Document QgY95jOd8D8yZQJRDdQw3wdo4

AR 226_ 190 Dracent Study Title 8.2 TeloBAmlceohorl: Acute Oral Toxicit-y FixedDose Method LaLboraatorbyrstory ProjectProject ID:ID: DuDPuPoont.676711 8g Sz on 3B sJEEEz< s "TEST GUIDELINE: OECD Guidelines for Testingof Chemicals Section 4: Health Effects, No. 420 (1992) AUTHOR: Carol Finlay, B.A. STUDY COMPLETED ON: September 17, 2001 PERFORMINGLABORATORY .HasI.kedlulPLoanbtodrNsoreyfo mHeaoanltdhuCaonmrdpEasmnryonmental Sciences NEelkwtaornk.RoDsesl,aw7.a0r.eB1o9x71560.0050 [-- Service ConeNumer: 25 --_-- 000003 2 TelomeBr Alcohol: Acute Oral Tricity- Fixed Dose Method DuPont6711 PAGE RESERVED FOR SPECIFIC COUNTRY REQUIREMENTS 2 000004 82 TeloBAmlceohrol Acute Oral Toneiy- Fixed Dose Method DuPon6711 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT "This study was conducted in compliance with U.S. EPA TSCA (40 CER part 792) Good Laboratory Practice Standards, which are consistent with the OECD PrinciplesofGood Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17 except for the items documented below. The items listed do not impact the validity of the study. `The test substance was characterized ater initiationofthis study. Although the characterization (ISO 9001) was not performed under Good Laboratory Practice Standards, the accuracyof the data is considered sufficient for the purposesofthis study. `The dosing preparations used in the study were not analyzed for stability, homogeneity, or accuracyofconcentration. The procedures used by trained staf to prepare the dosing preparations ensured: the accuracyofconcentration because the test substance was weighed on an analytical balance accurate to 3 decimal places and the vehicle in which it was suspended was. accurately measured in a flask graduated in 1 mL increments, homogeneity because the mixtures were stirred prior o dosing and while portions were removed for dose administration, and stability because the time between dose preparation and administration was kept to a minimum (less than 1 hou). Applicant/ Sponsor: Telomer Research Program Addington, Virginia USA. StudyDirector: 11 Finlay Staff Scientist / dBaelpt -2o01 EE 000005 5:2 TelomerB Alohol: Acute OralTosiity- Fixed Dose Method QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 2691 Dates of Inspections: Conduct: May17,2001 Records, Reports: April 5, 2001; September 9, 10, 2001 Dates Findings Reported to: Study Director: September 10,2001 Management: September 13,2001 Dupon11 Reportedby: Y> Cc y Sr. QuTaosyepAhs&suarancle Audicr 7-SeDapt-e 200] -_-- 000008 2 Tlomer B Aloha: Acute Oral Toxsy- Fixed Dos Method Dupencris CERTIFICATION Wfero,mtthheisunsdtuedrys.igned, declare that this report provides an accurate evaluationofdata obtained Pa{soBreirtons ' oaQelin Erin ravferri}308) Manalon Doe CUP a~ a Sapo a asap a gee wisi JashupFrgeE dde e Loy tty susvc: 00rteA rFcAsTi S 11 gpt 001 ~-------------------- 000007 8:2 Telomer B Alcohol: Acute Oral Tric-iFitxeyd Dose Method DuPont6711 TABLE OF CONTENTS Page PAGE RESERVED FOR SPECIFIC COUNTRYREQUIREMENTS conse 2 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT wos3 QUALITY ASSURANCE STATEMENT cocnvnssmmmmsssmsmmmsssssmmsssmsmss CRRTTINCATION smn STUDY INFORMATIONccosssmssmssmssmssmmsssmsmssmsmmsssmssssssms