiaanyypsooufpfpbaroegpdeuytia oi`wnneeirpgcohaststeowneinantpireneragtmdlieatnyetsr-r2be-al8sastaeidtnhmteohrehai3lg0ihetmsytg(Kd6goas/nedoiamfay3lgs0rtomouytpa/lk)oewn/addasayy.osbsS1e,tra,tviesadtniidcnalFlolyf sfileagmcnatialftieicsoann.t dAencreases 0o(nP0=1d)0a.iy0n5sa,obrs1op5l,=ut20e2.,0f1ao)onddinc2bo9onpdsouysmtwpweteiiagonhnitnswgea,rnaednobdbosddeuyrrviwenedgigldahuctrtiagtnaigoinnd.saywSseirg1en-i8of,ib-csa1enr5tvdepedocsirtnewahesiaegnshi-(ndpgo2sse0n.da0n5diumorarilnpsge 000...000432))) xvlaeucrtasaultsiocmnoanicrnuaarntrieomnantlsc(ottnhrteeraaovtleesdr(aw3gi6et.h6da3dya0oymfsog/vfkagga/igdneaaylv.eprasStutesantc3i4ys.t)iwcaedlralyeysosiobgfsaneigrfevi,ceadnretisndpeehclitagiyhvs-edl(yov)se.e0a.n0i1m)ailns `oFmrIedgPiean=nerla0o.t0b1ie)ostnroaafdtutmlhetenatlniriveemlraaltsto:emdoMedafeflreeacstt;seaNttcor3S,oisg1c0h,otpadinilcdat3eix0oanmmgoi/naktfthgi/odpnaeylrverivasenoagflienndgseftarotoirmsbtitocatanhllakyricsdainsgenyiisnf.itchaSenttaltait(esprtsailc0aa.lln0y5d aasliblgsntoilrfuaittceeandwteg(irpogu=hpss0..o05fTtohhree aplbi<svo0el.u0(1tp)e=,w0d.eo0is1eg)-hraseonldafttsehpdeldeeeecnfr(epaa=sned0so.0rir5nitogerhrtmpiK=niad0ln.0eb1yo)sdywweewrereiegsshiitggsnniiwffeiicrcaaenntotllbyyseddreevccerrdee.sasseTedhde(atns ad0.en0cd0r)eleafistneatddhre(epn3<a0l0m.gg0l/1a)kngdi/nwdhaeeyred1os0siagennigdfrio3cu0apn.mtlgyT/hkdegec/ardbeasayosldeuodts(eepwg=eri0og.uh0pt5s.oofrThtpheeeat0bh.s0yo1lm)uutsienwwatehseiag3lh0stomofgts/ihkgnegi/fpdiracoaysntdtaltoyes,agbreain `rKriooduunppes.y.sTTthhoeetahretatotiseorsomoiffntahhleebwowedeiyigghwhtetsisgoofhtfthtsehweesIrcaeenisntiaeglsntivife,iscwiacinlttehlsy,aniwndictrwheiatashneoddutw(iptt=hheo0ut.tu0nfilocuraida,pl=vbue0g.ri0n1ae)nadianenadlhltawhneedartiieggdhhtt thtoeisgtthiheser.ttoeTrthmheientraealtrimboiosnodafyltwbheeoiwdgeyhitwgewhietgrhset,osfiwtgehnrieefilscfiatgnnteilpfyiidciainndctyrlmeyiassi,endclre(fepta<scea0du.d(0ap5seop0ri.pd0i5<doy0rm.i0sp1,s)ra0it.g0h11t0)pmaitgd3i/dmdygmai/ysdaaannydd barnadin fmhiievgfehkrergw./ediTaghyheta-rnoad-tibhorisagoihefnrt,wheewiigwthehtigswhaettrioesfitscihgaenissfieigmcniainnftaillcyavniecnsecirc(elpaes<sewd0i.t0(h5p)f<lu0ait.d011t)oaintnhdeth1be0ram|mign/gkwgek/igdg/ahdyta.yweTarhneedchrraitegiahoessroefddotashtaeg| e dreo0cu.rp0es5a.soeardnp(d<pt<h0e.00r.1a0)t5iioonsraolpflt=thre0e.al0te1efd)t aagtrnod|uprmsig.g/htkTghK/eiddarnayeiyaonswodefihgithghshee-rso,p-labenreadniwtnehieegirhagtthi.ottso-wobfetrraheiensitwghenyiigfmihuctsanwwteelirygehitsni-cgtrnoei-afbsirecadain(ntply weight were significantly decreased (p< 0.05 or p< 0.01) at 10 and 30 mg/kg/day. The ratio ofhe left 286 0090185 Tmahnged/srdeigarhaytt.itoesstFweeesmrwaeeliesgsihg:tn-iStftaiotc-iabsnrttailicyanliwlnyecirsgiehgantsiefwdiec(rapen=tiin0nc.cr0re5eaaosseredpsi(<npt0<h.e001.3)01ma)gt/i1kn0gt/mhdegakayevgae/nrdadagyhei(ngihugemhrbtedoresssoaigfseoegnsrltoryuo)pusas.nd 30 dsstioaesgneeisafnipiceamrnal2d1secodrnaeyadssaeywsse(r5ep0<oab0nsd.e0r5v7oerdppons<thw0ie.ga0hn1-i)dnogis,nedbauonrdiiymnagwlepsirg(eh4ct.os7bavabenridsautbsiood5ny.4(wrieeniccgoohrntdtegrdaoio)nn.s twhSetradetasoyibccsaoelhrlavybeidtiatihoinghpdberecegrcaeonah.saewbshiae(tnpi<oFnI0.ag0ne5dneodrruarptii<nogn0.gae0ts1t)awtieniroanebsa9on2ld-u1tl0ea6cftdoataoidyosncooifnnsaguenm)pi.tmiaaonndtrwdeeuarrtieendogwbigseteshrtva3et0diomdngu/arknigdn/gdladacuytr.atiinogn, Significant eFl2atgeendeerfafteicotnsoofnfsapnriyngo:fthUendoebsretrhveecdopndairtaimoentserosfwteherestnuodtye,dnio stahetsFi2cgaelnycrsiaginoifnicoafnfts,prrienag.tmentRemarks: nePsrutimrobursetrsoaomgfaetisipnndgee,rpte2hn1ededsntatuydsoycicanuuhrtirhgoehrn-scdenososoeftaneesiadtmrasutlsastiins(t5ti.ch4aell2vy1ersdsiugansy4isfo.i7fcianontbscieonrncvtrareotalissoe)n.iwnFaotsrhedtahevitseerrcmaailgnceueldna.utmiobTneh,rishsetoyfpe of anbcaaellccyuoslniadtsuictohtnaetcdasnthoobdweeeutdeetrdhmeiarsne awwehsreeetrhneeorefftofhreerceetffsiescottnsrutolhnyeatehnsterfeufssetcrtc.uysclc3eysMclteCh,eorbmeuptwaeanrmyeon(ro2e0d0die2ft)fierlreeecdnecnaetnslay1lycsohimespslnheuotmuebldedarhnoefn a`fcemomonandlugecsttehwdeitbchoyn2ttrh3oeldUyaSansdEohPfiAgesh(tdr2u0os0s2eo)rgrawoliustpohsd.em4Tohndseaiycrsyoactfleeddsiwtehesatrtreuteshveairnleutwaheterecdeonntaorsodhliafavfniednrgehncicigethshedirnoestgehueglrsaortupr4e.o.5cydAcnalayelyses pdcioyesessltierbsuls(yR(p)d,seefuuindneoevpderanesgcn4ya-cn6ltid,nag(yP(dSIiPRe:;sdtdereuffsiinnpeeedrdiaaossdbs-r)gireeexfatpteeenrrdieodddasyesswtiortufshe(iudrkerofeeigyunlteaedrsa)psaot3treoprrenr4)siodsratypesnetroeifsotdcrsouosifl(pPerEdo:lsodmenefgaierndse)d, daisffSe-roerntgrienataenrydoafystohefpcaormaimfeiteedrssmmeeaarssu)r.ed.The dataarc summarized in below. The (wo groups were not ROvarian Pattern Ri -y PSP. PE Type Irregularity Total 43ddaayyEdsitersutrsus no patie 1C8ontrol 10 2 2 6 11 APFO 2(300mglkg) 9 1 2 6 1 tThheusw,atyheiniwnhcircehasethien tchaelcnuulamtbieonrowfastdronue,saangdesispoert21bidolaoygsictahlaltywmaesanniontgefdulb.y the study authors is du to Parental Males (0) 287 000186 OclnienicFaOl smiaglnesr(aetmaincitahteio3n0,mcgo/lkd-gt/od-atyoudcohs,eangdroduepcrweaassesdacmroiftiocredacotnividtay)y.45Noefctrhosecsotpuidcyedxuaemitnoaatdivoenrisnethat asncihmeadlulreedvesaaclreidficae.palSetaatnisdtitcaanlllyivseri,gnainfidcarnetd itensctrees.asAesllinoctlhienricFaOl sgiegnnesrawteiroenamlasloeoabtsesrsvuerdviivnemdatloe ras in the high-dose group that included dehydration, rine-stained abdominal fur, and ungroomed cot, `Saingdnicfoinctainntuirnegduuncttiliotienrnsmibnoadtyiowneoifghttheasntdudbyoidy twheeig3,ht10g,aianndwe3r0emrge/pkogrt/eddayfodromsoesgtrooufpst.he dAobssaolguetpeerfiooodd wh`ciolnessuimgpntiifoincavnatluienscrweearseesalisnoresliagtniivfeicfaonotldycroendsuucmepdtdiuorninvgaltuheessweepreerioobdsseartvtehdei3n0thmeg/3,kg1/0d,aaynddo3s0e group, mkgiday within those same periods. aNsosetsrseeadtmiennctlu-deilnagt,ednuefmfbeecrtssowferdeayrsep1o0rtiendseamtiannaytde,osneumlbeevrelsofforraansyothfatthmeatmeadt,infgertainldityfeirntdileixt,y npuarmabmeertserosf rpartesgnwaintth craotnsfpierrmerdatsmainticnoghadbaitteastidonu.rinAgtthneecfriorsptsay,ndnosneecoonfdthweeeskpoefrmcophaarbaimteatteirons,eavanlduantuemdbe(rspseorfm `number, motiorlmoirphtolyog,y) wereaffected by treatment at any dose level Amgt/nkegc/rdoapys.y,Asbtsaotilsutticealwleyigsihgtnsifoifctanhtelreefdtucatnidonrsigihntteeprimdiindaylmbidoedsy,wlefitgchtasudwaeerpeisdciednymaits,3,s1e0m,iananld v3e0sicles (siwgintihfiacnadntwliytrheoduutcfelduiadt),3p0romsgt/aktge/,dpaiyt.uitaTrhye,albesfolauntderwigehitgahdtroefnatlhse, ssepmleienna,lavnedsitchleysmwuisthwoeurtefallusiod was siingcnriefaisceadntilnyarlledduocsecd-girnouthpes.10Kimgd/nkegy/wdeaiyghdtossewegrroeups.ignTifhiecaanbtsloyliuntcerweeaisgedhtionftthhee1,li3v,earnwdas10simggn/ikfigc/adnatlyy dwoesieghgtroaunpds,rabtuitosswigenriefisciagnntilfyicdaenctrleyaisnecdreinastehde i3n0almgt/rkega/tdedaygrgoruopusp.. OArlglaonrgweainghwte-itgoh-tb-rtaoi-ntewremiignahlt body ratios owregraenssiagnmiofincganatlllytrreeadtuecdegdrofuorpss.ome organs at the high dose group, and significantly increased for other oNrogatnsr,eatwmietnh:trheelaetxecdepetfifeocntosfwienrceresacseedatthnieccknreospssyanodf uprpoomnimniecnrcoeoscfoptihceezxoanmaingaltoimoenruolfostahearnedproductive. vacuolationof thecel of the adrenal cortex in the 10-and 30 mg/kg/day dose groups. `prSeesreunmtainnalayllsissamfoprletshetFesOtegde,neinrcaltuidoinnmgacloenstrsolasm.plCeondtartolthmeaelnedsohfacdohaanbiatvaetriaogne scohnocweendtrtahtaitonPoFfO0A.0w3a4s4. 0.0148 ug/l mu/kg/day dPoFsOeAg.rouTpsr.eated males had 51.19.30 and 45 3212.6 ug, respectively for the 10 and 30 Parental Females (FO) NNoo ttrrecaattmmeennttr-erllaatteedd defefaetchtssowreardevreerpsoertcleidnifcoarlbsoidgynswweeigrhetsr,epboortdeydwienipgahrtengtaainls,faemnadleasbastolauntye daonsderleelvaetlive food consumption values. "nTahteurrealwdeerleivneorytraenadtmletnetr-eolbasteerdvaetfifoenctsswoenreesatfrfoeucsteedybcylictirye,atmmaetnitn,gtohartfies,rtitlhietynpuamrbaemertseorfs.daNmosnedeolfivtehreing (litntersu, tmhoebfdduearamrtsionwoitfhgeosnteatoiromn,otrhelaivveerboargnespfuoprs/imnpulmabnetratoifonprseigtneanpterradtesl),ivtehreednulmitbeer,rstohefdgaesmtsatiwointhindex 288 000187 `stmielalnbobrinrtphupwse,igdhatmsswweirtehcalol pmupps adyitrnogac,obnltilvreobelosrnamaonndgstaillllbtorrenatpeudpgsrovuiapbsi.lity index, pup sex ratios, and Nweeicgrhosp,syanadndorhgiasnt-otpoa-tthoelromgiincaallbeovdayluwaetiigonhtwraetrieoaslwsoeruencreomarmkapblae.rtoaTecbromnltirnoeall bvaolduyeswefiogrhatlsl,troeragtaend `tghreosuepso,rgexacnewpetigfhortsk-itdon-eteyramnindallivbeordwyeiwgehitgs.ht Tahndeofwetihgehtlsoetfktihednlyetwaeingdhrtitgoh-tbkriadinneyw,eiagnhdt the ratios were of wsiegingihfticwanatslyalrseodsuicgendifaitcatnhtelhyirgehedsutceddosaeto3 fa3n0d m1g0/kmgg//dkagy/.dayT.he ratio of liver weights-to-terminal body Rinesaullltssamopfltehse steesrtuedm, aenxacleypstisinincoFnOtrgoelnserwahteiroen females the level sampled on was below LD the l2i2mistshoofwqeudantthiattaPtiFoOn A was present (r0e.s0p0e5c2t8iuvge/l1y).forTtrheeat1e0dafnedma3l0esmgh/akdg/adnaayvdeorsageegcroonucpesn.tration of 0.37:0.0805 and 1.02+0.425 ugh, FI Generation - Males tNroeaetfefdeactnsdwceornterroelpgorrotuedpsawaenrye dnoosteedlefvoerltfhoerntuhmebveirabsiolfitpyuapnsd sluarcvtaitviionngipnedircelist.ter,Ntohedipfefrecreenntcaegsebemtawleeen spiugpnsi,filciatnetrlsyirzeedauncdedavienrtahgee3p0upmgb/okdgy/dwaeyigghrtoupeprolnitdtearyast 1b,ir5t,ha. ndPu8pobfodlayctwaetiiognh.tOoFntahpeerpuliptstenrebcarsoipsswiacds. abrtaiwne,ansipnlge,ennoanstdattihsytimcuasllaynsdigtnhiefircaatnito,sotrfeatthmeesnet-orreglaantewdeidgifhftesretnoctehsewteerremionbaslebrovdedy for the weight weightsof and brain the. weight Sdiogsneifgircoauntpoifnc3r0eamsge/skign/dtareya.tmeOnnte.rrealtatweadsdmoeriba(u7ntadnishamcarslisficteotdalo)nwdearye 3r9eppoorstetdweiannFi1ngmaalnedsaninotthheerhwigahs found dead on postweaning. day 107 postweaning, but the majorityofthe FI male rats were found dead on days 2-4 ofStaetnitsitriceaplloystsiwgenainfiicnagntpeirnicord.easTasheisneclsiingincsalisnicglnusdoefd atonxiicnictryeawseerdeianlcsiodeonbcseeorfveadnniunlFa1r cmoanlsetsridcutiroinnogfmothset tail and at all doses, with 30 mg/kg/day in sthaetintuicmablesroigfnimfailceanrcaetsattthahte w1e, r1e0,eamnacdi3at0emd;g/akngd/daaysi;gnaifsiicgannitfiicnacntreianscereinasteheat 10 incidenceof mekgiday. urine-stained abdominal fur, decreased motor activity, and abdominal distention at 30 `Bcoodhaybiwteaitigohntsanadnddubroidnyg wtheeigehnttirgeaidnosswinegrepesrtiatoidstiincaallllytsriegantiefdigcraonutplys.reSdtuacteisdtipcrailolrytsoigannidfidcuarntinrgeductions pinosbtowdeyanwienigg.htBsowdeyreweoibgshetrvgeadinast w1e0raenadls3o0smiggn/ikfgi/cadnatyldyurreidnugcdeadyisn t8h-e153,02m2g-2/9k,g/2d9a-y36g,r4o3u-p50o,n adnadys501--58.7 15-22, weigh 36-43, 57-64, and 64-70 gains were obscrved for pthoestewnetainreindgo.saSgteatpiesrtiiocadll(ydasyigsni1f-i1c1an3t,podsotswee-arneilnagt)e.d rAebdsucotliuotnes fionobdody p`ecroinosdum(pdtaiyosn 1v-a7l0uepsoswtewreeansiignngi)f,icwahnitlley rreeldautciveedfaotod1c0oannsdu3m0ptmigo/nkgv/adlauyesduwreirnegstihgeniefnitciarnetlpyreicnochraebaisetda.tion wStearteistoibcsaellryvesdiginnifhiicgahnt-d(opsse 0a.n0i1m)adleslvaeyrssiuns sceoxnucaulrrmeantturcaotnitoronl(sih(5e2.a2 vdearaygseodfaayogfeprveeprsuutsia4l8.s5epdaaryastoiofn)age, respactively). 289 000188 Nproeganpapnarceyntinedfifceecsts(nwuemrbeeorbosfeprrveegdnaonncaineys opfetrhne umamtbineogrforraftesrttihlaittympaatreadmeatnedrsraitsncilnucdoihnagbifterattiiloitny, and wriestphecctoinvfeliyr)m,edthmeantuimnbgedratoefsddauyrsitnog tihnesefmirisntawteee,kt.heNnoumsbtaetriostfiacatllsy sthiagtnimfaictaendt,, atnredatthmeennt-urmebleatroedfrefaftescts were observed on any of the sperm parameters (motility, concentration, or morphology). Nmeee/rkoes/cdoapyicraenxgaimnignfartioomntarnevaeraalesdisntatthistliactaelrlaylsaingdnifmiecdaintantrleoabtamseonft:trheleatleidvereftfoecmtosdaetra3,te1t0o, asnlidgh3t0dilation ofthe pelvis of aonrboeth kidneys. Sotbasteirsvteidc.allyThseignaibfsioclauntt,e dwoesieg-hrteslaotfedthdeeclirveearsweesrien stiegrnmiifniaclanbtolydyinwceriegahstesdoafnpdartehnetaablsoFlIutmealweesigwhersoefthe sKpildeneenyswewreeresisginginfiifciacnatnltylydeicnrceraesaseeddatinaltlhetr|ataenddg3romugp/s.kg/Tdhaeyadbossoelugtreowuepisaghntdsosfigtnhieficleafnttlaynddleocrreriagshetd in t1h0ean30d m3y0/kmgg//dkagy/ddaoysedogsreougpr.oupTsh.e Tahbseoalbustoelwuteeigwhetigofhtthoeftthheympurosstwaatse,ablrsaoisniagnnidfilceaftntaldyredneaclregalsaenddiwnetrhee sveisgincilfeisc,anwtiltyhdaecnrdewaistehdoiunttfhleui3d0, lmigv/erkga/nddalyefdtoasnadgreiggrhotuKpi.dnTehyesrtaotitohsoe ftetrhmeinwaeligbhotdsyowfeithgehtssemwienrael stihgentiufniciacnatallybiungcirneeaaseadndintahlel rtirgahttetdesgtrsoutpos.theThteerrmaitniaolsobfotdhyewweiegihgth,sweofrtehsig[nefitfitceastnitsl,ywiintchreaansdedwiatth3out empgi/dkiyd/ydmaiysaannddhbirgahienrt.otThhee rtaetrimoisnoafl tbhoedwyeiwgehitgshtofwetrhee lseifgtneipfiicdaindtylmyisin,clreefasceaduatd1e0pimdgi/dkygm/idsa,yriagnhdt h`imgyh/ekre./dTahyearnadtihoisoghfetr,hewiwtehigsthattoifsttihcael ssiegmniinfailcavnecseicaltes1 awnidth1f0lumigd/1kg/tdhaeyb.raiTnheweriagthiotsowferteheinicvreerasweedigatht1tofo-tbhreailnewfteiagnhdtriwgehrtekisdingneiyfiwceaingthltys-itnoc-rberaasiend iwneitghhet|wmeyr/eksei/gdnaiyficaanndtlhyiignhcerredaosseadgien galrloutprsea,teadndgrtohuepsr.atiTohse ftahteiroastoifotsohfe sthpeletehnywmeuisghwte-itgoh-tb-rtaoi-nbrwaeiinghwteiwgehrtewseirgenisfiigcnainftilcyandtelcyredaescerdeaaste|dmatg/1k0ga/ndday3a0nmdg/hkiggh/edra,y.anTdhe draotsiaosgeofgtrohuepsl.ftTahnedserirgahttiotseswteersweeisigghnti.ftioc-anbtrlayininwceriegahstedwaetre10inmcgr/ekags/eddaiyn t(rhiegh3tmtges/tkigs/odnalyy)aannddh3ig0her mgke/day. Hmiisctroopsactohpoilcogcihcanegxeasmiwnearteioonbosfertvheedireprtohdeuacdtrievnealorgglaannsdswaosf huingrhe-mdaorskeabalnei;mahloswe(vcyetro,pltaresamtimcenhty-preerltartoepdhy atrnedatveadcwuoiltaht3i,on10o,fatnhde c3e0lmsog/fkgt/hdeaayd.renNaol octohretrext)reaantdmeinnt.trheelaltiveedre(fhefpcattsocweelrleulraerpohrytpeed.rtrophy) of animals FI Generation ~ Females Ntroeaetfefdeactnsdwceornterroelpgorroteudpsatwaenrye dnoosteedlefvoerltfhoer ntuhmebveirabsioliftypuapnsd sluarcvtaitviionngpiendricleist.e,Nothedipfefrecreenntcaegsebemtawleeen paluspos.silgintitefricsiaznetalyndreadvuecreadgienptuhpe 3b0odmyg/wkegi/gdhatypegrroiutperoan dbaiytsh.I,P5u,pabnoddyofweliagcthattioonn.apOefrtfhiettperupbsasis was nweecirgohptssioefdtahtebwreaainni,ngs,plneoenstaatnidsttichaylmlyussiagnnidfitchaernat,tiroesaotfmetnhte-sreeloartgeadndiwfefiegrehnscetso wtehereteorbmsienravlebdofdoyr wteheight and brain weight 290 000189 Awdaenyrsein2rc-er8peoaarsttteehidenhtfiorrgehaaetnsmyetdndotosrseeellaoetvfeedl30mdoumrrgtian/lgditaaynyy(.6tainmNeiomo:fataldhveoetrasslte)udcwylaipsneirocibaosd.icrgvnesdoifn FeIstfmeemanlterseloantedposotwneaining acSontahitamibasilttisactaolinloyndsabiyegsgnai,nfi,c1aw5n,hte2d2ne,cF2rI9e,agse5e0ns,erianatbnioo5dnd7yaptwosesitwgwehertaesnai9n2ng-d,1b0do6udrdyianywgseiporgfeahctgoegb)aa,ibniastnawdteidoruner(ionbcgsoegrredvseetaddtiiononnhtiahgnehd-ddeaocysteion. cDporeneccsroeuhamaspbetisitotiniaovbnaslaouneldsutdwuefrroieondgcocgmeopsntasarutamibpolnteiaoanncdrwolesacrsteaatloibotsnreeiranvteeaddnigdmruoarulipsns.gradtayesd 1w-i5t,h83-105mgp/oksgt/wdeaayn.ingRedluartiinvge food rSoebtsstpeiercstviieavdelillyy),hsiiggnhi-fdiocsaenta(npi<ma0l.s01v)edresluasycsonicnusrerxeunatlcmoanttruorlasti(o3n6.(6thdeaayvseorfaaggeedavyeorsfusva3g4.inaldapyastoenfcyag)ew,ere odNufordiaenfygfsetcihtnescfworehsartbeiwtoeabetskieoronvf,ecndouhomanbbeietrsatstrioooufnsrcaaytnscdltinhcauitmym,baeotrredoo,fnrafaetrnstyiolpifrtyetghinneadenmxta,tpirrantgsatawsnidtihnfeccrootnihlfaiibtryittphaaetdriamomanettieTnrhgsrd(aentuewmsebreers dhoosweevaenri,maslasis(t4i.c7alvleyrssuisgn5i.f4icianntcointnrcorlesa)s.es in the average numbers ofestrous stages per 21 days in highNAilutlmebn,aettruhrsealogfeddsetalamitviseorndyeiolnbidsveeexrri(vnangtuimlobtnersrswo,efrthedaamdlsusroawatipitpohanrooefnnctgloeyrstumantoairfoefn,eicavtvecedbroabrgynestprfueapotsmiemunpmtlbaaentrtaaontfiyopdnroessigetneslaenvpetelr,radtesl),ivtehreed ncoummpbaerrasbolfedaammosngwittrheastteidllabnordncpounptsr,oldgarmosupwsi.th all pups dying nd Iveborn and stlbor pups were psNiiotgunititfraiarcytanmatenlnydtdetehlceartreaeardsoeesdfofaftett3shmewipeikrteeuiotdabrasyyewreavinedgdhhotingohte-erer,mribmnuiatnldaibldobdnoyodtswyehiwogihwgthsa.tdoTasnhed-era(e0bssptoohlenustbere.awineNiwogehiotgthhoetfrtwheere dreilfafteerdenecfefsecwtserweerreeproerptoerdtfedorftohlelaobwsionlgunteecwreoisgchotpsieo anradthioisstfoopraotthhoelrogoircgaenxsameivnaaltuaitoends. No treatment F2 Generation Offspring srNetolotamtraeedcahtefmifenencpttusrpewslaatrtheeadtrewapedovrreetresfdeoufcnoldlinldiocawadil.nsgingTenhcserwonesurcmeobpoiebcrsseexroavfmpeidunapatstiaofnnoy,undwdoistcehitltehhvreel.dxecaeLdipkoierowsnisloebf,onnroonmtiirledaktnmioentnts:how a. mdroeotsspese-icrgteniisvfpeiolcnya)snetaln(y3d1d2ti8hf,efer6reef2no5tr,efr1w0oe7mr2e8c,ounnt1lr0io2lks8e.l,yaArnbedlsao6tle2ud8teoiwnter0ie,agth1mt.e3sn,to.1f0t,Theearnbmdriai3nn0a,lmsgbpo/ldkeyegnwdaeainygddhttohssyeimngurFso2uappnsud,phsewearseics aonfdthceosnetoorlgagnrowuepisghts-to-terminal body weight antdo bran weight were also comparable among reed tpNuropesa.etfefdlaeicnttdsecwsoienzrteeraornledpgoarrvtoeeurdpasagtewaepnruyepdnbooostdeeydlewfvoeerilgtfhhoetrnptuhrmeblveiiraebsrilowifhtyepunapnmsdesaaucsrtuvariteviidonnogpniendLriDcleisse,r1,,N5,toh1edipfef.recreenn2tc2ae.gsebemtawleeen aAnmoognegnittahlfdiivsetdanocseasgemegarsouurpesdanodrdFi2d nmaolediafnfedrfseigmnailfeicpauntplsy.on LDs | and 22 were also comparable 201 009190 concuumons sfDeeopmsaairlnaegti1wointoohfrfAvsPpargFiinOnga.latpT3ah0teemnagcu/yt)khgoor/bsdsaoeyrfvtaehpdepesiantruhedidyghco-odndoteseleanydanttihhmetaoltnshseaertdeoefldasuyeesxtuionatlshmeeaxtfuuaarcltatmtiahotanurtahitenisobenoat(nhpirmmoaapllusetahalnadvae edinsetctarhteeiaoFsnOeadlgegaensgeteraatatipioponneaalurnaetgidetl,oeabvvaierdiednaecbcelroeefawssehedixcuihanlhthimegayht-uhdraoavsteeiodanenfiiimnnatelhdseaaFstItthgheeentteiirmamteeoiiofnn.daacqTyushiesfiratouimtohnco(vrtishdesetntaciteemoetfhwotmhaetning msoerneulimmamtautruarteiotnhawnatsherecaocnhterdo)l,gwrhoiucp,h itnhewyhibcelhietvhermeewaanstntohesaignniimfailcsanitndtihfafgerroeunpicnewesreexuyaolunmagteurraatnidon. aw1gi0 teohnwdetehrreeadt ceoltnaesyttsritihbniusstehixynupgaoltfhamecatsotirus.,rattWhiehoenaunitnhtoohresdreclotavoayddrseitieneedtsrhemexriudnaeelcwrmeahtaeusrteashteiioonrnbnowodetyrbewocedoiyvgahwrteiiaegndhdtwsiitnahngtdehsegteasstitigaontniiafolincaaalgnetly vreerdsuucsedp=bo0d.0y1.weTihgihs iantdtihceatteismethoafactqhueidseiltaiyoni,n stheexudailffmearteunrcaetwioanswtailslpsairgtnliyfieclaantt,edbuttoabtotdhye pweei0g.h0t5,. but sgneeosxttueaantltiiomrneaaltlyu.raagWtehioaentntbhteehtetwidemelenaoyfcsosneitxnruoslaeslxuamanaldtumhraiatgtuhiro-andt,oisotenheaornbeismweaalrssv.endoTahtstiisghneiihfnidicigachnattdedosistfehfagrtretonhucepeewifnefrteehteoctfoidvmeeelreaofdyoenwdisteht of sexual maturation could possiblybeattributedto decreased gestational ag. mi`Tnahckergeaa/usdtehasoyrinsaatnlhdseofaovcueonrvdaagrtieheandt ttuhhe ddmeiocffrbfeeraseestnercseoruibsnesbttowategheenbsotpdreyea2irweedidgaahnytdsactnohdnattrinowlegarenseitaomtbaisloesnravwleaadsgaestiwltilhteshihgtinhgiehfisdcioagnsntiefoifcan3t0 aWfhfieclte tiht eistikmneotwonsaenxduaclommamtuornaltiyona,ccwehpettehdetrhaotr cnhoatnggeesstaitniotnhael baogde,y awseidgehftisnoedfobfyfstphreianugthcoarns, palrsooviadfefedctbsytthheetaiumtehoofrsactqouissuipptoirotn tishipsurreellaytisopneschuilp.atiAvded,ietsipoencailallyl,ycsoivnacreitnhgertehewdaeslanyoidnasteaxual smiagunwirfaitciaontn cwhiatnhggeesitnattihoenallenagtgh oisfpgreosbtalteimoantiact 3f0rommg/aksgt/adtiasyt,icablassetadndopnoitnhte. auStihnocres"tdheefrienwitaisonnoof t"igemseta1t0isoenxaluaalgem'a,tutrhaetidoenc.reaTsheesreifnogrees,tasteixounaall maagteurwaotuilodn hisavesesetnotbiaeldlyuebemionsgtlcyovtaoricehdanwgietsh iintself mteirle,leyovfefneirsfa arneleaxtpiloannsahtiipobneftowretehnegoebssteatrivoendaldealgaeysanidn steixmuealtomsaetxuuraaltimoantuirnahtiigohn-wdeorsee asnhiomwanl,s,it but does not diminish is significance. REFERENCE 4AY1om3rm-k0o,2nR0i.,Gu.Smpo2Pn0es0r2of.rluSoOtrruoadolyct(NaGunaomvibacegre(:)APTTF-wO6o8)-8G9ien.n6Re,artaMst.airocAnhrg(2uO6sn,eR2e0Ls0i2ct.aerrchPeLraGbeonreatroartiieosn,)IRnce.proPrdoutcotcioolnNSutmubdeyr:of 3M Company, 2002. Submission dated September 17, 2002 to USEPA, AR226. 2U0S0E2PA 2002. Memorandum from Dr. Ralph Cooper, NHEERL, to Dr. Jennifer Seed, dated October 2, 292 0069191 Ecotoicity Study `TTEOSXTICSIUTBYSTTOANACQEUATIC PLANTS (SELENASTRUM CAPRICORNUTUM) rIedfeentrirteyd:toPearsfPluFoOroAoctteatnroiacbuatcyidl,amemtornaibuumtsyallta,mmonium sal; mayalsobe `tectroabmutpylooafmnmLo-e1n3in4u9mt2p.er(fluoOroacctaanctoiadt,eap,enNtn2a8d0e3oc-a2f,liouorracos-,a major tReetmraarbkust:ylTahmemo3nMiumprsoadlu,ctCiAonSl#ot9n5u6m58b-e5r3-w0a)s 2327. The test sample is nreufmebrreerd itso8b4y1tThHe.teTsthiengpulraibtoyraotfortyheassaLm-p1l3e49w2a.sTnhoet TsuRf.ficWiienltbluyry study 4ch4a.r9ac%tteetrriazbeudt,yalatmhmouognhicuurmrepnetrfilnufoorromoacttiaonnoaitned,ic2a7.t9%ews aittisearo,luatnidon27o.f2% isopropanol tTehstesfuoblsltoawnicneg isnuamnmairsoyparpoppliaensoltowattheertessotlsuatimopnlewiatsh ainmcioxmtpulreetoeflythe crehlaartaecttoexriiczietdyocfontcheenttreastsioanmspolfe iwmiptuhritthiaetso.fDtahteatemtaysunbosttaanccceu.rately METHOD TMeestth:oAdc:utUe.S.staEtiPcA-TSCA Guideline 797.1050 GeLaPr:cYoemspleted: 1995 SSpoeucricees::OSreilgeinnaaslliyrufmrcoampTrihceorCnuulttuumr.e CollectionofAlgae at the University oMfarTbelxcahseaatd,AuMsAt.in, maintained in culture medium at T-R. Wilbury, Inc.. Element basis: growth rat. "ETxesptosourrgeanpiesrmisodl:ab9o6-rhaotuorrsy culture: Algae cultures were growing in U.S. EPA-tccommended test initiation. sterile enriched medium for at least 14days prior to tSthaetniasttuircaall lmoegtohfotdhse: Tnhuembaevreorfagceeslplesc/imfLicatgrtohewtehxproatseurweaspecrailocdulmaitneudsasthe pneartiuorda.l lTohgeofpetrhceenntucmhbaenrgoeffcreolmltmhLe.coantt0rohlouwrassdciavlicdueldatbeyd tbhye exposure sauvbetrraagcetisnpgectihfeictrgeraotwmtehntraatvee,rdaigveidsipnegcitfhiec dgirfofwetrhenrcaetebyfrtohme atvheercaognetrol sEpCeSci0fivcaglureoswtwherreatecailncutlhaetceodntbraosle,doanndamunlotnilpilnycianrgrtehgartevsasliounebesyti1m0a0t.ioTnhe parpoacreadmuerteri(cBrouncce-uaanyd aVnearlsytsciesgo,f1v99a2r)i.anTcheeanNdOtEheCawvaersadgeetsepremciinfeicd using gTreostwtChonidnictaicohnst:es vessel at the endofthe test EDiPlAutiroencowmamteerndseodurccoen:ceTnhteraatligoancs mbeydsipuikmiwngasdepiroenpiazreeddwtaoteU.rSw,ith ninuittriiaetnitonstwoackss.7.5T.he pHofthe synthetic algal medium at test Stock and testsolutionspreparation: A 16 mg/L primary stock. 293 000192 `soalmuotuinotnswofatshipsresptaorcekdsionlusttieroinleweenrreiacdheddedmeddiireac.tlAypptroodpirliuatitoen water stoolfuotrimonulwaatestahlesotepsrtempeadriead. aAnd1e,v0a0l0uamtyed/.L isopropyl alcohol stock E1x00pomsLuroefvteesstseslosl:ut2io5n0. mL glass Erlenmeyer flasks containing NAguimtabteiron:ofrCeopnltiicnautoeuss: at 3 100 rpm NInuitmibalearlogfalccoenlclelnotardaitnigo:ns1:.0FXiv1e0pl4usceallnseg/amtLive control `LWiagthetrincgh:e~m4is0t0ryfi:-c from continuous cool-white fluorescent lighting 7P5H ra1n0g:e4:(c(o0n-tr9o6l ehxopuorss)ure) 774.7.46 10.(41(61,m0g0/0L.mge/xpLosiusroepr)opyl alcohol exposure) 2`T4es-t t2e3m7perCature range: (0-96 hours) NRoEmSiUnLaTlSconcentrations: Blak contro, 1.0, 2.0,4.0, 8.0, 16.0 mg/L. tAhattesrtepwraessepnetrsf2o7rm%edofsLim-u1l3t4a9n2c,ouatsl4y.4waitnhds1o,p0r0o0pmyg)/La.lcohol, acomponent 2EdlcehmoeunrtEvraCl1u0e(garnodw9t5h%ratceo)n=fi<d1.e0nmceg/inLter(vCa1l:not calculable) 2244--hhoouurr EEFrCCIS00 ((ggrroowwtthh rraattee))== >1156(9(.78.7->-1>61)6)mgm/gL/L 4488--hhoouurr EEXrCCS100 ((ggrroowwtthh rraattee)) == <114.(08m2g/-L16(C)I nmogt/Lcalculable) 4782--hhoouurr EErACC1O00((ggrroowwtthh arattee))== ><11.60mmgg//LL.((CC11nnoottccaallccuullaabbllee)) 7722--hhoouurr EERRCCS00 ((ggrroowwtthh rraatte)e=)= >7.116(m4.g1/L-. 