Document 85dqNoVOmoovxmn0Z0dBG3G4a

j O XM A - 6 - / 4 Final Summary Report Study Title E xtended R ecovery Study Follow ing a 2 6 -W e e k C ap sule Toxicity Study with P erfluorooctane Sulfonic Acid Potassium S a lt (P F O S ; T -6 2 9 5 ) in Cynom oigus Monkeys A u th o r P eter J. Thom ford, PhD Sponsor 3M S t. P aul, M innesota T e s t Facility C ovance Laboratories Inc. 3301 K insm an Boulevard M adison, W isconsin 5 3 7 0 4 -2 5 9 5 Laboratory S tudy Identification C ovance 6 3 2 9 -2 6 8 Sponsor Study Identification 3M T -6 2 9 5 .22 Report Issued 04 Decem ber 2001 Page Number 1 of 23 5 rsj vO --rm rxs: i?ir**3< V^O O C3 ro C ^ 'T im n o C B ! 000032 Covance 6329-268 3M T-6295.22 COMPLIANCE STATEMENT Extended Recovery Study Following a 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys All aspects of this study were in accordance with the Environmental Protection Agency Good Laboratory Practice Standards, 40 CFR 792. Study Director Covance Laboratories Inc. Andrew M. Seacat, PhD 3M Toxicology Services Date 000033 -2 - Covance 6329-268 ___ 3MT-6295.22 QUALITY ASSURANCE STATEMENT This report has been reviewed by the Quality Assurance Unit of Covance Laboratories Inc., in accordance with the Environmental Protection Agency (EPA) Good Laboratory Practice Standards, 40 CFR 792. The following inspections were conducted and findings reported to the study director and study director management. Inspection Dates From To Phase 02 Mar 00 02 Mar 00 Protocol Review 03 Apr 00 03 Apr 00 Protocol Amendment Review 04 May 00 04 May 00 Analytical Laboratory Inspection 05 JulOO 05 JulOO Body Weight 03 JulOO 03 JulOO. Data Review 20 Sep 00 20 Sep 00 Animal Observation 26 Sep 00 26 Sep 00 Data Review 27 Dec 00 28 Dec 00 Data Review 27 Feb 01 27 Feb 01 Protocol Amendment Review 09 Mar 01 09 Mar 01 Postlife 30 Mar 01 03 Apr 01 Data Review 24 Apr 01 24 Apr 01 Report Review 11 JunOl 11 JunOl Protocol Amendment Review 15 Nov 01 16 Nov 01 Report Review Date Reported to Study Director and Study Director Management 02 Mar 00 03 Apr 00 04 May 00 05 Jul 00 06 JulOO 20 Sep 00 28 Sep 00 28 Dec 00 27 Feb 01 09 Mar 01 03 Apr 01 24 Apr 01 11 JunOl 19 Nov 01 fllif kuhfil Representative Quality Assurance Unit Mhecmbir i Date G0OS4 -3 - Covance 6329-268 3M T-6295.22 KEY PERSONNEL Extended Recovery Study Following a-26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys Study Monitor: Study Director: Study Toxicologist: Study Coordinator: Supervisor, Large-Animal Toxicology: Associate Director, Laboratory Animal Medicine: Anatomic Pathologist: Supervisor, Anatomic Pathology: Principal Investigator: Andrew M. Seacat, PhD 3M Peter J. Thomford, PhD Dale Aldridge, BS Elizabeth A. Disch, BA Cynthia A Weber, AS, LATG Donna J. Clemons, DVM, MS Diplmate, ACLAM Robert A Leedle, DVM, PhD Diplmate, ACVP Laurie J. Schuller, BA LAT Kris J. Hansen, PhD 000035 -4. Covance 6329-268 3M T-6295.22 PURPOSE The purpose o f this study was to continue assessment of the toxicokinetics and distribution of the test material during an extended (approximately 1 year) recovery following daily administration by capsule to cynomolgus monkeys for at least 26 weeks and at least 52 weeks of recovery. The subject study was conducted at Covance Laboratories Inc., in Madison, Wisconsin, from 08 March 2000 through 09 March 2001. This document summarizes the major findings for the study. All aspects o f this study were done in accordance with the Environmental Protection Agency Good