STUDY PERSONNEL crsmsssssmssssssssssssssssd SUMMARY crs:10 INTRODUCTION ser: 1 MATERIALS AND METHODSmmm: I A. TES GUIGEHNES crs 1 B. TES SUDSIANCE ocr 1 C. Animal Husbandry... rms: LL ES EL DI. OSSIiNgGhing Studc y ss 22 2 MainStudy. te ei J 12 Fu O1. DSSiEgIhiVnAgUSOtNuSdyr ... rconr Creras-- 133 2 MainStudy. rre----------------s3 RESULTS ANDIISCUSSION ssi 3 TAAL TORImmm A S1.IGDHoseSInUfoArmatic on and Mortality Summary nn 114 23. BoCldinyicaWleiSgihgtns.......... a son rm 114 B. M1. aiDnosSetuIdnyformation and Morality Summar" y. " , _--14 25.. BCloidniycaWleSiigghnss III 11s5 PAADIRY ESD mmssmsmmsinmmtmmminmmonmnn 35 A. Gross ObSErVations......... -- CONCLUSION sss:13 RECORDS AND SAMPLE STORAGE vrs:15 -- =< 000008 2 TelomeBr Alcohol: Acute Ora Toxicity - Fixed Dose Method TABLE OF CONTENTS AA.PPIENDNIDVIICDUEASL oBOpDrY WEIGHTS 8. INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS. C._ INDIVIDUAL ANIMAL GROSS OBSERVATIONS. DuPont6711 Page " 2 2s -- i 000009 52 TeloBAmleeohorl: AceOraToxFiixedDioseyith-od DuPona11 STUDY INFORMATION 9thCollective Nomenclature: 3d,e3c,a4n.o4l,5.56.6,7,788,9.9,10,10,10-Heptadecafluoro-1- Smonms/Codes: Haskell Number: AS Registry Number: Composition: Purity; Known Impurities; Physical Characteristies: ++ (BP.e-r(fHleupotraodoeccrayfll)ueotrhoaonocltyl)ethanol ++ 11,112222TTeeathryadhryodrhoeppetraidleucoraofdleucoarno-d1-eoclanol + 1122Tetrahycroperfluorodecanol ++ 11H112H2,T2eHt2rHa-hPyedrrfolupoerroudoercoadn-e1c-yolalcohol 1H, 1H.2H2H-Perfluorodecanol ++ 22--((PHeerpftlaudorcoaofcltuyobreotohcainyollethanol ++ 2C(P-er8flTuoeroloBcoAtlymectoehhyorllalcohol ++ 28-2PeTrfleuorlooocBtyAmllceetohharonlol + P00OOI (LotNo.) 24691 678-39-7 C- TelomeBr Alcohol 99.2 We.% CTFISCF=CHCH20H (0.8 We. %) White to yellow wax. Stability: Tcohnedittesitonssubosfttahnecestaupdpye;anroedevtiodbeencsetoabflienustnadbeirlitthyewas observed. Sponsor: T1e2l0o0mSeorutRhesHeaayrechs PStrroegetram Arlington, Virginia 22202-5050 USA. StudyInitiated Completed: April 2,2001 / (see report cover page) In-Life Iniiated/Completed: April 25, 2001 /May 17,2001 --_-- 000010 2:22 TTeelloommeerrBBAAllccoohhooll::AAccuutteeOOrraallTToovxiiictiyty-FFiixxeeddDoseMethhoodd STUDY PERSONNEL Study Director: Carol Finlay, B.A. Management: Primary Technician: Judith James C. C. Stadler, Mackay PITh.D., D.AB.T. Pathologist: G. Tracy Makovec, D.V.M. Management: Pathology Report by: SLitseaveJ.nLRe.wFirsame, D.V.M., Ph.D. Toxicology Report Preparation: Wanda F. Dinbokowitz Laboratory Veterinarian: William Singleton, D.V.M., A.C.L AM. DDuuoPomn6t677i111 = ---------------------------------------- 000011 2 Telomer B Alcohol: Acute Oral Tonsiy- Fixed Dose Method Duboni6711 SUMMARY Single dosesof 8-2 Telomer B Alcohol were administered by intragastric intubation to fasted `male and female rats. In the preliminary sighting study, a single doseof 8-2 TelomeBr Alcohol was administered to fasted female ratsat a dose of 500 or 2000 mg/kg. Sinceno toxicity was seen in these ras, the limit doseof2000mg/kg was selected for the main study. Inthe main study, the test substance was administered (0 a group of fasted male rats and a `group of5 fasted female rats at a dose of 2000 mg/kg. The rats were observed