1(C)lmngo/tLc.alculable) 9966--hhoouurr EEFXCCIS0O ((ggrroowwtthh rraattee)) == 4<19.0(3.5mg-/L6(.C7)1 mngo/tLc.alculable) 96-hour 96-hour NErOCE9C0: (g1r.0owmtgh/Lrate)= >16 mg/L (CT not calculable) Algal 1.000 mgrLow.th was not affected by isopropy! alcohol concentrationsof 4.4 or Element values are based on nominal concentrations, 294 009193 Biological observations after 96-hours: CNoonmciennatlration,|NNiucamber [PIenrhciebinttion via| iPnehricbeinttion via my ofCells mL per | Density Growth Rate. [ComrolT0000 [|_| [Lo 7 Tisieoo [5 To 1 [207 ors000 Ts 13 [ao Tizeon Tor [so | [Bo Tsao Tos -- 156 | Oe Tore0 Tos -- [so | CBioonltorgoilcarlesopbosnesrev:atSiaotnissfaafctteorry96-hours for isopropyl alcohol: Nominal Mean Percent Cmonycentration,|oNfuCmeblelsr per | vIinahibition | mL Density [T 44 9000 |S [oTsoi3a70 [5 00| Ombesaenrsvoaftidoirnesc:t Amligcarlosceclolpceocuontusntisn weiatchhatehsetmvoecsysteolmweetreer.deAtfetremri9n6edhobuyrs oofftehxepoaslugraec,ttohtehree wflearseksnionstihgencsoonftraoglaorergaantyiont,estltroeactmcenut golrroauapd.theIirneoncne: amdodriptihoonl,otghyerwehweenreconmopanorteidcteaobltehecchoanntrgoels. in cell size, coloror Rdeevteerrsmiibnieldittyoobfe GarlgoiwsatthicInbhaisbeidtioonn:thEefrfeecstulosf otfhethteesptossutb-dsetfainncietiwvaestest eRxepmosaurrkes.: Testing was conducted on the mixture as described in the Test `nStubtshteanfcleuoRreomcahremkiscaflickc.omTphoenevanltuelsonre.ported apply to that mixture and "CTOheNtCesLtUsSamIpOlNeS96-hour ECS0 and 95% confidence interval for Scoenlfeindaesntcreuminctaeprvrailcoofr3m.u5tu-m 6w.a7smdg/eLt.erTmihneed96t-ohboeur4.n9omogb/sLerwvietdheaff9ec5t% cAolngcaeentgrraotwitohn (inNtOhEeCv)efsoserltsheconttesatinsiunbgstiasnocperoipnyslolluctoihoonlwwaass1.n0otmga/fLf.ected aint4L.-413or4912,0c0a0nmnoLt,,byinidtiscelaft,iancgctohuantttfhoercotnhecetnotxriactiitoynooffLi-s1o3p4r9o2pytloaallcgoah.ol No the steisgtnssoolfutaigoansr.egTahtiisont,etflsocucbusltaatnicoen,woarsaddehteerremnicneewdetrobe enotalegdisitnaaincy of SPauublm,itMtiennre:so3tMa,C5o5m1p3a3ny, Environmental Laboratory, P.0. Box 33331, St. 295 000194 DATA QUALITY oRfetleisatbisluibtys:taKnlciemciosncchenrtarnaktiinogns2. iTnhtehstteudtysollauctkisoannsalayntdicsaalmmpelaespuurreitmyenist not sufficiently characterized. 296 009195 REFERENCES "MTAhi,s sattutdhyewreaqsuecsotnodfutchteed3aMt TCRo.mpWainlyb,urLyaLbabRoerqauteosrtiensu,mIbnce.r, NMa2r3b3l2e,head, 1995, OTHER O`GNenLeYralNrOeMmIarNkAsL: TTEheSTmaCjHorEcMonIcCeArnLfCorONtrCyiEnNg TtoRdAeTteIrOmiNnSe twheervealuisdeid.ty fOoPrPthTisrteesctoimsmtehnatds cthhaetmimceaalsucroencdetnetsracthieomnticoawlhciocnhcetnotrtahteitoensstboerguasneids,mssoartehaexopnoesecda.n aIfcicturiastdeeltyedremtienremdintheatthtehetest vnaolmuiensalcacnobnecaenntdramtuisotnbaeraedojnulsyt,efdordeoxwanmwpalred5b0y%5o0f%t.heImfeaansaulyrteidcaclonmceeansturrateimoennst,sothfestooxmiecisyort vhoaldatibleietny,faunrdniosthehde,r wpheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcomviegrhyt roawtes,ratnhde tacatkuealintteosacocroguanntishmydrolysis, exposure concentrations, sPuormietyotefsttshiet atpesptemaarteedritahlatal1s00i%s atemsatjcorhceoncmewrianscaunsadewdla,sfnorotosutffiahciceehntelmryicchsaalraofctleersiszeerd pnurtihtiys test. In (otahpeprrofxesitmsa,tfeolryn8o59o%b)viwoauss ussteadt.ed Wreaatsoenr.,Isnolfvacetn,t3(iMsoipnrtohpeainrosl)umormaarcyoomfbcinaacthiotnetofbstoatte:h "wDaasrausmeadyinnot aadcdciutriaotne,lyiftrheilsatweatsoxiaci"ttyyopifcahle" TteSsCsAamspeclteiownith4 trheavtioefwt,hIewtoeustldsurbesjtecatncteh.e"se|satgurdieees,wiptehndthiinsgcornecceeirpnt. ofIn madeddiituimo,nal information on purityandstudies on analytical measurements of the test chemical in the tes 297 000196 Ecotoicty Study TTOEXSITCSIUTBYSTTOANACQEUATIC PLANTS (SELENASTRUM CAPRICORNUTUM) Identity: referred 10PearsfPluFoOroAoctteatnroaicbuatcyidl,amemtornaibuumtsyallta,mmonium sal; mayalso be `tceotmrpaobnuetnytlaofmmLo-n1i3u4m92p.er(fOlcutoarnoooictcaancoiadt,e,peNn2t8a0d3e-c2a,luoorraos-,a major teRterambaurtkysa:mTmhoen3iMumpsraoldtu,ctCiAonSlot95n6u3m8b-e5r3-w0a)s 2327, The test sample is rneufmebrererd itso8b9y0-tThHe.teTsthiengpulraibtoyraotfortyheassaNm2p8l0e3-w2a.sTnhotesTu.fRf.icWieinltbluyry study c4h4a.r9ac%tecrtirzaedb,utalytlhaomumgohnciuurmrepnetrfilnufoorromoacttiaonnoaitned,ic2a7te.s9i%t iwataesro,lautnidon27o.f2% isopropanol tTehstefsuoblsltoawnicnegisnuamnmairsoyparpopplaineosl1w0attheertseoslustaimopnlweitahs ianmciosmtpluerteeolfythe crehlaartaectteorixziedcocfiotntchyeenttersastaiomnpsloef iwmiptuhritthiaetso.fDtahtetaemtasyunbsottaanccceu.rately METHOD TMeestth:oAdc:utUe.Ss.taEtiPcA-TSCA Guideline 797.1050 GLP: Yes Year completed: 1995 SSpoeucricees::OSreilgeinnaalsltyrufmrcoampTrhiecoCrunluttuurme CollectionofAlgae atthe University oMfarTbelxeahseaadt,AuMstAin, maintained in culture medium at T-R. Wilbury, Inc, EExlpeomseunrtebapseirsi:odA:lg9a6l-cheolulrcsount (cells/mL), and specific growth rae. ETPesAt-otrcgcaonmimsemnsdleadbsotreartiloeryencruilcthuerde:meAdlgiaucmcfuolrtuartelseawsetre14gdraoywsinpgrioinr tU.oS. eStsattiinsitiicaatlonm.ethods: The average specific growth rate was calculated as ntahteunraatluoragl olfogtohfetnhuemnbuermobfecreolflcseilmil.s/amLt0haotutrhsedeixvpiodseudrebpyertihoedexmpionsuusrethe speurbitorda.ctTihngetpheercternetatcmheanntgaevefrraogmetshpeecciofnitcroglrowwatshcraaltceulfartoemd tbhye control sapveecriafgice gspreocwitfihcrgarteowinththreatceo,ndtirovli,dianngdtmhueldtiifpfleyrienngcethbayt tvhaeluaevebryag1e00. The dEeCtSe0rmvianleudesuswienrgecaaplacrualmaetterdicboynpero-bwitayanaalynsisa. loThfyevasNriOiaEnscCewaansd the avevsesrealgeatstpheeciefnidc gorfotwhtehtersta,e and the number ofcall. in each test Test Conditions: DEiPlAutrioencowmamteerndseodurccoen:ceTnhteraatligoancs mbeydsipuikminwgasdepiroenpiazreeddwtaoteU.rS,with innuittriiaetnitonstwoacsks.7.5T.he pH of the synthetic algal medium at test Stock and test solutions preparation: A 160 mg/L primary stock 298 009197 s`oalmuotuinotnswoaftshpirsepsatorcekdsionlusttieroinleweenrreiachdeddedmeddiirac.etlAypptroodpirliuattioen water to formulate the test media mExLpoosfuerset vsoelsusteilosn:.250 mL glass Erlenmeyer flasks containing 50 ANguimtabteirono:fCroenptliincautoeuss:ly3 at 100rpm NInuitmibalearlogfalcocnelclelnotardaitnigo:ns1.0: FXive10plucselalsn/emgLa.tive control Lfliugohrteisncge:ntColnatmipnsuous lighting at ~380 fic using cool-white `pWHatrearngceh:em(i0st-r9y6: hours) 77.558.410.8(1(6comntyr/oLl eexxppoossuurree)) 2T3es4t-t2e3mp7erCature range: (0-96 hours) RESULTS NEolmemiennatlvcaolnuceenatnrdat9io5n%s:cBolnafnikdecnocnetrionlt,e0r.v9a9l,; 2.0 4.0, 8.0, 16.0 mg/L. 2244-chhoouurr EECCS100 c(ceellll ddeennssitiyt)y=)=>4.116((00.97.0-)>1m6g)/mLg./L. 2244--hhoouurr EERCC9S00((ceglrlodwetnhsirtayt)e)==>>1166mmgg//LL((CC11nnoottccaallccuullaabbllee)) 4488--hhoouurr EECC1S0O ((cceellll ddeennssiittyy=)) 71..12 ((6<.00.9-98.6)1.m6)g/mLg./L 4488--hhoouurrECEr9C050((ceglrlodwetnhsiatyt)e) ==>>1166mmgg//LL((CC1lnnoottccaallccuullaabbllee)) 7722--hhoouurr EErCC1I0O((gcerloldwetnhsriattye))== <202.99(1(.6<-02..989)--m1g.9/)Lmg/L. 7722--hhoouurr EERCCSS00((cgerlodwetnhsirtayte))==2.118 ((19.1.4-- 51.58))mmgg//LL. 7722--hhoouurr EEXCC9900((ceglrlodwetnhsirtayte))~=8>.41(64.m5g/-L>1(C6I)nmogt/Lc.alculable) 9966--hhoouurr EEXCC1L0O((cgerlodwetnhsirtayt)e)==12..43((<<00..9999~-23..46))mmgg//LL 9966--hhoouurr EErCCSS00((ceglrlodwetnhsirtayt)e) =2.89 .4(51.09 -- 7.7) 14) mg/L. mg/L. 9966--hhoouurr EERCC9900((ceglrlodwetnhsirtayte))~=6>01(63.m5g-/>L1(6C)1 mnogt/Lcaleulable) 9966--hhoouurr NNOOEECC ((cgerlolwdtehnsriattey)):: 02..099mmgg//LL. CEolnetmreonlt vraelsupcosnswee:rSeabtiassfeadctoonrynominal concentrations. 299 000198 Biological observations after 96-hours: CNoonmciennatrlation,| MNuemabner |PIenrhciebinttion via| IPnehricbeinttion via mel mofLCells per | Density Growth Rate [Comeol [3227000 [1 - -7) [oso aeso00 Tix [7 | [20 oaa0000 24 5 [so Tssioo0 Teo J | pe 169.000 61,000 [os Tes `Ombesaenrsvaotfidoinrsec:tAmligcalrocseclolpce coouniutnsenwaictthhtaesshtemvoecsysteolmweetreer.deAtfetremri9n6edhobuyrs ooffetxhpeoaslugraec,1t0htehree wflasekns oirnsitgheenscoonftraoglgroergaantiyoen,stftlreoatcmecntugorlroauapd.hteIrineoncne amdodriptihoonl.otghyerwehweenreconmopanorteidctaobltehecchoanntrgoels. in cel size, color or dReetveerrsmiibnieldittyoobfeaGlrgioswttathicInbhaisbeidtioonn:thEeffreescutltosftohfethteesptossutb-dsetfainncietiwvaesest exposure. SRuebmsatraknsce: RTeemstairnkgswfaiesldc.onTdhuecvtaelduoesn rtehpeomritexdtuarpepalsydteostchraitbmeidxitnurteheaTnedst not the fluorochemical component alone. C"TOheNtCesLtUsSamIpOlNeS96-hour ECS0 and 95% confidenceinterval for Smeetlleondass.trTuhmecatepsrtiscuobrsmtuannucne w9a6-shdoeutreErmCiSnOedfoursiSnegletnwaostcraulcmulation cinatperrivacloronfutu1m.0w7a.s7 dmegt/eLr,miwnheedntocablecu2l.a9temdgu/sLinwgictehldae9n5si%tyc.onfTihdeenc9e6.-hour 9E5CS%0cofnorfiSdeelnecneasitntreurmvaclaporfico5.9r-nu1t4ummgw/aLsudseitnegrmgirnoewdthtorabtec.8.N4omsgi/gLnswoifth a asoglgurteigoanst.ioTn,hifslotcesctulsautbisont,anocreawdahesrdeentceerwmeinreedntootebdeianlgainsyatoift.he test PSauublm,itMtiennre:s3otMa,C5o5m1p3a3ny, Environmental Laboratory, P.O. Box 33331, St. DATA QUALITY ofRetleisatbisluitbys:taKnlciemicsoncchenrtarnaktiionn2gs.iTnhtehestteusdtysollauctkisoannsalayntdicsaalmmpelaespuurreitmyenist nRoEtFsEufRfiEcNieCntElSy characterized. M"TAhi,s sattutdhye wreaqsuecsotndofutchteed3aMt TC-Ro.mpWainlyb,urLyaLbabRoerqauteosrtiensu,mIbnce.r, MNa2r8b0l3e-h2e,ad, 1995. OTHER 300 009199 GOeNnLerYalNrOeMmIarNkAsL: T`TEhSemTaCjoHrEcMonIcCeArnLfCorONtrCyiEnNg TtoRdAeTteIrOmiNnSe twheervealuisdeid.ty fOoPrPthTisrteectoismmtehnatds cthhaetmimceaalsucroendcetnetsrtacthieomnitcoalwhciocnhcetntrtahteitoensstboerguasnedi,smssoatrheatexopnoesecda.n aIcifcturiastdeeltyedremtienremdintheatthtehetest nvaolmuiensalcacnonbceenatnrdatmiuosntsbaeracdojnulsyt,efdordcoxwanmwpalred0by%5o0ft%h.e1mfeanaasluyrteidcaclonmceeansturrateimoennst,sothfestooxmiecistoyrt hvoaldatbileietny,faunrdniosthehde,r wpheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcmoivegrhyt roawtees,ratnhde aackteualintteostacocroguanntishmydrolysis, exposure concentrations `Psuormietytoesftsthiet atpesptemaarteedritahlatal10s0i%staesmtajcohremciocnaclerwnasanudsewda,sfonrotosutffiahcicehenetlmryiccahsalroacftleersiszeerd piunrtihtiys test. In (otahpeprrotxesitmsa,tfeolryn8a59o%b)vwioauss ussteadt.ed Wreaatsoenr.,sIonlfvaectn,t3(iMsoipnrtohpeainrosl)umormaarcyoomfbcinaacthiotnesotfbstoatte:h "wDaastausmeadyinnot aadcdciutriaotne,lyifrtehliastweatosxicaity"tyopifcahle" TteSstCsAamspeclteiownith4 trheavtioefw,thIewteosutlsdubrsetjeacntcteh.e"se1satgurdieees,wiptehndthiinsgcroencceeirpnt. ofIn amdeddiituimo,nal information on purity and studies on analytical measurements of the fst chemical in the est 301 009200 Ecotoxicty Study TTOEXSITCSIUTBYSTTOANACQUEATIC PLANTS (SELENASTRUM CAPRICORNUTUM) aIsdePntFiOtyA: aPemrmfolunoiruoomctsaalnto,iAcmacmiod,niamummopneirfulmuosraolot;ctmaanyoaatles,obPFeO,referred to pFeCn-t1a1d6e,caFfClu-o1r2o6-,, FaCm-m1o69n,iourm FsCa-lt1,43C.AS(O#ct3a8n2o5i-ca2c6-i1d), RFCe-m1a4r3k,sr:efTehrere3d Mt pbryodtuhecttieotn llaotbonruatmobreyrawsaNs2840237-.4.ThTehteesTt.sR.ample is nWoitlbsuufrfyicsitenutdlyyncuhmarbaecrteirsiz8e9d5,-TaHl.ihTouhgehpcuurrirteyontfinthfeorsmaamtpilone was 3i.n5d%icCa6te,s iCt7s,aanmdixCt9urpeoerffl9u6o.r5o -an1a0l0og%uteesctosmupbosutanndcse and 0 -- MMeEtThoHdO:DU.S. EPA-TSCA Guideline 797.1050 Test: Acute static GYeLaPr:cYoemspleted: 1996 Species: Selenasirum capricornutum oSfouTrecxea:sOartigAuisntailnl,y mfarionmtaTihneedCuilntcuurletuCroellmeectdiiounomaftAlTgRa.eWaitltbhuerUyn,ivInecr.s.ity Marblehead, MA. EElxepmoesnutrebapseirsi:odA:lg9a6l-cheolulrcsounts (cell/mi), and specific growth ates Svtaaltuiesstiucsaeldmteotehsotdism:atCeeltlhedeEnCs1it0i,esE,CgSr0o,wtahndraEteCs9a0ndvapleurecseantndin9h5ib%ition `Sctoenpfhiadne.ncTehleimniotsowbeserrevceadlceuflfaecttecdounscienngtrtahteicoonm(pNuOteErC)sofwtawsarcealocuflatCeE.d uAsnianlgytoincea-lwmaoyniatnaolryisnigs:ofpHvaarinadncteem(peArNaOtVurAe). Test Conditions: Amlegdailumn,utprrieepnatrmeeddbiyums:pikUi.nSg.dEePioAn-irzeedcowmamteerndwietdhsntuetrrilieenetnrsiocckhse.d "STthoecpkHanodf ttheestsysnotlhuettiiocnsalpgralepmaerdatiiuomn:a Ate1st.0i0n0itimagti/oLn pwraisma7.r5y. astomckosuoolnufttithonisswastsocpkrespoalruetdioinnwseterreilaedednerdicdhierdecmteldyiato. dAilpuptrioopnrwiaatteer Etoxpfoorsmuurleatveestsheelst:est25m0edmiaL.glass Erlenmeyer flasks containing 50 Amglitoaftitoenst: solution. Shaken continuously at 100 rpm Numberofreplicates: 3 NInuitmibalearlgoaflccoenlcelnotardaitnigo:ns1:.0F.iXve1p40luscealnlesgiamtLive control LWiagthetrincgh:e~mi4s0t0ryf:ic from continuous cool-white fluorescent lighting p7.H59r.a6nge(:co(n0tr-o9l6exhpoousrusr)e) 5.4-7.4.(1,000 mg/L exposure) 302 000201 `2T3es5t te2m3p7eraCture range: (0- 96 hours) RESULTS Nominal Element vcaolnuceenatnrdat9io5n%s:cBoknfciodnetnrcole,i6n2t,er1v3a0l, 250, 500, 1000 mL. 7722--hhoouurr EErCCI100(c(eglrlodwetnhsirtayt)e)==341700((131800--4$4500))mmgg//L.L 7722--hhoouurr EEXCCSS00((ceglrlodwetnhsirty)a==t5>21e0,0()02050m-g/1L,0(0C0.1).mngo/tL.calculable) 7722--hhoouurr EEXCC9900((cgerlodwetnhsirtayte))==1>,10,00000mmgg//LL((CC.L1. nnoottccaallccuullaabbllee)) 9966--hhoouurrEErCCOI0((ceglrlodwetnhsirtayt)e)== 9272(07(71-6012-02)80m)g/mLg./L. 9966--hhoouurr EErCCSS00((cgerlodwetnhsirtayte))==3>110,0(02080m-g/35L0)(Cm..g/nLot calculable) 9966--hHoouurr EErCC9900((cglrlodwetnhsirtayt)e)==1>,10,0000(08m3g0/-L>1(,C0.100)nomtgc/aLl.culable) 9966--hhoouurr NNOOEECC ((cgerlolwdtehnsriatey)):: 6S200mgm/gL/.L. Element values based on nominal concentrations `BNioomliongailcal obserMveatainons after 9P6e-hrocuernst: Percent Cmogncentration,|ofNuCmelblesrp~e~r |[ DIenhnisbiittyion via| GInrhoiwbitthioRnvatiea mL [Control Tdoron0[----- ._--| [@ --Ta 3se Too ] 130 [29.000 20 Te 500 Coo [ass000 "Teo Tas | Thsioon [8j 7 e] `COobnsterrovlatrieosnpso:nsAel:gaSlatcielslfaccotuonrtys in cach test vessel were determined by. omfeeaxnpsoosfurdeir,etchtermeicwreorseconpoescigonusnotfs waigtghreagahteimoonc,yftolmeotecr.cAuoflerraad9ht6eihroeounrcnse oadfdtihteioanl,gtaheer10e twheerfelansoksnoititcheeabcloentcrhoalnogresaniyn cteeslt stirzee,atcmoelnotrgorroup. In mReovreprhsoilbiolgiytywohfenGrcoowmtpharIendhitboitthieonc:onEtfrofle,ctofthe test substance was dexeptoesrumrien.ed to be algistatic based on the results ofthe post-definitive test CThOeNtCesLtUsSamIpOlNeS96-hour ECS0 and 95% confidence interval for S`meeltehnodass.trBuym ccaeplrdiecnosrintyu,tuimwwaass3d1e0te(r2m8i0ne-d35u0s)inmggtw/oLacna,ldcublyatgironowth rate 303 009202 c1e,ll0d0e0nsmigt/yL.anTdh5e0096m-gho/uLruNsiOnEg Cgrwoawtshderattee.rmNionesdigtnosobefa6g2grmegg/aLtiuosni.ng tfelsotccsuulbasttiaonn,ceorwaasdhdeerteenrcmeinweedretonboeteadlgiinstaatniyco.fthe test solutions. This PSauublm,iMtitnenre:s3otMa,C5o5m1p3a3,ny, Environmental Laboratory, P.0. Box 33331, St. RDeAliTabAilQitUyA: LKlIiTmYisch rankin=g 2. The study lacks analytical tmheeassaumrpelmeenptuoriftyteisstnsoutbsstufafnicceiecnotnlcyecnhtarraatcitoenrsiziend.th tas solutions and TRhEisFEstRuEdyNCwaEsSconducted at T-R. Wilbury Laboratories, Inc., Marblehead, MOAT,HaERthe requestofthe 3M Company, Lab Request number N2803-4, OGeNnLerYalNrOeMmIarNkAsL: TTEheSTmaCjHorEcMoInCceArLn fCoONtrCyiEnNg TtoRdAeTteIrOmiNnSe twheervealuisdeid.ty OfoPrPthTisrteesctoimmtehnatds ncthhoaemtmiimnceaaallscucoronenccdeentntetrsratatctihioeonmnsitacoraelwhocniolcnyhc,e1nf0otrrtahetexiatoemnspstbloeergu5as0ne%ids,omfssotahtreheamteexoapnsoeusrecdea.dn acIocfinctcuerinasttdreealttyiedorenmsti,enrtemhdienttheoaxttihhceietfyost vhvoaalldautibelseietcnya,nfaubnrendiaosnthdehdem.rupwshetysbcioecuaoldcdjhucesamtlicecudalldatopewrcnohcweeamsrisdceasbltyhrae0tcmo%vi.egrhytIFaroanwtaesl,yrtaitnhcdealtaacmkteeuaaislnutroeesamcoecrnogtuasnontifshsmyodrmoelyssiosr,t exposure concentrations. 304 009203 Ecotoxicity Study "Tiles Muli-Phase Exposure/Recovery Algal Assay Test Method TESTSUBSTANCE dAemnmsoitnyi:umPeprefrlfulourooroocotcatnaoniocataeci,d,PFaOm,mFoCn-i1u1m6,saFltC;-1m2a6y,alFsCo-b16e9,reofreFrCe-d1t4o3.as (POFctOaAnoaimcmaocindi, um salt, pentadecalluoro-, ammonium salt, CAS # 3825-261) a`Rcneodmmap0lr-ek3ts.e:l5y%cTChiha,eraC3c,tMeparrinozdeddCu,yctpaelirtofhnlouulogotrhoniunamfnobarelmoragwtuiaeosnco3im7n.pdoicuTanhtdeess.tietsitTsshaaemmcpihlxeetmuwircaeoaslfFiC9s-61s.4o5l3-u.1b0l0eTphienerwcpaeutrneittrytaetwtaasmsubnbiosettnatnce room temperature, METHOD A`MGe.thPoadyingeu.idaeslidneesacrlilboewdedin:UMSoEdPifAie6d00f/r9o-m78a.n0d18m)odeled afer ASTM-E-35.23 Draft No. 2, OECD; Test types Static GLP (VIN: No Year study performed: 19581 Species: Sclenasirum capricomutum (7 day old stock) Supplier: USEPA ERL in Corvallis, Oregon. Measure ofgrowth used: biomassi cell dry-weight (mg/L); cell count (no mL) CMoanicnenstturday:tio0n,s10u0s,ed1:80R,a3n2g0e,-f5i6n0d,in1g0:0,0,1180000, m25g0/,L5(0n0o,m7i5n0a,l 1v0al0u0e,s)1.500 mg/L; Exposure period: 4.7. 10, and14days. TAnhaelryetwiacasl1m0oniintfoorrimnagt:ionTohnerdeetweacstinoon liinmfiotrsmoaftitohneocnhetmhiecamleaosruirmepmuerinttiosf.the chemical during the test, Smtoadteislti3cMal Smiextehuords: ECSO values and 95% confidence limits were calculated using the linear regression 305 000204 T- eTshtecaolngdailtciuolntsu:re was stored in the dark at 4C before use. The initial algal cell count in the stock culture was 277.000 cells/mL. -wiMtihnealrlalmiinneorraglannuitcr)iesnttasnedsasredntniuatlrifeonrtamlgeadligurmowwtah.s used The forculturingtestingalgae. This was pH was adjusted to 7.5 +.0.1priorto prepared use in the assays. ofstock This nutrient solutions. medium was the diluentforall operations that used algae including the preparation - Exposure autoclaved vessels were foam plugs. 250 mL Erlenmeyer flasks with 0 mL of test solution and stoppered with - During the test, the temperature candles + 10%, and cultures were was 23. 2C. agitated with The lightwasby fluorescent illuminationof a continuous shaking platform at 100 rpm. 400 ft ~ Initial algal loading was 1.0 x 10 cells/mL Algal recovery response was evaluated following the exposure periods. - There "Three was no information on replicates were taken at dcialcuhtidoonswea.ter source, contaminants, or chemistryof the water. Remarks: pH values were acceptable according to OPPTS Harmonized Guidelines. Water hardness was not presented. RESULTS Dose associated with each endpoint (as mg/L): ECS0s Number of Days Exposed Cell Dry Weight (mg/L) Cell-Count (no.cells/mL) 4 7 10 1 195% Confidence Limits 149 (57-340) 70 (34-118) 4915-96) 73 (25-147) 49.28.75) 30 21-40) 27 (8-50) 43 (14-81) ECI0s Number of Days Exposed Cell-Count (no. cells/mL) 4 7 10 195% Confidence Limits. Number of Days Exposed 530-7) 33024) 291-5) 528) EC90s Cell-Count (no. cells/mL) 4 624 (C.L not calculated)' 306 009205 7 283 (150-590) 1104 330876 ((CC1L. nnoottccaallccuullaatteedd)) 195% Confidence Limits `Was control response satisfactory (yes/no/unknown): unknown Statistical results, as appropriate: No p-values were reported rReesmuasrpkesn:dedAifntefrreesxhpnousturrieenctemaseeddi,utmheinaltghaelacbeslesncreecoofvetrheedteasntdsurbesstaunmceed. logarithmic growth when CONCLUSIONS cAomnmfiodneincueminpteerrfvlauloorofo1c4ta0no8a1temegx/hLi.bits a 14-day ECSO (cell count) value of43 mg/L with a 95% Squuablmiittytteersst"inrgeamtatrhkest:imTehitewaausthcoornsduicntdeidc.ataHeoKwleivmeirs,chthreasntkuidnygloa2fck.edTihnefosrtmuadtyimoneoetnstetshte csruibtsertiaancfoer purity and actual measurementsofthe test substance i solution. REFERENCE "ETlenstabMaertahvoyd,. M.RTe.por1t98N1.umb3eMrT0e0c6h.niPcraoljeRcetpNorutmbSeumrm9a9r7y0,03M0u0l0t0i.-PhOacsteobEexrpo1s6.ure/Recovery Algal Assay OTHER Gdeetnaeirleadlrreepomratrkwsa:s aTvhaiilsabslue.mmTahreyrewfaosreb,atsheedcoonnatenstusmomfatrhiysrseupmormtarayn,d oinnlryefleirmeintceed tdoattaheabplreost.ocoNlos and resultsofthe study, "The major concern faoretrliymiintgedt.o determine the validity for this test is that ONLY NOMINAL TEST CcoHnEcMenItCrAatLioCbnOesNuCsEedN,TsRoAthTatIOonNeScawneraeccuusreadt.elOy PdePtTerrmeicneomtmheentedsst cthhaetmimceaalsucroendcetnetsrtacthieomnitcoalwhich to 5h0e%toesft otrhegamneiassmusreardeceoxnpcoesnetdr.atiIonisi, tdhettoexrimciinteydvatlhuaesthceannobmeinaanld cmounsctenbteraatdijounssteadredoonwlny,wafrordebxyam5p0l%e aIfndantalaykteicianltomaecacsouurnetmheyndtrsoloyfssios,mveolsaotirltihtya,dabnedenotfhuerrnipshhyesdi,cowcehecmoiucladlcaplrcoucleastseeschtehmaticmailghrtecloovweerry trhatees, actual test organism exposure concentrations. As itis we are operating in the dark on thi issuc. 307 000206 INVERTEBRATE TOXICITY Title: Acute Toxicity to Aquatic Invertebrates (Summary of three 48-hour studies in dict) TESTSUBSTANCE pIedrefnltuitoyr:ooPcetrafnlouaotreo,oPctFaOn,oiFcC-ac1i1d6,,aFmCm-o1n26i,umFCs-a1lt6;9a,lsoor referred FC-143. to as PFOA ammonium salt, ammonium (Octanoic acid, pentadecafluoro-, ammonium salt, CAS# 3825-26-1) `Rceommaplrektse:ly cThahreac3teMripzreodd,uaclttlhootunghumibneforrmuasteidownaisn3d7i.caTthieedtwteastssaammpilxetuwraeosfFC9-61.453-.10I0t'%s epsutristuybwstaasncneo.t and 0-3.5% C6, C7, and C9 perfluoro-analogue compounds. METHODS Methodguideline followed: Not stated Test type: Static GLP (VN): No Year study performed: 1952 Species: Daphnia magna age = First-Instar young length = 0.5 ~ 1.5 mm Supplicr: 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 monitoring of the test substance concentrations was done: Statistical methods: Chi-square test was used Test conditions: "Ditelsuttsio(nthewatteemrp.usiendtwheasthciardrbtoenst-fwialserneodt well water given). (all three tests), with a temperature of 24C in two ""TTewsto sroelpultiicoantesswweerreemtaadkeenfrom a common stocksolutionwith a concentrationofSg/L. 308 009207 ""ENxupmobseurr"oeWfavtDeesarspechlhsneiwmaeisrwteer2ry5ed0u1rm0i-Ln2g0gtlphaeesrstrebeseptalwikcaearstseacsofnotlalionwis:ng 200 mL est solution (6 cm in depth) "`PTHemwpasra8.ngedfofrrtohem t2e2st.s24inCwhichi was reported (measured at 48 hours) (DmOeawsausre8d2a-t8458 phopumrsf)or tests in which it was reported and for which it could be read wRaesmanroktsp:respeHnteadn.d hInafrodrnmeastsimoenaosnurdeicmtenwtasswaelrsoennoottpprreesseenntetde.dfordition wate; hardness during the test RESULTS D1o0s00eomfg/eLa.ch endpoint (1s mg/L): 48-hour ECS0 ranged from 126 mg. (with C.1. 86 0 183 mg/L) to > Remarks~:Lowest test substance concentration causing 100% mortality was 500 mg/L (from both - Mortalirteypolifccaotnetsrooflas swiansgle10t%es)in one replicate ofonc test - Abnormal responses included marked reduction in locomotion at 1000mg/L in one test Wsaatissiccotnotrryo,lgrievsepnotnhseeisnaftoirsmfaatcitoonrypr(oyviedse/da.ounknown): It appesrs that the control response was Satsastoicsitaitceadl writheChsia-ssuqauplaprreotpterssitsa)t,,eb:utt isSounmcelesatratwihstaitcatllhyeysirgfneifric(0a.nt results are presented (p values sTuhgegetsetsttshaamtptlhiesrdeisfufletrse(nicce. mtahye lbaergdeueratnogediifnfeErCenSc0esvainludeise). were inconsistent. The authors aSinnuacbllmyuidtiitnctgae:lrcso"tnhrefiemrmematarthkiosod:nwoTafhtseesnoKttlsidumebisssctrcaihnbcereda,nckosinacnmegpntflroearttpiuhorenists.ytuwdTayhsewnyaosatl3ps.rooSnpeoevtreelrytahlcehraveraaalscuoteensrsifwzreeodrmeamniudnldtliicapacltkeeeddt,ests contradict cach other. The authors als note that they conducted th studies specificaltloy evaluatedit REeCvSi0e5w,enrosinrfeomramraktiso:n Aolntdhioeutsghsptrheesaeunttheodr.s indicate tha dit may be the cause of he differences in 309 000208 REFERENCE sNtoutdieensowuegrhe icnofnodrumcattieodnbeyxctehept3wMhaCtosmupbamniytt,erEsnviinrcolnumdeenitnatlheLiarbroerfaetroernyc,eSst.ectPiaounl,, wMhNi,chcosamtpels:ete"Tdhefsreo.m May 0 June, 1982" OTHER dGeetnaeilreadlrrepeomratrwksa:s aTvhaiilsabslue.mmTahreyrewfaorse,batsheedcoonntaenrtespoorftthainsdsounmlmyalriym,itiendrdeafteareabnlcees1. No the protocols and results of the study, are limited. T"TEheSTmaCjoHrEcMoIncCeArnLfCorOrNyCinEgNtToRdAetTeIrmOiNneStwheervealuisdeidt.y fOorPtPhTisrteesctoimmtehantdOsNthLatYmNeaOsMuIrNedALte.st `cchoenmciecnatrlactioonncetnotwrahtiicohns1bethuesteeds,t soorgtahantisomnseacaeneaxcpcousreadt.elyIFditetiesrdmeitneermthieneedstthcahtetmhiecnaolminal ``bceonacnedntmruastitonbseaardcjuosntleyd, fdoorwenxwaamrpdleby505%0o%f.thIefamnealaystuircealdmceonacseunrtermateinotnss,ofthseotmoexiscoirttyhvaadlubeesecnan afnurdniosthheedr,pwheysciocuolcdhecmailccuallatperoccheesmsiecsalthartecmoivgehrtylroatweesr, athnedatcatkuealintetsotaocrcgoaunnitshmyderxoployssuirs,e volatility, concentrations. 