Document LpL89wLz3mk3g6oR200zv6195
Final Summary Report
Study Title Author
Extended Recovery Study Following a 26-Week Capsule Toxicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys
Peter J. Thomford, PhD
Sponsor
.j
_
Test Facility
3M St. Paul, Minnesota
Covance Laboratories Inc. 3301 Kinsman Boulevard Madison, Wisconsin 53704-2595
Laboratory Study Identification Covance 6329-268
Sponsor Study Identification Report Issued Page Number
3M T-6295.22 04 December 2001 1 of 23
_2
i
Covanee6329-268 3MT-6295.22
COMPLIANCE STATEM_NT
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.
i
l_e'_J. Tl(e_ord, PhD_ -
Study Director
_7
Covance Laboratories Inc.
'Andrew M. Seacat, Phi3
3M
Toxicology Services
_ Date
I.. ,
Date
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Covance6329-268 3M T-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
02 Mar 00 02 Mar 00
03 Apr 00 03 Apr 00 04 May 00 04 May 00
05 Ju100 03 Ju100
20 Sep 00 26 Sep 00 27 Dec 00 27 Feb 01 09 Mar 01
30 Mar 01 24 Apr 01 11 Jun 01
15 Nov 01
05 Ju100 03 Ju100
20 Sep 00 26 Sep 00 28 Dec 00 27 Feb 01 09 Mar 01
03 Apr 01 24 Apt 01 11 Jur101
16 Nov 01
Phase Protocol Review
Protocol Amendment Analytical Laboratory
Inspection
Body Weight Data Review
Review
Animal Observation
Data Review Data Review
Protocol Amendment Postlife
Review
Data Review
Report Review Protocol Amendment Review
Report Review
Date Reported to Study Director and Study Director Management
02 Mar 00
03 Apr 00 04 May 00
05 Ju100 06 Ju100
20 Sep 00 28 Sep 00 28 Dec 00 27 Feb 01 09 Mar 01
03 Apr 01 24 Apr 01 11 Jun 01
19 Nov 01
i
RQeuparlietsyenAtastsiuvreance Unit
g
Date
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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 Diplomate, ACLAM Robert A. Leedle, DVM, Phi) Diplomate, ACVP Laurie J. Schuller, BA, LAT Kris J. Hansen, PhD
J
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:
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PURPOSE
Covance6329-268 3M T-6295.22
f
The purpose of 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 of 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
PMeorfnlkueoyros"o]c.tanDeurSinuglfoCnoievaAncceid6P3o2t9a-s2s2iu3m, thSealatn(iPmFaOlsS;reTce-i6v2e9d5)0.i1n5Cmyngo/kmgo/dlgauys of PFOS as a single daily capsule dose for at least 26 weeks followed by a 52-week recovery. At the end of the initial recovery, a partial hepatectomy was conducted on the animals, 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, I0, and I2 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.
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Covance6329-268 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.
i,
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.
I
Serum PFOS Level Determination
:7
Reporting of the results is the responsibility of the sponsor.
"67
Urine and Feces PFOS Level Determination Reporting of the results is the responsibility of the sponsor.
Liver Analysis Reporting of the results is the responsibility of the sponsor.
Additional Tissue and Serum Analysis Reporting of the results is the responsibility of the sponsor.
Covance6329-268 3M T-6295.22
#
CONCLUSIONS
After the completion of a previous study with 26 weeks of treatment and 52 weeks of recovery, two male and two female eynomolgus monkeys that underwent approximately 52 weeks of extended recovery bad no clinical observations or macroscopic findings that indicated any residual test material effects.
i:
SIGNATURES
EHzab_ A. Di_l_ BA
-
Date
Stud_C(_ordinator
Covancv Laboratories, Inc.
Y Covance Laboratories Inc.
Covance 632%268 3M T-6295.22
3
-L -8-
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 of 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 OaFOS; 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 of 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 632%268) for evaluation of extended recovery.
On Day 367 of the extended recovery, the monkeys were fasted overnight, anesthetized with ketamine and xylazine, weighed, exsanguinated, and necropsied. Asample 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 lung, 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.
5
,_
Macroscopic Observations
There were no macroscopic observations.
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Diplomate, ACVP
Covance 6329-268 3M T-6295.22
<.._,._,r,:_...'g,..,_e+/..g,/,.C.,.,.".3_.,0.i
Date
7 -/u-
Covance6329-268 3MT-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
D_ng Week 1, one male and each female had an observation of normal recorded more th_n once.
