Document mrL6eXd48XZ6oDLoqmpm2KdB
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FINAL REPORT
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS
IN RATS SPONSOR'S STUDY NUMBER: 6295.9 FINAL REPORT DATE: 10 JUNE 1999
00133
PROTOCOL 418-008
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS
IN RATS
SPONSOR'S STUDY NUMBER: 6295.9
TABLE OF CONTENTS
SUBJECT
1. SUMMARY AND CONCLUSIONS
A. Methods
B. Results
C. Conclusion
II. DESCRIPTION OF TEST PROCEDURES
A. Conduct of Study
A.1. Sponsor
A.2. Testing Facility
A.3. Study Number
A.4. Sponsor's Study Number
A.5. Purpose of the Study
A.6. Study Design
A.7. Regulatory Compliance
A.8. Ownership of the Study
A.9. Study Monitor
i
PAGE 1-1 1-1 I-5
1-10 11-1 11-1 11-1 11-1 11-1 11-1 11-1 11-1 II-2 II-2 II-2
0134
SUBJECT A.10. Alternate Study Monitor A.11. Study Director A. 12. Technical Performance A.13. Report Preparation A.14. Report Review A.15. Date Protocol Signed A.16. Dates of Technical Performance A. 17. Records Maintained B. Test Article Information B.1. Description B.2. Lot Number B.3. Date Received and Storage Conditions B.4. Special Handling Instructions B. 5. Analysis of Activity C. Vehicle Information C.1. Description C.2. Lot Numbers C.3. Dates Received and Storage Conditions C.4. Special Handling Instructions C. 5. Analysis of Purity D. Test Article Preparation D.1. Sample Information
"
PAGE II-2 II-2 II-2 II-2 II-3 II-3 II-3 II-4 II-4 II-4 II-4 II-5 II-5 II-5 II-5 II-5 II-5 II-5 II-6 II-6 II-6 II-6
000135
SUBJECT D.2. Analytical Results E. Test System E.1. Species E.2. Strain E.3. Supplier (Source) E.4. Sex E.5. Rationale for Test System E.6. Test System Data E.7. Method of Randomization E.8. System of Identification F. Husbandry F.1. Research Facility Registration F.2. Study Rooms F.3. Housing F.4. Lighting F.5. Sanitization F.6. Feed F.7. Feed Analysis F.8. Water F.9. Water Analysis F.10. Bedding F.11. Bedding Analysis
iii
PAGE II-7 II-7 II-7 II-7 II-7 II-7 II-7 II-7 II-8 II-8 II-9 II-9 II-9 II-9
11-10 11-10 11-10 11-10 11-10 11-10 11-11 11-11
0C 0136
SUBJECT G. Methods G.1. Dosage Administration G.2. Assigned Rat Numbers G.3. Rationale for Dosage Selection G.4. Route of Administration G.5. Rationale for Route of Administration G.6. Frequency of Administration G.7. Length of Study G.8. Method of Study Performance G.9. Gross Necropsy G.10. Statistical Analyses III. RESULTS - Fo GENERATION MALE RATS A. Clinical Observations B. Body Weights and Body Weight Changes C. Absolute (g/day) and Relative (g/kg/day)Feed Consumption
Values D. Mating and Fertility E. Necropsy Observations F. Terminal Body Weights, Organ Weightsand Ratios (%) of
Organ Weight to Terminal Body Weight IV. RESULTS - Fo GENERATION FEMALERATS A. Clinical Observations A.1. Mortality
PAGE 11-11 11-11 11-12 11-12 11-12 11-12 11-12 11-13 11-13 11-18 11-21 111-1 111-1 111-1
111-1 III-2 III-2
III-3 IV-1 IV-1 IV-1
IV 0C0137
SUBJECT A.2. Clinical Observations B. Body Weights and Body Weight Changes B.1. Precohabitation B.2. Gestation B.3. Lactation C. Absolute (g/day) and Relative (g/kg/day) Feed Consumption
Values C.1. Precohabitation C.2. Gestation C.3. Lactation D. Estrous Cycling, Mating and Fertility E. Necropsy Observations F. Caesarean-Sectioning and Litter Observations G. Natural Delivery and Litter Observations H. Clinical Observations from Birth to Day 21 Postpartum and
Necropsy Observations I. Reflex and Physical Development 1.1. Surface Righting I.2. Pinna Unfolding 1.3. Eye Opening I.4. Acoustic Startle 1.5. Air Righting 1.6. Pupil Constriction
PAGE IV-1 IV-1 IV-1 IV-2 IV-2
IV-3 IV-3 IV-3 IV-3 IV-4 IV-4 IV ^ IV-4
IV-5 IV-6 IV-6 IV-7 IV-7 IV-7 IV-7 IV-8
v
000138
SUBJECT
PAGE
V. RESULTS - F1 GENERATION MALE AND FEMALE RATS
V-1
A. F1 Generation Male Rats
V-1
A.1. Mortality and Clinical Observations
V-1
A.2. Body Weights and Body Weight Changes
V-2
A.3. Absolute (g/day) and Relative (g/kg/day) Feed Consumption Values
V-2
A.4. Sexual Maturation
V-2
A.5. Passive Avoidance Performance
V-3
A.6. Watermaze Performance
V-3
A.7. Mating and Fertility
V-3
A.8. Necropsy Observations
V-3
A. 9. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight
V-4
B. F1 Generation Female Rats
V-4
B.1. Mortality and Clinical Observations
V-4
B.2. Maternal Body Weights and Body Weight Changes
V-5
B.3. Maternal Absolute (g/day) and Relative (g/kg/day) Feed Consumption Values
V-6
B.4. Sexual Maturation
V-7
B.5. Passive Avoidance Performance
V-7
B.6. Watermaze Performance
V-7
B.7. Mating and Fertility
V-7
B.8. Necropsy Observations
V-8
B.9. Natural Delivery and Litter Observations vi
V-8
000139
SUBJECT
PAGE
B.10. Clinical Observations from Birth to Day 21 Postpartum and Necropsy Observations
V-9
REFERENCES
V-10
APPENDIX A - REPORT FIGURES
Figure 1. Body Weights - Fo Generation Male Rats
A-1
Figure 2. Body Weights - Fo Generation Female Rats
A-2
Figure 3. Body Weights - F1 Generation Male Rats
A-3
Figure 4. Body Weights - F1 Generation Female Rats
A-4
APPENDIX B - REPORT TABLES - Fo GENERATION MALE RATS
Table B1. Clinical Observations - Summary - Fo Generation Male Rats B-1
Table B2. Body Weights - Summary - Fo Generation Male Rats
B-2
Table B3. Body Weight Changes - Summary - Fo Generation Male Rats B-3
Table B4. Absolute Feed Consumption Values (g/day) - Summary Fo Generation Male Rats
B-4
Table B5 Relative Feed Consumption Values (g/kg/day) - Summary Fo Generation Male Rats
B-5
Table B6. Mating and Fertility - Summary - Fo Generation Male Rats B-6
Table B7. Necropsy Observations - Summary - Fo Generation Male Rats B-7
Table B8. Terminal Body Weights and Organ Weights - Summary Fo Generation Male Rats
B-8
Table B9. Ratios (%) of Organ Weight to Terminal Body Weight Summary - Fo Generation Male Rats
B-9
Table B10. Clinical Observations - Individual Data - Fo Generation Male Rats
B-10
Table B11. Body Weights - Individual Data - Fo Generation Male Rats B-20
vii
000140
SUBJECT
PAGE
Table B12. Feed Consumption Values - Individual Data Fo Generation Male Rats
B-30
Table B13. Mating and Fertility - Individual Data - Fo Generation Male Rats
B-40
Table B14. Necropsy Observations - Individual Data - Fo Generation Male Rats
B-50
Table B15. Terminal Body Weights and Organ Weights and Ratios (%) of Organ Weight to Terminal Body Weight - Individual Data - Fo Generation Male Rats
B-58
APPENDIX C - REPORT TABLES - Fo GENERATION FEMALE RATS
Table C1. Clinical Observations - Summary - Fo Generation Female Rats
C-1
Table C2. Body Weights - Precohabitation - Summary - Fo Generation
Female Rats
C-4
Table C3. Body Weight Changes - Precohabitation - Summary Fo Generation Female Rats
C-5
Table C4. Maternal Body Weights - Gestation - Summary Fo Generation Female Rats
C-6
Table C5. Maternal Body Weight Changes - Gestation - Summary Fo Generation Female Rats
C-8
Table C6. Maternal Body Weights - Lactation - Summary Fo Generation Female Rats
C-9
Table C7. Maternal Body Weight Changes - Lactation - Summary Fo Generation Female Rats
C-10
Table C8. Absolute Feed Consumption Values (g/day) Precohabitation - Summary - Fo Generation Female Rats
C-11
Table C9. Relative Feed Consumption Values (g/kg/day) Precohabitation - Summary - Fo Generation Female Rats
C-12
Table C10. Maternal Absolute Feed Consumption Values (g/day) Gestation - Summary - Fo Generation Female Rats
C-13
viii
000141
SUBJECT
PAGE
Table C11. Maternal Relative Feed Consumption Values (g/kg/day) Gestation - Summary - Fo Generation Female Rats
C-14
Table C12. Maternal Absolute Feed Consumption Values (g/day) Lactation - Summary - Fo Generation Female Rats
C-15
T a b le d 3. Maternal Relative Feed Consumption Values (g/kg/day) Lactation - Summary - Fo Generation Female Rats
C-16
Table C14. Estrous Cycling, Mating and Fertility - Summary Fo Generation Female Rats
C-17
Table C15. Necropsy Observations - Summary - Fo Generation Female Rats
C-19
Table C16. Caesarean-Sectioning Observations - Summary Fo Generation Female Rats
C-20
Table C17. Natural Delivery Observations - Summary - Fo Generation
Female Rats
C-21
Table C18. Litter Observations (Naturally Delivered Pups) - Summary -
F1 Generation Litters
C-22
Table C19. Clinical Observations from Birth to Day 21 Postpartum Summary -F 1 Generation Pups
C-25
Table C20. Reflex and Physical Development - Summary F1 Generation Litters
C-26
Table C21. Necropsy Observations - Summary - F1 Generation Pups C-31
Table C22. Clinical Observations - Individual Data - Fo Generation Female Rats
C-32
Table C23. Body Weights - Precohabitation - Individual Data Fo Generation Female Rats
C-40
Table C24. Maternal Body Weights - Presumed Gestation Individual Data - Fo Generation Female Rats
C-50
Table C25. Maternal Body Weights - Lactation - Individual Data Fo Generation - Fo Generation Female Rats
C-70
IX
000142
SUBJECT
PAGE
Table C26. Feed Consumption Values - Precohabitation - Individual Data - Fo Generation Rats
C-75
Table C27. Maternal Feed Consumption Values - Presumed Gestation
Individual Data - Fo Generation Female Rats
C-85
Table C28. Maternal Feed Consumption Values - Lactation Individual Data - Fo Generation Female Rats
C-105
Table C29. Estrous Cycling and Days in Cohabitation - Individual Data
Fo Generation Female Rats
C-110
Table C30. Necropsy Observations - Individual Data - Fo Generation
Female Rats
C-115
Table C31. Caesarean-Sectioning Observations - Individual Data Fo Generation Female Rats
C-121
Table C32. Litter Observations (Caesaren-Delivered Embryos) Individual D a ta -F 1 Generation Litters
C-126
Table C33. Embryonal Vital Status - Individual Data - F1 Generation
Litters
C-131
Table C34. Natural Delivery, Implantation Sites, and Pup Viability and Sex - Individual Data - Fo Generation Female Rats/ F1 Generation Litters
C-136
Table C35. Pup Body Weight Litter Averages from Birth to Day 21 Postpartum - Individual Data - F1 Generation Litters
C-141
Table C36. Pup Body Weights from Birth to Day 21 Postpartum Individual Data - F1 Generation Pups
C-146
Table C37. Pup Vital Status and Sex from Birth to Day 21 Postpartum -
Individual Data - F1 Generation Pups
C-176
Table C38. Clinical Observations from Birth to Day 21 Postpartum Individual Data - F1 Generation Pups
C-181
Table C39. Surface Righting - Individual Data - F1 Generation Litters C-182
Table C40. Pinna Folding - Individual Data - F1 Generation Litters
C-193
x 000143
SUBJECT
PAGE
Table C41. Eye Opening - Individual Data - F1 Generation Litters
C-203
Table C42. Acoustic Startle - Individual Data - F1 Generation Litters C-213
Table C43. Air Righting - Individual Data - F1 Generation Litters
C-223
Table C44. Pupil Constriction - Individual Data - F1 Generation Litters C-233
Table C45. Necropsy Observations - Individual Data - F1 Generation
Pups
C-243
APPENDIX D - REPORT TABLES - F1 GENERATION MALE RATS
Table D1. Clinical Observations - Summary - F1 Generation Male Rats
D-1
Table D2. Body Weights - Summary - F1 Generation Male Rats
D-3
Table D3. Body Weight Changes - Summary - F1 Generation Male Rats
D-4
Table D4. Absolute Feed Consumption Values (g/day) - Summary F1 Generation Male Rats
D-5
Table D5. Relative Feed Consumption Values (g/kg/day) - Summary F1 Generation Male Rats
D-6
Table D6. Sexual Maturation - Summary - F1 Generation Male Rats
D-7
Table D7. Passive Avoidance Performance - Summary F1 Generation Male Rats
D-8
Table D8. Watermaze Performance - Summary - F1 Generation Male Rats
D-9
Table D9. Mating and Fertility - Summary - F1 Generation Male Rats D-10
Table D10. Necropsy Observations - Summary - F1 Generation Male Rats
D-11
Table D11. Terminal Body Weights and Organ Weights - Summary F1 Generation Male Rats
D-13
XI
C0144
SUBJECT
PAGE
Table D12. Ratios (%) of Organ Weight to Terminal Body Weight Summary - F1 Generation Male Rats
D-14
Table D13. Clinical Observations - Individual Data - F1 Generation Male Rats
D-15
Table D14. Body Weights - Individual Data - F1 Generation Male Rats D-20
Table D15. Feed Consumption Values - Individual Data - F1 Generation
Male Rats
D-26
Table D16. Sexual Maturation - Individual Data - F1 Generation Male Rats
D-29
Table D17. Passive Avoidance Performance - Individual Data F1 Generation Male Rats
D-30
Table D18. Watermaze Performance - Individual Data - F1 Generation
Male Rats
D-33
Table D19. Mating and Fertility - Individual Data - F1 Generation Male
Rats
D-36
Table D20. Necropsy Observations - Individual Data - F1 Generation Male Rats
D-39
Table D21. Terminal Body Weights and Organ Weights and Ratios (%)
of Organ Weight to Terminal Body Weight - Individual Data -
F1 Generation Male Rats
D-43
APPENDIX E - REPORT TABLES - F1 GENERATION FEMALE RATS
Table E1. Clinical Observations - Summary - F1 Generation Female Rats
E-1
Table E2. Body Weights - Precohabitation - Summary - F1 Generation
Female Rats
E-4
Table E3. Body Weight Changes - Precohabitation - Summary F1 Generation Female Rats
E-5
Table E4. Maternal Body Weights - Gestation - Summary F1 Generation Female Rats
E-6
XII
00145
SUBJECT
PAGE
Table E5. Maternal Body Weight Changes - Gestation - Summary F1 Generation Female Rats
E-8
Table E6. Maternal Body Weights - Lactation - Summary F1 Generation Female Rats
E-9
Table E7. Maternal Body Weight Changes - Lactation - Summary F1 Generation Female Rats
E-10
Table E8. Absolute Feed Consumption Values (g/day) Precohabitation - Summary - F1 Generation Female Rats
E-11
Table E9. Relative Feed Consumption Values (g/kg/day) Precohabitation - Summary - F1 Generation Female Rats
E-12
Table E10. Maternal Absolute Feed Consumption Values (g/day) Gestation - Summary - F1 Generation Female Rats
E-13
Table E11. Maternal Relative Feed Consumption Values (g/kg/day) Gestation - Summary - F1 Generation Female Rats
E-14
Table E12. Maternal Absolute Feed Consumption Values (g/day) Lactation - Summary - F1 Generation Female Rats
E-15
Table E13. Maternal Relative Feed Consumption Values (g/kg/day) Lactation - F1 Generation Female Rats
E-16
Table E14. Sexual Maturation - Summary - F1 Generation Female Rats E-17
Table E15. Passive Avoidance Performance - Summary F1 Generation Female Rats
E-18
Table E16. Watermaze Performance - Summary - F1 Generation Female Rats
E-19
Table E17. Mating and Fertility - Summary - F1 Generation Female Rats
E-20
Table E18. Necropsy Observations - Summary - F1 Generation Female Rats
E-21
Table E19. Natural Delivery Observations - Summary - F1 Generation
Female Rats
E-22
XIII O C0146
SUBJECT
PAGE
Table E20. Litter Observations (Naturally Delivered Pups) Summary - F2 Generation Litters
E-23
Table E21. Clinical Observations from Birth to Day 21 Postpartum Summary - F2 Generation Pups
E-26
Table E22. Necropsy Observations - Summary - F2 Generation Pups E-27
Table E23. Clinical Observations - Individual Data - F1 Generation Female Rats
E-28
Table E24. Body Weights - Precohabitation - Individual Data - F1 Generation Female Rats
E-34
Table E25. Maternal Body Weights - Presumed Gestation - Individual Data - F1 Generation Female Rats
E-37
Table E26. Maternal Body Weights - Lactation - Individual Data F1 Generation Female Rats
E-43
Table E27. Feed Consumption Values - Precohabitation - Individual Data - F1 Generation Female Rats
E-46
Table E28. Maternal Feed Consumption Values - Presumed Gestation -
Individual Data - F1 Generation Female Rats
E-49
Table E29. Maternal Feed Consumption Values - Lactation - Individual
Data - F1 Generation Female Rats
E-52
Table E30. Sexual Maturation - Individual Data - F1 Generation Female Rats
E-55
Table E31. Passive Avoidance Performance - Individual Data F1 Generation Female Rats
E-56
Table E32. Watermaze Performance - Individual Data - F1 Generation
Female Rats
E-59
Table E33. Days in Cohabitation - Individual Data - F1 Generation Female Rats
E-62
Table E34. Necropsy Observations - Individual Data - F1 Generation Female Rats
E-63
XIV 0 0 1 4 7
SUBJECT
PAGE
Table E35. Natural Delivery, Implantation Sites, and Pup Viability and Sex - Individual Data - F1 Generation Female Rats/ F2 Generation Litters
E-67
Table E36. Pup Body Weight Litter Averages from Birth to Day 21 Postpartum - Individual Data - F2 Generation Litters
E-70
Table E37. Pup Body Weights from Birth to Day 21 Postpartum Individual Data - F2 Generation Pups
E-73
Table E38. Pup Vital Status and Sex from Birth to Day 21 Postpartum -
Individual Data - F2 Generation Pups
E-91
Table E39. Clinical Observations from Birth to Day 21 Postpartum Individual Data - F2 Generation Pups
E-94
Table E40. Necropsy Observations - Individual Data - F2 Generation Pups
E-95
APPENDX F - PROTOCOL AND AMENDMENTS
F-1 to F-63
APPENDIX G - DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY
G-1
APPENDIX H - TEMPERATURE AND RELATIVE HUMIDITY REPORTS
H-1 to H-9
APPENDIX I- STATEMENT OF THE STUDY DIRECTOR
1-1
APPENDIX J - QUALITY ASSURANCE UNIT FINAL REPORT STATEMENT
J-1 to J-8
xv
000148
TITLE:
418-008 PAGE 1-1
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS
ARGUS RESEARCH LABORATORIES, INC. PROTOCOL NUMBER: 418-008 SPONSOR'S STUDY NUMBER: 6295.9
I. SUMMARY AND CONCLUSION
A. Methods8
Text Figure 1 provides a schematic of the study design.
A.1. Fo Generation Rats/F1 Generation Litters:
One hundred seventy-five male and female Crl:CDBR VAF/Plus (SpragueDawley) rats were assigned to five dosage groups (Groups I through V), 35 rats per sex per dosage group. The rats were administered the test article, PFOS, or the vehicle, 0.5% Tween 80, orally (via gavage). The dosages were 0 (Vehicle), 0.1, 0.4, 1.6 and 3.2 mg/kg/day. The male rats were dosed once daily beginning 42 days before cohabitation and continuing through the day before sacrifice. The female rats were dosed once daily beginning 42 days before cohabitation and continuing through DGb9 (rats assigned to Caesareansectioning), DG 24 (rats assigned to natural delivery that did not deliver a litter), or DLC20 (rats that did deliver a litter). The dosage volume was 5 mL/kg.
All Fo generation rats were observed for viability at least twice daily during the study and for clinical signs of effects of the test article twice daily during the dosage period. Body weights and feed consumption values for male rats were recorded weekly during the dosage period and at sacrifice. Body weights for female rats were recorded weekly to cohabitation, daily during the gestation period, on DLs 1, 4, 7, 10 and 14 (rats assigned to natural delivery) and at sacrifice. Feed consumption values were recorded weekly to cohabitation, daily during the gestation period and on DLs 1, 4, 7, 10 and 14 (rats assigned to natural delivery).
a. Detailed descriptions of all procedures used in the conduct of this study are provided in the appropriate sections of this report and in APPENDIX F (PROTOCOL AND AMENDMENTS).
b. DG is used as an abbreviation for day of (presumed) gestation. c. DL is used as an abbreviation for day of lactation or day postpartum.
0C0149
418-008.PAGE I-2
The first ten female rats per dosage group with a confirmed date of mating were assigned to Caesarean-sectioning on DG 10. The remaining female rats were permitted to naturally deliver litters. These rats were evaluated for clinical observations during parturition, duration of gestation, litter size and pup viability at birth. Maternal behavior of the dams was evaluated daily when the pups were examined during the 21-day postpartum period.
Each litter was evaluated for viability at least twice each day during the 21-day postpartum period. Pups in each litter were counted once daily. Physical signs in the pups were recorded once daily for 21 days postpartum. Pup body weights and observed nursing behavior were recorded on DLs 1 (birth), 4, 7, 14 and 21. Surface righting reflex, pinna unfolding, eye opening, acoustic startle response and air righting reflex were monitored during the 21-day postpartum period until all pups in the litter reached the criterion for the specific test. Pupil constriction was evaluated once on DL 21. On DL 4, a table of random units was used to cull litters to four male and four female pups, where possible. On DL 21, a table of random units was used to select two male and two female pups from each litter from Groups I, II and III for continued evaluation.
Fo generation male rats were sacrificed after completion of the cohabitation period and necropsied; gross lesions were retained. The testes, epididymides, prostate and seminal vesicles (with and without fluid) were excised, individually weighed and retained.
Fo generation female rats assigned to Caesarean-sectioning were sacrificed on DG 10 and necropsied; pregnancy status was confirmed. Ovaries and gross lesions were retained. The rats were examined for the number and distribution of corpora lutea in each ovary and implantation sites, and viable and nonviable embryos. Embryos were discarded after examination.
Fo generation female rats assigned to natural delivery were sacrificed on DL 21 and necropsied. Ovaries and gross lesions were retained. The number and distribution of implantation sites was recorded.
At scheduled sacrifice after completion of the cohabitation period (male rats that sired litters of dams allowed to naturally deliver a litter) and on DL 21 (female rats allowed to naturally deliver a litter), blood samples (approximately 4 mL per rat) were collected from the inferior vena cava from five male and five female rats per dosage group and shipped to the Sponsor for pharmacokinetic analysis.
Pups not selected for continued evaluation on DL 4 were sacrificed and necropsied. The stomach contents (milk curd) were collected from all culled pups from five of the largest litters in Groups I, II and III, frozen and shipped to the Sponsor for analysis.
000150
418-008:PAGE I-3 The liver from each rat was excised, weighed, and a sample section (lateral lobe) was frozen and shipped to the Sponsor for analysis. The livers of the pups from the litters of the five dams in Groups I through IV selected for pharmacokinetic sample collection were excised, pooled per litter, frozen and shipped to the Sponsor for analysis. Dams in the 3.2 mg/kg/day dosage group (Group V) did not have surviving pups on DL 21.
A.2. F1 Generation Rats/F2 Generation Litters:
Only the 0.1 and 0.4 mg/kg/day dosage groups were continued into the second generation because of the excessive toxicity seen in the 1.6 and 3.2 mg/kg/day F1 generation pups.
There were 150 male and female F1 generation rats in the three dosage groups (Groups I through III), 25 rats per sex per dosage group. F1 generation male and female rats were given appropriate dosages of the test article orally (gavage) beginning on DL 22 and continuing through the day before sacrifice.
Beginning at 24 days of age, one male rat and one female rat from each litter in each dosage group were tested in a passive avoidance paradigm. Female rats were evaluated for the age of vaginal patency beginning on DL 28. Male rats were evaluated for the age of preputial separation beginning on DL 34. On postpartum day 70, one male rat and one female rat from each litter were evaluated in a water-filled M-maze. On approximately DL 90, rats within each dosage group were assigned to cohabitation.
F1 generation male rats were sacrificed after completion of the cohabitation period and necropsied, as previously described for the Fo generation male rats. All F1 generation female rats were permitted to naturally deliver litters. All dams that delivered litters were sacrificed on DL 21 and necropsied, as previously described for the Fo generation female rats.
On DL 21, all F2 generation pups were sacrificed and examined for gross lesions. Necropsy procedures were the same as those described for the F1 generation pups.
CCC151
Protocol 418-008: Combined Oral (Gavage) Fertility, Development and Perinatal/Postnatal Reproduction Toxicity Study of PFOS in Rata
MALE
Acclimation 14 d a y
Cohabitation 14 d a y
Pharmacokinetic Sample Cottoctioft S/group |
Fo Mala Rata Sacrificed
35 F, Mata Rata/Dosage Group Arrive at
Tatting Facility
O01 Period Bogina lor
W alt Rata
FEMALE
Eatrout AcdimaUon I Evaluation Cohabitation
35 Ft Fornaio Ooaing Rata/Ooaaga Period Group Arrivo at Bogina for
Tatting Facility Fornaio Rata
OG 10
C- Sectioning 10/group
D o ting Period Ends
for Mala Rats
DO 10
la i Potatio OaNvory (DO 21)
Last Potsibie Oefivery (DG 25)
PARTURITION Lactation Day 1 (OL 1)
Dosing Ported Ends for Femais Rats (OL 20)
Pharmacokinetic Sample Cofiection 5/group
I
Day of Sacrifie# (DL 21)
F I GENERATION
OosinQPeriod Bogina for FI Gonoration Rata
Cohabitation
1st Possible Delivery (DO 21)
Last P olitola Dallvary (OG2S)
e o o
On
w
OL 1
C uing:
25 mal and 25 (amalo pupa/group
continued on study (DU 4)
i
REFLEX AND PHYSICAL DEVELOPMENT: Surtaca R i^tUng. P to n i UftfoUine. Eya OparUftfi. Aooutbc
fo a rtia . A * R ighting R atax. P upl C oiuirictten
SEXUAL MATURATION:
OC 20: Vaginal Patancy OL 39. Prapwtial Sapaia lIon
P A S S IV E
Maternal M i* Collection (Groupa I, Hand V)
(v a ite i from OL 1 through OL 21)
A V O ID A N C E :
DL 24*1 daya 1 mala and 1
(m ala pup/Utter
A bbreviation:
DG * Day o f (Presum ed) G estation DL * Day o f Lactation
Dosage Period
WATERMAZE: OL 70.1 mala a n t 1 temolo pupAttor
0190
DGO E a riie il day of sacrifica for F1 mala rata
PARTURITION Lactation Day 1 (DL 1)
Last Potatola Day of
Doting for Mala and Female F1 R a il (DL 20)
F2 GENERATION
SACRIFICE OF F I DAMS/ F I UTTERS: OL 21
51 & T1 (O'
C
(B
418-008:PAGE I-4
B. Results
418-008:PAGE I-5
B.1. Fo Generation Male Rats:
No Fo generation male rats died during this study as a result of treatment with PFOS. All clinical observations (other than normal) were considered unrelated to the test article and not signs of compound toxicity.
Groups administered 0.4 mg/kg/day and higher dosages of the test article had reduced body weight gains for the entire study.
Absolute and relative feed consumption values were reduced in the 1.6 and 3.2 mg/kg/day dosage groups for the entire precohabitation period. After the cohabitation period, absolute feed consumption values were significantly reduced in the 0.4 and 1.6 mg/kg/day dosage groups.
Dosages of the test article as high as 3.2 mg/kg/day did not affect any mating and fertility parameters evaluated.
A significantly increased number of male rats in the 3.2 mg/kg/day dosage group had a light brown or brown liver, an observation attributed to effects of PFOS.
The 1.6 and 3.2 mg/kg/day dosage groups had significantly reduced terminal body weights. The absolute weights of the seminal vesicles with fluid and the prostate were significantly reduced in the 3.2 mg/kg/day dosage group.
B.2. Fo Generation Female Rats/F1 Generation Litters:
No Fo generation female rats died during this study as a result of treatment with PFOS.
Observations of localized alopecia were increased during the precohabitation, gestation and lactation periods in the 0.4, 1.6 and 3.2 mg/kg/day dosage groups.
Groups administered 1.6 mg/kg/day and higher dosages of the test article had significantly reduced body weight gains for the entire precohabitation period. The 1.6 and 3.2 mg/kg/day dosages of PFOS continued to reduce body weights and body weight gains during gestation. The 3.2 mg/kg/day dosage group had significantly reduced body weight on DL 1. Body weight gains tended to be reduced in the 0.4 mg/kg/day dosage group on DLs 1 to 4, when significant weight loss occurred in the 1.6 mg/kg/day dosage group (the 3.2 mg/kg/day dosage group was precluded from further evaluation because all pups died before DL 2).
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418-008:PAGE I-6
Absolute and relative feed consumption values were reduced in the 1.6 and 3.2 mg/kg/day dosage groups during the precohabitation period. The 1.6 and 3.2 mg/kg/day dosage groups continued to have reduced absolute and relative feed consumption values early in the gestation period. Absolute and relative maternal feed consumption values tended to be reduced in the 0.4 mg/kg/day dosage group and were significantly reduced in the 1.6 mg/kg/day dosage group for the entire lactation period, and at most intervals within this period. The 3.2 mg/kg/day dosage group was precluded from evaluation because there were no surviving pups after DL 1.
Dosages of the test article as high as 3.2 mg/kg/day did not affect estrous cycling in the 15 rats per dosage group that were evaluated. Mating and fertility parameters were unaffected by the 3.2 mg/kg/day dosage of PFOS.
All necropsy observations were considered unrelated to treatment.
There were no biologically important or statistically significant differences in the litter averages for corpora lutea, implantations, viable embryos or nonviable embryos at Caesarean-sectioning on DG 10.
The duration of gestation was significantly reduced in the 3.2 mg/kg/day dosage group, an observation associated with preimplantation loss [the average number of implantation sites per dam was significantly reduced, resulting in a significantly reduced litter size]. Pup viability was significantly reduced in the 1.6 and 3.2 mg/kg/day dosage groups. Reflecting these effects, the viability and lactation indices were significantly reduced in the 1.6 and 3.2 mg/kg/day dosage groups, the lactation index was also significantly reduced in the 1.6 mg/kg/day dosage group, as also were the averages for surviving pups in the 1.6 mg/kg/day dosage group beginning on DL 4 postculling, and in the 3.2 mg/kg/day dosage group on DL 1.
A dosage-dependent pattern of reduced pup body weight was evident in each group administered the test article. The 0.1 mg/kg/day dosage group tended to have reduced pup weights on DL 4 (pre- and postculling), compared to the control group value. The 0.4 mg/kg/day dosage group tended to have reduced pup body weights on DLs 1 through 4 (postculling), compared to the control group value. However, none of the differences in the 0.1 and 0.4 mg/kg/day dosage groups were statistically significant and may represent normal biological variations. The 1.6 mg/kg/day dosage group had significantly reduced pup body weights on all weighing days. The 3.2 mg/kg/day dosage group had a significantly reduced pup body weight on DL 1 (no pups survived to subsequent scheduled weighings).
Clinical and necropsy observations associated with reduced pup viability and potential reduction in maternal care occurred in the 3.2 mg/kg/day dosage group.
000154
418-008:PAGE I-7
Adverse clinical observations include three litters with pups that were not nursing (two of these litters had pups from which the placenta had not been removed, and one had pups that were not nested). Apparent maternal cannibalization was also evident in this dosage group (missing tail in one pup and a cannibalized forelimb in another pup). It was not possible to determine whether these occurred before or after these pups had died.
Necropsy observations in pups that were stillborn or found dead indicated many pups with no milk in the stomach in the 1.6 and 3.2 mg/kg/day dosage group pups. The 3.2 mg/kg/day dosage group also had evidence of increased maternal cannibalization at necropsy of stillborn and found dead pups. Nine of these pups had missing hindlimbs and/or portion of the tail.
Reversible delays in reflex and physical development that are highly correlated with body weight occurred in the 0.4 and 1.6 mg/kg/day dosage groups. Surface righting was delayed in the 1.6 and 3.2 mg/kg/day dosage groups. The time of development for pinna unfolding, eye opening, acoustic startle reflex and ability to air right were delayed in the 1.6 mg/kg/day dosage group (no 3.2 mg/kg/day dosage group pups were evaluated for this parameter). All live pups in the 0 (Vehicle), 0.1, 0.4 and 1.6 mg/kg/day dosage groups had the pupil constriction response when testing was done on DL 21 (end of lactation).
Upon weaning of the litters (DL 21), a decision was made regarding the F1 generation pups in the 1.6 mg/kg/day dosage group. The 1.6 mg/kg/day dosage group pups were small (they had gained 20% less weight during lactation than the control pups) and in the opinion of the attending laboratory veterinarian, the rats were not suitable for further experimentation. It had been determined that the dosage of 1.6 mg/kg/day was a level which produced compound toxicity. Continued dosing of 1.6 mg/kg/day most likely would not result in any additional information and would subject the pups to additional distress. Therefore, consultation with the Sponsor lead to the decision not to continue the 1.6 mg/kg/day dosage group F1 generation pups. Only the 0 (Vehicle), 0.1 and 0.4 mg/kg/day dosage group pups were continued to a second generation.
B.3. F1 Generation Male Rats:
No deaths in the F1 generation male rats at 0.1 and 0.4 mg/kg/day dosages were attributed to PFOS. All clinical observations were considered unrelated to the test article.
The 0.1 and 0.4 mg/kg/day dosage groups tended to weigh less than the control group on day 1 postweaning and generally gained one or two grams less body weight per week than the control group rats. Reflecting this pattern of weight gain, weight gains in the 0.1 and 0.4 mg/kg/day dosage groups for the precohabitation period were 98.4% and 97.6% of the control group value,
0C0155
418-008:PAGE I-8
respectively. Body weight gains in the 0.1 and 0.4 mg/kg/day dosage groups for day 1 to termination were 98.5% and 96.6% of the control group value, respectively. However, none of these body weight gain differences were statistically significant from control values.
Absolute feed consumption values for the 0.1 and 0.4 mg/kg/day dosage groups were significantly reduced on postweaning days 1 through 8. Relative feed consumption values tended to be reduced in the 0.1 and 0.4 mg/kg/day dosage groups during the first week of intubation but none were statistically significant.
Dosages of the test article as high as 0.4 mg/kg/day did not affect the average day of preputial separation in the F1 generation male rats. There were no biologically important differences in the values for learning, short-term retention, long-term retention or response inhibition in the F1 generation male rats, as evaluated by performance in a passive avoidance or watermaze performance paradigm.
Dosages of the test article as high as 0.4 mg/kg/day did not affect any mating and fertility parameters evaluated in the F1 generation male rats.
All necropsy observations in the F1 generation male rats were considered unrelated to the test article because. No statistically significant differences occurred in the absolute or relative values for the weights of the right or left testis, seminal vesicles, right epididymis or prostate. Terminal body weights tended to be reduced in the 0.1 and 0.4 mg/kg/day dosage groups but were not statistically significant from control values.
B.4. F1 Generation Female Rats/F2 Generation Litters:
No deaths in the F1 generation female rats were attributed to PFOS. All adverse clinical observations that occurred during the precohabitation, gestation and lactation periods were considered unrelated to the test article.
Body weights tended to be reduced in the 0.4 mg/kg/day dosage group on day 1 postweaning. Maternal body weights and body weight gains during the gestation period were unaffected by dosages of the test article as high as 0.4 mg/kg/day. Significant maternal body weight loss occurred on DLs 1 to 4 in the 0.4 mg/kg/day dosage group.
The 0.4 mg/kg/day dosage of the test article was associated with a significant reduction in absolute feed consumption and a tendency for reduced relative feed consumption on days 1 to 8 postweaning. Absolute and relative feed consumption values during the gestation period were unaffected by dosages of the test article as high as 0.4 mg/kg/day. The absolute and relative maternal
000156
418-008:PAGE I-9 REVISED PAGE
feed consumption values were reduced during lactation in the 0.4 mg/kg/day dosage group. Dosages of the test article as high as 0.4 mg/kg/day did not affect the average day of vaginal patency in the F1 generation female rats. There were no biologically important differences in the values for learning, short-term retention, long-term retention or response inhibition in the F1 generation female rats, as evaluated by performance in a passive avoidance or watermaze performance paradigm. Dosages of the test article as high as 0.4 mg/kg/day did not affect any mating and fertility parameters evaluated in the F1 generation female rats. All necropsy observations in the F1 generation female rats were considered unrelated to the test article. Pregnancy occurred in 22 (95.6%), 21 (84.0%) and 24 (96.0) of the 23, 25 and 25 female rats assigned to cohabitation in the 0 (Vehicle), 0.1 and 0.4 mg/kg/day dosage groups, respectively. All pregnant dams delivered litters. The gestation index was comparable across the three dosage groups. Viability and growth of the second generation offspring (F2 pups) to weaning were also unaffected by the highest dosage tested, 0.4 mg/kg/day. There were no toxicologically important differences from the control group values. No clinical or necropsy observations in the F2 generation pups were attributable to dosages of the test article as high as 0.4 mg/kg/day
C0157
C. Conclusions
418-008:PAGE 1-10 REVISED PAGE
On the basis of these data, the Fo generation maternal and paternal no observable-effect-level (NOEL) of PFOS is 0.1 mg/kg/day (0.4 mg/kg/day and higher dosages caused reductions in body weight gain and reduced feed consumption values).