310 009209 INVERTEBRATE TOXICITY "Title: Chronic Toxicity to Freshwater Invertebrates (Daphnia magna) TEST SUBSTANCE pIedrefnltuiotryo:osPiearnfclautoer,ooPctFaOn,oiFcC-ac1i1d6,,aFmCm-o1n26i,umFCs-a1l6t;9,alosro rFeCf-e1r4re3d.to(OasctPaFnOeAaacimdm,opnenituamdecsaalftl,uaormomno.nium ammonium sal, CASH 3825-26-1) `Rceommpalrektsel:y Tchhaera3ctMerpirzoedd,ucatltlhotounguhmbinefrorumsaetdiownasin2d6i4c.ateTdhiet wteasst saammipxlteurweaosfF9C6-.154-31.001%'spteusrtistuybwstaanscen.ot and 0-3.5% C6, C7, and C9 perfluoro analogue compounds METHODS Method/guideline followed: USEPA-1982, OECD 1951 Test type: Semi-statc life-cycle toxicity GLP (VIN): No ear study performed: 1954 Species: Daphni`aAgmea=g<na24-hour neonates Supplier: 3M Environmental Laboratory St. Paul, MN `CChornocneincttreastt:io0n,s5t,e8s,ted13:, A22c,ut3e6,teastn:d 6205,m4g0/,L6.3,no1m0i0n,al16c0o,n2c5e0n,tra4t0i0o,ns6.30 mg/L. (Results. however, were based on mean measured concentrations sce below.) Exposure period: 21 days Analytical monitoring: Not stated SCtoartpi.stDiucallutmhe,tMhoNdsr:ecaAlccuutleateesdt:statPirsotbiicts ainnal1y9s9i8s.. NCOhrEoCnsicatnedst:LOmEovCisnwgearveergaegneeraantgeldeumseitnhgodT.oxsAtastcl Rfoerpsruordvuivcatli.onIwCaSs0Sn(ofromralreapnrodduhcotmioong)enwoeurse tgheenreerfaotreedDuusminnegtI'CspTpersotgwraams.usSedu.rviFviaslheErC'sS0Tseswtowraes used encrated using "Trimmed Spearman-Karbar'. 3i 009210 Test conditions: "DDiilluuttiioonn wwaatteerr csohuermciestwrayswaaser:ated carbon lered well water hardness: 240 mg/L as CaCO3 palHkalinity: 12380 mg/aLs CaC03 CoD: 04mg ""EMxepdoisaurreenveewsaslelisnfwoerrmaeti2o5n0 mraitigolnaaslse:bemakeedrisu(mcownatasicnihnagng2e0d0omnLcoefesvoelruyttiownotdoaaysdepthofsbout S c~Amm;b1ieanntimlaalboprearto4r0ymlli,ghntoinagewraatsiounsdeudr(icnogolth-ewhtietset)fluorescent, at ambient levels, 16 hours per "Four redplaiyc)ate beakers were used ~"TWhaetreerwteemrpeer2a0taunriemdaulrsipnegrtchoentceesntwtraastio2n2 (+5 2per replicate) d=aAilsyusbpaseinssionoffish food and yeast containing mg dry solids per I ml mixture was fed on a hRaermmaornkisz:edpgHuiadnedlihnaersdsnteastse tmheaatshuarredmneenstsssohfowualtdebreduarminagxtihmeumtesotfw1e5r0emngot/LreassenCtaeCd.O3Aldsuor,intghethOePtePstSif wcahteemriswtarys ptoroihoitorghthe test was indicativeof during the test, the hardness value of 240 mg/Lofthe dilution RESULTS Doseofeach endpoint (as mg/L)*: 1144 ddaayy NNOOEECC ((sruerpvrivoadlu)c=ti6o0n~)mg8/mLg/L. 21 21 day day NOEC NOEC ((sruerpvriovdaulc)ti=on2)2 mg/L = 22 mg/L 2114 ddaayy ICC5500 ((rreepprroodduuccttiioonn)) ~= 4403 ((2385--4486)) mmgg//LL Aenldlpocilnetmevnatluceosncaernetfrratoimontshewreeraenablaysseisd ooftnhmeeadnatmaebaysuArsecld Ccoornpc.entratiaonnds the reported Remar ks: -mgAl/lLsturrevaitvmienngtsf,irsst guenerrwatavisonsitdaatvipshtnaiicadllslyapdpiefafrereedntnofrrmoamltahtetnheegeantidvoefctohnetrfoelst.groTunpt.he 36 and 60 h- eNecoonnattreosl (stDaurntneedttt'obs)eaprothdeuc13e,d2o2,n 3D6a,yan7.d 6R0epmroLd.uctcoinocnewntarsatsitaotnisstaifcatlely1s4idgnaiyfsi,caanntdlyidnitfhfer3en6tafnrdo6m0 m- g1/0L0%tesmtorstoalluittiyonwsaast 2n1otdoabyss.erved at any dose. - No mortality was seen inthe controls 312 009211 `moWraaslictoyn.trol response satisfactory (yes/ao/unknown): Yes, based on the fac that there was no cStoamtpiusttiecralprrientsouutss,. a Hoawpeprvoeprr,ialatcek:of infItoarmpapteiaorns msaodmee rheessuletsdiafriecuslitatiosiianleyptsi,gnificant, based on CONCLUSIONS There were no adverse effets on survival or reproduction at concentration<s 22 mg/Lfor 21 days. Sacucbomridtitnegrso" trheemmaertkhso:doTlhoegyKlaivmaiislacbhleraantkhinegtwiamseo3.f tThheetasrttudoyfhweaseaxptparently well conducted Reviewers' remarks: none 3M Company. Chronictoxicty to freshwater invertebrates. [No other information available] OTHER GNpreoontdeoerctaoallislreadenmdraerrpeoksrsut:lwtsaToshfiastvhaseiulsmbtlmuead.r,yTahrweearsmebifaocsree,dtohencaonstuemnmtsaorfytrheipsorStumamnadroyn.ly lirmeifteerdendcaeta10abhlees. Ahlesoa,cuatneatceustteweassnwoatsvecroyndculcetaredf,ropmostshieblsytada. range-fnding study. However,thepurpoosfe "TcThEheeSmiTmcaCajlHocEcoMonInccCeeArnnLtfCorrOatNbrtCyeiiEnuogNsnetTodsR.dAestoTeItrhmOaitNnoeSntewheecravenaluaiscdecidut.yraftOoePrlyPthTidsertsecrtcmosimnmetehtanhtdesOtNehsaLttYchmeNemaOiscMuarIleNdAeLst ccbooennaccenenndttrrmaaattsiitoobnnes0raewdhjoiunclshyt,0dfootrwheenxwtaeasmtrpdolerbgySa05n%0i%os.famtteshFeaenmaxelpayostsuiecrdae.ld Imceoiansicuserdneemtterenratmtsiinooef sndhesothmtaotexiscshieottynohvmaaildnubaelesccnan acfonunrdcnioesnththerdea,tpiwhoeynssciocuolcdhecmailccaullatperoccheesmsiecsatlhraecmoivgehrtylraotews, tahnedaactkuealnftestaocrcgoaunnitshmyedxrpoloyssuirse volatility, 313 009212 INVERTEBRATE TOXICITY Title: Acute toxicitytoaquatic invertebrates (Daphnia magna) TEST SUBSTANCE. pIedrefnltuiotryo:ocPtearnfolautocr,ooFcCt-a1n1o6i,c FacCi-d1,2a6m,mFoCn-1i6u9m,soarltFCa-l1s4o3r.ef(eOrcetdanooiacsaPciFdO,Apeantmamdoecnaifluumorsoal-t,, aammmmoonniiuumm salt, CASH 3825-261) RTiesmpaurriktsy:wsThneot3suMffpircoiednutcltyiochnalraoctneurmizbeedr, waaltsho39u0g.h cTuhrreenttestinsfaomrpmlaetiwoansinFdCi-c1at2e6s,taiswhaitmeixptouwrdeeorfy7s5o.lid. 93% test substance and 7-22%CS, C6, and C7 perfluoro analogue compounds METHODS Methodguideline followed: Not stated Test type: Static GLP (VIN): No ear study performed: 1987 Species: Daphnia magna Age = < 24 hour neonates Supplier: 3M Environmental Labs. Concentrations tested: 0, 100, 180, 320, 560, and 1000mg/L, nominal concentrations Exposure period: 48 hours Analytical monitoring: None because concentrations were nominal. Statistical methods: Probit analysis Test conditions: "Dillion water sourcewas carbon-filereTdewmelplwwaatse2r1wCith the following chemical characteristics: DO was 9.4 ppm pHwas 7.9 TSteasbtilsiotlyutoifotnhseweesrtecphreempiacraeld sboyludtiiroenctawseignhottsnaodtdeidtion 314 009213 "Exposure depth) vesselwas a 250 mL Pyrex glass beaker containing 200 mL test solution (tao 6 cm ""WNautmebrecrohefmdiastprhyniddusripnegrtresetp:licate was 10 DO control: 9.0 mg/L p1H000mg/Lexposure: 8.8 mg/L control: 80 1000 mg/L: 8.1 Temp 2c Remarks: No other detailsof the test conditions were presented, including water hardness. Dose of each endpoint (as mg/L): 48-hour ECS0 was 221 mg/L (95% CI: 186-261) Remarks: -reLpoliwceastets)test substance concentration causing 100% mortality was 560 mg/Lat 48 hours (both - There was no mortality in the controls `Was control mortality response satisfactory (yes/no/unknown): Yes,basedon the fact that there was no. Statistical results, as appropriate: CONCLUSIONS Not presented "The 48-hour ECS0wasdeterminetdo be 221 mg/L (with a95 % C.L. of 186-261) Steusbtimnig.tteHrosw"evreemra,rskasm:pTlhe epudraittayqwuaaslintoyt Klimisch properly crhaanrkaicntgewriazse2d.anTdeisttliancgkmedetatnhaleyctriictaelricaofnofrirqmuaatliiotny of test substance concentrations. Reviewers' remarks: none REFERENCE Ap3rMilCo3m0.pany. 1987. [Report title not given.] LabRequest Number 1282-1. Completed on OTHER GNeondeertaalilreedmraerpokrst:waTshiasvasiulambmlea.ryTwhearsefboarsee,dothne caosntuemnmtsaorfy trheipsorstumanmdaornyl,yinlirmeifteerdendcaetatotatbhlees. protocols and resultsof the study, are limited. 315 000214 T"TEheSTmaCjoHrEcMoIncCeArnLfCorOtNrCyiEngNtToRdAetTeIrmOiNneStwheervealuisdeidt.yfoOrPtPhiTs rteesctoimsmtehantdOsNthLatYmNeaOsMurIeNdAteLst ``ccchooennmccieecnnattrrlaattciiooonnnstcaorewehnoitnclrhy,a1bfteotiruhoseecxntdaess,mtpsoloregt5ahan0ti%soomnfsetachraeenemaxecpacoussreuadrt.eedlyIcfodnietctieesnrtdmreiatnteierotmnhisen,ettdehsetthctaohxeitmchiiectnyaolvmailnuaels can bfeuraninsdhmeud,swtebecoaudljdusctaeldcudlaotwe nchweamirbcaydl5r0ec%o.verIyfarnaatlsyt,iacnaldmteaskesuirnetomeancctosuonftshoydmreolsyosritsh,avdolbaeteinl.ity, c`aonndceontthreartipohnyss.icochemical processes that might ower the actual tes organism exposure 316 000215 TOXICITY TO INVERTEBRATES "Title: Static Acute Toxicity of FX-1003 to the Daphnid, Daphnia magna TEST SUBSTANCE aIdmemntointiy:umPeprefrlfulourooraocotcaannooiactaec,idP,FaOm,mFoCn-1i1u6m, sFaClt-;1m2a6,y FaCls-a16b9e,rFefCe-r1r4e3d,toorasasPaFOmaSjoarmmcoomnpiounmenstalto,f FX1003. (Octanoicacid,pentadecafluoro-, ammonium salt, CASRN 3825-26-1) suRffeimcaireknst:ly Tchhaera3ctMerpirzoeddu,ctthioounglhotanvauimlbabelre wiansfo2r3m2a7t.ioTnhiendpiucraitteydoiftwtahestaestsoslaumtpiloeno,fF<X-4150%03a,mwmaosnnioutm paenrafllougoureooccotmapnooautned,s.50% water, <3% inert perfluorinated compound, and 1 - 2% Cand C; perfluoro- METHODS Method/guidelinefollowed: OECD 202 Test type: Static GLP (YAN): Yes Year study performed: 1990 Sfpreocmieasn: inD-ahpohunsiedcsulutsuerde ithnatthweaesstmawienrteailnesesd tuhnadner24tehstoucrosndoiltdiaonsthfeorstaatrtloefastthe14 test. They were produced days. Prior to testing, dNaepwhnHiadmspwsehrierem)aiunntdaeirnestdatiinc 1co0n0di%tidoinlsu.tioDnurwiantgerac(ccloilmleacttieodn,frdoampwhenildlssawterEenvniotrotSryesatteedmsforindiHsaemapsteoann,d. wyeearset,ftrreoeuotfcahpopwa,reanntdstihceknfarsess,hiwnajtuerrisa,lgaanSdelaebnnoarsmtarluimticeaspraictohermbuetguimnnoinncgeofdaitlhye test. Daphnids before the test. were fed Daphnids were not fed during the test. `Supplier: EnviroSystems-3dM-atepshtsnubisdtasn,ce ``cCoonncceennttrartaitoinosonsfttehsetetde:st Asusbcsrteaenncienwgetreset0w.a1,s 1p,e1r0f0oramnedd 1p0ri0o0rmfgo/tLh;e dtehfeinniutmibveertooxfirceiptlyitceastt,esNowmaisnnaolt indicated. were used: Fo0r(tbhleadnekficnointtirvoel),tes1,50f,ou2r50r,ep4l0i0c,at6e0so0,faenadch1o0f0t0hmeg/fLo.llowing test substance concentrations Exposure period: 48 hours AnalyticDailssmoolnvietdoroixnygg:enT,esptH,scuobnsdtuacntcievciotnyc,enatnrdattieomnpserwaetruerenowtermeeamseuarseudredudrainndg the study. recorded daily in each test chamber containing live fest animals 317 000216 S(tSatteispthiacnal,m1e9t8h3o)d.s:TheRepsruolbtist,ofmothveintogxaivietryaegse,t worerleinienatreirnptreertpeodlabtyiosntamnedtahroddstwaatisstuiscealdtteocchanlicquuleaste the 48-hour ECs (based on immobilization) using nominal concentrations of the test substance. cToelsltecctoenddiftrioomnwse:llsWaatterEnuvsierdfooSyrsatcccmlsimiantiHoanmpotfonth,e NteestworHgaamnpisshmisr,e.anWdaftoerrawllatsoxaidcjiutsytteedsttionag,hwaardsness of a1c5c0limmga/tLi.onaspCeraiCoOd;(2a4n-dhoauerrsatperdioirn1S0t0h-egatlelstoninpiotliayteitonh)y,letnheedtialnuktsiopnriwoartteoretsetmpienirtaitatuiroen.waDsur1i9n.g8tCh.e No stetsotcvkesssoelultsiwointwhaoustptrheepaursecdo,faastohlevteenstt.sTubhsetastnacbeilwiatysoaftdhdeedtdeisrtescotlluytitoondsilwuatsionnowtaitnedriccaotendt.aiNneodmiinnatlhe creopnlciecnattreasotifoncsaocfh ttheestecsotncseunbtsrtaatnicoenwweerree0us(ebdl.anTkwceonnttyrodl)a,ph1n5i0d,s2w5e0,re40r0a,nd60o0m,lyanadnd10eq0u0amlgl/yLd.isFtoriubruted `ofatmhonegtefsotusrolruetpiloicnat(easoppfrocxaicmhatterleaytm7enctm. dEexptpho)s.urTeevsetsvseeslssewlserweer2e5r0amnid.omgllyasasrbreaankgeerdsicnoanntaiinnciunbga2to0r0 mL ddeutreirnmgintehde:48-Cohnoduurctteistv.itDyur8i0ng-0th9e0t0espt,mthhoesifoelmlo(wcionngtrwoalteexrpcohseumriesatnrdy r1a0n0g0esmg(0/L 48 hour) were. exposure); pH 8.1 -- 81.0200(cmongt/rLoleexxppoossuurree));,D8i.s3so-l8v.e4d(01;0090.0m~g9/.L5emxpgo/sLur(ec)o;ntTreomlpeexrpaotsuurree),199..51-2-09..15mCg/(Lco(nt1r0o0l0emxgpo/sLure and eaxcpcoesputraeb)l.e lAeevrealst.ioAn w1a6s-hnooutrrleiqguhtiraenddd8u-rhionugrthdearsktupdhyottoopmeariinotdaiwnasdiasustoolmvaetdiocaxlylgyemnaicnontcaeinnterdatwiiotnhscaobool.ve awphpirtoexfilmuaotreelsyce0n.t0l1i8ghgt/sL.that provided an intensityof45 Es m. Loading rate during the toxicity test was Remarks: No additional comments RESULTS Dose of each endpoint (as mg/L): Screening test: LC= 1000 mg/L, NOEC = 100 mg/L D=ef5i8n4itmiveLtes(t9(5b%asceodnfoindeinmcmoeblielviezlat=i4o0n0).: 241-0h0o0urmgE/CLs)>1000 mg/L, 48-hour EC R1e0m0a%rskusr:vivFaolrathaellscotrheeernitnegstteesdt,caofncteenrt4r5atihoonusr.soFforextphoesduerfei,nitthievreetwesa,s6al0l %essturvveissveallsamt1ai0n0i0aimnge/adL calnedar aanppaevaerraangceewtehtrowuegihgohutt(tbhleotstteuddyd.r1y)00o%fsu0r.0v0i0v7galaotctchuererenddoifntthhee ctoenstt.roLloeaxdpionsgurrea.teCdounrtirnogltdhaepthonxiidcisthyatdest wreassulatpepdrionxai4m8a-tehloyur0.L0C1:8ngoLf.33Exmpgo/sLuraeondfa4d3ap-hhnoiudrs tEoCtsheorfef1e6rmegn/cLe.toxicant, sodium dodecyl sulfate, `Was control response satisfactory (ves/no/unknown): yes Statistical results as appropriate: No additional comments. C"TOheNtCesLtUsSamIpOlNeS48-hour ECS0 for Daplnia magne was determined to be 584 mg/L, with a 95% confidence intervalof40-0 1000 mg/L. 318 009217 sSaumbpmlitetpeurrsi"tyrweamsarnkost:prKolpiermliyscchharraancktienrgiz2e. dTaensdtinnog mateteetmsptthweacsritmeraida ftoor cquoalniftyitetsesttinsg.ubHstoawnecveer, concentrations Reviewers" remarks: The submitters" conclusions appeartobeaccurate, based on the data. REEERENCI HEanvmiprtooSny,stNeHm.s,EInnvc.ir1o9S9y0s.teStmastisctuAdcyutneumTboexirc9i0t1y3-o3f.FX-1003 to theDaphnid, Daphnia magna. OTHER OGeNnLerYalNrOeMmIarNkAsL: TTEheSTmaCjHorEcMoIncCeArLn fCorONtrCyiEnNg TtoRdAeTteIrOmiNnSe twheervealuisdcid.ty fOoPrPthTirteesctoimsmtehnatds `tchahtemmiecaalsucroencdetnetsrtacthieomnitcoalwhciocnhcetnotrtahteitoensst boreguasneids,mssoatrhcatexopnoesecda.nIafcicturiatdeeltyedremtienremdintheatthtehetest vnaolmuiensalcacnonbceeantnrdatmiuosnts baereadonjluys,tefdordeoxwanmwpalred5b0y%5o0f%th.eImfaenaasluyrteidcaclonmceeansturrateimoennst,sothfestooxmiecitsyort vhoaldatbileietny,faunrdniosthehde,r pwheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcmoviegrhyt rlaotwese,ratnhed atcatkuealintteostacocroguanntishmydrolysis, exposure concentrations. tPesut.ryTonfstohmeetetsetstmsaittearpipaelaarlesdo tishaat m1a0j0or% cteosntccehnemaincdalwawsasnoutsesdu,fffiocrieonttlhyercahsarcahcetmeirciazledofinltehsisser wpuarsituys(eadpipnrooxtihmeartteelstys,8f5o%r)nowaosbvuiseodu.s sWtaatteedr,reaassoonl.venItn ifascotp,r3oMpaninolt)hoerirasucmommbairnyaotfioenaocfhbotetsth astgatre:ee"Dwaittha tmhaiys cnoontcearcnc.urIantealdydirteiloant,e itfoxtihciistywoafs tahe"ttyepsitcsaal"mpTlSeCwAitshecthtaitonof4hreevteisetws|,ubswtoaunlcde. " mreejaescturtehemseentsstuodfietsh,epteensdticnhgemriecceailpitoftahdedtietstiomneadliiunmf.ormation on purity and studies on analytical 319 000218 AQUATIC PLANTS TOXICITY "cTaipthrei:coGrrmouwntuhm and Reproduction Toxicity Test with N2803-3 and the Freshwater Alga, Seerastrum TEST SUBSTANCE peennttiadteyc:aflPueorrfol-u,orCoAocStaRnNoie33a5c-id6;71m)ay alsobe refered to as PFOA, FC-26,or FX-1001. (Octanoic acid, liRanebfmooarramrtakotsri:yonaTsihnNed2i83c0aM3t-e3dp.rioTdwuhacestipaounrmiiltxoyttouufrtmehboefers9a6wm.a5psl-e216w90a.0s%Tnhotetessttuessftufibscsaitmeanpntlcleey wachadasra0FcCt3-er.2i6z5,e%dr.eCfaoel.rtrCheodau0gnhdbcyuCrtorheentest ps`awemarptuleoeirspoor-pehrpoaorpmaaotnliooongsdouilructeiocotmnip.oonuIsngnditshv.eenprTothteohcteoeltlaasmbaoemrnpadltmoeerwynatws,eawrhefiosdtsitpkaootwelddvetrhta.thAtstheestSamatametpdelrbeiyaalhsien c8sou$mb0b.mi3in0etd,wtihteh isopropanol ina S0:50 rato prior to use METHODS Methoguideline followed: USEPA-TSCA Guideline 797.1050 Test types Static GLP (VN): Y ear study performed: 1995 Stfhpeeaesctdiee1fs4i:nditaTiyhvseepfarslitograwe(a0twsh efrerdoaecfmciln1iit0mi-avdteaeydesiot.lndsTechruetl,seu,ben-rsiacmhpeldeomfedailagaaendusmdainttaiimnoceudlaatteesmtecodndiattitohnssfaorr aotf SAuusptpilnier: The supplier ofthe algae eulure was the Culture CollectionofAlgae at theU ofTexas at Measureofgrowth used: numberof celsimL., grow rate oCusnoeendc:deinl0tu.tr0ia5ot0ni,wo0n.as5t0et,e5cs.ot0ne,tdr:aoFnlodarn5td0hmievreaanngo(emt-ihfeniannlduimcnbognectreesontf,trretaphteliifoconaltlweoeswriwenagusscenodnociesnnptterhcaeitfsiitouenddsy).oFfoTrtthehestSs0u:db5es0tfaminicxneteuwreseresoesf p(ies5or0pf%roorNpm2aan8no0cl3eo-a3nfdtahneesdtt5os0xui%bcsiittsyaontpcerseto.(paNAn2lo8ll0s)3u-al3n)tdswteawsestrcseuobnrssetipadonretcreeeadd.bfoortebhceeoi1v0et0dhe%(bNea2st8i0ss3ou-fb3setwsaitntcsheuobudstutraiinoncpgerotapha-encaslt)e.dThe 0au.sn-3dt2es.rt6se3da,cco13nt0ce,esnt2t5cro0an,tdiaiotnnidosn5sw0.e0r:mg/0L,.63T,hr1e2e5,re2p5l0i,ca5t0e0s,oafnedxc1h00c0onmtoLl antdheteasst-rceocnecievnetdractoinocnenwterraetitolnssewedre: Exposure period: 96 hours 320 000219 APnHaliynteiaccahl tmeosntivteosrseilngw:asComnecaesnutrreadtiaotntsohefbtehgeinensitnsguabnsdtaenncde owfertehentoetstm.eIanscuurbeatdodrutreimnpgerthaetusrteudwy.asThe `wmietahstuhreedteasntdversescelosr,dewdasdacloy.ntiTnhueoutselmyperreactorudreed.in a representative vesselof water, which was incubated Setsattiimsattieca7l2-meatnhdod96s-:hoCuerllECdeinqsivtaileuse,sgarnodwt9h5r%atec,onafniddpeenrcceenlitmiitnsh,ibwietrioencvaallcuuelsa,tewdhuiscihngwetrhee used to cbeilnlosm/imaLl,inttheerapvoleartaigoensmpeectihfiocdg(rSotwetphharna,te1s9,8a4)n.d Atlhle cnaolmciunlaalticoonnscweentrreatpieornfsoorfmetdheutseisntgstuhbestnanucmeb.erThoefno(obAsNerOvVeAd-)e,fftehcet-ncuomnbceenrtorfactieolnls(/NmOL,ECa)ndwtahse caavlecrualgaetesdpeucsiifnigc&gpraorwatmhetrartiecionncea-cwhatyesatnavleysssiesloaftvtahreiaenncde.of the test. "`Tceosmtbcionnidnigtdieo-niso:niTzhedewaaltgaelrmaenddinuumtriweanst sptroecpksa.reWdaatcecrorudsiendgftoorUthSeEaPccAlirmeactioomnmoefntdheedtceostncoerngtarnaitsiomnssabnyd fuosreal(lthteopxiHcoitfyttheestsiynngtwheatsicstaelriglael,meenrdiicuhmedamtetdeista,inaidtijautsitoendw1a0sa7t.4a)r.geAtlpgHalomfed7i.5uwmitwha0s.1usMedHfoCr cpurliuorritnog. afnordmauslattheetdeisltuemnt. eA wcdhaesmpiiecraflaocrhma,erdac.tePrhiozsapthioonroousfa, rmeitprraetsee,natnatdivcehlsoarmipdelewoefrteesdtetmeecdtieda,atantdhewfaotlelrowuisnegd to c`omnecdeinutrmatiinocnlsu:de0d.4c6a,d0m.i0u8m, a(0n.d001042mmyg//LL,)reasnpdectlievaedly(.0.H08eamvg/yL)m.etOatlhsedretpeoctteendtiainl cthoentdailmuiennatntasndweterset at or abcetliovwe itnhgerleedvieelnotfandedtetcotbieon.stTabhlee tuensdtesrubssttoarnacgee a(nasd-rteecsteiinvgedc)onwdaitsioansss.umAed10100h0amvge/La ppruirmiayroyfs1to0c0k% Seonlruitcihoendomfetdhiea.tesAtppsruobpsrtiaantceea(maso-uensttseod)ftwhaiss psrteopcakrseodlubtyiocnowmebrieniandgdeNd28d0i3re-c3tl(yatso-tdeisltuetdi)oannwdatsteerritloe, f1o0r,m0u0l0acteelltshiemtLe.stEmxepdoias.urAelvgeascsewlesrceondsiisstrtiebduotefd2a5m0omnLg tghlraeses rEerplleicnamteeysoerffclaacshkstcroenattamiennitngat5t0hemaLteofotfest dSoulruitnigont.heTetesstt.veTshseelpsHwoefrethrantedsotmsloyluatriroannsgfeodrothnea2r5o0t,ar5y00s,haaknedr a1d0j0u0stmeed/tLo e1x0p0osruprmeicnoannceinntcruabtaitoonrs awfefreectiendtthheersaunrgveivoalfan2.d9-s4.u0bastetqeusetnitnigtiraotwiotnh.oAfsthsetaatlegdacb.yTthhee smuebamsiutrierd,wthaitserlocwhepmHismtrayyvhaalvueesa(d0v-e9r6sely thoeumrpse)rawteurree arsafnogl=leow2s:3.5p-H24raCn.geA= 274.-4h--ou1r0.l3ig(hctoanntrdol0-ehxopuorsudraer)k,p2.h9 ot-op3.e0 r(i1od00wa0smagu/tLomeaxtpiocsaulrley), mean mfoaoitnctaanidnieesd.wAiltghaclocoell-lwchoiutnetfsluionreeascchenttesltigvhetssstehlatweprreovdiedteedrmailnieghdtdianitleynbsiytymoefaapnpsroofdxiimcattelmyic3r5o0scope counts witha hemocytometer. aRcecmeaprtekds:raWnagtefeorrhSa.rdcnaepsrsicwoarsmunottumintdoixciactietdy. tTeshteinpgH(7f.o5r+ma0.n1y).eAxsposstuarteedcboynctehnetrations was outside the. sluabbmoirtatteorr,y tahnedrethaeppperaorcsedtuorbeecaonddiusccrteepdanbcyytbheetlwaebeornattoherystaompplreepparreepatrheattieosnt sdoilruetcitoinosns given to the RESULTS deDfoisneitoifveesatcuhdye,ndtphoei9n6t-h(aosurmgE/CLs):(aTnhdeasNsOocEiaCtefdor9t5h%ercaonngfei-dfeinncdeinlgimsittsu)dywwasas15800 mmgg//LL. (F1o2r5t-he2.50 mmgg//LL)).. bbaasseedd oonn tteesstt ssuubbssttaannccee aass--reescteeivde(d.50T%heN29860-3ho-u3raNnOdE5C0%anidsoLprOoEpaCnovla)luaensdw9e0rmeg1/2L5 (a6n3d-251300 321 000220 am13l0Lemure.spercetsipveecltyi,veblays,edbaasedesotn shuebsttasncseubass-ttacnsceed,asTohce9d6-.houTrhNOclCgarnodwtLhOdEotCa vaplrsowmerse 63 and Table 1: Cell growth dataofacute toxiiy test with N2803-3 and thefreshwatersae, Selenasiram coa`nNscoetmnetisrnaeatdli.on| Hours ne `Numberofcells/ml x10"(hour) = IPnehriVcbaietniton|| aPehrvcaeint Deity | Growin [Comm [*10 [3=| m= e[= a 7r1e%n |] oe CEenToTaTow C0 0 <0Tio aw ow a AT | 0Tio to Too] CCT rs o T0 o a01 =il0o Ti1 ioo[<=i0o0 1100 | i[taoo ] chRheeamanagrgkeasi:tnocAthlfersTiaz9se6kscoounltohrrs,oaffecxmoponorvspouhrooelf,oagnhyyrw1shsewneercaeotmnepoansr!iegdrnso1oufh.aegnrceognsatotoli.on,T,hfetloehcceeulewatiiaoernN,poeIrpHadoRheormleonesce of (etWaattredd,nbayatath.et1os9bu9eb5ma)idltegepraolbnis,otlsnoogttiecdsaltedhaadtta,0g0eb0nearsaegtdLeodnobfyh'epprreeolvpiso!uosfsccfxohpnoPemosrdteddofnseotavheei1t0tstsoprEmwoopn.estT.chosnhpsoulting pGinTHdNimcIaaRtyIedShh.vaetTcehsaetssecuodbnscietnnahtnirbcaietticiooonnncoofefntsrgaoatpiopgnyso!abawolvcaeoth1ho2i3gihnmetrLhc.oernstceceehnedamiocpnaHsl ovifidueshsstsab4c.tonucnet.ohrThoheweewieteeyor Concematon ofet substance Gerd 10 cave 100%moray ws 250 mp Was control response satisfactory (yesinounknown): yes Statistical resus, as appropriate: No addin! comments concuusions NmTOhaeETCNObaEnaCdsLfooOnrEtthCesvrlsauunbsgsest-awfnencrdseiangS12-s54tSauidncyddw3aa5nsd095m00emllgLL(.a,sFbotrcdte)heoadnnefd5in9ituinvbedssat1nu3de0ss,mtahae.c9we6-vrheeoduc,eiETvhCeesdoSwonso1n5r0 realy pcSouenbacmreisntrebarteso'.nsrceirmnaetrphkass:ntcKlyoilnubitecithowner.eannSktaihmnegpsl3.eaTpruhertspyraespyanrtaltaciskosun adfniafrleyecttiricoanclshamSrevaacsetuerr0iesmteedhntAsobdfotoremsstoanslsuybis.tdasncce m 000221 procedure have been conducted by the laboratory adversely affected by inital to prepare the low pH values test solutions. in the higher Survival and test substance growth of the algac concentrations. may fRuervtiheerweirnsc'reraesemdargkrso:wthThienhcibointcilouns,iwoanss appear clearly tsotbateedsausppaorptoesdsibbyletshoeudractaeo. fTehrerolr.ow pH, which may have FTrRe.shWwialtbeurrAylgLaa,boSrealteorniaesst,ruInmc.ca1p9r9i5c.orGmruotuwmt.h and Reproduction Marblehead, MA. Toxicity Test with N2803-3 Study number B93.TH. and the OTHER OGeNnLerYalNOreMmIarNkAsL: TTEhSeTmaCjHorEcMoInCcAenL fCorOtNrCyiEngNTtoRdAeTteIrOmiNnSe the validity were used. fOoPr PthTisrteecstoimsmtehnatds cthhaetmimceaalsucroendcetnetsrtacthieomnitcoalwhciocnhcetnotrtahteitoensstboerugsaenids,mssoatrheatexopnoesecda.nIaFccituriastdeeltyedremtienremdintheatthtehetest v`naolmuiensaclacnonbceenatnrdatmiuosnts baereadonjluys,tefdordeoxwanmwpalred5b0y%o50f%t.he Imfaenaasluyrteidcaclonmceeansturrateimoennst,sothfestooxmiecitsyort had been volaility, furnished, and other we could calculate chemical recovery physicochemical processes that might rates, and lower the take into account hydrolysis, actual test organism `exposure concentrations. 323 009222 TOXICITY TO INVERTEBRATES "Titles Acute TonicityofN2803-3 to the aphid, Daphnia magna TEST SUBSTANCE peennttiatdeyc:afPteurofrlou,orCoAocStRanNoi3e3a5c-d6;71m)ay also be refered 1 as PFOA, FC-26, or FX-1001. (Octanoie acid, ssRuaefmmfpialcreik.ensFt:lCy-T2c6hha,eraw3catMserprierzfoeeddru,rceatdlitothonobulyogthtrhauevmtabeletarblwalbaoisrnaf2to6o9rr.myaaTtsihoeNn2tei8sn0td3isc-ua3btsetdTahintecwepawurastsymaiowxfhttiuhtreeespoafo9mw6pdl.eer5.vaTs1h0wo0tre%stest substance an0d 3.5% Co C, and Co perfluor- homologue compounds. METHODS Method/guideline followed: U.S. EPA-TSCA Guideline 797.1300 Test type: Static GL (VIN): Yes with ane exception: the stabilityofthe fest substance was assumed, but not verified. Year study performeds 1996 sSLppaebecociriaemtseo:nrsieWwsaetirneerMpaurrsobediducchfeoedraadbc,ylMiaAdmu.alttiDodanapphofhntiihddess eshmatptloworeygreaednimisanmitsnhtewaasistnuedddeyitwoinnedirezeredoletwsacttoehnradnciot2li4loenhcsotuefrdosraomtlodrTeR.TetWshitalnb7ury daaacbycnslo.irmmTaahtliieotnoi,reisdgaaitpntahelnsictdulsintiwutreieartewioanns.otTotbhrteearaietneewddafsforrnodomismeAoaqrsuteaa,ltiihtceyyRdeuwsreeiranergcihthcOeero4gf8anahipospumarsrs,epnHrteaScmiepcdtkinonengs.st,hNEeiLn.tjauDrrtuirso,iftnmghd test. dTahielycudlutrurienwaacsclismuaptpiloinc.d wDiatphhniydesawserroeuntotchfoedwdmuirxinagnhdethfeestf.reshwater alga Selenastrum copyioepmon Ssuubpsptlainecre: TR. Wilbur Laboratories supplied he test organisms. 