Document 3R31oNpN7jq15M7JL8MzdV36

ARA26 -- 1239 Telomer Research Program FP AGC = Clariant. QUAI -------------------------------------- Report Tile: $2 Telomer B Alcohol: Oral Gavage Rane-Finding Study in Rats Author(s): GregorSy Ladies, PhD Comteacors FHa.sk1edlloLnatbodreatNoerymfooruHarenasldtCoanmdpaEnnvyironmental Sciences g om ENlekwatarokrn,k,RDoeadlD,ealwPva.aOr.e B9o7x145-00050 Lv0 382 223 Study Dates: SSttuuddyy CInoimtpialteetd:ed:ApSeelpt2e0m0b1er 2001 = 8 STotxuidchytyObsjteucdtyiwviet:h T$h2eToebjleocmteirveBofAlhcioshosl.tudyInwaadsdittoiosne,tadnoasleytliecvaellsmeotrhoad9s0-wdearye sduebvcehlroopneidc f@or Looking a potential metabolitesof 2 Telomer B Alcohol C0Mra0tl.ei5rC.iDa"2l(5sSaDanYndIdGMS1e2tB3hRmodrkast:sdwYaeoryuennagdimalidnuhilesttmesrtaealdin8(m-1e20n/Ttgerolfoouspmt)eeraadnByd Afsleacmoelhobell(od/oagdirlfoyuubopry)ignaevlaegveelast, daonsdages lnoiwtesd afetcaolvefrufoorri75adnadypsaroenstmettadbolo(it3segsriowuanps,cmoanldeusctaendd dfuermianlget)he Sdeorsiiangbalnededriencofvoerry hlweearacedeysnosotaftetvehaelbulsaottouedddy..fluABotlroinnoeedclrfeolvpeusloysr,,intleh vleelvikevieldrnraeenyad,chkaeindddnseftytesawdoeyfrse$asmtaalvebesedtgwfreroeounmpfmwsaetlerdseayawsnedi6g0fh-ee8md4a:.lefAsetmfaolres afnraolmymsailoefspaanrdenfecmoalmepsouonvedr,tPhFeOdAur,atainodn PoEfNthAe. n-Iinfaeddpithiaosn,opfotohleedstpuldayswmearseamapnalleyszoebdafionred pearreentancaolmypsoeudnfdo.r hPFeO5A2, apcairde,ntPcFoOmAp,ouanndd,PaPnNdA.totaAltftluaoridneseavtestest day $4) pooled plasma ibFisintdifinngcsTe:ocsilcaoeldog,ytPoaxrcaomleotgeircsa:lyNositgensi:fiscuabntstiannrceea-srelaitnedthmeoirnacliidteyncoeccoufrsrterdiaitnedthteeestthudwya.s A test bweuiegnhataiinnsthweer1e25demcrekaseddeiy mmaallee arnads fienmhaele1d2o5smyggrkouep/sd.ayMdeoasne gfrinoaulpboondytewsteidagyhs81.andBbooddyy weights were similar to control at th end of the recovery period. Females body weights and body weight gains were not affected. Awoncaeetvioemriypc,aarmlaimPealttehrroasltsoogdcyo:csuerdTeewdsittisnhumb1as2li5easmncgaekdemri/enldsiaieydcrsnehddow1se2td5atirmsetvieckraslilbydialsiyitgynfioorffit$c1hanedtaoiyrsng.carneAawsfeeeisrgihn7t5idevfaefyrecstso.f "Does not contain TSCA CBI T 2 TRP (28-Apr-03) aFnedmasltaetirsattiscawlelryesingontifeivcaalnutaitnecdreoansetsestindlaiyve8r1.andAfktiedrn7e5y dwaeyisghotfpraercaomveertye,rsteosctc-usrurbesdtainncefermealalteesd administered 125 mg/kg/day. Mean Final Body and Organ Weights for Male Rats Sacrificed on Test Day 81 LiverC) Ritreys (a) Final bodyweight(g) 82 Telomer B Alcohol (mg/kg/day) [0 H 25 125 nar 21: 07: 279+ 3428 21 31 4s: 43: 41x 44s 047 034 031 0.68 So444l3E5 S5e0A0l8E 53532869+ SS048791 or Liver (% BW) 39: 37: 028 020 o Vives 05 BW) 076% 076+ 003 006 "NiSeatnscsaalnldyorsidgndiefviicaatnitond.ifTehreennce=f.rom contol (p 0.0). Al 55% 019 039% 075% 087+ 004 on ery Does not contain TSCA CBI r2 e----------pTRP (28-Arpr-r03)=e Mean Final Body and Organ Weights for Male Rats Sacrificed on Post Dose Day 75 Liver (g) 82 Telomer B Alcohol (mg/kg/day) 0 5 25 125 6392: 18276+ 169: 22 172% 22 Kidneys 2) 36+ 39+ 39: 40: 04s 0x 047 039 Testis ig) 36+ 3s: 36s 34 028 055 034 074 Final body weight (g) S35: S47: STS: S489: 082 57.07 $319 3678 Wrver (pBw) Kidneys (% BW) 3001:3 3011:4 29% 013 31: 02 065+ 067+ 069% 074% 07+ 06% 06: 06% Riu 010 008 0m on S# Staetistincallytsigneificarnt difWcencee frsom contol (p= 0.0). Mean Final Body and Organ Weights for Female Rats Sacrificed on Post Dose Day 75 Ler) Kms (a) Finalbody weight () 82 Telomer B Alcohol (mg/kg/day) 0 5 25 125 03 + Ia: 3s 127% 17 13 25 12 22 + 24: 24x 27: 021 004 037 00m 22 + MBI: MIE SSE as 2021 soe 3134 o Lives CBM) 32 = 32: 34% 36s 014 03 037 00st 070: 071: 073: 078% Vidya (4500) Trem sodGevmion 003 007 Th=Feunnes erie noel hens. 006 002% Suaisically significant diference rom contol (p~ 0.05). --Doe cs not contain TSCA CBI 3 TRP (28-Apr-03) ood orin ans: Blood Ravine evel sched sd sie beeen stdays 0.54. PAAR CATA . ETEeE i| - i ht i tus A Feson oma 2 ee, || J Does not contain TSCA CBI 4 "TRP (28-Apr-03) Analysis of 8-2 Telomer B Alcohol, PFOA, and PFNA in Serum and Selected Tissues: Pooled plasma PFOA. samples obtained from parent compound, and males and females at steady state (test day 84) were analyzed for total fluorine levels. The levelofparent detected did not exceed 0.074 ppm in either males or females. The following plasma levels of PFOA were detected in males and females dosed with 0, 5, 25, and 125 mg/kg/day 8-2 Telomer B Alcohol. Female | Female Male | Male PFOA| Male total | Female| PFOA total Dose Group | PFOA | converted to| plasma | PFOA| converted| plasma F (mg/kg/day) | (pm)| ppmF | F(ppm)' | (ppm) | toppmF| (ppm) 7 007 0.05 NM 00 00 NM Ss 219 151 NM 0.08 0.05 NM 2 8.47% 583 si | ose | 037 538 12s 65.60% 45.16 524 | 1850 127 23.20 "Determined using Wickbold Torch; *mean of two separate runs; NM- not measured fBlausoerdinoenprtehseednattianptrheesepnltaesdmaa,bohvoew,evteher,PtFhOisAisinnomtatlheescaacsceoufnortsfefmoarleas.larWgehiploretwiohnatofisthien the blood in males is predominately PFOA, it is not possible to determine what percentageofthe 8-2 Telomer B Alcohol dose is converted to PFOA (c.g., information is lacking on mass balance and biodistribution). parent and PFOA Further, it is less certain as were present in lowlevels to what and did the not metabolites account for may be the total in females as both fluorine levels in the blood. Tstiastseu(etessatmdpalyes81(f)atw,elrievear,naalnydzekdidfnoeryt)heobctoanicneendtraattnieocnorofppsayrefnrtomcommalpeosunadn.d