The Fo generation reproductive NOEL is greater than 3.2 mg/kg/day; no effects on mating, fertility or estrous cycling occurred. The NOEL for viability and growth in the F1 generation offspring is 0.4 mg/kg/day (1.6 mg/kg/day and higher dosages caused preimplantation loss and reductions in litter size, pup viability, growth and survival).
The F1 generation maternal and paternal NOEL of PFOS is 0.1 mg/kg/day (0.4 mg/kg/day dosage caused reductions in body weight gain and reduced feed consumption values).
The F1 generation reproductive NOEL is greater than a dosage of 0.4 mg/kg/day; no effects on mating or fertility occurred. The NOEL for viability and growth in the F2 generation offspring is also 0.4 mg/kg/day. There were no toxicologically important effects on pup survival or growth at the highest dosage tested, 0.4 mg/kg/day.
/
Mildred S. Christian, Ph.D., Fellow, ATS Date Executive Director of Research
OC0158
II. DESCRIPTION OF TEST PROCEDURES
418-008PAGE 11-1
A. Conduct of Study:
A.1. Sponsor:
3M Toxicology Services, 3M Center, Building 220-2E-02, St. Paul, Minnesota 55144-1000
A.2. Testing Facility:
Argus Research Laboratories, Inc., 905 Sheehy Drive, Building A, Horsham, Pennsylvania 19044-1297
A.3. Study Number:
418-008
A.4. Sponsor's Study Number:
6295.9
A.5. Purpose of the Study:
The purpose of this study was to test for toxic effects/disturbances resulting from PFOS treatment of Crl:CDBR VAF/Plus male and female rats before cohabitation through mating, gestation and lactation. This study was designed to evaluate ICH Harmonised Tripartite Guideline stages A through F of the reproductive process and detect effects on the estrous cycle, tubal transport, implantation, gestation, parturition, lactation and maternal behavior in female rats, on the development of the offspring of the treated male and female rats, and permit detection of functional effects (e.g., effects on libido or epididymal sperm maturation) that may not be detected by histological examinations of male rat reproductive organs. Because manifestations of effects induced during this period may be delayed in the offspring, observations were continued through production of F2 generation litters.
A.6. Study Design:
A modification of the requirements of U.S. Food and Drug Administration (FDA)(1) were used as a basis for the study design.
CC0159
A.7. Regulatory Compliance:
418-008:PAGE II-2
The study was conducted in compliance with the Good Laboratory Practice (GLP) regulations of the U.S. Food and Drug Administration (FDA)(2), the Japanese Ministry of Health and Welfare (MHW)<3) and the European Economic Community (EEC)(4>. There were no significant deviations from the GLP regulations that affected the quality or integrity of the study. Quality Assurance Unit findings derived from the inspections during the conduct of this study are documented and have been provided to the Study Director and the Testing Facility Management.
A.8. Ownership of the Study:
The Sponsor owns the study. All raw data, analyses, reports and all preserved tissues are the property of the Sponsor.
A.9. Study Monitor:
Marvin T. Case, D.V.M., Ph.D.
A.10. Alternate Study Monitor:
Andrew M. Seacat, Ph.D.
A.11. Study Director:
Raymond G. York, Ph.D., DABT (Associate Director of Research)
A.12. Technical Performance:
John F. Barnett, B.S. (Director of Laboratory Operations) Kristen landola Sherer, B.S. (Research Associate/Fetal Evaluation) Joseph W. Lech, B.S. (Team Leader - General Laboratory) Sharon Adamski (Laboratory Technician)
A.13. Report Preparation
Raymond G. York, Ph.D., DABT Michelle R. Rzaca, B.S. (Study Coordinator) Heidi M. Green, M.S. (Study Coordinator) Erin Hagan, B.A. (Data Management Specialist) Karen G. Parker, A.A. (Report Administrator)
0C0160
A.14. Report Review:
418-008: PAG E II-3
Alan M. Hoberman, Ph.D., DABT (Director of Research) Mildred S. Christian, Ph.D., Fellow, ATS (Executive Director of Research)
A.15. Date Protocol Signed:
21 May 1998
A.16. Dates of Technical Performance:
Fo Generation Male Rats
Rat Arrival Date Dosage Period (42 days before cohabitation, through a 14-day cohabitation
period and until sacrifice) Scheduled Sacrifice
12 MAY 98
26 MAY 98 - 30 JUL 98 31 JUL 98
Fo Generation Female Rats
Rat Arrival Date
12 MAY 98
Dosage Period - Female Rats Assigned to
Caesarean-Sectioning (42 days before
cohabitation and continuing through DGa9) 26 MAY 9 8 - 1 7 JUL 98
Dosage Period - Female Rats Assigned to
Natural Delivery [42 days before
cohabitation through DG 24 (rats that did
not deliver a litter) or DLb20 (rats that delivered
a litter)
26 MAY 98 - 30 AUG 98
Dosage Period Estrous
Cycle Evaluation
09 JUN 98 - 06 JUL 98
a. DG is used as an abbreviation for day of (presumed) gestation. b. DL is used as abbreviation for day of lactation.
0G01S1
(Fo Generation Female Rats Continued)
418-008:PAGE II-4
Cohabitation Period Male 1 Male 2
DG 10 Caesarean-Sectioning Natural Delivery Period (DL 1) DG 25 Sacrifice (rats that did not deliver
a litter) DL 21 Sacrifice (dams and pups not
selected for continued study)
06 JUL 98 PM - 13 JUL 98 AM 13 JUL 98 PM - 20 JUL 98 AM
17 JUL 9 8 - 3 0 JUL 98 28 JUL 9 8 - 1 0 AUG 98
01 AUG 98 - 07 AUG 98
17 AUG 9 8 - 3 0 AUG 98
F1 Generation Rats
Dosage Period (Male Rats)
19 AUG 9 8 - 1 6 NOV 98
Dosage Period (Female Rats)
19 AUG 9 8 - 2 7 DEC 98
Passive Avoidance Testing
20 AUG 9 8 - 1 0 SEP 98
Watermaze Testing
07 OCT 9 8 - 1 9 OCT 98
Cohabitation Period (Initiated when the rats are
approximately 90 days of age)
Male 1
02 NOV 98 PM - 09 NOV 98 AM
Male 2
09 NOV 98 PM - 16 NOV 98 AM
Male Rats Sacrificed
17 NOV 98
Natural Delivery Period (DL 1)
24 NOV 98 - 08 DEC 98
DL 21 Sacrifice
14 DEC 9 8 - 2 8 DEC 98
A.17. Records Maintained:
The original report, raw data and reserve samples of the bulk test article and vehicle components are retained in the archives of Argus Research Laboratories, Inc. Any preserved tissues are retained in the archives of the Testing Facility for one year after mailing the draft final report, after which time the Sponsor will decide their final disposition. All unused test article suspensions were discarded at the Testing Facility. Unused bulk test article was returned to the Study Monitor.
B. Test Article Inform ation:
B.1. Description:
PFOS - an off-white powder
B.2. Lot Number:
217 (Expiration Date: May 2000)
000162
B.3. Date Received and Storage Conditions:
418-008:PAGE II-5
The test article was received on 20 May 1998, and stored at room temperature. Prepared suspensions were stored at room temperature overnight.
B.4. Special Handling Instructions:
Standard safety precautions (use of protective clothing, gloves, dust-mist respirator and safety goggles) were taken when handling the bulk test article and prepared suspensions.
B. 5. Analysis of Activity:
Information regarding the purity, identity, strength and composition of the test article is on file with the Sponsor.
C. Vehicle Information:
C.1. Description:
0.5% Tween 80 in reverse osmosis membrane processed deionized water (R.O. deionized water).
C.2. Lot Numbers:
M03H05, K03737, M29477 and L06662
C.3. Dates Received and Storage Conditions:
The Tween 80 was received from J.T. Baker, Phillipsburg, New Jersey, on 15 August 1997 (Lot K03737), 22 May 1998 (Lot M03H05), 17 September 1998 (Lot M29477), 3 December 1998 (Lot M03H05) and 1 September 1998 (Lot L06662), and was stored at room temperature. R.O. deionized water is available from a continuous source at the Testing Facility and is maintained at room temperature. The vehicle was prepared weekly and stored at room temperature.
0C01S3
C.4. Special Handling Instructions:
418-008:PAGE II-6
Standard safety precautions (use of protective clothing, gloves, dust-mist respirator, safety goggles or safety glasses and a face-shield) were taken when handling the vehicle.
C. 5. Analysis of Puritv:
Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to be present in the vehicle that would interfere with the results of this study.
D. Test Article Preparation:
Suspensions of PFOS were prepared daily one day prior to the day of dosing at concentrations of 0, 0.02, 0.08, 0.32 and 0.64 mg/mL. The test article was considered 100% pure for the purpose of dosage calculations.
D.1 Sample Information:
Sample Type
Size
Date Retained
Shipping/Storage Conditions
Shipped To Date Shipped
Concentration (all levels) Homogeneity
5 mL* 5 mL 5 mL 5 mL
5 mLb
26 MAY 98 29 JUN 98 21 DEC 98 27 DEC 98
26 MAY 98
Room temperature Sponsor Room temperature Sponsor
26 MAY 98 29 JUN 98 04 JAN 98 04 JAN 98
26 MAY 98
Vehicle Component Reserve Tween 80 R.O. Water
5 mL 5 mL
25 MAY 98 10 SEP 98
10 NOV 98 25 MAY 98
Room temperature
Testing Facility Archives
09 JUL 98 01 OCT 98 25 NOV 98
09 JUL 98
a. A syringe was used to withdraw samples from each concentration during the first and sixth week of dosage administration for the Fo generation and during the first* and last weeks of dosage administration for the F1 generation. Each sample was divided into two aliquots (2 mL and 3 mL, respectively). One aliquot (2 mL) was shipped for analysis. The other aliquot (3 mL) was retained at the Testing Facility as a backup.
b. A syringe was used to withdraw samples from the top, middle and bottom of the highest concentration on the first day of preparation. Each sample was divided into two aliquots (2 mL and 3 mL, respectively). One aliquot (2 mL) was shipped for analysis. The other aliquot (3 mL) was retained at the Testing Facility as a backup.
Stability data for prepared formulations bracketing the range of concentrations are on file with the Sponsor. The Sponsor confirmed a 48-hour stability on the test article in 0.5% Tween 80 solutions.
a. See APPENDIX G (DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY), item 1.
D. 2. Analytical Results:
418-008PAG E II-7
Results of the concentration and homogeneity analyses were not available at the time of the writing of this report.
E. Test System:
E.1. Species:
Rat
E.2. Strain:
Crl:CDBR VAF/Plus (Sprague-Dawley)
E.3. Supplier (Source):
Charles River Laboratories, Inc., Raleigh, North Carolina
E.4. Sex:
Male and Female
E.5, Rationale fo r Test System:
The Crl:CDBR VAF/Plus (Sprague-Dawley) rat was selected as the Test System because: 1) this strain of rat has been demonstrated to be sensitive to reproductive and developmental toxins and has been widely used throughout industry for reproductive and developmental toxicity evaluations; 2) historical data and experience exist at the Testing Facility*5"7*; and 3) the test article is pharmacologically active in the species and strain.
E.6. Test System Data:
Male Rats
Female Rats
Number of Rats Approximate Date of Birth Approximate Age at Arrival Weight (g) on the Day after Arrival Weight (g) at Study Assignment
195 12 MAR 98
62 days 282 - 338 334 - 396
205 12 MAR 98
62 days 172-239 209 - 242
E.7. Method of Randomization:
418-008: PAGE 11-8
E.7.a. Fo Generation Rats
Upon arrival, Fo generation rats were assigned to individual housing on the basis of computer-generated random units. After acclimation, male and female rats were selected for study on the basis of physical appearance and body weights recorded during acclimation. Rats were assigned to five dosage groups (Groups I through V), 35 rats per sex per dosage group, using a computergenerated (weight-ordered) randomization procedure.
The first ten female rats per dosage group with a confirmed mating date were assigned to Caesarean-sectioning on DG 10. The remaining rats were permitted to naturally deliver litters.
A table of random units was used to assign five rats per group to pharmacokinetic sample collection either at scheduled sacrifice after completion of the cohabitation period (male rats siring litters with dams allowed to naturally deliver a litter) or on DL 21 (female rats allowed to naturally deliver a litter).
E.7.b. F1/F2 Generation Pups
On DL 4, a table of random units was used to select the pups to be culled and litters were reduced to eight pups each. Whenever possible, the same number of male and female pups per litter were continued on study.
At weaning of the F1 generation pups on DL 21, a table of random units was used to select 25 male and 25 female pups in each of Groups I, II and III, resulting in a total of 150 F1 generation rats (75 per sex) chosen for continued evaluation. At least one male pup and one female pup per litter were selected. There were no surviving pups in Group V after DL 2; pups in Group IV were not continued on the study because of severe toxic effects in the pups (death and retarded growth) during lactation. This decision was made in consultation with the study veterinarian and the Sponsor.
E.8. System of Identification:
E.8.a. Fo Generation
Rats were permanently identified using Monel self-piercing ear tags (Gey Band and Tag Co., Inc., No. MSPT 20101). Male and female rats were assigned temporary numbers at receipt and given unique permanent identification numbers when assigned to the study before administration of the first dosage of the test article.
E. 8.b. F1/F2 Generation Pups and Rats
418-008:PAGE II-9
Pups were not individually identified during lactation; all parameters were evaluated in terms of the litter both before and after culling on DL 4. At weaning, each F1 generation rat selected for continued observation was identified with a Monel self-piercing ear tag.
F. Husbandry:
F.1. Research Facility Registration:
USDA Registration No. 23-R-099 under the Animal Welfare Act, 7 U.S.C. 2131
e t seq.
F.2. Study Rooms:
The study rooms were maintained under conditions of positive airflow relative to a hallway and independently supplied with a minimum often changes per hour of 100% fresh air that had been passed through 99.97% HEPA filters. Room temperature and humidity were monitored constantly throughout the study. Room temperature was targeted at 64F to 79F (18C to 26C); relative humidity was targeted at 30% to 70%. See APPENDIX H (TEMPERATURE AND RELATIVE HUMIDITY REPORTS).
F.3. Housing:
All cage sizes and housing conditions were in compliance with the G u id e fo r the
C a re a n d U se o f L a b o ra to ry A n im a ls {8).
F.3.a. Fo Generation Rats/F1 Generation Litters
Fo generation rats were individually housed in stainless steel wire-bottomed cages except during the cohabitation and postpartum periods. During cohabitation, each pair of rats was housed in the male rat's cage. Beginning no later than DG 20, Fo generation female rats assigned to natural delivery were individually housed in nesting boxes. Each dam and delivered litter were housed in a common nesting box during the postpartum period.
F.3.b. F1 Generation Rats/F2 Generation Litters
After weaning, the F1 generation rats were individually housed before cohabitation, housed in pairs (one male rat per female rat) during cohabitation, and individually housed after cohabitation. The same type of caging was used as described for the Fo generation rats. Beginning no later than DG 20, F1 generation female rats were individually housed in nesting boxes. Each dam
CC01S7
418-008:PAGE 11-10
and delivered litter were housed in a common nesting box during the postpartum period.
F.4. Lighting:
An automatically-controlled fluorescent light cycle was maintained at 12-hours light: 12-hours dark, with each dark period beginning at 1900 hours EST.
F.5. Sanitization:
Cage pan liners were changed approximately three times each week. Cages were changed approximately every other week. Bedding was changed as often as necessary to keep the rats dry and clean.
F.6. Feed:
Rats were given a d lib itu m access to Certified Rodent Diet #5002 (PMI Nutrition International, Inc., St. Louis, Missouri) in individual feeders.
F.7. Feed Analysis:
Analyses were routinely performed by the feed supplier. No contaminants at levels exceeding the maximum concentrations for certified feed or deviations from expected nutritional requirements were detected by these analyses. Copies of the results of the feed analyses are available in the raw data.
Neither the Study Director nor the Sponsor was aware of any agent present in the feed that was known to interfere with the results of this study.
F.8. Water:
Local water that had been processed by passage through a reverse osmosis membrane (R.O. water) was available to the rats a d lib itu m from an automatic watering access system and/or individual water bottles. Chlorine was added to the processed water as a bacteriostat.
F.9. Water Analysis:
The processed water is analyzed twice annually for possible chemical contamination (Lancaster Laboratories, Inc., Lancaster, Pennsylvania) and monthly for possible bacterial contamination (Analytical Laboratories, Inc., Chalfont, Pennsylvania). Copies of the results of the water analyses are available in the raw data.
168
418-008: PAGE 11-11
Neither the Study Director nor the Sponsor was aware of any agent present in the water that was known to interfere with the results of this study.
F.10. Bedding:
Bed-o'cobs was used as nesting material (The Andersons Industrial Products Group, Maumee, Ohio).
F. 11. Bedding Analysis:
Neither the Sponsor nor the Study Director was aware of any potential contaminants likely to be present in the bedding that would interfere with the results of this study. Analyses for possible contamination are conducted annually and documented in the raw data.
G. Methods:
G.1. Dosage Administration:
Dosage Group
I II III IV V
Dosage (mg/kg/day)
0 (Vehicle) 0.1 0.4 1.6 3.2
Concentration (mg/mL)
Dosage Volume (ml_/kg)
Number of Fo Generation Rats
Per Sex
05 0.02 5 0.08 5 0.32 5 0.64 5
35 35 35 35 35
Number of F1 Generation Rats
Per Sex
25
25
25 _
-
The test article was considered 100% pure for the purpose of dosage calculations.
crcjf>9
G.2. Assigned Rat Numbers:
418-008:PAGE 11-12
Dosage Group
1 II III IV V
Assigned Fo Generation Rat Numbers
Male
Female
8101-8135
8801-8835
8136-8170
8836-8870
8171-8205
8871-8905
8206-8240
8906-8940
8241-8275
8941-8975
Assigned F1 Generation Rat Numbers
Male
Female
13101-13125
13201 -1 3 2 2 5
13126-13150
13226-13250
13151-13175 a
13251-13275 A
bB
a. On DL 21, all surviving pups in the 1.6 mg/kg/day dosage group (Group IV) were sacrificed because of severe toxic effects in the pups during lactation.
b. There were no surviving pups after DL 2 in the 3.2 mg/kg/day dosage group (Group V).
G.3. Rationale for Dosage Selection:
Dosages were selected by the Sponsor on the basis of previous studies conducted with the test article.
G.4. Route of Administration:
Oral (gavage)
G.5. Rationale for Route of Administration:
The oral (gavage) route was selected for use because: 1) in comparison with the dietary route, the exact dosage can be accurately administered: and 2) it is one of the possible routes of human exposure.
G.6. Freguencv of Administration:
The Fo generation male rats were given appropriate dosages of the test article once daily beginning 42 days before cohabitation (which continued for a maximum of 14 days) and continuing through the day before sacrifice.
The Fo generation female rats were given the appropriate dosages of the test article beginning 42 days before cohabitation (which continued for a maximum of 14 days) and continuing through DG 9 (rats assigned to Caesarean-sectioning), DG 24 (rats assigned to natural delivery that did not deliver a litter), or DL 20 (rats that did deliver a litter). The dosage volume (5 mL/kg) was adjusted daily on the basis of the most recently recorded body weight and given at approximately the same time each day3.
a. See APPENDIX G, item 2.
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Dams in the process of delivering pups were not dosed until completion of parturition, in order to preclude possible disruption of maternal behavior and/or cannibalization of the pups. Consequently, some dams were not administered one daily dosage during the delivery period. No dam missed more than one daily dosage.
F1 generation male and female rats were given appropriate dosages of the test article orally (gavage), beginning on day 1 postweaning (DL 22)a and continuing through the day before sacrifice. F2 generation pups were not directly given the test article, but may have been possibly exposed to the test article during gestation (in u te ro exposure) or via maternal milk during the lactation period.
G.7. Length of Study:
Approximately 7 months
G.8. Method of Study Performance:
G.8.a Fo Generation Rats
All Fo generation rats were observed for viability at least twice daily during all periods of the study. Rats were also observed for general appearance at least once during the acclimation period and for clinical observations of effects of the test article, abortions, premature deliveries, prior to and approximately one hour after dosage and on the day sacrificed.
Body weights for Fo generation male rats were recorded at least once during the acclimation period, weekly during the dosage period and at sacrifice. Feed consumption values for male rats were recorded weekly during the dosage period.
Body weights for Fo generation female rats were recorded at least once during the acclimation period, weekly to cohabitation, daily during the gestation period, on DLs 1,4, 7, 10 and 14 (rats assigned to natural delivery) and at sacrifice. Feed consumption values were recorded weekly to cohabitation, daily during the gestation period and on DLs 1,4, 7, 10 and 14 (rats assigned to natural delivery). Feed consumption values were not recorded after DL 14, when it was expected that the pups would begin to consume maternal feed. A table of random units was used to select 15 female rats per dosage group for evaluation of estrous cycling by examination of vaginal cytology for 28 days before the start of the cohabitation period.
a. See APPENDIX G, item 3.
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Within each dosage group, consecutive order was used to assign rats to cohabitation, one male rat per female rat. The cohabitation period consisted of a maximum of 14 days. During cohabitation, all female rats were evaluated daily until observation of spermatozoa in a smear of the vaginal contents and/or a copulatory plug in s itu (DG 0), following which they were assigned to individual housing. Female rats that did not mate within the first seven days of cohabitation were assigned alternate male rats that had mated (within the same dosage group) and remained in cohabitation for a maximum of seven additional days.
The first ten female rats per dosage group with a confirmed mating date were assigned to Caesarean-sectioning on DG 10. The female rats assigned to Caesarean-sectioning were examined for the number and distribution of corpora lutea, implantation sites and viable and nonviable fetuses. The remaining female rats were permitted to naturally deliver litters. These rats were evaluated for clinical observations during parturition, duration of gestation (DG 0 to the day the first pup was observed), litter size (all pups delivered) and pup viability at birth. Pups that either appeared stillborn or that died before initial examination of the litters for viability were examined for vital status at birth. The lungs were removed and immersed in water. Pups with lungs that sank were considered stillborn; pups with lungs that floated were considered liveborn and to have died shortly after birth. Each litter was subsequently examined daily for pup viability. Maternal behavior of the dams was evaluated daily when the pups were examined during the 21-day postpartum period. Observed maternal behavior was recorded on DLs 1, 4, 7, 14 and 21. Variations from expected maternal behavior were recorded, if and when present, on all other days of the postpartum period.
Fertility parameters were assessed for all dams assigned to natural delivery. These parameters included the fertility index (percentage of matings that resulted in pregnancies), gestation index (percentage of pregnancies that resulted in the birth of live litters), number of offspring per litter (live and dead pups), number of implantation sites, general condition of the dam and litter during the postpartum period, viability indices (percentage of pups born that survived 4 and 7 days), and lactation index (percentage of pups born that survived 21 days).
G.8.b F1/F2 Generation P u p s - Preweanina Observations
Day 1 of lactation (postpartum) was defined as the day of birth and was also the first day on which all pups in a litter were individually weighed (pup body weights were recorded after all pups in a litter were delivered and groomed by the dam).
Vital status at birth was determined for pups that either appeared stillborn or that died before initial examination of the litter for viability. Pups that either appeared
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stillborn or that died before initial examination of the litter for viability were examined for vital status at birth, as previously described.
Each litter was evaluated for viability at least twice each day during the 21-day postpartum period. Pups in each litter were counted once daily. Physical signs (including variations from expected nursing behavior and gross external physical anomalies) in the pups were recorded once daily for 21 days postpartum. Dead pups observed at these times were removed from the nesting box. When not precluded by autolysis or cannibalization by the dam, any pup found dead was necropsied and examined for the cause of death. Pup body weights were recorded on DLs 1 (birth), 4, 7, 14 and 21.
Reflex and physical development parameters in the F1 generation pups only were monitored during the 21-day postpartum period. Surface righting reflex [ability to right in 5 seconds (from DL 1)], pinna unfolding (from DL 2), eye opening (from DL 12), acoustic startle response (from DL 13) and air righting reflex (from DL 14) were monitored until all pups (100%) in the litter reached the criterion for the specific test. Pupil constriction was evaluated once on DL 21; the number of pups per litter with this reflex present was recorded.
G.8.C. F1 Generation Rats - Postweaninq Observations
"Postweaning day" observations were recorded beginning on DL 22. All F1 generation rats were observed for viability at least twice daily during all periods of the study. Rats were also observed for general appearance at least once during the acclimation period and for clinical observations of effects of the test article, abortions, premature deliveries prior to and approximately one hour after dosage and on the day sacrificed.
Body weights for F1 generation female rats were recorded weekly during the postweaning periods and at sacrifice. Feed consumption values were recorded weekly except during cohabitation and at sacrifice.
Body weights for F1 generation female rats were recorded once weekly to cohabitation, daily during presumed gestation, on DLs 1, 4, 7 and 14 (rats assigned to natural delivery) and at sacrifice. Feed consumption values were recorded weekly to cohabitation, on DGs 0, 7, 10, 14, 17 and 20 and DLs 1,4, 7, 10 and 14.
Beginning at 24 days of age, one male rat and one female rat from each litter in each dosage group were tested for learning, short-term retention and long-term retention in a passive avoidance paradigm. Each rat was tested on two days, separated by a one-week interval; the criterion for learning was the same for both days of testing. The passive avoidance apparatus consisted of a twocompartment chamber with hinged Plexiglas lids. One compartment was
0 0 0 1 .7 3
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outfitted with a bright light and Plexiglas floor. The other compartment was outfitted with a grid floor to which a brief (1 second) pulse of mild electric current (1 mA) was delivered. The two compartments were separated by a sliding door.
During each trial, the rat was placed into the "bright" compartment, the sliding door was opened and the light was turned on. The rat was allowed to explore the apparatus until it entered the "dark" compartment. The sliding door was then immediately closed, the light was turned off, and the brief pulse of current was delivered to the grid floor. The rat was then removed from the apparatus and placed into a holding cage for 30 seconds before the start of the next trial. Trials were repeated until the rat remained in the "bright" compartment continuously for 60 seconds on each of two consecutive trials (the criterion for learning) or until 15 trials were completed. The latency to enter the dark compartment or the maximum 60-second interval was recorded for each trial.
Dosage groups were compared on the following dependent measures: the number of trials to the criterion in the first session (overall learning performance); the latency (in seconds) to enter the "dark" compartment from the "bright" compartment on trial 1 of the first test session (activity level and exploratory tendency in a novel environment); the latency (in seconds) to enter the "dark" compartment from the "bright" compartment on trial 2 in the first test session (short-term retention); the number of trials to the criterion in the second test session (long-term retention); and the latency (in seconds) to enter the "dark" compartment from the "bright" compartment on trial 1 in the second test session (long-term retention).
On postpartum day 70, one male rat and one female rat from each litter were evaluated in a water-filled M-maze for overt coordination, swimming ability, learning and memory. Each rat was tested in a watertight 16-gauge stainless steel modified M-maze. The maze was filled with water to a depth of approximately nine inches, and the water was monitored for temperature (range of 21 C 1C). On each test trial, the rat was placed into the starting position (base of the M-maze stem farthest from the two arms) and required to swim to one of the two goals of the M-maze, in order to be removed from the water. On the first trial, the rat was required to enter both arms of the maze before being removed from the water. The initial arm chosen on trial 1 was designated the incorrect goal during the remaining trials. Rats that failed to make a correct goal choice within 60 seconds in any given trial were guided to the correct goal and were then removed from the water. A 15-second intertrial interval separated each trial. Each rat was required to reach a criterion of five consecutive errorless trials to terminate the test session. The maximum number of trials in any test session was 15. Latency (measured in seconds) to choose the correct goal or the maximum 60-second interval was recorded for each trial, as was the number of errors (incorrect turns in the maze) during each trial.
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Each rat was tested twice. The test sessions were separated by a one-week interval; the correct goal and the criterion were the same for both test sessions. Dosage groups were compared for the following dependent measures: the number of trials to criterion on the first day of testing; the average number of errors (incorrect turns in the maze) for each trial on the first day of testing; the latency (in seconds) to reach the correct goal on trial 2 of the first day of testing; the number of trials to criterion on the second day of testing; the average number of errors for each trial on the second day of testing; and the latency (in seconds) to reach the correct goal on trial 1 of day 2 of testing.
Female rats were evaluated for the age of vaginal patency, beginning on DL 28. Male rats were evaluated for the age of preputial separation, beginning on DL 34.
On DLs 85 to 98, the F1 generation rats within each dosage group were assigned to cohabitation, one male rat per female rat, based on random unit tables, with the exclusion of sibling matings. The cohabitation period consisted of a maximum of 14 days. Female rats with spermatozoa observed in a smear of the vaginal contents and/or a copulatory plug observed in s itu were considered to be at DG 0 and assigned to individual housing. Female rats that did not mate within the first 7 days of cohabitation were assigned alternate male rats from the same dosage group that had mated. Female rats were allowed to naturally deliver and maintain litters through a 21-day postpartum period.
These rats were evaluated for clinical observations during parturition, duration of gestation (DG 0 to the day the first pup was observed), litter size (all pups delivered) and pup viability at birth. Pups that either appeared stillborn or that died before initial examination of the litters for viability were examined for vital status at birth. The lungs were removed and immersed in water. Pups with lungs that sank were considered stillborn; pups with lungs that floated were considered liveborn and to have died shortly after birth. Each litter was subsequently examined daily for pup viability. Maternal behavior of the dams was evaluated daily when the pups were examined during the 21-day postpartum period. Observed maternal behavior was recorded on DLs 1,4,7, 14 and 21. Variations from expected maternal behavior were recorded, if and when present, on all other days of the postpartum period. Fertility parameters were assessed for all dams assigned to natural delivery. These parameters included the fertility index (percentage of matings that resulted in pregnancies), gestation index (percentage of pregnancies that resulted in the birth of live litters), number of offspring per litter (live and dead pups), number of implantation sites, general condition of the dam and litter during the postpartum period, viability indices (percentage of pups born that survived 4 and 7 days), and lactation index (percentage of pups born that survived 21 days).
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G.9. Gross Necropsy*:
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G.9.a Fo Generation Male and Female Rats Assigned to Pharmacokinetic Sample Collection
At scheduled sacrifice after completion of the cohabitation period (male rats that sired litters of dams allowed to naturally deliver a litter) and on DL 21 (female rats allowed to naturally deliver a litter) blood samples (approximately 4 mL per rat) were collected from five rats per dosage group from the inferior vena cava, into serum separator tubes and centrifuged. The resulting serum (approximately 2 mL) was immediately frozen on dry ice and maintained frozen (-70C) until shipment to the Sponsor for analysis. The liver was excised, weighed, and a sample section (lateral lobe) was frozen and retained at -7 0 C until shipment to the Sponsor for analysis.
The liver of each pup from the litters of the five dams in each of Groups I through IV that were selected for pharmacokinetic sample collection was excised, pooled per litter, frozen and retained at -70C, until shipment to the Sponsor for analysis. The dams in the 3.2 mg/kg/day dosage group (Group V) did not have surviving pups on DL 21.
G.9.b. Fo and F1 Generation Male Rats
Male rats were sacrificed by carbon dioxide asphyxiation after completion of the cohabitation period, and a gross necropsy of the thoracic, abdominal and pelvic viscera was performed. Gross lesions were retained in neutral buffered 10% formalin for possible future evaluation. Representative photographs of gross lesions are available in the raw data. The following organs were excised, individually weighed and retained for possible histologic evaluation: testes, epididymides, prostate and seminal vesicles (with and without fluid). The testes were fixed in Bouin's solution for 48 to 96 hours and then retained in neutral buffered 10% formalin for possible histopathological evaluation. The remaining organs were retained in neutral buffered 10% formalin.
G.9.c. Fo Generation Female Rats Assigned to Caesarean-Sectioning
Female rats assigned to Caesarean-sectioning were sacrificed on DG 10, and a gross necropsy of the thoracic, abdominal and pelvic viscera was performed. Uteri of apparently nonpregnant rats were stained with 10% ammonium sulfide to confirm the absence of implantation sites(9). All ovaries and gross lesions were
a. A table of random units was used to select one control group Fo and F1 generation rat from each sex from which all tissues examined at necropsy were retained, in order to provide control tissues for possible histopathological evaluations of gross lesions.
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retained in neutral buffered 10% formalin for possible future evaluation. Representative photographs of gross lesions are available in the raw data. The rats were examined for the number and distribution of corpora lutea in each ovary and implantation sites, and viable and nonviable embryos. A viable embryo was oval or crescent shaped, pink, firm and enclosed in an amniotic sac filled with clear fluid. A nonviable embryo was amorphous, small, pale pink to tan or deep red to black, soft and enclosed in an amniotic sac filled with clear, cloudy, or opaque fluid. Embryos were discarded after examination.
G.9.d. Fo Generation Female Rats Assigned to Natural Delivery and F1 Generation Female Rats
At the completion of the 21-day postpartum period, all dams that delivered litters were sacrificed on DL 21, and a gross necropsy of the thoracic, abdominal and pelvic viscera was performed. The number and distribution of implantation sites was recorded. Female rats assigned to natural delivery that did not deliver a litter were sacrificed on DG 25 and examined for gross lesions. To confirm the pregnancy status, uteri from rats that appeared nonpregnant were stained with 10% ammonium sulfide(9). Dams with no surviving pups were sacrificed after the last pup was found dead, missing or presumed cannibalized. A gross necropsy of the thoracic, abdominal and pelvic viscera was performed. All ovaries were retained in neutral buffered 10% formalin for possible future evaluation.
Rats that died were examined for the cause of death on the day the observation was made. The rats were examined for gross lesions. Pregnancy status and uterine contents were recorded. Ovaries were retained in neutral buffered 10% formalin.
G.9.e. F1/F2 Generation P u p s
On DL 21, F1 generation pups not continued on study and all F2 generation pups were sacrificed and examined for gross lesions. Necropsy procedures were the same as those used for pups culled on DL 4.
Pups that died before examination of the litter for pup viability were evaluated for vital status at birth, as described previously. Pups found dead were examined for gross lesions and for the cause of death. Pups with gross lesions found on DLs1 to 4 were preserved in Bouin's solution. Gross lesions from pups found on DLs 5 to 21 were preserved in neutral buffered 10% formalin. Representative photographs of pup gross lesions are available in the raw data.
Pups not selected for continued evaluation on DL 4 were sacrificed by carbon dioxide asphyxiation and examined for gross lesions. Necropsy included a single cross-section of the head at the level of the frontal and parietal suture and examination of the cross-sectioned head for apparent hydrocephaly. The
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418-008:PAGE II-20 stomach contents (milk curd) were collected from culled pups from Groups I, II and III. Samples were collected from all pups from five of the largest litters in these three dosage groups. Individual pup samples were combined by litter into polypropylene tubes and frozen at -20C. After completion of sample collection, samples were shipped (frozen on dry ice) to the Sponsor for analysis.
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G.10. Statistical Analyses:
418-008PAGE 11-21
The following schematic represents the statistical analyses of the data:
Type of Test3
I. Parametric1* A. Bartlett's Testd
II. Nonparametricc
A. Kruskal-Wallis Test (^75% ties)
Significant at ps 0.05
Not Significant
Significant atp^0.05
Nonparametric Analysis of Variance
Dunn's Test
Not Significant
Significant at p<. 0.05
Not Significant
B. Fisher's Exact Test (>75% ties)
Dunnett's Test
III. Test for Proportion Data
Variance Test for Homogeneity of the Binomial Distribution
a. Statistically significant probabilities are reported as either p<0.05 or p<0.01. b. Used only to analyze data with homogeneity of variance. c. Proportion data are not included in this category. d. Test for homogeneity of variance.
418-008.PAGE II-22 Proportion data were analyzed using the Variance Test for Homogeneity of the Binomial Distribution'10'. Continuous data (e.g., body weights, body weight changes and feed consumption data) were analyzed using Bartlett's Test of Homogeneity of Variances'11' and the Analysis of Variance'12', when appropriate [i.e., Bartlett's Test was not significant (p>0.05)]. If the Analysis of Variance was significant {p z 0.05), Dunnett's Test'13' was used to identify the statistical significance of the individual groups. If the Analysis of Variance was not appropriate [i.e., Bartlett's Test was significant (ps0.05)], the Kruskal-Wallis Test'14' was used (<;75% ties). In cases where the Kruskal-Wallis Test was statistically significant (p<,0.05), Dunn's Method of Multiple Comparisons'15' was used to identify the statistical significance of the individual groups. If there were greater than 75% ties, Fisher's Exact Test'16' was used. Fisher's Exact Test'16' was also used to evaluate necropsy data for the pups which were stillborn or found dead. Data obtained at Caesarean-sectioning, natural delivery, preweaning reflex/physical developmental data and postweaning behavioral data involving discrete data (e.g., number of corpora lutea, number of pups per litter, trials to a criterion), were evaluated by the Kruskal-Wallis Test'14', as described above.
CGOISO
III. RESULTS - Fo GENERATION MALE RATS
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A. Clinical Observations (Summary - Table B1: Individual Data Table B10)
No Fo generation male rats died during this study.