Laboratory Practice Standards, 40 CFR 792. PROCEDURES The animals used for this study (male and female cynomolgus monkeys; two animals/sex) were previously assigned to the recovery phase of a completed study for this sponsor [3M T-6295.7, Covance 6329-223, "26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys"]. During Covance 6329-223, the animals received 0.15 mg/kg/day of PFOS as a single daily capsule dose for at least 26 weeks followed by a 52-week recovery. At the end o f the initial recovery, a partial hepatectomy was conducted on the anim als, they were allowed to recover from the surgical procedure, then were transferred to the subject follow-up study (Covance 6329-268) for evaluation of extended recovery. Animals were not treated in the subject study. Animals were obtained from Covance Research Products Inc. (Denver, Pennsylvania) on 30 June 1998. At study initiation, the animals were young adult to adult and weighed 2.8 to 4.1 kg. Each animal was identified with a collar tag. The animals were housed individually in stainless-steel cages (except when pair-housed for environmental enrichment), and certified primate diet [#8726C, Harlan Teklad (through 22 January 2001)] and Teklad Global Diet [#2055, Harlan Teklad (beginning 23 January 2001)] was provided once or twice daily. Water was provided ad libitum. The animals were observed twice daily (a.m. and p.m.) for mortality and moribundity and once daily for signs of poor health or abnormal behavior; findings were recorded as they were observed. In addition, animals were observed once weekly, and any findings or an indication that the animal was normal was recorded (see Protocol Deviations for exceptions). Individual body weight data were recorded monthly (see Protocol Deviations for exceptions). Blood samples for serum PFOS level determination were collected after 2, 4, 6, 8, 10, and 12 months following study initiation. Urine and fecal samples were collected for PFOS level determination after 4, 8, and 12 months following study initiation and within one day of the serum PFOS collections. During Week 53, animals that were fasted overnight were anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. At the scheduled sacrifice, macroscopic observations were recorded, and selected tissues were collected and preserved. -5 - 000036 Covance 6329-268 3M T-6295.22 Please see Protocol Deviations on page 11 for a description of all deviations from the protocol. Study Timetable: Study Initiation Date: Inlife (Experimental) Start Date: Inlife Termination Date: Experimental Termination Date: 28 February 2000 08 March 2000 09 March 2001 30 November 2001 All raw data, documentation, records, protocol, specimens, and final report generated as a result of this study generated by Covance will be archived in the storage facilities of Covance for a period of at least 1 year following submission of the final report to the Sponsor. At least one year after, submission of the final report, all of the aforementioned materials will be sent to the Sponsor, and a return fee will be charged. The Sponsor may elect to have the materials retained in the Covance archives for an additional period of time, and Covance will charge a storage fee. If the Sponsor chooses to have Covance dispose of the materials, a disposal fee will be charged. All raw data stored on magnetic media will be retained by Covance. The Sponsor is responsible for retention of all raw data, documentation, records, specimens, and