Document n9ENeoMeYzen15qQEbVRp3nj2

Attachments toLetter to C. Auer dated May 18,2000 Per`fStluudoireosoacntdanOetShuelrfoInnaftoer-mRaetliaotnedonCoCmeprtoauinnds AR A ARRCN! MAL oSSf xo "oomi [rosa |Perfluorooctanesulfonamide EN --pg00- 373 1) Acute Oral Toxicity Screen with T-3421 in Albino Rats, Safety Evaluation Laboratory, Riker laboratories, Inc., Project No. 0883AR0287, 3M Reference No. T- 3421 (KTZ-15), January 17, 1984 2) Acute Ocular Irritation Test with T-3421 in Albino Rabbits, Safety Evaluation Laboratory, Riker laboratories, Inc., Project No. 0883EB286, 3M Reference No. T- 1 3421 (KTZ-15), August 24, 1983 3) Primary Skin Irritation Test with T-3421 in Albino Rabbits, Safety Evaluation Laboratory, Riker laboratories, Inc., Project No. 0883AR0288, 3M Reference No. T- 3421 (KTZ-15), August 9, 1983 Studies in Progress 1) Protocol, Feces MetOhSoEd,DPeFvOeSl,opamnedntFOMSeAt]a,bo3liMsmStSrattuedgyicfoTroxPeircfolluoogroyoLcatbanoersautlofroyn,ate: Derivatives [N-EtF Study Nos., T-636.17; T-6295.21; T-7132.3; ST-41, In-Life Start Date November 22, 1999, In-Life End Date November 24, 1999 2) Protocol, Pharmacokineti 3M Strategic Toxicology cLaSbtourdaytoofrPye,rSftluudoyroNoocst.a,nTe1`3S2u2l;f onamide ST-39, [FOSA] in Rats, In-Life Start Dat e October 4, 1999, In-Life End Date November 2,199 3) Protocol, Cell Proliferation)S,t`uPdeyrfwliutohroNo-cEttanheylSuPlefrofnliucorAocoicdtPaonetsauslsfiounmamSaildtoE(tPhFaOnSo;l (N-EtFOSE; 3M 3M T-6295.16), T-6316.11 and N-Ethyl `Perfluorooctanesulfonamide (PFOSA 3M T-7091.1) in Rats, Pathology Associates Intemational, Study No. 1132-100 INNA ili ors 0008118001 2. 000109 s& >SS > 3 xs 3 oF Experisent Nou: Conducted At: Dates Conducted: Conducted By: Reviewed By: Np acute Oral Toxicity Screen rp o883AR0287 Yay YD, "4, Ye SRSaie.fkeetrPyauLlaP,bvoarlMauitanotnrieiosenost,LaabIoncr.atory August 2, 1983 to Septenber 7, 1983 DTDoooxwicoTlaotgkiosst,aonFk, oBeS d Study pirector rzhiolt=y AgSRenSaioroTmoaxi= (iTceroyl0,ocgiB0ss0t n, Acute Toxicology Viaje% pa Greatat,, 55 B45ABa4tYe Supervisor, Toxicology Testing ac: wWwi. m7.pcraiseeeLt ". C. MeCormick 000110 1 Summary The acute oral toxicity screen vith T-3421 vas conducted from August 2, 1983 to September 7, 1983 at Riker Laboratories, Inc., St. Paul, Minnesota using male and female albino rats ranging in body weight from 191-258 grams. The test article vas administered by gastric intubation at dosage levels of 5,000, 2,000, 500 and 200 mg/kg body weight with mortalities of 10/10, 10/10, 10/10 and 2/10 noted respectively from one hour to six days post dose administration. The untoward behavioral reactions which occurred uring the 14 day observation period generally consisted of hypoactivity, Lethargy, prostration, diarrhea and unkempt appearance with the onset occurring from 1-30 minutes to day four post dose administration. Clonic convulsions were noted in two animals prior to death, trancient alopecia vas hoted in two aninals hile dyspnea and salivation were noted in one animal uring the stady. ALL reactions subsided by day eleven or death precluded recovery. Body weight gains vere noted in animals which survived the study period. Necropsies performed at temination of the study revealed no visible Lesions while hyperemic or hemorrhagic lungs and/or hemorrhagic intestinal race generally vere noted in the aninals which died during the conduct of the study. The acute oral LDSO of T-3421 is greater than 200 mg/kg and less than 500 mg/kg in male and female albino rats. Introduction the objective of this study vas to