All clinical observations were considered unrelated to the test article because the incidences were not dosage-dependent and/or the observation occurred in only one or two rats. These observations included localized alopecia on the limbs, comeal opacity, dental problems (missing, broken or misaligned incisors), abrasion on the neck, hyperactivity, excess salivation, chromodacryorrhea, swollen snout, chromorhinorrhea and dyspnea.
B. Body Weights and Body Weight Changes (Figure 1: Summaries Tables B2 and B3; Individual Data - Table B11)
Groups administered 0.4 mg/kg/day and higher dosages of the test article had reduced body weight gains. The values were significantly reduced (ps0.05 or p^O.01) in the 0.4 mg/kg/day dosage group on days 56 to 63 of study (DSs 56 to 63); in the 1.6 mg/kg/day dosage group on DSs 29 to 36; and in the 3.2 mg/kg/day dosage group on DSs 15 to 22, 29 to 36, 36 to 42 and 56 to 63. Reflecting these effects of the test article, body weight gains were significantly reduced (ps0.01) for the entire precohabitation period (DSs 1 to 42) in the 1.6 and 3.2 mg/kg/day dosage groups. The 0.4, 1.6 and 3.2 mg/kg/day dosage groups had significantly reduced (p<0.05 or p<0.01) body weight gains for the entire study, calculated from DSs 1 to 63 or from DS 1 to termination.
Body weights were significantly reduced (p*0.05) in the 1.6 mg/kg/day dosage group on DSs 56, 63 and at study termination. The 3.2 mg/kg/day dosage group had significantly reduced (p<0.01) body weights on DSs 36, 42, 56, 63 and at study termination.
Body weights and body weight changes were unaffected by the 0.1 mg/kg/day dosage of the test article.
C. Absolute fq/davl and Relative (q/ka/dav) Feed Consumption Values (Summaries - Tables B4 and B5: Individual Data - Table B121
Relative feed consumption values were significantly reduced (p<0.05) in the 1.6 and 3.2 mg/kg/day dosage groups on DSs 8 to 15. Absolute (g/day) and relative (g/kg/day) feed consumption values were significantly reduced (psO.01) in the 3.2 mg/kg/day dosage group on DSs 15 to 22, 29 to 36 and 36 to 42. As a result of these effects of the test article, absolute and relative feed consumption values were reduced and/or significantly reduced in these two dosage groups for
eccisx
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the entire precohabitation period (DSs 1 to 42). After the cohabitation period (DSs 56 to 63), absolute feed consumption values were significantly reduced (p<0.05 or p<0.01) in the 0.4 and 1.6 mg/kg/day dosage groups. Absolute and relative feed consumption values were significantly reduced in the 3.2 mg/kg/day dosage group during this period.
Absolute and relative feed consumption were unaffected by the 0.1 mg/kg/day dosage of the test article.
D. Mating and Fertility (Summary - Table B6: Individual Data Table B13)
Dosages of the test article as high as 3.2 mg/kg/day did not affect any mating and fertility parameters evaluated. Values for the fertility and pregnancy indices (number of pregnancies per number of rats in cohabitation and rats that mated, respectively), the number of days to inseminate, the number of rats that mated and the number of rats with confirmed mating dates during the first week of cohabitation were comparable among the five dosage groups.
E. Necropsy Observations (Summary - Table B7: Individual Data Table B14)
A significantly increased (p<0.01) number of male rats in the 3.2 mg/kg/day dosage group had a light brown or brown liver, an observation attributed to effects of PFOS. The gross lesions of the liver were considered related to the test article because the incidences were dosage-dependent.
One 1.6 mg/kg/day dosage group rat (8214) and three 3.2 mg/kg/day dosage group rats (8245, 8252, 8257) had small, flaccid and/or purple testes3. All four of these male rats mated but did not impregnate a female rat. One 3.2 mg/kg/day dosage group male rat (8243) had a small prostate; this rat impregnated a female rat. The gross lesions observed in the testes and prostate were not considered test article-related as they are common findings in control group male rats and did not vary from Historical Control incidence at the Testing Facility. No other male rats had gross lesions of the reproductive organs.
All other necropsy observations were considered unrelated to the test article because: 1) the observation occurred in only one rat in a group; or 2) the incidences were not dosage-dependent. These observations included a large liver, a liver with a rough surface, constricted papillary process of the liver with
a. In 2079 control group rats from 91 studies conducted at the Testing
Facility from August, 1992 to April, 1999, there were 21 rats with small flaccid and/or purple testes.
0C0IS2
418-008:PAGE III-3 pinpoint raised tan areas, opaque lens of the eye, large kidneys, kidneys with cysts in the parenchyma, dilation of the renal pelvis and a large spleen.
F. Terminal Body Weights. Organ Weights and Ratios 1% ) of Organ Weight to Terminal Body Weight (Summaries - Tables B8 and B9: Individual Data - Table B15)
The 1.6 and 3.2 mg/kg/day dosage groups had significantly reduced (ps0.05 and p 0.01, respectively) terminal body weights. The absolute weights of the seminal vesicles with fluid and the prostate were significantly reduced (p<;0.05 or p0.01) in the 3.2 mg/kg/day dosage group, compared to the control group. Epididymides and testes weights and weights of the seminal vesicles without fluid were unaffected by dosages of the test article as high as 3.2 mg/kg/day. The ratios of the weight of the left and right testes to terminal body weights were significantly increased (p0.01) in the 3.2 mg/kg/day dosage group, as compared to the control group values. These observations were associated with the significantly reduced (p<;0.01) terminal body weights in this dosage group. The ratios of the weights of the epididymides, seminal vesicles and prostate were generally comparable among the five dosage groups.
CCQ1S3
IV. RESULTS - Fo GENERATION FEMALE RATS
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A. Clinical Observations (Summary - Table C1: Individual Data Table C22)
A.1. Mortality
No deaths were attributable to PFOS. The only death occurred in a 1.6 mg/kg/day dosage group rat, an event attributable to an intubation accident.
Female rat 8938 in the 1.6 mg/kg/day dosage group was moribund sacrificed on study day (DS) 36 after administration of 35 daily dosages. Adverse clinical observations included chromodacryorrhea and a clear oral exudate on DSs 35 to 36, and ptosis, hunched posture and labored breathing on DS 36. Observations of chromodacryorrhea and ptosis were confirmed at necropsy; all other tissues appeared normal at necropsy. This rat lost body weight and had reduced feed consumption on DSs 29 to 36. The clinical observations indicated this rat was misintubated on or about DS 35. All other Fo generation female rats survived to scheduled sacrifice.
A. 2. Clinical Observations
Observations of localized alopecia were increased during the precohabitation, gestation and lactation periods in the 0.4, 1.6 and 3.2 mg/kg/day dosage groups. The incidence of localized alopecia at any area was significantly increased (p<0.05 or p<0.01) in the 0.4, 1.6 and 3.2 mg/kg/day dosage groups during the gestation period. The incidence of localized alopecia on the back was significantly increased (p<0.01) in the 3.2 mg/kg/day dosage group during the lactation period.
All other clinical observations during the precohabitation, gestation and lactation periods were considered unrelated to the test article because: 1) the incidences were not dosage-dependent; and/or 2) the observation occurred in only one rat. These observations included chromodacryorrhea and dental problems (missing, broken or misaligned incisors). Clear oral exudate, ptosis, hunched posture and labored breathing occurred during the precohabitation period in the 1.6 mg/kg/day rat that was moribund sacrificed, as previously described.
B. Body Weights and Body Weight Changes (Figure 2:Summaries Tables C2 through C7: Individual Data - Tables C23 through C251
B.1. Precohabitation
Groups administered 1.6 mg/kg/day and higher dosages of the test article had significantly reduced (p<0.01) body weight gains for the entire precohabitation
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period (DSs 1 to 42). During this period, values were significantly reduced (p<;0.01) in the 1.6 mg/kg/day dosage group on DSs 29 to 36; and in the 3.2 mg/kg/day dosage group on DSs 8 to 15, 22 to 29 and 29 to 36, as compared with the control group value. Body weights were significantly reduced (p<;0.01) in the 3.2 mg/kg/day dosage group on DSs 15, 22, 29, 36 and 42, as compared with the control group values.
Body weights and body weight gains during the precohabitation period were unaffected by dosages of the test article as high as 0.4 mg/kg/day.
B.2. Gestation
The 1.6 and 3.2 mg/kg/day dosages of PFOS continued to reduce body weights and body weight gains during gestation. Reflecting effects that occurred during the precohabitation period, the 1.6 mg/kg/day dosage group tended to weigh less and the 3.2 mg/kg/day dosage group weighed significantly less (p<0.01) than the control group on day 0 of gestation (DG 0). Weight gain was significantly reduced (p<.0.05) in the 1.6 mg/kg/day dosage group on DGs 0 to 7 and then essentially comparable to the control group values at all intervals throughout the remainder of gestation, beginning with DGs 10 to 12. Weight gains were significantly reduced in the 3.2 mg/kg/day dosage group on DGs 0 to 7 and 10 to 12, after which this group also had weight gains comparable to the control group. Reflecting these effects, body weight gains were significantly reduced (p^0.01) in the 3.2 mg/kg/day dosage group for the entire gestation period (DGs 0 to 20) and body weights were significantly reduced (p<,0.05 or ps0.01) in the 1.6 and 3.2 mg/kg/day dosage groups on DGs 3 through 11 and 0 through 20, respectively.
Body weights and body weight gains during gestation were unaffected by dosages of the test article as high as 0.4 mg/kg/day.
B.3. Lactation
The 3.2 mg/kg/day dosage group had significantly reduced (p<0.01) body weight on DL 1, as compared with the control group value. Body weight gains tended to be reduced in the 0.4 mg/kg/day dosage group on DLs 1 to 4, when significant weight loss (psO.01) occurred in the 1.6 mg/kg/day dosage group (the 3.2 mg/kg/day dosage group was precluded from further evaluation because all pups died before DL 2). A significant increase (p 0.05) in body weight gain on DLs 10 to 14 in the 1.6 mg/kg/day dosage group was possibly associated with reduced litter size and associated with reduced milk demand and production.
Body weights and body weight gains during lactation were unaffected by the 0.1 mg/kg/day dosage of the test article.
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C. Absolute (g/dav) and Relative (g/kq/dav) Feed Consumption Values /Summaries - Tables C8 through C13: Individual Data - Tables C26 through C281
0.1. Precohabitation
Absolute (g/day) and relative (g/kg/day) feed consumption values were reduced in the 1.6 and 3.2 mg/kg/day dosage groups during the precohabitation period. These effects were significant (p<;0.05 or ps0.01) in the 1.6 mg/kg/day dosage group on DSs 22 to 29 and 29 to 36 (absolute only), and in the 3.2 mg/kg/day dosage group at most tabulated intervals. Reflecting these effects of the test article, the 3.2 mg/kg/day dosage group had significantly reduced (psO.01) absolute and relative feed consumption values for the entire precohabitation period (DSs 1 to 42).
Feed consumption values during the precohabitation period were unaffected by dosages of the test article as high as 0.4 mg/kg/day.
C.2. Gestation
The 1.6 and 3.2 mg/kg/day dosage groups continued to have reduced absolute and relative feed consumption values early in the gestation period. Absolute and relative feed consumption values were significantly reduced (p<;0.05 or p<;0.01) in the 1.6 mg/kg/day dosage group on DGs 0 to 7 (absolute only) and 7 to 10, and in the 3.2 mg/kg/day dosage group on DGs 0 to 7, 7 to 10, 10 to 12 (absolute only). Significantly increased (p<.0.05 or p<.0.01) feed consumption values occurred in the 1.6 and 3.2 mg/kg/day dosage groups on DGs 15 to 18 (absolute and relative) and DGs 18 to 20 (relative only), observations interrelated with reduced body weights and the later stages of gestation, when maternal feed consumption tends to increase. Despite the increases in relative feed consumption values, the 3.2 mg/kg/day dosage group had a significantly reduced (ps0.01) absolute feed consumption value for the entire gestation period (DGs 0 to 20).
Feed consumption values during gestation were unaffected by dosages of the test article as high as 0.4 mg/kg/day.
C.3. Lactation
Absolute and relative maternal feed consumption values tended to be reduced in the 0.4 mg/kg/day dosage group and were significantly reduced (ps0.01) in the 1.6 mg/kg/day dosage group for the entire lactation period (DLs 1 to 14), and at most intervals within this period. The 3.2 mg/kg/day dosage group was precluded from evaluation because there were no surviving pups after DL 1.
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Feed consumption values during lactation were unaffected by the 0.1 mg/kg/day dosage of the test article.
D. Estrous Cycling. Mating and Fertility /Summary - Table C14: Individual Data - Table C29)
Dosages of the test article as high as 3.2 mg/kg/day did not affect estrous cycling (number of estrus stages per 28-days) in the 15 rats per dosage group that were evaluated. All female rats mated except one in the 0.4 mg/kg/day dosage group. The number of days in cohabitation, the fertility and pregnancy indices (number of pregnancies per number of rats that mated and rats in cohabitation, respectively), and the number of rats with confirmed mating dates during the first and second week of cohabitation were comparable in the five dosage groups. Pregnancy occurred in 33, 32, 28, 29 and 30 female rats in Groups I through V, respectively.
E. Necropsy Observations (Summary - Table C15: Individual Data Table C30)
All necropsy observations were considered unrelated to treatment. One rat in the 0.4 mg/kg/day dosage group had moderate dilation of the pelvis of the right kidney, an observation that is common in this species and strain. One rat in the 1.6 mg/kg/day dosage group had adhesion of abdominal adipose tissue and the spleen. No other gross lesions occurred in the female rats in this study.
F. Caesarean-Sectioning and Litter Observations (Summary Table C16; Individual Data - Tables C31 through C33)
Caesarean-sectioning observations on DG 10 were based on 10 (100%), 7 (70.0%), 6 (60.0%), 9 (90.0%) and 9 (90.0%) pregnant dams in each of the five respective dosage groups.
There were no biologically important or statistically significant differences in the litter averages for corpora ltea, implantations, viable embryos or nonviable embryos. No dam had litter in which there were no live embryos.
G. Natural Delivery and Litter Observations (Summaries - Tables C17 and C18: Individual Data - Tables C34 through C37)
Although 25 presumed pregnant rats in each dosage group were assigned to natural delivery, because one rat (1.6 mg/kg/day dosage group) was moribund sacrificed during the premating period (on DS 36), as previously described, this dosage group had only 24 rats assigned to natural delivery. Of these rats, 20 to 25 were pregnant and delivered litters.
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The duration of gestation was significantly reduced (p<0.01) in the 3.2 mg/kg/day dosage group, an observation associated with preimplantation loss [the average number of implantation sites per dam was significantly reduced (p<0.01), resulting in a significantly reduced (p<0.01), litter size] and an effect of the test article.
Pup viability was significantly reduced (p<0.05 or p<0.01) in the 1.6 and 3.2 mg/kg/day dosage groups, as described in the following information. Although the gestation index (the percentage of pregnant rats with live offspring) was comparable across all five dosage groups, the 1.6 mg/kg/day dosage group had increased numbers of pups that died or were presumed cannibalized on DL 1, and significantly increased (p<0.05 or p<0.01) numbers of pups dead or presumed cannibalized on DLs 2 to 4 and 5 to 7. The 3.2 mg/kg/day dosage group had postimplantation loss evident as reduced pup viability at birth [one litter had no liveborn pups, the number of dams with stillborn pups was significantly increased (p<0.01), the litter average and number of stillborn pups were significantly increased (p<0.01), and the litter average and number of liveborn pups were significantly reduced (p<0.01)], as well as peripartum deaths [significant numbers (p<0.05 orp<0.01) of dead and presumed cannibalized pups on DLs 1 and 2 to 4 (all liveborn pups died by DL 2) and significant numbers (p<0.01) of dams had all pups dead or presumed cannibalized on DLs 1 to 4]. Reflecting these effects, the viability index was significantly reduced (p<0.01) in the 1.6 and 3.2 mg/kg/day dosage groups, the lactation index was also significantly reduced (p<0.01) in the 1.6 mg/kg/day dosage group, as also were the averages for surviving pups (p<0.05 or p<0.01) in the 1.6 mg/kg/day dosage group beginning on DL 4 postculling, and in the 3.2 mg/kg/day dosage group on DL 1.
A dosage-dependent pattern of reduced pup body weight was evident in each group administered the test article. The 1.6 mg/kg/day dosage group had significantly reduced (p<0.01) pup body weights on all weighing days. The 3.2 mg/kg/day dosage group had a significantly reduced (p<0.01) pup body weight on DL 1 (no pups survived to subsequent scheduled weighings).
The percentage of male pups was comparable across all five dosage groups.
H. Clinical Observations from Birth to Pav 21 Postpartum and Necropsy Observations (Summaries - Tables C19 and C21; individual Data - Tables C38 and C451
Adverse clinical and necropsy observations associated with reduced pup viability and potential reduction in maternal care occurred in the 3.2 mg/kg/day dosage group. Adverse clinical observations include three (p<0.01) litters with pups that were not nursing (two of these litters had pups from which the placenta had not been removed, and one had pups that were not nested). Apparent maternal
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cannibalization was also evident in this dosage group (missing tail in one pup and a cannibalized forelimb in another pup), which may have occurred after these pups died.
Necropsy observations in pups that were stillborn or found dead included significant increases (p<0.05 or p<0.01) in the numbers of pups with no milk in the stomach in the 1.6 and 3.2 mg/kg/day dosage group pups. No pups (p<0.01) in the 0.1 mg/kg/day dosage group had this observation, as compared with two control group pups. The 3.2 mg/kg/day dosage group also had evidence of increased maternal cannibalization at necropsy of stillborn and found dead pups. Nine of these pups had missing hindlimbs and/or portion of the tail.
All other clinical and necropsy observations in the F1 generation pups were considered unrelated to the test article because: 1) the incidences were not dosage-dependent; or 2) the observation occurred in only one litter. Clinical observations included a domed head, portion of the tail missing, umbilical hernia, missing digits and bent tail. One 1.6 mg/kg/day dosage group stillborn pup had anasarca (edema of the entire body). Necropsy on DL 21 revealed two 0. 4 mg/kg/day dosage group littermates with moderate or severe dilation of the lateral ventricles of the brain, and one pup from a different 0.4 mg/kg/day dosage group litter with slight dilation of the renal pelvis.
1. Reflex and Physical Development (Summary - Table C20: Individual Data - Tables C39 through C44)
Reversible delays in reflex and physical development that are highly correlated with body weight<1,17) occurred in the 0.4 and 1.6 mg/kg/day dosage groups, as described below.
1.1. Surface Righting
Surface righting was delayed in the 1.6 and 3.2 mg/kg/day dosage groups, as described below. The percentage of pups that could surface right was significantly reduced { p i0.05 or p^0.01) in the 1.6 mg/kg/day dosage group on DLs 3, 4, 5, 6, 7, 8 and 10, and in the 3.2 mg/kg/day dosage group on DL 1, after which there were no surviving pups in this dosage group. The average day that at least 50% of the pups in a dosage group had the ability to surface right was significantly increased { p i0.05) in the 1.6 mg/kg/day dosage group. All surviving pups ultimately attained the ability to surface right.
The ability to surface right was unaffected by the 0.4 mg/kg/day dosage of the test article.
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1.2. Pinna Unfolding
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Pinna unfolding was delayed in the 0.1, 0.4 and 1.6 mg/kg/day dosage groups (no 3.2 mg/kg/day dosage group pups were evaluated for this parameter). The effect was transient (evident on only one day) in the 0.1 and 0.4 mg/kg/day dosage groups, and considered of no toxicological importance [the percentages of pups per litter with pinna unfolding were significantly reduced (p<0.05 or p<0.01) in the 0.1 and 0.4 mg/kg/day dosage groups on DL 3 only]. The percentage of pups with an unfolded pinna was significantly reduced (p<0.01) on DLs 3, 4 and 5) in the 1.6 mg/kg/day dosage group, and the average day that at least 50% of the pups in a dosage group had an unfolded pinna was significantly increased (p<0.01) in this dosage group. All surviving pups ultimately had unfolded pinnae.
1.3. Eve Opening
Eye opening was delayed in the 0.1, 0.4 and 1.6 mg/kg/day dosage groups (no 3.2 mg/kg/day dosage group pups were evaluated for this parameter). The effect was transient (evident on only one day) in the 0.1 and 0.4 mg/kg/day dosage groups, and considered of no toxicological importance [the percentages of pups per litter with open eye lids were significantly reduced (p<0.05) in the 0.1 and 0.4 mg/kg/day dosage groups on DL 14 only]. The percentage of pups with at least one open eye was significantly reduced (p<0.01) in the 1.6 mg/kg/day dosage group on DLs 14, 15 and 16. The day that at least 50% of the pups had at least one open eye was significantly increased (p<0.01) in the 0.4 and 1.6 mg/kg/day dosage groups. All pups had open eyelids by DL 21, when pupil constriction was tested.
1.4. Acoustic Startle
The time of development of the acoustic startle reflex was delayed (p<0.05 or p<0.01) in the 1.6 mg/kg/day dosage group; no 3.2 mg/kg/day dosage group pups survived to be tested for this reflex. The percentage of pups in the 1.6 mg/kg/day dosage group with this reflex was significantly reduced (p<0.05 or p<0.01) on DLs 13, 14, 16, 17, 18, 19 and 20, resulting in a tendency for an increase in the average day that at least 50% of the pups had the acoustic startle reflex.
The development of the acoustic startle reflex was unaffected by the 0.1 and 0.4 mg/kg/day dosages of the test article.
1.5. Air Righting
The ability to air right was delayed (p<0.01) in the 0.4 and 1.6 mg/kg/day dosage groups; no 3.2 mg/kg/day dosage group pups survived to be tested for this
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I.6. Pupil Constriction
All live pups in the 0 (Vehicle), 0.1, 0.4 and 1.6 mg/kg/day dosage groups had the pupil constriction response present on DL 21.
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V. RESULTS - F1 GENERATION MALE AND FEMALE RATS
A. F1 Generation Male Rats
A.1. Mortality and Clinical Observations (Summary - Table D1: Individual Data - Table D131
A.1.a. Mortality
No deaths in the F1 generation male rats were attributed to PFOS. Two control group rats were found dead on days 86 and 87 postweaning. These deaths were attributed to intubation errors. One 0.1 mg/kg/day dosage group rat was found dead on day 66 postweaning; this death was considered unrelated to the test article because it was a single, nondosage-dependent effect. Observations for these rats that died are provided below.
Control group male rat 13105 was found dead on day 87 postweaning, one hour and 11 minutes after the 87th daily dosage. No other adverse clinical observations occurred in this rat, and its body weight gains and feed consumption values were comparable to other rats in this dosage group. Necropsy of the rat revealed that all lung lobes were dark red, which in association with the time death occurred, is compatible with an intubation accident.
Control group male rat 13116 was found dead on day 86 postweaning, after it had been administered 85 daily dosages. Additional adverse clinical observations in this rat were limited to chromorhinorrhea (days 67 to 72 and 79 postweaning). Body weight gains and feed consumption values in this rat were comparable to those of other rats in this dosage group. Necropsy of the rat revealed dark red clotted material (presumed to be blood) in the thoracic cavity and a red perinasal substance, observations compatible with an intubation accident.
Male rat 13138 (0.1 mg/kg/day dosage group) was found dead on day 66 postweaning, after it had been administered 65 daily dosages. No other adverse clinical observations occurred in this rat, and its body weight gains and feed consumption values were comparable to those of other rats in this dosage group. All tissues appeared normal at necropsy.
A.1.b. Clinical Observations
All adverse clinical observations were considered unrelated to the test article because: 1) the incidences were not dosage-dependent; and/or 2) the observation occurred in only one or two rats. A significant increase (p<0.01) in the incidence of localized alopecia on the back in the 0.1 mg/kg/day dosage
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group was not considered treatment-related because the value was not dosagedependent. No other statistically significant increases in an adverse clinical observation occurred. Additional adverse clinical signs observed and considered unrelated to the test article included dental problems (missing, broken and/or misaligned incisors), chromorhinorrhea, abrasion on the head, near the eye, forelimb or back, chromodacryorrhea, laceration at the base of the tail, a swollen snout, a red perioral substance, a red substance on penis, localized alopecia on the back, limbs and/or head, a scab on the back, urine-stained abdominal fur, soft or liquid feces, swollen and purple ears, rales, gasping, excess salivation and dilated pupils.
A.2. Body Weights and Body Weight Changes (Figure 2: Summaries Tables D2 and D3: Individual Data - Table D14)
The 0.1 and 0.4 mg/kg/day dosage groups tended to weigh less than the control group on day 1 postweaning and generally gained one or two grams less body weight per week than the control group rats, with the exception of days 71 to 78, when these groups had significant reductions (p<0.05 orp<0.01) in body weight gains, as compared with the control group value. Reflecting this pattern of weight gain, weight gains in the 0.1 and 0.4 mg/kg/day dosage groups for the precohabitation period (day 1 postweaning to precohabitation) were 98.4% and 97.6% of the control group value, respectively. Body weight gains in the 0.1 and 0.4 mg/kg/day dosage groups for day 1 to termination were 98.5% and 96.6% of the control group value, respectively.
A.3. Absolute (q/davl and Relative (q/kq/davl Feed Consumption Values (Summaries - Tables D4 and D5: Individual Data - Table D15)
Absolute (g/day) feed consumption values were significantly reduced (p<.0.05 and p<;0.01, respectively) and relative (g/kg/day) feed tended to be reduced in the 0.1 and 0.4 mg/kg/day dosage groups during the first week of intubation (days 1 to 8 postweaning), as compared to the control group values. These observations commonly occur and were associated with the tendency for reduced body weight in these two dosage groups on day 1 postweaning. A significant increase (p<0.05) in the relative feed consumption value in the 0.1 mg/kg/day dosage group on days 22 to 29 postweaning was considered unrelated to the test article because the value was not dosage-dependent. No other statistically significant differences occurred in the feed consumption values for this portion of the study.
A.4. Sexual Maturation (Summary - Table D6; Individual Data - Table D16)
Dosages of the test article as high as 0.4 mg/kg/day did not affect the average day of preputial separation in the F1 generation male rats. No significant differences occurred among the three dosage groups.
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A.5. Passive Avoidance Performance (Summary - Table P7: Individual Data - Table D17)
There were no biologically important differences in the values for learning, short term retention, long-term retention or response inhibition in the F1 generation male rats, as evaluated by performance in a passive avoidance paradigm. No statistically significant differences occurred in the number of trials to criterion, trial latencies or numbers of rats that failed to learn.
A.6. Watermaze Performance (Summary - Table D8: Individual Data Table P181
No biologically important dosage-dependent differences occurred in watermaze performance of the F1 generation male rats regarding learning, short-term retention, long-term retention or response inhibition. No statistically significant differences occurred in the number of trials to criterion, trial latencies or numbers of rats that failed to learn.
A.7. Mating and Fertility (Summary - Table D9: Individual Data Table P19)
Dosages of the test article as high as 0.4 mg/kg/day did not affect any mating and fertility parameters evaluated in the F1 generation male rats. Values for the fertility and pregnancy indices (number of pregnancies per number of rats that mated and rats in cohabitation, respectively), the number of days to inseminate, the number of rats that mated and the number of rats with confirmed mating dates during the first week of cohabitation were comparable among the three dosage groups. Of the male rats assigned to cohabitation, 82.6%, 83.3% and 96.0% impregnated the cohort female rat.
A.8. Necropsy Observations (Summary - Table D10: Individual Data Table D20)
All necropsy observations in the F1 generation male rats were considered unrelated to the test article because: 1) the incidences were not dosagedependent; and/or 2) the observation commonly occurs in this strain of rat.
Gross lesions of male reproductive organs included flaccid, small and/or purple testes and epididymides in three (p<0.01) 0.1 mg/kg/day dosage group male rats (13134, 13145, 13148), each of which sired a litter). These observations were considered unrelated to the test article because: 1) the incidences were not dosage-dependent; and 2) these findings are known to be genetically mediated and common in this rat strain. No other gross lesion occurred at a statistically significant incidence.
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Additional necropsy observations considered unrelated to the test article included red abdominal adipose tissue with firm areas (one 0.4 mg/kg/day dosage group male rat; 13162), and urinary tract lesions, as described in the following information. One 0.1 mg/kg/day dosage group male rat (13143) had a dilated ureter; another rat in this dosage group (13134) had slight dilation of the renal pelvis. One 0.4 mg/kg/day dosage group male rat (13173) had large kidneys with numerous fluid-filled cysts in the parenchyma; the left kidney had slight dilation of the pelvis, in which there were six calculi, and thickened urinary bladder walls associated with the presence of numerous calculi. Necropsy observations in the control group rats that died as the result of an intubation error were described previously.
A. 9. Terminal Body Weights and Organ Weights and Ratios 1%) of Organ Weight to Terminal Body Weight (Summaries - Tables D11 and D12: Individual Data - Table D21)
No statistically significant differences occurred in the absolute or relative (to body weight) values for the weights of the right or left testis, seminal vesicles (with and without fluid), right epididymis or prostate. Terminal body weights tended to be reduced in the 0.1 and 0.4 mg/kg/day dosage groups; the terminal body weights in the 0.1 and 0.4 mg/kg/day dosage groups were 98.3% and 96.4%, respectively, of the control group value.
B. F1 Generation Female Rats
B.1. Mortality and Clinical Observations (Summary - Table E1: Individual Data - Tables E231
B.1.a. Mortality
No deaths in the F1 generation female rats were attributed to PFOS. One control group rat was sacrificed on day 7 postweaning, because it was a male rat that had been incorrectly identified as a female rat. One control group rat was found dead on day 28 postweaning; no cause of death was identified for this rat. One rat in the 0.4 mg/kg/day dosage group was found dead on day 10 of lactation (DL 10) as the result of an intubation accident. Observations for these rats are provided below.
No gross lesions were revealed by necropsy of control group rat 13205 on day 7 postweaning.
The control group female rat (13221) that was found dead on day 28 postweaning, after it had been administered 27 daily dosages did not have any other adverse clinical observations, and its body weight gains and feed
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consumption values were comparable to other rats in this dosage group. All tissues appeared normal at necropsy.
Female rat 13257 (0.4 mg/kg/day dosage group) was found dead on the morning of DL 10, after it had been administered a total of 106 daily dosages. No other adverse clinical observations occurred in this rat, although it lost weight on DLs 1 to 7. Its feed consumption values were unremarkable. This rat delivered 15 liveborn pups, of which seven were culled on DL 4 and eight were sacrificed after the death of the dam. Necropsy of the dam revealed gross lesions compatible with an intubation accident (white foam in the trachea, approximately 2 mL of a light orange fluid in the thoracic cavity, and dark red lungs).
B.1.b. Clinical Observations
A red perivaginal substance occurred in one and two dams in the 0.1 and 0.4 mg/kg/day dosage groups, respectively, on days 21 or 22 of gestation, and red perivaginal substance was also observed on DL 1 in five (p<;0.01) dams in the 0.4 mg/kg/day dosage group. These observations probably were associated with parturition, rather than an effect of the test article, and did not appear to adversely affect the health of the dams or their offspring. No other adverse clinical observation occurred at a statistically significant incidence.
All other adverse clinical observations that occurred during the precohabitation, gestation and lactation periods were considered unrelated to the test article because: 1) the incidences were not dosage-dependent; 2) the observation occurred in only one or two rats; and/or 3) the observation is common in the laboratory environment. These observations included dental problems (misaligned, missing and/or broken teeth), chromodacryorrhea, swollen and purple ears, localized alopecia on the back, head, limbs and/or underside, abrasion or scab on the back, urine-stained abdominal fur, missing hindpaw digits, perivaginal swelling, swollen forepaw, chromorhinorrhea, soft or liquid feces, missing tail sheath, tip of tail black or missing and abrasion on the chest.
B.2. Maternal Body Weights and Body Weight Changes (Figure 4: Summaries - Tables E2 through E7: Individual Data - Tables E24 through E26)
B.2.a. Precohabitation
Body weights tended to be reduced in the 0.4 mg/kg/day dosage group on day 1 postweaning. No statistically significant or dosage-dependent differences in precohabitation body weight gains or body weights occurred in the F1 generation female rats during the precohabitation period.
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B.2.b. Gestation
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Maternal body weights and body weight gains during the gestation period were unaffected by dosages of the test article as high as 0.4 mg/kg/day. All values were comparable among the three dosage groups and did not significantly differ.
B.2.C. Lactation
Significant (p<.0.05) maternal body weight loss occurred on DLs 1 to 4 in the 0.4 mg/kg/day dosage group, as compared to the control group value, after which body weight gains were greater than, or weight loss less than the control group values.
Maternal body weights and body weight gains during the lactation period were unaffected by the 0.1 mg/kg/day dosage of the test article.
B.3. Maternal Absolute fa/davl and Relative (a/ka/dav) Feed Consumption Values (Summaries - Tables E8 through E13: Individual Data Tables E27 through E291
B.3.a. Precohabitation
The 0.4 mg/kg/day dosage of the test article was associated with a significant reduction (p<0.05) in absolute (g/day) feed consumption and a tendency for reduced relative (g/kg/day) feed consumption on days 1 to 8 postweaning, observations that were associated with the tendency for smaller body weight in this group on day 1 postweaning. Absolute and relative feed consumption values for the remainder of the precohabitation period were comparable and did not significantly differ among the three dosage groups.
B.3.b. Gestation
Absolute and relative feed consumption values during the gestation period were unaffected by dosages of the test article as high as 0.4 mg/kg/day. All values were comparable among the three dosage groups and did not significantly differ.
B.3.C. Lactation
The absolute maternal feed consumption value was significantly reduced {p<.0.05) on DLs 1 to 4 in the 0.4 mg/kg/day dosage group, as compared to the control group value. The relative feed consumption value was also reduced, however not significantly (p>0.05). These observations were associated with the significant weight loss that occurred in this group on DLs 1 to 4 and attributed to the test article.
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Absolute and relative feed consumption values during the lactation period were unaffected by the 0.1 mg/kg/day dosage of the test article.
B.4. Sexual Maturation (Summary - Table E14: Individual Data Table E30)
Dosages of the test article as high as 0:4 mg/kg/day did not affect the average day of vaginal patency in the F1 generation female rats. No significant differences occurred among the three dosage groups.
B.5. Passive Avoidance Performance (Summary - Table E15: Individual Data -Table E31)
There were no biologically important differences in the values for learning, short term retention, long-term retention or response inhibition in the F1 generation female rats, as evaluated by performance in a passive avoidance paradigm. No statistically significant differences occurred in the trial latencies or numbers of rats that failed to learn.
The number of trials to criterion was significantly reduced {p<, 0.05) for the female rats in the 0.4 mg/kg/day dosage group, as compared to the control group value. This observation was not considered an effect of the test article because an increase in the number of trials to criterion, rather than a decrease, would be expected as an indication of toxicity.
B.6. Watermaze Performance (Summary - Table E16: Individual Data Table E32)
No biologically important dosage-dependent differences occurred in watermaze performance of the F1 generation female rats regarding learning, short-term retention, long-term retention or response inhibition. No statistically significant differences occurred in the number of trials to criterion, trial latencies or numbers of rats that failed to learn.
B.7. Mating and Fertility (Summary - Table E17: Individual Data Table E33)
Dosages of the test article as high as 0.4 mg/kg/day did not affect any mating and fertility parameters evaluated in the F1 generation female rats. Values for the number of days in cohabitation, the number of rats that mated, the fertility and pregnancy indices (number of pregnancies per number of rats that mated and rats in cohabitation, respectively), and the number of rats with confirmed mating dates during the first and second week of cohabitation were comparable among the three dosage groups.
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B.8. Necropsy Observations (Summary - Table E18: individual Data Table E341
All necropsy observations in the F1 generation female rats were considered unrelated to the test article because: 1) the observations occurred in rats in the control group; and 2) the observation commonly occurs in this strain of rat. These observations included rough and/or pitted cortex of the kidneys with calculi in the kidney and/or urinary bladder of two control group rats. One of these rats also had a tan granular material in the renal cortex and thickened walls of the urinary bladder. Necropsy observations for the 0.4 mg/kg/day dosage group dam that died as the result of an intubation error were described previously.
B.9. Natural Delivery and Litter Observations (Summaries - Tables E19 and E20: Individual Data - Tables E35 through E38)
Pregnancy occurred in 22 (95.6%), 21 (84.0%) and 24 (96.0%) of the 23, 25 and 25 female rats assigned to cohabitation in the 0 (Vehicle), 0.1 and 0.4 mg/kg/day dosage groups, respectively. All pregnant dams delivered litters. The gestation index (the percentage of pregnant rats with live offspring) was comparable across the three dosage groups.
The viability of the second generation offspring (F2 pups) was unaffected at the highest dosage tested, 0.4 mg/kg/day. Small increases in the number of dams with stillborn pups and in the number of pup deaths after DL 2 in the 0.4 mg/kg/day dosage group were not toxicologically important because: 1) the values were not significantly different from the control group values; 2) the average for live litter sizes delivered and surviving to DL 21 were greater than or comparable to the control group values; and 3) neither the viability or lactation indices for the 0.4 mg/kg/day dosage group remarkably differed from the control group values.
Pup body weights of the second generation offspring (F2 pups) were unaffected at the highest dosage tested, 0.4 mg/kg/day. Small reductions in pup body weights in the 0.1 and 0.4 mg/kg/day dosage groups were not toxicologically important because: 1) the small differences between the pup body weights for the control and 0.1 mg/kg/day dosage groups were not statistically significant and were associated with the larger live litter sizes of the 0.1 mg/kg/day dosage group on DLs1 through 4, as compared with the control group values, and the random selection of pups for continued observations on DL 4; 2) the small reductions in pup body weights in the 0.4 mg/kg/day dosage group were associated with a minimally larger live litter size at birth (DL 1) and on DL 4 preculling, as compared with the control group values, and the random selection of pups for continued observation on DL 4; the statistically significant reductions
000199
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(p<0.05 and p<0.01, respectively) present on DLs 7 and 14, as compared to the control group values, were transient and disappeared by DL 21. Administration of the test article at dosages as high as 0.4 mg/kg/day did not adversely affect any other parameter evaluated at natural delivery or during the 21-day lactation period (duration of gestation, averages for implantations and live litter sizes, numbers of dams with all pups dying during lactation, viability and lactation indices, surviving pups per litter and pup sex ratios).