final reports generated as a result of this study by the Sponsor. RESULTS AND DISCUSSION Observations of Animals Clinical Observations Clinical observations are presented in Table 1. All animals survived to the end of the study and were sacrificed on Day 367. Clinical observations throughout the study were typical of cynomolgus monkeys in a recovery phase, with no evidence of test material effect. Body Weights Body weight data are summarized in Figure 1 and presented in Table 2. Body weights for the animals remained normal throughout this extended recovery phase. Individual Anatomic Pathology Data Individual anatomic pathology data are presented in Table 3. There were no macroscopic observations noted at necropsy. Serum PFOS Level Determination Reporting of the results is the responsibility of the sponsor. 00003*? -6- Urine and Feces PFOS Level Determination Reporting of the results is the responsibility o f the sponsor. Liver Analysis Reporting of the results is the responsibility o f the sponsor. Additional Tissue and Serum Analysis Reporting of the results is the responsibility o f the sponsor. Covance 6329-268 3M T-6295.22 CONCLUSIONS After the completion o f a previous study with 26 weeks o f treatment and 52 weeks of recovery, two male and two female cynomolgus monkeys that underwent approximately 52 weeks of extended recovery had no clinical observations or macroscopic findings that indicated any residual test material effects. 000038 -7 - SIGNATURES Covance 6329-268 3M T-629S.22 A. Disch, BA S tu d j(j2 6 o rd in ato r Covance Laboratories, Inc. J Date pd / V&kU/TbojtfSvf, PhD Study D irector Covance Laboratories Inc. 0 e/ / .* .^ - < o D ate -8- 000039 Covance 6329-268 3M T-6295.22 ANATOMIC PATHOLOGY REPORT SUMMARY Four cynomolgus monkeys, two males and two females, were used in an extended recovery study (52 weeks), following a 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295). On Day 367 of the extended recovery, the monkeys were fasted overnight, anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. All animals survived until the scheduled sacrifice. There were no macroscopic observations at necropsy. Samples o f liver, lung, kidney, spleen, thyroid, brain, abdominal fat, heart, and bile and serum were collected, flash-frozen in liquid nitrogen, and shipped to the sponsor for analysis or storage. METHODS Four cynomolgus monkeys, two males and two females, were used in an extended recovery (52 weeks) study. The animals were previously assigned to the recovery phase of a completed study for this sponsor [3M T-6295.7, Covance 6329-223, "26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys"]. During this study, the animals received 0.15 mg/kg/day of PFOS as a single daily capsule dose for at least 26 weeks followed by a 52-week recovery. At the end o f the initial recovery, a partial hepatectomy was conducted on the animals, they were allowed to recover from the surgical procedure, and then they were transferred to the subject follow-up study (Covance 6329-268) for evaluation of extended recovery. On Day 367 o f the extended recovery, the monkeys were fasted overnight, anesthetized with ketamine and xylazine, weighed;, exsanguinated, and necropsied. A sample liver (approximately 10 g) was flash-frozen in liquid nitrogen, stored in a freezer set to maintain -60 to -80C, and shipped to the sponsor for analysis. Samples of hmg, kidney, spleen, thyroid, brain, abdominal fat, heart, (approximately 3 g each, if possible), and bile and serum (each as much as possible) were collected and flash-frozen in liquid nitrogen and stored in a freezer, set to maintain -60 to -80C, until shipped to the sponsor. RESULTS AND DISCUSSION Mortality All animals survived to the scheduled sacrifice at Day 367. Macroscopic Observations There were no macroscopic observations. 