Document wKRz6REdJg6wXpL26wQzBOazQ

0 @ . TRHesEearRchICoMrpMorUatNionE Cc 0 Rous C Bui3ldMinCgo2r2p0o-r2aEt-e0T2o,xi3cMolCoegnyter St. Paul, MN 55144-1000 C Cc FINAL REPORT 0 al Cell Proliferation Study with N-Ethyl Perfluorooctanesulfonamido Ethanol (N-EtFOSE; C 3M T-6316.11), Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; 3M T-6295.16), and N-Ethy| Perfluoroctanesulfonamide (PFOSA 3M T-7091.1) in Rats C Test Articles: C N-EtFOSE PFOS C PFOSA 0 Authors: a} Gary W. Wolfe, Ph.D., D.A.B.T. Kimberly A. Layton, B.S. b SCtuodympletionDate: 0 May 2, 2000 G `Therlmmune Research Corporation nC Gait1h5erFsibrustrfgi,eMldDRo2a0d878 C TRCStudy Number: G 1132-100 L -C N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 C `TABLE OF CONTENTS o COMPLIANCESTATEMENT ceeceases [I a STUDY IDENTIFICATION +11 ceesesinie | STUDYPERSONNEL J---- SR ARTE HE 6 | 0 SUMMARY mt nih 4 4 $8SETHE TR EE wpe 0 TERIce re 53 ARTS 5 FET ORE 022 "TEST AND CONTROL ARTICLES .........oonnnn ree | 0 TEST ANIANMDHAUSBLANDSRY oo. ooscsescnnnnns J METHODS +...o. oo. ooseessseseosiennieseesessesenssenesn 1 ||| C 7AE SLDORLPsregeswat vesea sme aram eneusereamereween I | C TCeOisvtiAhcratiCcrlheeFmoasirmmsuRltaaetidsonCnooalmnsvpdoeAuMIngdiLSetvrealtL iAonn.a. .s..+..1I .-.-.1..o1o1v1 ennn1stpwes ve wu visas 1UW | | 0 FCaCRnriatmint LdTiassLsCTaneCnlsondnIann mAiisscchBoii+saooln 111111111111Cu4 C TimeColston orHestonMirmeops raat Cm 0 RReivpdaRiermyon o |. CIs I || C3 FeTedteyWCmomagmptiCnoodnmBmopdiyoWneigh 1Gu1ns1111111nn Se || o ChTmeOroBoodyeWegradmLivLe WeiLghs 11111110 Lm C SIGNATUREPAGE ........coovunen Merrie .9 C I~ SUOMFBOMDYWRAIGHRT (GYum) [ROOTS C IA SUMMARYOFBODYWEIGHTGAINS Gram) -....ce...vevevrsr3s z 2. SUMMARYOFFEEDCONSUMPTGImON) .-.......oveovsevsrses. 2 3 SUM OFCLM IVICAA LOBSR ERVATYIONS .............eoooeererrs. is 38 C 3 | 3MCorporateToxicology | B N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 B Bf T--T mm Em s, n C TABLE OF CONTENTS (contd.) 0 APPENDIXTABLES Co 1. MALES: INDIBOVDYIWEIDGHUTS(AGRALBS) +. ro veovrreessnss3s2 C 2 - INDFI EEV DCOI NSUD MPTU IONA (GraL ms) +. + vovenensnnnnnnnnnnns 37 C 3 = INDIVIDUAL CLINICALOBSERVATIONS ............. 40 5 - INDIVIDUAL ABSOLUTE LIVER WEIGHTS (Grams) AND ORGAN TO BODY | C 0 0 0 | C C C C o | tC MCoporateToxicon 3 b Cc N-E(FOSE, PFOS, PFOSA TRC No. 1132-100 | COMPLIANCE STATEMENT C Cell Proliferation Study with N-E(FOSE, PFOS, and PFOSA in Rats L `This study was conducted in the spirit of the Good Laboratory Practice Regulations as o set forth in Title 21 of the U.S. Code of Federal Regulations Part 38, issued December 22, 1978 (effective June 20, 1979) and was not reviewed by Quality Assurance. There were no 0 deviations from the aforementioned regulations which affected the quality or integrityofthe c study or the interpretation of the results n the report. 0 C Study Director: C | C WH shh Cc Gary|. Wolfe, Ph.D. JD.AB.T. Date | GC B 3 Corporate Toxicology 1 | in N-E{FOSE, PFOS, PFOSA TRC No. 1132-100 i STUDY IDENTIFICATION C Cell Proliferation Study with N-ECFOSE, PFOS, and PFOSA in Rats C TRC Study Number: 0 Test Articles: o a Sponsor: 0 0 Sponsor'sRepresentative: o C Study Director: O 4 C - Study Monitor/Principal Investigator: o C StuSdtyudTyimIenittaibatlieon: C : 4In8i-tiHaotuiornPoofsiD-osDionsge:Sacrifice: C 71-4D-aDyayPPoossttDDoosseeSaScarcirfiifciec:e: 1-Week Recovery C 4-Week Recovery Study Termination: C 3M Corporate Toxicology 1132100 N-Ethyl Perfluorooctanesulfonamido Ethanol (N-E(FOSE) PNe-rEfilhuyolroPoecrtfalnueorSoucltfaonniecsuAlcfiondamPiodteas(sPiFumOSSAal)t (PFOS) B3uMildCionrgpo2r2a0t-e2T6o0x2i,co3loMgyCenter St. Paul, MN 55144-1000 | MarviTn. Case, D.V.M., Ph.D. | S3tM. PCaourlp,oMraNte5T5o1x4i4c-o1lo0g0y0 Phone: 651-733-5180 i Fax: 651.733.1773 Gary W. Wolfe, Ph.D., D.A.BT. Therlmmune Research Corporation | G1a5itFhierrsfsibeulrdg,RoMaDd 20878 | Phone: 301-330-3723 | SPaanthdorlaoRg.y EAlsdsroicdigaet,esPIhn.tDe.rnational Phone: 301-663-2036 January 12, 1999 FFeebbrruuaarryy 2253,, 11999999 MMaarrcchh 92,, 11999999 March 16, 1999 April 6, 1999 April 6, 1999 5 Ei g N-EFOSE, PFOS, PFOSA TRC No. 1132-100 O Cell Proliferation StudySwTiUtDh YN-PEE(FROSSOEN,NPEFLOS, and PFOSAinRats | C Study Director: Gary W. Wolfe, Ph.D., D.ABT. | b Study Pathologist: Carolyn Moyer, D.V.M., A.C.V.P. c Veterinarian Edward T. Greenstein, D.V.M., A.C.L.AM. | C Quality Assurance Director E. Paige Lacy, B.S. i 0 FHaecailltihtyaMndanSaagfeetry Officer/ Robert K. Blackford, A.A., LATG L | C Technical Supervisor: Patrick Benson, B.S., LATG | 0 Report Supervisor: Lori B. Kaiser, B.S. { C Technical Writer/Project Leader: Kimberly A. Layton, B.S. 0 Laboratory Head Technician: G C Technicians: o C Paula Davis,B.S.Sharron Stewart Daniel A. Jack BKerleltyCMhuasnseeyl,maBn.,S.B.LS.ATG Felecia Bishop, A.A., LATG Francis Onvuemene JLaorAinsnsaMNuerhprhebyeckyj, B.S. Paul Martin, B.S. 3M Corporate Tosicology 6 B C C N-E(FOSE, PFOS, PFOSA TRC No. 1132100 | C SUMMARY | | G `This study was designed to assess cell proliferation and peroxisome proliferation in rats | administered N-Eihy! Perfluorooctanesulfonamid, Pefluorootane Sulforic Acid Potassium Salt i Oo N-Ethyl Perfluoroctanesulfonamide and Wy-14,643 in the diet. Animals in Groups 1, 2, and 3 | received the test antics in the feed for 48 hours, 7 days, and 14 days, respectively, and were | CL necropsied immediately following completionofexposure. Animalsin Groups 4 and recived c the test articles in th feed for 14 days followed by a 1-week and 4- week recovery period, respectively, and were necropsied following the recovery period. All Groups were divided into 0 Subgroups. Subgroups 1,2, 3,4, 5, 6, and7 received 0, 300, 100, and 30 ppm of N-EFOSE, Co 20 ppm of PROS, 100 ppm of PFOSA, and 100 ppm Wy 