3M, th sponsor, supplied the est `(caaCsco-hnrcececonenticrveaentdti)roawntesiroetn:eswt0ee.rd:e05uF0sod,r.t0.5hT0,hs5e0af,toel50ls,ocwraiennedgni5nn0og0miemnsata/,lLt.choenFcnoeornmttihrneaatslitoacntoisnccwdeeenrftiernailttiiizvoeensde:sotft,h0tew(obtearsnetpksluiccboasnttveasonyoc,ef an1no3dm0i.Sn20a00l0,mco3n6gc0e,nt6r0a0t,iaonnodf1t0e0st0smugb/sLt.a(ntceest(eads-aresace5i0v:ed5)0 imnixstoluurteoiofn west sa0u(bbslsiaannkeecaonndtrios)op65r,op1a1n0a,h15T0h,e300, 324 000223 Exposure period: 48 hours Afensatlsyetircealbmaosneditoonrinnogm:inTaelsctosnucbesnttarnacteicoonncofetnetsrtatsiuobnsstawnecree. nDoitssmoelavseudroexdydgeunr,inpit,hcostnudduyc.tiAvliltyt,oxaincdity ttteeestmm.ppeerraattuurree winaerbeeamekaesruroefdwaantderienccourbdaetdeddaalmyoningctahcehtefssttvceshsaemlbsewratsharteccoonrdteadincgodnltiivneauonuismlaylsd.uTnhgethe Satvaetriasgteicamletmheotdh,oodrsb:inLomCialanpdroEbaCb.ilivtayluweisthwenroen-clailnceualraitendt,erwphleantipono(Stsepshbaynb,pri1o9b8,3i)t.analysis, moving Test conditions: aWtaTtRe.r uWsieldbfuorryacLcalbiomraattoiroineosfihneMatrebsleohregaadn,isMmAs.anWdatfoerrawlatsoxaidcjiutsytetdesttiong hwaarsdndeesisonoifze1d60w-a1te50comlgl/eLc.ted CrtehaprCreoOsu,egnaathnatdpiavsretiosrlaeemdpfilneerSo,0f0u-dlgitalrlualtvoiioonlnepwtoalsyteeietihdzyeeltree,ncetaetndadnikarsc,otiwavh1aet0re.d0e3ciatmrwgbao/nsL.:acAarlactahetedmhniecdpaoltceconhntatiriaanlcutcoeuorsniltzyaamtpiiaonsnasnoeftdsare vboecleoiwvetdhefrloevmeltoh fsdpeotnescotri,onwoirthnoitsopprresoepnatn.olThine fe5s0t:s5u0bsrttan.ceHwoawesvperre.pathredfbesyt csoubmsbtiannicnegpNr2ep8a0r3a-t5i,onav. "dTihriesct0i:on5s0gmiivxetnutroetwhaeslatbhoernatcoornysiwdeerreed00dibseso1lv0e0%thteetsetsstumbastteainacleidnuring0:t5h0e twoaxtiecirtsyotprso,pbauntolallSlreusiuolnts. aisroprreoppoarnotle)d.onThaentaecsttisvuebisntgarnecdeiewnatsbaassissu(maecdtive ihnagvreediepnutrti yhoef t1e0t0s%uabcstiavneceinag-reTdcieenitveadndmi(0nubse hsteable 1u0ntdheer ssttaorrtaogfetahneddteefsitniintgivceontedsittiwointsh.NF2o80t3h-e3esitndoircgaantiesdmsc,ulmteuraesutermepmeernattsurmeardaengduerionfg 1t9.5h-e270d.a5ysCpriaonrd acfiodnmailbsisvnoolilvnuegdm2eo0ox.fyg2eo0nf00tchomenLct.eensttTrshauetbistoetnsaotnfcveeast(se5ll0es:a5ws0etmrie9.1x3tmg0u/r0Lem.oif.ANl21a800s030-bme3ga/kaLen.rdssiotshcoakptrscoooplnautntaoiilon)neadwna2ds5d0pirlmueitp.iaoronefedwatbtyer 0a s`awodeldrueetdiiontnodi(dsaicplrupitrmioioxnniamtweaalttyeeadneindptechsqtuwaavlselsysedclisms)r0bdufutoreridmnualtamhtoeentfgesstt.wmoAeppdrreipoalpiwrciiaatttheestohafemaoucusenhtoscfaostfstcolhovenecsnettn.otcrTkawtseionolnuttyiTodenasptwhenrieds dveefsisneiltsivweerteestr,atnh dofmollyloawrirnagngaendgeinsawneirnecuebsattiomrataenddflrooomsemleyacsouvreemreendtdsu:rindgitsshoelv4e8d-hooxuyrgetent. D8u.r1ing8the amned/LK,-htoeumrpedraartkurpeho=to1p9e:r4i-o2d0w.i7thC., 1co5n-dmuicntuitveittyra=ns$it7i0on p6e1ri0oudmwhaoss/auetmo,maptHic=al3l.y3m8a.i5n.taiAned16w-ihtohurcoloiglh.t mwahiintaiflnuodriessscoelnvtedliogxhtysgtehnatcopnrcoevntirdaetadioinsghatboinvteenasnitaycocfep5t8abfloeotlceavenld.les. Acration was not required eAacsthatciocncteesnttrwaatsiocnonadnudct1e0ddawpihtnhi3d9s0rempgl/iLc.atseowperroepausneld.enThdisdeisltutwioanswcaotnedruccotnetdroiln.aTmwaonnreeprliScmatietsaof(0 he fest with N2803-3. Measurements made during the 7days prior fo ai2rn0irta.ina1gti2eod0n i9onf aatnhwdaaitsedoipsbrsaootplhavnaeondldottxhoyegceiignyhctoesnntct.ennTsthiretasyteiwomnaesoafs1ut3ref-- ma2es5tnto5os.t3icnamdngi/dcLla.etse.TdhTaehceutlefttoulrveleostwseiemnlpgewrreaatnrugereesrawrnaednrogemeloyf 2e0s.t9imCa,tecdonfdruocmtimveiatsyu=re5me3n0t-s4d0urimnhgotshieesmt, pdtis=solv8e.d3O.5;. 8.1 8.5 mg/L, temperature = 20.4 325 009224 Remarks: No additional comments RESULTS DosofBaacshedeondnpeoisntbr(aasnmeg/sL)se:seLcCcsneadnd ECs values and 5% confidence nervals 2244chhoouurr LECCs, =- 430200 (G37000-549000))mmLg/.L. 48-hour LCs= 400 (350 460) mg/L. 48-hour ECs = 360 (300 - 500) mg/L. Based on248it-hehsotouusrrubNLstOCaEn-cCes1=01s08e00st(em6dg0/(0LS-0150000ra)tomoLfN2803 isopropanol: 28h4ouhr LECCs - 84000 ((714000.992700)) mmilLl. i8chou EC - 720 (560 750) mg. 48-hour NOEC = 360 mg/L oRbesmearrvkeds:anDdurtihneg48h-ehotuorxEiiCyotasndwLitChs39va0lmuegs/wLersoop5ro3p0a0nml,ilnlo mFoar trheiscorresnubilnettheaslt f(e45c-thsowuerrpeost exposure), there was at least 95% survival at 0 (blank control),0.050,0.5, and 5.0 mg/L. Also, there was Cd1x5ep%onsnurrtveivttaohlxiacctoint5yt0rt0oelsmtdgaw/ipLthhn(isNdu2srBvOai3vd.i3nsg,hdnvaoepihTnnasigodelsuwbelexetpomwasetieegdrhitaol(5w0oa0stmngho/lLoodfwde0r.u5en3igmmgmt.ohbeiTlehisezte.fdA)s. hsDuut4rai%nnhgcuethge of C(oNn2trRo0l3s.d3udriidnmtoht Genitive tes cdauesn1t00%etmoorSaeleiteynaitnagnyocto.neTaanbilreti1 odnepeicetsdcuNmuolamtaivretpyrcweams mobosevrvaed of thhee Table 1. Cumulative Percent Morality WsaaSsfaccotnotrroyl| co[nceontriatiooina(imeg/dL) response I oe --0---- 0 -- Ce se 00 0 Coee oT TsT o wis] (esmatunknown Yes Statistical results, as appropriate: No additional comments ONCLUSIONS o50u0rmtEeCelSOdwfiotshDa9ps5hn%icanognfnid(eaNn2c8we0an5se:rd3ve)at4le5rombfion1see0d0tLo9CbS2e)07f3mo0gD/mL.E.pThwiamlehateg9un5e%dwsacsotndfbiedtoenecnremesie4or5.ebof 326 000275 6w6a0s ~367080mgm/LL..ThTehe48a-sh-otuesrteLdCtSeOstfsourbDstaapnhcnei4a8-mhaogunra,nob-aosbesderovnedt-heeffceocntc-ecnotnrcaetnitornaotfitoens(tNOEC) s4u6b0stmanLc.e iTnhseol4u8t-iohnouwrasECd.eotefrormiDnaepdhnobiaem4a0g0nam,g/bLa,sewditohnath9e5c%onccoennftirdateinocneoiftnesttesroubfvs3ta5a0ln.ce in s4o8l-uhtoiuorn nwoa-sodbesteerrvemdi-neefdfetcobt-eco3n6ce0nmtrga/tLi,onw(iNtOhaE9C5)%fcoontfheidteenstcesiunbtsetravnacleoifn 3so0l0u-tio5n00wamsg/1L5.0The mel. ``cSounbcmeintttreartsi'onrseimnatrhkest:estKlsiolmuitsicohnsraannkdinsgam3p.lTehpeusrtiuydyislnaoctkssuafnfailcyiteinctally mcehaarsaucrteermieznetd.ofAdtdeisttisounbasltlayn,cet.here apprpoecaerdsurteobceonadduicstcerdepbayntchyebleatbowreaetnortyhetosparmepplaereprtehpeartaesttiosnolduitrieocntsi.ons given to th laboratory and the. Reviewers! remarks: The author's conclusions appear to be supported by the data. REFERENCE `TDRaphnWiidl,buDraypLhanbioaramtaogrniaes.,MIaner.bl1e9h9e6.adA.cMuAte. TSotxuidcyitnyuomfbNe2r80$932--3THto.the OTHER General remarks: The major concern for tying to determine the validity or tis test is that OthNatLmYeaNsuOrMeIdtNeAstLchTeEmiScTalCHcoEnMceIntCrAatLioCnsONbeCuENsTResoAdtThI,atONonSe wcearneacucseudr.ateOlyPPdTetreecrommimtnehendesst cnhoemmiincaallccoonncceennttrraattiioonns taorewhonilcyh,0fortheexatemsptloerg0an%iosmfstahreemeexapossuerde.d cIoFnicteisndtertateiromnis,nethdetthoaxtitchiety vhaalduebseecnanfubreniasnhdedm,uwset bcoeualddjucasltceudldatoewcnhweamridcablyr5ec0o%v.eryIFraantaesl,ytaincdalamkeeasinutroeamcecnotusntofhysdormoelyssoirst, volatility, exposure caonndceontthreartipohnyss.icochemical processes that might lower the actual test organism 327 000226 AQUATIC PLANTS TOXICITY "Title: Growth capricormutum and reproduction toxicity test with FC-1015 and the rashvwater alga, Selenastrum TEST SUBSTANCE IAdmemntointyi:umPerpefrufllourooroocotcatnaoniocaiaeci,d,PFaOm,mFoCn-i1u1m6,saFlCt;-1m2a6y, aFlCs-o1b6e9,reFfCer-r1e4d3toor2sasPtFhOeAmaajmormocnoimpuomnesanlt,of FC-1015. (Octanoicacid,pentadecafiuoro- ammonium sal, CAS #3825-26-1) Rinefmoarrmaktsi:onTihnedtiecstessaitmpislea i3s0F%C-s1t0r1ai5g.ht cTiasrpbuornitcyhwaiansvneortsisounffoifciFeCnt-l1y4c3hairnac8t0er%izweadt,ert.hoTuhgeh c3uMrrepnrtoduct sTott nsuumbbstearncwea.s D"aHtaOGweEre20u5s.e"dDtaotcaommpaayrenottoaxiccciutryoatfetlhyereblartaencthoexdiicsittyraoifghtthectheasitnsaammpmloenwiiutmh thtof the paemrmflounoirouomctpaenralauteorhooomcotlaongotmeixitnuFrCe-1in01F5C.-143 v. what is supposed to be the 100% straight carbon chain METHODS `Method/guideline followed: OECD 201, USEPA-TSCA, Guideline 797.1050 Test type: static GLP (YN): N ear study performed: 1996 Species: Selenastrum capricornunum `Supplier: UniversityofTexas at Austin Measureofgrowth used: algal cell counts (cells/mL), cell dry weights Concentrations used: 0,210, 430, 830, 1670, and 3330 mg/L. The concentrations were nominal. Three. replicates at each concentration were ested. Exposure period: 96 hours Analytical monitoring: none Statistical methods: Probit analysis aTensdtwCeornediatliloonwse:d 1T4hedaaylsgafeorwaecrceligmratoiwonnion sttheericloenednirtiiocnhse.d nTuhtreiennuttrmieendtimuemdpieurmUpSrEovPiAde1d9a7l8l mgiuniederlailne snuytnrtiheenttisc easlsgeanltimaeldfiourmalwgaalsgardojwutshteadn0d a7l.s5opsreiorrv0e aussethiendaislsuaeynst. foFroarlpraelpgaalraotpieornatoifontsh.e eTshtesoplHutoifotnha,is 3330 mg/L stock solution was prepared by diluting 3.33 g oftest substance in 1 literofwater. Aliquots 328 009227 uwseerde wteherne a2d5d0edmLdirEcrclielynmteoydeirlsutcioonntwaaitneirngin10te0stmvLestseesltssooluctrieoanteantedstcsaoplpuetidonwsi.thTihneveerxtpeodsgulraessvebsesaekelrss. `1T0h0e rvpems.selFsowuerrheluonadrdeeddwfiootth-caanndiincitsiaolfcloingchetnitnrgawteiorne oprfov1i.0dxed10byceclolnst/imnuLoaunsdcosohla-kwehnitceonftliunouroeuscselnytat l7i.g4ht7i.n6g.(3T3h3e0 wmagt/eLr ecxhpeomsiusrter)y apnadratmeemtpeerrsamtueraesu=re24d.d0u-r2i4n.g2 t(ihnectuebsattoirn)c.ludTehdr:eepHrep=li7c.a5t-e1s0o.f8t(hceontrol) and `Aepxppeenrdimiexntfowrepraerapmereftoerrmseda.nd Mdeetaescutrioenmelnimtistso).f dTihluetioonnlywactheermcihceamlidsettreyctweedrewaaslsiorponerafto0r.m0e3dm(gs/ceL:. Remarks: within the The pH range for acceptable range. the control was Water hardness, outside during acceptable limits, the study,was not but the other indicated. tested sample was RESULTS Doseof each endpoint (as mg/L): Val2u4ehs cEaClScu0la=te2d5u1s0i(n1g3c4e0ll-3c3o3u0nt) (mcgel/lLs/mL): 48HECS0> 3330 mg/L. 7926hh ECS0 = ECS=0 2040 1980 (1190-3330) (1710-2360) mg/L. mg/L. 961 96h NLOOEECC~=423100 mmgg//LL. 2Va4lhueEsCcSa0lc=ula1t7e0du0s(i6n7g3t-h33e00a)vemrga/gLe.specific growth rate: 48HECS0> 3330 mg/L. 7962hHEECC5500>> 33333300 mmgg//LL. 961 NOEC= 430 mg/L 96h LOEC = 830 mg/L Rhoeumrsa.rkBsa:seAdlioqnuogtrsoowfththoebs3e3r3v0edmgin/Lthteesrtescoolvuetriyonphwaesre,e dthieluetfefdecwtitohn aallggaall mgerodwituhmwaansdfcouulntudrteod bfeo.r 72 algistaic `Was control response satisfactory (yes/no/unknown): yes Statistical results, as appropriate: none CONCLUSIONS rFaCt-e1v0a1l5ueexohfi=bi3t3s30a9m6g/hLo.urTEhCeS9O6chelolurcoNuontOvbasleureovefd 1E9f8fe0c(t1C7o1n0c-e2n3tr6a0tmiogn/L()NaOnEdC)a 9i6s 2h1o0urmEg/CLS0fogrrcoewllth count and cell count 430 and mg/L for growth rate. 830 mg/L for growth The rate. TLhoiwsestetstOsbusbesrtvaendceEfwfaesctdeCtoencremnitnreadttioonbe(LalOgEisCt)aici.s 430 mg/L for Submitters" remarks: For data meets criteria for quality testing. reliability, However, tithilsacsktsudiynfwoarsmaatsisoingonendtaheKpluirmiitsyocfh trhateintgeostf2su.bsTthaencsetaudnyd atchteu4al8 mhoeuarsuvraelmueenstswoefrtehien amountof excessof test substance 24 hour values. in solution. Also, no explanation is given as to why 329 000228 Reviewers' remarks: none REFERENCE `fWraersdh,wTa.t,erNalega,vSieJl.ueannsads,Rir.umBocaip.ric1o9r9n6u.tumG.rowTtRh.aWnidlrbeuprryodLuacbtoiroantoorsiiesc,itIyntc.estLwaibthReFqCu-e1st01n5uamnbderthe P1624. 3M Company, St. Paul, MN. OTHER General remarks: ONLY NOMINAL The major concern TEST CHEMICAL for trying to determine CONCENTRATIONS the validity were used. for this test is that OPPT recommends cthhaetmmiceaalsucroencdetnetsrtacthieomnitcoalwhciocnhcetnotrtahteitoensst be used,so organisms that one can are exposed. aIccfuriastdeeltyedremtienremdintheatthtehetest `vnaolmuienscalancobnecenatnrdamtuiosntsbaercaodnjluys,tefdordeoxwanmwpalredb5y0%5o0f%t.heImFaenaasluyrteidcaclonmceeansturrateimoennst,stohfestoomxiecitsyort vaodlatbileietny, faunrdniosthheedr. pwheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcmoivgehrty rlaotwese,ratnhde atcatkuealintteostacocroguanntishmydrolysis, `exposure concentrations. Purityof the test material also test. Tn some tests it appeared ia that major 100% ctoenstcecrhnemaincdalwwaassnoutsesdu,fffiocrieontthleyrscahcahraecmtierciazleodfinltehsisser wpuarsituys(eadpipnrotxhiemrateesltys,8f5o%r)nowaosbvuisoeuds. sWtaatteedr,reaassoonl.venItn fiascotp,r3oMpaninolt)hoerir asucmommbairnyaotfioenaocfhbtoetsth staatger:ee"Dwaittha mthaisycnoontcearcnc.uraItnealdydirteiloant,eitfotxihciistywaosftahe"ttyepsiscaalm"pTlSeCwAitshetchtaitonof4threevtiesetw,suIbwsotaunlcde." rmeejaescturtehemseentstsoudfitcsh,epteensdticnhgemriecceailptionftahdeditetsitomneadliiunmf.ormation on purity and studies on analytical APPENDIX Parameter: Metals Aluminum Arsenic BoCardomnium CCohbraolmtium Copper iron Lead Mercury NSiilcvkeerl Zine Detection Limit 00.011mmgL 05mg 00..00100m2gm.g/L. 0.03 mg/L 0.005 mg/L. 0.03 mg/L. 0.005 mg0/.L0003 mg/L 00..0032 mmgp/ll. 002mg 330 000229 Nitrate Chloride Fl"uTootralidoerganic carbon "Total phosphorous Organochlorine Pesticides. OrgTaonxoapphhoesnpehorous Pesticides Dimethoate MToEnPocrotophos PCBs 0.05 mg NIL 01 1mgmllg,. 1 mg/L 00.503umg/lg 0.5 pg/L2pgll 20ugL 20 pL 0250 uplgl 331 009230 INVERTEBRATE TOXICITY "Title: Acute toxicityof FC-1015 to Daphnid, Daphnia magna TEST SUBSTANCE AIdmemntointyi:umPerpefrlfulourooroocotcatnaoniocataeci,d,PFaOm,mFoCn-i1u1m6,saFlC;-1m2a6y,alFsCo-b16e9,reFfCer-r1e4d3tooraassPtFhOe Amaajmormocnomipuomnesanltt,of FC-1015. (Octanoic acid, pentadecafiuoro- ammoniumsal, CAS #3525-26-1) iRnefmoarmraktsi:onTihnedicteasttessaitmpilea 3is0F%C-s1t0r1aiSg.htItcasprubroincthyawiansvenrostisounfofifciFeCnt-l1y4c3hairnac8t0er%izweadt,ert.hoTuhgeh c3uMrrepnrtoduct fot number was "HOGE 205. METHODS Methodguideline 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 Creopnlciecanttersaattieoancshucsoendc:en0tr,a4t3i0o,n7w3e0r,e1t2e0s0t,ed2000, and 3300 mg/L. The concentrations were nominal. Two, Exposure period: 48 hours Analytical monitoring: none Statistical methods: Probit analysis "mTges/tLC(oansdCitaiCoOn)s:, wThhiechdeiisowniitzheidnditlhuetaiocncewpattaebrleursaendgein. tTheheeswtatwearswaadsjupsatsesdetdotahrhoaurgdhneasspaorfti1cu6l0a-t1e8f0iler, aullkraalviinoilteytosfte1r0il8izmerg,/aLndasaCcatCivOayt,edancadrbiotnc.onWtaaitneerdu<s0e.d01fomrgt/heLtpesatrthicauldaatheamradtnteesrsaonfd1<716mmgg//LL. taontdalan ofrorgapnaircamceartbeorns.anFdurdtehteerctmieoansluirmietms)e.ntTsohefdoinlluyticohnemwiactaelrdcehteemcitsetdrywawserieroanlsato 0p.e0r3fomrg/mLe.d (sTceestApspoleuntdiioxn.s dweeprteh)crweearteedubsycddiarsceetxpwoesiugrhetsveasdsdeiltsi.on.ThGelyaswserbeealkiegrhtsly(3c0o0vemrLe)d dcounrtianignithnege2x5p0ermiLmetne.s sTowluotiroenpl(i9c.atcems, cachof10 daphnids, were ested at each concentration. Cool-swhite fluorescent lights at 130 foot-candies 3 000231 wpeerrieodusweadsfmoarilnitghatiinneg.d tAhrdoauiglhyoupthotthoepetresitoidngofper1i6odh.ours light and hours dark witha 15 minut transition m"Thheoswa/teermc(hceomntirsotlr)yapnadra7m1e0t-e7r2s0myeuamshuorseidedmu(r2in0g00thmegs/tLudeyxpionsculurdee)d,:pcHon=du8c.t2i-v8i.t3y(rcoanntgreol=) 6a1n0d-86.21-08.2 d(i2s0s0o0lvmegd/oLxyexgpeonsu=re8).,1.t9e.m1pmerga/tLur(eco=nt2r0o.l4)-a2n0.d78.1C.9(.c1onmtrgo/l)La(n2d00200.m3-2L0.8expCos(u2r0e0).0 mTgh/eL2e0x0p0osmgu/rLe.) and 4(8sehcoounrds.highest) concentration was used because the highest concentration resulted i total morality by Remarks: Water hardness, during the study, was not indicated RESULTS Doseofeach endpoint (as mg/L): 4284 hhoouurr EECCS500 == 11729000 ((1753500--22000700))mmgg//LL. 48 hour NOEC = 730 mg/L Remarks: none `Was control response satisfactory (yes/no/unknown): yes Statistical results, as appropriate: none ONCLUSIONS 2T0h7e0FmCg-/1L0.15T4h8e h4o8uhroEurCSN0owOabssedrevteedrmEifnfeedct(0Cobnece1n2t0r0atmigo/nL(wNiOtEhCa)9w5a%sc7o3n0fimdge/nLc.e interval of 730`mSeuebtmsitttheercsr'itrereimaafrokrsq:ualFiotrydtaetstainrge.liabHiolwiteyv,etrh,e tshteudsytuwdasy laascskisginnefdoarmKaltiiomnisocnhpruartiitnyg ooftf2h. Ttheset ssutbusdtyance. `and actual measurements of the amountof est substance in solution. Reviewers' remarks: none REFERE`WNaCrdE, T, Nevius, J..and R. Bocri. 1996. Acute toxicityof FC-1015 to Daphnid, Daphnia MmaNg.na. TR. Wilbury Laboratories, Inc. Lab request number P1624. 3M Company, St. Paul, OTHER OGeNneLrYalNrOemMaIrkNs:ALThTeESmaTjCorHcEoMncIeCrAn LforCtOrNyiCngEtNoTdReAtTeIrOmNitSnhewevraleiduisteyd.forOPthPisTtersetcios mtmhaetnds cthhaetmmiecaalsucroencdentetsrtacthieomnitcoalwhciocnhcoentthreatteistobnoesrguasneids.mssoatrheatexopnoesecda.n aIcFciutriastdeeltyedremtienremdintehatthtehetest vnaolmuiensalcacnonbceenatnrdatmiuosnts baercaodnjluys,tefdordeoxwanmwpalred5b0y%o5f0t%h.eImfeaznsaulyrteidcaclonmceeansturrateimoennst,sothfestooxmiecitsyort had been furnished, we could calculate chemical recovery rates, and take into account hydrolysis, 333 000232 `veoxlpaotisluirtye,coanncdenottrhaetriopnhsy.sicochemical processes that might lower the actual test organism Purityof test. In stohmeetteessttsmaittearpipaleaalrseod is a that major 100% ctoesntccehrnemaincdalwwaassnoutsesdu,fffiocrieontthlyercahsarcahcetmeirciazledofinletshsiser wpuarsituys(eadpipnrooxtihmeartteelstys,f5o%rn)owoabsvuisoedu.s sWtaattederrae,assooln.venItn (faicst3M,oipnthreoiorrapscuoammmbnairnoyaotlfio)enaocfhbtoetsth astgatre:ee"Dwaittah mthaisycnoontcearcnc.uraItnealdydirteiloant,eifttoxhiicsilwyaosftahe"ttyepsitcasla"mpTlSeCwAitshctihaotnofh4 erevtieestw,su|bswtoaunlced. mreeacsturtehemseentsusodfietsh,epeesntdicnhgemriecceailpitoftahdeditetsitomneadliiumn,formoantpiuroitny and studies on analytical APPENDIX Parameter: Detection Limit: Metals Aluminum BArosreonnic Cadmium CChorboalmtium Croopnper Lead Mercury SNiilcvkeerl Zine CNhiltorartiede: Fluoride `"TToottaall porhgoasnpihcorcoaursbon `Organochlorine Pesticides `Or`gTaonxoapphhoesnpehorousPesticides Dimethoate MToEnPoPcrotophos PCBs 00011mmgg.lL 0.5mg 0.0002 mg/L 00..0013 mmgg/llL 0005 mg/L. 0.005 0.03 mL mglL 0.0003 mg/l. 00..0023 mmge/ll 0.02 mg 01 .m05g/mLg NIL Ol mgL 0I.m0g3/mL.gt. 05 0.5pg/L.2pgll 22004mgg 20pgl 05g 334 000233 Ecotoxicity Study TAECSUTTESUTBOSXTIACNICTEY.TO AQUATIC INVERTEBRATES (DAPHNIA MAGNA) aIsdePntFiOtyA: aPemrmfolunoiruoomctsaalnto,iAcmamciod,niamummopneirfulmuosraolot;ctmaanoyatael,soPbFeO,referred to pFenCt-a1d1e6c,afFlCu-o1r2o6-,,FaCm-m1o6n9i,uomr FsCa-lt1,43C.AS(O#ct3a8n2o5i-c2a6c-i1d), RFCe-m1a4r3k,sr:efTehrere3d M10 pbryodtuhecttieosnt loafbonruatmobreyrawsaNs2840237.-4.ThTehteesTt.sR.ample is nWoitlsbuuffricsiteundtylyncuhmarbaecrteirsiz8e9d5,TaHlt.hTohugehpcuurrirteyntoftinhfeorsmaamtpilone was 0in3di.ca5te%s Cit6i,s Ca 7m,ixatnudreC9ofp9e6r.f5lu-or1o0a0n%altoegstuesucbosmtpaonucnedasn.d MMeEtThoHdO:DUS. EPA-TSCA Guideline 797.1300 Test type: Acute satic: GYeLaPr:CYoemspleted: 1995 `Species: Daphnia magna. SIuncp,plMiaerr:blOebhteaaidn,eMd AfrformocmulatnuroersigmianialntcauilnteudrebfyrTo-mRA.qWuialtbiucrRyesLaebaorrcahtories Organisms, Hampton, NH. AEnxaploystuircaelpmeorniiotdo:r4i8n-gh:ouDrOs, conductivity, pH, and temperature. "Test organism age: < 24-hours CStoamtpisuttiecarlmmeetthhooddss:(StInetpehrapnr,e1t9ed83b)ywsetranedaursdedsttaoticsatilccaullattecehLniCqSue0ss. and ECS0s. DTielsuttcioonndwiattieorn:s Deionized water adjusted to hardneosfs 160-180 melas CaCO. DHialrudtnieosns:wa1t6e4r mcghe/mLisatsrCya:CO3 Alkalinity: 106 mgas/CaCLO3 TOC: < 10 mg/L. RLiegshitdiunagl:cCholoorli-nweh:it<e0.f1lumogre/sLcent bulbs with an intensity of 110 fi-c. tPrhaontsoitpieorniopedrioofd.16-hours light, -hours dark with a 15 minute SSttoacckksaolnudtitoenstwsaosluptrieopnasrepdreipnadrialtuitoinon: wAate1r,.00A0flmegr/mLixpirnigm,artyhe pprreipmaarrey hsteoctkestwacosncpernotproarttiioonnsa.llNyodiilnustoeldubwliethmadtielruitailonwwaastenrotteod dEuxrpionsgutrhee tveesst.sels: 300 mL glass beakers containing 250 mL of Nteustmsboelurtioonf.repTlhiecaatpepsr:ox2imate depthof est olution was 9 cn. Number of daphnids per replicate: 10 Number of concentrations: five pluas negative control 35 000234 WDiastseorlvcehdeomxiysgterny druarnigneg(t0 h4s8tuhdoyu:rs): 8S41-887 mmg/yL ((1co.n0t0r0olmeex/pLoseuxrpeo)sure) C5o4n0d-u5ct6i0viptmyiroasngeem((0c-o4n5tehoeuxrpso)sure) 7p1H0r.a7n2g0e y(m0h-o4s5'chomur(s1)000 mg/L exposure) 800-8-35(c2ont.ro(ml eg1xpo,seux0rpeo)s0ur0e) 1T9e.s1t te2m0.5perat(ucroentrroalngeexp(o0su4re8) hours) R19E.S4UL2T0S.5C 1,000 me/L exposure) ENloemmiennatl bcaosnicse:nmtorrattailointsy:aBnldainmkmcoobnitloilz,ati13o0n, 220, 360, 600, 1.000 mg. 2E4l-ehmoeunrtEvCaSlu0e=a7n5d09(560%0con1f.i0d00e)ncmegi/nLterval: 2448--hhoouurr ELCCSS0O = >712,00(06000mg-/L10(0C.0L). mngot/Lcleulabl) 4488--hhoouurr NLCOSEOC==732600(m60g0/L- 1,000) me. Element values based on nominal concentrations. `Cumulative perceNnotmiimnmaalbTielsitzat|on24(i-nhcoluudses m|or4t8a-lhours Cone. mg/L [Conwol To "To | Te To [e 2 e pe To To | feo To Tis | bo Two Tio] Nao1t4e8: hAour1s000 mg/L, al aphids were immobilizeda 24 hours and dead CCoOnNtCroLlUrSeIspOoNnsSe: saisictory "bTehe72te0stmsgu/bLstwaincteha489-5h%oucronLfCiSd0enfcoeriDnatperhvnalioafm6a0g0na- w1a.0s0d0emtgelrLm.inTehdetotest s7u2b0stmayn/cLe 4wi8t-hhoaur95E%CScOonffoirdDeancpehninitaermvaalgonfa6wa0s0ai1s.o0d00etmegr/mLi.neTdhte 4b3eHSouubrmintoteorbsse3rvMedCoemfpfeatnyc,oncEennvtirraotnimoenn(taNlOELaCb)orwaatsor3y,60P.mOg./LB.ox 33331, St. PDaAulT,AMiQnnUeAsLotIaT,Y55133 oRfeltieasbtisluitbys:taKnlciemicosnccherntarnaktiinogn2s.iTn hthestteudtysollauctkisoannsalayntdicsaalmmpelaespuurreitmyenist not sufficiently characterized. 336 009235 "RThEiFs EstRuEdyNCwaEsSconducted at T.R. Wilbury Laboratories, Inc., Marblehead, OMTA,HEaRthe requestofthe 3M Company, Lab Request number N2803-4 GOeNnLerYalNOreMmIarNkAsL: TTEheSTmaCjHorEcMoInCcAenLfCorOtNrCyiEnNg TtoRdAeTteIrOmiNnSe twheervealuisdeid.ty fOoPrPthTisrteesctoimsmtehnatds cthhaetmimceaalsucroendcetnettracthieomnitcoalwhciocnhcetnotrtahteitoensst oberguasneids,mssoatrehaexopnocsecda.n aIcfcituriastdeeltyedremtienremdintheatthtehetest vnaolmuiensalcacnobnecaenntdratmiuosntsbaeraedojnulsyt,efdordeoxwanmwpalred5b0y%5o0f%th.eIfmeaansaulyrteidcaclonmceeansturrateimoennst,sothfestooxmiecitsyort hvoaldatibleietny,faunrndiosthehde,r wpheysciocuolcdhceamliccuallatpercohceemsisceaslthraetcmoivgehrty roatwees,ratnhde tacatkuealintteostacocroguanntishmydrolysis, exposure concentrations. 337 000236 Ecotoxiciy Study TEST SUBSATCAUNTCEE TOXICITY TO AQUATIC INVERTEBRATES (DAPHNIA MAGNA) rIedfeenrtrietdy:0PearsfPluFoOroAoctteatnroaibcuatcyidl,atmemtornaibuutmysaalmt,monium salt; may also be `tceotmrpaobnuetnytloafmmL -o1n3i4um92p.erf(lOucotraonoociteanaocaitde.,poerntaasdeacmafaljuoorro-, Rctermaabruktsy:laTmhmeo3niMumprsoadlu,ctCiAonSl#ot9n5u6m58b-e5r3-w0a)s 2327 TTRh.e tWesitlsbaumrpylsetuisdyrenfuermrbeedrt0ibs y840th-eTHt.estTihneg l3aMborEantvoirryoansmeLnt-1a3l49L2a,boTrhaetory cRheaqruaecstetrNizuemd,bearltihsoNug2h33c2u.rrTenhteipnufroirtmyoatfiotnheinsdaimcpalteeswiat is naostosluuftfiiocnieonftly 4is4o.p9r%optaenotlrabutylammonium perfluorooctanoate, 27.9% water, and 27.2% teTshteSfuoblsltoawnicneg isnuwmamtaerrysoalpuptliioens wtiotthheintceostmpslaemtpelleyacshaaramcitxetruirzeeodfthe ocfotncheenttersattsiaonmspolfeiwmiptuhritthiaetos.fDtahtetaesmtasyunbsottaanccceu.rately relate toxicity METHOD Method: U.S. EPA-TSCA Guideline 797.1300 TGeLsPt:tyYpees: Acute siatic Year Completed: 1995 Species: Daphnia magna. ISnucp,plMiaerrb:leOhbetaadi,neMdAfrofmrocmulatnuroersigmianialntcauilnteudrbeyfromT.RA. qWuialtbiucrRyesLaebaorrcahtories Organisms, Hamplon, NH. `Amnoanliyttoirceadldamiolnyi.toring: DO, conductivity, pH,and temperature were. Exposure period: 48-hours TSteasttisotricgaalnimestmhaogdes::<L2C4S-0hoaunrds ECS0 values calculated, when possible, by iprnotbeirtpoalnaatliyosnisu,simnogvtihnegcaovmepruatgeermseotfhtwoadreorobfinoCm.E.iaSltepprhoabna.bility with non-linear Test conditions Dmigl/uLtiaosnCwaatCeOrI:LD.eionized water adjusted to hardiess of 160-150 Dilution water chemistry: Not given. BPhAotCoKperTiOodMoAfI1N6.