9- - 000040 // y zy /// '/ z M Z4/ J 7 g jL ^ i f Robert . Leedle, DVM, PhD Diplomate, ACVP Covance 6329-268 3M T-6295.22 S i 1/ Date ij c r Z / 600041 -10- Covance 6329-268 3M T-6295.22 Protocol Deviations Protocol Husbandry. Environment. "Environmental controls for the animal room will be set to maintain 18 to 29C, a relative humidity of 30 to 70%, and a 12-hour light/12-hour dark cycle." Actual Procedure On Days 352 and 366 the light cycle was inadvertently interrupted. Protocol Observation of Animals. Clinical Observations. "Once weekly, each animal will be observed; abnormal findings, or an indication that the animal is normal will be recorded." Actual Procedure During Week 1, one male and each female had an observation of normal recorded more than once. On Day 28 the weekly observations were made by exception, and an indication o f normal was not recorded when appropriate. During Week 29, the required observation of normal or abnormal was not recorded "weekly" for Animal No. 105552. The observation was recorded on Day 197, which immediately followed the previous week's scheduled normal observation day. The observation should have been recorded on Day 203. Protocol Observation of Animals. Body Weights. "Monthly" Actual Procedure The animals were weighed on Day 1 and again on Day 7, in order to accommodate the weighing schedule o f the remainder o f the stock colony. Protocol Serum PFOS Level Determination. Sample Handling. "Samples will be centrifuged within 1 hour after collection, and serum will be harvested. Serum samples will be stored in a freezer set to maintain -60 to -80C." Actual Procedure Samples collected on Day 114 were centrifuged several minutes after 1 hour had elapsed from the time of collection On Day 226, documentation was not made regarding the storage of serum samples prior to centrifugation and after harvest. 000042 -li- Covance 6329-268 3M T-6295.22 Protocol Urine and Feces PFOS Level Detenninatioa Method of Collection. "Animals will not be fasted; urine (approximately 2 mL) and feces (approximately 5 grams) will be collected overnight." Actual Procedure The amount of urine collected on Day 113 cannot be verified. The documentation for fecal collections on Day 113 indicates "at least" rather than "approximately" 5 grams were collected. Protocol Postmortem Procedures. Additional Tissue and Serum Samples. "S am ples of lung, kidney, spleen, thyroid, brain, abdominal fat, heart, (approximately 3 g each, if possible), and bile and serum (each as much as possible) will be collected from animals at scheduled and unscheduled sacrifices." Actual Procedure Serum was not collected from three o f the four monkeys at the necropsy. These deviations are not expected to have affected the results of the study. 