14,643 respectively. In Group 1, each Subgroup contained 10 animals withth exceptionof Subgroup 7 with only animals. In Groups L 2,3, 4, and 5, Subgroup 1 contained 10 animals and received the control diet, The remaining Subgroups contained 5animalseach. Criteria evaluate for test atile effect included mean body 0 `weights and body weight gains, feed and test material consumption, clinical observations, clinical D opauthmolboigys,ctoirsgatny.wepigmhtso, Cgorossaxpiasthoalocgy,y ahidstcopaothnologiy, ocelsl proliferation, O `There were no treament related findingsforfeed consumption, test material consumprion, | and clinical observations. However, there were treatment-related effects found in the mean body | 0 `weights nd mean body weigh gains ofthe recovery animals. There were decreases seen in mean ! " `body weights on Study Day (SD) 15for the 1-week recovery animals in the 300 ppm N-E(FOSE, | C PFOSA, and Wy-14,643 groups. In addition, there were decreases seen in mean body weight | o gains on SD 8-15 for the 1-week recovery animals in the 300and 100 ppm N-EFOSE, PFOSA, and Wy-14,643 groups and for the 4-week recovery animals on SD 8-15 in the 300 ppm N- in EXFOSE group and on SD 22-29 in the 30 ppm N-EtFOSE group. "Treatment related findings were also seen in absolute and relative (g liver weight/g body C weight) liver weights. Increases were seen in the absolute liver weights ofthe 48-hour post dose GC sacrifice animals in the 100 ppm N-E(FOSE and 100 ppm Wy-14, 643 groups and an increase in o 3M Corporate Toxicology 7 i g C MNEFOSEPFO ~~S.PF TRCO NeS MSAN o the relative liver weight in the 100 ppm Wy-14,643 group. For the 7-day post-dose sacrifice animals, absolute liver weights were increasedin the 100ppm PFOSA and 100 ppm Wy-14,643 o granodreu lativpeors ganweightswereincrinethae3s00eppdm N-EtFOSE, 100ppm PFOSA, and 100 ppm Wy-14,643 groups. Absolute and relative liver weightsofthe 14-Day post-dose: O sacrificeanimals wereincreasedinthe300ppm N-EGFOSE(relativeonly), 100ppm PFOSaAn,d C 100 ppm Wy-14,643 groups. Terminal body weights of the one week recovery animals were decreased in the 300 ppm N-E(FOSE, 100 ppm PFOSA, and 100 ppm Wy-14,643 groups. ! Cc `Absolute liver weights were increased in the300ppm N-E(FOSE groupoftheseanimals. Also, relative liverweights were increasedinthe 300ppm N-E(FOSE, 100ppm PFOSA, and100ppm C `Wy-14,643 groups. In addition, absolute and relative liver weightsofthe four week recovery C `animals were increased in the 300 ppmN-EtFOSEand100ppm PFOSA (relative only) groups. | Result of clinical pathology, histopathology, cell proliferation, immunohistochemistry, | o palmitoyl-CoA oxidase activity, and electron microscopy will be reported separately. | 0 | C C C 0 Cc | C 3M Corporate Toxicology 8 C B C N-E(FOSE, PFOS, PFOSA : INTRODUCTION TRC No. 1132-100 | GC Tis study was designed to assess cel proliferation and peroxisome proliferation in rats administered N-E(FOSE, PFOS, PFOSA and Wy-14,643. The design of this study included 5 0 groups of animals. Each Group contained 7 Subgroups. Subgroups 1, 2, 3, 4, 5, 6, and 7 | c received the following: Control (0 ppm), N-EAFOSE (300 ppm, 100 ppm, 30 ppm), PFOS (20 | ppm), PFOSA (100 ppm) and Wy-14,643 (1000 ppm), respectively. Dosing was nied on | o February 23, 1999 for all groups. Groups I, 2, and 3 cach received te test dies for 48 hours, | 7 days, and 14 days, respectively and interim necropsies occurred on February 25, March 1, and C March 8, 1999, respectively. Groups 4 and received the same test diets for 14 days and C terminal necropsies occurred ater a 1 and d-week recovery period on March 16 and April 6, 1999, respectively. In Group 1 th est diet were administered to 10anmals/Subgroup with the C exceptionof Subgroup7 wi5antimahls.InGroup2s,3, 4, an,dtetestdiets were administered | 10.5 animals/Subgroup, with the exception of Subgroup 1 with 10 animals which received the o control diet. | a TEST AND CONTROL ARTICLES | One 34.88g sample of N-ELFOSET-6316 (Lot No. 30035, 30037,and30039 combined), 0 a waxy sold, was received from Covance Laboratories, Inc., Madison, WI, on December 31, 0 1998 and stored at ambient temperature. The purity was 98.1% and was stableforgreater than : 5 years. One 81.97g sample of Fx12 Fluorad T-7091 (PFOSA) (Lot No. not provided), an C amber waxy sold, and one 97.13 g sample of FC-95 Fluorad T6295 (PFOS) (Lot No. Not provided), a white powder, wer received from 3M, St. Paul, MN, on December 31, 1998 and LC storedatambient temperature. Both testarticleshad apuriy assumed to be 100 % and were both C sable for greater than 5 years. A 1 gram sample of Wy-14,643 (Lot No. 119904), a white powder, was received from Cayman Chemical, Ann Arbor, MI, on February 22, 1999 and stored C at ambient temperature. The puriy was greater than 98% and was stable or a least two years. C 30 Corporate Toxicology 5 0 C Cc N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 A reserve sampleofeach lot was taken and stored at ambient temperature, These samples L were transfered to the Sponsor after the completion of the in-life phase. Any remaining test G material wil be retumed to the Sponsor's representative a TEST ANIMALS AND HUSBANDRY 0 Rats were used because of the extensive historical ata base, and FDA requirements for i arodent species. Two hundred forty-ight male approximately five weeks old Cr:CD(SD) IGS | C BR ras were received from Charles River Laboratories, Raleigh, North Carolina on February 9, 1999. The animals were assigned temporary animal numbers upon receipt. The rats were | 0 acclimated to laboratory conditions for thirteen days prior to initiation of treatment. Each rat was o identified by an ear tag and cage card bearing aunique animal number. Animals were housed one per cage