-Lhoiugrhstilniggh:t,Coo-lh-owuhristdearfkluwoirtehscaen1t5bmulibnsutweith an intensity of 20 fic. transition period. sSotlauctkioannwdastesptrespoalruetdiionnsdiplruetpiaornatwaitoenr:. AAf10i0mmigx/iLng,prtihmearpyrismtaorcyk stetsotcckowncaesntprraotpioornts.ionNaolliyndsiolluutbelde wmiatthedriilaultwiaons wnaotteerd 0durpirnegpatrheethe eEsxtposure vessels: 300 ml glass beakers containing 250 mL of test solution. The approximate depthof est solution was 9 cn. 338 009237 Fallal `NNhuuemmbbveeesrrsoeolfsfdwraeepprhleiaociadstseespercorveeplriecdatde:r1o0ge tes WDNiauslmseobrlevrcedohfoexcmyoigne,enednruatrnaigtneog0ntsh-ev8sethypoh:uorss:egaive onl 53557-8877 mmepn ((1c0o0ntmolaeTxpeoxspuorseu)re conc) oC66o22Hn00dr-ua6c6nt34gi00evim(ut0bmy-ohr4ava8nesghmemou(((r0c1)o0-n04t8molheoeuxrxps)opseo)s onc) FSTea3st5Vt6eompc1eo0rn0avtmoulpree1xrpeoasnuxgrep()0o-c4so8neheo)urs) E23l00e33me2n20t00bai(t(1cm0o0nrmveixtpaenodxsm)pootcsoineco) n RNoEmSiUnLaTlSconcentrations: Blank conol, 13,22, 36,60, 100 mL. Element vai: 24-hour ECS0+ 89.60 100) mg 24-hour LCS0 = >100 mg/L (CI not calculable) 48-hour EC50= 34 (30 - 39) mg/L. S4RE8elh-emhmaooerunwkrtsNL:vCaOlT5Kue0euCs=i-bn7ag7swe(da6m0once-onn10di0u)nctmaegd/cLoo.nncemniiatiroensa.s described in the Test SoutbshteanRceurRaecmhaerkmsicealdc.omTphoneanltelsornp.ored apl ot mire and Cumulative percent immobilization (cludes mrtaliy: CCEoncy-- mgl ---- s f h ess h s] T-- f T -- oT-- o w | CCoOnNtrCoLlUrSeIspOoNnsSe: stisfcory T5Suh7bes7tcasmntceeslu4b8swt-iahtnohcwae #DE-6hCocuforomrLiDdCaepSnhcwefoirmaeDmarpaahlnaioaf6wmaasgdne1at0e0wrammsiende.editTebhmeiente3sd4 to hmSuEobmiuwtielnrho:ao3b3s1e0rCvocemodpnlaindfyet,neEcsonmnvceoennnmaatoinofinl0(.LNaOb3oE9rCam)towrgya,s PT1Oh3.emeeBlot.xuS3b3e11, 339 000238 Paul, Minnesota, 55133 DATA QUALITY ofRetleisatbisliutbys:taKnlciemicsoncchenrtarnaktiion2ngs.iTnhtehestteusdtysollauctkisoannsalayntdicsaalmmpelaespuurreitmyenist not sufficiently characterized. REFERENCES "MTAhi,s sattutdhye wraeqsuecsotndoufcttheed3aMt TC.Ro.mpWainlyb,urLyaLbabRoerqauteosrtiensu,mIbnce.r, NMa2r3b3l2e,head, 1995. OTHER General remarks: ONLY NOMINAL The major concern TEST CHEMICAL for trying to determine CONCENTRATIONS the validity were used. for this test is that OPPT recommends. cthhaetmimceaalsucroendcetnetsrtacthieomnitcoalwhciocnhcteontthreatteisotbnoesrguasneids,smsotahraetexopnoesecda.n accurately determine the test If it i determined that the `vnaolmuiensaclacnonbceenatnrdatmiuosntsbaeraedojnulsyt,efdordeoxwanmwpalred5b0y%o50f%t.he Imfeaanasluyrteidcaclonmceeansturrateimoennst,sothfestooxmiecitsyort vhoaldatbileietny,faunrdniosthehde,r wpheysciocuolcdhceamliccuallatpercohceemsiscesalthraetcmoivegrhyt rlaotwese,ratnhde atcatkuealintteostacocroguanntishmydrolysis, `exposure concentrations. Purityofthe some tests it test material also is appeared that 100% amajor concern and was not sufficiently characterized test chemical was used, for others a chemical of lesser in this purity test. In o(tahpeprrotxesitmsa.tfeolryno5o%b)viwoauss ussteadt.ed Wreaatsoenr.a. Isnolfvaectn,t 3(iMsoipnrtohpeainrosl)umormaarcyoomfbienaacthiotneostfsbtaotte:h "wDaastausmeadyinnot aadcdciutriaotne,lyifrtehliastweatsoxaici"ttyyopifcatlh"eTteSstCsAamspeclteiownith4 trheavtioefw,th|ewtoeustldsurbesjteactncteh.e"se1 satgurdieees,wiptehndthiinsgcroencceeirpnt.ofIn additional `medium. information on purity and studies on analytical measurements of the test chemical in the test 340 000239 Ecotoxicity Study ACUTE TOXICITY TEST SUBSTANCE. TO AQUATIC INVERTEBRATES (DAPHNIA MAGNA) rIedfeentrirteyd:t0PearsfPluFoOroAocttearnoaibcutacyilda,memtornaibuumtysallta,mmonium sal; mayalsobe: `tceotmrpaobnuetnytlaomfmLo-n1i3u4m92p.er(fOlcutoarnoooictcaancoiadt,e,peNn2t8ad0e3c-a2foluroarso-am, ajor tRtermaabruktsy:laTmhmeo3niMumprsoadltu,ctCiAonSl#ot9n5u6m58b-e5r3-w0a)s 2. "TT.hR.e tWesitlbsuarmyplsetuisdyrenfuemrbreertodisb8y89th-eTHt.estTihngelpaubroirtayotfortyhaes sNa2m8p0l3e-2w.aTshneot Ssoulffuitciioennotfly44ch.a9ra%ctteertizreadb,utalytlhaomumgohnicuurmrepnetrfilnufoorromoacttianoonaitned,ic2a7t.es9%it wiastaer, and 27.2% isopropanol teTshtesfuoblsltoawnicneg isnuamnmairsoyprapopplaineoslitwoattheertseostlustaimopnlweitahs ianmcoimpxlettoeulfyrthee crehlaartaecttoexriiczietdyocfotncheenttersattsiaonmspolfe iwmiptuhrtithiaetso.fDtahteaemstaysunbosttaanccceu.rately METHOD TMeestthotydp:e:U.ASc.utEePAsu-tTicSCA Guideline 797.1300 GYLeaPr:CYoemspleted: 1996. Species: Daphnia magna SInucp,plMiaerrb:leOhbetaadi,neMdAfrformomcualtnuorreisgimnaailntcauiltnuerdebfyroT.mR.AqWuiatlibcurRyesLeaabrocrahtories Organisms, Hampton, NH. `Amnoanliyttoirceadldamiolnyi.toring: DO, conductivity,pH, and temperature were. Exposure Period: 48-hours TSteasttisotricgaalnmiestmhaogdes::<L2C4S-0hoaunrds ECS0 values calculated, when possible, by ipnrtoebriptoalnaatliyosnisu,simnogvtihnegcoavmepruatgeermseotfhtwoadreoorfbinoCm.E.iaSltepprhoabna.bility with non-linear "Test conditions Dilltion melas CwaatCerO:IDLeionized water adjusted to a hardness of 160-150 Dilution water chemistry: Hardness: Not noted AplHk:alNiontitny:otNeodt noted PLihgohttoipnegr:ioCdooofl1-6w-hhioteurfsluloirgehts,ce8nt-hbouulrbssdwairtkhwainthinate1n5smitiynoutfe110 fic. transition period. SSotlouctkioannwdastesptrespoalruetdiionnsdiplruetpiaornawtaitoenr:. AAf2te0r0 mmigxi/nLg,prtihmeaprryismtaorcyk stetsotcckowncaesntprraotpioornts.ionNaolliyndsiolluutbeldewmiattherdiiallutwiaosn wnaotteerd0durpirnegpatrheethe test 341 000240 E C S n E i pT aa n m e . Si E L F E EF arE Er ,EE F 2RI Ca EoE EiTET a E a S E T a E T E e Es m E E-- a-- n E rr, A i-- r i r [Comrol "To "To | lo e T es pe Th e s] R T I Sn e R " fo10o0 50 Taf s -- 000241 CONCLUSIONS "bTehe93temstgs/uLbswtiatnhcea 9485-%hocuornfLiCdSeOnceforinDtaerpvhalnoifa 7m4ag-n>a10w0asmgd/eLt.erTmhienetdestto msugb/sLtawnicteh4a8-9h5o%urcEonCfSiOdefnocreDianptehrnviaalomfa3g6na-- w1a00s mdge/tLe.rmTinheedtoesbt e 62 substance mg/L 48-hour no observed effect concentration (NOEC) was 13 `PSauulb,miMtitnenre:so3tMa,C5o5m1p3a3ny, Environmental Laboratory, P.O. Box 33331, St. DATA QUALITY Roefltieasbtisliutbys:taKnlciemicsocnhcernatnkriantgio2i.nnsThtehestteusdtysollauctkisoannsalayntdicsaalmmpelaespuurreitmyenist not sufficiently characterized. "RThEiFs EstRuEdyNCwaEsSconducted at T.R. Wilbury Laboratories, Inc., Marblehead, M19A9,6,atthe request of the 3M Company, Lab Request Number N2803-2, OTHER `OGNenLeYralNrOeMmIarNkAsL: T`TEhSeTmaCjHorEcMoInCceArLn fCorOtNrCyiEnNg TtoRdAeTteIrOmiNnSe twheervealuisdeid.ty fOoPrPthTisrteectoimsmtehnatds tehhaetmimceaalsucroencdetnetsrtacthieonmiocalwhciocnchenttortahteiotnesstboergwasneids,mssoatrheatexopnoesecda.n a[cfcturiastdeeltyedremtienremdintheatthtehetest nvaolmuiensalcacnonbceenatnrdatmiuosntsabreeaodnjluys,iefdordeoxwanmwpalred3b0y%o50f%.the Imfaenaasluytriecdaclonmceeansturrateimoennst,sothfestooxmiecitsyort vaodlatbileietny,fanudronthierswphehycesoiduclo,cdhceamliccuallatpercohceemsiscesalthraetcmoivegrhyt rlaotwese,ratnhde facatkuealinttoesacocroguanntishymdrolysis, exposure concentrations. sPuormietytoesftsthiet atepsptemaarteedrtihaata1l0s0i%s atemsatcjhoermciocnaclewransanudsewda,sfonrotosutffiahciceehntelmryicchsaalraofctleersiszeerd piunrtihtiys test. In (otahpeprrotxesitmsa,tfeolryn8o57o%b)viwoauss ussteadt.edWreaatsoenr.a,Isnolfvaectn,t3(iMsoipnrtohpeainrosl)umormaarcyoomfbicnaacthiotnesotfbstoatte:h "wDaastausmeadyinnor aadcdciutriaotne,lyiftrheilsatweatsoxaic"ittyyopifctahl"e TteSstCsAamspeclteiownith4 trhevaioefw,thewtoeustldsurbesjtecatncteh.e"se|satgurdeices,wiptehndtihnsgcornecceerinp.t ofIn| additional medium, information on purity and studies on analytical measurementsof the test chemical in the test 343 000242 TOXICITY TO FisH Title: Acute Toxicity to Fish TEST SUBSTANCE AIdmemntointyi:uPmerpfelrufolruooorcotoacntoaineaaatcci,d,PaFmO,moFnCi-1u1m6,salFtC;-1m2a6y,aFlCs-o1b6e9,reofrerFrCe-d1t43o.2s(POFctOaAnoaimamcoidn,ium sal, pentadecafluoro-, ammonium salt, CASRN 3825-26-1) wRaesmanrotkss:uffTichieen3tlMy cphraordaucctterlioztendu,mtbheorugwhacsur8r3.enTthienftoerstmastaimopnliendwiacsatFeCs-i1t4i3.a mTihxetuprueroiftyo96f.t5he sample 100% test substance and 0- 3.5% Ce, Cs and Cs perluoro analog compounds. METHODS Methodguideline followed: Not sated Test type: Static GLP (VIN): No ear study performed: 1974 Species:`AFvaetrhageeadwmeiingnho=tw 1(P6igmephalespromelas) Average length= 2 inches Supplier: No 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. Sdteatteirsmtiicnaeldmgertaphhoidcasl:ly.There were no statistical methods given by the study authors: theLCepwas Test Conditions: ~DOinsesorlevpelidcaotxeywgaesn prearnfgoerm(e2d4,-96 hours) = 4.7 - 5.7 mg/L (control) and 4.0 - 4.9 mg/L (50 mg/L) ""TpeHmpreanrgaetu(r2e4-r9a6nhgo=eurs7)0=- 772.0d-eg7.r1ee(scoFnathrroeln)haenidt 6.4 - 6.5 (50 mg/L exposure) ""DWialtleirohnarwdanteesrwsawsascanrobtoni-nfdiiclatteerde.d city water from St. Paul, MN, Remarks: Further details on the est conditions and procedures were not provided. 344 009243 ee RESULTS Doseof each endpoint (as mg/L): concentrations, 96 hour LCq= 70 mg/L (C.1 not calculated) based on nominal Remarks: Observed mortality `mortality with the exceptionof ofthe controls 20% mortality was 10% in the SO at both 72 and mg/L group. 96 hours. There was no other `Was control response satisfactory (yes/no/unknown): unknown, see Remarks above Statistical results, as appropriate: obtain acalculated LCs value. Percent survival versus concentration (mg/L)wasplotted to CONCLUSIONS. "The study authors concluded that the acute LC calculated) based on nominal concentrations. to fathead minnow was equal to 70 mg/L (C.1. not ``mSeutbhmoidtoltoegrys. RTehmearLkCss: wRaesliaebxitlriatpyol-atKeldimfirsocmharnaninksiunfgfi3.cieTnhterneumwbaesrionfsudfaftiacipeonitndtso.cuTmheentgaetnieornaolfptrhe-etest health and analytical ageoffish were not noted. Sample purity was confirmationof test substance concentrations. not properly characterized and it lacks Reviewer's Remarks: the water hardness was The pH levels during the not given. Testing should test period have been were done within the acceptable range; however, with two replicates. The number of organisms per dose and the loading rate were not indicated. REFERENCE 3M Company. [No title given). Lab Request number 2340. St. Paul, MN. OTHER Remarks: This summary was based on a summary report and only limited data tables. No detailed report was available. the study, are limited. Therefore, the contentsofthis summary, in reference to the protocols and results of The major concen for trying to determine CHEMICAL CONCENTRATIONS were the validity for this test is used. OPPT recommends that that ONLY NOMINAL TEST measured test chemical cthoencteensttroartgiaonnsisbmes uasreede,xspoostehda.t oInfeitcaisndaectceurrmaitneleyd dtehtatertmhienneotmhienatelstcocnhceemnitcraalticoonnsceanrteroantliyo,n ftoorwehxiamcphleto: 5IF0an%aloyftitchaelmemaesausurreedmceonntcseontfrastoimones,sotrhtehtaodxibcieteyn vfaulurensicsahnebwdee,acnodulmdusctalbceualadtjeucshteemdidcaolwnrwecaorvderbyyr5at0es%, aacntduatlakteesitnotrogaacnciosumntexhpyodrsoulryesicso,ncveonltartaitliitoyn,s.andAsothiteirs pwheysairceoocpheermaitcianlg pirnotcheessdeasrkthoant tmhiigshitssluoe.wer the. 345 009244 TOXICITY TO FISH Title: Acute Toxicity to Fish TEST SUBSTANCE pIednetnatdietcya:flPueorrfol-u,orCooAcStaRnoNic33a5ci-d6:7-m1a)y also be referred to as PFOA, FC-26, or FX-1001. (Octanoic acid, sRuelmliacrieknst:ly 3chMarpacrtoedruiczteido,ntlhootunguhmcbuerrre2n6t9.inTfhorematetsitosnaimnpdliceawteassitFCis-a26m.ixTthureeopufri9t6yo.5f-t1h0e0s%atmepsltewas not substance and 0-3.5% Ci. Cr, and Cs perfluoro homologue compounds. METHODS Method/guideline followed: Not stated Test type: Static: GLP (Y/N): No Year study performed: 1974 Species:"AFvaetrhaegaedlemnignthn=ow2(iPnicmheepshalespromelas) Average weight = 1.5 Supplier: Notstated Concentrations used: 0, 50, 125,250, 375, 500 mg/L nominal Exposure period: 96 hours Analytical monitoring: Nominal concentrations were not measured Statistical methods: There were no statistical methods givenby determined graphically. the study authors; the LC was T~eOsnte Croenpldiictaitoenwsa:s performed. "Temperature 69-70 degrees Fahrenheit "Dissolved oxygen range (24-96 hours) was between 4.7 and 5.7 mg/L for the control exposure and. Wbaettewreheanrd3n.e8sasnwda5s.2nomtgg/iLvenf,or the 375mg/L test exposure. pH range (24-96 hours) was 7.0 10 7.2for the control exposureand 6.0 10 6.7 for the 375 mg/L exposure. 346 000245 Remarks: No further details were provided on the test condiotrmietohondss, RESULTS Daseof each endpoint (as mg/L): concentrations, 96-hour LCs = 440 mg/L (C.1. not calculated) based on nominal Rsuermvaivraklsw:aFso1r0c0on%ceantt2r4athioounrss,obf0utt0o %37a5t m4g8/.L9,6 shuorurvsi.val was 100%. For the S00mg/L concentration, `Was control response satisfactory (ves/no/unknown): Yes Statistical results, as appropriate: obtain an LCe. Concentration (mg/L) versus percent survival wasgraphedto CONCLUSIONS iSnufbomrimtatteiro'nsoRnetmhaermkest:hodRoelloiagbyi.litSya-mpKlleimpiusrcihtyrwanaksinngotopfr3o.peTrhliys study lacks documentation and characterized. Test concentrations were not characterized. Conditionofthe fish prior to study initiation is not known. sRteuvdiyewpeerri'osdRweamsanroktsg:iveTne.stiTnhgesnhouumlbdehraovfeobregeannipsemrsfopremreddosien tawnod trehpelilcoaatedsi.ngWraatteerweharrednnoetssindduirciatnegd.the REFERENCE 3M Company. [No title given]. Lab Request Number 2485. St. Paul, MN. OTHER Remarks: This this summary, in summary reference w(a0sthbeaspreodtoocnoalssaunmdmarersyultrseopfortthseubsmtuidtyt,edarbeyli3mMit,edt.herefore, the contents of "The major concern for trying to determine CHEMICAL CONCENTRATIONS were the validity used. OPPT for this test is recommends that that ONLY NOMINAL TEST measured test chemical concentrationsbeused, so that the test organisms are exposed. one can accurately IFit is determined determine the test chemical concentration that the nominal concentrations are only, to for which to example: 50%ofthe measured concentrations, the toxicity [Fanalytical measurementsofsome sort had been values can fumished, be we and must be adjusted downward by could calculate chemical recovery 50% rates, and take into account hydrolysis, volatility, and other actual test organism exposure concentrations. As it i physicochemical we are operating processes that in the dark on might lower this issue. the 347 000246 TOXICITY TO FISH "Title: Acute Toxicityto Fish TEST SUBSTANCE IAdmenmtoitnyi:uPmerpfelrufolruooorcotoacntoaincoaatcei,d,PaFmO,moFnCi-1u1m6,salFtC;-m1a2y6,beFCr-e1f6e9r,reodrtoFCa-s14P3F.OA(Ocatmamnooinciaucmid,salt pentadecafluoro-, ammonium salt, CASRN 3825-261) wRaesmanroktss:uffTihcieen3tlMy pchraordaucctteiroinzeldo,t tnhuomubgehrcwurarsen8t3.inTfhoermtaetstiosnamipndliecawtaessiFtCi-s1a43m.ixTtuhreeopufri9t6yo.f5-t1h0e0s%atmepslte substance and 0-3.5% Ci, Cs, and Cs perfluoro analogue compounds. METHODS Method/guideline followed: Not sated Test type: Static GLP (VIN): No. ear study performed: 1975 Species:`ABvleurcaggielllesnugntfhis=h 4(Lcempomis machrochirus) Average weight = 0.20 g `Supplier: Not stated Concentrations used: 0, 135, 180, 240, 320, 420 mg/L nominal Exposure period: 96 hours Analytical monitoring: Concentrations were not measured. Statistical methods: Not stated Test Conditions: ""DDiilluuttiioonn: wcaatrebronc-hfeimtisetrreyd:well water, temperature=19 degrees Celsius dPiHss-ol7v9ed oxygen = 9.1 ppm ""EOxnpeorseuprleicvaetsesels were tanks containing 16 liters of test solution 2"L0oafdiishngperratree-pli0c.a2t5e gL 348 000247 "Water cheistry during study (24-96 hours): dpiHssroalnvgeed o=x7y.g9e(nco=nt5r.o3l-)6.,97.8m-g8/.0L((4c2on0trmogl/),L 5ex.p1o7s.u3rem)g/L (420 mg/L exposure) "Wfaetstertehmaprdenreastsuwrae=s1n8o-t19sadteegdrees Celsius Remarks: No furtherdetailswere proviodnethde test methods or conditions. RESULTS Doseofcach endpoint (as mg/L): 96-hour LCS0> 420 mg/L based on nominal concentrations. 4R2e0mamrgk/sL:grNouopsmobrtoatlhitcioenssiosctceudrorfedoni etihnetcwoennttroylfsioshrd1e3a5d-2at4072mgh/oLurgsroups. Mortalites in the 320 and `Was control response satisfactory (yes/no/unknown): Yes Statistical results as appropriate: Not stated CONCLUSIONS `fSolulbomwiedt.teNrsoRienfmoarrmkasti:onReolniabsitloictkyo~rKtleitmisoslcuhtiroannkpirnegpa3r.atTieosntsinwgaslapcrkosviindfeodr.maAtvieornagoen tfhisehmweetihgohdt is ssuusbpsetcat.nceSacmonpcleentpruartiitoynsw.as not properly characterized and it lacks analytical confirmationoftest Rnoetviiendwiecra'tsedR.emarks: Only one replicate was performed. Water hardness during the study period was REFERENCE 3M Company. [No tile given]. Lab Request number 3844. St. Paul, MN. OTHER Rtheismasrukmsm:arTyh,isinsruemfemraerncyew(a0sthbeapsreodtoocnolassaunmdmraersyultrsepoofrtthseusbtumdiy,ttabreeydli3mMit,edt.herefore, the contents of "CTHheEmMaIjoCrAcLonCcOerNnCfEorNtTrRyiAngTItoOdNetSerwmeirneeutsheed.valOidPiPtyTfrorecthoimsmteesntdiss tthhaatt OmeNaLsuYreNdOtMesIt cNhAemLicTaElST cthoencteensttroartgiaonnisbsemsuasrecd,ex5p0ostehda.t on[Feitcaindaectceurrmaitneleyddtehtaertmhienneomtihenatelsctocnhceenmtircaatliocnosnceanrteroantliyo,ntfoorwehxiacmhpltoe 5IF0a%nalofyttihcealmmeeaassuurreedmceonntcseontfrsatoimoens,sotrhtehtaodxibceiteynvfaulruneisshceadn, bweeacnodulmduscatlcbuelaatdejucshteemdidcaolwnrwecaorvderbyyr5at0es%, aacntduaalkteesitnotrogaacnciosumntexhpyodrsoulryesicso,ncveonlartaitliiotyn,s.and other physicochemicalprocessesthat mightlowerthe 349 000248 TOXICITY TO FISH Titles Acute Toxicityto Fish TEST SUBSTANCE AIdmemntointyi:uPmerpfelrufolruooorcotoacntoaincoaatcei,d,PaFmO,moFnCi-1u1m6,salFtC;-m1a26y,aFlsCo-1b6e9r,efoerrFreCd-1t4o3a.s PFOA ammonium (Octanoic acid, salt, pentadecafluoro-, ammonium salt, CASRN 3825-261) Remarks: sample was The not s3uMffipcrioendtulcyticohanralocttenruimzebde,rtwhaosug8h3.curTrheentteisntfsoarmmaptlieonwaisndFiCc-a1te4s3.it The purityofthe i a mixtureof96.5 100% test substance and 0.- 3.5% Ce, Cr, and Cy perfluoro analogue compounds. METHODS Method guideline followed: Not stated Test type: Static GLP (VIN): No Vear study performed: 1978 Species: Blucgill sunfish (Lepomis machrochirus) Average lengih~ 3.0 cm 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 stated TDeisltlCioonndiwtaitoenrss:ource: carbon-filtered well water D"iOlnuetireopnliwcaattee,r2c0heimsishtrpye:r rteepmlipceartae.ture 19 degrees C, dissolved oxygen = 9.9 ppm, pH = 7.6. T"Leosatdipnegrfroarteme=d 1i.n5tga/nLks containing 16 liters test solution "WDaitsesorlcvheedmoisxtyrgyendurrainnggete=st5.(62410~.69.65 hours): mg/L (control) and 4.9 0 5.9 mg/L (750 mg/L exposure) PH range = 7.8 (control) and 7.6 to 7.8 (750 mg/L exposure) 350 000249 "TWeamtpererhaatrudrneess 1no9t.0gi2v0endegrees C Remarks: No furtherdetailswere provided on the esting methods or conditions. RESULTS Doseofeach endpoint (as mg/L): 96-hour LCS0 = 569 mg/L, based on nominal concentrations Rtheema10r0k0s:andTh1e35905%mgc/oLnfciodnecnecnetrianttieornvaglrwouapss.500 636 mg/L. 100% mortality occurred by 48 hours in cWoantsroclongtroruopl.response satisfactory (yes/no/unknown): One outoftwenty fish died at 48 hours in the Statistical results, as appropriate: Not sated CONCLUSIONS Sfoulblmoiwtedt.erN'soRienmfoarrmkasti:onRoelnisatboiclkito~yr tKelsitmsioslhutriaonnkpirnegpa3.ratTieosntsinwgalsacpkrsoviindfeodr.matSiaonmploenptuhreitmyetwhaosdnot properly characterized and the study lacks analytical confirmationoftest substance concentrations. nRoetvigeivweenr.'s Remarks: Only one replicate was performed and water hardness during the test period was REFERENCE 3M Company. [No tte given). Lab Request number 3844. St. Paul, MN. OTHER tRheismasrukmsm:aryT,hiisnsruefmemraenrcyewtaosthbeaspreodtoocnoalssaunmdmraersyultrseopofrtthseubsmtuidtyt,edarbeyl3imMit,edt.herefore, the contents of "CTHheEmMaIjCorAcLonCcOeNnCfEorNyTiRnAgTtIoOdNetSerwmeirneeutsheed.valOidPiPtyTfrorecthoimsmteesntdiss tthhaatt mOeNaLsuYreNdOteMstIcNhAeLmicTaElST cthoencteensttroartgiaonnissbmesusaered,exspoostehda.t an[Feitcaindaectceurrmatienleyddtehtaertmhienneomthienatelstcocnhceemnitcraalticoonnsceanrtroantliyo,nftoorwehxiacmhplteo 5[a0n%aolyfttihcealmmeeaassuurreedmceonntcseontfrsatoimoens,sotrthhtaodxibceietynvfaulruneisshceadn, bweeacnodulmduscatlbcuelaatdejucshteemdidcoalwnrweacorvderbyyr5at0es%, `aacntduatlakteestinotrogaacnciosumntexhpyodrsoulryesicso,ncveonltartaitliitoyn,s.and other physicochemical processes that might lower the 351 000250 TOXICITY TO FISH Title: ChronicToxicitytoFish TEST SUBSTANCE sIadlte,ntaimtym:onPeirufmlupoerrofolcutoarnoooicctaacnioda,tea,mPmFoOn,iFuCm-1s1al6t,; mFaC-y1a2l6s,oFbCe-r1e6f9e,rroerd FoC-115437.5.0(3O,ctPaFnoOiAe aacmidm,onium pentadecafluoro-, ammonium salt, CAS # 3825-26-1) Rreefmerasrtkos:it aTsh"e783.M03.p"roTdhuectpiuornitlyootfntuhmebsearmwpalse 8w3a.s Tnohtestuefsftisciaemnptlley cwhaasracFtCe-r1i4z3e.d,Tthheoutgeshticnugrrleanbtoratory pienfflouromraotiaonnaliongduiecactoemiptobuenidnsg.a mixtureof96.5% - 100% tes substance and 0 -3.5% Cp Cs, and Cy METHODS pMreetshenotdegdiuind"ePlrionpeofsoeldlorweecdo:mTmheendmeedthboidooalssoagyypfroorctehdeuergegfoarnedgfgryanedxfproysusraegcelsooseflyfrfeoslhlwoawteedr tfhiasth," U.S. EPA, 1972. Test type: Flow-through GLP (VIN): No ear study performed: 1978 Species: Fathead minnow (Pimephalespromelas) ePlriem-itnraetaetmpeonsts:ibElgeefsunwgeursegprloawctehd. ina 60 mg/L malachite green solution for 15 seconds to Test fish age: gas within 48-hours afer fertilization Supplier: U.S. Environmental Protection Agency's Environmental Research Laboratory in Duluth, MN, Concentrations tested: Blank control, 62, 12.5, 25, 50, 100 mg/L Exposure period: 30 days post hatch AWneaelkyltyicsaalmmpolneistwoerriengt:eTnemfpreormatcuarceh, adqiussaorlivuemd fooxrydgeetnercmoinncaetnitornatoifona,mamnodnpiHumweprerefmluoonriotoocrteadnodaatilcy 3co1n,c1e9nt7r8at1i0otnh.eA3llMsCaompmlpeasnyt.aken during the test were stored in polyethylene bottles and shipped on May aStnaatliysstiiscoaflvmaertihaondcse:(SMteeealnesanodf Tmoerarsiue,re1d96b0i,olcoogmipcalletpealryamreatnedrosmfirzoemd bdulpolcikcadteesiagqnu,arPi-a0.w0e5)r.e sDuabtjaecftoerd to percentage analysis. survival and percentage hatch were transfotromaerdcsin square rootofpercentage prior to 352 009251 "TDeisltutcioonndiwtaitones:source and contaminanis: Well water pumped to a concrete reservoir where it was arated "Dibleuftoiroenowwatierncghteomitshtereyxp(o0s-u3r0edasyyss)t:em through aged PVC pipe atlotkaallihnairtydne~s2s6 -3312.m3g8/mL ags Ca/saCCLaO,C.O; PSpHec-if7ic0c-o7n4ductance= 149 - 170 | mhosm Sutsoedc.kTahned deisltustoelduetiloinveprreedpafriavteionno:minAalmocdoinfcieendt,raptrioopnosrtaiomnmaolniiluumerpewriftlhuaro0o.c5t0adniclautteioAnnagcitonrfwraosm 100 1s0y.s6t.e2mmwya/sLuasneddc1o0ntdreollivweart6e.6tmoLdupolfiacantoemtienstalagauamrmiso.nAiu4 mlpieterrflluaosrsooMctaarnciattebHooctk tcooxnicceannttradteiloinveorfy F2r0y.4exmpgos/umreivnedsisetlilylpeed:watGelrasos ttehsetmaiqxuianrgiucmhammebaesruroiftnhge30d.i5lu5e3r0:.5530.5 cm with a 17.5 om high Egg cups: Acrylic tubes (3 om 0s.t3a.nd7piepme odrnagin),wwiatthe4r0vmoelsuhmeNoifx16stcreese.n on one end. An egg cup ovsocckielrlaarhmeapepgagrcatuupss,iansthdeeessctrwiabtebedry Mount (1968), was used 10 gently "Diluer: Delivered 0.50 ler oefwasterwraetpleatcoemceancthiamqueaorfiaupmpr1o9x5imtaitmelsyp,e1r0dhyo,sy.ielding a 90% est Feeding: Fry werefe live bine`wseherkiemnpdsnatuhproluigthhourtetthiemeesxpdoasiluyreonperwieoedk.days and wice daily on "Numberofreplicates: Two repliecaactehs.eggTchuepre were 80 eggsfor the atchabilt test and 40fy from "Water chemiDsitsrsyoldvuerdinogxyegsetn: >95% saturation PTeHm:pe7r0at-u7re3: 25 1 degrees Celsius, maintained by wate bah R`weemrearprkess:erAvtedthien t1em0n%inbautfifoenreodf ftohremtaelitntwhheiflrey tfhreofmythfercoomnttrhoeloathnedrttheesthqiugharcioancweenrteatfiroonze(n.10T0onmg/L) fHiosrtmoaplaitnh-oplroegsiccravleedxfamyin(5atfiroonmoefachtrraenpslviecartsee)sefcrtoimontoh fchoentrnoalrensdantdh cehpihgahlicconecxetnetnrsaitoinonofunhceetreernat] atimnem. oTnhieurmempaeifnliunogroporcetsaenrovaetdefcyonacenndtrfartoizoenns.ry were analyzeda a later dat (by 3M Compan) for RESULTS Dose of cach endpuin (1s mg/L): 30-day NOAEL > 100 mg/L CNoonmceinntaraltion (mg/L) Control I Replicate| Watch | Survival %|30 aMyeasnPolesntgFtha|tehMean weight iSn mDm nme x5 a9s 9 95 202)16; 7@s ATs Tes we se | 353 009252 7s 5 x5 w 5& ww5 | 3T1m0o) oie 27 = x 1500 55 F2i6te) 5 So) &Z7i 5 >" on 5 25000) 200 @a5 eae ObsNearmvbateiroonrs | FivopateTlionggs Conia iS1o0LNiovremralfychange TOOT Ammon To $$1p100iGNliolilrmmnaygponisd Peaoroocanont. L | 33E11p00itGLliilierumnyugpyercihsaange roRetemhaerkvdcsr:,ThSTehuebosnmeliyHtAdssRsENSohtWearneOgnJlsyetchhdossresesbduewemesirwnheYiscehndwlerSeeiofnE tsoirice oCnthansionendbe dsemoanesnnsosihe ane coaothpyenTchr.aAonuotfohelobfpuisrecdfborwmaaslsobosetrevepdonmoseovrerdaolrsaahl.pTohsochoangtwa robin is Was contra response stator (yesiolanknowa): Ys Startesiults,asatpprioprciataes No aisieallysignificant finsweereporcd concuusions adirvloeourigchaa3lc0ddtagtaegppeonoesrhateteed.EHiDs sta<dry 6in4d5icaatAe hna the nsoemrinvael canodncsnrtiionofof10h0mge/L.shadnnoy Siptruwobdmauicttctiooenndrusoctrteemdm,abrbuktts:haosKmslevWeiriasclhfahokeintnestg2.S.Tphi1lsewskauesdymamkoeee.mtsmTlhlaehroen+rpooriresifooroFqunaslnestaoienmtchhe inmee nis of the tt solution oncenaionsof on he pence ya tn soe 2Revaierwteorst"hrnemaarykss:ofWnttconhdaitnieosns.was notmonitored ding the sta perorisotady comploon 354 000253 REFERENCE "fTahteheeafdfemctisnofocown(tPiinmueopuhsaleexspopsruomreela(0s)7.8.01397o8n. haRcetpcohratbi#lBtWy-o7f8.c6g-g1s75a.nd Rgersocwatrhcahnrdepsourrtvisvuablmiotftfeyd toof3V1 Company, St. Paul, MN by EG&G Bionomics Aquatic Toxicology Laboratory, Wareham, MA. OTHER `NGOenMeIraNlArLemTaErkSsT:CTHhEeMmIaCjoArLcoCnOcNeCrfEoNrTtRryAiTngItOoNdeStewremrieneustedh.e vOalPidPiTtyrfeorcothmimsetnedstsisthtahtatmeOaNsuLrYed test wchheimcihcatoltchoentcesetnotragtaniiosbnmessuasrecde,x5p0ostehda.t on[feictasndaectceurrmaitneelyd dtheatterthmeinneomtihenatlestcohnecremnitcraalticoonnscrenetroantliyo,nftoor ebyxa5m0pl%e.SI0Fa%noalfyttihecamlemaesausruerdecmoennctesnotfrastoiomnse, sthort thoaxdicbiteyenvafluurensischaendb, ewaencdoumludstalbeeualdtjeusctheedmdicoawlnward rmeicgohvterlyowreartetsh,eaancdtutaalketeisnttooragcacnoiusnmtehxypdorosluyrseisc,onvcoelnattrilaittiyo,nsa.ndAostheitrips hwyesiacroccohpeemriactailngprionctehsesedsartkhaotn this 3ss 000254 FISH ECOTOXICITY "Title: 96-hour acute static toxicity to fathead minnow -- FX-1001 TEST SUBSTANCE Identity: Perfluoroctanoic acid, also referred to as PFOA, FC-26,or FX-1001. pentadecafluoro-, CAS # 335-67-1) (Octanoic acid, nRoetmcaormkpsl:eteTlhyec3haMracptreordiuzcetdi,onalltohtonuugmhbienrfowramsatniootnnointdeidc.ateTdheitwteasst samwaspFX-l100e1. Tis purity a mixtureof95.98 percent test was substance and 1-5 percent perfluorochemical inerts METHODS Method/guideline followed: Not noted Test type: Static GLP (VN): No Year study performed: 1985 Species: Pimephales promelas, average length = 4.1 cm; average weight = 0.50 g; age not noted `Supplier: Dale Fattig of Brady, NB. Concentrations used: 0, 690, 750, 810, 870, 930 mg/L (nominal values). Exposure period: 96 hours. Analytical monitoring: limitsofthe chemical or No measurements were impuritis in the sample. taken. Also, there was no information on detection Statistical methods: Probit analysis 356 009255 `Test Conditions: - DFiilsuhtwieonrewaptreertrcehaetmeidstwriyt:h 25.0 mg/L tetracycline HCI, S months prior o study to fight diseases Carbon-filtered well water DO 9.5 ppm pH 78 Temp 19C - Water chemistry during the test Dissolved oxygen range (24-96 hours): 7.37.7 mg/L (control) 6.16.7 mg/L (870 me/L)* 7P.H5-ran7g.e7 ((2co4n-t9r6olh)ours) 7.5 - 7.5 (870 mg/Ly* #870 in the mg/L test group (second highest highest test concentrationby 48 concentration) hous. data given because total mortality occurred `Test temperature (24-96 hours): - Stock solution 1920C was prepared by dissolving 45 g test substance (neutralized with NaOH to pH 7.5) in 5liters 3 liters water. at the selected Test solutions were test concentrations. prepared by transferring stock solution aliquots to make - Loading rate: 0.50 g fish'L. - Stability of the test chemical solutionswasnot noted - Exposure vessels were glass beakers contained $ liters test solution. witah 24 cm inside diameter and a 26 em depth, and "Two replicates were taken at cachdose,with 5 fish per replicate Remarks: harmonized Wgauitdeerlihnaesr.dness was not presented. The pH values are acceptable according to the OPPTS RESULTS Dose of each endpoint concentrations. (as mg/L): 96-hour LCS0: 843 me/L (CL: 11-878), based on nominal Remarks: - 930 mg/L hours) was the lowest est substance concentration causing 100% mortality (seen at 45. - Therewas no 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. 