determine the acute oral LDSO of 13421 in albino rats. This study vas conducted in accordance with the Food and Drug Adninistration's Good Laboratory Practice Regulation of 1976. The Law data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 000111 2 hethos and Resuits young atbine rate vere used in this test. ALL animals vere held under quarantine for several days prior to testing vith only animals Which appeared to be in good health and suitable as test anisals at the initiation of the study uses. The rate vere housed in stock cages in temperature and humidity controlled rooms and permitted a standard laboratory diet? plus water 88 Libitun except during the 16 hour period immediately prior to gastric intubaFtiivoenmwahleenanfdoodfivvaesfweimtahlheelrda.ts were adsinistered the test material at preselected dosage levels. The doses were adsinistered at a constant vole of 10 m1/ks directly into the stomachs of the zats using a hypodersic syringe equipped with an intubation needle. After gastric adainistration of the test material, the rats vere Leturned to their cages and observed for the following 14 days. Initial, seven day and final body weights, mortalities (Table 1) and adverse reactions (rable 2) vere recorded. A necropsy vas conducted on all anipals that died suring the study as well as those euthanatized at the end of the 14 day abservation period (Table 1). The protocol, principal personnel involved in the study, composition characteristics and Quality Assurance statement are contained in Appendices I - IV. 2Bxing g tabsr, eoregoTna,borWEatory Cho, Ralston Purina, St. louis, HO 000112 ACUTE ORAL TOXICIaToYLSzTU1DY - ALBINO RAIS Mortality, wath T-3421 Necropsy and Body Weight Data 3. %, 7) %, cose &N animal (ng/kg) Sex Number soo M 33mR3S5S534 33mm3855556 3m3557 soo Fo 33RR3I5S7T4 R3m3375756 33577 TrdiTveisdutalDayBodNuymbWeeri:ghts ) o 7 18 220280 Gaayy6)) -= 12937 D(aHyou)) =- 24 Gaye) - 210911 Q(HHooww)) -= 2100 (HHuonw)) -205 Gay 1 - 2000 M353r535589 3m0s3s5e6l0 3m3s62 1209051 O@eayy 6)) = 2a019 aayye)) =200 ay 2000 F 33Rm3S57789 3r3R33558810 3m3s82 soo CM 3RR0O7710 3R3R44007723 3R4074 219298 D(Haoyw)) 220005 ((Haoywn) -203 (Lown) 2202 aayyyH 2231 Gwaayyes)) 26 (ay) - so0 PF 33Rr4a110067 3ra108 33Rmaa110180 220000 aOayy 4)) = 22015 O(aayy 5) Be ay FuNrubmebrerTeDsetaedd sss s/s 5/5 s/s s/s s/s PeDrecaednt 100 100 100 100 100 100 000113  BEST COPY AVAILABLE ACUTE ORAL mastz 1 TOXICITY STUDY (conciusea) - ALSIKD RATS . wien 7-321 Jortatity. Necropsy and Body Height Data orneayz sex Daunmimmearl AToTeEstaRS"aySeMyembier:iEe @ SJosmbeerrmpeetsets rexrceeant oom ohhmoeenss BmEe1 dmmGeeo a=omwe vs Tnee ddee dosem oews N nhaanh EdI Rse aawx ws 20 TBaann 3 B Buew- Sores Figures in parenchesie inficete tine of death 2E TepesTtEe arfteimcallee ae sdimbiinniesr taecree.d rasenatesrusCphenasnio2n60in53w/antgera.nd less than 500 mg/kg in fested NED O E eecroe o pr sy eaEthhemoaenimaanlteeswihloifecrnnhosmsestuhmrevFiievs2ceo0dr0idesinhea/esgKigcdcuhraGsisohnscagsvialctGhiEieoonnutpec.spotenirdniuOeocndtevzaoiefsnvceintshdoleetenedcdsetnuaodtoyfvtihgmseeointoetlrl5eae0ld0lly1el3si/ivNc1een3rds Ceres at ene 3 000 mak aevel- 000114 . cs on. rcsasca- ae rs is N SorN wm Seim.n ,WoovU Booon w wpoonne Fwr mhie one worwrTeirns v9naYY wn fimpETohieneenrs, WvoBnnowmBao eww;:o- wLS$oormpEmimeTs sp wn amas "omBo"nne . B guemes wan ers os vc sm xn 5 wen res aryof scons pret COPY AVAILABLE a a ta el w p.v Sse sex. 1-30 60 120 ST whonn T 2 3 4 5s 5 7 0 9 1m 1w UM ET mir wg JAN 2gg2 g -FSik cr es re -- ATE-- ,S--T ert ESenTd COPY AVAILABLE Riker Experiment No: APPENDIXI PROTOCOL owas 2 JesT.