from receipt to termination. During the study, all | o aniwemrehaousledsin stainlesssteel suswirpecaegesonnstdanleess-stdeel racksequippedwith | plastic backed polylners. Animals were provided with fllered tap water ad libitum via an | C Edstrom automatic watering system or water bottle. TekladTM 7012 Certified Rodent diet was 0 available ad lifitum in glass jars with stainless tee lids and followers. Fresh food was provided | - Weekly. The wate is analyzed at east two timesperyear for contaminants and specific microbes. [ o "The feed is analyzed by the manufacturer for concentrationsofspecified heavy metals, aflatoxin, | chlorinated hydrocarbons, organophosphates, and specified nutrients. The results ofthe feed and 0 waler analyses are on file at Therlmmune Research Corporation. No contaminants were known c 10 be present inthediet or water at levels which might interfere with achieving the objectives of the study. C During the study period, the temperature and relative humidity of the study room were recorded twice daly. In addition, the anima roomtemperatureand humidity were continuously 0 monitored by a ReesTM Scientific Monitoring System. The animal room was set to maintain temperaturaets 64 and79Fand relative humidity between 30%and 70%. A 12-hourlight 12- - hour dark cycle was maintained through the acclimation and study periods C TC 3M Corporate Toxicology 0 C o C N-E{FOSE, PFOS, PFOSA C METHODS TRC No. 1132-100 EE EE [Group 5 AssignandmDoeseLnevetls Following examination by a staff veterinarian for physical condition, the rats were assigned to the study: Time Poin) | Om) [o oy TT ange| 20 | COOP | 00pm)| of mimi| | CE I TeIe] (CG[|ie_cssDneiuo)ms[ [ o |"[=T~To Te-T1e-]1| 0 e|ep [oo oT T=] 0fijoese |" [P [1L >Te] | [P4 wEk rIecove CN EEEN CO IE BE EE Computer-generated random numbers were used for assignment to groups. At the ime 0 of randomization, the weight variation ofthe animals used did not exceed 28.D. of the mean D weight, and the mean body weights for cach group and sex were not statistically different. The - body weighis at initation of treatment ranged from 175.2 g 0 271.1 g. Extra animals were c removed and discarded without necropsy Test Article Formulation and Administration C Dietary formulationsofthe test articles and Teklad 7012C Feed were prepared using the C following procedure: For Group 1, the appropriate amount of feed was weighed into a plasic container and c Stored at ambient temperature and protested from light, For each dose level, the appropriate C 301 Corporate Toxicology i B SE r | D N-EtFOSE, PFOS, PFOSA- TRC No. 1132-100 quantityofTeklad 7012C feed was accurately weighed into plastic containers. The properamount L of the test article was weighed, using a stainless steel spatula, into a glass beaker. The oC appropriate amountofacetone was added to allow the test material to go nto solution. A dietary premix was prepared for each dose levelof ach test article by adding the appropriate amount of C feed with the test article with a sinless steel spatula until no feed/chemical agglomerates C remained. Additonal feed was added in increments that approximately doubled the amount of premix until an adequate premix was achieved. Following cach addition, the formulation was | C `mixed throughlywith stainlesssteel spatula. Whenthetes artcle/feed mix was transferred from one container to other, the container was rinsed at least three times with premix feed. All feed C used for rinsing and preparing the premix was taken from the preweighed feed in the plastic | C containers for each dose level. | From the preweighed feed, 10 kilograms was layered evenly into the Patterson-Kelly 0 Blender. The premix wasthenpouredinequal amounts into therightand left blender ports and spread evenly. The premix container was then rinsed three times with the vehicle, from the r preweighed feed. Eachrinsewaspoured evenly intotheblender. Theremaining preweighed feed | 0 was evenly poured into the blender. The blender was sealed and the dietary formulation was | blended for approximately 30 minutes. C Dietary formulationswere stored in sealed plasticcontainersand were sablefor21 days at room temperature. The formulations were dispensed into glass jars with stainless steel 0 followers and lids. Diets were prepared forthe entire study in one Mix. | C Two 100 g samples of each batch (per mix) of each dose level of the test article | formulation and stored were sored in heat sealable foil bags protected from light at room | c temperature. At the request ofthe Sponsor, samples will be returned for analysis. Unless used c for analysis, sampleswil bediscatalearstodnemeondthafterthecomploefttheiino-lnfephase. C Observations andRecords | Each animal was observed twice daily (am. and p.m.) for mortality and moribundity. C Findings were recorded as they were observed. o 3M Corporate Toxicology 2 o ree ---------- ieee --------egee] C o N-E(FOSE, PFOS, PFOSA TRC No. 1132-100 Individual body weights and physical examinations were recorded prior 10 treaument (at L randomization (physical examinations not reported) and weekly for Week 1 through 4 weeks of C recovery, starting on Study Day (SD) 1. Body weights and physical examinations were also recorded prior to SD 1 and not used of reported becauseof adelayinthe startofthestudy. Food cg consumption was measured weekly for Week 1 through 4 weeks of recovery, starting on SD 1. tC ClinicalChemistryandCompoundLevelAnalysis | oc Samples were taken for clinical chemistry evaluation and compound level analysis from | al animals immediately prior to scheduled sacrifices. Bloodwascollected from the jugular vein C 0 a serum-separator tbe. Serum enzyme levels of alanine aminotransferase (ALT), alkaline 0 phosphatase, asparatate aminotransferase (AST), cholesterol