B.10. Clinical Observations from Birth to Day 21 Postpartum and Necropsy Observations (Summaries - Tables E21 and E22: Individual Data - Tables E39 and E40)
No clinical or necropsy observations were attributable to dosages of the test article as high as 0.4 mg/kg/day because: 1) the incidences were not dosagedependent; and/or 2) the observation occurred in only one or two pups. These clinical observations included one control group pup that was not nesting or nursing, had decreased motor activity and was cold to the touch, one pup in each of the control and 0.4 mg/kg/day dosage groups that had a missing tip of tail and one 0.4 mg/kg/day dosage group pup that had an umbilical hernia. No milk in stomach occurred in 2, 4 and 4 pups that were found dead in the three respective dosage groups. One control group pup had hydrocephaly and one 0.1 mg/kg/day dosage group pup had a raised tan area on the median and left lateral lobes of the liver at necropsy on DL 21.
CCC2Q0
REFERENCES
418-008:PAGE V-10
1. Study Design as Modification of: U.S. Food and Drug Administration (1994). International Conference on Harmonisation; Guideline on detection of toxicity to reproduction for medicinal products. Federal Register, September 22, 1994, Vol. 59, No. 183.
2. U.S. Food and Drug Administration. Good Laboratory Practice Regulations; Final Rule. 21 CFR Part 58.
3. Japanese Ministry of Health and Welfare (1997). Good Laboratory Practice Standard for Safety Studies on Drugs, MHW Ordinance Number 21, March 26, 1997.
4. European Economic Community (1989). Council decision on 28 July 1989 on the acceptance by the European Economic Community of an OECD decision/recommendation on compliance with principles of good laboratory practice. Official Journal of the European Communities: Legislation. 32 (No. L 315; 28 October): 1-17.
5. Christian, M.S. and Voytek, P.E. (1982). In Vivo Reproductive and Mutagenicity Tests. Environmental Protection Agency, Washington, D.C. National Technical Information Service, U.S. Department of Commerce, Springfield, VA 22161.
6. Christian, M.S. (1984). Reproductive toxicity and teratology evaluations of naltrexone (Proceedings of Naltrexone Symposium, New York Academy of Sciences, November 7, 1983), J. Clin. Psychiat. 45(9):7-10.
7. Lang, P.L. (1988). Embryo and Fetal Developmental Toxicity (Teratology) Control Data in the Charles River Crl:CD7BR Rat. Charles River Laboratories, Inc., Wilmington, MA 01887-0630. (Data base provided by Argus Research Laboratories, Inc.)
8. Institute of Laboratory Animal Resources (1996). Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, D.C.
9. Salewski, E. (1964). Farbemethode zum makroskopischen Nachweis von Implantationsstellen am Uterus der Ratte. Arch. Pathol. Exp. Pharmakol. 247:367.
10. Snedecor, G.W. and Cochran, W.G. (1967). Variance test for homogeneity of the binomial distribution. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 240-241.
C C O fcO l
418-008: PAGE V-11 11. Sokal, R.R. and Rohlf, F.J. (1969). Bartlett's test of homogeneity of
variances. Biometry, W.H. Freeman and Co., San Francisco, pp. 370-371. 12. Snedecor, G.W. and Cochran, W.G. (1967). Analysis of Variance. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 258-275. 13. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc. 50:1096-1121. 14. Sokal, R.R. and Rohlf, F.J. (1969). Kruskal-Wallis Test. Biometry, W.H. Freeman and Co., San Francisco, pp. 388-389. 15. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6(3):241-252. 16. Siegel, S. (1956). Nonparametric Statistics for the Behavioral Sciences, McGraw-Hill, New York, pp. 96-104. 17. Lochry, E.A., Hoberman, A.M. and Christian, M.S. (1984). Positive correlation of pup body weight with other commonly used developmental landmarks. Teratology 29(2):44A.
0C0202
APPENDIX A REPORT FIGURES
BODY WEIGHTS
Fo GENERATION MALE RATS Figure 1
0 (VEHICLE) MG/KG/DAY
0.1 MG/KG/DAY
0.4 MG/KG/DAY
1.6 MG/KG/DAY
-- X--
3.2 MG/KG/DAY
*p<0.05 " p0.01
a
a DAY OF STUDY
o M
a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
O c. Terminal body weight.
ki*
418-008: PAGE A-1
BODY WEIGHTS
Fo GENERATION FEMALE RATS Figure 2
iro O
418-008:PAGE A-2
BODY WEIGHTS
F1 GENERATION MALE RATS
600 - ,
Figure 3
500 -
400 -
0
f--
X 300 -
0
200 -
100 -
418-008-.PAGEA-3
lo
CD
T
15
22
2iT
36
~l
43
I----------Y~
50 57
4
T'
a
7i
k
b
DAY POSTWEANING
a. Precohabilation body weights.
O b. Terminal body weights.
no
&
BODY WEIGHTS
F1 GENERATION FEMALE RATS
Figure 4
3 0 V d ;8OO-8l.fr
APPENDIX B REPORT TABLES - Fo GENERATION MALE RATS
0C0208
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B1 (PAGE 1): CLINICAL OBSERVATIONS - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III IV
V
0 (VEHICLE) 0.1 0.4 1.6 3.2
MAXIMUM POSSIBLE INCIDENCE
2345/ 35 2345/ 35 2345/ 35 2345/ 35 2345/ 35
MORTALITY
00000
LOCALIZED ALOPECIA: LIMBS
102/ 4 54/ 2 37/ 2 100/ 4
3/ 2
LEFT EYE: CORNEAL OPACITY
0/ 0
0/ 0
0/ 0
0/ 0 34/ 1
INCISORS: TOTAL MISSING/BROKEN MISALIGNED
78/ 3 45/ 3 51/ 1
2/ i 2/ i 0/ 0
102/ 4 68/ 4 80/ 2
66/ 2 19/ 1 47/ 1
12/ 1 12/ 1
0/ 0
NECK : ABRASION
0/ 0
0/ 0
0/ 0
0/ 0
3/ 1
HYPERACTIVITY
0/ 0
0/ 0
0/ 0
0/ 0
1/ 1
EXCESS SALIVATION
0/ 0
0/ 0
0/ 0
0/ 0
1/ 1
CHROMODACRYORRHEA
24/ 1
0/ 0 34/ 2 41/ 1
0/ 0
SNOUT : SWOLLEN
0/ 0
0/ 0 27/ 1 43/ 1
0/ 0
CHROMORHINORRHEA
0/ 0
1/ 1
0/ 0
4/ 1
0/ 0
DYSPNEA
0/ 0
0/ 0
0/ 0
4/ 1
0/ 0
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP, N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION.
418-008:PAGE B-1
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B2 (PAGE 1): BODY WEIGHTS - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0 .1
RATS TESTED
N 35
35
BODY WEIGHT (G)
DAY 1
MEAN+S.D
388.9 + 22.0
390.1 4 25.7
DAY 8
MEAN+S.D
417.2 25.8
419.8 4 24.9
DAY 15
MEAN+S.D
441.0 + 30.1
441.1 4 28.4
DAY 22
MEAN+S.D
459.1 4 36.3
460.8 4 32.1
DAY 29
MEAN+S.D
471.3 + 43.9
476.7 + 36.5
DAY 36
MEAN+S.D
488.4 + 42.4
488.5 + 36.4
DAY 42a
MEAN+S.D
501.7 45.3
503.1 + 40.8
DAY 49
MEAN+S.D
509.8 4 46.2
513.2 4 42.3
DAY 56b
MEAN+S.D
520.2 4 48.8
518.6 + 45.0
DAY 63
MEAN+S.D
538.0 52.1
535.2 4 48.6
TERMINAL BODY WEIGHT
MEAN+S.D
542.6 4 52.3
539.3 + 49.2
DAY = DAY OF STUDY a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
* Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
III 0 .4
35
389.8 4 23.6 417.1 24.0 438.1 4 28.4 456.4 4 32.1 472.1 34.3 482.3 4 36.1 494.8 + 34.0 501.2 4 33.6 507.9 37.2 520.2 4 39.7
522.6 4 43.2
IV V 1.6 3.2
35 35
390.8 4 16.4 414.8 4 21.6 437.2 4 25.2 449.6 4 30.9 463.5 4 29.4 472.1 4 30.4 484.2 4 33.8 492.5 4 35.2 496.9 4 36.5* 510.9 4 39.4*
512.8 4 40.5*
391.1 4 18.0 415.6 _4 21.8 436.9 4 25.8 448.0 4_ 30.2 458.0 _4 34.3 461.7 4 36.1** 468.8 4 37.7** 469.4 4 37.8** 473.2 4 37.9** 480.8 4 41.8**
482.1 4 41.5**
418-008:PAGE B-2
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B3 (PAGE 1) : BODY WEIGHT CHANGES - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
h
0.1
III 0.4
RATS TESTED
N 35
35
35
BODY WEIGHT CHANGE (G)
DAYS 1 - 8
MEAN+S .D .
+28.2 + 16.1
+29.-7 + 11.4
+21.3 + 12.7
DAYS 8 - 15
MEAN+S.D.
+23.8 + 7 .8
+21.3 + 6.6
+21.0 + 7.4
DAYS 15 - 22
MEAN+S.D.
+18.1 f 9.3
+19.8 + 7.8
+18.3 + 8.1
DAYS 22 - 29
MEAN +S .D .
+12.2 + 17.2
+15.9 + 7.5
+15.7 + 6.5
DAYS 29 - 36
MEAN+S.D .
+17.1 4- 15.7
+H .8 + 5.6
+10.2 + 5.7
DAYS 36 - 42a
MEAN+S.D.
+13.3 7.8
+14.6 + 6 .9
+12.4 + 12.1
DAYS 1 - 42a
MEAN+S.D . +112.8 + 33.7
+113.0 + 25.8
+105.0 + 24.6
DAYS 56b- 63
MEAN+S.D .
+17.7 5 .8
+16.6 + 7 .2
+12.2 + 8.8*
DAYS 1 - 63
MEAN+S.D . +149.0 + 40.3
+145.1 + 33.6
+130.3 + 30.8*
DAY 1 TERMINATION
MEAN+S.D . +153.6 + 41.5
+149.2 + 34.5
+132.8 + 34.0*
DAY(S) = DAY(S) OF STUDY a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
* Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
IV 1.6
35
+23.9 + 8.4 +22.5 + 6.8 +12.3 + 16.6 +13.9 + 8.8
+8.6 + 7.4** +12.1 + 7.2 +93.4 + 22.4** +14.0 + 6.6 +120.0 + 28.9**
+121.9 + 30.2**
V 32
35
+24.5 + 6.5 +21.3 f 7.3 +11.1 f 10.7* +10.0 8.2
+3.6 + 6.7* +7.2 + 6.3** +77.8 + 25.2** +7.7 + 11.4** +89.8 + 29.6**
+91.0 29.9**
418-008:PAGE B-3
000211
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B4 (PAGE 1) : ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III
IV
0 (VEHICLE)
0.1
0.4
1.6
RATS TESTED
N 35 35 35 35
FEED CONSUMPTION (G/DAY)
DAYS 1 - 8
MEAN+S.D .
26.6 + 3.0
26.7 + 2.2
26.8 + 2.1
26.4 + 2.4
DAYS 8 - 15 DAYS IS - 22 DAYS 22 - 29
MEAN+S.D . MEAN+S.D. MEAN+S.D .
27.0 + 2.8
27.8 + 3.4 t 34) a
28.0 + 3.6
27.0 + 2.2 I 34] a
27.9 + 3.0
28.5 + 2.4
26.8 + 2.4 27.4 + 2.8 27.9 + 2.2
25.9 + 2.0
26.3 + 2.8 [ 34] a
26.8 + 2.4
DAYS 29 - 36 DAYS 36 - 42b
MEAN+S.D . MEAN+S.D .
29.5 + 3.7 27.8 + 3.2
29.2 + 2.4 l 34 ]a
27.4 + 2.3
28.7 + 2.4 [ 34 )a
27.0 + 2.9
27.8 + 2.6 l 33] a
26.6 + 3.7
DAYS 1 - 42b
MEAN+S.D .
27.8 + 2.8
27.8 + 2.1
27.4 + 1.9
26.6 + 2.0*
DAYS 56c- 63
MEAN+S.D.
28.0 + 2.7 ( 34 )a
27.6 + 2.4
26.6 + 2.2*
25.8 + 2 .3**
DAYS = DAYS OF STUDY ( ] = NUMBER OF VALUES AVERAGED a. Excludes values that were incorrectly recorded, as well as those associated with spillage or wet feed. b. Last value recorded before cohabitation. c. First value recorded after cohabitation. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (P5O.OI).
V 3.2
35 i
26.8 + 2.3
25.8 + 2.3
25.1 + 3.4**
26.4 + 2.5
25.6 + 2.5** l 34) a
24.2 + 2.1**
25.7 + 2.0**
23.7 + 2 .4**
418-008:PAGE B-4
000212
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629'.. .9)
TABLE B5 (PAGE 1) : RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
IV 1.6
RATS TESTED
N 35 35 35 35
FEED CONSUMPTION (G/KG/DAY)
DAYS 1 - 8
MEAN+S.D .
65.8 + 5.4
65.9 + 4.6
66.4 +_ 4.6
65.5 + 4.2
DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29
MEAN+S.D. MEAN+S.D. MEAN+S.D .
63.0 + 4.0
61.5 + 4.4 l 34) a
60.2 + 6.7
62.8 + 3.6 1 34 ]a
61.9 + 4 .a
60.9 + 3.6
62.7 + 3.9 61.4 + 4.9 60.2 + 4.0
60.9 + 3.3*
59.2 + 5.2 t 34) a
58.9 + 4.4
DAYS 29 - 36 DAYS 36 - 42b
MEAN+S.D. MEAN+S.D .
61.5 + 5.8 56.2 + 4.2
60.2 + 3.1
[ 34 )a 55.2 + 2.4
59.9 + 3.3 [ 34] a
55.3 + 5.7
59.3 + 4.7 [ 33) a
55.6 + 5.9
DAYS 1 * 42b
MEAN+S.D.
61.4 + 3.3
61.2 + 2.4
61.0 + 2.7
59.9 + 2.8*
DAYS 56c- 63
MEAN+S.D.
52.8 + 2.5 ( 34 )a
52.4 + 3.4
51.7 + 3.3
51.2 + 3.3
DAYS = DAYS OF STUDY l 1 = NUMBER OF VALUES AVERAGED a. Excludes values that were incorrectly recorded, as well as those associated with spillage or wet feed. b. Last value recorded before cohabitation. c. First value recorded after cohabitation. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p<0.01).
V 3.2
35
66.3 + 3.8 60.6 + 3.6* 56.7 + 6.3** 58.3 + 4.7 55.8 + 3.1**
[ 34] a 3.0**
58.4 + 2.3** 49.6 + 2.6**
418-008:PAGE B-5
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000213
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6205.9)
TABLE B6 (PAGE 1) : MATING AND FERTILITY - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III IV
V
0 (VEHICLE)
0.1
0.4
1.6
3.2
RATS IN COHABITATION
N
35
35
35
34a 35
DAYS IN COHABITATION b MEAN+S.D
2.7 + 1.8 [ 34]
2.6 + 1.3
2.5 + 1.8
2.1 + 1.2 ( 31]
2.7 + 1
RATS THAT MATED c
N(%)
35(100.0)
35(100.0)
33 ( 94.3)
34(100.0)
32 ( 91.4)
FERTILITY INDEX d,e
N/N (%)
33/35 ( 94.3)
32/35 ( 91.4)
27/33 ( 81.8)
29/34 ( 85.3)
28/32 ( 87.5)
RATS WITH CONFIRMED
MATING DATES f
N 34
35
33
31
32
RATS MATING g DAYS 1-7
N (%)
34(100.0)
35(100.0)
33(100.0)
31(100.0)
32(100.0)
RATS PREGNANT/RATS IN COHABITATION f
N/N <*>
33/35 ( 94.3)
32/35 ( 91.4)
27/35 ( 77.1)
29/34 ( 85.3)
28/35 ( 80.0)
( ) = NUMBER OF VALUES AVERAGED a. Excludes values for rat 8238, which was not assigned to cohabitation because there were no available female rats. b. Restricted to rats with a confirmed mating date on days 1 to I of cohabitation and rats that did not mate. c. Includes only one mating for each male rat. d. Number of pregnancies/number of rats that mated. e. Includes only one pregnancy for each rat that impregnated more than one female rat. f. Includes only one confirmed mating for each male rat. g. Restricted to rats with a confirmed mating date on days 1 to 7 of cohabitation.
418-008:PAGE B-6
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B7 lPAGE 1): NECROPSY OBSERVATIONS SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 11 III
IV
V
0 (VEHICLE)
0.1
0.4
1.6
3.2
RATS EXAMINED a N 35 35 35 35 35
MORTALITY
N0 0 0 0 0
APPEARED NORMAL N 33 35 34 32 29
TESTES:
BILATERAL, SMALL, PURPLE
AND/OR FLACCID
N
0
0
0
1
3
LIVER:
LIGHT BROWN OR BROWN
N
0
0
0
0
3**
LARGE
N1 0 0 1 0
ROUGH SURFACE
N
0
0
0
i
0
PAPILLARY PROCESS,
CONSTRICTED AND NUMEROUS
TAN, RAISED AREAS
N
0
0
0
i
0
PROSTATE: SMALL
N1 0 0 0 1
EYES:
LEFT, LENS OPAQUE
N
0
0
0
0
1
KIDNEYS:
BILATERAL, LARGE
N
1
0
0
1
0
PARENCHYMA, CONTAINED
MULTIPLE, PALE, FLUIDFILLED CYSTS N 0 0 0 1 0
e
RIGHT, PELVIS, SLIGHT DILATION
N
0
0
1
0
0
o
to0 SPLEEN: LARGE
N1 0 0 0 0
p 01
a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
418-008:PAGE B-7
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B8 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III
IV
0 (VEHICLE)
0.1
0.4
1.6
RATS TESTED
N 35
35
35
35
TERMINAL BODY WEIGHT
MEAN+S.D .
542.6 + 52.3
539.3 + 49.2
522.6 + 43.2
512.8 + 40.5*
EPIDIDYMIS LEFT
MEAN+S.D .
0.70 +_ 0.08
.72 + 0.08
0.70 + 0.06
0.70 + 0.07
TESTIS LEFT
SEMINAL VESICLES WITH FLUID
SEMINAL VESICLES WITHOUT FLUID
MEAN+S.D. MEAN+S.D. MEAN+S.D .
1.72 + 0.19 1 33) b
2.07 + 0.34
0.99 + 0.23
1.76 + 0.14 2.11 + 0.32 1.01 + 0.21
1.72 + 0.15
1.97 + 0.33 ( 34) b
0.95 + 0.18
1.74 + 0.13 l 34) b
2.01 + 0.35 1 34) b
0.98 + 0.17
EPIDIDYMIS RIGHT
MEAN+S.D .
0.12 + 0.08
0.74 + 0.07
0.72 + 0.06
0.70 + 0.08
TESTIS RIGHT PROSTATE
MEAN+S.D. MEAN+S.D.
1.75 + 0.16
1.18 + 0.27 l 34)b
1.75 + 0.15 1.28 + 0.28
1.71 + 0.16 1.15 + 0.31
1.74 + 0.14 1 34) b
1.13 + 0.29
ALL WEIGHTS WERE RECORDED IN GRAMS (G). ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rats that had abnormal organs (weight affected) or organs damaged (weight affected). * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p<0.01).
V 3.2
35
482.1 + 41.5"
0.68 + 0.07
1.79 + 0.22 I 32) b
1.77 + 0.28" l 34) b
0.92 + 0.19
0.69 + 0.08
1.78 + 0.22 1 32 ]b
1.02 + 0.22* [ 34 ]b
418-008:PAGE B-8
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B9 (PAGE 1): RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III IV
V
0 (VEHICLE)
0.1
0.4
1.6
3.2
RATS TESTED
N 35 35 35 35 35
TERMINAL BODY WEIGHT
MEAN+S.D .
542.6 + 52.3
539.3 + 49.2
522.6 + 43.2
512.8 + 40.5*
482.1 + 41.'s**
EPIDIDYMIS LEFT
MEAN+S.D .
0.131 + 0.018
0.134 + 0.016
0.134 + 0.016
0.136 + 0.016
0.141 + 0.018
TESTIS LEFT
SEMINAL VESICLES WITH FLUID
SEMINAL VESICLES WITHOUT FLUID
MEAN+S.D.
0.319 + 0.043
MEAN+S.D. MEAN+S.D .
0.382 + 0.062 [ 33) b
0.183 + 0.046
0.327 + 0.032 0.391 + 0.054 0.186 + 0.036
0.331 + 0.037
0.380 + 0.067 l 34 ]b
0.182 + 0.035
0.339 + 0.032 [ 34 ]b
0.394 + 0.068 ( 34)b
0.192 + 0.035
0.369 + 0.046** 1 32] b
0.368 + 0.061 ( 34 1b
0.191 + 0.040
EPIDIDYMIS RIGHT
MEAN+S.D .
0.134 + 0.018
0.138 + 0.016
0.137 + 0.015
0.137 + 0.016
0.142 + 0.016
TESTIS RIGHT PROSTATE
MEAN+S.D. MEAN+S.D.
0.324 + 0.038
0.218 + 0.053 ( 34 ]b
0.327 + 0.038 0.239 + 0.057
0.328 + 0.034 0.220 + 0.062
0.340 + 0.035 t 341b
0.219 + 0.054
0.370 + 0.046** l 32)b
0.212 + 0.045 ( 341b
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
( ] = NUMBER OF VALUES AVERAGED
a. Excludes values for rats that had abnormal organs (weight affected) or organs damaged (weight affected).
* Significantly different from the vehicle control group value (p<0.05).
** significantly different from the vehicle control group value (p<0.01).
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 1): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP I-
0 (VEHICLE) MG/KG/DAY
RAT #
DESCRIPTION
8101 DS( 16- 23)
INCISORS: MISSING/BROKEN
DS ( 24 )
INCISORS: GROWN IN
8102
NO ADVERSE FINDINGS
8103
NO ADVERSE FINDINGS
8104 DS ( 5- 33)
INCISORS: MISSING/BROKEN
DS ( 34 )
INCISORS: GROWN IN
DS ( 6- 17)
CHROMODACRYORRHEA
DS ( 17- 67)
INCISORS: MISALIGNED a
DS ( 20- 30)
CHROMODACRYORRHEA
DS { 67 )
CHROMODACRYORRHEA a
DS ( 67 )
INCISORS: MISSING/BROKEN a
8105
NO ADVERSE FINDINGS
8106
NO ADVERSE FINDINGS
8107
NO ADVERSE FINDINGS
8108
NO ADVERSE FINDINGS
8109
NO ADVERSE FINDINGS
8110
NO ADVERSE FINDINGS
8111
NO ADVERSE FINDINGS
8112
NO ADVERSE FINDINGS
8113 DS ( 66- 67)
LOCALIZED ALOPECIA: LIMBS a
8114 DS ( 66- 67)
LOCALIZED ALOPECIA: LIMBS a
8115 DS ( 56- 62)
INCISORS: MISSING/BROKEN
DS ( 63 )
INCISORS: GROWN IN
8116
NO ADVERSE FINDINGS
8117 DS ( 21- 67)
LOCALIZED ALOPECIA: LIMBS a
8118
NO ADVERSE FINDINGS
8119
NO ADVERSE FINDINGS
8120
NO ADVERSE FINDINGS
8121
NO ADVERSE FINDINGS
8122
NO ADVERSE FINDINGS
8123
NO ADVERSE FINDINGS
8124
NO ADVERSE FINDINGS
o 8125
NO ADVERSE FINDINGS
o DS = DAY OF STUDY
o a. Observation confirmed at necropsy.
M
03
418-008.PAGE B-10
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT n
DESCRIPTION
B126 8121 8128 8129 8130 8131 8132 8133 8134 8135
DS( 17- 67)
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS NO ADVERSE FINDINGS
LIMBS a
DS = DAY OF STUDY a. Observation confirmed at necropsy.
418-008.PAGE B-11
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 3) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT #
DESCRIPTION
8136 8137 8138 8139 8140 8141 8142 8143 8144 8145 8146 8147 8148 8149 8150 8151 8152 8153 8154 8155 8156 8157 8158 8159 8160 8161 8162 8163 8164 8165
DS ( 16- 67) DS< 66- 67)
DS< 66- 67)
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS
DS = DAY OF STUDY a. Observation confirmed at necropsy.
418-008:PAGE B-12
0C0Z20
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 4) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT H
DESCRIPTION
8166 8167 8168 8169 8170
DS( 67 )
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA a
DS = DAY OF STUDY a. Observation confirmed at necropsy.
418-008PAGE B-13
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 5) CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT #
DESCRIPTION
8171
DS ( 9- 16)
DS< 17 )
INCISORS: MISSING/BROKEN INCISORS: GROWN IN
8172 DS ( 38- 67)
CHROMODACRYORRHEA a
DS ( 38- 67)
INCISORS: MISSING/BROKEN a
DS ( 38- 67)
INCISORS: MISALIGNED a
DS ( 41- 67)
SNOUT : SWOLLEN a
8173
NO ADVERSE FINDINGS
8174
NO ADVERSE FINDINGS
8175
NO ADVERSE FINDINGS
8176
NO ADVERSE FINDINGS
8177
NO ADVERSE FINDINGS
8178
NO ADVERSE FINDINGS
8179
NO ADVERSE FINDINGS
8180
NO ADVERSE FINDINGS
8181
NO ADVERSE FINDINGS
8182
NO ADVERSE FINDINGS
8183
NO ADVERSE FINDINGS
8184
NO ADVERSE FINDINGS
8185 DS ( 9- 11)
CHROMODACRYORRHEA
DS ( 9- 16)
INCISORS: MISSING/BROKEN
DS ( 17- 67)
INCISORS: MISALIGNED a
DS ( 34 )
CHROMODACRYORRHEA
DS ( 52- 67)
INCISORS: MISSING/BROKEN a
DS ( 66- 67)
LOCALIZED ALOPECIA: LIMBS a
8186
NO ADVERSE FINDINGS
8187
NO ADVERSE FINDINGS
8188
NO ADVERSE FINDINGS
8189
NO ADVERSE FINDINGS
8190
NO ADVERSE FINDINGS
8191
NO ADVERSE FINDINGS
8192
NO ADVERSE FINDINGS
8193
NO ADVERSE FINDINGS
8194 DS ( 33- 67)
LOCALIZED ALOPECIA: LIMBS a
8195
NO ADVERSE FINDINGS
o
o
8196 8197
NO ADVERSE FINDINGS NO ADVERSE FINDINGS
y <
o DS = DAY OF STUDY 0 a. Observation confirmed at necropsy.
I)
418-008:PAGE B-14
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 6) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT #
DESCRIPTION
8198 8199 8200 8201 8202 8203
8204 8205
DS< 7- 12) DS( 13 )
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: GROWN IN NO ADVERSE FINDINGS NO ADVERSE FINDINGS
DS = DAY OF STUDY a. Observation confirmed at necropsy.
:
418-008.PAGE B-15 000
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PROTOCOL 418-008: COMBINED ORAL iGAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (.`PONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 7) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP IV
1.6 MG/KG/DAY
RAT H
DESCRIPTION
8206
NO ADVERSE FINDINGS
8207 DS( 25- 67)
LOCALIZED ALOPECIA: LIMBS a
8208
NO ADVERSE FINDINGS
8209
NO ADVERSE FINDINGS
8210
NO ADVERSE FINDINGS
8211
NO ADVERSE FINDINGS
8212
NO ADVERSE FINDINGS
8213
NO ADVERSE FINDINGS
8214 DS< 14- 67)
LOCALIZED ALOPECIA: LIMBS a
8215
NO ADVERSE FINDINGS
8216
NO ADVERSE FINDINGS
8217 DS( 66- 67)
LOCALIZED ALOPECIA: LIMBS a
8218
NO ADVERSE FINDINGS
8219
NO ADVERSE FINDINGS
8220
NO ADVERSE FINDINGS
8221
NO ADVERSE FINDINGS
8222
NO ADVERSE FINDINGS
8223
NO ADVERSE FINDINGS
8224 DS( 17 )
CHROMODACRYORRHEA
DS< 17- 20)
CHROMORHINORRHEA
DS( 17- 20)
DYSPNEA
DS( 17- 59)
SNOUT: SWOLLEN
DS( 21- 58)
CHROMODACRYORRHEA
DS( 21- 67)
INCISORS: MISALIGNED a
DS< 65 )
CHROMODACRYORRHEA
DS< 67 )
CHROMODACRYORRHEA a
8225
NO ADVERSE FINDINGS
8226
NO ADVERSE FINDINGS
8227
NO ADVERSE FINDINGS
8228
NO ADVERSE FINDINGS
8229
NO ADVERSE FINDINGS
8230
NO ADVERSE FINDINGS
8231
NO ADVERSE FINDINGS
o 8232
o o
8233 8234 8235
N
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS
DS = DAY OF STUDY
a. Observation confirmed at necropsy.
418-008:PAGE B-16
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.91
TABLE BIO (PAGE 8): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP IV
1.6 MG/KG/DAY
RAT H
DESCRIPTION
8236 8237 8238
8239 8240
DS ( 13- 31) DS ( 32 )
DS { 67 )
NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: GROWN IN NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a
DS = DAY OF STUDY a. Observation confirmed at necropsy.
418-008:PAGE B-17
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 9) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP V
3.2 MG/KG/DAY
RAT (t
DESCRIPTION
8241 8242 8243 8244 8245 8246 8247 8248 8249 8250 8251 8252 8253
8254 8255 256 8257 8258 8259 8260 8261 8262 8263 8264 8265 8266
8267
DS ( 66- 67)
DS( 54 ) DS ( 54 ) DS { 34- 67)
DS ( 65- 67) DS ( 32- 43) DS( 44 )
NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS HYPERACTIVITY EXCESS SALIVATION NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LEFT EYE: CORNEAL OPACITY a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NECK: ABRASION (3.0 CM X 0.5 CM)a INCISORS: MISSING/BROKEN INCISORS : GROWN IN NO ADVERSE FINDINGS
DS = DAY OF STUDY a. Observation confirmed at necropsy.
418-008:PAGE B-18
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIO (PAGE 10) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP V
3.2 MG/KG/DAY
RAT U
DESCRIPTION
8268 8269 8270 8271 8272 8273 8274 8275
DS( 67 )
NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS
LIMBS a
DS = DAY OF STUDY a. Observation confirmed at necropsy.
418-008:PAGE B-19
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 1): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56 63b
RAT n
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8101 8102 8103 8104 8105 8106 8107 8108 8109 8110 8111 8112 8113 8114 8115 8116 8117 8118 8119 8120 8121 8122 8123 8124 8125 8126
354 . 434 . 400 . 393 . 362 . 410 . 394 . 386. 361. 412 . 391. 394 . 365. 410. 380. 400. 380. 414 . 391. 395. 359. 418. 391. 411. 373 . 321.
371. 477. 428 . 390. 383 . 468. 409. 400 . 387. 440. 427. 425. 382. 436. 397. 432. 398. 439. 416. 421. 377. 446. 414 . 442 . 401. 417.
363. 508 . 450. 416 . 410. 505. 440. 422. 412 . 467. 453 . 451. 402 . 454. 416. 458. 412. 465. 437. 456. 407. 467. 436 . 467. 423. 453 .
377. 549. 462. 437. 422 . 546 . 453 . 438 . 430 . 495. 461. 476. 420. 473. 434. 478. 429. 495. 454 . 466. 425. 488 . 453 . 494 . 442 . 476 .
385. 566. 485. 366 . 432 . 532 . 476 . 439. 435 . 514 . 493 . 486 . 430. 486. 450 . 505. 438. 516 . 454 . 483 . 432. 501. 477 . 503 . 462 . 491 .
392 . 591. 485. 452. 452. 586. 486 . 443 . 449. 529. 504 . 498 . 439. 495. 463 . 516 . 451. 541. 470 . 504 . 433 . 507. 494 . 506. 470. 505.
398. 613. 513 . 478. 476. 606. 491. 454. 459. 528. 501. 504 . 447. 507. 467. 526. 466. 564. 492. 516. 443 . 520. 498. 529. 484 . 518.
411. 628. 519. 480 . 474 . 622 . 502 . 470. 470. 553. 512. 499. 453. 520. 481. 535. 458. 562. 498. 528. 4SI. 532. 510. 531. 486 . 527 .
409 . 637 . 526 . 483 . 477. 643 . 510 . 478 . 476 . 567. 513 . 525 . 461 . 525. 491 . 546 . 484 . 573 . 516 . 526. 462 . 54 8. 521. 542 . 495 . 550.
420. 659. 551. 496 . 492. 661. 523 . 494 . 488. 589. 537. 537. 471. 551. 502 . 561. 498. 596. 524. 552. 481. 561. 539. 567. 513 . 566 .
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
418-008PAGE B-20
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 2) : BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
6 15 22 29 36 42a 49
RAT It
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8127 8128 8129 8130 8131 8132 8133 8134 8135
393. 407. 377. 399. 381. 397. 364. 398. 398.
418. 453 . 413 . 427. 402 . 419 . 376. 440 . 430 .
446 . 473 . 438. 453. 424 . 437. 389. 465. 460.
461. 495. 450. 479. 426. 431. 394 . 477. 484.
480. 531 . 458. 492. 446 . 443 . 411. 500 . 499.
502. 549. 472. 510. 466 . 481 . 425. 518. 511.
515. 569. 46B . 525. 479. 497. 424 . 536. 530.
523. 577. 502. 522. 488. 503. 436. 545. 536.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
56 63b
525. 595. 518. 538. 500 . 520 . 434 . 551. 544 .
550. 624 . 534 . 557. 511 . 538. 446 . 580 . 561.
418-008:PAGE B-21
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER; 6295.9)
TABLE Bll (PAGE 3) : BODY WEIGHTS INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56 63b
RAT ft
DOSAGE GROUP II
0.1 MG/KG/DAY
8136 8137 8138 8139 8140 8141 8142 8143 8144 8145 8146 8147 8148 8149 8150 8151 8152 8153 8154 8155 8156 8157 8158 8159 8160 8161
353. 433 . 383 . 385. 367. 418. 379. 390. 357. 408. 404. 398. 373. 416. 384 . 400. 379. 414 . 391. 374. 430. 388. 375. 402. 290. 404 .
365. 472. 410 . 409. 390 . 461. 404 . 425 . 390. 434 . 436. 427 . 398 . 446 . 410 . 436. 412. 444 . 424 . 412 . 466 . 408 . 402 . 423 . 368 . 431 .
372 . 497. 422. 426. 409. 490. 423 . 450 . 404 . 456. 459. 452 . 417. 460. 431. 456 . 435. 480. 452. 430. 500. 423 . 422. 447 . 396 . 452 .
384 . 525 . 453 . 444 . 422. 521. 436 . 467 . 423 . 467. 483 . 465. 426. 483 . 456 . 467. 462. 512. 471. 454 . 530 . 447. 445. 474 . 420 . 469.
378. 547, 461. 468 435, 536. 449. 472. 433 , 487. 508. 486. 431. 498. 474 . 477. 475. 540. 486. 472. 550. 472. 450. 479. 439. 485.
393. 556. 474 . 466 . 452. 539. 465. 482. 435. 496 . 522. 492 . 437. 511. 489. 479. 494 . 549. 494 . 489. 567. 486. 460. 495. 450 . 491.
396. 578. 492 . 478. 466 . 563. 467. 496 . 448. 512. 537. 507. 447. 513. 500 . 492 . 504 . 567. 500. 504 . 594 . 509. 474. 502. 455. 508.
401. 584 . 491. 485. 476. 574. 478. 508. 452. 524. 550. 521. 458 . 531. 515. 509. 517 . 572. 515 . 504 . 603 . 508. 484. 512. 464 . 514.
409. 600 . 507. 489. 478. 583. 476 . 508. 453 . 520. 542. 522 . 463. 532. 526. 509. 526. 594 . 525. 500. 622. 519. 490. 517. 467. 519.
408. 615 . 515 . 504 .
491 . 597. 493 . 528. 457. 524 . 559. 538. 474 . 556. 544 . 525 . 546. 612 . 539. 522. 648. 543 . 518. 538. 486 . 533 .
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
418-008:PAGE B-22
o
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PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 4) : BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56
RAT H
DOSAGE GROUP II
0.1 MG/KG/DAY
8162 8163 8164 8165 8166 8161 8168 8169 8170
378. 404. 381. 406 . 387. 407. 379. 404 . 412.
392. 426. 390. 437. 425. 447. 408. 426. 438.
410 . 456 . 413. 462. 444 . 456 . 424 . 443 . 469.
426. 481. 434 . 479. 443 . 469. 433. 460. 499.
435. 507. 450. 499 466 487 450 483 521
450. 520. 467. 509. 477. 511 . 466. 502. 534 .
467. 54 9. 482 . 529. 501. 527. 471. 518. 556.
474 . 556 . 492. 546 . 517. 537. 476. 531. 582.