.OnDay 28 the weekly observations were made by exception, and an indication of normal was not recorded when appropriate.
During Week 29, the required observation of normal or abnormal was not recorded "weekly" for Animal No. I05552. 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 of the remainder of 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
i_
to centrifugation and after harvest.
!<!_
- 11 .
Covance6329-268 3M T-6295.22
Protocol Urine and Feces PFOS Level Determination. 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. "Samples 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 of the four monkeys at the necropsy. These deviations are not expected to have affected the results of the study.
i
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3_ T._29S.22
Figure1
Covance6329-268
Mean Body Weight Data (kg) - Males and Females
EXTENDEDRECOVERYSTUDY FOLLOWINGA 26-WEEKCAPSULETOXICITY STUDY WITH PERFLUOROOCTANESULFONICACIDPOTASSIUMSALT (PFOS;T-6295)
IN CYNOMOLGUSMONKEYS
5.5
Males Females
,,
13.5
I
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i
i
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[
i
i
i
i
1
i
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i
i
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]
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 4g 51 53
a Week 1, Day7
Week
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Covanc, _ 6329-268 3M T-6295.22
Table 1: Individual CHnical Observations
Covance 6329-268
EXTENDED RECOVERY STUDY FOLLOWING
A 26-WEEK CAPSULE
STUDY WITH PERFLUOROOCTANE
SULFONIC ACID POTASSIUM
IN CYNOMOLGUS
MONKEYS
........................................................................................................
SALT
TOXICITY (PFOS;T-6295)
PAGE_ 1 _ ...........................
ANIMAL NUMBER
DEATH CODE
WK OF DEATH
CATEGORY KEYWORD QUALIFIER
GROUP: M1
DAYS
1-367
- OBSERVED DURING THE DAYS LISTED BELOW; 'C' - COMMENTS LISTED AT END OF OBSERVATIONS
I05505
T
53
DISCHARGE
VOMITUS
CONTAINING
FOOD
SKIN & PELAGE ALOPECIA LIMB-FRONT-LEFT
NORMAL NO REMARKABLE
OBSERVATIONS
I05523
T
QUALITATIVE LOW NONE
FOOD CONSUMPTION
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, 120, 126, 224, 231, 315, 522,
21, 133, 238, 329,
35, 42, 49, 140, 147, 245, 252, 336, 343,
56, 168, 259, 350,
63, 175, 266, 357,
70, 77, 84, 182, 189, 273, 280, 364, 367
91, 196, 287,
98, 105, 112 203, 210, 217 294, 301, 308
227 312
36-37 9
64, 162
8 i, 4
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_- , _, "" ,_
_,- _
_,_
,_ --,,L ___
._ '.L _
.... "_*_'-_:!'-_._.c_i
"L'_'_L'_-:_-'_'__'w':''_'_ ......._.''_ ......_.=_,L__:_,_
3N T-6_2g_._
,
-L
Individual
Table 1 Clinical Observations
EXTENDED RECOVERY STUDY FOLLOWING
STUDY WITH PERFLUOROOCTANE
SULFONIC
IN CYNOMOLGUS
....................................................................................................................................
A 26-WEEK CAPSULE TOXICITY
ACID POTASSIUM MONKEYS
SALT (PFOS;T-6295)
Covance 6329-268 PAGEz 2
ANIMAL NUMBER
DEATH CODE
WK OF DEATH
CATEGORY
KEYWOED QUALIFIER
GROUP: M1
(CONTINUED
I05523
T
FROM
PREVIOUS PAGE)
53
SKIN & PELAGE
ALOPECIA
LIMB-FRONT-LEFT
SCAB(S)
HEAD-MAXILLARY-RIGHT
NOSE
NORMAL NO REMARKABLE
OBSERVATIONS
QUALITATIVE LOW NONE
FOOD CONSUMPTION
DAYS 1-367
- OBSERVED DURING THE DAYS LISTED BELOW;
C' - COMMENTS
LISTED AT END OF OBSERVATIONS
15_, 161
37 14
7. 21, 35. 126, 133, 231, 238, 322, 329,
42. l&0, 245, 336,
49. 147, 252, 343,
56. 63. 70. 77. 168, 175, 182, 259, 266, 273, 350, 357, 364,
84. 189, 280, 367
91. 98, 105, i12, 120 196, 203, 210, 217, 224 287, 294, 301, 308, 315
9, 227, 254. 317 8
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...........................