and triglycerides were determined. | - `Serum samples for clinical chemistry were sent to PAL in Chevy Chase, MD for analysis. Serum | C sample for compound level analysis are being sored in a freezer at approximately -80 C until | _ shipped to Dr. KriJs. Hansen, 3M ET. & S., St. Paul, MN. The results will be reported | C separately. C Termination C Interim sacrifices were conducted after 48 hours, 7 days, and 14 days of exposure to the | test diets, following blood collection. The animals scheduled for interim sacrifices were 0 anesthetized with CO,, weighed,and exsanguinated. The abdominal cavityofeach animal was | " opeth lniveerremdove,d, weighedand liversamplescollected.Theanimalswerediscaradfteedr A liver collection. o Terminal necropsies were conducted, following blood collection, on animals scheduled for 1 and 4 week recovery after 14 days of exposure to the test diets. The animals were c anesthetized withCO, weighed, exsanguainndnaectroepsdie,d. Necropsiesincludedexamination of the external featuresofthe carcass, all extemal body orifices, and the cranial, thoracic, and C abdominal cavities, organs and tissaes. In addition, the liver was removed, weighed and liver | o samples collected. 0 3M Corporate Toxicology 3 C ----------------------eeeerease] C C NE(FOSE, PFOS, FFOSA TRC No. 1132-100 C Oren Weights ~ "The liver was weighed fo all surviving scheduled necropsy animals. Cc Cell Proliferation Tissue Collection snd Immunobistochemical Evaluation 0 `Representative samplesofthe left lateral lobe of theliver and any microscopic lesions of 1 o the liver were collected and preserved in formalin. Afer fixation, the samples were delivered to | Dr. Sandra Eldridge at Pathology Assocites Internationa, Frederick, MD. Proliferation cell a nuclear antigen (PNCA) evaluation was performed on the samples. In addin, liver sections prepared from the same tissue block were sained with hematoxylin and eosin and examined | C microscopically. The results will be reported separately. C Palmitovl-Co Oxidase Tissue Collection and Analyses c A sample (approximately 500 mg) of the right lateral lobeofthe liver was also collected from select animals and Nash-frozen in liquid nitrogen. The liver tissue was sored frozen at C approximately -80C uniil they were shipped on dry ice to Dr. Ron Markevitch, Covance 0 Laboratories, Madison, WI for palmitoyl-CoA Oridse activity. The liver samples analyzed included all study animals,withtheexception oftheWo-14,643animalsandthed-week recovery | | C Group. The results will be reported sparately. C `Tissue CollectionforElectronMicroscopie Evaluation 9 Sections of the lef lateral lobe of the liver from all animals were collected, minced to f| approximately ane millimeter cubesandplaced in a fixative pproprie for lectron microscopy. i C The containers and fixative were provided by PAI, Frederick, MD. Samples were shipped (0 Sharon Ambrose, Pathology Associates Intemational, Durham, NC. Electron microscopy was Cc performed on one animal per treatment group exhibiting the highest cell proliferative response as o well as ane control anala the discretion ofthe Sponsor, from one time point as wel asth 4- week recovery. Thus, EM will be performed on one animal from the control, N-E(FOSE (one C dose only to be determines), PFOS, PFOSA, and the Wy-14,643 Subgroups at one of the time 0 3 Corporate Toicology Im - L N-EAFOSE, PFOS, PFOSA TRC No. 1132-100 C points, as well as the 4-week recovery, for a totaloften animals. The results will be reported separately Remining Liver Tissue 0 `The remaining liver tissue was frozen and stored at approximately -80C at Pathology C Associates International, Frederick, MID in the long-term archive for possible future analysis. C `Histopathology Livers from each animal that was examined for cell proliferation were stained with Co hematoxylin and eosin, and examined microscopically for histopathological changes. The results | C will be reporied sprately. | z RecordRetention | All raw data, documentation, records, protocol, specimens, and final report generated as | C a result of this study will be archived in the storage facilities of PAI for a period of one year | 0 following submission of th final report to the Sponsor. One year after submission of th final | report, allofthe aforementioned materials will be sent to the Sponsor and a return fee will be 1 o charged. All raw data sored on magnetic media will remain at PAL EC C C g C n 3M Corporate Toxicology [5 0 C C N-E{FOSE, PFOS, PFOSA | TRC No. 1132-100 | Body Weights and Body Weight Gains RESULTS c Mean body weights are summarized in Table 1 and presented individually in Appendix C Table 1. Mean body weight gains are summarized in Table 1A and presented individually in Appendix 1A. Mean bodyweightsand body weight gains were comparable inal groups throughout the | t studywiththe exception ofthe 1-Weekrecovery aniomnaSDl1s5.Therewasa 14, 8,and 12% | C decrease in mean body weights in the 300 ppm N-E(FOSE, PFOSA, and Wy-14,643 groups, B respectively. Mean body weight gains were decreased by 62, 32, 36, and 35 % in the 300 and 100 ppm N-EGFOSE, PFOSA, and Wy-14,643 groups, respectively on SD 8-15. In addition, | | C meanbodyweightgainswere decrease inthe4-Week recoveryanimals by 40%inthe 300 ppm N-EIFOSE group on SD 8-15 and by 385% in the 30 ppm N-ELFOSE group on SD 22-29, 2 | GC FeedConsumption Mean feed consumption is summarized in Table 2 and presented individually in Appendix i C Table 2. | = Mean feed consumpion was comparable in all groups withthe excepionofdecreases of | C 16 % inthe 14-Day PFOSA group animals on SD 14and20 % and 14 % inthe 1-Week recovery C 30 ppm N-EUFOSE and PFOSA groups, respectively on SD 15. C TestMaterialConsumption - Mean test mateial consumption