476. 557. 498. 552. 523. 550. 477. 532. 590.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
63b
497. 580. S22. 571. 534 . 572. 486 . 536. 621.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 5) : BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56 63b
RAT H
DOSAGE GROUP III
0.4 MG/KG/DAY
8171 8172 8173 8174 8175 8176 8177 8178 8179 8180 8181 8182 8183 8184 S185 8186 8187 8188 8189 8190 8191 8192 8193 8194 8195 8196
354 . 437. 394 . 396 . 360. 408. 385. 392 . 361. 408 . 396. 399. 373. 417. 382. 408. 377. 404 . 379. 404 . 380. 406 . 389. 389. 298. 408.
366. 480. 422. 421. 384. 448 . 411. 418. 385. 427. 423. 417. 386. 448. 407. 429. 406. 430. 391. 422 . 401 . 437. 415. 405. 378. 436 .
375. 517. 436 . 443 . 392. 478 . 424 . 445. 416. 452. 438 . 437. 412. 477. 415. 451. 431. 455. 406 . 447 . 427. 456. 439. 428. 400. 463 .
379. 543 . 456. 462 . 398. 500 . 446 . 469. 436 . 476. 459. 464 . 430. 508. 433 . 460. 446 . 477. 433 . 463. 447 . 477 . 466 . 434 . 424 . 481 .
387. 565. 467. 478 410. 511. 467. 484 453 , 485. 468. 472. 435. 533 . 443 . 466 . 455. 496 . 451. 475 . 470. 490. 481. 465. 434 . 502.
390. 578 . 474 . 486 . 425. 523 . 468. 491. 454 . 492 . 479. 482. 444 . 546 . 456. 466. 473 . 507. 449. 482 . 482 . 500. 486. 477. 444 . 513.
402 . 528. 485. 503 . 448 . 544 . 491. 503 . 470 . 511. 490. 499. 448. 559. 461. 467. 485. 521 . 465. 493 . 490 . 514. 511. 489 . 458. 530.
409. 542. 494 . 498. 458. 542. 501. 511. 475. 522. 490. 502 . 452. 574 . 474 . 477. 499. 519. 474. 499. 497. 513. 518. 505. 468. 535.
416 . 575. 489. 516 . 462. 54 9. 511. 515 . 472. 528 . 483 . 514 . 460. 588. 471 . 482 . 507. 536. 475. 506 . 499. 515. 526. 522. 479. 551.
418 . 566. 486. 522. 482. 573 . 528. 530. 489. 535. 490. 532 . 468. 604 . 491 . 488. 515. 534. 486. 528. 521. 534. 546. 536. 491. 577.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
U
i0
418-008.PAGE B-24
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 6): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56 63b
RAT It
DOSAGE GROUP h i
0.4 MG/KG/DAY
8197 8198 8199 8200 8201 8202 8203 8204 8205
389. 399. 386. 409. 384. 417. 374 . 397. 385.
428. 422. 416. 448. 405. 465. 404 . 406 . 412.
442 . 444 . 440 . 482 . 413 . 485 . 417 . 422 . 430 .
467, 453 . 466 . 509. 413. 487 . 424 . 438. 451.
484 . 467. 485 529 437 515 445 447 472
502. 484 . 502 . 538. 446 . 540. 459. 463. 481.
518. 494 . 518 . 549. 460. 563. 478. 474 . 499.
516. 499. 514 . 553. 467. 574 . 489. 474 . 510.
516. 501. 513 . 571. 466 . 576. 491. 484. 513 .
518. 518. 539. 583. 469. 601. 498. 490 . 520.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
418-008:PAGE B-25
o >
O
M U
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 7): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56 63b
RAT ft
DOSAGE GROUP IV
1.6 MG/KG/DAY
8206 8207 8208 8209 8210 8211 8212 8213 8214 8215 8216 8217 8218 8219 8220 8221 8222 8223 8224 8225 8226 8227 8228 8229 8230 8231
354 . 428. 384 . 399. 364 . 402 . 387. 392. 375. 422. 387. 398. 363. 403 . 395. 402. 379. 405. 385. 400. 380. 405. 373. 408. 382. 405.
361. 463 . 409. 427. 376. 426. 420. 411. 393 . 448. 412 . 428. 383. 436 . 421. 433 . 406 . 432. 415. 402. 407 . 438. 385. 428. 396. 434 .
383 . 496 . 430 . 446 . 394 . 454 . 436. 429. 412 . 477. 437. 450 . 402. 456 . 437. 461. 423 . 453 . 437. 437 . 429. 468 . 394 . 456. 418 . 466 .
395. 506. 453 . 465. 408. 474 . 446 . 446 . 424 . 491. 464 . 472. 423. 473 . 451. 471. 446 . 471. 367. 462. 444 . 478 . 392. 478. 431 . 484 .
407. 523 . 463 . 472. 413 . 486 . 462. 453 . 435. 495. 471. 484 . 438. 485. 467. 482 . 454 . 497. 408 . 473 . 459. 497. 405 . 495. 446. 487.
417. 524 . 464 . 485. 419. 486 . 470. 460. 444 . 502 . 487. 492 . 435. 498. 475. 489. 470 . 524 . 438. 484 . 472 . 508. 402 . 494 . 458. 491.
428 . 539. 479. 498. 434 . 500. 480. 468. 460 . 532. 510. 503 . 439. 504 . 492. 501. 473 . 540. 461. 495 . 478. 528. 412 . 510. 466 . 494 .
428. 546 . 488. 506 . 442. 507. 502 . 512. 463 . 538. 514 . 511. 443 . 515. 490. 502. 472 . 554 . 477. 508. 490. 530. 415. 512. 468. 498.
433 . 563 . 508. 517. 455. 514 . 491. 493 . 474 . 535. 520. 518. 448. 517. 493 . 514 . 465. 567. 486. 518. 494 . 538. 416. 517. 462. 495.
444 . 576. 520. 531. 464 . 532 . 514 . 499. 486 . 551. 547. 531. 460. 538. 496. 535. 482. 579. 494 . 534 . 505. 562. 419. 534 . 488. 512 .
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
418-008:PAGE B-26
o o o w
u
PROTOCOL 410-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 8): BODY WEIGHTS INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56 63b
RAT H
DOSAGE GROUP IV
1.6 MG/KG/DAY
8232 8233 8234 8235 8236 8237 8238 8239 8240
390. 397. 376 . 397. 373 . 406 . 380 . 406. 378.
411. 422 . 402 . 435. 392 . 443 . 400. 418. 404 .
437 . 452. 42B . 441 . 405. 47a . 421 . 439. 422.
438. 471 . 449 . 469. 401 . 478 . 421. 447. 447.
450, 488. 466 486 440 503 433 442 457
459. 494 . 468. 498. 452 . 523. 438. 442. 462.
471. 501. 470 . 512. 455. 554. 440. 448. 474.
487 . 505. 481 . 526. 460. 567. 454 . 449. 477.
485. 515. 493 . 526. 463. 567. 450. 451. 490.
501. 523. 512. 538. 481. 589. 458. 456. 491 .
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
1
418-008: PAGE B-27
o
t:
u
ui
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 9) : BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56 63b
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
8241 8242 8243 8244 824S 8246 8247 8248 8249 8250 8251 8252 8253 8254 8255 8256 8257 8258 8259 8260 8261 8262 8263 8264 8265 8266
354 . 439. 390 . 395. 366. 410 . 377. 388. 367 . 405. 384 . 391 . 359. 415. 390 . 398. 378. 405. 388. 413 . 370. 409. 379. 403 . 374 . 401 .
380. 477. 415. 410. 378. 432 . 404 . 420. 388. 431. 402. 415. 375. 438. 413 . 417. 393. 439. 407. 439. 394 . 425. 408. 436. 397. 429.
392 . 507. 441. 426 . 400 . 448. 425. 434 . 396. 450. 422 . 434 . 398. 461. 444 . 439. 403 . 460. 428. 463 . 408 . 434 . 439. 461. 406 . 450.
393 . 528 . 458. 445. 413 . 474 . 426. 453 . 406 . 463 . 438. 446 . 421 . 480. 461. 449. 411. 481. 438 . 491 . 425. 448 . 465. 486 . 395 . 440 .
396. 553. 466. 456 421 480, 425 451 413 476 . 445. 449 432 491 469. 4S3 . 409. 486 , 438. 504 424 447, 483 . 502 , 410. 452 .
391. 554 . 470. 462 . 422. 497. 421. 459. 408. 476 . 444 . 451 . 436. 494 . 478 . 447. 415. 490. 432. 517. 431. 445 . 492. 493 . 414 . 464 .
394 . 559. 486 . 469. 436 . 500. 429. 472. 417. 477. 453 . 458. 435. 500 . 473 . 443. 416. 485. 440. 527. 435. 450 . 500. 505. 413. 466 .
395 . 572. 482. 473. 437. 497 . 425. 482 . 418. 481 . 456 . 468. 436. 502 . 467 . 451 . 414 . 492 . 434 . 516. 437. 450. 498. 503 . 413. 474 .
393 . 566 . 483 473 . 444 . 508. 427. 481 . 421. 478 . 466 . 470 . 436. 500 . 476 . 442 . 420. 497 . 433 . 521. 445. 457 . 511. 510. 424 . 477 .
400 . 578. 513. 482. 451. 515. 430. 447. 431. 496 . 447. 474 . 448. 511. 490. 462. 425. 498. 432. 555. 453. 466. 520. 516. 423 . 488.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
418-008:PAGE B-28
o
N CJ
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Bll (PAGE 10) : BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAY 1
8 15 22 29 36 42a 49 56 63b
RAT It
DOSAGE GROUP V
3.2 MG/KG/DAY
8267 8268 8269 8270 8271 8272 8273 8274 8275
375. 410. 382 . 403 . 386 . 405 . 379. 400. 400.
395. 448. 415. 428. 410. 439. 399. 423 . 427.
410. 484 . 440. 456 . 432. 470. 435. 443 . 452.
403 . 498. 453. 457. 432. 464 . 432. 453 . 454 .
414 . 516. 470. 479. 456 . 494 440. 460 472
415. 517. 479. 481. 474 . 493 . 442. 467. 488.
423 . 531. 493 . 500. 483. 512. 456 . 477. 497.
422 . 528 . 494 . 491 . 489. 512. 460 . 481. 480.
430. 534. 498 . 492 . 495. 520 . 455. 491. 487.
432 . 544 . 507. 498. 510. 529. 458. 497. 504.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL.AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR1S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 1): FEED CONSUMPTION VALUES - INDIVIDUAL.DATA - Fo GENERATION MALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
RAT #
DOSAGE GROUP
0 (VEHICLE) MG/KG/DAY
8101 8102 8103 8104 8105 8106 8107 8108 8109 8110 8111 8112 8113 8114 8115 8116 8117 8118 8119 8120 8121 8122 8123 8124 8125 8126
158. 229. 173 . 164 . 168. 226 . 180. 167. 148 . 181. 189. 206 . 160. 185 . 172 . 186 . 170 . 208. 184 . 179 . 166. 197 . 199. 208. 169. 212 .
147. 232. 174 . 164. 184. 229. 188. 178. 159. 188. 189. 219. 168. 182 . 185. 193 . 177. 213 . 190. 178 . 181. 193 . 193 . 192 . 171. 204 .
149. 253. 183. 173 . 187. 254 . 193. 183 . 171. 201. 202 . 224 . 176. 195 . 191. 199. 185. 222. 194 . 191 . 201. 203 . 197. 205. 178 . 201.
165 . 233. 185. 108. 179. 202. 190 . 188. 162. 208. 213 . 231. 174 . 190 . 200 . 199. 175. 224 . 176 . 184 . 184. 193. 207. 185. 183 . 193 .
151. 254 . 189. 228 . 195. 279. 197. 169. 16B . 213. 222 . 230. 177. 201. 196 . 201 . 186. 230. 196. 197. 186. 208. 212 . 196. 182. 196 .
130. 193 . 160. 182. 172 . 213 . 153 . 146 . 145. 154 . 146. 175. 146. 160. 147. 160. 156. 198. 174 . 169. 144 . 167. 162. 173. 150 . 159.
158 . 232. 190.
c 192. 242. 183 . 184 . 166. 215. 194 . 211. 168. 206 . 190 . 192. 188 . 216. 195. 191. 179. 200 . 195. 187. 172. 198 .
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value.
418-008:PAGE B-30
o >
O M
U00
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 2): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAYS 1- 8 8- 15 IS- 22 22- 29 29- 36 36 - 42a 56b- 63
RAT #
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8127 8128 8129 8130 8131 8132 8133 8134 8135
191. 222. 207. 192 . 189. 177. 155. 199. 199.
194 . 204 . 204 . 199. 206 . 180. 158 . 206. 211.
191. 228 . 203 . 201. 169.
c 131. 185. 198.
189. 231 . 202 . 205. 243. 213 . 195. 226. 225.
196 . 235. 210 . 223 . 237. 233. 182. 234. 228.
170. 196. 174 . 189. 191. 176 . 142. 184 . 183.
200 . 225. 200. 202. 214 . 203 . 159. 211. 204.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value.
418-008: PAGE B-31
o
o
o
n u <>
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 3) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAYS
RAT (t
8136 8137 8138 8139 8140 8141 8142 8143 8144 8145 8146 8147 8148 8149 8150 8151 8152 8153 8154 8155 8156 8157 8158 8159 8160 8161
1- 8 8- 15 15- 22 22- 29 29 36 36- 42a 56b- 63
DOSAGE GROUP II
0 , .1 MG/KG/DAY
149. 205. 168. 169. 166. 217. 171. 200. 1B2. 179. 192. 188. 169. 208. 184. 199. 189. 200. 195. 172. 198. 177. 167. 206 . 195. 200.
157. 209. 163 . 170 . 183. 209. 172 . 210. 185, 188. 201. 196. 171. 195. 181. 186. 197.
c 196. 187. 207 . 166 . 175. 208. 188. 215.
172. 214 . 180. 185. 202. 228. 184. 214. 182. 196. 208. 202. 173. 208. 183. 196. 199. 243 . 198 . 198. 228. 184 . 198. 217. 196. 206.
167. 206. 181. 189. 178. 225. 184. 201. 179. 186. 215. 217. 179. 191. 192. 188. 197. 227. 201. 200. 214 . 200. 197. 214 . 198. 200.
c 208. 182 . 193 . 191. 243 . 185. 199. 177 . 203 . 214 . 208 . 178. 212. 203 . 189. 196. 234 . 191. 205. 214 . 206 . 198. 217. 194 . 203 .
132 . 172. 157. 154 . 151. 181. 157 . 167. 153 . 168. 170. 163. 140. 158. 161. 149. 154 ; 187. 153. 169. 189. 173 . 158. 175. 161. 167.
174. 204 . 181 . 193. 179. 213 . 183. 196. 163 . 149. 186. 203. 175. 204. 188. 188. 192. 216. 181. 188. 231. 191. 213. 199. 189. 186 .
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value.
418-008:PAGE B-32
00C240
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 4) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA Fo GENERATION MALE RATS
DAYS 1- a 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
RAT
DOSAGE GROUP II
0 .1 MG/KG/DAY
8162 8163 8164 8165 8166 8167 8168 8169 8170
168. 198. 174 . 205. 194 . 196 . 183 . 187. 189.
175. 208 . 180. 205. 193 . 198. 173. 175. 197.
174 . 226 . 182 . 211. 147. 189 . 151 . 172. 201.
176. 212 . 180 . 212 . 219. 238. 194 . 220. 213 .
179. 234. 198. 220 . 221. 223 . 195. 227. 220 .
152 . 183. 150 . 183. 169. 177. 1S1. 182. 185.
181. 212. 196. 207. 194 . 212 . 177. 197. 214 .
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
1
418-008:PAGE B-33
o o
e
h*
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR' S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 5): FEED CONSUMPTION VALUES - INDIVIDUAL DATA. - Fo GENERATION MALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
RAT
DOSAGE GROUP III
0.4 MG/KG/DAY
Bill 8172 8173 8174 8175 8176 8177 8178 8179 8180 8181 8182 8183 8184 8185 8186 8187 8188 8189 8190 8191 8192 8193 8194 8195 8196
155. 218. 190. 176 . 168. 205 . 180 . 192. 202. 177 . 186. 185. 169. 210 . 174 . 196. 182. 193 . 178. 193. 192. 168 . 182 . 166 . 200. 195 .
156. 221 . 176 . 180. 168 . 214 . 174 . 196 . 208. 188 . 170. 195. 180. 214. 161 . 191. 193 . 192. 181. 193. 187. 189. 190 . 177. 192. 205.
162. 228. 186. 191. 168. 218. 194. 200. 193. 199. 192. 217. 190. 223 . 195. 182. 192. 197. 198. 192. 209. 190. 206. 174 . 194 . 203 .
159. 213 . 105. 186 . 167. 205. 191 . 192. 202 . 194 . 184 . 207. 183. 222. 201. 171. 197. 206. 191. 188. 202 . 195. 194 . 184 . 192 . 198 .
156 . 217 . 186. 197.
c 214 . 182 . 205. 204 . 191. 192. 215. 181. 227. 191 . 192. 210. 208. 198. 201. 202. 202. 211. 191. 187. 190.
132. 96 .
155. 153 . 159. 182 . 162 . 154 . 160. 163 . 160 . 180. 150. 171. 174 . 144 . 160. 164 . 164. 158. 172 . 159. 184 . 159 . 160 . 178.
153 . 177 . 160 . 183 . 186. 205. 187. 178. 175. 176. 165. 207. 182. 194 . 188. 175 . 186. 177. 178. 188. 201. 186. 199. 188. 181. 205.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Spilled feed precluded the calculation of this value.
418-008:PAGE B-34
O
a o
0
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 6) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
RAT tt
DOSAGE GROUP III
0 .4 MG/KG/DAY
8197 8198 8199 8200 8201 8202 8203 8204 8205
193 . 181. 180. 198. 180. 227. 183 . 177. 187.
178. 186 . 198 . 218 . 164 . 216 . 172 . 171. 177.
192. 185 . 204 . 227. 135. 162 . 162. 167. 195.
185. 173 . 207. 226. 198. 226 . 218. 193. 208.
195. 198. 209. 234. 180. 245. 207 . 192 . 220 .
161 . 161. 164 . 172 . 148. 208. 164 . 157. 174 .
170. 175. 20a. 216. 177. 217. 183. 179. 204 .
DAYS DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
418-008:PAGE B-35
C4
PROTOCOL 4 1 -008 : COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 7): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAYS
RAT ft
8206 8207 8208 8209 8210 8211 8212 8213 8214 8215 8216 8217 8218 8219 8220 8221 8222 8223 8224 8225 8226 8227 8228 8229 8230 8231
1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
DOSAGE GROUP IV
1.6 MG/KG/DAY
152 . 191. 184 . 178. 1S3 . 200 . 196. 171 . 173 . 217. 187. 185 . 167. 191. 189. 190 . 183. 200 . 197. 163 . 186 . 201. 158. 213 . 173 . 210.
164. 193 . 179. 172. 163 . 204 . 190. 171 . 166 . 199. 177. 192 . 165. 172. 177. 182. 177. 193 . 191. 183 . 179. 193 . 157. 210. 181. 194 .
166 . 196. 194 . 180. 168. 207. 197. 176 . 176 . 185. 187. 197. 186 . 193 . 190. 184 . 186. 189.
b 199. 189. 204 . 155. 228 . 182 . 188.
167. 186 . 185. 178. 167. 195. 193 . 176. 176. 182 . 188 . 198. 162. 177. 188 . 185 . 176. 212. 154 . 195 . 188. 196 . 163. 219. 183 . 197.
167. 186.
c 188 .
48. d 182. 201. 178 . 182. 211 . 185 . 192. 173. 201. 197. 193. 188. 228. 202. 168 . 192. 221. 171. 229. 194 . 205.
137. 155. 153 . 155 . 127. 161 . 144 . 144 . 150 . 171. 161. 172 138. 146 . ISO. 159. 145. 254 . 189. 167 . 161. 181 . 134 . 176. 158. 157.
166. 188. 180 . 184 . 146. 180. 185. 178 . 174 . 189. 202 . 185 . 153 . 190. 170 . 183 . 149. 203. 199. 186 . 180. 198. 157. 210. 189. 160.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation. c. Wet feed preclueed the calculation of this value. d. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses.
418-008PAGE B-36
00244
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR1S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 8) : FEED CONSUMPTION VALUES INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
RAT It
DOSAGE GROUP IV
1 .6 MG/KG/DAY
8232 8233 8234 8235 8236 8233 8238 8239 8240
157. 204 . 174. 198. 174. 202 . 183 . 177. 195.
205. 193 . 173 . 163 . 166. 201 . 181. 170 . 177.
194 . 199. 188. 210. 125. 156 . 148. 161. 185 .
198 . 193 . 185. 213 . 217. 223 . 200. 172 . 197.
227. 201. 167. 212. 203 . 231. 184 . 175. 196.
183 . 156. 163 . 161. 148. 185. 149. 143. 161 .
194 . 169. 185. 183 . 182 . 207. 167. 169. 164 .
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
418-008: PAGE B-37
245
o o
o
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 9) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DAYS
RAT H
8241 8242 8243 8244 8245 8246 8247 8248 8249 8250 8251 8252 8253 8254 8255 8256 8257 8258 8259 8260 8261 8262 8263 8264 8265 8266
1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
DOSAGE GROUP V
3 .2 MG/KG/DAY
173 . 236 . 202 . 177. 160 . 194 . 183 . 185. 161. 188. 186. 187. 167. 190. 182. 188. 166. 208. 179. 193 . 182. 179. 190 . 219. 178. 182 .
168. 220 . 198 . 181. 170 . 181. 171. 176. 153. 181. 189. 171. 164 . 184 . 178 . 174 . 162. 196. 174 . 178. 165. 160. 186 . 202. 162 . 181.
158. 227. 198 . 180. 176 . 197. 166. 194 . 158. 183. 199. 178. 175. 188 . 191. 187. 154 . 201. 186 . 186 . 181. 176. 213 . 204 . 115. 138 .
189. 210. 190. 102. 166 . 200. 151. 166 . 150. 182. 185. 205 . 167. 186. 177. 173 . 158 . 184 . 176 . 181. 153. 166 . 204 . 200. 180 . 188.
138. 207.
c 179.
168. 209. 147. 179. 153 . 188. 172. 195. 184 . 189. 191. 181. 156. 185. 172. 192. 169. 164 . 201. 171. 157 . 177 .
117. 170. 155. 142 . 138 . 154 . 128. 149. 122. 140. 148. 162. 127 . 147. 137 . 132 . 125. 140 . 144 . 152 . 144 . 129. 164 . 149. 140 . 144 .
142. 199. 177 . 169. 157. 177. 150. 135. 141 . 170. 163. 160. 155. 167. 175. 164 . 149. 176. 148 . 162 . 154. 157. 186. 204 . 141. 169.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
6 b. First value recorded after cohabitation. c. Wet feed precluded the calculation of this value.
o N
a
418-008:PAGE B-38
418-008:PAGE B-39
000247
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B12 (PAGE 10) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA Fo GENERATION MALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29 36 36- 42a 56b- 63
RAT H
DOSAGE GROUP V
3 .2 MG/KG/DAY
8267 8268 8269 8270 8271 8272 8273 8274 8275
172 . 215. 171. 190. 207 . 196. 192. 198. 189.
173. 223 . 164 . 194 . 199 . 190. 194 . 189. 186 .
130 . 189. 173 . 166 . 153 . 149. 148. 187. 151.
184 . 219. 184. 204 . 208. 201. 194 . 199. 205.
165. 203. 183 . 201 . 202 . 188. 175 . 184 . 184 .
136 . 160. 147. 155. 160 . 156 . 153 . 157. 151.
156. 185. 162. 174 . 182. 192 . 158 . 172 . 176 .
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. First value recorded after cohabitation.
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE B13 (PAGE 1): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT ft
DAYS IN COHABITATION
MATING STATUS
MATING DATE
FEMALE PREGNANCY STATUS
8101 8102 8103 8104 8105 8106 8107 8108 8109 8110a 8110b 8111 8112 8113 8114 8115 8116 8117 8118 8119 8120 8121 8122 8123 8124 8125 8126 8127 8128 8129 8130
2 1 2 3 7 1 2 2 1 1 7 4 7 3 3 1 1 7 3 3 1 2 1 4 4 i 4 7 2 1 3
M M M M M M M M M M DID NOT MATE M M M M M M M M M M M M M M M M M M M M
C
C
C
C
C
C
C c
C
C
-
C
NC
C c
C c c c c c c c c c c c c c c_ c
P (8601) P (8802) P (8803) P (8804 P (8805) P (8806) P (8807) P (8808) P (8809) P (8810) -(8812) P (8811) P (6812} P (8813) P (8814) P (8815) P (8816) N P (8817) N P (8818) P (8819) P (8820) P18821) P (8822) P (6823) P (8824) P (8825) P (8626) P (8827) P (8828) P (8829) P (8830)
M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT P = NOT PREGNANT a. Result of first cohabitation period. b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat.
418-008.PAGE B-40
000248
PROTOCOL 418-00B: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 2) : MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT #
DAYS IN COHABITATION
MATING STATUS
8131 4 M
8132 3 M
8133
1M
8134 4 M
8135 4 M
M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT P = NOT PREGNANT
MATING DATE
c C c c c
FEMALE PREGNANCY STATUS
P (8831) P (883 2) P (883 3) P (8834) P (8835)
418-008:PAGE B-41
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 3): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT #
DAYS IN COHABITATION
MATING STATUS
8136 1 M 8137 1 M 813B 3 M B139 1 M 8140 3 M 8141 5 M 8142 2 M 8143 1 M 8144 1 M 8145 3 M 8146 3 M 8147 3 M 8148 1 M 8149 4 M 8150 1 M 8151 4 M 8152 4 M 8153 3 M 8154 4 M 8155 4 M 8156 i M 8157 4 M 8158 4 M 8159 1 M 8160 4 M 8161 1 M 8162 3 M 8163 3 M 8164 1 M 8165 4 M
M MATED ( ) = FEMALE RAT NUMBER
C CONFIRMED NC = NOT CONFIRMED P PREGNANT P = NOT PREGNANT
0
0to1
MATING DATE
C
C
C
C
C c c
c
c c c c c c c c c c c c c c c c c c c c c c
FEMALE PREGNANCY STATUS
P (8836) P (8837) P (8838) P (8839) P (8840) P (8841) P (884 2) P (8843) P (8844) P (884 5) P (8846) P (884 7) P (8848) P (884 9) NP (8850) P (8851) P (8852) P (8853) P (8854) P (8855) NPI8856) P (8857) P (8858) P (8859) P (8860) N P (8861) P (8862) P (8863) P (8864) P (8865)
418-008:PAGE B-42
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 4): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT ft
DAYS IN COHABITATION
MATING STATUS
8166 2 M 8167 3 M 8168 3 M 8169 4 M 8170 1 M
M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT P = NOT PREGNANT
MATING DATE
c c C c c
FEMALE PREGNANCY STATUS
P (8866) P (8867) P (8868) P (8869) P (8870
418-008:PAGE B-43
o N M
H
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 5) : MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT H
8171 8172 8173 8174 8175 8176 8177 8178 8179 8180a 8180b 8181 8182 8183 8184 8185 8186 8187 8188 8189 8190 8191 8192 8193 8194 8195 8196 8197 8198 8199 8200a 8200b
DAYS IN COHABITATION
7 i i 3 4 4 i i i i 7 4 4 1 1 4 i i i 7 i 4 5 1 1 1 4 4 3 4 4 7
MATING STATUS
DID NOT MATE M M M
M
M
M
M M
M
M
M M M M
M
M
M
M DID NOT MATE M M M
M
M
M
M M M M
M
DID NOT MATE
MATING DATE
_
C
C
C c c c c c c c c c c c c c c c
c c c c c c c c c c c
-
FEMALE PREGNANCY STATUS
-(8871) P (8872) P (8873) P (8874) P (8875) P (8876) P (8877) N P (8878) NP (8879) P (8880) P (8889) P (8881) P (8882) N P (8883) P (8884) P (8885) NPI8886) P (8887) P (B888) - (8889) P (8890) P (8891) P (8892) P (8893) P (8894 ) P (8895) P (8896) P (8897) P (8898) P (8899) P (8900) -(8871)
o M MATED ( ) = FEMALE RAT NUMBER
0
to
C CONFIRMED NC = NOT CONFIRMED P PREGNANT P = NOT PREGNANT
a. Result of first cohabitation period.
01 b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat.
to
418-008:PAGE B-44
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 6): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT tf
DAYS IN COHABITATION
MATING STATUS
8201 4 M 6202 1 M 8203 1 M 8204 1 M 8205 1 M
M = MATED ( ]1 = FEMALE RAT NUMBER C = CONFIRMED NC = HOT CONFIRMED P = PREGNANT P = NOT PREGNANT
MATING DATE
C C C C C
FEMALE PREGNANCY STATUS
P(8901) P (8902) N P (8903) N P (8904) P (8905)
418-008: PAGE B-45
o o
0
01 CO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 7) : MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP IV
1.6 MG/KG/DAY
RAT #
DAYS IN COHABITATION
MATING STATUS
MATING DATE
FEMALE PREGNANCY STATUS
8206 7 M NC P (8906)
8207a
1
M
C N P (8907)
8207b
7
DID NOT MATE
-
- (8930)
8208a
1
M
C P (8908)
8208b 8209 8210 8211 8212 8213a
7 4 1 1 1 4
DID NOT MATE M M M M M
-
c c c c c
-(8906) P (8909) P (6910) P (8911) P (8912) P {8913)
8213b 8214 8215 8216 8217 8218 8219 8220 8221 8222 8223 8224 8225 8226
7 3 1 1 1 4 3 4 2 1 3 1 1 3
DID NOT MATE M M M M M M M M M M M M M
-
c c c c c c c c c c c c c
-(8939) N P (8914)
P (8915) P (8916) P (8917) N P (8918) P (8919) P (8920) P (8921) P (8922) N P (8923) P (8924) P (8925) P (8926)
8227 1 M c P (8927) 8228 3 M c P (8928)
8229 3 M c P (8929)
8230 7 M NC P (8930)
8231 4 M c P (8931) 8232 1 M c P (8932) 8233 2 M c N P (8933) 8234 2 M c P (8934)
o 8235 3 M c P (8935)
oo M = MATED ( ) FEMALE RAT NUMBER
C CONFIRMED NC = NOT CONFIRMED
to P = PREGNANT P = NOT PREGNANT
a. Result of first cohabitation period.
b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat.
418-008: PAGE B-46
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 8) : MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP IV
1.6 MG/KG/DAY
RAT ft
DAYS IN COHABITATION
MATING STATUS
MATING DATE
FEMALE PREGNANCY STATUS
8236 8237 8238a 8239 8240
3 1
7 2
M C P (8936) M C P (8937)
M NC
P (8939)
M C P (8940)
M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT P = NOT PREGNANT a. Rat 8238 was not assigned to cohabitation because there were no available female rats.
418-008:PAGE B-47
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o
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Cfl cn
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 9): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP V
3.2 MG/KG/DAY
RAT )t
DAYS IN COHABITATION
MATING STATUS
MATING DATE
FEMALE PREGNANCY STATUS
8241 8242 8243a 8243b 8244 8245 8246 8247 8248 8249 8250 8251 8252 8253 8254 8255 8256 8257 8258 8259 8260 8261 8262 8263 8264 8265 8266 8267 8268 8269 8270
1 7 4 7 4 2 7 1 1 3 4 1 2 1 1 2 3 4 i 7 5 4 2 1 3 1 1 2 4 2 3
M DID NOT MATE M M M M DID NOT MATE M M M M M M M M M M M M DID NOT MATE M M M M M M M M M M M
C
-
C
C c
C
-
C c c c
C c
C c c c c c
-
c
C c c c c c c c
C c
P (8941) -(8942) P (8943) P (8959) P (8944) N P (8945) -(8946) P (8947) P (8948) P (8949) P (8950) P (8951) N P (8952) P (8953) P (8954) P (8955) P (8956) N P (8957) P(B958) -(8959) P (8960) P (8961) P (8962) N P (8963) P (8964) P (8965) P (8966) P (8967) P (8968) P (8969) P (8970)
O 5
M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT P = NOT PREGNANT
e a. Result of first cohabitation period.
b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat.
&
418-008-.PAGE B^t8
PROTOCOL 418-008; COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B13 (PAGE 10) : MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP V
3.2 MG/KG/DAY
RAT 1f
DAYS IN COHABITATION
MATING STATUS
MATING DATE
FEMALE PREGNANCY STATUS
8271 1 M C P (8971)
8212a
1
M
C N P (8972)
8272b
5
M
C P(8946)
8273 2 M C P (8973)
8274 3 M C P (8974)
8275a
4
M
c P (8975)
8275b
6
M
c P (8942)
M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED NC = NOT CONFIRMED P = PREGNANT P = NOT PREGNANT a. Result of first cohabitation period. b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat.
418-008:PAGE B-49
o
o e ro CA
vl
o
a
0
M 01 QC
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B14 (PAGE 1) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I
0 (VEHICLE)
RAT NUMBER
8101 8102
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
DS 67 66 ALL TISSUES APPEARED NORMAL. DS 67 66 ALL TISSUES APPEARED NORMAL.
8103 DS 67 66 PROSTATE: SMALL. ALL OTHER TISSUES APPEARED NORMAL.
8104 DS 67 66 ALL TISSUES APPEARED NORMAL. 8105 DS 67 66 ALL TISSUES APPEARED NORMAL. 8106 DS 67 66 ALL TISSUES APPEARED NORMAL. 8107 DS 67 66 ALL TISSUES APPEARED NORMAL. 8108 DS 67 66 ALL TISSUES APPEARED NORMAL. 8109 DS 67 66 ALL TISSUES APPEARED NORMAL. 8110 DS 67 66 ALL TISSUES APPEARED NORMAL. 8111 DS 67 66 ALL TISSUES APPEARED NORMAL. 8112 DS 67 66 ALL TISSUES APPEARED NORMAL. 8113 DS 67 66 ALL TISSUES APPEARED NORMAL. 8114 DS 67 66 ALL TISSUES APPEARED NORMAL. 8115 DS 67 66 ALL TISSUES APPEARED NORMAL. 8116 DS 67 66 ALL TISSUES APPEARED NORMAL. 8117 DS 67 66 ALL TISSUES APPEARED NORMAL. 8118 DS 67 66 ALL TISSUES APPEARED NORMAL. 8119 DS 67 66 ALL TISSUES APPEARED NORMAL. 8120 DS 67 66 ALL TISSUES APPEARED NORMAL. 8121 DS 67 66 ALL TISSUES APPEARED NORMAL. 8122 DS 67 66 ALL TISSUES APPEARED NORMAL. 8123 DS 67 66 ALL TISSUES APPEARED NORMAL.
8124 DS 67 66 LIVER: LARGE (49.71 G ) . KIDNEYS: BILATERAL, LARGE (LEFT = 4.37 G; RIGHT = 4.38 G ) . SPLEEN: LARGE (2.54 G ) . ALL OTHER TISSUES APPEARED NORMAL.
8125 DS 67 66 ALL TISSUES APPEARED NORMAL. 8126 DS 67 66 ALL TISSUES APPEARED NORMAL. 8127 DS 67 66 ALL TISSUES APPEARED NORMAL. 8128 DS 67 66 ALL TISSUES APPEARED NORMAL. 8129 DS 67 66 ALL TISSUES APPEARED NORMAL.
DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
418-008:PAGE B-50
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B14 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
I (Cont.) 0 (VEHICLE)
8130 DS 67 66 ALL TISSUES APPEARED NORMAL 8131 DS 67 66 ALL TISSUES APPEARED NORMAL 8132 DS 67 66 ALL TISSUES APPEARED NORMAL 8133 DS 67 66 ALL TISSUES APPEARED NORMAL 8134 DS 67 66 ALL TISSUES APPEARED NORMAL 8135 DS 67 66 ALL TISSUES APPEARED NORMAL
DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
418-008:PAGE B-51
o o
o
M
CC/DT
PROTOCOL 418-008: COMBINED ORAL IGAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B14 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
II 0.1
o q
8136 DS 67 66 ALL TISSUES APPEARED NORMAL. 8137 DS 67 66 ALL TISSUES APPEARED NORMAL. 8138 DS 67 66 ALL TISSUES APPEARED NORMAL. 8139 DS 67 66 ALL TISSUES APPEARED NORMAL. 8140 DS 67 66 ALL TISSUES APPEARED NORMAL. 8141 DS 67 66 ALL TISSUES APPEARED NORMAL. 8142 DS 67 66 ALL TISSUES APPEARED NORMAL. 8143 DS 67 66 ALL TISSUES APPEARED NORMAL. 8144 DS 67 66 ALL TISSUES APPEARED NORMAL. 8145 DS 67 66 ALL TISSUES APPEARED NORMAL. 8146 DS 67 66 ALL TISSUES APPEARED NORMAL. 8147 DS 67 66 ALL TISSUES APPEARED NORMAL. 8148 DS 67 66 ALL TISSUES APPEARED NORMAL. 8149 DS 67 66 ALL TISSUES APPEARED NORMAL. 8150 DS 67 66 ALL TISSUES APPEARED NORMAL. 8151 DS 67 66 ALL TISSUES APPEARED NORMAL. 8152 DS 67 66 ALL TISSUES APPEARED NORMAL. 8153 DS 67 66 ALL TISSUES APPEARED NORMAL. 8154 DS 67 66 ALL TISSUES APPEARED NORMAL. 8155 DS 67 66 ALL TISSUES APPEARED NORMAL. 8156 DS 67 66 ALL TISSUES APPEARED NORMAL. 8157 DS 67 66 ALL TISSUES APPEARED NORMAL. 8158 DS 67 66 ALL TISSUES APPEARED NORMAL. 8159 DS 67 66 ALL TISSUES APPEARED NORMAL. 8160 DS 67 66 ALL TISSUES APPEARED NORMAL. 8161 DS 67 66 ALL TISSUES APPEARED NORMAL. 8162 DS 67 66 ALL TISSUES APPEARED NORMAL. 8163 DS 67 66 ALL TISSUES APPEARED NORMAL. 8164 DS 67 66 ALL TISSUES APPEARED NORMAL. 8165 DS 67 66 ALL TISSUES APPEARED NORMAL. 8166 DS 67 66 ALL TISSUES APPEARED NORMAL. 8167 DS 67 66 ALL TISSUES APPEARED NORMAL. 8168 DS 67 66 ALL TISSUES APPEARED NORMAL. 8169 DS 67 66 ALL TISSUES APPEARED NORMAL. 8170 DS 67 66 ALL TISSUES APPEARED NORMAL.
DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
418-008:PAGE B-52
260
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B14 (PAGE 4) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
hi
0.4
RAT NUMBER
8171
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
DS 67 66 ALL TISSUES APPEARED NORMAL.
8172 DS 67 66 KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION ALL OTHER TISSUES APPEARED NORMAL.
8173 DS 67 66 ALL TISSUES APPEARED NORMAL. 8174 DS 67 66 ALL TISSUES APPEARED NORMAL. 8175 DS 67 66 ALL TISSUES APPEARED NORMAL. 8176 DS 67 66 ALL TISSUES APPEARED NORMAL. 8177 DS 67 66 ALL TISSUES APPEARED NORMAL. 8178 DS 67 66 ALL TISSUES APPEARED NORMAL. 8179 DS 67 66 ALL TISSUES APPEARED NORMAL. 8180 DS 67 66 ALL TISSUES APPEARED NORMAL. 8181 DS 67 66 ALL TISSUES APPEARED NORMAL, 8182 DS 67 66 ALL TISSUES APPEARED NORMAL, 8183 DS 67 66 ALL TISSUES APPEARED NORMAL. 8184 DS 67 66 ALL TISSUES APPEARED NORMAL. 8185 DS 67 66 ALL TISSUES APPEARED NORMAL. 8186 DS 67 66 ALL TISSUES APPEARED NORMAL. 8187 DS 67 66 ALL TISSUES APPEARED NORMAL,
8188 DS 67 66 ALL TISSUES APPEARED NORMAL
8189 DS 67 66 ALL TISSUES APPEARED NORMAL 8190 DS 67 66 ALL TISSUES APPEARED NORMAL.
8191 DS 67 66 ALL TISSUES APPEARED NORMAL. 8192 DS 67 66 ALL TISSUES APPEARED NORMAL 8193 DS 67 66 ALL TISSUES APPEARED NORMAL 8194 DS 67 66 ALL TISSUES APPEARED NORMAL 8195 DS 67 66 ALL TISSUES APPEARED NORMAL 8196 DS 67 66 ALL TISSUES APPEARED NORMAL 8197 DS 67 66 ALL TISSUES APPEARED NORMAL 8198 DS 67 66 ALL TISSUES APPEARED NORMAL 8199 DS 67 66 ALL TISSUES APPEARED NORMAL 8200 DS 67 66 ALL TISSUES APPEARED NORMAL 8201 DS 67 66 ALL TISSUES APPEARED NORMAL
o 8202 DS 67 66 ALL TISSUES APPEARED NORMAL a 8203 DS 67 66 ALL TISSUES APPEARED NORMAL o 8204 DS 67 66 ALL TISSUES APPEARED NORMAL
to 8205 DS 67 66 ALL TISSUES APPEARED NORMAL pa DS = DAY OF STUDY
a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
418-008:PAGE B-53
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B14 (PAGE 5) : NECROPSY OBSERVATIONS INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
IV 1.6 8206 DS 67 66 ALL TISSUES APPEARED NORMAL.
8207 DS 67 66 ALL TISSUES APPEARED NORMAL.
8208 DS 67 66 LIVER: PAPILLARY PROCESS, CONSTRICTED AND NUMEROUS TAN RAISED AREAS, (PINPOINT). ALL OTHER TISSUES APPEARED NORMAL.
8209 DS 67 66 ALL TISSUES APPEARED NORMAL. 8210 DS 67 66 ALL TISSUES APPEARED NORMAL. 8211 DS 67 66 ALL TISSUES APPEARED NORMAL. 8212 DS 67 66 ALL TISSUES APPEARED NORMAL. 8213 DS 67 66 ALL TISSUES APPEARED NORMAL.
8214 DS 67 66 TESTES: BILATERAL, SMALL, PURPLE AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL.
8215 DS 67 66 ALL TISSUES APPEARED NORMAL.
8216 DS 67 66 ALL TISSUES APPEARED NORMAL.
8217 DS 67 66 ALL TISSUES APPEARED NORMAL.
8218 DS 67 66 ALL TISSUES APPEARED NORMAL.
8219 DS 67 66 ALL TISSUES APPEARED NORMAL.
8220 DS 67 66 ALL TISSUES APPEARED NORMAL.
8221 DS 67 66 ALL TISSUES APPEARED NORMAL.
8222 DS 67 66 ALL TISSUES APPEARED NORMAL.
8223 DS 67 66 ALL TISSUES APPEARED NORMAL.
8224
DS 67
66 ALL TISSUES APPEARED NORMAL.
8225 DS 67 66 ALL TISSUES APPEARED NORMAL.
8226 DS 67 66 ALL TISSUES APPEARED NORMAL.
8227 DS 67 66 ALL TISSUES APPEARED NORMAL.
8228 DS 67 66 ALL TISSUES APPEARED NORMAL.
8229 DS 67 66 ALL TISSUES APPEARED NORMAL.
8230 DS 67 66 ALL TISSUES APPEARED NORMAL.
o 8231 DS 67 66 LIVER: LARGE (28.83 G), ROUGH SURFACE.
KIDNEYS: BILATERAL, LARGE (LEFT: 4.23 G; RIGHT; 4.22 G),
PARENCHYMA, MULTIPLE PALE, FLUID-PILLED CYSTS (PINPOINT
n o 0 DS = DAY OF STUDY
TO 0.1 CM IN DIAMETER). ALL OTHER TISSUES APPEARED NORMAL.
a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
418-008:PAGE B-54
PROTOCOL 418-008; COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B14 (PAGE 6) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
IV (Cont.)
8232 8233 8234 8235 8236 8237 8238 8239 8240
DS 67 DS 67 DS 67 DS 67 DS 67 DS 67 DS 67 DS 67 DS 67
66 ALL TISSUES APPEARED NORMAL 66 ALL TISSUES APPEARED NORMAL 66 ALL TISSUES APPEARED NORMAL 66 ALL TISSUES APPEARED NORMAL 66 ALL TISSUES APPEARED NORMAL 66 ALL TISSUES APPEARED NORMAL 66 ALL TISSUES APPEARED NORMAL 66 ALL TISSUES APPEARED NORMAL 66 ALL TISSUES APPEARED NORMAL
DS = DAY OF STUDY a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
418-008:PAGE B-55
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B14 (PAGE 7): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
V 3.2 8241 DS 67 66 ALL TISSUES APPEARED NORMAL.
8242 DS 67 66 ALL TISSUES APPEARED NORMAL.
8243 DS 67 66 PROSTATE: SMALL. ALL OTHER TISSUES APPEARED NORMAL.
8244 DS 67 66 ALL TISSUES APPEARED NORMAL.
8245 DS 67 66 TESTES: BILATERAL, SMALL AND FLACCID. LIVER: ALL LOBES, BROWN. ALL OTHER TISSUES APPEARED NORMAL.
8246 DS 67 66 ALL TISSUES APPEARED NORMAL. 8247 DS 67 66 ALL TISSUES APPEARED NORMAL. 8248 DS 67 66 ALL TISSUES APPEARED NORMAL. 8249 DS 67 66 ALL TISSUES APPEARED NORMAL. 8250 DS 67 66 ALL TISSUES APPEARED NORMAL. 8251 DS 67 66 ALL TISSUES APPEARED NORMAL.
8252 DS 67 66 TESTES: BILATERAL, SMALL AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL.
8253 DS 67 66 ALL TISSUES APPEARED NORMAL. 8254 DS 67 66 ALL TISSUES APPEARED NORMAL. 8255 DS 67 66 ALL TISSUES APPEARED NORMAL. 8256 DS 67 66 ALL TISSUES APPEARED NORMAL.
8257 DS 67 66 EYES: LEFT, LENS OPAQUE, b TESTES: BILATERAL, SMALL, PURPLE AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL.
8258 DS 67 66 ALL TISSUES APPEARED NORMAL. 8259 DS 67 66 ALL TISSUES APPEARED NORMAL.
o 8260 DS 67 66 ALL TISSUES APPEARED NORMAL.
8261 DS 67 66 ALL TISSUES APPEARED NORMAL.
O 8262 DS 67 66 ALL TISSUES APPEARED NORMAL.
M 8263 DS 67 66 ALL TISSUES APPEARED NORMAL.
a DS = DAY OF STUDY
a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
b. Confirms a clinical observation (corneal opacity).
1
418-008:PAGE B-56
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B14 (PAGE 8) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
V (Cont.)
8264 DS 67 66 LIVER: LIGHT BROWN. ALL OTHER TISSUES APPEARED NORMAL.
8265 DS 67 66 ALL TISSUES A p p e a r e d NORMAL. 8266 DS 67 66 ALL TISSUES APPEARED NORMAL.
8267 DS 67 66 LIVER: DISCOLORED BROWN. ALL OTHER TISSUES APPEARED NORMAL.
8268 DS 67 66 ALL TISSUES APPEARED NORMAL. 8269 DS 67 66 ALL TISSUES APPEARED NORMAL. 8270 DS 67 66 ALL TISSUES APPEARED NORMAL. 8271 DS 67 66 ALL TISSUES APPEARED NORMAL. 8272 DS 67 66 ALL TISSUES APPEARED NORMAL. 8273 DS 67 66 ALL TISSUES APPEARED NORMAL. 8274 DS 67 66 ALL TISSUES APPEARED NORMAL. 8275 DS 67 66 ALL TISSUES APPEARED NORMAL.
DS DAY OF STUDY a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necropsy.
418-008: PAGE B-57
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PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS LEFT
ABS. REL. WT. % TBW
TESTIS LEFT
ABS. REL. WT. % TBW
SEMINAL VESICLES WITH FLUID
ABS. REL. WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. W T . % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. % TBW
TESTIS RIGHT ABS. REL. WT . % TBW
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8101 8102 8103 8104 8105 8106 8107 8108 8109 8110 8111 8112 8113 8114 8115 8116 8117 8118 8119 8120 8121 8122 8123 8124 8125 8126 8127 8128 8129 8130
428. 664 . 563 . 492. 502. 674 . 526. 499. 490. 588 . 538. 535. 478 . 544 . 508. 565. 506. 606 . 530 . 556 . 486 . 551 . 549. 562. 521. 573. 554. 631 . 543. 572.
0.67 0.82 0.72 0.69 0.58 0.64 0.75 0.52 0.68 0.61 0.58 0.73 0.74 0.66 0.73 0.69 0.75 0.67 0.75 0.64 0.68 0.76 0.81 0.85 0.81 0.78 0.84 0.75 0.67 0.67
0.16 0.12 0.13 0.14 0.12 0.09 0.14 0.10 0.14 0.10 0.11 0.14 0.15 0.12 0.14 0.12 0.15 0.11 0.14 0.12 0.14 0.14 0.15 0.15 0.16 0.14 0.15 0.12 0.12 0.12
1.47 1.79 1.55 1.54 1.49 1.85 1.67 1.65 1.73 1.69 1.63 1.78 1.61 1.81 1.63 1.79 1.96 1.65 1.98 1.58 1.83 1.95 1.77 1.98 1.97 1.90 1.80 1.83 1.83 1.66
0.34 0.27 0.28 0.31 0.30 0.27 0.32 0.33 0.35 0.29 0.30 0.33 0.34 0.33 0.32 0.32 0.39 0.27 0.37 0.28 0.38 0.35 0.32 0.35 0.38 0.33 0.32 0.29 0.34 0.29
2.00 2.11 1.83 1.53 1.86 2.96 2.51 1.90 2.22 1.85 1.69 2.23 2.25 2.13a 2.02 1.81 1.67a 2.16 2.39 2.02 2.07 2.37 2.03 2.99 2.09 2.15 2.04 2.17 2.09 2.13
0.47 0.32 0.32 0.31 0.37 0.44 0.48 0.38 0.45 0.31 0.31 0.42 0.47 0.39a 0.40 0.32 0.33a 0.36 0.45 0.36 0.42 0.43 0.37 0.53 0.40 0.38 0.37 0.34 0.38 0.37
1.17 0.73 0.82 0.79 0.86 1.44 1.17 1.01 1.21 0.50 0.82 0.70 1.12 1.47 0.94 0.97 1.26 1.14 1.09 1.11 0.83 1.14 0.73 1.54 0.98 0.87 1.03 1.00 1.11 0.89
0.27 0.11 0.14 0.16 0.17 0.21 0.22 0.20 0.25 0.08 0.15 0.13 0.23 0.27 0.18 0.17 0^25 0.19 0.20 0.20 0.17 0.21 0.13 0.27 0.19 0.15 0.18 0.16 0.20 0.16
0.69 0.85 0.71 0.71 0.63 0.60 0.76 0.59 0.70 0.61 0.57 0.80 0.76 0.70 0.76 0.73 0.79 0.72 0.78 0.63 0.68 0.63 0.77 0.90 0.80 0.76 0.75 0.80 0.77 0.73
0.16 0.13 0.13 0.14 0.12 0.09 0.14 0.12 0.14 0.10 0.10 0.15 0.16 0.13 0.15 0.13 0.16 0.12 0.15 0.11 0.14 0.11 0.14 0.16 0.15 0.13 0.14 0.13 0.14 0.13
1.54 1.88 1.59 1.59 1.53 2.04 1.68 1.76 1.72 1.67 1.62 1.84 1.66 1.80 1.65 1.84 1.97 1.65 2.05 1.53 1.74 2.00 1.73 2.01 1.97 1.89 1.76 1.75 1.85 1.57
0.36 0.28 0.28 0.32 0.30 0.30 0.32 0.35 0.35 0.28 0.30 0.34 0.35 0.33 0.32 0.32 0.39 0.27 0.39 0.28 0.36 0.36 0.32 0.36 0.38 0.33 0.32 0.28 0.34 0.27
Ci
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100
o a. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
ro
a
a
418-008:PAGE B-58
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BI5 (PAGE 2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS LEFT
ABS. REL. WT. 1 TBW
TESTIS LEFT
ABS. REL. WT. % TBW
SEMINAL VESICLES
WITH FLUID
ABS.
REL.
WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. % TBW
TESTIS
RIGHT
ABS.
REL.
WT. % TBW
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8131 8132 8133 8134 8135
524 . 542 . 450 . 582. 558.
0.73 0.63 0.73 0.59 0.74
0.14 0.12 0.16 0.10 0.13
1.74 1.00 1.81 1.57 1.89
0.33 0.18 0.40 0.27 0.34
1.74 2.21 1.59 1.35 1.96
0.33 0.41 0.35 0.23 0.35
0.68 1.08 0.81 0.72 1.01
0.13 0.20 0 .IB 0.12 0.18
0.72 0.70 0.73 0.62 0.82
0.14 0.13 0.16 0.11 0.15
1.69 1.58 1.78 1.53 1.89
0.32 0.29 0.40 0.26 0.34
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
418-008:PAGE B-59
00267
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 3) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE ABS. REL. WT. % TBW
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8101 8102 8103 8104 8105 8106 8107 8108 8109 8110 8111 8112 8113 8114 8115 8116 8117 8118 8119 8120 8121 8122 8123 8124 8125 8126 8127 812B 8129 8130
428 . 664 . 563 . 492 . 502 . 674 . 526. 499. 490 . 5B8 . 538. 535 . 478 . 544 . 508. 565 . 506. 606 . 530. 556 . 486. 551 . 549 . 562.
521. 573 . 554 . 631 . 543 . 572.
0.67 1 .37 0.44a 0.96 1.19 1.00 0.85 0.62 1.16 1.22 1.34 0.93 1.47 0.81 1.24 1.15 1.62 1.10 1.60 0.90 1.31 1.09 1.00 0.94 1.23 1.68 1.47 0.95 1.39 1.40
0.16 0.21 0.08a 0.20 0.24 0.15 0.16 0.12 0.24 0.21 0.25 0.17 0.31 0.15 0.24 0.20 0.32 0.18 0.30 0.16 0.27 0.20 0.18 0.17 0.24 0.29 0.26 0.15 0.26 0.24
^
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. * TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
O a . Rat 8103 had a small prostate; values excluded from group averages and statistical analyses. See the individual
o necropsy observations table (Table B14).
w
a
oo
418-008:PAGE B-60
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 4): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE
ABS.
REL.
WT. 4 TBW
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8131 8132 8133 8134 8135
524. 542. 450. 582. 558.
1.60a 1.21 1.24 1.19 1.13
0.30a 0.22 0.28 0.20 0.20
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT.
a. Damaged during processing (weight not affected).
ORGAN WEIGHT.
REL. % TBW (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIS (PAGE 5): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
DOSAGE GROUP II
EPIDIDYMIS LEFT
ABS. REL. WT. % TBW
TESTIS LEFT
ABS. REL. WT. % TBW
0.1 MG/KG/DAY
SEMINAL VESICLES WITH FLUID
ABS. REL. W T . % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. % TBW
TESTIS RIGHT ABS. REL. WT. % TBW
8136
415.
0.58
0.14
1.43
0.34
1.63
0.39
0.59
0.14
0.59
0.14
1.48
0.36
8137
617.
0.75
0.12
1.91
0.31
2.38
0.38
1.24
0.20
0.73
0.12
1.92
0.31
8138
524 .
0.70
0.13
1.69
0.32
1.31
0.25
0.78
0.15
0.80
0.15
1.63
0.31
8139
503.
0.72
0.14
2.04
0.40
2.22
0.44
0.95
0.19
0.75
0.15
1.99
0.40
8140
502.
0.75
0.15
1.69
0.34
2.19
0.44
0.73
0.14
0.72
0.14
1.63
0.32
8141
610.
0.90
0.15
1.95
0.32
2.71
0.44
1.17
0.19
0.85
0.14
2.01
0.33
8142
498.
0.65
0.13
1.72
0.34
1.99
0.40
0.99
0.20
0.71
0.14
1.79
0.36
8143
538.
0.84
0.16
1.96
0.36
1.80
0.33
0.79
0.15
0.81
0.15
1.94
0.36
8144
455.
0.70
0.15
1.72
0.38
2.13
0.47
0.81
0.18
0.77
0.17
1.77
0.39
8145
528.
0.56
0.11
1.78
0.34
1.92
0.36
1.07
0.20
0.57
0.11
1.84
0.35
8146
562 .
0.77
0.14
1.82
0.32
2.34
0.42
1.19
0.21
0.80
0.14
1.72
0.31
8147
540.
0.70
0.13
1.70
0.31
2.24
0.41
1.22
0.22
0.73
0.14
1.75
0.32
8148
480 .
0.64
0.13
1.68
0.35
2.10
0.44
0.86
0.18
0.67
0.14
1.62
0.34
8149
561.
0.60
0.11
1.54
0.27
2.36
0.42
1.25
0.22
0.72
0.13
1.56
0.28
8150
546 .
0.68
0.12
1.57
0.29
2.00
0.37
1.15
0.21
0.72
0.13
1.56
0.28
8151
525 .
0.76
0.14
1.98
0.38
2.36
0.45
1.31
0.25
0.75
0.14
2.06
0.39
8152
547.
0.62
0.11
1.54
0.28
2.25
0.41
1.14
0.21
0.62
0.11
1.50
0.27
8153
615.
0.62
0.10
1.70
0.28
2.24
0.36
0.94
0.15
0.71
0.12
1.71
0.28
8154
535.
0.84
0.16
1.88
0.35
2.33
0.44
1.01
0.19
0.83
0.16
1.93
0.36
8155
529.
0.60
0.11
1.78
0.34
2.16
0.41
1.35
0.26
0.60
0.11
1.74
0.33
8156
663 .
0.74
0.11
1.81
0.27
2.34
0.35
0.81
0.12
0.71
0.11
1.79
0.27
8157
532.
0.76
0.14
1.75
0.33
1.87
0.35
1.01
0.19
0.78
0.15
1.80
0.34
8158
519.
0.76
0.15
1.76
0.34
2.05
0.39
1.12
0.22
0.73
0.14
1.78
0.34
8159
539.
0.83
0.15
1.61
0.30
1.60
0.30
0.73
0.14
0.79
0.15
1.64
0.30
8160
493.
0.72
0.15
1.76
0.36
2.14
0.43
0.97
0.20
0.78
0.16
1.81
0.37
8161
533 .
0.69
0.13
1.83
0.34
2.12
0.40
1.08
0.20
0.64
0.12
1.52
0.28
8162
494 .
0.80
0.16
1.87
0.38
1.67
0.34
0.82
0.16
0.76
0.15
1.97
0.40
8163
582.
0.74
0.13
1.69
0.29
2.94
0.50
1.38
0.24
0.67
0.12
1.65
0.28
o
8164 8165
536. 576.
0.73 0.74
0.14 0.13
1.73 1.76
0.32 0.30
1.78 2.03
0.33 0.35
0.81 1.04
0.15 0.18
0.75 0.83
0.14 0.14
1.72 1.74
0.32 0.30
Ci
roo
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. 4 TBW : (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100
vol
418-008:PAGE B-62
PROTOCOL 4IB -008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OP PFOS IN RATS (SPONSOR'S STUDY NUMBER. 6295.9)
TABLE B15 (PAGE 6): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (4) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS LEFT
ABS. REL. WT. % TBW
TESTIS LEFT
ABS. 1REL. WT. % TBW
SEMINAL VESICLES
WITH FLUID
ABS.
REL.
WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. 4 TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. % TBW
TESTIS
RIGHT
ABS.
REL.
WT. % TBW
DOSAGE GROUP II
0. 1 MG/KG/DAY
8166 8167 8168 8169 8170
539. 578. 500 . 538. 624 .
0.80 0.79 0.66 0.70 0.71
0.15 0.14 0.13 0.13 0.11
1.67 1.99 1.70 1.67 1.88
0.31 0.34 0.34 0.31 0.30
2.30 2.61 2.01 1.78 1.90
0.43 0.45 0.40 0.33 0.30
1.29 1.28 0.67 0.88 0.88
0.24 0.22 0.13 0.16 0.14
0.81 0.85 0.73 0.75 0.75
0.15 0.15 0.15 0.14 0.12
1.68 1.94 1.74 1.66 1.83
0.31 0.34 0.35 0.31 0.29
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
418-008: PAGE B-63
o a o
M
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 7): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE
ABS.
REL.
WT. % TBW
DOSAGE GROUP II
0 .,1 MG/KG/DAY
8136 8137 8138 8139 8140 B14 1 8142 8143 8144 8145 8146 8147 8148 8149 8150 8151 8152 8153 8154 8155 8156 8157 8158 8159 8160 8161 8162 8163 8164 8165
415. 617 . 524 . 503 . 502 . 610. 498. 538 . 455. 528. 562. 540. 480. 561. 546. 525. 547. 615. 535. 529. 663 . 532 . 519. 539. 493. 533 . 494. 582 . 536 . 576 .
1.17 0.94 1.06 1.35 1.27 1.47 1.27 1.10 0.97 0.73 1.37 1.45 1.45 0.84 1.31 1.23 1.54 0.74 1.29 1.50 1.19 1.31 0.85 1.61 1.33 1.74 1.28 1.00 1.64 1.56
0.28 0.15 0.20 0.27 0.25 0.24 0.26 0.20 0.21 0.14 0.24 0.27 0.30 0.15 0.24 0.23 0.28 0.12 0.24 0.28 0.18 0.25 0.16 0.30 0.27 0.33 0.26 0.17 0.30 0.27
cS ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
n
si
to
418-008:PAGE B-64
PROTOCOL 41B-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 8) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE ABS. REL. WT. % TBW
DOSAGE GROUP II
0 .1 MG/KG/DAY
8166 8167 8168 8169 8170
539. 578. 500 . 538. 624 .
1.33 1.77 1.79 1.04 1.30
0.25 0.31 0.36 0.19 0.21
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. \ TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
418-008:PAGE B-65
O o
o ro
CO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 9) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS 1%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS
LEFT
ABS.
REL.
WT. % TBW
TESTIS LEFT
ABS. REL. WT. % TBW
SEMINAL VESICLES WITH FLUID
ABS.. REL. WT. % TBW
SEMINAL VESICLES
WITHOUT FLUID
ABS.
REL.
WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. % TBW
TESTIS
RIGHT
ABS.
REL.
WT. % TBW
DOSAGE GROUP 111
0 .4 MG/KG/DAY
8171
426 .
0.80
0.19
1.73
0.41
1.71
0.40
0.73
0.17
0.77
0.18
1.65
0.39
8172
596.
0.73
0.12
1.75
0.29
1.86
0.31
1.09
0.18
0.80
0.13
1.80
0.30
8173
492 .
0.63
0.13
1.86
0.38
2.10
0.43
1.03
0.21
0.69
0.14
1.99
0.40
8174 8175
526. 481 .
0.78 0.72
.0.15 0.15
1.99 1.69
0.38 0.35
2.39 2.22
0.45 0.46
0.94 1.04
0.18 0.22
0.81 0.77
0.15 0.16
2.02 1.66
0.38 0.34
8176
581.
0.71
0.12
1.79
0.31
1.86
0.32
0.91
0.16
0.71
0.12
1.87
0.32
8177
535.
0.71
0.13
1.88
0.35
1.66
0.31
0.80
0.15
0.75
0.14
1.88
0.35
B178
530.
0.74
0.14
1.90
0.36
1.50
0.28
0.77
0.14
0.71
0.13
1.89
0.36
8179
486 .
0.61
0.12
1.57
0.32
1.20
0.25
0.60a 0.12a 0.59
0.12
1.53
0.31
8180
545.
0.69
0.13
1 .58
0.29
2.24
0.41
i .ii
0.20
0.72
0.13
1.51
0.28
8181
483 .
0.72
0.15
1.67
0.34
1.40
0.29
0.79
0.16
0.64
0.13
1.61
0.33
8182
538.
0.76
0.14
1.60
0.30
1.95
0.36
1.05
0.20
0.72
0.13
1.63
0.30
8183
471.
0.63
0.13
1.55
0.33
2.02
0.43
1.00
0.21
0.68
0.14
1.52
0.32
8184
606.
0.79
0.13
1.92
0.32
1.82b 0.30b 1.01
0.17
0.74
0.12
1.84
0.30
8185
460.
0.66
0.14
1.73
0.38
1.83
0.40
0.84
0.18
0.67
0.14
1.72
0.37
8186
492.
0.79a 0.16a 1.97
0.40
2.40
0.49
1.23
0.25
0.80
0.16
1.86
0.38
8187
512.
0.65
0.13
1.46
0.28
2.21
0.43
1.24
0.24
0.81
0.16
1.51
0.29
8188
535.
0.64
0.12
1.39
0.26
1.91
0.36
0.70
0.13
0.66
0.12
1.42
0.26
8189
489.
0.67
0.14
1.87
0.38
1.92
0.39
0.80
0.16
0.68
0.14
1.73
0.35
8190
525.
0.64
0.12
1.80
0.34
2.16
0.41
1.25
0.24
0.70
0.13
1.81
0.34
8191
518.
0.70
0.14
1.78
0.34
1.98
0.38
0.89
0.17
0.74
0,14
1.77
0.34
8192
533.
0.76
0.14
1.83
0.34
2.44
0.46
1.13
0.21
0.83
0.16
1.79
0.34
8193
557.
0.73
0.13
1.77
0.32
2.19
0.39
0.91
0.16
0.79
0.14
1.68
0.30
8194
544 .
0.55
0.10
1.49
0.27
2.08
0.38
0.77
0.14
0.61
0.11
1.61
0.30
8195
500.
0.68
0.14
1.74
0.35
1.81
0.36
1.07
0.21
0.68
0.14
1.74
0.35
8196
585.
0.69
0.12
1.75
0.30
1.68
0.29
0.82
0.14
0.75
0.13
1.83
0.31
8197
507.
0.70
0.14
1.63
0.32
2.21
0.44
1.00
0.20
0.72
0.14
1.67
0.33
8198
512.
0.64
0.12
1.57
0.31
2.34
0.46
1.09
0.21
0.66
0.13
1.40
0.27
a
8199
553 .
0.77
0.14
1.83
0.33
1.98
0.36
1.02
0.18
0.79
0,14
1.85
0.33
a
8200
590.
0.76
0.13
1.82
0.31
2.70
0.46
1.37
0.23
0.76
0.13
1.81
0.31
o
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
n a. Damaged during processing (weight not affected).
vl b. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
418-008:PAGE B-66
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 10): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS <%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS LEFT
ABS. REL. WT. % TBW
TESTIS LEFT
ABS. REL. WT. % TBW
SEMINAL VESICLES WITH FLUID
ABS. REL. WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. % TBW
TESTIS RIGHT ABS. REL. WT. % TBW
DOSAGE GROUP III
0 .4 MG/KG/DAY
8201 8202 8203 6204 8205
422 . 605. 498. 494 . 515.
0.65 0.61 0.70 0.68 0.71
0.14 0.10 0.14 0.14 0.14
1.49 1.77 1.64 1.92 1.56
0.32 0.29 0.33 0.39 0.30
2.27 1.52 1.85 1.46 1.82
0.48 0.25 0.37 0.30 0.35
0.98 0.73 1.00 0.73 0.84
0.21 0.12 0.20 0.15 0.16
0.61 0.68 0.68 0.70 0.79
0.13 0.11 0.14 0.14 0.15
1.45 1.82 1.63 1.90 1.62
0.31 0.30 0.33 0.38 0.31
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
418-008:PAGE B-67
o6
0 M
01
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 11): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE ABS. REL. WT. % TBW
DOSAGE GROUP III
0.4 MG/KG/DAY
8171 8172 8173 8174 8175 8176 8177 8178 8179 8180 8181 8182 8183 8184 8185 8186 8187 8188 8189 8190 8191 8192 8193 8194 8195 8196 8197 8198 8199 8200
426 . 596. 492 . 526. 481. 581. 535. 530 . 486 . 545. 483 . 538. 471. 606 . 460. 492. 512. 535. 489. 525. 518. 533 . 557 . 544 . 500. 585. 507. 512. 553. 590.
1.01 0.56 1.57 1.74 0.69 0.59 1.40 0.97 0.90 1.01 0.99 1.44 0.56 1.14 1.30 0.86 1.24 1.24 1.50 1.31 1.43 1.27 1.41 1.27 1.27 1.52 1.35 1.38 1.48 0.69
0.24 0.09 0.32 0.33 0.14 0.10 0.26 0.18 0.18 0.18 0.20 0.27 0.12 0.19 0.28 0.17 0.24 0.23 0.31 0.25 0.28 0.24 0.25 0.23 0.25 0.26 0.27 0.27 0.27 0.12
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. ORGAN WEIGHT.
\
REL. \ TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
418-008-.PAGE B-68
vl
&
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR* S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 12) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE ABS. REL. WT. % TBW
DOSAGE GROUP III
0 .4 MG/KG/DAY
8201 8202 8203 8204 8205
472 . 605 . 498 . 494 . 515.
1.20 1.07 0.65 1.10 1.11
0.25 0.18 0.13 0.22 0.22
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 13): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS LEFT
ABS. REL. WT. % TBW
TESTIS LEFT
ABS. REL. WT. * TBW
SEMINAL VESICLES WITH FLUID
ABS. REL. W T . % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. I TBW
TESTIS RIGHT ABS. REL. W T . % TBW
DOSAGE GROUP IV
1.6 MG/KG/DAY
8206
442 .
0.71
0.16
1.74
0.39
2.18
0.49
0.96
0.22
0.69
0.16
1.74
0.39
8207
572.
0.69
0.12
1.77
0.31
1.42
0.25
0.78
0.14
0.75
0.13
1.85
0.32
8208
519.
0.70
0.13
1.68
0.32
2.42
0.47
1.12
0.22
0.71
0.14
1.67
0.32
8209
540 .
0.76
0.14
1.85
0.34
1.66
0.31
0.82
0.15
0.77
0.14
1.90
0.35
8210
459.
0.64
0.14
1.68
0.37
1.76a 0.38a 1.00
0.22
0.68
0.15
1.78
0.39
8211
540.
0.80
0.15
1.68
0.31
1.89
0.35
0.62
0.11
0.82
0.15
1.70
0.31
8212
502.
0.70
0.14
1.74
0.35
2.16
0.43
1.00
0.20
0.70
0.14
1.76
0.35
8213
503 .
0.67
0.13
1.78
0.35
2.65
0.53
1.18
0.23
0.81
0.16
1.79
0.36
8214
496.
0.45
0.09
0.80b 0.16b 2.51
0.51
1.32
0.27
0.45
0.09
0.72b 0.14b
8215
548.
0.68
0.12
1.81
0.33
1.90
0.35
1.03
0.19
0.71
0.13
1.88
0.34
8216
546.
0.75
0.14
1.66
0.30
2.08
0.38
1.03
0.19
0.71
0.13
1.65
0.30
8217
537.
0.70
0.13
1.63
0.30
1.96
0.36
1.05
0.20
0.71
0.13
1.64
0.30
8218
460.
0.65
0.14
1.29
0.28
2.32
0.50
0.96
0.21
0.62
0.13
1.26
0.27
8219
533.
0.64
0.12
1.83
0.34
2.51
0.47
1.19
0.22
0.64
0.12
1.73
0.32
8220
508.
0.68
0.13
1.91
0.38
1.89
0.37
0.91
0.18
0.65
0.13
1.83
0.36
8221
533.
0.80
0.15
1.77
0.33
2.34
0.44
0.77
0.14
0.71
0.13
1.79
0.34
8222
477.
0.63
0.13
1.48
0.31
1.81
0.38
0.79
0.16
0.69
0.14
1.50
0.31
8223
588.
0.77
0.13
1.92
0.33
2.73
0.46
1.44
0.24
0.78
0.13
1.95
0.33
8224
494 .
0.64
0.13
1.81
0.37
1.94
0.39
0.94
0.19
0.65
0.13
1.88
0.38
8225
537.
0.72
0.13
1.83
0.34
2.23
0.42
1.12
0.21
0.79
0.15
1.79
0.33
8226
503.
0.79
0.16
1.87
0.37
2.05
0.41
1.04
0.21
0.75
0.15
1.84
0.36
8227
563 .
0.73
0.13
1.70
0.30
1.53
0.27
0.82
0.14
0.79
0.14
1.63
0.29
8228
418.
0.66
0.16
1.76
0.42
1.83
0.44
0.95
0.23
0.64
0.15
1.72
0.41
8229
540 .
0.71
0.13
1.75
0.32
1.87
0.35
0.90
0.17
0.64
0.12
1.69
0.31
8230
492 .
0.77
0.16
1.75
0.36
1.96
0.40
1.04
0.21
0.78
0.16
1.75
0.36
8231
519.
0.75
0.14
2.00
0.38
2.00
0.38
0.85
0.16
0.81
0.16
2.06
0.40
8232
500 .
0.73
0.15
1.79
0.36
2.16
0.43
0.98
0.20
0.73
0.15
1.88
0.38
8233
523 .
0.64
0.12
1.64
0.31
1.85
0.35
0.95
0.18
0.64
0.12
1.67
0.32
o
8234
520.
0.62
0.12
1.74
0.33
1.71c 0.33c 1.07
0.20
0.63
0.12
1.62
0.31
a
8235
541.
0.80
0.15
1.76
0.32
1.97
0.36
0.97
0.18
0.85
0.16
1.94
0.36
o
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
k a. Damaged during processing (weight not affected).
VI b. Rat 8214 had small, purple and flaccid testes; values excluded from group averages and statistical analyses. See the
00 individual necropsy observations table (Table B14).
c. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
418-008:PAGE B-70
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 14): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS LEFT
ABS. REL. WT. * TBW
TESTIS LEFT
ABS. REL. WT. % TBW
SEMINAL VESICLES WITH FLUID
ABS. REL. WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. V TBW
TESTIS
RIGHT
ABS.
REL.
WT. % TBW
DOSAGE GROUP IV
1 .6 MG/KG/DAY
8236 8237 8238 8239 8240
489. 596. 460. 455. 495.
0.68 0.70 0.85 0.63 0.66
0.14 0.12 0.18 0.14 0.13
1.75 1.77 1.76 1.60 1.65
0.36 0.30 0.38 0.35 0.33
1.94 2.47 1.34 1.40 1.68
0.40 0.41 0.29 0.31 0.34
1.18 1.22 0.76 0.98 0.74
0.24 0.20 0.16 0.22 0.15
0.70 0.68 0.72 0.60 0.66
0.14 0.11 0.16 0.13 0.13
1.73 1.72 1.81 1.58 1.62
0.35 0.29 0.39 0.35 0.33
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
418-008:PAGE B-71
o
o
oto
C
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 15) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS <%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE
ABS.
REL.
WT. % TBW
DOSAGE GROUP IV
1 .6 MG/KG/DAY
8206 8207 8208 8209 8210 8211 8212 8213 8214 8215 8216 8217 8218 8219 8220 8221 8222 8223 8224 8225 8226 8227 8228 8229 8230 8231 8232 8233 8234 8235
442. 572. 519. 540 . 459. 540. 502 . 503. 496 . 548 . 546 . 537 . 460. 533 . 508. 533 . 477. 588 . 494 . 537. 503 . 563. 418. 540 . 492. 519. 500. 523 . 520 . 541.