for mortality, body weight effects, and clinical signsof oxicity for 14 days after dosing. The rats were necropsied to detect grossly observable evidenceoforgan or tissue damage or dysfunction. No deaths occurred during the study. The rats exhibited no clinical signs of toxicity. No significant body weight losses occurred after dosing. No gross lesions were present in the rats at necropsy. Under the conditionsofthis study, the minimum lethal dose was greater than 2000 mg/ke. According to the guidance provided in the OECD testing guideline, 8-2 Telomer B Alcohol is a compound which does not presenta significant acute toxic riskifswallowed. _-- 000012 2 Tomer B Alcohol: Acute Oral Tosi- Fixed Dose Method Durontan11 INTRODUCTION "The purpose of his study was to assess the acute oral toxicityof 8-2 Telomer B Alcohol when 2ad0m0i0nimsgt/ekrge,dwbaysordaelrigvaevdagferotmo amaplreelainmdinfaermyaslieghrattis.ng Tsthuedyd.osIen tsehleescitgehdtfionrg tshteudmya,innosttouxdiyc,ity was observed in rats dosed at S00 or 2000 mg/kg MATERIALS AND METHODS A Test Guideline "The study design complies with the following testing guideline: + Organisation for Economic Co-Operation and Development (OECD) (1992). 420 Acute Oral Toxicity - Fixed Dose Method. Guidelinefor TestingofChemicals. B. Test Substance The test substance, 8-2 Telomer B Alcohol, was supplied by the sponsor as a white to yellow wax. The test substance appeared to be stable under the conditionsofthe study. No evidence of instability, such as a change in color, was observed. C. Animal Husbandry RMaalleeigahn,dNfoermtahlCeaCrorlii:naC.DR(aStDs)wIeGrSeBhRoursatesdwesirnegrleycienivseudspefnrdoemd,ChsatarilnelsesRsivsteerelL,awbiorraet-omreisesh,cIangce.s,. Each rat was assigned a unique identification number which was recorded on a card affixed to the cage. The rats were tail-marked,using 2 water-insoluble marker, with the last 3 digitsofthe animal number. PMI Nutrition Intemational, Inc. Certified Rodent LabDiet 5002 and water were available ad libitum except as noted in ection E. Dosing. As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrityof the study: + Water samples are analyzed for total bacterial counts, and the presenceofcoliforms, lead, and other contaminants, + Feed samples are analyzed for total bacterial, spore and fungal counts. -_-- 000013 2 Telomer B Alohol: Acute Oral Tosi- Fixed Dose Method Dupont6711 + Sbyamtphleecsagferwoamshferress.hly washed cages and cage racks are analyzed to ensure adequate sanitation rCeerqtuiifrieemdeanntismaanldfneoetd tios eusxecde,egdusatraatnetdemedaxbiymtuhemmcaonnucfeancttruartieorntsoomfekeetyscpeocnitfaimeidnannuttrsi,tiionncalluding psrpeecsiefniceed ohfteahveysemectoanlts,amaifnlaantotxsinb,eclholwortihneatmeadxhiymdruomcacrobnocnesn,traantdioonrsgtaantoepdhobsypthhaetemsa.nufTahceturer would not be expected to impact the integrityof the study. l"Tahbeoraantiomraylanheiamlatlh vaentderiennavriirano.nmeEnvtaalluamtoinointoofritnhgesperdoagtraadmiids naodtmiinnidisctaetreedanbyyctohnediattitoennsditnhgat affected the validity ofthe study. mRaatisntwaeirneedquoanraanttiimneerd-,cownetirgohlelde,d,a1n2d-ohbosuerrivgehdt/fo1r2-gheonuerradlarhekaclytchlef.or E6ndvaiyrs.onmAennitmaallcornodoimtisownesroef