is summarized in Table 4 and presented individually in C Appendix Table 4. | Test acle consumption averaged 31.6 mg/kg for 300 ppm N-EIFOSE, 11.1 mg/kg for C 100 ppm N-EXFOSE, 3.3 ppm for 30 ppm N-EGFOSE, 2.2 mg/kg for FOS, 10.8 me/ke for o PROSA, and 10.9 mg/kg for Wy-14,643. Ix | a WM Coporate Toricology 16 C A --| C C N-EtFOSE, PFOS, PFOSA I TRC No. 1132-100 C Clinicalobservation aresummarizedin Table3,and presented indiviidnuApapelnldiyx C Table 3. Notreatmentrelated clinical observations were noted, however the following clinical C observationswereseenduring SD2-15inmostoftheGroups: thinness,abrasions,alopecia, rough haircoat, lacrimation,softfeces, and diarrhea. One 48-Hour PFOSA animal had paraphimosis on | SD'3.One1-Weekrecoverycontrolanimalwasmoribundkilleddueto adislocatednasalbone C ons21. C TerminalBodyWeightsandLiverWeights "Terminal body weights and absolute and reave liver weights are summarizedin Table 5, C andpresented indiviniApdpeundaixTlablley5. | C `Terminalbodyweightsofthe48-hour, 7-day,and 14-day postdosesacrificeandd-week recoveryanimalswerecomparableto thecontrols.Decreases wereseeninthe terminalbody Cc weights in the 300 ppm N-ECFOSE (14%), 100 ppm PFOSA (9%), and 100 ppm Wy-14,643 (15%) groups ofthe 1-Week recovery animals. C Forthe48-hourpos-doseanimals, absoluteliverweightswereincreasbeyd13%and27% | O in the 100 ppm N-EXFOSE and 100 ppm Wy-14,643 groups, respectively. Relative iver weights were also increased by 225% in the 100ppm Wy-14,643 group. The 100 ppm PFOSA and 100 Cc `ppm Wy-14,643 groups ofthe 7-day post dose animals had absolute iverweightincreasesof20% and 90%, respectively. Relative liver weights for these animals were increased in the 300 ppm 0 N-EIFOSE (20%), 100 ppm PFOSA (165%), and 100 ppm Wy-14,643 (86%) groups. Increases o were seeninthe absolute ivr weights in the 300 ppm N-E(FOSE (44%) and 100 ppm Wy-14,643 (104%) groups ofthe 14-daypostdosesacrificeanimals. Relative liver weights were increased 0 12.in4th9e3%0, 100,and300ppm N-EtFOSEgroups,22%inthe100ppmPFOSA groupand 114% inthe 100ppm Wy-14,643group. Incorf25e%aand4s4eviser seen intheabsoluteand c relative liver weights ofthe 1-Week recovery animals in the 300 ppm N-EFOSE group. Relative C liver weight increases of 23-25% were seen in the 100 ppm PFOSA and 100 ppm Wy-14,643 - 3M Corporate Tosicology 7 C | 0 N-EtFOSE, PFOS, PFOSA TRC No. 1132-100 o groups. For the4-Week recoveryanimalsinthe300ppmN-ECFOSE group, increaseswereseen in the absolute and relative liver weightsof34% and 29%, respectively. Relative liver weights C wereincreasedinthe 100ppmPFOSAgroupby 27%. C Gros Observations 0 Notreatmentrelatedgross findings were seen. The following incidental findings were noted: an enlarged spleen in the 100 ppm WY-14,643 group of 1-week recovery animals, a o `mottledliverinthe20ppmPFOSgroup,andasmal righttestisandfocusonthe leftcauda 0 `epididymis in the 100 ppm Wy-14,643 groupofthe4-week recovery animals. Cc Cc C L C_ 3M Corporate Toxicology 8 C 0 C NE(FOSE,PFOS,PFOSA 0 SIGNATURE PAGE TRCNo.13200 | o Study Director: Technical Writer: 0 C WL shi = x , Q fad sf2loo GaryYq Wolfe, Ph.D, D.A BT. Date Tberly A. L4yton, B.S. 0 C Report Supervisor: C | As Bee Sofro = Lori B. Kaiser, B.S./Date C 0 | 0 C C C C C 3 Corporate Toxicology B C ere ere 19 mm -------- sess  wee, oo, oro ee, 132100 o cu rottensoSmoa,or 0ie eioS s come) rst 1 te | C aTwTTott:ar Ta u EEPra R Pw er DG PB DP n ww: w oEmsutmmaow vaese mWai emmei omami wuwee} | C R --Mee. GT B LTTBFT TiBN T 0&, 8 04 C wwF w oomozmt oamemoaMs aWny? mT e? Eme7 aom3 | po SR ed TT RR Re Cc pERICO. SusGROP: In 2H 3 an SH oh In g wn i momeBe omWywy moeOmms3 moem? m me4 omms3 || ve 0 wwF wooommgnftoEmgas5Bmoam moa}momme} mWes3 mwse? || Cc R we oSse:eRB aRHTR 8T 008 08 04 04 0 Es wwf nooRmesTomoesmoOmRsRe mOaT? mtek3 mWss owmes? 0 c ws wW: woOEmReohwwee mOaW mosw3 poam2 mTae3 wwes3 0 w=; w oEogmBomWeee mWee mWeg1 mWe: waeme? mOsW7 ES ST Fe | Cc NOTE: Terminal body weights for all Groups were food-fasted weights and will be reported separately. g B&S6S12LiI=tT hcoRanitrvonElea0n dmmoar C (3) = N-EXFOSE 100 ppm c corse Tntnton 2 o eto, pro, pron ve, zn soBmea ocso rnonrs | C C ow TEToSe.ee Coll PraoliferSatioSn SG tEudy fEewitG h WT-ELFOSE, PFOS, and PFOSA in Rats G we 8 0w&e4 aoo } 0 = ww w sme{ mW r3 Twss moew7 mWa5 owme3 moew? || C ore wwi woomse# mWa3 omamss mWop{ oomWe3 moumse3 mwew7 || C ons ww me we me mo ms ow ws || iso. W27.4 39.60 7nor 3 30.35 72.67 38.32 ?2.02 | 0 n wa w W owomes3 wMe3EOwWee3 Wxemds omen:3 mBe? oBas} || wr o iw SOr Ws wWamt Wmm a7 WmNe4 W mes7 owwes: wWmma? | || 0 one wwv a owesre3 mWee? Wmam3 wway7 8aw8a3 wWame3 d2st !|i C TTTEs TTrenintency05fh for tLWGarloysglsseofeVaoriafnce rusingweDigUhWtEsTTn'dS LPrLoc8edurreor spree. || o @B &BCT+ vciointrtoem ets0oom [| n B&BiIE ainE.. 0 34 Corporate Toxicology 21 ee o vemgospon mewwmw | 0 cot rotorsvsaSr hos sHcoTabSeIiGrHtGABSacCorSam)es in acs | 0 dTawTTosSeu:es WtW nETEfn(ae Fo pon Gn STpif i H 0&0 0a | o wiown wwrtH omszoom3W3 oeEms3 eo1n1 moew3 aow 21 o T wo oSsee:wer E 0hRS aBIh R 8E B 08 R & faa C ww V oaaaTko W ws omwe: oeem: Wssm3 d eo3 wws3 0 oars wood CI E CT E I E Wo Tn Ci o B ot:i To Ta"3 E S 3 s 3 a4 o Eay -ww Qa es ome mos om 8 wr 8 oa M sme owsma 8 omNe a4 woo n || | - 7? 3 t 3 : oC oars ow moh ErJB od 8G i 83 S 3 ? 