1.07 1.38 1.04 1.36 0.93 1.43 1.39 1.51 0.66 0.84 1.59 0.95 0.98 0.66 1.16 0.81 1.02 1.38 1.56 0.89 0.87 1.00 0.80 1.06 1.17 1.13 1.58 1.22 1.07
1.61
0.24 0.24 0.20 0.25 0.20 0.26 0.28 0.30 0.13 0.15 0.29 0.18 0.21 0.12 0.23 0.15 0.21 0.23 0.32 0.16 0.17 0.18 0.19 0.20 0.24 0.22 0.32 0.23 0.20 0.30
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. W T . = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
418-008:PAGE B-72
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 16): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE ABS. REL. WT. % TBW
DOSAGE GROUP IV
1 .6 MG/KG/DAY
8236 8237 8238 8239 8240
489. 596 . 460. 455. 495 .
0.76 1.60 1 .22 0.62 1 .17
0.16 0.27 0.26 0.14 0.24
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 17) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS
LEFT
ABS.
REL.
WT. % TBW
TESTIS
LEFT
ABS.
REL.
WT. % TBW
SEMINAL VESICLES
WITH FLUID
ABS.
REL.
WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. * TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. 1 TBW
TESTIS
RIGHT
ABS.
REL.
WT. \ TBV^
DOSAGE GROUP V
3 .2 MG/KG/DAY
8241
404 .
0.78
0.19
1.63
0.40
2.08
0.51
0.95
0.24
0.69
0.17
1.56
0.39
8242
578.
0.76
0.13
1.85
0.32
1.67
0.29
0.97a 0.17a 0.82
0.14
1.92
0.33
8243
516 .
0.73a 0.14a 1.87
0.36
1.98
0.38
1.09
0.21
0.73
0.14
1.89
0.37
8244
486 .
0.65
0.13
1.67
0.34
1.73
0.36
0.88
0.10
0.61
0.12
1.60
0.33
8245
454 .
0.69
0.15
0.59b 0.13b 1.78
0.39
0.93
0.20
0.67
0.15
0.66b 0.14b
8246
517.
0.62
0.12
1.32
0.26
1.74
0.34
0.97
0.19
0.64
0.12
1.36
0.26
8247
428.
0.73
0.17
2.01
0.47
1.92
0.45
0.91
0.21
0.72
0.17
2.04
0.48
8248
467.
0.68
0.14
1.66
0.36
1.99
0.43
1.29
0.28
0.74
0.16
1.72
0.37
8249
437.
0.58
0.13
1.57
0.36
1.94
0.44
1.28
0.29
0.61
0.14
1.54
0.35
8250
496.
0.72
0.14
2.05
0.41
1.98
0.40
0.88
0.18
0.76
0.15
2.03
0.41
8251
457.
0.56
0.12
1.82
0.40
1.58
0.34
0.68
0.15
0.57
0.12
1.82
0.40
8252
469.
0.49
0.10
0.85b 0.18b 1.19
0.25
0.50
0.11
0.47
0.10
0.87b 0.18b
8253
441.
0.67
0.15
1.68
0.38
1.37
0.31
1.02
0.23
0.64
0.14
1.62
0.37
8254
506.
0.63
0.12
1.84
0.36
1.98
0.39
0.87
0.17
0.64
0.13
1.80
0.36
8255
492.
0.63
0.13
1.76
0.36
2.09
0.42
1.13
0.23
0.73
0.15
1.74
0.35
8256
436 .
0.70
0.16
1.81
0.42
1.11
0.25
0.83
0.19
0.65
0.15
1.86
0.43
8257
425.
0.61
0.14
0.94C 0,22c 1.61
0.38
0.64
0.15
0.62
0.14
1.21c 0.28c
8258
506.
0.63
0.12
1.96
0.39
1.79
0.35
0.84
0.17
0.68
0.13
1.94
0.38
8259
440 .
0.65
0.15
1.60
0.36
1.47
0.33
0.77
0.18
0.60
0.14
1.59
0.36
8260
545.
0.65
0.12
1.80
0.33
1.87
0.34
0.93
0.17
0.71
0.13
1.74
0.32
8261
453.
0.69
0.15
1.61
0.36
1.95
0.43
0.95
0.21
0.65
0.14
1.58
0.35
8262
464 .
0.70
0.15
2.04
0.44
1.62
0.35
0.81
0.17
0.76
0.16
1.97
0.42
8263
530.
0.73
0.14
1.71
0.32
1.70
0.32
0.90
0.17
0.77
0.14
1.73
0.33
8264
506.
0.71
0.14
1.85
0.36
2.16
0.43
1.06
0.21
0.74
0.15
1.86
0.37
8265
422.
0.66
0.16
1.74
0.41
1.33
0.32
0.62
0.15
0.69
0.16
1.67
0.40
8266
498.
0.68
0.14
1.71
0.34
1.99
0.40
i.ii
0.22
0.70
0.14
1.71
0.34
8267
438.
0.68
0.16
1.25
0.28
1.40
0.32
0.73
0.17
0.69
0.16
1.37
0.31
8268
541.
0.79
0.15
2.19
0.40
1.64
0.30
0.85
0.16
0.77
0.14
2.05
0.38
8269
514 .
0.65
0.13
1.65
0.32
1.20
0.23
0.69
0.13
0.68
0.13
1.67
0.32
8270
507.
0.72
0.14
1.93
0.38
1.54
0.30
0.77
0.15
0.66
0.13
1.07
0.37
e
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
o a. Damaged during processing (weight not affected).
n b. Rat had small and flaccid testes; values excluded from group averages and statistical analyses. See the individual
oc
necropsy observations table (Table B14). c. Rat 8257 had a small, purple and flaccid left testis; values excluded from group averages and statistical analyses. See the
individual necropsy observations table (Table B14).
418-008:PAGE B-74
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 18): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS
LEFT
ABS.
REL.
WT. % TBW
TESTIS LEFT
ABS. REL. WT. % TBW
SEMINAL VESICLES WITH FLUID
ABS. REL. WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. V TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. % TBW
TESTIS RIGHT ABS. REL. WT. % TBW
DOSAGE GROUP V
3 .2 MG/KG/DAY
8271 8272 8273 8274 8275
505. 534. 457. 493 . 511.
0.72 0.73 0.77 0.64 0.80
0.14 0.14 0.17 0.13 0.16
2.08 1.92 1.79 1.62 2.24
0.41 0.36 0.39 0.33 0.44
1 .88a 2.49 1.75 1.98 1.92
0.37a 0.47 0.38 0.40 0.38
1.01 1.40 0.95 1.04 0.80
0.20 0.26 0.21 0.21 0.16
0.70 0.78 0.78 0.60 0.84
0.15 0.15 0.17 0.12 0.16
2.21 2.01 1.78 1.59 2.30
0.44 0.38 0.39 0.32 0.45
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100
a. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
418-008:PAGE B-75
o a o
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CO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE BIS (PAGE 19): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE ABS. REL. WT. % TBW
DOSAGE GROUP V
3.2 MG/KG/DAY
8241 8242 8243 8244 8245 8246 8247 8248 8249 8250 8251 8252 8253 8254 8255 8256 8257 8258 8259 8260 8261 8262 8263 8264 8265 8266 8267 8268 8269 8270
404 . 578 . 516 . 486. 454. 517 . 428 . 467. 437. 496 . 457. 469. 441. 506. 492 . 436 . 425. 506. 440 . 545. 453 . 464 . 530. 506. 422 . 498. 438. 541. 514 . 507.
1 .15 1 .27a 0 .43b 0. 79 0 .94 0. 96 1..27 0 .69 0 .91 0..93 0..92 1..15 0..89 1..04 0..77 0. 61 1..13 1..25 0,.91 0 .45 1 .20 1,.04 1..22 1 .38 0 .68 1 .08 1 .11 1 .2B 1 .26 0 .94
0 .28 0 .22a 0. 08b 0. 16 0 .21 0 .18 0 .30 0..15 0 .21 0 ,.19 0 .20 0 .24 0 .20 0 .20 0 .16 0..14 0 .26 0,.25 0 .21 0 .08 0 .26 0 .22 0 .23 0 .27 0 .16 0 .22 0 .25 0 .24 0 .24 0 .18
o o
onoo
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
a. Damaged during processing (weight not affected).
b. Rat 8243 had a small prostate; values excluded from group averages and statistical analyses. See the individual
necropsy observations table (Table B14).
418-008:PAGE B-76
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE B15 (PAGE 20): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS <%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - Fo GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE
ABS.
REL.
WT. % TBW
DOSAGE GROUP V
3 .2 MG/KG/DAY
8271 8272 8273 8274 8275
505. 534. 457. 493 . 511.
1.02 1.25 1.04 1.22 1.05
0.20 0.23 0.23 0.25 0.20
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
418-008:PAGE B-77
O
o
Mcn
APPENDIX C REPORT TABLES - Fo GENERATION FEMALE RATS
00236
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cl (PAGE 1): CLINICAL OBSERVATIONS - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III IV
V
0 (VEHICLE) 0.1 0.4 1.6 3.2
PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION):
MAXIMUM POSSIBLE INCIDENCE
1470/ 35 1470/ 35 1470/ 35 1464/ 35 1470/ 35
MORIBUND SACRIFICED
0 0 0 la 0
LOCALIZED ALOPECIA: TOTAL LIMBS UNDERSIDE
0/ 0 0/ 0 0/ 0
0/ 0 0/ 0 0/ 0
83/ 4 83/ 4
0/ 0
43/ 3 32/ 2 11/ 1
65/ 3 60/ 2
5/ 1
CHROMODACRYORRHEA
16/ 1
2/ 1
0/ 0
2/ la 3/ 1
INCISORS: MISSING/BROKEN
0/ 0 47/ 2 11/ 1
0/ 0
6/ 1
CLEAR ORAL EXUDATE
0/ 0
0/ 0
0/ 0
2/ la 0/ 0
PTOSIS
0/ 0
0/ 0
0/ 0
1/ la 0/ 0
HUNCHED POSTURE
0/ 0
0/ 0
0/ 0
1/ la 0/ 0
LABORED BREATHING
0/ 0
0/ 0
0/ 0
1/ la 0/ 0
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION, a. Rat 8938 was moribund sacrificed on day 36 of study.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cl (PAGE 2): CLINICAL OBSERVATIONS - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III IV
V
0 (VEHICLE) 0.1 0.4 1.6 3.2
PRESUMED GESTATION: a
MAXIMUM POSSIBLE INCIDENCE
649/ 34 660/ 35 647/ 34 581/ 31 666/ 35
MORTALITY
00000
LOCALIZED ALOPECIA:
TOTAL LIMBS BACK UNDERSIDE
0/ 0 0/ 0 0/ 0 0/ 0
19/ 1 19/ 1
0/ 0 0/ 0
75/ 4* 75/ 4
0/ 0 4/ 1
45/ 4** 83/ 8" 38/ 3 40/ 3
7/ 1 18/ 3 0/ 0 31/ 3
INCISORS: TOTAL MISSING/BROKEN MISALIGNED
0/ 0 0/ 0 0/ 0
22/ 1 22/ 1
0/ 0
2/ 1 2/ 1 0/ 0
0/ 0 0/ 0 0/ 0
33/ 2 21/ 1 12/ 1
CHROMODACRYORRHEA
4/ 2
0/ 0
0/ 0
0/ 0 12/ 1
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS) /NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION, a. Restricted to rats with a confirmed mating date.
* Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p<0.01).
418-008:PAGE C-2
o w 0 GO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cl (PAGE 3): CLINICAL OBSERVATIONS - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 1IIII
0 (VEHICLE) 0.1
0.4
IV 1.6
LACTATION:
MAXIMUM POSSIBLE INCIDENCE
483/ 23 525/ 25 462/ 22 384/ 20
MORTALITY
0 0 00
LOCALIZED ALOPECIA:
TOTAL BACK UNDERSIDE LIMBS HEAD
41/ 3 0/ 0 0/ 0
21/ 2 20/ 1
22/ 2 0/ 0 0/ 0
22/ 2 0/ 0
6S/ 4 0/ 0
21/ 1 65/ 4
0/ 0
65/ 5
21/ 1 1/ 1
43/ 3 0/ 0
INCISORS: TOTAL MISSING/BROKEN MISALIGNED
0/ 0 0/ 0 0/ 0
21/ 1 21/ 1
0/ 0
0/ 0 0/ 0 0/ 0
0/ 0 0/ 0 0/ 0
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. ** Significantly different from the vehicle control group value (p<0.01).
V 3.2
31/ 21
0
7/ 5 4/ 3** 2/ 2 2/ 1 0/ 0
3/ 2 2/ 1 1/ 1
418-008:PAGE C-3
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C2 (PAGE 1) : BODY WEIGHTS - PRECOHABITATION SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED BODY WEIGHT (G)
DAY 1 DAY 8 DAY 15 DAY 22 DAY 29 DAY 36 DAY 42a
I 0 (VEHICLE)
N 35
II 0.1
35
III 0.4
35
MEAN+S.D MEAN+S.D MEAN+S.D MEAN+S.D MEAN+S.D MEAN+S.D MEAN+S.D
237.2 + 12.2 243.8 + 14.5 253.6 + 17.3 256.2 + 19.0 265.2 + 20.4 269.5 + 22.9 274.4 + 24.1
236.4 + 9.4 243.8 11.3 252.4 11.8 255.4 + 12.4 263.0 + 14.1 268.7 + 13.5 272.4 + 15.1
237.1 + 11.8 245.7 + 13.5 251.9 + 15.5 255.8 15.9 265.3 18.2 268.8 + 19.3 271.6 + 18.8
DAY = DAY OF STUDY ( ) = NUMBER OF VALUES AVERAGED a. Last value recorded before cohabitation. b. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. ** Significantly different from the vehicle control group value (p<0.01).
IV 1.6
35
238.4 + 11.7 243.9 + 13.6 251.5 13.6 252.1 + 17.8 259.2 4- 18.0 259.5 + 19.9 263.6 19.1
( 34 ]b
V 3.2
35
236.0 + 10.2 239.4 + 12.3 239.6 + 13.6" 238.6 + 15.0** 239.9 15.6" 237.2 jf 14.5** 241.4 + 15.7**
418-008:PAGE C~4
o
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C3 (PAGE 1): BODY WEIGHT CHANGES - PRECOHABITATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY) RATS TESTED BODY WEIGHT CHANGE (G)
DAYS 1 - 8 DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 42a DAYS 1 - 42a
N
MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D. MEAN+S.D . MEAN+S.D . MEAN+S.D.
I 0 (VEHICLE)
35
+6.6 1 7.3 +9.8 6.3 +2.6 + 6.7 +9.0 + 5.6 +4.3 + 6.0 +4.8 + 6.8 +37.1 + 15.8
ii 0.1
35
+7.5 + 6.4 +8.5 + 4.5 +3.0 + 5.7 +7.6 + 6.3 +5.8 + 5.1 +3.7 + 4.8 +36.0 + 10.5
III 0.4
35
+8.6 + 5.7 +6.2 + 10.6 +3 9 + 9.0 +9.5 + 6.6 +3.4 + 5.2 +2.8 + 4.1 +34.5 + 12.9
DAYS = DAYS OF STUDY [ ] = NUMBER OF VALUES AVERAGED a. Last value recorded before cohabitation. b. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. ** Significantly different from the vehicle control group value (p<0.01).
IV V 1.6 3 .2
35 35
+5.5 + 5.7
+7.6 + 4.5
+0.6 + 7.0
+7.0 + 7.0
+0.3 + 6.7**
+2.9+ 4.5 ( 34 )b
+25.0 + 11.9** t 34 )b
+3.4 + 5.6 +0.2 + 5.2** -1.0 + 5.5 +1.3 + 5. B* * -2.7 + 6.5** +4.3 + 4.7 +5.4 + 10.2**
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C4 (PAGE 1) : MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED
N 35 35 35
PREGNANT
N 33 32 28
INCLUDED IN ANALYSES
N
32b
32
28
MATERNAL BODY WEIGHT (G)
DAY 0
MEAN+S.D .
270.2 + 18.9
271.0 + 15.9
272.7 20.0
DAY 1
MEAN+S.D .
277.1 + 18.2
276.5 + 15.4
278.2 + 20.4
DAY 2
MEAN+S.D .
281.8 17.2
281.4 + 14.6
282.6 + 20.3
DAY 3
MEAN+S.D .
284.3 + 18.3
285.0 + 16.0
286.2 f 20.9
DAY 4
MEAN+S.D .
287.9 18.1
288.1 + 15.9
286 .a + 21.4
DAY 5
MEAN+S.D .
290.4 + 19.1
289.5 + 15.8
290.6 20.9
DAY 6
MEAN+S.D .
293.5 + 18.5
293.1 f 16.5
293.1 + 20.4
DAY 7
MEAN+S.D .
295.5 + 19.2
293.7 + 16.7
294.3 + 20.4
DAY 8
MEAN+S.D .
299.3 + 19.7
296.1 + 17.0
297.5 + 21.0
DAY 9
MEAN+S.D .
302.7 + 19.7
300.3 + 17.1
301.2 + 20.9
DAY 10
MEAN+S.D.
307.8 19.3
305.8 + 18.0
306.2 + 20.0
DAY = DAY OF GESTATION a. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. b. Excludes values for rats that did not have a confirmed mating date.
6 * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
o M CD ro
IV 1.6
34a
29
26b
V 3 .2
35
30
30
262.0 + 21.0 268.8 + 21.5 272.2 + 21.0 273.0 _+ 20.1* 276.3 + 21.3* 277.8 + 22.4* 280.9 + 21.9* 282.5 23.0* 285.4 22.2* 288.0 22.5** 293.5 + 22.7*
240.0 + 17.6** 244.2 16.0** 245.3 17.8** 246.0 18.3** 247.2 18.8** 250.1 18.5** 253.2 + 19.4** 254.6 + 19.3** 255.8 19.4** 258.3 f 18.9** 264.3 + 18.9**
418-008PAGE C-6
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C4 (PAGE 2) : MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III IV
0 (VEHICLE)
0.1
0.4
1.6
RATS TESTED
N 35 35 35 34a
PREGNANT
N 33 32 28 29
INCLUDED IN ANALYSES
N
22b,c
25c
22c
17b ,c
MATERNAL BODY WEIGHT (G)
DAY 11 DAY 12
MEAN+S.D . MEAN+S.D.
312.5 + 19.2 317.0 + 20.0
313.5 + 15.9 317.2 + 16.5
313.4 . 19.5 316.7 +_ 20.6
298.5 + 21.4* 303.6 + 22.6
DAY 13
MEAN+S.D .
320.2 + 19.8
320.4 + 16.7
320.6 + 19.4
306.9 + 21.3
DAY 14
MEAN+S.D .
325.0 + 20.0
325.4 + 17.0
326.2 + 19.7
311.2 + 22.1
DAY 15
MEAN+S.D .
332.2 + 20.1
332.7 + 17.9
333.1 + 19.3
320.2 + 22.2
DAY 16
MEAN+S.D .
342.0 + 21.9
342.7 + 17.6
343.9 19.0
330.6 + 22.8
DAY 17
MEAN+S.D.
356.3 + 23.5
357.6 + 18.2
358.4 18.5
345.4 + 24.9
DAY 18
MEAN +S .D .
370.9 + 25.9
371.0 + 19.9
370.6 + 19.7
359.7 + 26.4
DAY 19
MEAN+S.D .
383.5 + 26.0
383.1 + 18.6
384.5 + 19.7
373.2 + 28.2
DAY 20
MEAN+S.D.
396.4 + 27.3
397.5 + 19.8
397.8 + 21.7
386.1 + 29.6
DAY = DAY OF GESTATION a. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. b. Excludes values for rats that did not have a confirmed mating date. c. Excludes values for rats that were assigned to Caesarean-sectioning on day 10 of
* Significantly different from the vehicle control group value (p0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
gestation.
V 3.2
35 30 21C
266.0 + 20.9** 268.1 20.8** 271.9 + 21.7** 276.7 + 23.5** 283.4 + 23.1** 294.1 + 21.8** 308.6 + 21.9** 325.0 + 22.0** 339.6 + 22.4** 348.8 + 23.3**
'
418-008.PAGE C-7
n
o o ro
CO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C5 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - GESTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III
IV
0 (VEHICLE)
0.1
0.4
1.6
RATS TESTED
N 35 35 35 34a
PREGNANT
N 33 32 28 29
INCLUDED IN ANALYSES
N
32b
32
28
26b
MATERNAL BODY WEIGHT CHANGE (G)
DAYS 0 - 7
MEAN+S.D .
+25.3 + 7.5
+22.7 + 7.4
+21.6 + 6.5
+20.5 + 7.1*
DAYS 7 - 10
MEAN+S.D .
+12.2 + 4.4
+12.0 + 5.2
+12.0 + 5.6
+10.9 + 6.0
DAYS 10 - 12 DAYS 12 - 15 DAYS 15 - 18 DAYS 18 - 20 DAYS 0 - 20
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
+10.2 + 3.4 ( 22]C
+15.3 + 4.2 l 22) c
+38.7 + 7.8 ( 22) c
+25.5 + 6.8 [ 22) c
+125.1 + 15.9 [ 22] c
+10.3 + 4.6 [ 25] C
+15.5 + 4.7 ( 25) c
+38.2 + 7.4 ( 25) C
+26.5 + 5.5 [ 25) C
+123.8 + 13.3
[ 25] C
+8.8 + 4.1 [ 22] C
+16.4 + 5.5 [ 22 ]c
+37.4 + 8.8 [ 22] C
+27.2 + 7.4 [ 22] C
+121.9 + 20.2 t 22 ]C
+10.5 + 5.5 [ 17] C
+16.6 + 4.8 ( 17] c
+39.5 + 8.0 ( 17] c
+26.4 + 7.4 1 13] C
+123.1 + 18.3 [ 17]C
DAYS = DAYS OF GESTATION [ ) = NUMBER OF VALUES AVERAGED a. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study, b. Excludes values for rats that did not have a confirmed mating date. c. Excludes values for rats that were assigned to Caesarean-sectioning on day 10 of gestation. * Significantly different from the vehicle control group value (pi0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
V 3.2
35
30
30
+14.6 + 6.5**
+9.7 + 7.6
+5.3 + 6.3** ( 21] c
+15.3 + 6.7 [ 21] c
+41.5 + 6.2 1 211 C
+23.8 + 4.2 ( 21 ]C
+108.0 + 10.6** I 21 ]c
418-008:PAGE C-8
e o o M
**
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C6 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RATS ASSIGNED TO NATURAL DELIVERY
N
PREGNANT
N
DELIVEREDI LITTERS
N
MATERNAL BODY WEIGHT (G)
DAY 1
MEAN+S.D.
DAY 4
MEAN+S.D.
DAY 7
MEAN+S.D.
DAY 10
MEAN+S.D.
DAY 14
MEAN+S.D.
DAY 21
MEAN+S.D.
I 0 (VEHICLE)
25 23 23
298.3 + 19.4 303.8 + 24.0 311.8 + 21.3 325.1 + 20.7 327.0 + 19.6 331.2 + 21.3
II 0.1
25 25 25
299.0 + 18.0 t 24] b
304.0 + 17.9 306.0 + 14.9 318.0 + 15.3 326.5 + 19.5 326.4 + 14.9
HI 0.4
25 22 22
298.0 + 23.2 299.4 + 21.3 305.5 + 18.9 320.3 + 16.6 324.0 + 22.4 331.8 + 16.1
DAY = DAY OF LACTATION ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. b. Excludes values for dam 8842, which delivered one additional pup on day 2 of lactation. c. Excludes values that were not recorded. d. Excludes values for dams that had no surviving pups. ** Significantly different from the vehicle control group value (p<0.01).
IV 1.6
24a 20 20
V 3.2
25 i
21
21
297.8 + 21.6
290.7 + 22.5 t 18] d
294.7 + 22.7 l 18] d
306.4 + 20.2** [ I8]d
321.4 + 22.2 [ 18) d
329.4 + 20.4 ( 18] d
273.3 + 19.7** I 19] c d
418-008:PAGE C-9
00295
o
PROTOCOL 416-006: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C7 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - LACTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS ASSIGNED TO
NATURAL DELIVERY
N
25
25
25
PREGNANT
N 23 25 22
DELIVERED LITTERS
N
23
25
22
INCLUDED IN ANALYSES
N
23
25
22
MATERNAL BODY WEIGHT CHANGE (G)
DAYS 1 - 4 DAYS 4 - 7
MEAN+S.D. MEAN+S.D .
+5.5 + 11.0 +8.0 + 10.8
+5.3 + 8.4 ( 24 ]c
+2.0 + 7.6
+1.4 + 11.1 +6.1 + 11.5
DAYS 7 - 10
MEAN+S.D .
+13.3 + 17.4
+12.0 + 6.0
+14.8 + 5.9
DAYS 1 0 - 1 4
MEAN+S.D .
+1.9 + 18.4
+8.5 + 10.7
+3.6 + 15.2
DAYS 14 - 21
MEAN+S.D .
+4.1 + 19.4
-0.1 + 10.0
+7.8 + 15.2
DAYS 1 - 21
MEAN+S.D.
+32.8 + 19.7
+27.8 + 12.3 ( 24 ]c
+33.8 + 17.8
DAYS = DAYS OF LACTATION ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. b. Excludes values for dams that had no surviving pups. c. Excludes values for dam8842, which delivered one additional pup on day 2 of lactation. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
IV 1.6
24a 20 20 18b
-6.7 + 11.0** +4.0 + 7.9 +11.7 + 6.4 +15.0 + 6.4* +8.0 + 9.3 +32.0 + 14.6
V 3.2
25 21 21
0b
418-008:PAGE C-10
n6
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PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C8 (PAGE 1): ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - PRECOHABITATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED
N 35 35 35
FEED CONSUMPTION (G/DAY)
DAYS 1 - 8 DAYS 8 - 15 DAYS 15 - 22
MEAN+S.D. MEAN+S.D. MEAN+S.D.
19.2 + 2.2 { 34 ]a
19.8 + 2.2
19.3 + 2.6
19.6 + 3.0
19.9 + 2.1 I 31] a
19.7 + 1.8
19.3 + 2.6
18.8 + 2.4 [ 32] a
19.4 + 2.0
DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 42b DAYS 1 - 42b
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
20.0 + 2.5
19.2 + 2.2 [ 34 )a
19.3 + 2.0
19.5 + 1.9
19.5 + 2.0
19.1 + 2.0 ( 34] a
19.4 + 2.0 [ 34 ]a
19.6 + 1.5 l 34] a
19.3 + 2.0 ( 34] a
18.6 + 2.0
18.9 + 1.8
19.1 + 1.7
DAYS = DAYS OF STUDY [ ) = NUMBER OF VALUES AVERAGED a. Excludes values that were incorrectly recorded, as well as those associated with spillage. b. Last value recorded before cohabitation. c. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p<0.01).
IV 1.6
35
19.7 + 3.0
19.3 + 2.3 I 34] a
18.4 + 1.8 ( 34 ]a
18.5 + 2.2**
18.0 2.7*
18.7 + 2.5 [ 34]tc
18.9 + 2.1 { 34]1c
V 3 .2
35
17.8 + 1.9* 17.2 + 2.8** 16.0 + 2.0** 16.2 + 1.8** 14.7 + 1.7** 16.3 + 2.7** 16.4 + 1.6**
418-008:PAGE C-11
0297
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C9 (PAGE 1): RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - PRECOHABITATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED
N 35
35
35
FEED CONSUMPTION (G/KG/DAY)
DAYS 1 - 8 DAYS 8 - 15 DAYS 15 - 22
MEAN+S.D. MEAN+S.D. MEAN+S.D.
7 9 .7+ 7.2 I 34)a
79.a + 7.8
75.7 + 7.6
81.5 + 11.5
79.8 + 8.5 ( 31) a
77.6 + 6.9
80.0 + 9.2
75.5 + 8.0 [ 32] a
76.3 + 6.1
DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 42b DAYS 1 - 42b
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
76.6 + 7.1
71.5 + 5.2 ( 34) a
71.0 + 5.9
75.7 + 4.5
75.4 + 5.7
72.0 + 6.9 [ 34] a
71.9 + 5.8 [ 34 )a
76.5 + 4.4 i 34) a
73.8 + 5.9 [ 34 )a
69.6 + 4.7
69.9 + 4.7
74.3 + 4.3
DAYS = DAYS OF STUDY [ ) = NUMBER OF VALUES AVERAGED a. Excludes values that were Incorrectly recorded, as well as those associated with spillage. b. Last value recorded before cohabitation. c. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p<0.01).
IV 1.6
35
81.6 + 11.8
78.1 + 8.1 ( 34] a
73.3 + 5.8 1 34) a
72.4 + 6.3**
69.0 + 7.5
71.2 + 7.4 [ 34]c
74.5 + 6.0 1 34 ]c
V 3.2
35
74.6 + 6.2* 71.6 + 10.2** 66.8 + 6.0** 67.8 + 5.5** 61.6 + 5.2** 68.2 + 10.4 68.5 + 4.3**
418-Q08.PAGE C-12
86Z00
PROTOCOL, 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE CIO (PAGE I): MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - GESTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III
IV
0 (VEHICLE)
0.1
0.4
1.6
RATS TESTED
N 35 35 35 34a
PREGNANT
N 33 32 28 29
INCLUDED IN ANALYSES
N
32b
32
28
26b
MATERNAL FEED CONSUMPTION (G/DAY)
DAYS 0 - 7
MEAN+S.D .
21.8 + 2.1
21.6 + 2.1
21.0 + 2.1
20.4 + 2.2*
DAYS 7 - 10
MEAN+S.D .
23.4 + 2.2
23.6 + 2.4
22.6 + 3.0
21.0 + 2.8* *
DAYS 10 - 12 DAYS 12 - 15 DAYS 15 - 18 DAYS 18 - 20 DAYS 0 - 20
MEAN+S.D. MEAN+S.D . MEAN+S.D. MEAN+S.D. MEAN+S.D.
24.2 + 3.0 [ 22] c
2 3 . 8 + 2.4 [ 22) C
24.8 + 2.8 [ 22] C
22.2 + 2.6 ( 22] C
23.0 + 1.9 [ 22] c
24.3 + 2.5 [ 25] c
23.6 + 2.1 ( 25] c
24.4+ 2.3 ( 25] C
22.4 + 2.3 I 24]c,d
22.9 + 1.2 [ 24]c,d
22.9 + 3.2 [ 22] C
22.8 + 2.5 [ 22] C
24.2 + 1.9 [ 22] c
22.9 + 2.5
( 22] C 22.4 + 2.0
( 22] C
23.6 + 3.4 1 17] C
23.4 + 2.8 ( 17) c
26.6 + 2.9* 1 17] C
23.6 + 3.3 I 17] C
22.8 + 2.2 ( 17] C
DAYS = DAYS OF GESTATION l ] NUMBER OF VALUES AVERAGED a. Excludes values for rat 8938, which was moribund sacrificed on day 36 ofstudy. b. Excludes values for rats that did not have a confirmed mating date. c. Excludes values for rats that were assigned to Caesarean-sectioning on day 10 of gestation. d. Excludes valuesthat were associated with spillage or wet feed. * Significantly different from the vehicle control group value (p^O.OS). ** Significantly different from the vehicle control group value (p^O.Ol).
V 3.2
35
30
30
17.0 + 2.1**
17.7 + 2.6**
18.6 + 3.3** [ 21 ]C
19.6 + 2.7** [ 21] c
23.3 + 2.7 [ 20]C,d
21.2 + 2.5 l 21] c
19.1 + 1.8** t 21] c
418-008:PAGE C-13
o
o
M
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cll (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - GESTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III
IV
0 (VEHICLE)
0.1
0.4
1.6
RATS TESTED
N 35
35
35 34a
PREGNANT
N 33 32 28 29
INCLUDED IN ANALYSES
N
32b
32
28
26b
MATERNAL FEED CONSUMPTION (G/KG/DAY)
DAYS 0 - 7
MEAN+S.D .
76.7 + 6.6
75.9 + 5.6
73.7 + 6.4
7 4 .6 + 5.9
DAYS 7 - 10
MEAN+S.D .
77.7 + 5.4
78.8 + 5.4
75.3 + 9.2
72.8 + 7.4*
DAYS 10 - 12 DAYS 12 - 15 DAYS 15 - 18 DAYS 18 - 20 DAYS 0 - 20
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
77.2 + 6.3 [ 22] C
73.5 + 5.6 ( 22] C
70.7 + 6.1 ( 22] c
58.1 + 6.1
( 22] C 72.7 + 4.3
( 22] C
77.8 + 7.3 [ 25) c
72.8 + 5.4 [ 25) C
69.4 + 6.3 [ 25] C
5 8 .7 + 6.1 ( 24]c,d
72.4 + 2.9 ( 24]c ,d
73.2 + 9.7 ( 22 ] c
70.4 + 6.6 22] C
69.0 + 5.7 [ 22] c
59.7 + 6.7
f 2 2 ]c 70.5 + 5.3
[ 22] c
78.7 7.4 [ 17] c
75.4 + 6.2 [ 17] c
78.5 + 5.8** ( 17] C
63.4 + 8.0* [ 17] c
74.8 + 4.4 [ 17] c
DAYS = DAYS OF GESTATION [ ) = NUMBER OF VALUES AVERAGED a. Excludes values for rat 8938, which was moribund sacrificed on day 36 ofstudy. b. Excludes values for rats that did not have a confirmed mating date. c. Excludes values for rats that were assigned to Caesarean-sectioning on day 10 of gestation. d. Excludes valuesthat were associated with spillage or wet feed. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
V 3.2
35
30
30
68.8 + 6.0**
6 8 . 7 + B .4 * *
70.1 + 12.1 ( 21] c
71.3 + 8.5 ( 21]1c
77.4 + 7.4** ( 20]c , d
62.8 + 6.9* ( 21] c
70.0 + 4.7 ( 21 ]c
418-008:PAGE C-14 000300
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C12 (PAGE 1): MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) LACTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
1 II III
IV
V
0 (VEHICLE)
0.1
0.4
1.6
3.2
RATS ASSIGNED TO
NATURAL DELIVERY
N
25
25
25
24a 25
PREGNANT
N 23 25 22 20 21
DELIVERED LITTERS
N
23
25
22
20
21
INCLUDED IN ANALYSES
N
23
25
22
18b
0b
MATERNAL FEED CONSUMPTION (G/DAY)
DAYS 1 - 4 DAYS 4 - 7 DAYS 7 - 10 DAYS 10 - 14e DAYS 1 - 14e
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
25.4 + 6.9 [ 221 c
37.5 + 7.5
47.2 + 5.2 ( 22 ]c
56.9 + 5.1 ( 22) c
43.4 + 5.4 l 221 c
2 4 . 0 + 4.4 [ 23)c,d
37.6 + 5.4
44.8 + 4.4
56.7 + 5.8
42.5 + 4.5 l 24Id
22.0 + 4.5 t 211 C
36.3 + 8.7 [ 20) C
45.3 + 5.1
53.6 + 9.2
41.0 + 6.9
16.7 + 4.0** 28.9 + 6.6** 36.6 + 7.6** 46.8 + 9.2** 33.4 + 6-5**
DAYS = DAYS OF LACTATION I ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. b. Excludes values for dams that had no surviving pups. c. Excludes valuesthat were not recorded, as well as those associated with spillage or wet feed. d. Excludes values for dam 8842, which delivered one additional pup on day 2 of lactation. e. Because it is presumed that the pups begin to consume maternal feed after day 14 of lactation, maternal feed consumption values
were not tabulated on days 14 to 21 of lactation. ** Significantly different from the vehicle control group value (p<0.01).
418-008:PAGE 0 1 5
0301
r> 6
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cl3 (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - LACTATION - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III
IV
V
0 (VEHICLE)
0.1
0.4
1.6
3.2
RATS ASSIGNED TO
NATURAL DELIVERY
N
25
25
25
24a 25
PREGNANT
N 23 25 22 20 21
DELIVERED LITTERS
N
23
25
22
20
21
INCLUDED IN ANALYSES
N
23
25
22
18b
0b
MATERNAL FEED CONSUMPTION (G/KG/DAY)
DAYS 1 - 4 DAYS 4 - 7 DAYS 7 - 10 DAYS 10 - 14e DAYS 1 - 14e
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
84.6 + 22.2 I 22 ]c
122.2 + 24.7
147.9 + 15.6 [ 22) C
174.0 + 14.1 [ 22 ]C
137.8 + 16.2 [ 22] c
79.9 + 14.1 ( 23]c,d
123.6 + 19.8
144.0 + 15.4
175.9 +17.7
136.9 + 15.5 I 24 )d
74.4 + 17.0 [ 21] C
120.0 + 28.3 [ 20] c
145.4 + 18.6
166.7 + 29.0
133.0 + 23.8
56.9 + 13.8" 98.6 + 20.0" 121.7 + 23.5** 148.9 + 25.9** 110.4 + 19.6"
DAYS = DAYS OF LACTATION ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 8938, which was moribund sacrificed on day 36 of study. b. Excludes values for dams that had no surviving pups. c. Excludes values that were not recorded, as well as those associated with spillage or wet feed. d. Excludes values for dam 8842, which delivered one additional pup on day 2 of lactation. e. Because it is presumed that the pups begin to consume maternal feed after day 14 of lactation, maternal feed consumption values
were not tabulated on days 14 to 21 of lactation. " Significantly different from the vehicle control group value (P5O.OI).
418-008:PAGE C-16
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cl4 (PAGE 1): ESTROUS CYCLING, MATING AND FERTILITY - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
ESTROUS CYCLING
RATS EVALUATED
ESTROUS STAGES/ 28 DAYS
RATS WITH 6 OR MORE CONSECUTIVE DAYS OF DIESTRUS
RATS WITH 6 OR MORE CONSECUTIVE DAYS OF ESTRUS
N MEAN+S.D .