000043 - 12- m mm m m Man rnMtrnmm* m t-m m in Figure 1 Mean Body Weight Data (kg) - Males and Females EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-268 a yveeki,Day7 W eek 000044 ' _______________________________ . Covance 6329-268 3M T-6295.22 Table 1: Individual Clinical Observations Covance 6329-268 EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS PAGE! 1 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP! Ml DAYS 1-367 - OBSERVED DURING THE DAYS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS 105505 T 53 DISCHARGE VOMITUS CONTAINING FOOD SKIN & PELAGE ALOPECIA LIMB-FRONT-LEFT NORMAL NO REMARKABLE OBSERVATIONS 105523 T QUALITATIVE FOOD CONSUMPTION LOW NONE 53 APPEARANCE SWOLLEN HEAD-MAXILLARY-RIGHT NOSE DISCHARGE VOMITUS CONTAINING FOOD EXCRETION FEW FECES NON-FORMED FECES 64, 116, 162 _ 154, 161 1, 7 , 14, 21, 35, 42 49,, 56, 63. 70, 77 , 84,, 91, 98, 105, 112 120, 126, 133, 140, 147, 168, 175, 182, 189, 196, 203, 210, 217 224, 231, 238, 245, 252, 259, 266, 273, 280, 287, 294, 301, 308 315, 322, 329, 336, 343, 350, 357, 364, 367 227 312 36-37 9 64, 162 8 1, 4 -14 000045 frriv^Tiiii>tiWr#MW*iaW!i>iitfWili>P|I!lW<jl(^^ (MtfHNMm Table 1 Individual Clinical Observations EXTENDED RECOVERY STODY FOLLOWING A 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOSjT-6295) IN CYNOMOLGUS MONKEYS Cavan.ce 6329-268 PAGE; 2 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER . GROUP: MI (CONTINUED FROM PREVIOUS PAGE) 105523 T 53 SKIN & PELAGE ALOPECIA LIMB-FRONT-LEFT S CAB(S ) HEAD-MAXILLARY-RIGHT NOSE NORMAL NO REMARKABLE OBSERVATIONS QUALITATIVE FOOD CONSUMPTION LOW NONE DAYS 1-367 - OBSERVED DURING THE DAYS LISTED BELOW,1 *C' - COMMENTS LISTED AT END OF OBSERVATIONS 154, 161 , 37 14 7, 21 , 35,, 42, 49, 56, 63 , 70,i 77, 84, 91, 98, 105 , 112 , 120 126, 133, 140, 147, 168, 175, 182, 189, 196 , 203, 210, 217, 231, 238, 245, 252, 259, 266, 273, 280, 287 , 294, 301, 308, 322, 329, 336, 343, 350, 357, 364, 367 9, 227, 254, 317 8 000046 -15- mm*mmm*m*rnimmmm mm GoVaftBpiS^S Tabla 1 individual Clinical Observations EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covanoe 6329-268 PAGE: 3 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP: FI DAYS 1-367 - OBSERVED DURING THE DAYS LISTED BELOW} 'C' - COMMENTS LISTED AT END OF OBSERVATIONS 105539 T 53 DISCHARGE VOMITUS CONTAINING FOOD APPEARS TO BE MENSTRUATING NORMAL NO REMARKABLE OBSERVATIONS 105552 T QUALITATIVE FOOD CONSUMPTION LOW 53 DISCHARGE APPEARS TO BE MENSTRUATING EXCRETION LIQUID FECES NON-FORMED FECES SKIN & PELAGE ALOPECIA LIMBS-ALL LIMBS-FRONT SACRAL NORMAL NO REMARKABLE OBSERVATIONS 64 164, 247, 276, 362 1, 5 , 7, 14, 21-, 35,, 42, 49, 56, 63 , 70, 77, 84, 91, 98 , 105 112, 120, 126, 133, 140, 147, 154, 161, 168, 175, 182, 189, 196 203, 210, 217, 224, 231, 238, 245, 252, 266, 273, 280, 287, 294 301, 308, 315, 322, 329, 336, 343, 350, 357, 364, 367 1, 5, 116-117, 227, 259, 317, 353 365 31, 37, 213-214, 223 35, 209 227 , 230-231, 233, 238, 245, 252, 329 266 , 273, 280, 287, 294, 301, 308 , 312, 315, 317, 322 11, 14, 21, 31 , 35, 37 1, 5, 7, 42, 49, 56 , 63, 70, 77, 84, 91 , 98, 105, 112, 120,, 126 133 , 140, 147, 154, 161, 168, 175 , 182, 189, 196- 197, 210, 217 224 , 259, 336, 343, 350, 357, 364 , 367 000047 mMH rtiniliHMW^nw hH m IMIAmmh Cavanefe6S2&-28 BM T-oe.22 Table 1 Individual Clinical Observations EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT <PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-268 PAGE: 4 CATEGORY ANIMAL DEATH WK OF KEYWORD NUMBER CODE DEATH QUALIFIER GROUP! FI (CONTINUED FROM PREVIOUS PAGE) 105552 T 53 QUALITATIVE FOOD CONSUMPTION LOW DAYS 1-367 - OBSERVED DURING THE DAYS LISTED BELOW; `C ` - COMMENTS LISTED AT END OF OBSERVATIONS 5, 163-164, 203, 214, 227, 312, 317, 322, 353 000048 17 ANIMAL NUMBER WEEl Ka GROUP! MALE 1 105505 105523 3.5 3.3 GROUP: FEMALE 1 105539 105552 24..81 a Week 1, Day 1 b Week 1, Day 7 ttNStjSiikeijsi Table 2: Individual Body W eight Data (kg) EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY Covance 6329-268 3M T-6295.22 Covance 6329-268 3M T-6295.22 . . < - .;... 