Individual
Table 1 Clinical Observations
EXTENDED RECOVERY STUDY FOLLOWING
A 26-WEEK CAPSULE
STUDY WITH PERFLUOROOCTANE
SULFONIC ACID POTASSIUM
SALT
IN CYI_OMOLGUS MONKEYS
--........................................................................................................
TOXICITY (PFOS;T-6295)
Covance 6329-268 PAGE: 3
CATEGORY
GROUP: F1
ANIMAL DEATH WK OF
KEYWORD
DAYS
NUMBER CODE DEATH
QUALIFIER
.....
_ ..............................................................................................................................
1-367
- OBSERVED DURING THE DAYS LISTED BELOW;
'C' - COMMENTS
LISTED AT END OF OBSERVATIONS
I05539
T
53
DISCHARGE
VOMITUS
CONTAINING
FOOD
APPEARS TO BE MENSTRUATING
NORMAL NO REMARKABLE
OBSERVATIONS
I05552
T
QUALITATIVE LOW
FOOD CONSUMPTION
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
i, 5, 7, 112, 120, 203, 210, 301, 308,
14. 21, 35. 42. 126, 133, 140, 217, 224, 231, 315, 322, 329,
49. 147, 238, 336,
56. 63. 70. 77, 154, 161, 168, 245, 252, 266, 343, 350, 357,
84, 91, 98, 105 175, 182, 189, 196 273, 280, 287, 294 364, 367
I, 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
I, 5, 7, 42, 49, 56, 63, 133, 140, 147, 154, 161, 224, 259, 336, 343, 350,
70, 77, 84, 91, 98, 168, 175, 182, 189, 357, 364, 367
105, I12, 120, 126
196-197,
210, 217
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o_,,_,__..,.._,T_._a._,_. .... _:,..-..,.,........................................
,,:,, ,,,i,_*,_r'_'-"':: ............ ......._:_'_-:_"-_"............. wi_'i_'_"'-"'"_'_ ..... _""_'_ ..........."._. "-iiiiiTf '_'';'_:_'_'-_"_:_'_"k'li;-_'"_"i[i'_i1_;:_''''-......................;..... '_"_'_'"_':'- ..................................... '_ ....................
"...... ;'_"'_'": II Ill
3M T-6295,22
............................
Individual
Table 1 Clinical Observations
EXTENDED RECOVERY STUDY FOLLOWING
A 26-WEEK CAPSULE
STUDY WITH PERFLUOROOCTANE
SULFONIC ACID POTASSIUM
SALT
IN CYNOMOLGUS
MONKEYS
--------....................................................................................................
TOXICITY (PFOS;T-6295)
Covance 6329-268 PAGE: 4
ANIMAL NUMBER
DEATH CODE
WK OF DEATH
CATEGORY
KEYWORD QUALIFIER
GROUP_ F1
(CONTINUED
I05552
T
FROM
PREVIOUS PAGE}
53
QUALITATIVE
LOW
FOOD CONSUMPTION
DAYS
1-367
- OBSERVED DURING THE DAYS LISTED BELOW;
*C L - COMMENTS
LISTED AT END OF OBSERVATIONS
5, 163-164, 203, 214, 227, 312, 317, 322, 353
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Table 2: Individual Body Weight Data (kg)
EXTENDED RECOVERY STUDY FOLLOWING
A 26-WEEK CAPSULE TOXICITY
Covance 6329-26_ 3M T-6295.22
Covance 6329-268 3M T-6295.22
_-'::,ii:_;:_iI_
I05505
3.5
I05523
3.3
GROUP : FEMALE 1
I05539
4.1
I05552
2.8
a Week i, Day 1 b Week i, Day 7
3.8
38
4.0
4.1 ,:...!.::_.";-"_._,':_'-.,_
_3
'_.';,._:_.,,,.___
3.2
3.9
4.0
4.0
:::!i_471"! : i_,:' i_,5
4[5
417 ' '"'/"_:_'/_",:Pa__Y=_
'_'_
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 .B
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Individual
Table 2 Body Weight
Dat_
(kg)
...........................
EXTENDED RECOVERY STUDY FOLLOWING
A 25-WEEK CAPSULE
STUDY WITH PERFLUOROOCTANE
SULFONIC ACID POTASSIUM
SALT
IN CYNOMOLGUS
MONKEYS
- ........................................................................................................
TOXICITY (PFOS;T-6295)
ANIMAL
WEEK
WEEK
NUMBER
37
41
...........................................................