357 009256 CONCLUSIONS `The test sample 96-hour LCS0 811-878 mg/L. for fathead minnow was determined to be 843 mg/L with a 95% C.I. of `fSorubqmuialtitteyr treestmiangr.ksH:owTehveerda,tsaaqmupallietpyurriatnykiwnagswanostaprKolpiemrilsychchraraacntkeriioznfe2dgabnedcaitulsaectkeesdtianngalmyetticcarliteria confirmationoftest substance concentrations. Reviewer remarks: none REFERENCE 3M Company. Laboratory, St. 1985. Paul, 96-hour MN. Lab aRceuqteuessttatiNcutmobxiecritCy1t0o06f.athFeeadbrmuianryno2.w -- FX-1001. Environmental OTHER GNeondeertaalilredemraerpokrst:waTshiasvasiulambmlea.ryThwearsefboarsee,dtohne caosntuemnmtsaorfytrhesporstumamnedroyn,lyinlirmeifteerdendcaetatotathbel.es. protocols andresultsof the study, are limited. The major concern TEST CHEMICAL fCorOtNryCiEngNtToRdAetTeIrOmNinStwheervealuisdeidt.y for this OPPT rteesctoimsmtehantdOs NthLatYmNeaOsMurIeNdAtLest ccohnecmeinctarlatcioonncetnotwrahtiicohnstobethuestceds,t soorgtahnatisomnsearcacneaxcpcousreadt.eIlyfidteitserdmeitneermtihenetdestthcahtetmhiecnaolminal cboenacenndtmrautsitonbseaardejuosntlye,d dfoorwenxwaamrpdleby505%0o%ft. hIefanmaelaystuircaeld mceonacseunrtermateinotnsso,fthseotmoexiscoirtty hvaaldubeesecnan afnurdniosthheedr,pwheysciocuolcdhecmailccaullatperoccheesmsiecsatlhartecmoivgehrtylroatweesr, tahnedatcatkuealintetsotaocrcgoaunnitshmyderxoployssuirs,e volatility, concentrations, 358 000257 FISH ECOTOXICITY Title: Acute Toxicity to Fish TEST SUBSTANCE Ipdeernftliutoyr:ooPceirafnloutoer,ooFcCt-a1n1o6i,c aFcCi-d1,2a6m,mFoCn-i1u6m9os,arl;FCa-l1s4o3r.efe(rOrcetdatnooaisaPciFdO,Apeantmamdoccnaifluumosralot-,,aammmmoonniiuumm salt, CAS 3825-2611) sRoelimd.arkIs's:puTrhiety3wMasprnoodtuccotmlpoltentuelmybechraurascetderwiazsed3,90a.lthTohueghteisntfsoarmmpaltieownaisndFiCc-at1e2d6,itawwhaisatemipxotwudreeroyf 7893% test substance and 7-22% C6, C7, and C9 perfluoro analogue compounds. METHODS Methodguideline followed: Not stated Test type: Static GLP (Y/N): No, Year study performed: 1987 Species: Pimephales promelas Average length = 3.5 cm Average weight + 0.30 `Supplier: Dale Fattig of Brady, NB Concentrations tested: 0, 100, 150, 320, 560, and 1000 mg/L Exposure period: 96 hours Analytical monitoring: None because nominal concentrations were used. Statistical methods: Probit analysis Test conditions: ""DDiilluuttiioonn wwaatteerr schoeumricsetcrayr:bon-ileredwell water DTOemopfo9f.231pCpm PHOS "Test solutions were prepared by direct weights addition 359 000258 E"Sxtpaboisluitryoefvtehsseeltseswtecrheem4iLciatlersoPlyurteixongslwasassbneoatkenrostecdontaining 3 liters test solution "STwiofriesphlpiecartersepwleicraeteusweedre used "Loading rate was 0.6 gL "Water chemiDsOtryradnugrein(g24t-es9t6: hours): PH range (24-96 hours): 56.6676.64 mmgL/L ((c3o2n0trmogl)/L?) 777.:28709 (Gc2on0trmogl/)L*) "*TTehimsp g(r2o4u-p96whaosuruss)e:d2b0eCcause toal mortality occurred at higher doses wRietmhainrkasc:cepNtoabolteherrandgeteasilasccoonrdteisntgctoondOiPtiPoTnSs wHearremgoinviezne,dignucilduedliinngesw.ater hardness. The pH values are RESULTS Dose mg/L o(f9e5a%chCI:end2p4o4-i3n7t0)(a.s mg/L): The 96-hour LCS0 for fathead minnow was determined to be 301 Remarks: -- SLuorwfeasctinegsotffsiubsshtawnacseocbosnecrevnterdatatio1n80caaunsdin3g2010m0g%/Lmo(rbtoatlhitryepwlaiscatSe6s0) mg/L - No mortality was observed in the controls m`oWratsalciotnytrol response satisfactory (yes/no/unknown): Yes, based on the fact that there was no Statistical results, as appropriate: Not presented CONCLUSIONS wRaosunddeitnegrmtihneerdestuoltbse1300.20smiggn/iLfiwciantth faig9u5re%s,ctohnefitdesetncseamipnlteerv9a6l-ohfou2r40L-C3S700 fmogr/Lf.thead minnow qSuuablmiittytteerstsi"ngr. emHaorwkesv:erD,atthaeqsuaamliptlye wpausrgitiyvewnasanKoltipmriospcehrlryanckhianrgaoctfe2r.izeTdesatnidngit mleatcktehde acnrailtyetriiacaflor confirmationofthe test substance concentrations. Reviewers' remarks: none REFERENCE 3M Company. 1987. St. Paul, MN. Lab Request Number E128201, completed on May | 360 000259 OTHER GNeonedertaalilreedmraerpkorst:waTshiasvasiulambmlae.ry"Twhaesrebfoarsee,dtohen caonstuemnmtsaorfy treipsorstumamnadroyn,lyinlirmeifteerdendcaetatotatbhlee.s. protocolsand resultsofthe study, are limited. The major concern TEST CHEMICAL for trying to determine CONCENTRATIONS the validity were used. for this OPPT test is that ONLY NOMINAL recommends that measured test ``ccohnecmeinctarlactioonncetnotwrhaitcihontsobethuesteeds,tsoorgtahantisomnse acraeneaxcpcousreadt.elyIFdiettiesrdmeitneertmhienteedstthcahtetmhiecnaolminal c`boenacenndtmrautsitonbse aardejuosntlye,d fdoorwenxwaamrpdleby505%0o%ft.Ihfeanmaelaystuircaeld mceonacseunrtermateinotnsso,ftsheomteoxiscoirtty hvaadlubeesecnan afnurdniosthheedr,pwheysciocuolcdhecmailccuallatperoccheesmsiecsalthartecmoivgehrtylroatweesr, tahnedtaactkuealinttesotaocrcgoaunnitshmyderxoployssuirse,. volatility, concentrations, 361 000260 TOXICITY TO FisH Titles Static Acute ToicityofFX-1003 to the Fathead Minow, Pimephalespromelas TEST SUBSTANCE aIdmemntointiy:umPeprefrlfulourooroocotcatnaoniocataec,idP,FaO,mmFoCn-1i1u6m,sFaClt-;1m26a,yFaCls-o1b6e9,reFfeCrr-ed1too4ra13s ,PaFmOaAjoarmcmoomnpiounmenstaolf, FX. 1003. (Octanoic acid, pentadecafluoro-, ammoniumsalt, CASRN 3825-26-1) RFeXm-a1r0k0s:3 waTsheno3tMsufpfriocdiuencttliyonchlaortanctuemrbizeerd;wahsow2e3v2e7r.,TahveaitleasbtlseaimnpfloermwaatsioFnX-i1n0di0c3a.teTdhietwpaursitay of aSonldut1io-n2o%f <C4s5a%ndamC;mopnerifulumorpoe-rfalnuaolroogauceiacnooamtpeo,uSnd0s%. water, <3% inert perfluorinated compound METHODS Methodguideline followed: OECD 203 Test type: Static GLP (VIN): Yes ear study performed: 1990 Supnedceiresf:lowP-rtiohrrotuogthesctoinndg,itjiuovnesniilneanfaatlhlegaldamssinanquoawrsiuwme.reFiaschclwiemraeteadccfloirm6a3teddatyostihne 1ta0r0ge%tdeisltution water temperature disease and w(e2r3e+f2reeC)offaoprpa14rednatyssibcekfneosrse,teisntjuirniietsi,ataionnd. During acclimation, abnormalities at test fishwere initiation, nFiosthtrweearteedfefdora v`acloumemseorfcitahlefifsihshfwooedr,eo3n.c8ecomr tawnidc0e.d4a5ilgyr,afmosrt(hweeta)c,clreismpaetcitoinvelpye.riod. The average length and weight RSuepspelairecrh:OrTghaenifsimshs,usHcadmpintothne,tNoxHi)c.itTyhteestspwoenrseorp,u3rcMh,asperdovfidreodamthceotmemsetrscubisatlanscuep.plier (Aquatic `coCnocnecnetnatatriaotniso:ns0t.e1s,te1d,:10A, 1s0c0r,oeannidng1t0o0x0icmigt/yLt.esFtowratshepedreffionrimteidvewtiotxhictihtey fteosltl,ofwiivnegnfoimviennaolminal cuosnecdenintrtahteidoenfsinaintdivoenteoxbilcaintyk dtiesltutainodn wthaetenromcoinntarlolcownecreentursaetdi.onTswtoesrteepdliwcearte:esof0,ea15c0h, c2o5n0c,e4n0t0r,at6i0o0n,waenred. 1000 me/L. Bothtestswere performed under static conditions. Exposure period: 96 hours Arencaolrydteidcadlaimloyniintocraicnhgt:esDticshsaolmvbeedrotxhaytgecno,ntpaHi,necdonldvuectfiivshi.tyC,oancnednttreampteiroantsuorfetwheerteesmtesausbusrteadncaenwdere not measured during the test. 362 000261 o`Sftatthiesttiocxailcimteyttheosdt sc:oulNdonn-oltibneeianrtienrtperreptoeldatiboyn,stmaonvdiarndg satvateirsatgieca,ltaencdh/noirqpureosbdituacnatloys1i0s;0%hoswuervveirva,lraetsutlhtes highest tested concentration. Test conditions: "The screening test substance utensdtewrassimpielarrfocromenddusiintagisnotohmnoisnsealofcotnhceednetfriantiitoinvse (te0s.t1, 1.0, 10, 100, and 1000 mg/L)of the fWraotmerweulslesdatfoErnavcicrloiSmaytsitoenmsofinthHeatmespttoorng,anNiHs.msW,aatnedr fwoarsalaldtjouxsitceidtytoteasthianrg,dnweasssowfel$l8wmagte/rLcaosllCeactCeOd, naantdursaolrweedllinwatatnekrs,uswehderase tithewadisluateriaotnedw.atAercfhoermtihcealtocxhiacriatyctteersitzwataisonpoerffaroerpmreeds:etnhteatfiovleloswainmgplveaolfuetshe `woerrgeandoeptheorsmpinheodr:ouspHpe=sti7c.i4d,ecs,onadnudctPivCiBtSy w=e1r5e0b0eulmohwotsh/ecmle.veOlrogfadneotcehcltoironi,neorpneostticpirdeesse,nt, The test vcme)s.selSstawbielrietyo19f.t6hLe gtlesatsssuabqsutarainacethwaatsconnottaiinndeidca1t5edL.oNfotsetstocskolsuotliuotnio(napwparsoxpirmeaptaerweadtears depth was 17 test material was naodmdiendadlirceocntcleytntordaitliuotnisonwewraeteursceodntianitnheeddeifnitnhiteivteesttevsetss0e,ls15w0i,th2o5u0t, t4h0e0,us6e00o,faansdolv1e0n0t0. mTgh/eL.foTllwoewnintgy. dfiestherwmeirneedratnodboemlaypparnodxiemqautaelllyy 0di.s3t0rigb/uL.tedTeasmtovnegssetlwsowreerpleicraatnedsoomflcyacahrrtarnegaetdmeinnt.a The loading rate was. water bath during the. 9ph6o-thoopuerrtieostd. wSatastiacuctoonmdatiitciaolnlsywmearientmaaiinnetdaiwnietdh throughout cool-white tfhleuosrteusdcy.entAli1g6h-thsotuhratlpigrhot vainddead-hloiughrtdark intensityof 35 concentrations Es", Acration was above acceptable levels. employedafer Fish were not 48 fed hdouurrisngtothmeaitenstt.aiTnhdeisfsoolllvoewdinogxywgaetner chemistry ranges 1300- (106--0096ymhhoourss/)ewmer(e10d0e0temrgm/iLneedx:pocsounrdeu)c;tipvHitrya=nge1=2007-.--41580.04 pmhos/cm (control (control exposure), exposure), = 7.8 8.2 = (1000 9m.g2/mLge/Lx.po(scuornet)r;olteexmppoesruarteu)r,e =ra6n.g2e-=92.11.(01-00202mCg/(cLonetxrpoolsuarned). 1T0h00e mpgH/aLnedxphoasrudrnee)s;s dwiesrseolwvietdhiOns the6.1 aceepied ranges (6.0 < pH <8.5; 40<hardness<180 mg/L) for the duration of the study. Remarks: No additional comments RESULTS Doseofeach endpoint (as mg/L): Screen9i6n-ghoteusrt LCS0 > 1000 mg/L, 96-hour NOEC > 1000 mg/L Definit9i6v-ehoesutr: LCS0> 1000mg/L, 96-hour NOEC > 1000 mg/L `Reexmpoasrukrse:anAd lallesotthveerssteeslts erxepmoasiunreeds clear throughout in the screening the test test. and i1n 0t0he%sdeufrivniivtailveocteesutrred in the control Was control response satisfactory (yes/no/unknown): Yes Ssttaattiissttiiccaallmeretshuoltdss, dauscatpopr1o0pr0i%atseur:vival Ratestuhletshoigfhtehste tteosxtiecditcyontcesetntcroautlidonn.ot be interpreted by standard 363 000262 C"TOheN9C6L-hUoSuIrOLNCS50 and 96-hour NOEC were determined tobe >1000mg/L. Sscouanbmcmpeilnttertpaeutrrisoi'ntsyr.weamsarnkost:prKolpiemrilsycchharraanctkeirni2zg.edTaensdtitnghmteesettlatchkeecdriatnearliyatfiocalqcuoalniftiyrmtaetstiionng.ofHoewsetvseurb,stance Reviewers' remarks: The conclusions appear o be suppobryttehed data REFEREEnNvCirEoSystems, nc. 1990, Static Acute ToxiofcFXi-1t00y3 to the Fathead Minnow,Pimephales promelas Hampton, NH. Study numberwas 9014.3, omer "The majoGrenceornaclerrefmoarrykis:ng t0 determine the validity for this test s that ONLY NOMINAL TEST CtchoHencEteeMnsttIroCartAgiaLonnisCsObmesNuCasrEeedNe,xTspRoosAtehTda.tIoO[nNfeiStcaiwsnedraeectceuusmremadti.enleyOdPdhePtaTertrmheiecnneoomtmmhieennateldsstcoctnhhcaetemnimtceraaalstiucoronensdcaetrneetsaotnclihyoe,nmif0coarwlehxiacmhplteo I5Fa0n%aloyfttihcealmmeesassuurrcedmceonntcsenotfrsaotimoens,sohrtehtaodxibceietynvfaulmuiesshceadn,bweeacnodulmdusctalbceulaatdejucshteemdicdaolwnrwecaorvderbyyr0as%, aacntduaalkteesitnotorgaacnciosumntexhpyodsroulryesicso,ncveonltatrialtiitoyn,sa.nd othr physicochemical processes that ight lowe the 364 009263 TOXICITY TO FisH Title Acute toxicity of N2803-3 10 the Fathead Minnow, Pimephales promelas TEST SUBSTANCE pdeenntsaidteyc:aflPueorrfol-u,oCroAoSctRaNnoi3c35a-ci6d7;-1m)ayalsobe referred to as PFOA, FC-26,or FX-1001. (Octanoic acid, `Rseammpaler.ksF:C-2T6h,ew3aMs prreofdeurcetditoonblyottnhuemlbaebrowraasto2ar69sy.NT2h80e3t-e3s.t sTuhbsetpaunrcietywaofsthaewhsiatmeplpoewwdears,nTothe test ssuufbfsitcainecntelsyncdh0arac3te.r5iz%edC:i,hCorw,evaenrd,Casvapielrafbllueorion-fohrmoamtoilonoguiendciocamtpeodunitdwsa.sTahmeiexstturseoubfst9a6n.c5e-("1s0-0% test rmeicxetiuvreed"w)aswarsefceormebdifnoeadswtihteh"iassoepsrtopeadn"olsuibstaan5c0e:.50 ratio prio use. Th substance resuling from this METHODS Methodguideline followed: U.S. EPA-TSCA Guideline797.1400 Test type: Static GLP (VIN): Yes Year study performed: 1996 Stapnekc.ieDsu:rinJugvaecncilliemaftaitohne,adthmeifninshowwserweernoetarccclaitmeatfeodrudnisdeearsef.loTwh-ethfrioshugwhercoendfrieteioofnsianppaar2en7t 0sLicfkinbeesrsg,lass iDnujruirinegs,thaend14a-bdnoarympaelriitoidesbeaftotreesttiensittiiantiitoina.tioMno,rttahleiatcycdliumraitnigotnhtefmipnaelra4t8urheourrasnogfeacwcalsi2ma1t0ioCn -wa2s2.<33C% aexncdepthtedduirsisnoglvtehde o48xyhgoeunrscoinmcmeendtiraatteiloyn wparesceatdifneagstth8e.0esmt.g/TL.heDauvreirnaggeactcoltiamlalteinognt,hfaisnhdwweertewfeeidgdhatloyf,the test organisms were 3.4 mm and 0.35 grams, respectively. sSpuopnpsloire,r:3MJ,uvseunpiplleiefdatthheeadtemtisnunbostwasncwee.re procured from Aquat Biosystems, Fort Collins, CO. The w`Ceornecuesnetdr:ati0o.n0s.t0e5s,ted0:50,F5o.0r,t5he0,satantdic5s0c0remegn/iLn.g fFeosrt,htehesftaotlilcodweifnignintoimvientaeslt,cothnecefnotrlaltoiwoinnsg,naosm-irnecaelived, icosnocpernotpraantoilo,nns,omai-ntaelstceodn.cwenetrreatuiseodn:s o0,f01(3d0i,l2u2ti0o,n3w6a0t,er6c0o0n,tarnold)1a0n0d0Sm0L0.mg/FoLritshoeprstoaptaincotleswtewriethsed. Exposure period:96 hours Arencaolrydteidcadlaimloyniintocraicnhgf:stDicshsaomlbveerd.oTxhyegeenm,ppeHr,autermepeirnaotunree,tesatnvdecsosenlduwcatsivriteycowredreed matealesausrtehdouarnldy during the test. Concentrationsof the test substance were not measured during the study. 365 009264 Sptoastsiisbtliec,alusmiengthpordobsi:t aLnCailygsvisa,lumeosvwienrgeacvaelrcaugleatmedetbhyodn,ono-rlibnienaormiinatlerpproolbaabtiilointy(.Stephan, 1983), when "Test conditions: wFaotretrhecosntartoilc).sc0r.e0e5n,i0n.g50te,st5,.0n,om50i,naalndco5n0c0enmtgr/aLt.ionTshoefstchreeetensitngsutbessttawnacse,paesr-froecremievdedu,nwdeerresi0mi(ldairlution conditions as those of the definitive test. cWoaltleerctuesdeadt fTo.rR.acWcillibmautriyonLoabfotrhaetotreisetsoringaMnairsbmisc,haenadd,foMrAa.ll Wtoaxtiecritwyatsestaidnjgu,swteads1d0eaiohnairzdendeswsaotfer40 -- 45 pmags/sLedasthCraoCugOh,aapnadrtsitcolreefdilienr,poullytcratvhiyolleentesttearniklsi.zerI,natnhedtaacntkisv,attehdecwaartbeonr,waIsn aaecrhaetmeidcaanldchcaornatcitneuroiuzsaltyion ocofantarmepirneasnetnstawteirvee scaitmhpelreobefldoiwlutthieonlewvaeltoerf,deitroenctwiaosn,doertencottedpraetse0n.t,03 Tmhge/Lt.estOtshuebrstmaentcael,sasa-nrdecpeoitveendt,iawlas c1o0m0b%inteesdt wsiutbhstiasnocperdouprainonlg tinheat5o0xi:c5i0tyratteiso. pTrihoer tteostusseu.bTshtiansc5e0w:a50smaisxstuumreedwtaoshtahveenacpounrsiitdyeroefd1t0o0be%. aaqcutairvieai.nwgrheidcihenctoanntaditnoedbe15saLbolfetuesntdesrolsuttoiroange(aapnpdrotexsitmiantgecownadtietriodnesp,thThweastes1t8vcems)s,elTswweenrtey2f0atLhgelaadss `Apmpirnonporwisatweeraemoiundnitsscorifmiensattesluybsatnadnceequwaelrleyaddidsterdidbiurteedctalmyotnogditlwuotiornepwliactaetresinoftheeactehstirveeastsemlesntto faonrdmu1l0a0t0emtgh/eL.medTihae. tTehstevteesssteclosnwceenrtealtoioosnesl,yasc-otveesrteedd,anfodrrtahneddoemflinyitairvreatnegsetdweirnea: wa0,te1r30b,at2h20d,ur3i6n0g,t6h0e0, `9a6u-thoomautricteaslt.lyAma1i6n-thaoiunreldigwhitthancdoo8l--hwohuirtedafrlkuoprheostceonpterliiogdh,tswtihtaht apr1o5v-imdienduatelitgrhatnsiinttieonnsipteyroifod3.1was afcooctecpatnadbllces.leAveelrsa.tiMoenaswuarseidniwdaatteerdcahfetmeris7t2ryhoduurrsintgo mthaeinttesatinprdoivsisdoeldvetdheoxfyoglleonwicnogncreanntgreasti(o0n.s s9b6ohvoeurs) D1i1s0s-o3l7v0edyu0m;ho=s6/.4em- (c8o.n7trmoel/aLnd(c2o2nt0romlge/xLpoesxuproes)u,re=);5.p2H-=9.70.1mg/7L.6((c2o2n0tmrgol/Lexepxopsousruer)e,);=C3o.nd0--uc7t.i4vi(t2y20 mfegst/Lsoleuxtpioosnusref)o;r Ttheemp3e6r0,at6u0r0e, =an2d1.180~0022m.g6/LCe(xcponotsruorleacnodnc2e2n0trmatLi.onsexwpeorsuerein).thTehreanpgHe voaflue3s.o0f4.t3heat t<epsHt<i8n.i5ti)a.tioHn.arTdhneesses lwoaws pwiHthvianlutehse waeccreepotuatbsliedreatnhgeeafcocretpotxaibclietyrsatnugdeiefsor(a4q0uati1c50tomxgi/ciLt,yasstuCdaieCsO()6..0 FscorretehneinsgtaatincdtdoexfiicniittyivteesttopxeirciftoyrmteesdtswwiitthhiNs2o8p0r3o-p3a.n0,as(diimliutliaornwpartoetroccoolntwraosl)faonldloSw0ed0 amsLt.haifsoarptrhoepanl (inntoemnisnitaylwcaonsce2n8trfaotoitocna)nlweesr.e uscd. Test vessels were randomly arranged in a water bath and the light Remarks: No additional comments RESULTS DoseofeaTecshtesnubdsptoainncte(caosncmegn/trLa)tiionn,thaes-dteefsitneidt,iavendfeasst:sociated 95% confidence limits: 2448--hhoouurr LLCCss== 228800 ((222200-- 336600)) mmgg//LL. 7926--hhoouurr CLCeso== 226800 ((22--203366200))mmg0//lL 96-hour NOEC= 220 mg/L. 366 000265 Test substance concentration, as-receivaendd, 24-hour LCs =140 (110 - 180)mg/L associated 95% confidence limits: 48-hour LCs=p140 (110 -180) mg/L 72-hour LCs= 140 (110-180)mg/L 9966-h-ouhroLNuCOrEC==14101(01m1g/-0L.180) mg/L cRoenmtraorlk,s9:0%Fosrurtvhievaslcraete0n.i0n5g mtegs/t,L,the10f0ol%lsowuinrg svuraivti0vv.a5la0r,altes5.0,wearned o5b0semrgv/eLd,: a1n0d00%%susruvrivviavlalinatthSe00 mg/L. study. F1o0r0t%hesudrevfiivnailtiovectecsutr,rnieondintshoelcuobnltermoalteerxipaolsuwraesaonbdsetrhevseed fiantahneayod fmitnhenotwesst dviedssneolts edxuhriibnigt tahney wsuabsleotbhsaelrevfefedctwsi.thFiinsh2i4nhtohuers13i0n athned326200, 6m0g0/,Laenxdpo1s0u0r0emgco/nLceentxrpaotsiuornes caopnpceeanrteradtinoornmsa;lt,heTroetfaolrem,otrhteality mlogw/eLstiscoonpcreonptarnaotli,onn,o wmohritcahlictayousresdub1l0et0h%almoerftfaelcittsy,wewraeso3b6s0ermvge/dL;.thDeu9r6i-nhgotuhre LtoCxsicivtayluteestwawisth>550000 mg/L. `Was control response satisfactory (yes/no/unknown): Yes Statistical results, as appropriate: No additional comments CONCLUSIONS mTgh/eL.as-Ttheesteads-9te6s-theodu9r6-LhCosurwnao-sodbeertveerdm-ienfefdectot-bceon2c8e0ntmrga/tLi,onwi(tNhOaEC9)5%wacson2f2i0demngc/eL.intTehrveal9o6f-h2o2u0r C- a36,0 based on Of 110. the 130 tmegs/tLs.ubTshtean9c6e-ahsoruerceNiOveEdC,wfaosr determined to be the test substance, 140 mg/L, with a as-received, was 95% 110 confidence mg/L. interval c`oSnucbemnittrtaetriso'nrseimnatrhkest:estKsloilmuitsicohnsraanndksian3mg.plTehpeursittuydwyalsacnkoetdsaunfafliyctiiecnatllymcehaasruacrteemreiznetdo.fAtdedsittsiuobnsatlalnyc,e. tthheerperaopcpeedaurreedtcoonbdueacteddisbcyretphaenlcaybboreattwoereyntothperespaamrpelethperteepsatrsaotliuotniodnisr.ecTthieonasbgsievnecneotofptahretliaablomroarttoarlyiatnydat sitnutderymmedaiyatneotdoascecsurraetseullyterdefilnecatshtaherptrduoesteo-xriceistpyoonfsethceursvoel.utAiosn.areTshueltl,otwhepHLCv.aqluveasluoebssdeertveerdmiinnetdheihnitghhis concentrations tested may have had an adverse effect on survival. Reviewers" remarks: The conclusions appear tobe supported by the data, REFERENCE pTrRo.melWaisl.buMrayrbLlaebohreaatdo,riMeAs,. InSct.ud19y96n.umAbcuetre 8t9o1x-iTcHi.tyof N2803-3 (0 the Fathead Minnow, Pimephales OTHER General remarks: ONLY NOMINAL The major concen TEST CHEMICAL for trying to determine CONCENTRATIONS the validity were used. fOoPr PthTisrteecstoimsmtehnatds cthhaetmimceaalsucroencdetnetsrtacthieomnitcoalwhciocnhcetonttrhaetitoensst be used,so that one can organisms are exposed. accurately determine the test Iift is determined that the v`naolmuiensalcacnonbceenatnrdatmiuosntsabreeaodnjluys,tefdordeoxwanmwpalred$b0y%oS0f%.the Imfaenaasluyrteidcaclonmceeansturrateimoennst,sothfestooxmiceitsyort had been furnished, we could calculate chemical recovery rates, and take into account hydrolysis, 367 000266 evoxlpaotisluirtey,caonncdenottrhaetriopnhsy.sicochemical processes that might lower the actual test organism tPeustr.ityIonfstohmeetetsetstmsaittearpipaelaarsedo itshaatm1a0jo0r%cteosntccehremaincdalwawsasnoutsesdu,fffiocrieontthlyerchs2arcahcetmeirciazledofilnesthsiesr wpuarsituyse(adpipnrooxtihmeartteelsyt,85fo%r)nowaosbvuisocud.s sWaatteedr,raeassoonl.venItn (faicsto,p3roMpainnolt)hoeirr scuommmbairnyaotifoenoacfhbtoetsth satgatree:e"Dwaittha mthaisycnoontcaecnc.uraItnealdydirteiloant,e tifotxhiicsitwyoafs tah"ettyepsitcasla"mpTlSeCwAitshetchtaitoonf4threevtiesetsw,ub|swtoaunlcde." rmeejaescturtehemseentsstoudfitesh,epetensdticnhgemriecceailptionfthaeddtietsitomneadliiunmf.ormation on purity and studies on analytical 368 009267 FISH ECOTOXICITY Title: Acute toxicity ofFC-1015 to the fathead minnow,Pimephalespromelas TEST SUBSTANCE IAFdCme-mn1t0oi1nt5yi.:umP(eOprcfetlrufaolnrueooorcaoctoiacdn,toaipcnelnsetc,iadd,PeFcaOamf,mluFooCnr-io1u-1m6a,msamFltCo;-n1mi2au6y,maFssCa-lo,1b6Ce9A,rSeFfCe#r-3r18e42d35t-oo2r6aas.s1P)tFhOe Amaajmormoconmipuomnesanltt,of iTRonetfmnoarumrmakbtsei:ornwTiahnsedi"cteaHsttOessGaiEmpi2l0ae5.3is"0F%DCa-st1tar0a1mi5ga.hyt TcniaosrtpbuaorcnicctuyhraawtiaenslvyenrorsetiloasntueftocofixeiFncCit-tly1yo4fc3hatirhnea8cte0ers%tizsweaadtm,eprlt.ehowTuhigheh3ctuMhrarteponrtfodtuhcet pafeemsrtmfslouunboisrtouaomncciepa.enrofaDltauetoarhoowomecotralenouogastcmedixittnouFcrCoe-mi1pn0aF1rC5e-t1o4x3icivst.y wohfatthebirasnucphpeosde!sdtr0aibgehtthheai1n00a%mmstoenaiiguhmcarbon chain METHODS Method/guideline followed: USEPA-TSCA 1993. 797.1400 Test type: sac GLP (VN): N Year study performed: 1996 Swpeeicgihets:ofPi0m.e36pgh(awlee)s.promelas The fish werejuveniles with an average lengthof 35 mm and average Supplier: Aquatic Biosystems `reCpolnicceantetsraatticoancshucsoendc:en0t,ra5t3i0o,n$w3e0r,e1p3e3r0f,or2m1e0d0.. 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 computer program, 1983 aaTsepsaftrotlCilocounwldsa:ittehiaofrnldsen:e,sTslhr=aev4di4iollmuetgti/osLntewarsailtCiezareCru,Ossae,nddawlaakcsatlidivneaiittoeyndi=cza2er9db-own3a.0temTrgh/aedLjduaissltuCetdaioCfnOorwya,htaaernrddncehTsesOmCain<sdep|awmsags/seLdm.ethaFrsooururgehd afleinsgdthtsionlhguo,tuicroosnosdla-wwrehkriewtiectrfhelauatoer1deSsbmcyeinndtuitrieegchtttrsiannadstiivt3ii0odnufaoploetrw-iecoiadgnhwdtiacsasddmwiaetirinoetnasu.isendeA.dfttAehdrra.oiug1l4hyodupathyottahocepce(lreisimtoaidtnoigofpn1erp6ieordhi.ooudr,Tshtehieght fish were exposed, at a loadingof024g fh. in 20 L glass aquaria containing 15 tes est solution at 369 000268 an in caapcphrorxepilmiacattee.depth of 18 em. Two replicates were tested at each concentration. Twenty fish were used (wT2hm1eh0o0wsam/tgeer/mLc(hceeoxmnptiorssotulrr)yea)pn,adrtae3mm0ep0te-er3ra2st0umrueeam=shuo2rse/d2edmu.(r2i10n0gC0-t(mhceyo2n/sttL2ruodeylx.)piaon4nsculdurde2e)1d,.:8p-cH2o2=n.d5u7c.3t-Ci7.v(9i2(t1yc0o0rnatmnrggoe/lL=)ea1x8np0ods-a71r.9e20).,7.7and h(doisuserscsoo.lnvdeTdhhieogxhpeyHsgtre)annco=gnec5e.wn8at9sr.a2wtiimtoghn/iLwn.ats(hceuoasncetedrcopbDieacabanludes5er.a7tn-hg9ee..h2igmMhgee/asLstuc(ro2en1mc0ee0nnttmrsgoa/tfiLdoinelxrupetossiuuolrntee)wd.iateTrthocetahle2m1mi0osr0ttramylgi/wteLyraet 72 also performed a10.03 mL. (see Appendix for parameters and detection limits). The only chemical detected was iron Remarks: Water hardness, during the study, was not indicated. PSULTS Doseofcach endpoint (as mg/L): 96 hr LCS0 = 2470 (2100-3330) mg/L. 96 hr NOEC = 830 mg/L. Remarks: none `Was control response satisfactory (yes/no/unknown): yes Statistical results, as appropriate: none CONCLUSIONS cTohnefitdesetnscaemipnlteerv9a6lohfou2r1L0C0-S3033f0ormfga/tLh.ead minnow was determined to be 2470 mg/L with a 95% tShuebmcriittteeriras"orreqmuaalriktsy:tesFtoinrg.datHaorweelivaebril,itsy,amtphleesptuurdiytywawsasasnsotigpnreoapderKllyimcihasrcahctreatriinzgedoaf2n.d Testing it lacks mets `analytical confirmationoftest substance concentrations. OReNvLieYweNrOs"MIreNmAarLksT:ESTTheCmHaEjMorIcCoAncLerCnOfNorCtErNyiTngRAtoTdIetOeNrSmiwneerteheusvcadl.idiOtyPfPoTr trheiscotemsmteinsdthsat chtehamtimceaalsucroencdentetsrtacthieonmitcoalwhciocnhcetnotrtahteitoensst obreguasneids,mssoatrheatexopnoesecda.n aIcficturiastdeeltyedremtienremdintehatthtehetest `vnaolmuiensalcacnonbceenatnrdatmiuosntsabreeoandjluys,tefdordoexwanmwpalredSb0y%5o0f%.the Imfeaanasluyrteidcaclonmceeansturrateimoennst,sthoef stooxmiecitsyort `aoldatibleietny,fanudrotnhierswpehhycesoiduclo,dchceamliccuallatpercohceemsiscesalthraetcmoivegrhyt rlaotewse,ratnhde atcatkuealintteostacocroguanntishmydrolysis, exposure concentrations. tPeustr.ityTnofSotmheettesetstmsaittearpiapleaarlesdo tishaat m1a0j0or%ctoesntccehrenmaincdalwwaassnoutsesdu,fffiocrieontthleyrscahcahraecmtierciazleodfinlethsiss:er wpuarsituys(eadpipnrooxtihmeartteelstys,8f5o%r)nowaosbvuisoedu.s Watera, solvent stated reason. In (isopropanol) or fact, 3M in their a combination ofbol summaryofeach test Fstaatger:ee"Dwaittah mthaisycnoontcearcnc.uraIntealdydirteiloant,e tifoxtiicsitwyoafstah"ttyepsitcsala"mpTlSeCwAitshctchtaitonof4threevtieestw,suIbwstoaunlcde." 