3 | oz wa m1 wa ome me mr ma ma g So . SooTNsa en3 oz3 Go3 aa3 fis3 g on eiwm Lms(Aoomme WonWs3 twCaw7 W 50.13 W 52.93 W5.07 | 0 C owes ovonw o nr7 m oma ame3 mms3 owme3 me 7 moomt ||i TE TT RR R C ote neEea ni erapsT.ra1n48wHetFsSt.amoisSSaeyrsFev) nadBe2h-dtayiPsst DdoostSaornFiaenteer.s nt reorted di 0 o QB (+ucoI EntrEo 0R REemE B@SciInmeRtaTnD = 1 10m 0 Corporate entctony n o wespospow mew.upew | C cot pot tratisonoSaoyor urtehmEeCSoR2s,minPHc,ormmsd) pros in ate |[| . uSEwTTERoSsawaWor AE,fo n Ga $1 aS (8 Bur PBaht Dene er&&ie oa & aa || C we ooyn mBe oMm1 W mr fme mWms ms m2 ||| 0 Ot % ti % ? | a D ne wSmoasarit y ( Oh EH GH )y 6w ER aio || Ea ww owwmsa mWen owvee wYee mtom wWes m5ma 0 %: 3 : 5 3 3 | 0 maw ERSos we Eofn GSCReEF8e Bee Bea&5e a a 1a | TC wiww oomsaEP mWos5 mWufeo wSesd% omews1 mWme% wWsa% o wm v w omve7rowwe3 moeer3 mms7owwses3 mwir3 uoems3 | Cc B a oMsea:daw a in )fn SL w @ G a@ @a || o we w wa omme Wmso omwees Wwes mWoo wYsS mWaa | i ti 3333s | q oar 1s wwowo ams aWmes owgmlomms wTee vw er wwe || v tH] 3 3 3 s 3 C ova w0w Wweeoowwaeos mWSo mTews wWeh mWes tWess | | o EEi %TTT s eros a5ie BETTSs Process s 3 : | C oNtoe + rCeeed rcorTmmeptiacvnnma1n0n1e1d fGore6docyinogn 0h7e,re1c4e,en2y1.period (50 21:8 423. o @& =5Kceeonrttrroolo01e00mon wero 0m g B8CIhNeGnEmmBe | Cc 0 corporate Teniotony 2 | g | 0 [r---- nse, zee C ETEcot petssomSahn8y ta a Ce 2 OeCntORineEssBrmy prt tn Bat || c piH)h Bae&Sa H 0&4 0 4 00 | 0 wwi o owwse7 W mrt omma: wWeo} omr3momwa3 omswt | 0 ors ww w mmtei mWes3 wWme1 wWem} mme3 owwe: wwm m2 | o ova w iww ommer3 worw1 wW e? wma7 owme? ommr? mo 3 | o om ww i o ommss3 wwmma1 moew: monw? mWem? morm7 mowg? | g o ow 3s wimu owmse3 mRige4 mm e3 Wwa7 mme{ emme} aomme3 o wm v a owme5 woewe? wwe: owme} wma1 owws: wwem3 | e Te mm m --" 0 oE t= eendI contepeoT n ear SfoLr A8dans 2R04.ar prt 0 21:0 0. g B B= icE oree0. pnm Bi 5 |[| o- BBBoIInEeRa [ [ | 5 corporate Toxtestons 2% 0 wes, ores, bron ee, vsz100 o TTT cut prcsoSmhaLorhcnlReinsEpemBr10inpsros fn tats EGR T (a FopeteTrc aa IE |i C =n_AT__ap-- See Bh HO GB 0B 4 w BuxlBom owSr m RomwBux n RowsSem | 0 fr grow ux 3m ge few ger | C] oAT--sgari oe WBtTrhoEoexRwoHNiuEmo w BETumhm wBTIuERew R ROEUmIIwumVRmR sSiiuWle i o MAtatmstceoe (C m STwooEpef tb tgm gs Sm wbgoles edg2m ig 8 || E 0Oo R wR m ET tm mTE oaBemmiT we ia ii oo | o Rooeee cered See poi GB G8 6G w Buxslox s Jussjem s uxsfem 6 um | C imation C wATegaare s 3 5 3 Tmo0 wBioososJus sSon s Jussdew s JumsSus | || = wo PTeEEoOlmm oPe w Uoimm oam m Iie W w3 m o TR ae oMre. s m haw mT OGahBGwo0 | g BNso2.%tserved 0Bum 5fu 5Jem sJue sJem sue sSew || g o0Easeret PPTeaHxONPlo ox BJPoe ue Bjie em Sdieen um Bdiu om JSum || C opnorfrosecotarimds BwTrooew slGlus a JlulmsdSomm s jiumm sGieWasjWuwm | C Thin re TdEp m PEEoe iimm 2Ee m 08 i C} 0n choioel:n 0ogmm C BfBriiR haienvE e oEw | o a eco--pra--tnts--tony------------2s ------------------ ------------------ Serres] | o weve, oo, srs ne to. usz00 | r- cot pottersSsoHnara5 c3 NckoAnStTiInSOk N168 1 tte 3 TT Gos (Te Rant ||| | 0 a osSe:ee $O0"TEB TIH ET 8we86 8e 6 o00 | pehiocecared wBuos sfur s fomsSux s JomsJom um C ohoeoatonerea Bwuossfuse Js om sJusslex s lwsam | C Sat QSrR ER gL ue dgem Ltmeoi0 m om || o onbnoshrres S RwuomEsSAorRJsomsgSe ue ds eorm sple axsLex | o mrieen SCooatm 08 8 itT m im | C oNrnmoearagniara PBBuRmoOIfsuEesJOoImW SWsumxsJoeiwE JUsuEmsSiumm | o SSbhhienn S TRIo8 e E dim8 E oIpv R 0t% amF3iE iilE o a oDiearrhes osSe:ee E ThTm Eo Bh B 00T E0B 8-- @4 ||| 0 EonEr noervea Bnuos sfue fs om fs u Gs em S5 um Ss ue || 0 nepephyh PPwaoxEoGsum fAs TR em semsDiamx is JomsGoa | | Bien fw 8 2 8 30 | C- oSAsLgoacrtination 11 0 o 1am | wPooo sJum s dom sfmsde s Pumsfue || C RbiSvhitenn wr d FSo wFo8 gme 08ve8SaEgetOIeE d 8 od | | C 3 i TShiimehnoaais.8r:em | C B tIrom tEum C 3M Corporate Toxicology 26 C TTR pr | o. TTT cot raters Ssayoi5eihA 3 coompnirniBoonsrot nts || o REwp -Be. 0TeEHaR OGORooe0E h8 p8WE oop8F P0n | i nm es 88 888d o 2ooRieyetos s fJPo emws offam omst8dux em fs J5en em sil3m exsl1Femmdue Romtien im vf81 8fF 8i. s 8 e2 | CC owsa oemrs FPrTFT dum EdumEjeEm lem jem lem | RNoiwtren fR i amLm5 s4 38 t% a 51tam22fo 8 8 C o on13LF26hyrevs s fPe w sJomslpm ox s jlam slfe ewselm ow um }| | o i TSteetn HtIPARwELOoEASsS 5 A 238 8 tm o 8 |||| .ed sss sss || oO -- Taoermimnal KHL sGT tTR iweEosSodE e ix Sgf5mtowex Sw etoErmoSdfw e tm SgEetommod5eptmuoon | o in Alopecia aTTM m f0p ! t w T maSo OG o T SS=icap rmE s eoEe. 0 GGBiinNomEeT || | o Ii C 3M Corporate Toxicology 27 | 0 ome er me, 00 nc | CC omT e Eueh i a efarSOUMtMa ART&Y TO2F TESTAMPATEa 8RE eIAL A CONSUMPTOEIHSON (PhP)s a8 s 6oo0 ||||| Be 0 aB 7 odo%nomwaMEEmoemosshe aaH1 m mi" mws} |||i 01 R oEmoe MseE EB a T H a eT8a Se 08 I 8EE08 0a m ae Roo momz OwNr os%s 822 m aw omme GC w es REE 10SETT ap5 e --5--------.----------5 --------= C o Peri Gepm n suB=m :GROw:odiE xwno tM2mxE o3mIan}Eooauvn? aSxn 83 eohn oIw m s w? ||||| o rw i$wmr odono osM ms Nep3 si ? aae: se } owms? || Cc R me oWseo.es, a BtE He 85 @@ T 08 4@&4 @ao 00 pom; oodo2o MmHBe ommia osNe7 aacs omws? ns 3 | 01 n ws om F e oooio m#m5eooeeJ S se7 H20} se } owmss ||||| 1) = control 0 ppm | ~ BL rm c (3) = N-EXFOSE 100 ppm | . o Diper neEr,nE [ 0 7) = Wy 14,643 100ppm 2 corre tes = C N-ELFOSE, PFOS, PFOSA nae connie RC Mo. 1132:100 | | oC c TT ee. JBa i cSUeMr& ARTYr OF TEG STleFMyATeEwRyIiALnmkCONSaUyMPT8IlON (PpP)o PEA 6 Gf |||| 0 wiwnmEoEdoe%o mFr?oodme3 a3s3 W2y33 mN et Eone3 || ] ons C nwieoa 0.40 zm z? M10.2? o3.a0: a2.01 9a.883 t10.0 | o e &BCTheEimm Beemn s | B&iThaahniiea | C 7) =uy 14,643 100pom | c | C | | B z e--e --------------------------------------e--ee cpa Toteteny 2 --_-- c N-ECFOSE, PROS, PROSA TRC No. 1132-100 | C a = Somat ofeRS Sn E LIT VER GaIEOC)t,HOAc4t 1To s0o1r, eitt aro cs o || 0 hoa oa 8 oa 8 0 | 0- BODY WEIGfiH4To(6) wTee2 owmmsL poR uamna oo wowsW p Wmomse momrmyooWmuay C tr ga-fastos JTEwBOWJnaEEm ResRsWp oSnAmme JrioePm emdamoeuemsede ve c==:g eis dsiemEI OaER SsEwEE SssoNEsmEE SsEm cwee | [orem | nH Dose: oho&@ o&a " 8 oa a") m a | sor vg=+ o f wWoi3O maTToOmRe wwesoO wwe mws3 omae2 {| 0 tr so7%nsa SsRnEgh oowms sus SR SeEswh SsamaRocWeoHm tIesEse C Liver =i3 (X BODY WEIGHT) SoEn5 WOeENRu HsmEe SseEeOSusSe saaea a eeswe || | Bg B=oTTR IEG 2 RE8Ry pe 8RbE4e Ree & a awma ||! 