GROUP:
MALE 1
I05505
4.9
5.1
I05523
4.7
4.9
GROUP:
FEMALE 1
I05539 I05552
4.5
4.5
2.9
3.0
WEEK 45
4.9 4.8
4.5 3.0
WEEK 49
4.9 4,6
WEEK 53
_ ........................................................................
4.9 4.7
4.6
4.7
3,0
3.1
Covance 6729-268 3M T-6295.22
PAGE: 2
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Covance 6329-26B 3M T-6295.22
Table 3: Individual Anatomic Pathology Data
Covance 6329-268
STUDY
............................................
WiTH
PERFLUOROOCTANE _ " ' _:_ .7 :.IN
SULFONIC ACID POTASSIUM CYNOMOLGUS MONKEYS '
SALT >
(PFOS;T_6295)::'_
_ _,][_3;[! i' _:{;_t :;!_-_i_:_
. :_; i'_'.'_<_!_I_!__._ _[i:'-:}i_i ::_'_'_!_._,_ _L_
: .... 7rr---r- .... : ....... : ...... _-- ............. -77_q-ZrT_7_:_Z:_7_
__
ANIMAL NUMBER: I05505
MALE
! DOSE GROUP:
SACRIFICE
STATUS: SCH_DULED,_R_A:_A,_I_I'I_:_
DATE AND TIME OF NECROPSY:
03/09/01
POST-FIX WEIGHER
NOT AVAILABLE
7:37'
CATEGORY
** KEYWORD
:'PROSECTOR: JOHN S. HALFORD
':
PATHOLOGIST:
AS ASSIGNED
! !REeORDE_"%. _.;_R_H_'i'_ WEiGHER_i_ TRb_::_H_'ST_F_
LAST
IN L I F E
OB SE RV AT IO N S
*" *
QUALIFIER
/ FREE-TEXT COMMENT
',_i_,' _#_i
.....
.....
'" " :
NORMAL
NO REMARKABLE OBSERVATIONS
.....................................................................................................................................
* *
GROSS
PATHOLOGY
OBSERVATIONS
***
ORGAN NAME
SEVERITY,
KEYWORD(S)
OR PHRASE
FREE-TEXT
COMMENTS AND NOTES
..............................................................................................................................
GENERAL COMMENT
(GC)
-NO MACROSCOPIC
LESIONS
......................................................................................................................................
'
'[i_'-{_
"_i_
,_
'
_ -_j_!:_
''
[ i. !
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...:..,.,J..i'i' _ "
:.:-
:..
".
Cov_
.....................................
Individual
Table 3
Anatomic
Pathology
Data
EXTENDED RECOVERY STUDY FOLLOWING
A 26-WEEK CAPSULE
STUDY
WITH
PERFLUOROOCTANE
SULFONIC ACID POTASSIUM
IN CYNOMOLGDS
MONKEYS
SALT
...............................................................................................
TOXICITY (PFOStT-6295)
Covance 6329-268 PAGE : 2
ANIMAL NUMBER: I05523
SEX:
DATE OF DEATH: 03/09/01 DATE AND TIME OF NECROPSY:
STUDY 03/09/01
POST-FIX WEIGHER: NOT AVAILABLE
MALE
DAY OF 8;07
DOSE GROUP: 1
DEATH: 367 PROSECTOR:
STUDY JOHN
PATHOLOGIST:
AS
SACRIFICE
WEEK OF DEATH: S. HALFORD
ASSIGNED
STATUS: 53
SCHEDULED,
TERMINAL
SACRIFICE
TERMINAL BODY WEIGHT:
4525.0
RECORDER:
TROY CHRISTOFFERSON
WEIGHER"
TROY CHRISTOFFERSON
GRAMS
_ **
LAST
INLIFE
OBSERVATIONS
CATEGORY
KEYWORD
QUALIFIER
/
____ ......................................................................................................................
FREE-TEXT
* ** COMMENT
NORMAL
..........
NO REMARKABLE
OBSERVATIONS
_ .........................................................................................................................
ORGAN NAME
** SEVERITY,
GROSS KEYWORD(S)
PATHOLOGY OR PHRASE
OBSERVATIONS
FREE-TEXT
COMMENTS
** * AND NOTES
..................
T ..........................................................................................................
GENERAL COMMENT
(GC)
. . o . , . . . . o . o , 0 ,
-NO MACROSCOPIC
LESIONS
....................................................................................................................................
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. .... , ....... . _,_._]._-_._:_. ._,._,:_, , .......
.. .....
'. !-.:. :_:_=.ii.;_,,,,.,..,.:..