370 000269 rmeejaescturtehemseentstsuodfiest,hepteensdticnhgemriecceailptinoftahdedtietsitomneadliiunmf.ormation on purity and studies on analytical REFERENCE Ward, T., promelas. Nevius, I. and TR. Wilbury RL.abBooreartio.rie1s9,96I.nc.AcLuatbe toxicity Request onfumFbCe-r10P11562t4o.the3MfatChoemapdamniyn,noSwt., Pimephales Paul, MN. OTHER General remarks: none APPENDIX Chmemeicaal sureomfdeilutniontwatser Parameter: Detection Limit: Metals AArlsuemniincum Boron Cadmium Chromium Cobalt Copper Iron Lead Mercury Nickel Silver Zine Nitrate Chloride. Fluoride Total organic carbon OTrotgaalnopchholsoprhionreouPessticides Toxaphene `Organophosphorous Dimethoate: Pesticides TEPP PCBsM.onocrotophos 0.1 mL 0.01 mgL 0.5 mel 0.0002 mg/L. 0.01 mg/L 0.03 mg/L 0.005 mg/L 0.03 mg/L 0.005 mg/L 0.0003 mg/L. 0.03 mylL 0.02 0.02 mglL mg/L 0.05 mg NIL. mg/L 0.1 mg mg 0.03 mg/L. 0.5 ug 2pg/ll 0.5 pg/L 20g 20g 20 ug 0.5 pg 3n 000270 TACEUSTTESTUOBXSITCAINTCYETO FISH (FATHEAD MINNOW) aIsdePntFiOtyA: aPemrmfolunoiruoomctsaalnto,iAcmacmiod,niamummopneirfulmuosraolot;ctmaanoyatael,soPbFeO,referred to pFeCn-t1a1d6ec,aFfCi-u1or2o6-,, FaCm-m1o69n,iuormFsCa-lt1,43C.AS(Ofct3a8n2o5i-c2a6c-i1d), FRCe-m1a4r3k,sr:efTehrere3d Mto pbryodtuhecttieosn llaofbonruatmobreyrawsaNs2840237.-4.ThTeheteTst.Rs.ample is nWoitlsbuuffricsiteundtylyncuhmarbaecrteirsiz8e9d5,-TaHl.thTouhgehpcuurrirteyntofinthfeorsmaamtpilone was 3i.5%nCdic6at.es iCt7i,s aa nmdixCt9urpeeorffl9u6o.r5o -an1a0l0og%uetesctosmupbosutnadnsce.and 0 -- MMeEthToHd:ODUS. EPA-TSCA Guideline 797.1400 TGyLpPe:: YAecsute static SYpeeaciresc:ompPliemteepdh:ale1s99p5romelas ASunpapllyiteirc:alAqmuoantiitcorBiinogs:ysDtOem,s,coFnodrutctCiovliltiyn,s,pCHOand temperature ExStpaotisstuircaelpemreithoodd:s:96-LhCoSur0svalues calculated, when possible, by probit iannatleyrspiosl,atmioonviunsginagvtehreacgeommpeuttheordsoorftbwianroemoifalC.pEr.obaStbeiplhiatny.with non-linear "LTeenstgtfhishanadge:weNiogthtn:otAedv.erage length = 28.6 cm LAovaedriangge:w0e.i1g3htg/=L0..19 (wet) "PTreesttrceoantdmietnito:ns:None mDigl/uLtiaosnCWaaCteOrI:LDeionized water adjusted to hardnessof40-48 LDiilguhttiionngswaCtoeolr-cwhheimtiesftlruyo:reNsocetntnobtueldbs with an intensityof30 f-. tPrhaontsoitpieorniopedorifod1.6-hours light, 8 -hours dark with a 15 minute dSitroecctklyantdo ttheestdisloultuitoinonwsatperrepinartahteitoenst:vTeessstelssubstance added SCtoanbcielnittyroafttiohnestdesotsicnhgemriactae:lOsnocleu.tions: No insoluble material wEaxsponsoutrede dveusrsienlsg: the 20 est. L glass aquaria containing approximately 15 NL uomfbteesrt sooflurteipolni,cawtaets:er2depth approximately 18 cm. NNuummbbeerrooffcfoinschenpterrarteipolnisc:atef:iv1e0planeugatsive control DWiastseorlvcehdeomxiystgreyn druarnigneg(t0he 9s6tuhdoyu:rs): 677-825 8.5mmg/LL ((c1o0nt0r0olmgex/pLoesxuproes)ure) 32 000271 C1o40n.duc1t8i0viptmyhorasn/geem((0co-nt9r6olhoeuxrpso)sure) p28H0r-a3n8g0e (pm0h-o9s6/heomur(s1),000 mg/L exposure) 7734--77..56 ((c1o,n0t0r0olmexLposeuxrpeo)sure) 2"2T.0est te2m2p.e6raCt(ucroentrroalngeexp(o0su-r9e6) hours) R21.8ES-UL2T2S5C (1000mg/L exposure) Nominal Element vcaolnuceenatnrdat9io5n%s:cBonfciodnetnrocle,i1n6t0e,rv2a5l0:, 400, 630, 1,000 mg/L. 824--hhoouurr LLCCSS00 ==>7910,0(06030mg/1L,0(0C0.)1mngo/tL.calculable) 9762--hhoouurr LLCCSS00 =776400 ((6660--13$,3000)00)mg/mLg./L 9E6l-ehmoeunrt NvaOlEueCsba=s4e0d0omng/nLo.minal concentrations wStearteisdteictaelrmEivnaelduabtyiobninoofmiMaolrtianltiertpyo:laTtihoen.48Praonbdit7w2a-hsouusreLdC0S0calvcaulluaetse: the 96-hour LCS0. 2B5i0o,loagnicda4l0o0bsmeer/vLateixopnossuafrteecro9n6c-ehnoturrast:ionFsisahppientahreedconnotrrmoalla.nDdatrhke 160, odibssceorlvoartaitoinonpearnidoderirnattihces1w,i0m00mimngg/oLfetxwpoosfuirseh cwoansceonbtsreartvieodn at the 24-hour Cumulative percent mortality: TNeosmtinal Cone. my F1o60od 250 400 630. 1.000. | 24 hours 7% hours { hours fT o Too TToo To Too | ff o "Too "TToo--o T Too]| Df" o5 TT ooTToo oo TT" ooo]] MLoowretsatlciootnfycecnotnrtartoilosn: cNaounes:ing 100% mortality: None 37 000272 CONCLUSIONS "7T4h0e mtegst/Lsawmiplteah996-5h%oucronLfCiSde0ncfeorifnattheeadorfmvi6an6nl0o-w83wa0smdge/tL.ermTihneed960-hboeur Snuobombitsteerrv:ed3eMffeCcotsmpcaonncye,ntErnavtiiornon(mNeOntEaCl)Lwaabosra4t0o0rym,g/2L..0, Box 33331, St. PDaAulT,AMiQnUneAsLotIaT,Y55133 mReelaisabuirleitmye:ntKolfimtiesstchsurbasntkainncge=co2n.cTenhterasttiuodnysliancktsheantaeltytsioclaultions and sRaEmFpEleRpEuNriCtEySis not sufficiently characterized. MThAi,sastutdhye wreaqsuecsotnodfutchteed3aMt TCRo.mpWainlyb,urLyaLbaRbeoqruaetsotrin,umIbnce.r MNa2r8b0i3c-h4ead, OTHER OGeNnLerYalNOreMmIarNkAsL: TTEheSTmaCjHorEcMoInCceArLn fCorOtNyCiEngNTtoRdAeTteIrOmiNnSe twheervealuisdeid.ty fOoPrPthTisreesctomimtehnatds tchhaetmmiecaalsucroencdetnetsrtacthieonmitcoalwhciocnhcteonttrhaetitoensst boreguasneids,t5s0atrhcatexopnoesecda.n a[cfcituriastdeeltyedremtienremdintehatthtehetest nvaolmuiensaclancobnecenatnrdatmiuosntsabrecandjluys,ifcodrdexoamwplnewb5a0y%5ro0f%d.theIfmeanaasluyrteidcaclonmceeansturrateimoennst,sothfestooxmiecitsyort vHoaldatibleietny,faunrndiosthehde,r pwheycsoiuclodchceamliccuallatpercohceemsiscesalthraetcmoivgehrty roawtees,ratnhde atcatkuealintteostacocroguanntishmydrolysis, exposure concentrations. 374 000273 ACUTE TOXICITY TO FISH (FATHEAD MINNOW) ITdEenStTityS:UPBeSrfTlAuoNrCooEctanoic acid, tetrabutylammonium salt; may also be treefterrarbedut0ylaasmmPoFnOiAumtpeertfalubourtooycltaanmoamtoe,nsNia2ultm0,3-2, or as a major tceotmrpaobnuetnytloafmLm-o1n3i4u9m2s.alt(,OCctAaSnoi#c95a6c5id5,-5pe3n-t0a)decafluoro-, rReefmearrrekdtso:bTyheth3eMtepsrtiondgucltaiboornatlootrymuamsbLe-r1w34a9s22..TThheeT-tRe.st Wsialmbpalreyisstudy '`Nn2u3m3b2e.rTish8e3p9u-rTiHt.yoTfhtehe3MsamEpnlveiwroansmennottaslufLfaibcioernattloyrcyhaRreaqcuteesrtizNedu,mber is taletthroaubguhtyculrarmemnotniinufmorpmeartfliuoonrionodcitcaantoeasteit,s2a7.s9o%luwtaitoenro,fa4n4d.297%.2% Tishoepfroolpalnoowling summary applies to thetestsample as a mixtureofthe ctehsatrsaucbtesrtiaznecdecionnacennitsroaptrioopnasnoofliiwmaputreirtiseosl.utDiaotnawimtahyinncootmapclceutrealtyely MreElaTteHtOoxDicityofthe estsample with that ofthe testsubstance. TMyepteh:odA:cuUt.eS.stEatPicA-TSCA Guideline 797.1400 eGLaPr: cYoemspleted: 1995 `SSpuepcpileiser::PiAmqueapthiacleBsiopsryosmteelmass, Fort Collins, CO mAnoanliyttoirceadldmaiolnyi.toring: DO, conductivity, pH and temperature were SEtxaptiosstuircaelpmeertihodo:ds9:6-LhCouSr0svalues calculated, when possibybplroebi,t `ianntaelryspiosl,atmioonviunsignagvtehreagceommpeuttheordsoorftbwianroemoifalCEpr.obaSbtielpihtayn.with non-linear Test fish age: Not noted. ALveenrgatgheawnedigwhetig=h0t.o2f8 fgish in control: Average length = 32.8 mm. PLroeatdrienagt:me0n.t1:9giNosnhe/L BTeAstCcKonTdiOtiMonAs:IN mDigl/uLtiaosnCWaaCteOrI:LDeionized water adjusted to. hardnessof40 - 48 LDiilguhttiionng:waCotoelr-wchhietmeifslturoyr:esNcoetntnobtueld.bs with an intensityof28 fic. tPrhaontsoiptieorniopedrioofd.16-hours light, Hoursdark with a 1 minute SAetroactkiaonn:d Itneisttisatoeldutaitoenrstphree7p2a-rhaotuironD:OTemsetassuubrsetmaennctes.was. waedidgehdtd/ivroelctulmyetboastihse. dNiloutiinosnowlaubtleermianttehreiatleswtavsesnsoetlesddonuraingthe 375 000274 est CEoxnpcoesnutrreatveisosnelss:do2s0inLg rate: glas Once aquaria containing approximately 15 lLooosfetleystcSoovleurteidond,uwraitnegrtdheeptteht.approximately 18 cm. Vessels were Number of replicates: 2 NNuummbbeerrooffcfoisnhcepnetrrarteipolnisc:atei:ve10plus a negative control `sWaamtpelreocfhdeimliusttiroynduwartienrg):the study (from a representative HAlakradlniensitsy::4348mmgg//LLaassCCaaCCO033 PDiHssoYlved oxygen range (0-96 hours): 6.18.8 5.1-8.9 mmgg//LL((1c,o0n0t0romlge/xLpoesxuproes)ure) hNooutres acration was supplied to test vessels at 72- C1o70n.duc1t8i0viutmyhorasn/geem((0co-n9tr6olhoeuxrpso)sure) 2p0H0r-a2n1g0e (u0mho9s6'ehmour(s1),000 mg/L exposure) 7.27.9 (control exposure) 737.8100 mg/L exposure) 2T2e.s1t-te2m2p2eraCt(ucroentrroalngeexp(o0su-r9e6) hours) 2B1A9CK2T2O2CMA(I1,N000 mg/L exposure) RESULTS NEloemmiennatl vcaolnuceenatnrdat9io5n%s:cBolnafnikdecnocnetrionlt,er1v3a0l.:220, 360, 600, 1.000 mg/L. 824--hhoouurr LLCCSS00 == 914,000(06(06000- >-1>.10.0000)0)mgm/Lg./L 7926--hhoouurr LLCCSS00 ==8$9900 ((66000-0- >>11,,000000)) mmgg//LL.. 9E6l-ehmoeunrt NvaOlEueCs b-a6s0ed0omng/nLo.minal concentrations RSuebmsatraknsce: RTeemstairnkgswfaiseldc.oTndhuecvtaeldueosn rtehpeomritexdtuarpeplasydteostchraitbmeidxitnurteheaTnedst not the fluorochemical component alone. CNoummiunlaaltive percent mortality: [24-48-72 Test Cone, hous | hours | hours mal [Como To "To To To | 130 lo To TT o o] 376 00927 E-- =E T-- o To-- JT o -- o] fC-- lCo Ts-- o Teo-- Tm -- tm] MLoorwteasltitcyonocfecnotnrtartoilosn cNaourseing 100% mortality: None eTChO5eN9tC0eLtmUsLSub.IsOtwaNintSche9965-h%oucroLntSdenfocr ifnakthhveaald omf6in0n0o-w 1w0as0d0etmepa.miTnhetedo metysubsiance 96-hour bse ffs concentration (NEC ws 600 SBuAbmCiKttTerO 3MMAICNompany. Paul. Minnesota, 5155 Environmental Laboratory, P.O. Box 3333151 oRDfeAleiTsatbAislQuitbUysA:iaLKnIcneTiYcsonhcenatsraktiionn2s.iThh setutdysloalctksonasnaalydticaalmpmleesspuruemrcnt RnoEtFuElRfcEiNoCnElyS characterised ThM1i9A9s,%sattutdhye wreaqsuecsotnodfucttheed3sMt .CRo.mpWainbya.rLybLaRbeoqruaetsotrimsanbce. MNa3bl3ehed, omOGeNnLeYraNrOeMmIarNkAsL: TTEheSTmCoHrEcMoInCcAenL fCorOtNrCyiEngNT0RdAeTteIrOmNinShweervealuisdcid.ty fOorPtPisrsetciehantt mtchhiaetnmimacelaalscucoronenccdeenenttrtraatctihioeonmnsitrcoaslWahcniocynhc,e0fnotrrhactxiatomentpslobeerSug0sa7dno,fithathraetexopnsoeseard,n cS1oecnucreenGltyoenasn.teheetsoithheeenst vFKoaalldautbeilseietcnya,nfabnrednatnihdesmuwphshetyecsboideuclod,dchiceamdilccalldteprocohceewmsiecsdablytrt0ecio%vgehrty1aoscwase,lrtahncedashmteeaumtn1oisneeecnxotuspnossaohnmymderrot, xpos cmeemons, (sPaorpmipeyrotoevsfittmshaetlatyepspt5emaart)eedrwihaaalstau1ls0sc0.i%Weamttoec,eheSmciacolalenwnasa(nhwowdparsoonproatontshoelrrus)saeccoymhboircmheaaatroafcnteeproiozseld pinwofaisseesdt. inTn aatchdcedurriia,scy,iroheirslnewoaoosbvvaii"osuyspofsctah"adT15Sr1aCssAaanm.spiltIeinownfitch4 hr3eavMiefiwnh.te1hvleeoutmldsartreoyenoetfhec-saec1hhsteertcsswtipaes:nd"ingDceosmmreoorf rdieoyn! information on purity an sisson analy cl measurementsof he en chemise an 000276 ATECSUTTESUTBOSXTIACNICTEY.TO FISH (FATHEAD MINNOW) Iredfeenrtrietdy:0Pe2r5fPluFoOroAocttearnoaibcutacyilda,mtmtornaibuumtysallta,mmonium salt; mayalsobe te`tcroambpuotnyenatmofmLo-n1i3u4m92p.er(fOlcutoarnoooictcaancoiadt,e,peNn2t8ad0e3c-a2f,louroraos-,amajor eRtermaabruktsy:laTmhmeo3niMumprsoadlu,ctCiAonSl#ot9n5u6m58b-e5r3-w0a)s 2. The test sample is rneufmebrreerdio8b8y8-thTeH.teTsthiengpulraibtoyraotfortyheassaNm2p8l0e3-w2a.sTnhotesTu.fRf.icWieinltbluyry study e4h4a.r9ac%tteertirzaebdu,tyalatmhomuognhicuurmrepnetrfilnufoorromoacttiaonnoaitned,ic2at7e.s9i%t iwsataeorl,uatnidon27o.f2% iTshoeprfooplalnoolw.ing summary applies to the testsample asa mixtureofthe tcehsatrsaucbtsetriaznecdecionnacennitsroaptrioopnasonofl/iwmpautreirtsieosl.utDiaotnawimtahyinnoctomapclceutrealtyely MreElaTteHtOoxDicityof thetes sample with thatof the tet substance. MTeytpheo:dA:cuUt.eS.stEatPicA-TSCA Guideline 797.1400 GLP: Yes SYpeeacriecso:mPpliemteepdh:ale1s99p5romelas SAunpapllyiteirc:alAqmuoantiitcorBiinogs:ysDtOem,s,conFdorutctCiovliltiyn,s,pCHOand temperature were mEoxnpiotsourreed dpeariiloyd: 96-hours Satnaatliysstiisc,amlomveitnhgodasv:erLagCeS0mevtahlouedsocralbciunloamtieadl, wprhoebnabiploistsiybwlei,thbynopnr-olbiintear "iTnetsetrpfoilsahtiagoen:usNiontgntohteedc.omputer software of C.E. Stephan. ALveenrgatgheawnedigwhet-ig0ho3tf6gfish in control: Average length = 34.9 mm Loading: 024 g fish/L TPersettrceoantdmietnito:ns:None mDigl/uLtiaosnCWaaCteOrI:LDeionized water adjusted to a hardnessof40-45 LDiiglhuttiionng:wCaotoelr-cwhheimticsftlruyo:reNsoctenntobteudl.bs with an inensityof25 fc. Ptrhaontsoiptieorniopderioofd.16-hours light, 8 -hours dark witha 1S minute ASetraactkiaonn:d Itneisttiastoelduatfitoenrstphree7p2a-rhaotuironD:OTemsetassuubrsetmaennctes.was. awedidgehdtd/ivroecltulmye1batshise.dilution wate in the test vessels ona CEoxnpcoesnutrreatviesosnesls:do2s0inLggrlaatses:aOqnucaer.ia containing approximately 15 tLooofsetleystcsoovleurteidond,uwraitnegrtdheepttesht.approximately 15cm. Vessels were 378 009277 NNuummbbeerroafffroephlipcearter:ep2licate: 10 NWautmebrerchaefmciosnrcyendturartiinognst:he vsetudpyls negative contol 6SD3i67s-al8Rv4EedmmevaLg((nLe0o0rm0aonlmggeex0pe-oxs3peo)nhroeu)s) hNooten: action wis supped 1 et vl at 72 C1o40ndu1c5t0imiyirahngie ((0G-o9t6thoeuxrpso)sure) p17i0ran1g3e0 (u0 m9e6 hsow(s1)000 mgt. exposure) T77e.5s4-t77t.7e7m0p(.ec0rona0tt0ruorlmeearxlpaonseguxerpe(0o)r9t) hours) 206-215 (coral expose RN2oE1mS.iU6nLa2Tl1S.c9onCc(e1n,tr0a0t0iomngs/:L exposure) Blak cool, 160, 250, Element value and 95% confidence nfeval: 400,630, 1.00 mpl. 254 hhour LLCCSSDD 211,,000000 mmaaT ((CCll nnto cnaeelnaibl)y 7926--hhoouurr LLCCSSDD 996700,(653300.11000000) mmpe.. 9Ele6mehntNvaOlEugCs w-r6e30bmasLed.on nominal oncenratons, nSRouetbmisatrahkncsee:uRTreeomsctaihrnekgsmwiaicska.lcocTohnmepdovuanlecunoettnsersheodepnoemr.tiexdtpulrayes dteshcartibmedinsttheaTnedst Cumulative percent morality: TNouom fo3urs Con. h= ows | ours CmSet wo CO T--oTo--fe----]| a0ER Jo 0 To fToo TfoT T o o o] ] ECT LMoorwteasltitcyonocfcenotnetartoilosn Ncaourseing 100% mortality: Noe CONCLUSIONS ED 400278 b"Teh9e6t0estmsgu/bLstwaincteha969-5h%oucronLfCiSd0enfcoerifnattehrevaaldmoifn$n30ow- >w1a,s00d0etmegr/mLi.neTdheto mtegs/tL.substance 96-hour noobservedeffect concenration (NOEC) was 630 PSauublm,itMtienrn:es3otMa,Co5m5p1a3n3y, Environmental Laboratory, P.O. Box 33331, St. RDeAliTabAilQitUyA: LKIliTmYisch rankin2g.The study lacks analytical measurement onfottessutffsiucbisetnatlnycechcaornaccetnetrriazteido.ns in thetest solutions and sample purity is "RThEiFs EstRuEdyNCwaEsSconducted at T.R. Wilbury Laboratories, Inc., Marblehead, M19A95,. at the requestofthe 3M Company, Lab Request number N2803-2, OTHER O`GNenLeYralNrOeMmIarNkAsL: TTEheSTmaCjHorEcMoInCcAenL fCorOtNrCyiEngNTtoRdAeTteIrOmiNnSe twheervealuisdeidt.y fOoPr PthTisrteesctoimsmtehnatds cthhaetmmiecaalsucroendcetnetsrtacthieomnitcoalwhciocnhcetnotrtahtitoensst obregwansissmesodtahre,atexopnoesecda.n a[cfciutriastdeeltyedremtienremdintehatthtehetest vnaolmuiensalccaonncbeenatnrdatmiuosnts baercaodnjluys,tefdordeoxwanmwpalred5b0y%o5f0%t.heIfmeanaasluyrteidcaclonmceeansturrateimoennst,sothfe stooxmiceitsyort vaodlatbileietny,faunrdniosthheedr,wpheysciocuolcdhceamliccuallatpercohceemsiscesalthraetcmoivegrhyt rlaotwese,ratnhde atcatkuealintteostacocroguanntishmydrolysis, exposure concentrations. sPaormietyotefsttshiet atepsptemaarteedrtihaata1l0o0is%atemsatjcohremciocnaclerwnasanudsewda,fsonootthseufrfsicaiecnhtelymicchaalraocftelreiszseedr piunrtihtiys test. In o(tahpeprroexsitmsa,tfeolryn8o5o%b)viwoauss ussteadte.d Wraeatseorn,. asInolfvacetn,t3(iMsoipnrtohpeainrosl)uomrmaarcyoomfbianacthiotnestofbstoatte:h w"Daastausmeadyinnot aadcdciutriaotne.lyifrtehliastweatsoxaici"ttyypoifcahle" TesStCsAamspeclteiownih4 hreavtioefw,thewtoeusltdsurbesjtecatncteh.e"se1satgurdeiees,wiptehndthiinsgcroencceeirpnt.of[n additional medium. information on purity andstudies on analytical measurements of the test chemical in th test 380 0900279 ee TOXICITY TO MICROORGANISMS. Title: Microtox Toxicity Test TEST SUBSTANCE pIedrefnltuitoyr:oocPtearnfolautoer,oaFcCt-a1n1o6i,c aFcCi-d1,26a,mmFoCn-1i6u9m, soarltFCa-l1s4o3r.efe(rOrcetdantooiacs aPcFidO,Apeanmtamdoenciafulmuosraolt-, ammonium ammonium salt, CASH 3825-261) fRiesmpaurriktsy:waTshneot3Msufpfriocdieuncttliyonchlaortacntuemrbizeerd,waalsth39o0u.ghTihnefotremsattsiaomnpilnediwcaasteFdCit-w1a2s6aa, mwihxittuerepoowfd7e5r.y93solid percent test substance and 7-22 percentCS, C6, and C7 perfluoro analogue compounds. METHOD Methodiguideline followed: Beckman's Microtox "BASIC Procedure: Test type: Static GLP (YN): No Vear study performed: 1987 Species/strain: Photobacterium phosphoreum `Supplier: Not noted 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~eDisltlccnotndwiatsio2ns%: NaCl Microbic's Reagent -"ADei2o0n0i0zemdgw/aLtesrtopcHkwsaolsu6ti.o5n was prepared by dissolving 200 mg - Test solutions were prepared using aliquooftthse stock solution. test solution in 100 mL diluent. - Media was not "Stabilityofthe renewed test chemical solutions was not noted. ""ETxwpoosruerpleicvaetsesselwsewreerteakceunv.ettes. Remarks: none RESULTS 381 009280 Dose of cach endpoint (ss mg/L): SS mmiinnuuttee EECC2500 -->811000m0gm/gl/L S15mimniunteECE2C0S0~ =5>20 1m00y0 mg/L 1155 mmiinn EECCSS00 ~ >11000000 mmg/LL 3300mmiinn EECC2S00-- 487200 m(8p1l0..930) mg/L 30 min EC80- > 1000 mg/L Was control response satisfactory (vesmofunknown): unknown Statistical results, as appropriate: Not noted Remarks: none. CoNCLUSIONS he 30-minute ECS0 was determined t be $70 mg/L. with 95% confidence intervalsof $10 930 mg/L. `qteSusuatblmsiiaytmtpteelrsetsi'insge,smsbaourlkaascc:kiknAga.nKallyitmiicsaclhcdoantfairqmuaatliiotnyorfatneksitngsuobsf2tawnacse cgoinvceenn.traTteisotnisn.g meCehatrsacatlercriiztaetriioanfoorfthe Reviewers' remarks: none 3M Company. [No ie given. Lab Request Number E1282. St. Paul, MN. OTHER drGeeetsnaeuilrseaodlfrrethpeeomratsrtwkuadsys:,aaTvraheiilsiabstlued.m.mTahreyrewfoarse,batsheedcoonntaenstusomfmatrhiysrseupmormtarayn,d ninlryefleirmeintceed tdoattahetapbrloest.ocoNlos and 38 009281 TOXICITY TO MICROORGANISMS DATA "Titles MicrobiesMicrotox. Toxicity Test sI1ad2le6tn,tCiFtCAy-S:1R6P9N,F3OF8AC25-a-1m264m-3o1on,),iauassmatlamtatejdoalrisncootrmheepfoesnrueebndmit1totfars'FsXa-smu1mm0om0na3iru(yom.ctpearnfoliuoarcodo,ctpaennotaatdee,caPfFlOu,orFo-C,-1a1m6m,oFnCi-um oRfetmhaerktses:t sTuhbest3anMceprwoadsucntoitonsuflofticniuenmtbleyrchwaarsac2t3er2i7z:edt,hethteosutgshubcsurtraenncteiwnafsorFmXa-t1io0n03i.ndTihcaetepduriitty wcoamspaousonldu,tiaonndo1f< 425%%CasmamnodnCisupmerpfelrufolruoo-raonoacltoangousetceo,mSp0ou%nwdast.er, < 3% inert perfluorinated METHOD Methodguideline followed: Microbics Microtox "BASIC" Procedure Test types Static GLP (YIN): No Year study performed: 1990 Species/srain/supplier: Photobacteriumphosphoreun/3M Doses (concentrations) tested: 0 (blank control),125, 250, 500, and 1000 mg/L Exposure period: 30 minutes Analytical monitoring: Concentrations ofthe test substance were not measured during the study. "uNTsaeiCsntlgcaMolinicdqriuotobitioseno'sfs: tRhTeeawgsoteonrctekpwlsiaocslauttueissoenod,feaasc2t0hh0e0odftimlhguee/nLtf.osuTorlhuteetsiitonnictoipnarlceeppnaHtrreoadtfiionn6.Ms8iwalanlsdipabodlrjaeunsMktIecIdo-ntGtor)oplHwwe6a.7rteerwpirt2ehp0adreidl cHlLeaSr:andfocroloosrmlaesrsi.c Cadujvuesttimesntwse,re20u0scmdgasNtahCelewxpaossaurdedveestdsoels1.0 mPlerocfesnatmopfllei.ghTth-elofsinbayl stohludtoiosnesdwere otorxgiacniitysomsf,tihnerteesftesruebsntctaonecet.he mean light generated by the control organisms, was used to asses the SptraotviisdteidcalfomreMtihcorodtso:x.C1 and ECq values were calculated usaistatnistigcal lincar-egression program Remarks: The test conditions and procedures were not further described. 383 000282 RESULTS Dose of each endpS-oaimnitn E(cCasl0cu>l1a0t0e0d bmyg/Lst.atistical linear-regression program): 15-min ECo 1000 mg/L. 30-min EC >1000 mg/L. Was control response satisfactory (yes/no/unknown): Unknown `Statistical results, as appropriate: Not specified oSfubtmeisttt-seurb'streamnacrekcso:ncTeensttriantgiomnest. Aalllsoc,rittheerriae fwoarsqauallaictkyotfecshtianrga,cbtuetrilzaactkieodnoafntalhyetitceasltcsoanmfpilrem.ation Reviewer's remarks: Unable to determine % mortality of the controls. CONCLUSIONS. "The authors conclude the FX-1003 30-minute ECsafor Photobacterium phoshphoreun to be >1,000 mg/L (nominal concentration). Sthuebmteistttseurb'sstarnecmeariknsw:ateKrlismoilsutciho-nrawniktihngin2c.oTmphleetsetluydychsaurmacmtaerryizaepdpcloinecseonttrhaetitoensstosfaimmpplueriatsieasm.iDxattuare of may not accurately relate toxicityof the test sample with that ofth test substance. Reviewer's remarks: None R3EMFEEnRviErNonCmEental Laboratory. 1990. Microbics Microtox:| Toxicity Test. St. Paul, Minnesota. Lab request number G2882. OTHER Remarks: This summarywasbasoenda summary report and limited raw data. No detailed report was available. Therefore, the contentsofthis summary, in referenctoe the protocols and results ofthe study, are limited. 384. 000283 TOXICITY TO MICROORGANISMS. "Title: Microbies Microtox Toxicity Test of FC-143 TEST SUBSTANCE IAdmenmtoitnyi:umPeprefrliulourooroococttaanniocataeci,d,PFaOm,mFoCn-i1u1m6,saFltC;-1m2a6y, aFlCs-o1b6e9,reofrerFrCe-d1t4o3.as (POFctOaAnoaimcmaocindi,um salt, pentadecafluoro-, ammonium salt, CAS # 3825-26-1) iRnefmoarrmaktsi:onTihneditceasttessaimtpislea misixFtCu-r1e43o.f 9I6s.5p-uri1t0y0w%asesntotsusbusftfiacniceentalnydch0a-ra3ct.e5r%izCeed,, Ctrh,ouagnhdcCuyrrpeenrtfluoro analog compounds. The 3M product lot number was 421. METHOD `Methodguideline followed: Microbics Microtox "BASIC" Procedure Type (test type): sutic GLP (VIN): N ear study performed: 1995 Speciesistrain: Photobacterium phosphoreun Supplier: Microbics rCeopnlciecanttersaotfieoancshtewsetreed:es0t,ed12a5f,e2a5c0h,c5o0n0c,enainrdati1o0n0.0 mg/L. The concentrations were nominal. Two Exposure period: 30 minutes Analytical monitoring: none SMtiacttiosttiocxa'l.methods: ECS0 values were calculated by a statistical linear regression program provided for P"THestofctohnedisttioocnks:solAutpironimwaarsy 2th0e0n0amdgju/sLtesdtofcrkomso5l.u8titoon7w.a6suspirnegpa1r.e0dNinNMaiOlHl.iporAenMoislmolt-iQcTMadwjautesrt.menTthe Awpapsemaaradnecueosfintges2t00somlugtiNoansClwadsisnsootlevdedasin"c1l0eamrLinsdtoccoklosrolleustiso.n". AlTlhteeswtastoelruthiaorndsnewsesrewamsadnoetbryeported. vpersospeolrs.tioTnawlodirleuptliiocnast.esTahtecatceshtotfemfpoeurractounrceewnatrsatniootnsnowteedr.e tCeusvteedt,teaslo(n3gmwLi)thwtewrae cuosnetdroalss.the exposure iRnedimcaartekds.: The numberof microbes per replicate and the growth phase of the microbes were not RESULTS 385 009284 Doseofeach endpoint (as mg/L): S minute ECS0> 1000 mg/L 3105 mmiinnuuttee EECCSS00-= 873000 ((76930--0882500)) mmgg//LL `Was control response satisfactory (vesno/unknown): unknown Statistical resasuaplprotprsiat,e: none Remarks: none CONCLUSIONS 9"T5he%FcCo-n1f4id3e3nc0emiinntuetrvealEoCfSO63f0o1r0Ph8o5t0ombga/cLte.rium phosphoreum was determined to be 730 mg/L with a m`Seuebtmsitaltlercsri'terreiamafrorksq:ualFiotry edsattianrge,libaubitliltayc,ktshaenasltyutdiycawlacsonafsisrimgatnieoadnKolftiemsitscshubrsatnaknicnegcoonf2ce.ntTreasttioinnsg. There is alsoa ackof characterization ofthe test sample. Reviewers' remarks: none REFERENCE 3LMabERnevqiureosntmennutmableLrabPo1r6a2t6o.ry.St. 1P9a96u.l, MMiicnrnoebsioctsa Microtox Toxicity Test of FC-143, OTHER GdeetnaeirleadlrReepomratrwkass:avTahiilasblseu.mmTaherryefwoarse,bathseedcoonnteantssuomftmhairsy sreupmomratrayn,di onrleyfelriemnicteedtdoatthae apbrloetso.colNsoand results of the study. are limited. 386 00028s TOXICITY TO MICROORGANISMS. Title: Microbics Microtox Toxicity Test ofFC-118 TEST SUBSTANCE IAdmemntointyi:umPerpefrlfulourooroocotcatnaoniocataeci,d,PFaOm,mFoCn-i1u1m6,saFlC;-1m2a6y, aFlCs-o1b6e9,reFfCe-rr1e4d3,tooarsatPhFeOAmaajmomrocnoimupmonseanltt of FC-118. (Octanoicacid,pentadecafluoro-, ammonium salt, CAS # 3825-26-1) iRnefmoarmraktsi:onTihneditceasttessaitmpile20is%FFC-C1-1184.3 itns8p0ur%itwyatwear.s nTohtesu3ffMicpiernotdluyccthalortacntuemrbizeerd,wtahsonuogthncoutrerde.ntData may not accurately relate toxicity of the test sample with that ofthe test substance. METHOD Method/guideline followed: Microbics Microlox "BASIC Procedure: Type (est type): static GLP (VIN): N ear study performed: 1996 Species/strain: Photobacterium phosphoreun Supplier: Microbics TDowsoesre(pcloicnacteenstrwaetrieontse)stuedseadt:ea0c,h6c2o5n,ce1n2t5r0at,i2on5.00, and 5000 mg/L. The concentrations were nominal. Exposure period: 30 minutes Analytical monitoring: none STtoartMisitcircoatlomxet.hods: ECS0 values calculated by statistical linear regression program provided o"TfesttheCosntodciktisoonlsut:ioAn wparsim6a.r0y(n1o0 ga/dLjussttomceknts)olauntdioannwoassmoptriepcaardejdusintmMeinltliwpaorsemMaidlelu-sQinTMgw2a0t0erm. gThNeaCplh dteisstssoollvuetdioinns1w0emreLmsatodcekbsyoluptrioopno.rtiAopnpaeladrialnutcieonso.f tTethesotleusttitoenmspwearastunroetewdaassn"octlenaorteadn.d cCoulvoertlteesss.