__ceuwe Dmed lowtclwr fea SPONSOR: aM__lewoweisl Chodend GONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, Inc. St. Paul, Minnesota Division TesTARTCLE: feel coNmoLARTCLEERC eropostosTARTNGCONPLETONDRTE OF Tes sem fp TestsvsTem: fizino SAT LD source: K 136 ies, ORT con, (4 Nsoember: < oF > WeightCRaenegee:n2" = 39 OBJECTIVE: METHOD: wUTr "4 Somer TThesepoonbsjieen,ctaihlivsoetnoogrficthalsiustese,st6eawsi.le ibnehBatondcihinargaacltnedrigzeewneetrrhaeel saecluelceted as availabilty. oartaelst system fortorxiecpirtoyduocftbtihletyloosft Tcohnetraonlailmemtdailarstoowwimilslbdbeuerhiodnugensbteoidtihiendthsbetyaqiuncaloerlsaosnrtscitonedeeilansgnu,dsatpecescntodrpededirniwgoidrste,o wmtiheteshhlfaocboooadrgt?aehtsaoerniydon'uswttaessitmtdepaerenrodoafafttfruhedrereeocdpaaeagnrodda.lthiiAubnimgstiiunpdmgrily.oe oa e ewolth5ecnha1 wrilalcctoerrmirzeeksptohnewdi1l0oxbihecetyaadonmfiimtnahilestnteauerdsmetdbdiaetrreoianscaceolh,ndaaaondscidamaiargtldeo,nalahfelovxweaelondsviewmria,llsbffewihldilosbceduomasedanmgtieendilseaovnerldeddfolheoedswtnieotstht re raioee2oot,npawlTvaohitmeooernn1at0oa!rfleatarhdctoticisltoaeengsswteiflalorebivteechlesea,.dfmtoAilhnlneoiywasintniegmrae1dl4s1dwaiytlsh.ebeIannirtiiematlaulansnadidnfttinohaelthbfeoiordycarwgeeceiesgihvatensddwfiolrlbosbmeetrhrveeecdsorpfdooenrds.aonrAy eGIirosaewsanrreecsrusompisynwgiwlhhibecshfcowoislntldpnuocrutoded.ed ,oAnnbyuatllgnraoontsisbmaealbslniomwrihtmieacdlhitiodeihseewdahurri,icnlhgunatgrhsee,ocvboesnred,ruvKceitddondfeuyrtsihneagnttedhstegecansoanrwdae)lulcgaaosfsttehrce o eraasnsee.wia(lbLsbDeasn)arteoifcootnrhdepeetdreiswotdi.tahtAslilpcercawiiwillcdbameteanctagileconunelra1at0etdet,dheibopyrotsgshaienbslaetn,uddluyosridnisgriecaetoporrbosabeintrdvaetndha.elyTfsiihnsaelmarecetpuhotrostdmwaileltdh Stored in the Riker Laboratories Archive, St. Paul, Minnesota. R-TSWED 2 B Purina Laboratory Fen wate. Chow, Ralston Purina, St. 86 wi THHAD For Lous, A Missouri be20 JUN 131883 Vor. Frpaoh ORIO% TO DOSING. SLogeaonsell erat -CO). am mg T{EoIanTer TEAe LUAe TTICgN Dae SudyDiecior Bat 000117 "EST COPY AVAILABLE rar een so SOO. p tts A umm mt st 4 eat ccs Sh ces meson de shld be spt " . . 000118 wm BEST COPY AVAILABLE > principal Appx IT paceicipating personnel Involved in che Sut) vase 0. K. wackos, Jr. BS L. Dbens, BS 0. o'milley, BS Gc. recor function TSotxuidycolpoigriescttor sTuhpceorvliosgoyr mating i SeniorrTooxxiiccoolloongist seupaarlvizLoarsoracory 000119 10. . nF"FSTCOPY AVAILABLE appovoIx 311 KT 2-15 cc 3y- sve sauneicy serena, unsformicy. compositiTon3, 4pu3ri1sy or repre Na JP 1 ove pur Sh 2. The method of synthesis or origin of the test and control substances, - ene vor no Te 0% Setermined as of 25 Jue 3 ox tu off esl ges pid Ai.4 shsles ce pb winder 236-28 w.c. he WK 230-28 OH. Probar 223-5 Panty 26-7 =TD MA 31 1983 inoas 00120 Feoe)n June' Ltor ageiy sBVaALnLATeILE n. APPENDIX TV QUALITY ASSURANCE STATEMENT Acute Toxicology Laboratory Studies study No: [7I3JLER22 nis shore term study vas audited by against the Tau Compliance Audit, date on Deng and 25 18 the ihe final report examined results of the audit were reported to the study director nd to management on esses, DE 180 Ln atdision to the data audit, different significant phases fof Laboratory aie inspected weekly Studies underay ia the Acute un a recurring cycle, snd che Toxicology facilities are examined BYcompliance Audit on a three month schedule. :J (--pe--al . Compiisce Await Pr5 ams 25 LT. Bate 000121