Table 3
Individual Anatomic 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 PAGE : 5
ANIMAL NUMBER: I05539
SEX; FEMALE
DATE OF DEATH: 03/09/01
STUDY DAY OF
DATE AND TIME OF NECROPSY: 03/09/01 8:50
POST-FIX WEIGHER: NOT AVAILABLE
DOSE GROUP: 1
SACRIFICE
DEATH: 367
STUDY WEEK OF DEATH:
PROSECTOR: JOHN S. HALFORD
PATHOLOGIST: AS ASSIGNED
STATUS: 53
SCHEDULED, TERMINAL SACRIFICE TERMINAL BODY WEIGHT: 4530.0 GRAMS
RECORDER: TROY CHRISTOFFERSON WEIGHER: TROY CHRISTOFFERSON
* * * LAST
INLIFE
OBSERVATIONS
CATEGORY
KEYWORD
QUALIFIER / FREE-TEXT
..........................................................................................................................
* * COMMENT
NORMAL
NO REMARKABLE OBSERVATIONS
....................................................................................................................................
** * GROSS
PATHOLOGY
OBSERVATIONS
**
ORGAN NAME
SEVERITY, KEYWORD(S) OR PHRASE
FREE-TEXT COMMENTS AND NOTES
GENERAL COMMENT
{GC)
..............
.........
o o .....
-NO MACROSCOPIC LESIONS
....................................................................................................................................
o o, ., o ,o . 0 , o ., ,
_',,_. ,,
-22-
II IilI|:1' _.',...'_'...Jl_.............. ........_...-._.'.l.li.iI....1.".1..1.1..1.1.1..1.1YI
: ....
iI'll|'lillin .....-......_..'.=..=...'._.. ":_.."..h:...i..l...=.....'.....-..-."."..=.-.'._.'._...:_..'"..-._.:.".".'".'._.".._..<._..-'.".".t_.;.'",_:_i'_ _ . .:.. --,,:-_<._:,:._-_._t,_-,;:_:-i,;:,_'
_
........... _ :._:_::_:__":__............... '. "_ .."._."..............
' = " C0_n_:_f_%9'_65
........ . ....:'_ v_:.';._,-'.,,."'.,._:_..-,:,._,._: _. _:.,.._,',_:_'::.;_:';.__,.,,_,_ _,_'.,_:._.r._,,'_.__ :::_' ,-
: .' .': .... _..... ..: _.t_-.'_.,..___,':_i_..4:._' _...... :? _;.;. _'_._,_:_;.]._I._,.. _,'b'._,'y".: ..:'L?,"- ', "
:[
,,
,
Covance 6329-268
Table 3
Indivldual Anatomic Pathology Da_a
STUDY WITH PERFLUOROOCTANE IN CYNOMOLGUS MONKEYS
EXTENDED RECOVERY STUDY FOLLOWING A 26-WEEK CAPSULE TOXICITY SULFONIC ACID POTASSIUM SALT (PFOS_T-6295)
PAGE : 4
ANIMAL NUMBER: I05552
SEX: FEMALE
DOSE GROUP: 1
SACRIFICE STATUS:
DATE OF DEATH: 03/09/01
STUDY DAY OF DEATH: 367
STUDY WEEK OF DEATH: 53
DATE AND TIME OF NECROPSY= 03/09/01 POST-FI_ WEIGHER: NOT AVAILABLE
8:48
FROSECTOR: JOHN S. HALFORD PATHOLOGIST: AS ASSIGNED
....................................................................................................................................
SCHEDULED, TERMINAL SACRIFICE
TERMINAL BODY WEIGHT: 2985.0 GRAMS
RECORDER: TROY CHRISTOFFERSON WEIGHER: TROY CHRISTOFFERSON
* * LAST
INL I FE
OBSERVATIONS
CATEGORY
KEYWORD
QUALIFIER / FREE-TEXT
..........................................................................................................................
*** COMMENT
NORMAL
NO REMARKABLE OBSERVATIONS
....................................................................................................................................
* * GROSS
PATHOLOGY
OBSERVATIONS
ORGAN NAME
SEVERITY, KEYWORD(S) OR PHRASE
FREE-TEXT COMMENTS
.............................................................................................................................
AND NOTES
* **
GENERAL COMMENT (GC)
....
. , , . . . . . . o ......
, , ....
-NO MACROSCOPIC LESIONS
....................................................................................................................................
o , o , , . . .....
, ,
__1rjiI
.-,-4!?: :
- 23-
i