("3 AmlLl) cwoenrtreolu,sed as the exposure vessels. Two replicates were tested at each concentration, as well as the Rinedmiacartkesd.: The number of microbes per replicateandthe growth phaseof the microbes were not RESULTS 387 000286 Doseof cach endpoint (as mg/L): 5 minute ECS0 = 460 (40--429500) mg/L. 15 minute ECS0 = 3360 (3-306419)mg0/L 30 minute EC5=0 3150 (2910- 3420) mg/L `Was control response satisfactory (yes/no/unknown): unknown Statistical results, as appropriate: none Remarks: none CONCLUSIONS `The 95% FC-118 30 minute ECSO for Photobacterium confidence intervalof 2910-3420 mg/L. phosphoretm was determined to be 3150 mg/L with a `alSlubcrmiittetreiarsf'orrequmaalriktys:tesFtoinrg,dabtuat rlealciakbsilaintayl,yttihceasltcuodnyfwiramsataisosnoigfnteeadstKsluibmsitsacnhceractoinncgenotrf2a.tioTness.tinTghemreeetiss also a lackofcharacterizationof the test sample, Reviewers" remarks: none REFERENCE 3M Environmental Laboratory. 1996. number P1626. St. Paul, Minnesota. Microbics Microtox Toxicity Testof FC-118. Lab Request OTHER `deGteanielreadlrRepeomratrwkass:avTahiilasblseu.mmTaherryefwoarse,batsheedcoonnteantssuofmtmhairsy sruepmomratrayn,dionnrleyfelriemnicteedtdoatthae tparbolteso.coNlsoand results of the study, are limited. 388 009287 TOXICITY TO MICROORGANISMS Title: Microbics Microtox Toxicity Test ofFC-1015-X TEST SUBSTANCE AIdmemntointyi:umPeprefrlfulourooroocotcatnaoniocataeci,d,PFaOm,moFCn-i1u1m6,saFlCt;-1m2a6y,aFlCs-ob16e9r,efFeCr-r1e4d3,too2rsaPs FthOeAmaajmomrocnoimupmonsealntt, of FC-1015or FC-1015-X.(Octanoicacd, pentadecafluoro-, ammonium salt, CAS f 3825-261) Rinefmoarrmaktsi:onTihnedicteasttessaitmpisle2 3is0F%C-s1t0ra1i5g-hXt.carItbsonpucrhiatyinwavesrsniootnsoufffFicCi-e1nt:l3y icnha8ra0c%tewraitzeerd., t`hThoeug3hMcuprrroednutct lsoutbsntuanmcbee.r wDaatsanwoterneotuesd.cdtDoatcaommpaayrenottoxaiccciutryaotfeltyherelbartaenctohxeidc!itsytorfaigthhte ctheastinsaammpmloenwiituhmthatof the est perfulorooctancate homolog mixture in FC-143 vs. FC-1015-X. METHOD Methodiguideline followed: Mictobics Microtox "BASIC" Procedure Type (est type): static GLP (VIN): N Year study performed: 1996 Species/strain: Photobacterium phosphoreun Supplier: Microbics "DTowsoesre(pcloicnacteenstrwaetrieontses)tuedseadt:ea0c,h4c1o6n,ce8n3t2r,at1i6o6n.5, and 3330 mg/L. The concentrations were nominal Exposure period: 30 minutes. Analytical monitoring: none Statistical methods: Tor Microtoxte, ECS0 values calculated by statistical linar regression program provided "PTHestofCothnedisttioocnkss:oluAtipornimwaarsy66..96a6n0dgaLn osstmoocktiscolaudtjiuosntwmaenstpwreapsarmeaddeinuMsiilnlgip2o0r0e mMigllN-aQC"TMdiwsatseorl.vedThine 10 mweLrestmoacdkesoblyutpiroon.porAtpipoenaalradnilcuetioofns.testTshoelutteisotntsewmpaesrantoutreedwasas"noct naolnteddec.olCaourvleerstst.e"s (A3llmLte)stwseorleutuisonesd as the exposure vessels. Two replicates were tested a cach concentration, as well as two controls, iRnedmicaartekds.: The numberof microbes per replicate and the growth phase of the microbes were not RESULTS 389 000288 Dosesofcach endpoint (as mg/L): S m1i5numtienuEtCeSE0C=S023=0019(62007(017-3025-602)21m0g)/mLg/L 30 minute ECS0= 1950 (176-0 2160) mg/L `Was control response satisfactory (yes/nofunknown): unknown Statisticalresults,as appropriate: none Remarks: none `ONCLUSIONS "9Th5e %FCc-o1n0f1i5d-enXce30inmtienruvatleoEfC1S7O60f-or21P6h0otmogb/aLc.terium phosphoreun was determined to be 1950 mg/L with aSlulbemrittetreiarsf'orRqeumaalirtkyst:estFiongr,dbauttarellaicakbsilaintayl,yttihcealstcuodnyfiwramastaisosnoigfnteedstaKsluibmsitsancchercaotnicnegntoraf2t.ionTse.stiTnhgermeeeitss also a lackof characterization ofthe test sample. Reviewers' Remarks: none REFERENCE 3M Environmental number P1626. St. LPaabuolr,atMoirnyn.eso1t9a9.6. Microbics Microtox Toxicity Test of FC-1015-X. Lab Request OTHER `deGteanielreadlrReepomratrwkass:avTahiliasblseu.mmTahreryefwoarse,btahseedcoonnteantssuomfmtahrisy sreupmomratrayn,doinnlryefelrimeintceedtodatthaeapbrloetso.colNsoand results of this study, are limited. 390 000289 TOXICITY TO BACTERIA Title: Activated Sludge Respiration Inhibition TEST SUBSTANCE AIdmemntointyi:uPmerpfelrufolruooorcotoacntoaincoaatcei,d,PaFmOm,oFnCi-1u1m6,salFtC;-m1a26y,alFsCo-1b6e9r,efoerrFreCd-1t4o3a.s (POFcOtaAnoaimcmaocindi,um salt, pentadecafluoro-, ammonium salt, CAS # 3825-26-1) sRuebmsatrankcse:waThseno3tMsupfrfiocdiuecnttilyonchlaotrancutemrbiezredw,atsho37u.ghTchuerrteenstt sianmfporlmeawtiaosn FiCn-d1i4c3a.teTihtewpaursaitmyoifxttuhreeof96.5 = 100% test substance and 0 ~ 3.5% Ce, Cy, and Cs perfhuoro analogue compounds. METHODS Methodguideline followed: Protocol reference EAR, 11/8779 Test type: Not noted GLP (VIN): No ear study performed: 1950 Test organism: Activated sludge mixed liquor `Souree: Metro Wastewater Treatment Plant, St. Paul, MN. Concentrations tested:Blankcontrol, 1000 mg/L Exposure period: Seven minutes Analytical monitoring: None Statistical methods: Graphed dissolved oxygen versus time in minutes. "mTLestwcitohndDi.tI.ionwsat:erN.ot noted other than the stock solution was prepared with 0.6 g FC-143 diluted to 100 Remarks: No furtherdeailson testing methods were provibdyethde submiter. RESULTS 91 009290 mDgo/sLeowfiethacahcoenntdapcotitnitme(aos f7mg/miLn)u:teNs,o acute inhibitory effect on activated sludge respiration rate at 1000 Remarks: Results based on nominal concentrations. `Was control response satisfactory (ves/no/unknown): unknown Statistical resultsas, appropriate: Not noted CONCLUSIONS ofLiamcittievdatceodntsalucdgtei.me estimates that ammonium pefluorooctanoate is not expected to inhibit the activity Snoutbmainttaegresn'cyreampparrokvse:d Kmeltihmoids.chTrhaenrkeinigs3l.ackTeosftcihnagralcatceksrirzeactoirodnooffmtehtehtoesdtoslaomgpyleuseadn.d tTehstesmoleutthioodnswnaost. analyzed for tes substance concentrations. Reviewers' remarks: No ECorSoth0er effet level was given. 3M Company. [No ite given. Lab request number 56255. St. Paul, MN. OTHER NGeonedertaalilredemraerpokrst:waTshiasvasiulambmlae.ryThwearsefboarsee,dtohen caosntuemnmtsaroyf trheipsorstumamndaroyn,lyinlirmeifteerdendcaetatoabthlees protocols and resultsofthe study, are limited. 392 0600291 TOXICITY TO BACTERIA Titles Activated Sludge Respiration Inhibition Test TEST SUBSTANCE. pIedrefnltuitoyr:ooct_aPnerofaltueo,roFoCc-t1a1n6o,icFaCc-id1,26a,mmFCo-n1i6u9m, osralF;C-a1l4o3.ref(eOrrcetdatnooaisacPiFd,OpAenatmadmeocnafiluumorosa-l,t,aAmmmmoonniuimum salt, CAS 3825.26-1.) "RTehmeaprurkist:y wTahsen3otMcpormopdluectteiloynclhoatrancutmebriezredi,s 3a9l0t.houTghheitnefsotrsmaamtpilone wsuagsgeFsCt-e1d2i6t,waaswhaitmeixptouwrdeoerfy7s8o.li9d3. percent est substance and 7-22 percent CS, C6, and C7 perfluoro analogue compounds. METHODS Methodguideline followed: OECD 209 Test ype: Static GLP (VIN): No ear 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. Coconncternoltsra- t0imongs/tLe-stweedr:e u0s,ed1,00a,s1w8e0l,la320a, r5e6f0e,raenncde1s0ub0s0t0ancmeg.)/L test material solution. (Two blank Exposure period: 30 minutes:3 hours Analytical monitoring: It was not stated whethectonchentreatirons were monitored throughout the fest, Statistical methods: Not stated. Test conditions: -- SDiylnutthieotnicwasteewragweaswaaseraptreedp,ardiesdtiallcecdo.rddeiinogntiozeOdEwCaDterGuwiidtehlianpe#H o20f9 6.7 - Suspended solids were 2.7 gL -diTsetisltlesdolwuattieorn,s1w6ermeL.psryenptahreetdicbyseawdadgiengfeiendd,ivainddua2l0w0eimgih.tisnotocusloulmu.tioTnhsecopnHtaoifnitnhge2s8ol4utmiLons was asdojluutsitoendotfo37,.50-duisoicnhglo|rNophNearoOlH,. The reference solutions were created using 500 mg/L stock 393 009292 cponHcenotfrtahteioanctwiavaste7d.4sl(uidnigteiam)iaxendd8l.i1qfuiornaw)as 7.8 initia) and 8.0 (final); pH of he 1000mg/Ltest Tempera~tEuxrpeoosufrteheveesssetlwtayspe20w-a2s1 nCot(fdoerscortibhed3.0 min and 3 hr). RNeusmpbireartioofnreipnlhiicbaittieosnowtassadteetde,rmeixnceepdtbtyhamtetawsuorbilnagnkdicsosnotlrvoelds owxeyrgeeunsecdo.nsumption. Remarks: Hardness ofth dilution water was no presented. RESULTS Dose ofeach endpaint (as mg/L): AC30 min: ECSO (or respiration inhibition=) > 1000 mg/L AUS hrs: ECS0 (for respiration inhibition) = > 1000 mg/L Remarks:A reference substance was sed, but no results were presented. ~Noneofthe doses resulted in 100 percent iibiton. pWearcsenctonrtersopilrarteisopnornasce sianthiibsiftaicotnoroycc(uyreresd/.no/Aulsnok,notwhen)d:iffCronetnrcoelbreetswpeoennsethaepptewaorecdonatrdoelqsuawtae;s 2le.s2sptehracnen|t ca8ac3h0omtihneurtes and 08 percent at 3 hours; this meets the guideline criterionofbeing within 15 percent of Statistical results, as appropriate: none CONCLUSIONS m"ThLe auatfheorrs shaoturtshotfetxhpeotseustrema.terial induced 38 percent inhibition in respiration rate at 1000 mSeuebtmsitttheerrs"irteamafrokrsq:ualTihtey ateustthiongr.s sHaotweetvheart,thteheKlsitmuidsyclhacdaktead cquhaalriatcyterrainzkatiinognwoaftsh2e, atensdt tshuabtstthancsetudy cpuormiptoyuanndd.analytical confimmation of concentrations. Also, no results were presented for the reference Reviewers' remarks: REFERENCE R3eMquCeosmtpNanuym.berAcEt1i2v8a2t.ed SStl.uPdaguel,ReMsNp.iration Inhibition Test Environmental Labortory: Lab OTHER NGeondeertaalilredemreaprorktswaTshiasvasiulmblmea.ryTwhearsebfaosre,dtohen csountmemntasorfy trheipsorstumamndaroyl,yinlirmeifteerdendcaeta(0(a(lhees. protocols and resuls ofthe study, are limited. 394 0609293 TOXICITY TO BACTERIA Title: Activated Sludge Respiration Inhibition TEST SUBSTANCE AIdmemntointyi:uPmerpfelrufolruaoorcotoacntoaincoaatcei,d,PaFmO,moFnCi-1u1m6,salFtC;-m1a26y,alFsCo-1b6e9r,efFeCr-r1e4d3t,ooarsaPsFaOmAajaomrmconoimumpsoalnto,efFnXt1003. (Octanoic acid, pentadecafluoro-, ammonium salt, CASRN 3825-26-1) sRuebmsatrankcse:waTsheno3tMsufpfriocdiuecnttilyonchlaotrancutemrbiezerdw,atsho2u3g2h7.avTahielatbelset sample was information FX-1003. indicated The itwas apusriotlyutofitohneoftest C<,45pe%rfalmuomroo-nianuamlopgeureflcuoomropoocutnadnso.ateT,h5e0te%stwastuebrs,ta<n3ce%wiansertacpleerafrluloirqiuinda.teTdhceormepfoeruenndceansudbs1t2an%ceC;usaendd for this study, 3.5-dichlorophenol,was Aldrich red label, lot number D7-060-0. METHODS Methodiguideline followed: OECD 209 Test type: Static GLP (Y/N): No Year study performed: 1990 TTehsettoesrtgoarngiasnmi:smMsiwxeerdeluisqeudoroancttihveatdeadysolbutdaigneedw.asThcoellceocntdeidtifornoomfMtehetroorgWaansitsemwsatwearsTnroetatsmpeecnitfiPclda.nt `Supplier: Metro Wastewater Treaument Plant C(3o0ncmeinnturtaetsiaonnds 3tehsotuerds:). 0T(wbolarnekpcloincattreoslo)fatnhde1b0l0a0nkmgco/nLtrFoXl-a1n0d0o3nweerreepluisceatdefoofr c1a0c0h0 emxgp/oLsuFrXe-p1e0r0i3o.d cwoenrceenutsreadtifoonrocfac1h0emxgp/oLs.urOenpeerrieopdl.icAateroeffertehnecreecfoenrternocle, c3o,n-tdrioclhwlaosroupsheednoflo,r weaacshienxcplousdeudreatpeariod. Nominal concentrationsofthe test substance and reference control were used during this study. Exposure period: 30-minutes and 3-hours Analytical respiration monitoring: inhibitioans, dDeitsesromlivneeddobxyygoexnygceonncceonntsruamtpitoinosnw.ere monitored in order o determine Statistical methods: Not specified "wTaesstccroenadtietdiboynsa: mTahses aidndoictuilounmtocoanstoaluitnieond c3.o2 ngt/aLinoifnmgix2e84d mliLquMoirlsluispopreendMeidlsloili-dsQ. wTatheer,tes1t6smuLb.stance 395 009294 synthetic reference sewage feed, solution was and 200 mL inoculum. The test createdusing a 500 mg/L stock ssoluutibonosfwat35s-aadpipncahrlceonrtoelpyhemnioslc.ibTlheewiintihtiwalataenr.d A fmign/alLptHesotfstohleutiaocntiwvaatsed7.3s.luTdhgee miniixtieadl pliHqouforthweasr6e.f7eraenncde7s.o1l,urteisopne,ct1i0vemlgy./LTh3,e5-indiitcihalloprHopohfentohle, 1w0a0s0 7.5. rTehpelitcaetmepoefractaucrhercaonngceenwtraasti2o0n--of21FXC-1d0u0r3ing(1t0h0e0stmugdy/.L)Tawnod r3e.p5l-idciactehsloofropthheenbollan(k1c0onmtgr/oLl),,awnedreonuesed for cach exposureperiod (30 minutes and 3 hours). Remarks: No additional comments. RESULTS Dose of each endpoint (as mg/L): 30-m3i-nhuotuer EECCS500 >>11000000 mmgg//LL aRpepmlayrtkost:hatTemsitxitnugrewaasndconnotdutchteetdesotnsutbhsetmainxcte.ure of the described test substance, The values reported `Was control response satisfactory (yes/no/unknown): Yes `Statistical results, as appropriate: No additional comments CONCLUSIONS "The FX-1003 mel. 3-hour ECS0 for activated sludge respiration inhibition was determined to be >1000 Submitters" remarks: analytical confirmation oKflitemsitsscuhbsrtaannkciengco2.ncTenetsrtaitnigonmse.etTshealrlecirsitaerliaacfkoorfqcuhaalriatcytteersitziantgi,obnuotflatcheksfest sample. The testingprocedure was not fully documented. Reviewers' available to remarks: adequately Tahsseescsontchleusstiuodnys. appear tobe supported by the data, however, limited data were REFERENCE, R3eMquEensvtirnounmmbeenrtaGl28L8a2b.oratory. 1990. Activated Sludge Respiration Inhibition. St. Paul, Minnesota. Lab OTHER `General detailed remarks: report was This summary was based on a summary available. Therefore, the contents oftis report and summary, limited data in reference tables. to the No protocols and resulsofthe study, are limited 396 009295 TOXICITY TO BACTERIA Title: Activated Sludge Respiration Inhibition Test TEST SUBSTANCE sMadlte,ntAitmym:onPeiruflmuopreorofcltuaonrooioectaacindo,ataemPmFoOn,iFuCm-1s1at6;, mFaC-y1a2l6s,o FbCe-r1e6f9e,rrFedC-t1o4a3s, PoFraOsAatmeatjroarbuctoymlpaomnmeonntiuomf GC-1015 or FC-1015-X. (Octanoic acid, pentadecafluoro-, ammonium sal, CAS # 3825-261) iRnefmoarrmaktsi:onTihneditceasttessaitmpslea 3wa0s%FsCt-ra1i0g1h5t-cXh.ain10vserpsuirointyofwaFsC-n1o4t3suifnfi8c0ie%ntwlaytecrh.araTchteeri3zMed,prtohdouucgthlcoutrrent anummmboenriwuamsp"erHfOluGoEroo2c0t5a.n"oaDtaethaowmeorleoguuseedmtioxtcuormepainreFCt-he14t3oxiwciitthy wohfattheissbruapnpcohsede!d sttorabieghtthech1ai0n0% straight carbon chain ammonium perfluorooctanoate in FC-1015-X. METHODS Methodiguideline followed: OECD Test #209 Test type: static GLP (VIN): no Year study performed: 1996 Test Organism: activated sludge iSnupSptl.iPearu:l,TMhNe.activated sludge mixed liquor was collected from the Metro Wastewater Treatment Plant w`Ceorneceanlstoratteistoends. tTeshteedc:onc4e2n0t,r8a4t0i,on1s66w0e,reanndom3i3n2a0l mg/L. Two blank controls and areference substance. Exposure period: 30 minutesand 3 hours Analytical monitoring: none Statistical methods: none "rTeefsetrecnocnedistuibosntsa:nceT,he3,d5il-udtiiocnhlwaotreorphuseenwdoalws,asprMeiplalriepdorbeyMdiilslsio-lvQi"ngwa5t0er0.mgA isnto1c0kmsoLluItiNonNoafOtHh,e diluted o10f.t3h0emrLe,fertehnecnebsrooluugthiton0wathsempeoaisntuorfedintcoibpieen7.t2.preTchiepittaesttiosnubwsittahncIeNwHa,sSaOd,daendddidrielcuttleydttoot1hLe. esTthe pH vessels. Synthetic sewage per OECD guidelines (Test #209) was used. 397 0609296 "ATthtehteemepnedraofttuhreertaensg,eTdSfSro=m1.139.g1L.10.2T2h.1e iCn.icaIlniptiHal=ly,1.t8o,tawlhsiulesptehnedfeidnasloplids=we7.r9.e mTehaesuwraetderatha3r.d2n2cga/sL. was not indicated "The clement basis was respiration inhibition a determined by oxygen consumpion. 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 3NECS02 3320 mel rReemmaarrkkssf:ieldT.estTihnegvwaalsuecsonredpuocrtteedd oanpptlhyeomitxhtautremoixfttuhree taenstdsnoutbhesteasttssdauebssnctracinbceee.d iAn trheefetrsetncseubstance substance of 3,5-dichlorophenol was used, but ECS0 values were not reported `Was control response satisfactory (yes/nofunknown): unknown Statistical results, as appropriate: none CONCLUSIONS g"TrheeatFeCr-t1h0an153-3X203 mhgo/uLr.ECO for activated sludge respiration inhibition was determined to be: qSuuablmiittytteerssti"ngr,ebmuatrklsac:ksTahnealsyttiucdaylwcaosnfaisrmsaitginoenoadfKlteismtissucbhstraannckeincgonocef2n.traTteisotnisn.g mTeheetrseailslacrliatcekrioaffor characterizationofthe test sumple. Reviewers' remarks: none REFERENCE, 3M Company Environmental Laboratory. 1996. Lab Request N2169. St. Paul, MN. otHER GNeondeertaalilredemraerpokrst:waThsiasvasiulambmlea.ryThwearsefboarsee,dthoencaonstuemntmsaroyfthriepsorstumamnadroyn,lyinlirmeifteerdendcaettotatbhlees protocols and results of th study, are limited. 398 009297 MICROBICS' MICROTOX TOXICITY TEST TEST SUBSTANCE rIedfenetrirteyd: 10PearsfPluFoOroAoctteatnroiacbuatcyidl,amemtornaibuumtsyallta,mmonium sal; may also be tceotmrpaobnuetnytloafmmLo+n1i3u49m2p.er(fOlcutoarnooocitcanacoiadt,e,peNn2t8a0de3c-a2f,luoorroa-s,s major tReetmraarbkust:ylTahmemo3niMumprsoadliu,ctCiAonSl#ot9n5u6m58b-e5r3w-a0s)2. The test sample is wreafsernroetd subffyicitehnetltyescthianrgacltaebroirzaetdo,ryalatshLo-u1g3h49c2u.rreTnhteinpfuorirtmyatoifonthiensdaimcpatlees: it wiaasters,olauntidon2o7f.424%.i9so%prtoeptarnaobl.utylammonium perfluorooctanaate, 27.9% eTshtesfuoblsltoawnicneg sinuamnmairsoyprapopplaineoslitowatthertseosltustaimopnlweitahsianmciomxptluerteoelfythe rcehlaartaecttoexriiczietdyocfontcheenttersattsiaonmsploefiwmiptuhritthiaetos.fDtahtetaemstaysunbsottaanccceu.rately METHOD: Method: Microbics" Microtox "BASIC" Procedure GYLeaPr:CNoompleted: 1995 S`Apneacliyetsi:caPlhomtoonibtaocrtienrgi:umppHh,olsipghhtooruetupnut Replicates: 2 rSteagtriesstsiicoanl pmreotghroadms:prEoCviSd0edvafloureMsiccarlcoutloaxted by statistical incar Test organism source: Microbics Corporation, Carlsbad, CA Test Conditions: SDitlouctkioanndwatteesrt:soMliultliiopnorpereMpilalria-tQioTn:MAwapterri.mary 2000 mg/L stock Solution was prepared in Millipore Mill-QTM water. The pH of the Satnodckansoolsumtoitoincwaadsjutshtemneandtjuwsatsedmfardoemu4s.i7ng10260.07 NuasiCnlgd0i.s1sNolvNeadOinH "1c0lmeaLr asntdocckolsoorlluetsiosn".. AAp1petaertasnocleuotfiotnesswesroleumtaiodnesbwyapsronoptoerdtiaosnal dilutions. NExupmobseurreofversespellisc:at4esm:LTgwloass cuvettes. Number of concentrations: Four plus blank control RElEeSmUeLntTSBasis: Percent light loss. NEloemmiennatlvcaolnuceenatnradt9io5n%s:cBolnafrikdecnocnetrion,ter1v25a,l 250, 500,1000mg/L. S1e5m-imniuntueteECCS500==633000(5(92070- -66353)0)mmyg//LL. 3E0l-emmiennuttevaEluCc5s0b~ase2d60on(2n2o0mi- n3a0l0)comngce/nLtrations. RSuebmsatrakncse:RTeemstairnkgswfaicsldc.onTdhuectvaelduoens arempioxrtteudreapapsldyetsocrtihbaetdmiinxttuhreeTaenstd ot the fluorochemical component lone. CONCLUSIONS 399 409298 dTehteertemsitnseadmtpolebe320-6m0imngut/eLEwCitSh0afo9r5P%hoCtoonbfaicdteenrcieumInptherovsaplhoofr2e2u0m-3w0a0s mg/L. SPauublm,itMtinenre:so3tMa,C3o5m1p3a3ny, Environmental Laboratory, P.0. Box 33331, St. DReAliTabAilQitUyA: LKIliTmYisch rankin2g. Testing meets al criteria for quality testing, but lacks analytical confirmation ofest substance concentrations iRnEtFheERteEstNsColEuStions and sample purity is not sufficiently characterized. This study was conducted by the 3M Company, Environmental OLaTbHorEatRory, St Paul, MN, Lub Request number N2169, 1995 400 000299 Title: using Bioconcentration Perfluorooctanoic taesctiodf(TePsetrfsluubosrtoaanlckeylncuarmbboexrylki-c15ac1i9d)](Ci=n7c-a1r3p) [This test is performed TEST SUBSTANCE Identity: K-1519. Perfluorooctane sulfonic acid, potassium salt. Lot number A376265 Remarks: Test substance number K-1519. The test substance is a white powder. Purity determined tobe 98%. The test substance was treated as 100% purity. MMeEtThHodO/Dg:uideline followed: Method for Testing the Degree of Accumulation of Chemical S1u9b7s4,taRnecveissiendFOicsthoBbeordy8", 1st9i9p8u,laKtaendpiongtyheo"NToe.st5,MPeltahnondinfgoranNdeCwooCrhdeimniactailonSuBbusretaaun,ce" July 13, Environmental Agency: No.615, Pharmaceutical Aflairs Bureau, Ministryof Health and JWaeplafna)r.e:anadnBdioNcoo.nc3e92n.traBtaisoinc :IFnlduoswt-rtihesroBuugrheaFui,shMtienstis(tGruyoidfelIinnteer3n0at5i,onJaulnTera14d,e 1a9n9d6)I"ndiunsttrhye, OECD Guidelines for TestingofChemicals. `Type: Flow-through system GYeLaPr:(YD/eNc)e:mbYeers 18, 2000 Species: Carp (Cyprinus carpio) Supplier: Fuluokaken yabeqawa fishermen' cooperative association Length aMnedanweliegnghttha=t t6e.s8t8t.e6rmination: LoadingM:ea2 nanwdei2g0htug=/LNorewspeeicgthitverleycorded Fish Age: Yearling fish Analytical monitoring: High-performance liquid chromatography-Mass spectrometry Pretreatment: "Test water: Aliquot of test water for level | and level 2 were one and two mi respectively for HPLC-mass spectrometry. Test Fish: Fish were taken from each test tank and pretreated for HPLC-Mass Spectrometry. Measurement of body weight and length, chopped into pieces, making sample fine, taking out | Supegmraamtsa.ntT-reFaitlterdatwiiotnhaancdetsoanmitprlielde (f2or0 mLLC)-,MhSomaonagleynsiizsed, washed, and centrifuged. Residue Numbeorf concentrations: Two plus a negative control "UTpesttackoencpeenrtiorda:ti2o8n:da(ymsean measured): Negative control, and 50 ug/L Depuration period: Not stated. Test cDoinlduittiioonnsw:ater: Groundwater from the premisesofKurume Laboratory Dilution water chemistry Specific conductance: Not recorded Hardness: 111 mg/L. Alkalinity: 96.1 401 009390 pH: 78 Dissolved Oxygen: <6 Temperature: 24.3 10 25.6C vSatloucek aannddantaelstytsioclaultdieotnecptrieopnarliamtiitos,n:tesBt acsoendceonntrparteiloinmsionfartyhetetsetstressuublststafnocretwheer9e6 dheocuirdeLdCSas0 follows. The test substance control was set was dissolved as a with biloann-kextecsht.angLeedvewlat1ewratso 5pruegp/aLrea5n0d0Lemvge/lL2 stwoacsk 5s0oluutgi/oLn.. The Diluter flow litersiday for rate: 2 mL/min test water were sfuoprplsiteodc.k solution and 800 mL/min for dilution water; 1155 Exposure Vessels: 100 liter glass tank Numberofreplicates: None Number of fish per vessel: Level 1 and 2: 28 Diet: NippoCnonFtoorlm:ula Feed Mfg. Co.,Ltd. Water chemistry ranges during the study: bow: 76-78 [76-78 76-78 | Photoperiod: Artificial lightofwhite fluorescent lamp (14 hrs./day) Light intensity: Artificial lightofwhite fluorescent lamp. Cduorlalteicotnioofnoefxptoissusruee.saFmopulrefsi:shAwnearlyestiaskoefn toeustt aftisehawcahssapmeprlfionrgmetdimseixatnidmedsivaitdceadcihntloevtewloin `threouepxsp,erainmdetnhteanl bsotatrhtiwnegraenadnaafltyezretdheinedxipveirdiuamlelnyt.alAcnoamlpylseitsoiofnc.onFtoruorl ifsishh wwearseptearkfeonromuetdabtecfaocrhe swaemrpelsianmgptliemdefaonrdthdeirveidleidpidinctoonttwenotgbryoufpisx,inagndthtehmeen binotchhlwoerroefoarnma-lmyezetdhainnodliveixdturalalcyt.ionThweitfhish gravimetric analysis. S1t0a0tistical methods: Calculationoflipid content was as follows: Lipid content (%=) (T-To)'$ x Where To = Weiogfvhesstel (g) T= Weightofsample ofgravimetric analysis (containing vessel) (2) = Weightoffine sample taken out for analysis of lipid content. 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 oreuarcshewdewrehewnitthhienre20su%cocefsesaivceh aontahleyr.sisWohfeBnCFBsCFmsadweeroenalseasmspltehasnta1k00e,n iattwiantseervvaallsuoaftaetd tlheaatsta4 steady-state had been reached after 28 days even ifBC were over 20%of each other 0 000301 RESULTS MNoemainnamleacsouncreendtrcaotnicoennst:raNteigoantsi:ve5 caonndtr5o0l,ug/L Bioconcentration factors (BCF): Level 1(5 ug/L) apparent steady-state BCF Time to reach 50% clearance: CPoFneO.ACo[ncAefntetrration in testAwfaetrelr0:| Aer 16 | After 2| Aer 35| Average Diy [Das |b | Das |Days | Dus | STD) SuglTox Tare 1469"Tasi 1467 ass [souwgtTass Taeo Tae Tae [ass |a61 CPonFe.OA C|onAceerntra| tiAofnerilndT|isAsfuteerof16Carp ExposAleldert2o8 and 50 ug/L: TTw E[D2e9vs" E[[2D4aBw E[D3u0sNE|DAos |FaE2Days wn [sesi S | TJos Je51 [dn "Test organism mortality: Negative control: None documented. Level 1 (5 ug/L): None documented. Level 2 (50 ug/L): None documented. Analytical methodology: cAhnarloymsaitsogorfaPpFhyO-Amaisnsthsepetcesttrowmaetterrya(nHdPcLarCp-MwaSs) panearlfyosirsm.edTuhseinegshtiwgaht-epreorffocracmhancleevleilqwuaisd. SantaelaydzyesdtaotnecweabsefroeraechfeidstwahnealnystihsroeefstuesctceissshivaenadnaatlytsheessoafmBeCtFismemaasdteheonansalaymspilsoesfttahkeenteatt fish. intervalsofat was evaluated ltehaastta48stheaoduyr-sstwaetreehwaidthbienen=r2e0ac%hoefdeaafcthr o2t8hedra.ys.When BCFs were less that 100, it Concentrationof test substance in test war at a steady-state: nTohmeimnaetaendccoonncceennttrraattiioonnso.f the test substance in test water at a steady state were 94% of The after measured lipid contents in termination ofexposure. the test fish were 3.10% before initiationof exposure and 2.82% CONCLUSIONS "ITnestthicsonstcuednyt,raPtiFoOnsAoB5fCFanrdanSgOedugf/rLomwe3r1efuosredl.eveTlhe1 afnisdh5w.e1r.9e.1exfpoorsleedveflo2r 2in8 tdhaeyst.issuesof carp. REFERENCES Kurume 51520 Laboratory (2001). Chemicals Evaluation and Research Institute, Japan. Test number: 03 09302