Ethxecurrosoimosnswoeurtesitdaergtehteesdefroarnagetsemwpeerreaotufresomafll23ma&gn1itCuadnedanrde/laotribvreiehufdmuirdaittiyoonfa5n0d=di1d0n%o.t adversely affect the validityofthe study. D. Test Substance Preparation a"Tphperotexsitmsautbesltya3nc0emwianustmeeslttoedasasnudrestuinrirfeodrimnitaywbaetfeorrebaetahc(haspupsrpoexnismiaotnelwya7s5-pr8e0paCr)ed.for E. Dosing I. Sighting Study A single oral doseof 8-2 TelomeBr Alcohol, melted and suspended in 0.5% aqueous 5me0t0hymlec/eklel.uloSsien,cewatsoxaicdimtiyniwsatserneodtbsyeeinntartagthaisstrdiocsien,taunbaottihoenrtfoasatefdasfteemdafleemaraltewraatsadtoaseddosaet of 2000 mg/kg. The rats were fasted returned to the rats approximately approximately 17 or 3 hours after dosing. 18 hours The rats prior were to dosing with approximately food being 9 weeks old coonnctehentdraaytoiofndaonsidngt.he Tfahseteidnbdiovdiyduwaelidgohsteovbtoaliunmeedsprwieorreocadlocsuilnagt.edTuhseinrgattshewesruespdeonsseidonat a volume of 10 mL per kgofbody weight. throughout the dosing procedure The dosing suspensions were stirred prior to and 2. MainStudy Single oral dosesof 8-2 Telomer B Alcohol, melted and suspended in 0.5% aqueous. amegtrhoylucpelolfuSlofsaes,tewderfeemaadlmeirnaitssteatreaddboyseiontfra2g0a0st0rimcg/ikngt.ubaTtihoenr(a0tsawgerroeupfaostf$edfaapsptredoxmiamlaeterlatys and d1o5sihnogu.rsTphreiorrattso wdoesrienagpwpirtohxifmoaotdebleyi9ngwereetkusrnoelddtoontthheeadtasyoapfpdroosxiinmga.teIlnydi3.v5idhuoaulrdsoasfetevrolumes --_-- 000014 2 Telomer B Alcohol: Acute Oral Toxicit-y Fixed Dose Method DuPone711 dwoesriengc.alcTuhleatreadtsuwsienrgetdhoesseudsaptenasvioonlucmoencoefnt1r0atmioLnpaenrdktghoeffabsotdedybweoidgyhtw.eigThhtesdoobstianigned prior to suspension was stirred prior to and throughout the dosing procedure. FE. Observations I. Sighting Study tOhbrsoeurgvhaotuitontshefosrtumdoyr.talTihtey raantds swiegrnesoobfsielrlvneesds,foirnjculriyn,icoarlasbingonsromfaltobxeihcaivtyiotrwiwceereonmathdeeddaayiloyf dosing and 7. and On once each test day 7, day thereafter. The rats the ratswere euthanized wbeyrceawreboinghdeidoxoindeteasstpdhayyxisa--t1i,on0. (dayofdosing), 1, 2 Main Study tOhbrsoeurgvhaotuitontshefosrtumdoyr.taTlihtey raantds wsiegrnesoofbislelrnveesds,foinrjculriyn,icoarlasbingonrsmoafltboexihcaivtiyotrwwiecreeonmathdeeddaayiloyf dosing 2,3,7, and and once each day thereafter. The rats were weighed 14. On test day 14, the rats were euthanized and on test days -1, 0 (dayofdosing), necropsied to detect grossly 1, cobasrebrovnadbiloexeivdiedaesnpcheyoxfiaotrigoannfoorlltoiwsesudebdyamexasgaengourindaytsifounn.ction. The rals were euthanized by EE 000015 52 TelomeBr Alohol Acute Oral Tnisity- Fixed Dose Method DuPone6711 RESULTS AND DISCUSSION In-life Toxicology A. Sighting Study 1. Dose Information and Mortality Summary No deaths below occurred. The dose information and the morality data are summarized in the table FASTED SUSPENSION DOSE BODY |CONCENTRATION moke) | WEIGHT (g mg/mL) FEMALE 500 2174 0 2000 213.7 200 DOSE VOLUME (ml) | MORTALITY 22 No 21 No 2 Body Weights (Appendix A) "The rats exhibited no body weight losses after dosing. 