PfFemOaAl,esaantdsPteEaNdAy. "The data are summarized below. `Tissue Analyses from Range-Finder Study (Test Day 81) [TT 2 Teclomer B Alcohol (mg/kg/da -- [ --T r T [7_ s s T | Bs || [-- [iver J | 1 w 00w2p000)a || o0.o3t0ee 03o)n[|0o7y r7e0o59]| [PC roAGet m [Pa-- sa r |200 ___rTr837 TTre 1| [[ CC Tiwe --T [Toewo6e09n0|| Reee dwown]]Slwoooo]| r C-- [Kiny |lei@T sn) | saiT| w_a_r_n_s|] [F[ FAGemT[vFae T|osoiooom | | o0s00t0o0a0y|[ 0L0oid0a0sn|| CC [Rag | owen | oiiem| ossee | Does not contain TSCA CBI 3 TRP (28-Apr-03) [4 dSoesreumgrsoaumppl(peesrwseerxe) fcoorllaencatleydsitshorfoupgahroeuntttchoemipno-uinfed.phPaFseOoAf,thPeNsAt,udyanadndthpeo8o-l2edacwiidthin cach p(oCsuitoilvleliy0i1sd)Fe.ntiSfiynctehisthsepreeciisesnoinstthaendpalradsamvaai(lfaatb,lelifvoerr athned8k-i2danceiyd,wewreeanroetuannaabllyezetdo).quaHntoiwteavteero,r sthpeerceieiss aanppuenarksntoowhnaavtemaasdso/scehraersgpeornasteioroefla4ti7o7n,shwihpi,cfhuritshceornssuipspteonrttiwnigththtehper8e-m2isaceidt.hatThtihiss477 hSpaevceiepsreissernetleadtetdhetodtahteamaestaarbcoalciosumnotfs rtahtehe8r-2thaalncohaobls.oluStienccoencitenistrnaottipoonsss.ibAlletthoouqugahntwietatcea,nnwoet qquuaantlittaotet,hiefrwesepoanssseumfaecttohratfotrhePrEeNsApo,nstehefnactthoercfoonrcetnhitsrautnikonnsowwnoumledtabbeoliintteheis laopwprpopximmartaenlgye (ic. more similar to PENA than PFOA). The data are presented below. Docs not contain TSCA CBI 5 TRP (28-Apr-03) 7 TT remotaners - , i [3 [Z=omonaty = Ho i2m - |e So [=e 125mgrgitny 0 7 unm mee owe Dow | Teta TT = rmarroncomammonnronserts - | i5x --v--omuaisn gu asin, So YSmygitay | s o I- S A Tosa Does not contain TSCA CBI 7 "TRP (28-Apr-03) mes2TemaCraionk wweo HEhE | fo wT = ron [oa5omoronse iron Senet ome Rc ne goo! 3400 | HfEe 100 eT olan Ste fe _ --m ee-- eSma oekey] Does not contain TSCA CBI 8 7 TRP (28-Apr-03) So Plasma PFA Concentration in Mae Rats oo | 200 | 5 150 oman $i asnota 3 |e motosey 8 os me 125matey || : om 0 1 won om om oweom wos WoT 1| Testy PlamaPrkConcontration in Famaie fas | 2, = 150 fe 2 8 -- ee]_ | asmoa | a 21255mmahoidaayn | | 000k0 e t 7 e wow amt om ok wot ws wo | Testy Docs not contain TSCA CBI 9 /0 TRF (28-Apr-03) Fr -------- 2eTo0nm0ao0nn0 Tomo | el| Troonooms eboe [I 8op0r0eo0s0so0e]0 oTe wn m e om se eea --3--sSeirizesd] Testor Plasma Met477 Concentration in Female Rats 1 sToonnoos hSaesoocoooc0da|0 (s_ ora ~ tooao o| motasmoonro 6G00o0n00o0 |p 2 | | 2000E0|EPAET LalA oA e Testany oes not conan TSCA CBI 0 TGR5APEG) Conclusion: Based on the data from this range-finder study, dose levels of 1,5, 25, and 125 mg/kg/day were selected for the 90-day subchronic toxicity study. Publications / Presentations: None. Does not contain TSCA CBI i 123 TRP (28-Apr-03)