0 C sor wTio?n4@ TmeBaOBmmgrmsomeRg oommeRy moamong wowanwg woamwy C tr so3-nsa GamBoEcEae nOoNEmemg wOeNsE hmaEeade E woeoomcnogs 0 vr -x ion : A Lae m vemE tEiTrE tMiEmM MSeEs eon tvrme a3 r ESH mEEe ETTEl R RiGea E Tn SeEMvTaTIn:NenSya. r 3 Corporate Toxicology 30 o Somr a of Isn sue LieSsy EnSeOaTh5 GcALDiSa)nepchs10Ptoin wBettarcs | C ofa ra Ba hFoI&HED8 &wma o8aw aoo i 3 C [F-- oAw V T ssocwansOMY EwweEp mEeRRho mOWsE caCmWe? caCmle3 | C3 Lier E@uionswanes nTaEpL%OCcIouea mMeMwBR DseOhep LmEmwe O we?RE nm: | 0g ver x =iaowa sero S goRE eBmoRm E SLm N E Eueshy. sWhoRxuy sWeEsag 0 a fSr ro E EGi oa f E o8 aEaEfo | oC -- prA:o wwsaSoRoWwYRs oEwseEY wOeWRy w8s8RY mWrTOTVmYEr | 0 Ler soi-ow us mmaRmS cpOaCeTw Wmmm GmuemeMg meEr sONaE: N na3 { [| C 0 erppctregoyr snsons ESasGSoecEees osmaywemg osumem SsRaey eGssEeTs 2sa8n | || EStreom 12 om coro) C Sio3=gNErCGoE 100om | | e rnlR a.e Subgroup & = N-EXFOSE 30 ppm a ren 7 Tie, 15 em ||! 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Z[EEREHEEE HEBER | doReRgl pRESESE raaveny i i EE% cosme ret Eok: ED nro vrs 2512028 | | D C wars, brs, oro nee, 13210 a]8 STE TT envirSemaaene3 on Col1l (ProelisferpaotiontStudys pweith N-ELFOSE, $10S5,e and PFOSA fatsin Rats. i C Si + tarTuoeremncic LoImee owain o ltemau wonyvows o vas hTooten it ww-ii | | C as Tieemta xi wwwtii | o ow Toemlit ine wwoyii | C ow Tefoymmi cite AworHit C a El he Tota an IwonHit wi |i C ness eTrmoalh a owryoars || C a ESpetoramten LL wu wwWaiii || 0 oo LiomL, ontii g Si T+ tTauGa Ra FTHeBretTEfoe" re consia s C RO lENohrstat ait wNTvii || 0 wo Twerht an woariour 3 | 0 wo TTeoonmma xt oohinH t3 0 no Pimyltt as Wwotii | C rrEEeeTTsdTiEeRTmm | 0 rfHroaescmld iHc ni kciJ. | o FPErum | D corporate Tonfoteny "0 | 0 N-ELFOSE, PFOS, PFOSA TRC No. 1132-100 1 LoTrOto,n STean,3 (ScoTntIin)S og Hi TTarTenes CSolalrprolivfereatsiTonaTSitudyrnewnith1eaN-rECFGeSE, hPTeOS,caaondmePeFOSA in Rats Cc T0375. NoTresarlm. a itt we DAY T-0AY 3 | o ome h om n woarivows | or ofrmu woariroars || g wwe omrmau owaryroars |i| o om ETohotit itt wwoarii1 o iT oio TET TNTormoal RT Se re oWlarioSaL rR3E oC Fa nT | || Taot mi wwii C oz oTorrmna nt ownirans o Er -- Rohan awayivows || 0 re-- Toh an wonipons | wos Toormmi kit wonivows | { 0 os Tderomamla xn owariour 3 || 0" Pr Terminal Kitl ooaarrsroars | Cc, vous eornt Terminal itt owrit iH | | o R10409. Ym Normal au wiDAY 1-DAY 3 || 0 oto boTrnommi oa3wri1 || simran 1+ 0 gm cnI r) || o M Sr nhei Cr n dnei mN, 08epmm | C HEE Be or D 0 Corporate Tosfoteny a | -- 0 be, en ete, 1320 i o ctorvJSnbia aB3rCSoannrttin, ro at C Ri ToTT: +T1s20oe0trwmalm GROUP 1 Tom it ns (G6-Wour Post Dose Sacriofiece)SoonSUBGROUP: & wwwTii ki || 03 wee fwreo wopiprs | C Hemm wonyvows or rpemt in oWripours | C ws Temm owa rians o we eHrnm in woayvans || or emt wt C ThTino.m in wiOAY 3 o nem iy woti | Tots i ni | CJ ory tTpoeottiriente wwwoiiit | 0 a wee +TsELeumea TTotToir TGt ecWosuivsansR o He [== wii T | og now PaEeramghteiros)is orotiy ||| Oo or ThTeineml xt wawyi3 ||| 0 oa JLTehmint ot Bwyi || 0 os Teomrn in wouytons 0 or oemtm Fowo)rons 0 HMe sternel in120 iimammaBR,sEE C SSrrl ihehnm, ee C [S---- 2 C ---- Fp | C TEE ct ortooracsS EaenAn ,S3 cSEriPsksdd SE pos Inetaee ia+ sem 138 acots || p TRToRoSm xt 0 ee wm ew3mai ------------ i ws | Preim ou wBiH Cc R10629 Yh Normal an wyDAY 1-DAY 3 | o [ T haEa-- teuce ou TFoee GTE TeoWcritvSsowTsE | C A e Tom et T wy i C --fTye--t eat w-wii || 0 om tTeom mo wouyvos |i wo pTearms an worivows o om efmrt on oWxivow 3 i 0 10436 fNfiormarl wwoYii1 | C eTmm ou 0 os eHmto it wouyvow 3 ownirows || ow [teoman wouivows 0 wa pReormhou awairons y o SE wsirrte1dE i2r0htoimoR eenmtel)m 0 se SerE in neE Ee C | ere eee 0 rare Tiss " | ee e rr leo ----------r -------- 0 eomesee pr C TT n a n aaonrpceB Stne,3T mSeneu,seeyRg 1 a+ atari in Le Tesont ||| gp eee[i Swi T 0 wo ais [= wa3i C rHlma an Jwi . | 0 wp WTwnilext -wwwiii o os rT ebPhrt rp RT 1wi3 {| oo a R+e ebTaonomsan mio oecorwsteese | | o [a Eh cn owriows o og EiPinlls it owEreHs || a rfme owuevon a [ wo pBo h wu wpe -- ( 0 em gHmh aEHrows || 0 wr hn ooru vows | 0 JE Hh an oEuHvows J pu si owuyvows || GC oss wHorhm on itors PSeLerRliimnaon | o Hr HenIle eE [|! 0 + Yr pen i ren | | C 0 Corparate Toseaton w" 0D we pm ons [awe en 1 1 vi C e orcie ane 3 cCanaintes, TTEE T -- GGolYproolifneratR eioSntuecho wia th h-EXiTOSeE,sc7o08t, ard PFOAineRaets | | op tesTao 1 || o nor Tpth wu woreans C pm [LEN E+wiH) R10459 he Normal. wiDAY 1-DAY 8 || C o ows dorm EE a Isis assur ro er re o#ar1Svopws Severe "ioe Toecco | Tm we | o --E-- n wourrvon | o os yhom n owripobre 0 "pom - woryvans [EE ETEhurr ro prs me nyipe ||| a] o umd caTseBRomutaanTioins n sseevenniry t"sloc Tine omwececnoeismsmep | ---- or vars Terminal Kitt oAY 8 | |- wy oO R10469 [. Normal on o mte weDAY 1-0AY 8 ooyspos | | 0 oEr SarEeeaem11limiosm aEcoRnb,eesm id ineor | || er | 0 Subgroup 7 = Wy-14,643,100ppm 0 ------------------------------------------------ 3 Corporate Toxicology 45 e -- eee-- es -- SS ----S | 0 west, pros, prost The to. 1132-100 | C aETmImr Coll prt eratriToSenaASPbPotrEruaNDyIlXWiSThaAeBLnMeE-E,3X"FOT(CShCEeo,noctiFonFAuOnSae,tdT)ena PsEOSA fn fats ! C A Tom att oon we on vanes | {{ o Toma an we RIT NToermraml a itt wiAY 1-DAY 8 1 O wre oHroth in wonevanes | o oa rs TEToemt iu rTmeirre eTia se nonymreaener comes {||| C 10476LacrTmaTtioonmiemBtHC LN wre ore -- -- o rr oTtT wn owneone || 0 wom Toomma xt owaeans | 0 wo oHomh int wo wwJeo--w.s i || In ETI term iru rTr Runa, coserunrions peeeveainy + ecocTThe Wemee comes Mm s Tom wt T we | o os oTromma a oAn)rane C re Tom int woaeanes || 0 wos oTrhmat wn owueroars | ow oTomm wu Woneane | C oC S fprraam1os2ImsE gmrtCR onea tvreed)s E S SareDeI s tehnS e,mmBe 0 7 = th es Cc EE-------------- Gare | o 3M Corporate Toxicology 46 ll [mse von er vm | 0 mr LI A Jh-- i i-- s, ANE | | [BeemLi. Sen Sweemy o wr ejne) owis ws || 0 eee em rps o hn ny | 0 wr pLm T lwye | wyhc wpys || 0 wow p.erm - 1 on town 15 | 1 R10452 Normal. AY 1-DAY 15 | wp ho | C opEee Terminal Kill oowAyYy1p5.ow || 0 wn pe J | [- 3] | Oo 0 HtSTV: anon TET00 "GROUP: 3 C16-Day Post Dose i of er Sacrifice) "SUBGROR: 2 wr yt ps | 0 wn am Bp | OLempha 0 wp on J 1 p mys op E HSFE urbgopronupl m ti1 = 0Lm i pmmle(Cnon nteroly) | || Elimite | Go Subgroup 7 = Wy-14,643 100 ppm b : | peo || C wast, ors, pros ne te. ys2-00 || Iron Le 3 consis) | C iETasTsets Cell pro3li(feeratbiTonFeoSatukdy ra witShLoWc-EeC1FO0S8E,ocPaImSa,egsanyd PFOA in Rats || C Amr uorsp wWonyiETOE | o1 wos2 dTeermramla itt ownny vow 15 o om Toemrma itt woarsvow 15 | -- Toma itt aEnyow 1s { Bg wo Toermral 1 oouiron 1 u0 L RooTEosseruTions GPT CeSevFeeRritTyBe SLaocrIeTIeNE occumnSed. w i| Terminal itt ws o or dTeorrmana itt onnsrow 15 ! o os oTerrmma itt owursony 5 || 0 os eTemrminal wonsow 15 | R10510 Normal DAY 1-0AY 15. 1 o a wE al # osseTRevrAsTiinaolNsKill Svein Loee Tine oDcAoYm1e5D | | Terral Kill EE O rose Tpeerrmmianal itt woarhvow 1s 01 ost TSdehorirmnalFeces roowoiws us wi i 0 wos Toerrmmat kit ooarstown 1s | o nests pToomritne itt ooaar on 15 i o3 SrStoanrpe 1tL+ M0Eeigsmroes(,,Es31r00a00)opmm || C SSaH ubagnronuspI & t= hNe-ehEE ts,FOSwE0,8m30pRmpoem |[| o | 0 3 Corporate Toxicology 48 oC was, ores, psn ne vo, 132100 [ g TTT Gaol SprolibferwatioOnAFTPSaPty ENsDIoXwiSTtSAihBcLAEek-E,3XFyO(RSCEo,nAtiPnRTuOeS,dSS) aRndRPFOA in Rats in 1 census Tenino Te ccomts 1 ||1 C EE Toman ee EU I NE ese o str holoemtt tt oJ WwE. || n on oTimma ownsrow 5 | wore ofrrmu owa iow 5 C wom oiheimt git ooinis wr 8 o Sinn2STpsEemons Ty Iroenr eTEtoe Ti castmT |i n Hot Tot an T wso || - R052 TNoromalm nt wi DAY 1-0AY 15. | g -- ohh ownsron 5 | g os oTomh int owa irow 5 || G oss TEbroo mNY Bina+ taurine oouhr oi w 15 Tom" _Loc Tie ccnmses | | o ont Toma eit S weE | wor pderrma op owratow 2 || oO osm oTroalman owrarow 2 | 0 -- iSoinim ean oWwnyEatow 1s | C ow Toomt itt WoarEvow 2 [ C --T--han oown ron2 || wom Tommt int oWrEvow 2 | a wom pTeormm owxiow 22 | C oo Tom in ownivow 2 | G1 wEEosDTLTSyEoomom aouop SEE TTI ReoNnEowhe2n TW wep sin pn c Mri RE ERIE | 3 corporate Toxicology 49 --T ---- te i ------ree C was, oes, ors ne veo i| C ot prtsSrhrth T-- ERE Ftdpe intats | | C EaE +EeErs : Ei i" Loc oe cS WooEnT wtea ane wwii C i -- py o Hh wu w4oWni]Evows 0 iJemL wowaya115 o --_ ETiora et oWWniEroar 1 a ehrm u oonu vow 32 | C i SBT: +T1c21tB[0eitoEe neGRODP: moc (1-Week Recovery). STGoRsOeP:at3 s WE | ju os elrim an owuitow2 || o se fTyoa it oWwrEaows ! | o: eHmh iu W[rpE | oJ oo TIE oHmh oT u r Tec oonu roar22 | ju}) i Hate + eur Terminal lt mc oe sranzaeaa 0 nor oomh au wWwEoz ! wo eHmh oWrEow | n wos perm au WouErow 22 || C} oso tHemh wu oan row 2 o sHPFtaraeen o12rm0sgnemhcomsyE o. H HHeEiIneE A R C | Corporate Toxicology 50 o wees, pros, pros ne to, 132-100 | C TT ol ott(earosTJ SneeS-- a,rSS hahsEand ro na ||| po m + te[nduyicsin e nn 1 e woWwen e | | I ni C wos dform p oWnHvow 2 || 0 ws eHml an oWrEvor 0 10556 NHormanl an AWYE1-0AY 22 | i) wo eHmh au w oyz C1 o TSTV:aT21m0R[0Ees=meeei "GROUP? 4 (1-Weowkl Reeconvery)rSGP:eB6Eee { C oe,Eh en Tom itt " wBWilEows wn | {| 0 R10558. rma Normal it wi DAY 1-0AY 22 i wo phene a WouEvows 0 e woe TaEsel er i a srmowenyvow z | 0 FetEesn a wen eWueeEesow 0 ose Tvierysatl it owWanyEon 5 | a Coss Tbdornesalm wWoaryEvow 1s 0 woe Heml woxiow 2 0 ese Le awrypa { 0Do SS M E oreni12e 0 a oe n Bwrorsr radi { | oLl Er IA Re wen on | G M1 = Ventral side of Neck | n 3M Corporate Toxicology 51 G M-ELFOSE, PFOS, PFOSA TRC No. 1132-100 | C TET catl paa tsome onons I at o3 hcSeoieiann ro tn || [0 r big --e H-n st weerneio p A dEwe3yeE 5mel, E---- | C wr AoEpomge HZ a [0BBw4eliomws we || o Ho Edermaa n womn rane 5 0 wow Eemh an wqie o] [----h= uen war EWWwiAdha i|| 0 won e we s wJa-- || ah22e O Reddened or pow We naeDAY 36 | 0 R-- E=N. . nS-- eons || C R057 he Normal oDr onmrh rirr oi DAY 1-DAY 43. esi ps | 0Le ETT Li ewhyak || 0 Pe oh xt woyiow 8 | 0 MT om h dp| ermoal o waLwvFy,mowa3 ||| Cc opSerato 111 owipe 0 SE oji ioreorlse1ee 0mlpmiaicon8b rE.stms oo E eE dE p oO hHME1 =e VaEem ntral m Side ofeNeecke es : |||| 0 3M Corporate Toxicology 52 c --E --eee --] o wars, prs, prow eo. 13200 ovoritnoan vaat,3 oStRiS G o HiaTrTtoTFtaoramiatsxCGotllSproli(feratCiSonaSucRmowith:A-ESXTF0heSE,asS WPaROESpmo,eaTnd PFOA in Rats || 0 rE roc wonytowas nos Homa au ownhrow i C R10584. ia Noraal au WE ORY 1-DAY 43 { C Snois1TSEepegourmmoscGisS TTR on Loc a "hota s5row | o eTomra xt nyaE o oer efomr onnysow 68 | C [rR Ha ona xe WWnoNuaELrooww2s2 | 0 #10589 Noobrmhanl. o LL wWWOAYEES17-DoAYw8s ||||| 1 oo etrmtaiteer go WoBvEvoowu2 || o LSacErimAtion woNoEs i [0 FI AEFnA hema E TTCTon oo ok eteleseon ||| 0 NTorsala. u wa DAY 22:0AY 43. || on a om a nonytour i || C o om jretHemrrae 0u0 ooWWnwEEovorwsn || x MrfSaoarilnestea whigroomBws EH | Toma a Eon95vow || C o wows Tdmioormhm a oFWnfiHoonwy8s | || G SSSEeaTiTnR2nTbvveaBT ianieg rSJnont2mesE bSeE8wTND-TvaoRDoupHosme he TW | | FL 0 0 Corparace Teteteny 3 0 ew ve ven ' pr | o frTT-- T Cit peetortAa PnPnEeNDIXdATABoLc,BErp3io(tSkCsopnatisne ntuehde) rcA ntntsase | | CoE rn 5TT |i 0 or eoEKormtn in WWEoNuEfBvaow15 || 0 wom rEemh on owxyvow 13 | 0 eTmm an ny-- | Mo oi rmt o2ne ton 43 || g ST aisiEe en STV: 1132-100 "GROUP: 5 saow= v rlmeoymee (4- week Recovery). 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C ELE EERE E Tak IE EE fist ! i ec} rd C3g SBHEiS EdpbR deidasE p feY dsaB i iaH Ei-d Eg