4.5 ; 4 '.7 4.0 4.1 4.3 4.2 4.2 4.3 4.3 4.3 4.4 2.7 2.7 3.0 3.0 3.0 3.1 3.0 2.8 2.8 900049 . 18 WMt MMMlM m rnm m m m m m *m m m m m m m m giungi ANIMAL NUMBER WEEK 37 GROUP: 105505 105523 GROUP: 105539 105552 MALE 1 4.9 4.7 FEMALE 1 4.5 2.9 Table 2 Individual Body Weight Data (kg) EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS WEEK 41 WEEK 45 WEEK 49 WEEK 53 5.1 4.9 4.9 4.9 4.9 4.8 4.6 4.7 . 4.5 4.5 4.6 4.7 3.0 3.0 3.0 3.1 Covance 6329-268 3M T-6295.22 PAGE: 2 000050 iStgdg iiiii^iwiiiiiiiili lt^tfitiHWWiiiiiW iii,liilitliliiiW Covanee 6329-268 3M T-6295.22 Table 3: Individual Anatomie Pathology Data EXTENDED!RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXIOITY Covanee 6329-268 ANIMAL NUMBER) 105505 SEX: MALE ' > DOSE GROUP: 1 SACRIFICE' STATUS: CHEDyEEni'&EJtBf] DATE OF DEATH: 03/09/01 STUDY DAY OFDEATH:-^67 STUDY WEEK OF DEATH: '53 <"1 TERMiNAp^BDDYfi DATE AND TIME OF NECROPSY: 03/09/01 '7Y3$f-,*>?*''^PROSECTOR: SS `'ALFORD '' 1 'EGOiffiEpS'W POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: AS ASSIGNED VJEIGHERi1 TAO^i'^jlRtSTO CATEGORY * * * L AS T INLIF.E O B S E R V A T I O N S *** KEYWORD QUALIFIER / FREE-TEXT COMMENT NORMAL NO REMARKABLE OBSERVATION^ ORGAN NAME *** G R O S S P A T H O L O G Y O B S E R V A T I O N S * * * SEVERITY, KEYWORD(S) OR PHRASE FREE-TEXT COMMENTS AND NOTES GENERAL COMMENT (GC) ...................... -NO MACROSCOPIC LESIONS 000051  4- S v ; ?i f 1 . ' ' ... : ..- ------------i-m----- -- tu sam t mm m m m.22 Table 3 Individual Anatomic Pathology Data EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOSjT-6295) IN CYNOMOLGUS MONKEYS Covance 6329-268 PAGE: 3 ANIMAL NUMBER: 105539 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 03/09/01 STUDY DAY OF DEATH: 367 STUDY WEEK OF DEATH: 53 TERMINAL BODY WEIGHT: 4530,0 GRAMS DATE AND TIME OF NECROPSY: 03/09/01 8:30 PROSECTOR: JOHN S. HALFORD RECORDER: TROY CHRISTOFFERSON POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: AS ASSIGNED WEIGHER: TROY CHRISTOFFERSON CATEGORY * * * LAST KEYWORD INLIFE OBSERVATIONS *** QUALIFIER / FREE-TEXT COMMENT NORMAL NO REMARKABLE OBSERVATIONS ORGAN NAME * * * GROSS PATHOLOGY OBSERVATIONS * * * SEVERITY, KEYWORD(S) OR PHRASE FREE-TEXT COMMENTS AND NOTES GENERAL COMMENT (GC) -NO MACROSCOPIC LESIONS 000053 -22- Table 3 Individual Anatomie Pathology Data EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY STUDY WITH PERFLUOROOCTANE SULFONIC ACID POTASSIUM SALT (PFOS;T-6295) IN CYNOMOLGUS MONKEYS Covance 6329-268 PAGEi 4 ANIMAL NUMBER: 105552 SEX: FEMALE DOSE GROUP: 1 SACRIFICE STATUS: SCHEDULED, TERMINAL SACRIFICE DATE OF DEATH: 03/09/01 STUDY DAY OF DEATH: 367 STUDY WEEK OF DEATH: 53 TERMINAL BODY WEIGHT: 2985.0 GRAMS DATE AND TIME OF NECROPSY: 03/09/01 8:48 PROSECTOR: JOHN S. HALFORD RECORDER: TROY CHRISTOFFERSON POST-FIX WEIGHER: NOT AVAILABLE PATHOLOGIST: AS ASSIGNED WEIGHER: TROY CHRISTOFFERSON CATEGORY * * * LAST KEYWORD INLI F E O B S E R V A T I O N S *** QUALIFIER / FREE-TEXT COMMENT NORMAL NO REMARKABLE OBSERVATIONS ORGAN NAME * * * G R O S S P A T H O L O GY O B S E R V A T I O N S * * * SEVERITY, KEYWORD(S) OR PHRASE FREE-TEXT COMMENTS AND NOTES GENERAL COMMENT (GC) -NO MACROSCOPIC. LESIONS -23- 00054