3. Clinical Signs (Appendix B) "The rats exhibited no clinical signs of toxicity. B. Main Study 1. Dose Information and Mortality Summary No deaths occurred. The dose information and the morality data are summarized in the table below. -_-- 000016 8:22TTeelloommeerr BAAllocohhooll:: AAccuutteeOOraalTTooxsiicetyy -FFiixxeeddDDoosseeMMeetthhoodd AVERAGE DOSE FASTED BODY | COSNUCSEPNETNRSAITOINON mgke) | WEIGHT (g mg/ml) AVERAGE DOSE VOLUME (mL) DuDuppoomntean7t11t MORTALITY RATIO FEMALE 249.6 200 2103 I 200 a3 os 21 os. 2. Body Weights (Appendix A) `The rats exhibited no significant body weight losses after dosing 3. Clinical Signs (Appendix B) dTuhreinragttsheexhstiubdiyt.ed no clinical signs of toxicity. Theendofthe tail was missing from one male rat Pathology Evaluations A. Gross Observations No gross lesions were present in the rats. CONCLUSION AUcncdoerrdtihnegctoondtihetigounisdoafncteisprsotvuiddy,edthien mthieniOmEuCrnDlettehsatlindgogsueidwealsinger,e8a-t2erTtehlaonm2e0r0B0 me/ke. Alcohol is a `compound which does not presenta significant acute toxic riskifswallowed. RECORDS AND SAMPLE STORAGE NSepweacrimke,nDse(liafwaaprplei,coarblaet),IrroanwMdoautnat,aainndRtehceofridnsalMraenpoargtewmielntb,eWrieltmaiinnegdtoatn,HaDseklealwlarLea.boratory, -_-- ee 000017 222TTeelloomemreBrAlAolocohhooll::AAccuutteeOOrraallTToovxiiciittyy-FFiixxeeddDDoosseeMMeetthhoodd _____ DuDuPpoomr6t767i111. APPENDICES eT 000018 282:2TTeelloommeerrBBAAllccoohhooll:: AAccuutteeOOrraaTToonsiiicittyy-FFiixxeeddDDoosseeMMeetthhoodd____ DuDuPpoomn6t67711i1 APPENDIX A Individual Body Weights -- -- 000019 2 Teer Alb NetOlTony-Finedoe Metod INDIVIDUAL BODY WEIGHTS OF FEMALE RATS FROM SIGHTING STUDY. DOSE: SMmgrks WE awer owe wa oy? Dury DOSE: 200mers +*FWuoddtwahg 000020 2 Tele Nb ot Ot ovis Fin Do Metod INDIVIDUAL BODYWEIGHTS OF MALE RATS FROM MAIN STUDY DOSE: 2000mei Damen * WFeaidgbedeyiweiihn 000021 2 Fler cto Ace Onl Tosi Fed Doe Method INDIVIDUAL BODY WEIGHTS OF FEMALE RATS FROM MAIN STUDY DOSE: 2000 mg Darn + WFeattetiyeweiih -_-- 000022 82:2 TTeelloomemrebBrAAllocoohhooll:: AAccuutteeOOrrsaTToonriisiittyy -FFiixxeeddDDoosseeMMeetthhoodd_______DDuupPoormt6771111 APPENDIX B Individual Clinical Observations and Mortality Records Ed 000023 2 Teor Ak Ast Or Tost Fis os Med Duress INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS IN FEMALE RATS FROMSIGHTING STUDY: DOSE: $00 mel, T-- . DOSE: 2000mgr Saceiticnd by desion . 000021 2 Teme Nolo:Ace Onl Tovey FdDoe Mth Duman INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS IN MALE RATS FROM MAIN STUDY DOSE: 2000mere -- u sacriticnd by dasisn w Sacriticed by destn 0 -_-- 000025 2 Tlioer Nol Ace Ol Toy FdDoeMethod Dues INDIVIDUALCLINICAL OBSERVATIONS AND MORTALITY RECORDS IN FEMALE RATS FROM MAIN STUDY DOSE: 2000 mere [---- w sacriticnd by dnsian w Sacriticnd by deston [-- " 000026 2 Telomer B Alcohol: Acute Oral Tric-iFitxeyd Dose Method DuPont6711 APPENDIX C Individual Animal Gross Observations --_-- 000027 2 TeAkm ActOlTvs FieDose Mod Deny INDIVIDUAL ANIMAL GROSS OBSERVATIONISNMALE RATS FROM MAIN STUDY |7 | sasions I TTT as[tFoenimveroammen]| 1[maa | # iso | |Jfeeizsssiaes]) 000028 $2 Att ee Toy cs ed Din INDIVIDUAL ANIMAL GROSS OBSERVATIONSINFEMALE RATSFROM MAIN STUDY | aston [| || | iis) | amr. oxo | xo soma rrr @| Li | [iE 1 Rent RR EE SS in 000025