N N
I II h i IV V
0 (VEHICLE)
0.1
0.4
1.6
3.2
15 6.5 + 0.7
15 6.5 +
0.8
15 5 .7 +
1.3
15 6.1 +
0.8
15 6.7 +
0.7
34520 i0100
418-008'.PAGE C-17
a a
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CO
eco
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C14 (PAGE 2): ESTROUS CYCLING, MATING AND FERTILITY - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
MATING AND FERTILITY
RATS IN COHABITATION
N
35 35 35
DAYS IN COHABITATION b MEAN+S.D.
2 . 7 + 1.8 [ 34]
2.6 + 1.3
2 . 9 + 3.1
RATS THAT MATED
N (%)
35(100.0)
35(100.0)
34( 97.1)
FERTILITY INDEX c
N/N <%)
33/35 ( 94.3)
32/35 ( 91.4)
28/34 ( 82.4)
RATS WITH CONFIRMED MATING DATES
N
34 33 34
MATED BY FIRST MALE d DAYS 1-7
N <%)
34(100.0)
33(100.0)
33 ( 97.0)
MATED BY SECOND MALE d DAYS 8-14
N {%)
0( 0.0)
0( 0.0)
K 2.9)
RATS PREGNANT/RATS IN COHABITATION
N/N <%)
33/35 ( 94.3)
32/35 ( 91.4)
28/35 ( 80.0)
[ ] = NUMBER OF VALUES AVERAGED a. Excludes values for female rat 8938, which was moribund sacrificed on day 36 of study. b. Restricted to rats with a confirmed mating date and rats that did not mate. c. Number of pregnancies/number of rats that mated. d. Restricted to rats with a confirmed mating date.
IV 1.6
34a 2. 1 + 1.2
1 31] 34(100.0)
29/34 ( 85.3)
31
31(100.0)
0< 0.0)
29/34 ( 85.3)
V 3.2
35 3.2 +
3.2
35(100.0)
30/35 ( 85.7)
35
32( 91.4)
3( 8.6)
30/35 ( 85.7)
418-008:PAGE C-18
00304
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C15 (PAGE 1): NECROPSY OBSERVATIONS SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III
IV
0 (VEHICLE)
0.1
0.4
1 .6
RATS EXAMINED a
N
35
35
35
35
MORIBUND SACRIFICED
N
0
0
0
lb
APPEARED NORMAL N 35 35 34 34b
SPLEEN:
ADHERED TO ABDOMINAL
ADIPOSE TISSUE
N
0
0
0
1
KIDNEYS:
RIGHT, PELVIS, MODERATE
DILATION
N0 0 1 0
a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at necropsy. b. Rat 8938 was moribund sacrificed on day 36 of study.
V 3.2
35 0
35
0
0
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C16 (PAGE 1): CAESAREAN-SECTIONING OBSERVATIONS - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RATS ASSIGNED TO CAESAREAN-SECTIONING
N
PREGNANT
N (%)
RATS PREGNANT AND CAESAREAN-SECTIONED ON DAY 10 OF GESTATION
N
CORPORA LUTEA
MEAN+S.D .
IMPLANTATIONS
MEAN+S.D .
VIABLE EMBRYOS
N MEAN+S.D .
NONVIABLE EMBRYOS
N MEAN+S.D .
DAMS WITH ANY NONVIABLE EMBRYOS
N (%)
DAMS WITH ALL NONVIABLE EMBRYOS
N
DAMS WITH VIABLE EMBRYOS N (%)
% NONVIABLE EMBRYOS/LITTER
MEAN+S.D .
I 0 (VEHICLE)
10 10(100.0)
10 16.6 + 3.6 13.5 + 4.0
133 13.3 + 4.1
2 0.2 + 0.6
1( 10.0)
0 10(100.0)
1 . 7 + 5.3
II 0.1
10 7( 70.0)
7 14.6 + 6.6 11.8 + 5.6
83 11.8 + 5.6
0 0.0 + 0.0
0( 0.0)
0 7(100.0)
0.0 + 0.0
III 0.4
10 6( 60.0)
6 1 4.8+ 4.3 12.2 + 5.6
73 12.2 + 5.6
0 0-0 + 0.0
0( 0.0)
0 6(100.0)
0.0 + 0.0
IV 1.6
10 9( 90.0)
9 15.7 + 4.6 12.9 + 4.2
115 12.8 + 4.1
1 0.1 + 0.3
H 11.1)
0 9(100.0)
0.6 + 1.8
V 3.2
10 9( 90.0)
9 16.2 + 3.2 13.1 + 4.0
118 13.1 + 4.0
0 0.0 + 0.0
0( 0.0)
0 9(100.0)
0 . 0 + 0.0
418-008: PAGE C-20
e
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cl7 (PAGE 1): NATURAL DELIVERY OBSERVATIONS - SUMMARY - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II III
IV
V
0 (VEHICLE)
0.1
0.4
1.6
3.2
RATS ASSIGNED TO
NATURAL DELIVERY
N
25
25
25
24a 25
PREGNANT
N <%)
23( 92.0)
25(100.0)
22 ( 88.0)
20 l 83.3)
21 ( 84.0)
DELIVERED LITTERS
N (%)
23(100.0)
25(100.0)
22(100.0)
20(100.0)
21(100.0)
DURATION OF GESTATION b MEAN+S.D.
22.7 + 0.4 1 22)
22.8 + 0.4 ( 24]
22.5 + 0.7 l 22]
22.4 + 0.5 [ 17]
22.2 + 0.4** t 21]
IMPLANTATION SITES PER DELIVERED LITTER
N MEAN+S.D .
342 1 4 .9+ 1.9
384 15.4 + 2.2
323 14.7 + 3.5
295 14.8 1.7
262 12.5 + 1.4**
DAMS WITH STILLBORN PUPS N(%)
51 21.7)
2( 8.0)
5( 22.7)
4( 20.0)
IS( 71.4)*
DAMS WITH NO LIVEBORN PUPS N(\)
0( 0.0)
0< 0.0)
0( 0.0)
0< 0.0)
K 4.8)
GESTATION INDEX C
% N/N
100.0 23/ 23
100.0 25/ 25
100.0 22/ 22
100.0 20/ 20
95.2 20/ 21
DAMS WITH ALL PUPS DYING DAYS 1-4 POSTPARTUM
N (%)
0( 0.0)
0( 0.0)
0( 0.0)
2( 10.0)
20(100.0)**
DAMS WITH ALL PUPS DYING
DAYS 5-21 POSTPARTUM
N
0
0
0
0
0
a. Rat 8938 was moribund sacrificed on day 36 of study. b. Calculated as the time (in days) elapsed between confirmed mating (arbitrarily defined as day 0) and the time (in days)
the first pup was delivered. c. Number of rats with live offspring/number of pregnant rats. ** Significantly different from the carrier group value (p<0.01).
418-008:PAGE C-21
0307
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE CIS (PAGE 1): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP
I II III
IV
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
1.6
DELIVERED LITTERS WITH
ONE OR MORE LIVEBORN PUPS1 N
23,
25
22
20
PUPS DELIVERED (TOTAL)
N
MEAN+S.D .
323 14.0+ 2.1
350a 14.6+ 2.3a
303 13.8 + 3.4
260 13.0+ 2.5
LIVEBORN
MEAN+S.D. N (%)
13.6 + 2.3 313( 96.9)
14.4 + 2.5a 346( 98.9)a
13.5 + 3.3 297( 98.0)
12.7 + 2.6 254( 97.7)
STILLBORN
MEAN+S.D. N (%)
0.3 + 0.7 7( 2.2)
0.1 + 0.3a 2 ( 0.6 )a
0.3 + 0.6 6( 2.0)
0.3 + 0.6 6( 2.3)
UNKNOWN VITAL STATUS
N
3
2a 0
0
PUPS FOUND DEAD OR PRESUMED CANNIBALIZED
DAY 1 DAYS 2- 4 DAYS 5- 7 DAYS 8-14 DAYS 15-21
N / N (%) N / N (%) N / N (%) N / N (%) N / N (%)
2/313 ( 2/311( 0/184( 0/184( 0/184(
0.6) 0.6) 0.0) 0.0) 0.0)
3/346( 3/358( 0/2001 0/200( 0/200(
0.9)a 0.8) 0.0) 0.0) 0.0)
1/297 ( 4/2961 0/169( 1/169( 2/168(
0.3) 1.4) 0.0) 0.6) 1.2)
27/2541 10.6) 59/227( 26.0)*
6/131( 4.6)** 1/125( 0.8) 0/124( 0.0)
VIABILITY INDEX b
%
98.7
N/N 309/313
98.3 340/346a
98.3 292/297
66.1* 168/254
LACTATION INDEX c
V N/N
100.0 184/184
100.0 200/200
98.2 166/169
94.6** 124/131
DAY(S) = DAY(S) POSTPARTUM a. Excludes values for litter 8842; the dam delivered one additional pup on day 2 of lactation. b. Number of live pups on day 4 (preculling) postpartum/number of liveborn pups on day 1 postpartum. c. Number of live pups on day 21 (weaning) postpartum/number of live pups on day 4 (postculling) postpartum.
* Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
V 3.2
20 200 10.0 + 3.4" 7.8 + 4.0** 156 ( 78.0)** 2.2 + 2.3** 44( 22.0)**
0
71/156( 45.5)** 85/ 85(100.0)**
0.0** 0/156
o o
418-008:PAGE C-22
0308
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cl8 (PAGE 2) : LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
DELIVERED LITTERS WITH ONE OR MORE LIVEBORN PUPS
N
'SURVIVING PUPS/LITTER a
DAY 1 b
MEAN+S.D .
DAY 4 PRECULLING
MEAN+S.D .
DAY 4 POSTCULLING MEAN+S.D .
DAY 7
MEAN+S.D .
DAY 14
MEAN+S.D.
DAY 21
MEAN+S.D.
I 0 (VEHICLE)
23
13.6 + 2.3 13.4 + 2.1
8.0 + 0.0 8.0 + 0.0 8.0 + 0.0 8.0 + 0.0
II 0.1
25
14.4+ 2.4 l 24]c
14.2 + 2.4 8.0 + 0.0 8.0 + 0.0 8.0 + 0.0 8.0 + 0.0
III 0.4
22
13.5 + 3.3 13.3 + 3.3
7.7 + 1.1 7.7 1.1 7.6 1.1 7.5 + 1.2
IV 1.6
20
12.7 + 2.6 8.4 4.0 6.6 + 2.6* 6.2 2.8** 6.2 + 2.8** 6.2 + 2.8**
V 3.2
20
7.8 + 4.0** 0.0 + 0.0** 0.0 + 0.0 0.0 + 0.0 0.0 + 0.0 0.0 + 0.0
418-008: PAGE C-23
0309
PERCENT MALE PUPS PER NUMBER OF PUPS SEXED
DAY 1 b DAY 4 PRECULLING DAY 4 POSTCULLING DAY 7 DAY 14 DAY 21
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S. D.
46.3 + 17.0 46.8 + 16.9 48.9 + 11.2 48.9 11.2 48.9 + 11.2 48.9 + 11.2
53.9 + 14.4 t :24]1C
53.2 15.0
49.0 6.2
49.0 + 6.2
49.0 + 6.2
49.0 + 6.2
52.8 + 11.9
53.0 + 11.6
50.8 5.5 [ 20) e
51.9 + 6.3
51.6 + 5.9
52.4 6.7
55.1 + 17.8
57.0 + 21.4 l 18] d
53.8 + 19.7 ( 18] d
51.7 + 23.2 ( 18] d
51.8 + 23.0 ( 18] d
51.8 + 23.0 [ 18] d
46.7 + 22.0 d
DAY = DAY POSTPARTUM
o
o
I ) = NUMBER OF VALUES AVERAGED a. Average number of live pups per litter, including litters with no surviving pups.
b. Includes pups born alive, found dead day 1 postpartum.
c. Excludes values for litter 8842; the dam delivered one additionalpup onday 2 oflactation.
d. Excludes values for litters that had no surviving pups.
e. Excludes values for litters 8874 and 8899; a sexing error wasfoundprior to weighing on day 1 postpartum.
* Significantly different from the vehicle control group value (p<0.05).
** Significantly different from the vehicle control group value (p<0.01).
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C18 (PAGE 3): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP
I II III
IV
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
1.6
DELIVERED LITTERS WITH
ONE OR MORE LIVEBORN PUPS
N
23
25
22
20
INCLUDED IN ANALYSES
N
23
25
22
20
LIVE LITTER SIZE AT WEIGHING
DAY 1 DAY 4 PRECULLING DAY 4 POSTCULLING DAY 7 DAY 14 DAY 21
MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D .
13.6 4 2.2 13.4 4 2.1
8.0 1 0.0 8.0 4 0.0 8.0 4 0.0 8.0 4 0.0
14.3 + 2.4 l 24 ]b
14.2 + 2.4
8.0 + 0.0
8.0 + 0.0
8.0 + 0.0
8.0 + 0.0
13.4 4 3.4 13.3 4 3.3
7.7 4 1.1 7.7 4 1.1 7.6 4 1.1 7.5 _4 1.2
11.6 + 3.5
9.3 + 3.0** [ 18] a
7.3 + 1.4 ( 18] a
6.9 + 1.9* 18] a
6.9 + 1.9** [ 18] a
6.9 + 1.9** [ 18] a
PUP WEIGHT/LITTER (GRAMS)
DAY 1 DAY 4 PRECULLING DAY 4 POSTCULLING DAY 7 DAY 14 DAY 21
MEAN+S.D . MEAN +S .D . MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D .
6.6 jf 0.6 9.2 + 1.2 9.4 4 1.2 14.8 4 1.9 31.1 4 3.3 49.8 4 5.1
6.6 + 0.5 [ 241b
8.9 + 0.8
9.0 + 0.7
14.3 + 1.2
30.5 + 2.3
48.6 + 3.6
6.4 4 0.7 8.9 4 1.3 9.0 4 1.3 14.0 _4 1.4 29.9 4 2.3 48.2 4 4.5
5.7 + 0.5**
7.3 + 1.1** [ 18] a
7.5 + 1.2** [ 18] a
11.0 + 1.8** I 18] a
24.4 + 3.3** ( 18] a
40.3 + 4.3** ( 18] a
5 DAY = DAY POSTPARTUM [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for litters that had no surviving pups. b. Excludes values for litter 8842; the dam delivered one additional pup on day 2 of lactation. * Significantly different from the carrier group value (p<0.05). ** Significantly different from the carrier group value (p<0.01).
V 3.2
20 11a
9.1 + 3.7** a
5.3 + 0.4** I 10] a a
418-008:PAGE C-24
0310
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Cl 9 (PAGE 1) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 21 POSTPARTUM - SUMMARY - FI GENERATION PUPS
MATERNAL DOSAGE GROUP
I II III
IV
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
1.6
LITTERS EXAMINED (N)
23 25 22 20
TRANSIENT CLINICAL OBSERVATIONS: a
TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS
NOT NURSING
N/N 0/ 0
0/ 0
0/ 0
0/ 0
PLACENTAS NOT REMOVED
N/N 0/ 0
0/ 0
0/ 0
0/ 0
NOT NESTING
N/N 0/ 0
0/ 0
0/ 0
0/ 0
PERSISTENT CLINICAL OBSERVATIONS;; a
TOTAL FREQUENCY (DAYS x PUPS)/LITTERS WITH OBSERVATIONS
TAIL: MISSING
N/N 0/ 0
0/ 0
0/ 0
0/ 0
LEFT FORELIMB: CANNIBALIZED N/N
0/ 0
0/ 0
0/ 0
0/ 0
HEAD: DOMED
N/N 0/ 0
0/ 0
17/ 1
7/ 1
PORTION OF TAIL MISSING
N/N 0/ 0
0/ 0
0/ 0
20/ 1
UMBILICAL HERNIA
N/N 0/ 0
15/ 1
0/ 0
0/ 0
LEFT HINDPAW: DIGITS, MISSING N/N
21/ 1
0/ 0
0/ 0
0/ 0
TAIL: BENT
N/N 8/ 1
0/ 0
0/ 0
0/ 0
STATISTICAL ANALYSES WERE RESTRICTED TO THE NUMBER OF LITTERS WITH OBSERVATIONS. N/N = TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS a. Tabulation restricted to adverse observations; all other pups appeared normal. ** Significantly different from the vehicle control group value (p<0.01).
V 3.2
20
24/ 3** 22/ 2
2/ i
1/ i 1/ i 0/ 0 0/ 0 0/ 0 0/ 0 0/ 0
418-008:PAGE C-25
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C20 (PAGE 1) : REFLEX AND PHYSICAL DEVELOPMENT - SUMMARY - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP
i II III
IV
V
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
1.6
3.2
SURFACE RIGHTING' a DAY 1 DAY 2 DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 DAY 8 DAY 9 DAY 10 DAY 11 DAY 12 DAY 13 DAY 14
N MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN*S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D. MEAN+S.D . MEAN+S.D. MEAN+S.D . MEAN+S.D. MEAN+S.D.
23
46.0 +_ 20.0
38.7 + 24.7
47.8 + 27.6
71.0 + 31.4
85.9 + 21.8
90.8 + 21.7
94.6 + 13.0
96.7 + 8.6
97.8
6.1
99.4 + 2.6
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
25 51.6 + 24.3
[ 241 c 34.0 + 24.8 43.4 + 27.4 74.4 + 22.7 91.0 + 20.6 95.5 +_ 12.4 93.5 + 16.2 95.5 + 10.8 98.5 +_ 5.5 99.5 + 2.5 99.5 + 2.5 100.0 + 0.0 100.0 + 0.0 100.0 + 0.0
22
37.0 22.0
32.7 + 17.9
39.4 + 28.6
61.5 + 28.1
84.1 + 19.0
90.9 + 17.3
93.8 + 13.2
98.3
5.8
99.4 + 2.7
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
20
29.4 + 23.5
20.4 + 16.1 l 19] b
11.9 + 10.7** I 19] b
32.4 + 21.5** [ 18 ]b
41.2 + 32.9** l 18] b
47.1 + 30.1** ( 18] b
60.2 + 33.6** ( 18] b
77.6 + 29.3** [ 18] b
85.4 + 27.9 [ 18] b
89.6 + 28.5* l 18] b
94.4 + 16.2 [ 18]b
93.0 + 24.0 t 18]b
94.4 + 23.6 [ 18] b
94.4 + 23.6 [ 18] b
10b
3.8 + 8.1**
b
DAY = DAY POSTPARTUM [ ] = NUMBER OF VALUES AVERAGED a. The average percentage of pups meeting the criterion for the developmental landmark tested on each day postpartum. b. Excludes values for dams that had no surviving pups.
6 c. Excludes values for dam8842, which delivered one additional pup on day 2 of lactation.
n * Significantly different from the vehicle control group value (p<0.05).
** significantly different from the vehicle control group value (p<0.01).
o
418-008:PAGE C-26
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C20 (PAGE 2) : REFLEX AND PHYSICAL DEVELOPMENT - SUMMARY - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
SURFACE RIGHTING1 (Cont.)a N
INCLUDED IN ANALYSES
N
DAY 15
MEAN+S.D .
DAY 16
MEAN+S.D .
DAY 17
MEAN+S.D .
MEANI+S.D.C
I 0 (VEHICLE)
23 23 100.0 + 0.0 100.0 + 0.0 100.0 + 0.0 2.4 4- 1.8
II 0.1
25 25 100.0 + 0.0 100.0 + 0.0 100.0 + 0.0 2.0 + 1.2
III 0.4
22
22
100.0
0.0
100.0 + 0.0
100.0
0.0
2.7 + 1.6
IV 1.6
20 18b 97.2+ 11.8 97.2 + 11.8 100.0 + 0.0 4.6 + 2.6*
PINNA UNFOLDING a
N
23
25
22
19b
DAY 2
MEAN+S.D .
16.3 + 36.6
3.2 + 12.6
6.0 + 22.1
1. 6 + 7.1
DAY 3
MEAN+S.D .
73.1 4 33.5
50.8 + 35.4*
43.9 f 38.8*
8.4 + 19.8**
DAY 4 DAY 5 DAY 6 DAY 7
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEANI+S.D.C
99.2 + 3.7 100.0 + 0.0 100.0 + 0.0 100.0 + 0.0
3.1 0.7
97.6 + 8.5
100.0 + 0.0
100.0 + 0.0
100.0
0.0
3.4 + 0.6
98.3 6.3 100.0 + 0.0 100.0 + 0.0 100.0 + 0.0
3.5 + 0.7
47.7 + 47.6** ( 18] b
81.9 + 32.1** ( 18] b
93.0 + 20.7 l 18] b
100.0 + 0.0 [ 18] b
4 . 7 + 1.0** l 18)b
DAY = DAY POSTPARTUM l ] = NUMBER OF VALUES AVERAGED a. The average percentage of pups meeting the criterion for the developmental landmark tested on each day postpartum. b. Excludes values for dams that had no surviving pups. c. The average day postpartum that at least SOI of the pups had the developmental measure present.
* Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p;c0.01).
418-008:PAGE C-27
C0Q313
i
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C20 (PAGE 3): REFLEX AND PHYSICAL DEVELOPMENT - SUMMARY - FI GENERATION LITTERS
MATERNAL.DOSAGE GROUP
I II III
IV
V
MATERNALiDOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
1.6
3.2
EYE OPENING a
N 23
25
22
18b
0b
DAY 12
MEAN+S.D .
0.0 + 0.0
0.5 + 2.5
0.6 + 2.7
3.5 + 12.0
DAY 13
MEAN+S.D .
7.1 jf 14.0
3.5 + 11.1
3.9 + 9.2
4.2 + 12.9
DAY 14
MEAN+S.D .
55.4 + 32.6
34.0 + 31.1*
32.0 + 30.6*
13.9 + 21.4**
DAY 15
MEAN+S.D .
93.5 + 9.9
86.0 + 25.6
83.5 + 24.2
37.9 + 38.1**
DAY 16
MEAN+S.D .
100.0 + 0.0
100.0 + 0.0
99.4 + 3.0
74.8 + 33.9**
DAY 17
MEAN+S.D .
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
98.6 + 5.9
DAY 18
MEAN+S.D .
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
MEAN%+S.D.C
14.3 + 0.6
14.8 + 0.7
14.9 + 0.5**
15.7 + 1.3**
DAY = DAY POSTPARTUM a. The average percentage of pups meeting the criterion for the developmental landmark tested on each day postpartum. b. Excludes values for dams that had no surviving pups. c. The average day postpartum that at least 50% of the pups had the developmental measure present.
* Significantly different from the vehicle control group value (p^O.OS). ** Significantly different from the vehicle control group value (p^O.Ol).
418-008:PAGE C-28
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C20 (PAGE 4): REFLEX AND PHYSICAL DEVELOPMENT - SUMMARY - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP
I II III
IV
V
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
1.6 3.2
ACOUSTIC STARTLE: a
N
23
25
22
18b
0b
DAY 13
MEAN+S.D .
75.5 + 31.9
83.0 + 20.4
69.7 + 21.0
39.3 + 27.4**
DAY 14
MEAN+ S .D .
84.2 + 25.1
87.0 + 18.2
78.6 + 23.7
52.3 + 40.8*
DAY 15
MEAN+S.D .
88.6 + 21.9
78.5 + 34.1
77.1 + 27.7
68.7 + 29.6
DAY 16
MEAN+S.D .
95.1 + 14.5
81.5 + 32.9
80.9 + 29.7
67.3 + 36.0**
DAY 17
MEAN+S.D .
98.9 + 5.2
91.5 + 20.6
89.2 + 22.9
76.6 + 35.1*
DAY 18
MEAN+S.D .
100.0 + 0.0
95.5 + 14.4
96.0 + 11.8
81.9 + 36.2**
DAY 19
MEAN+S.D .
100.0 + 0.0
99.0 + 5.0
98.3 + 8.0
84.5 + 32.1**
DAY 20
MEAN+S.D .
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
94.4 + 16.2*
DAY 21
MEAN+S.D .
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
97.2 + 11.8
MEAN%+S.D .C
13.3 + 0.6
13.1 + 0.3
13.0 + 0.2
14.0 + 1.4
DAY = DAY POSTPARTUM a. The average percentage of pups meeting the criterion for the developmental landmark tested on each day postpartum. b. Excludes values for dams that had no surviving pups. c. The average day postpartum that at least 50% of the pups had the developmental measure present.
* Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p^O.Ol).
418-008:PAGE C-29
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C20 (PAGE 5) : REFLEX AND PHYSICAL DEVELOPMENT - SUMMARY - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
AIR RIGHTING a
N
DAY 14
MEAN+S.D .
DAY 15
MEAN+S.D .
DAY 16
MEAN+S.D .
DAY 17
MEAN+S.D .
DAY 18
MEAN+S.D .
DAY 19
MEAN+S.D .
DAY 20
MEAN+S.D .
DAY 21
MEAN+S.D.
MEANl+S.D .C
I 0 (VEHICLE)
23 23.9 + 27.7 48.4 + 28.8 64.7 + 26.8 79.3 + 25.7 97.8 + 8.1 100.0 + 0.0 100.0 + 0.0 100.0 + 0.0 15.5 + 1.2
II 0.1
25 13.5 + 14.4 33.5 + 22.2 66.0 + 21.5 77.0 + 19.0 90.5 + 15.0 99.0 + 3.5 100.0 + 0.0 100.0 + 0.0 15.9 + 0.8
III 0.4
22 13.0 + 15.8 35.5 + 23.0 46.8 + 26.3* 73.0 + 21.9 93.9 + 13.3 98.3 + 8.0 100.0 + 0.0 100.0 + 0.0 16.1 + 1.1
IV 1.6
18b 3.5 + 8.4** 3.5 + 5.8** 21.3 + 25.0** 40.8 + 31.5** 60.6 + 22.5** 75.2 + 30.1** 93.8 + 16.2** 93.8 + 16.2** 17.5 + 0.8**
418-008: PAGE C-30
000316
PUPIL CONSTRICTION a
N
23
25
22
18b
DAY 21
MEAN+S.D .
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
100.0 + 0.0
DAY = DAY POSTPARTUM [ ) = NUMBER OF VALUES AVERAGED a. The average percentage of pups meeting the criterion for the developmental landmark tested on each day postpartum. b. Excludes values for dams that had no surviving pups. c. The average day postpartum that at least 50% of the pups had the developmental measure present. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p-c0.01).
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C21 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION PUPS
MATERNAL DOSAGE GROUP
I II III IV
V
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0 .1
0.4
1.6
3.2
LITTERS EXAMINED (N)
23 25 22 20 21
TOTAL PUPS STILLBORN
OR FOUND DEAD a
N8
6
8 71 172
STILLBORN
N 5 1 4 6 41
FOUND DEAD
N 3 5 4 65 131
NO MILK IN STOMACH b
N(%)
2 ( 66.7)
0< 0.0)
3( 75.0)
49( 75.4)
102( 77.9)
HINDLIMBS AND/OR PORTION OF
TAIL: MISSING C
N (%)
0( 0.0)
0< 0.0)
0( 0.0)
0( 0.0)
9( 5.2)
WHOLE BODY EDEMA
N (%)
0( 0.0)
0( 0.0)
0( 0.0)
1( 1.4)
0( 0.0)
PUPS SACRIFICED AND NECROPSIED ON DAYS 4 OR 21 POSTPARTUM a
LITTERS EVALUATED
N 23
25
22
18d
PUPS EVALUATED
N 259 305 209 161
Od 0
APPEARED NORMAL LITTER INCIDENCE PUP INCIDENCE
N (%) N (%)
23(100.0) 259(100.0)
25(100.0) 305(100.0)
20( 90.9) 206( 98.6)
18(100.0) 161(100.0)
BRAIN: LATERAL VENTRICLES, iMODERATE TO SEVERE DILATION
LITTER INCIDENCE
N(%)
0( 0.0)
PUP INCIDENCE
N (%)
0( 0.0)
0( 0.0) 0( 0.0)
H 4.5) 2< 1.0)
0( 0.0) 0( 0.0)
KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION
LITTER INCIDENCE
N (%)
0( 0.0)
PUP INCIDENCE
N (%)
0( 0.0)
0( 0.0) 0( 0.0)
K 4.5) 1( 0.5)
0( 0.0) 0( 0.0)
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. b. Analysis restricted to pups found dead or moribund sacrificed and necropsied. c. Presumed cannibalized by dam. d. Excludes values for litters that had no surviving pups.
o
418-008:PAGE C-31
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C22 (PAGE 1) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT ft
DESCRIPTION
8801 8802 8803 8804 8805 8806 8807 8808 8809 8810 8811 8812 8813 8814 8815 8816 8817 8818
8819 8820 8821 8822 8823 8824 8825 8826 8827 8828 8829 8830 8831 8832 8833 8834 8835
DG ( 11- 12) DL( 2- 21)
DS( 27- 44) DG ( 0- 1)
DL ( 2- 21) DL ( 21 )
CHROMODACRYORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMODACRYORRHEA CHROMODACRYORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS
HEAD
LIMBS a LIMBS a
DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
QO
418-008:PAGE C-32
GTCO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C22 (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT #
DESCRIPTION
8836 8837 8838 8839 8840 8841 8842
8843 8844 8845 8846 8847 8848 8849 8850 8851 8852 8853 8854 8855
8856 8857 8858 8859 8860 8861 8862 8863 8864 8865 8866
8867 8868 8869 8870
DS( 5- 6) DS ( 2- 43) DG( 0- 21) DL( 1- 21)
DG( 3- 21) DL ( 1- 21)
DL( 21 ) DS ( 37- 43) DG( 0 )
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMODACRYORRHEA NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: MISSING/BROKEN a INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS INCISORS: MISSING/BROKEN INCISORS: GROWN IN NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS
DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL DAY OF LACTATION a. Observation confirmed at necropsy.
418-008.PAGE C-33
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C22 (PAGE 3) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT It
DESCRIPTION
8871 DS ( 58- 64)
CHROMODACRYORRHEA
8872
NO ADVERSE FINDINGS
8873 DS( 21- 42)
LOCALIZED ALOPECIA: LIMBS
DG ( 0- 10)
LOCALIZED ALOPECIA: LIMBS a
8874
NO ADVERSE FINDINGS
8875
NO ADVERSE FINDINGS
8876
NO ADVERSE FINDINGS
8877
NO ADVERSE FINDINGS
8878
NO ADVERSE FINDINGS
8879
NO ADVERSE FINDINGS
8680
NO ADVERSE FINDINGS
8881
NO ADVERSE FINDINGS
8882
NO ADVERSE FINDINGS
8883 DG( 9- 10)
INCISORS: MISSING/BROKEN a
8884
NO ADVERSE FINDINGS
8885
NO ADVERSE FINDINGS
8886
NO ADVERSE FINDINGS
8887
NO ADVERSE FINDINGS
8888
NO ADVERSE FINDINGS
8889
NO ADVERSE FINDINGS
8890
NO ADVERSE FINDINGS
8891
NO ADVERSE FINDINGS
8892 DL ( 20- 21)
LOCALIZED ALOPECIA LIMBS a
8893
NO ADVERSE FINDINGS
8694
NO ADVERSE FINDINGS
8895
NO ADVERSE FINDINGS
8896 DS ( 34- 45)
LOCALIZED ALOPECIA LIMBS
DG ( 0- 20)
LOCALIZED ALOPECIA LIMBS
DL( 1- 21)
LOCALIZED ALOPECIA LIMBS a
8897 DS ( 21- 45)
LOCALIZED ALOPECIA LIMBS
DG ( 0- 20)
LOCALIZED ALOPECIA LIMBS
DL ( 1- 21)
LOCALIZED ALOPECIA LIMBS a
8898
NO ADVERSE FINDINGS
8899
NO ADVERSE FINDINGS
8900 DS( 13- 45)
LOCALIZED ALOPECIA LIMBS
DG ( 0- 21)
a DG (
21)
LOCALIZED ALOPECIA LIMBS LOCALIZED ALOPECIA UNDERSIDE
DL ( l- 21)
LOCALIZED ALOPECIA LIMBS a
tow
DL( l- 21)
LOCALIZED ALOPECIA UNDERSIDE a
DS = DAY OP STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION
a. Observation confirmed at necropsy.
418-008:PAGE C-34
1 CrDH
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C22 (PAGE 4): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT It
DESCRIPTION
8901 8902 8903 8904
8905
DS( 16- 26) DS( 27 )
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: GROWN IN NO ADVERSE FINDINGS
DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION
418-008:PAGE C-35
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6
O
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C22 (PAGE 5): CLINICAL OBSERVATIONS INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP IV
1.6 MG/KG/DAY
RAT #
DESCRIPTION
8906 DS ( 10- 23)
LOCALIZED ALOPECIA: LIMBS
DS ( 24 )
ALOPECIA NO LONGER APPARENT
8907
NO ADVERSE FINDINGS
8908
NO ADVERSE FINDINGS
8909 DS ( 21- 31)
LOCALIZED ALOPECIA: UNDERSIDE
DS ( 32 )
ALOPECIA NO LONGER APPARENT
DL ( 21 )
LOCALIZED ALOPECIA: UNDERSIDE a
8910
NO ADVERSE FINDINGS
8911
NO ADVERSE FINDINGS
8912
NO ADVERSE FINDINGS
8913
NO ADVERSE FINDINGS
8914
NO ADVERSE FINDINGS
8915
NO ADVERSE FINDINGS
8916 DG ( 9- 10)
LOCALIZED ALOPECIA: LIMBS a
8917
NO ADVERSE FINDINGS
8918
NO ADVERSE FINDINGS
8919
NO ADVERSE FINDINGS
8920
NO ADVERSE FINDINGS
8921
NO ADVERSE FINDINGS
8922
NO ADVERSE FINDINGS
8923
NO ADVERSE FINDINGS
8924
NO ADVERSE FINDINGS
8925 DG ( 14- 20)
LOCALIZED ALOPECIA: BACK
DL ( 1- 21)
LOCALIZED ALOPECIA: BACK a
8926
NO ADVERSE FINDINGS
8927
NO ADVERSE FINDINGS
8928 DS ( 25- 44)
LOCALIZED ALOPECIA: LIMBS
DG ( 0- 21)
LOCALIZED ALOPECIA: LIMBS
DL ( 1- 21)
LOCALIZED ALOPECIA: LIMBS
8929
NO ADVERSE FINDINGS
8930
NO ADVERSE FINDINGS
8931
NO ADVERSE FINDINGS
8932
NO ADVERSE FINDINGS
8933 DG ( 12- 25)
LOCALIZED ALOPECIA: LIMBS a
o
8934 DL ( 21 )
LOCALIZED ALOPECIA: LIMBS a
o 8935
o
8936 8937
w
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS
w DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION
418-008:PAGE C-36
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL. REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C22 (PAGE 6): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP IV
1.6 MG/KG/DAY
RAT It
DESCRIPTION
8938
8939 8940
DS( 35- 36) DS( 35- 36) DS( 36 ) DS ( 36 ) DS ( 36 ) DS ( 36 ) DS ( 56- 67) DL( 1- 21)
CHROMODACRYORRHEA a CLEAR ORAL EXUDATE PTOSIS a HUNCHED POSTURE LABORED BREATHING MORIBUND SACRIFICED LOCALIZED ALOPECIA: LOCALIZED ALOPECIA: NO ADVERSE FINDINGS
LIMBS LIMBS a
DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
418-008:PAGE C-37
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oo
CO
to
CO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C22 (PAGE 7) : CLINICAL OBSERVATIONS INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP V
3.2 MG/KG/DAY
RAT tt
DESCRIPTION
8941 DS( 6- 42)
LOCALIZED ALOPECIA: LIMBS
DG ( 0- 10)
LOCALIZED ALOPECIA: LIMBS a
8942
NO ADVERSE FINDINGS
8943
NO ADVERSE FINDINGS
8944 DG( 18- 20)
LOCALIZED ALOPECIA: UNDERSIDE
8945
NO ADVERSE FINDINGS
B946
NO ADVERSE FINDINGS
8947
NO ADVERSE FINDINGS
8948
NO ADVERSE FINDINGS
8949 DG< 3- 20)
LOCALIZED ALOPECIA: LIMBS
DL( 1- 2)
LOCALIZED ALOPECIA: LIMBS a
8950
NO ADVERSE FINDINGS
8951
NO ADVERSE FINDINGS
8952
NO ADVERSE FINDINGS
8953
NO ADVERSE FINDINGS
8954 DS( 20- 42)
LOCALIZED ALOPECIA: LIMBS
DG ( 0- 10)
LOCALIZED ALOPECIA; LIMBS a
8955
NO ADVERSE FINDINGS
8956 DG ( 15- 20)
LOCALIZED ALOPECIA: BACK
DL ( 1 )
LOCALIZED ALOPECIA: BACK
DL( 2 )
ALOPECIA NO LONGER APPARENT
8957
NO ADVERSE FINDINGS
8958
NO ADVERSE FINDINGS
8959
NO ADVERSE FINDINGS
8960
NO ADVERSE FINDINGS
8961
NO ADVERSE FINDINGS
8962 DG ( 10- 21)
INCISORS: MISALIGNED
DL ( 1 )
INCISORS: MISALIGNED a
8963
NO ADVERSE FINDINGS
8964
NO ADVERSE FINDINGS
8965
NO ADVERSE FINDINGS
8966
NO ADVERSE FINDINGS
8967 DG ( 15- 20)
LOCALIZED ALOPECIA: UNDERSIDE
DG ( IS- 20)
LOCALIZED ALOPECIA: BACK
DL ( 1 )
LOCALIZED ALOPECIA: UNDERSIDE a
r>
DL ( 1 )
LOCALIZED ALOPECIA: BACK a
8968
NO ADVERSE FINDINGS
DS = DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
418-008:PAGE C-38
COD
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C22 (PAGE 8) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP V
3.2 MG/KG/DAY
RAT It
DESCRIPTION
8969
8910
8971 8972 8973 8974 8915
DS( 38- 43) DG ( 0- 21) DL ( 1 ) DS( 37- 44) DS( 38- 40) DG ( 0- 20) DG ( 9- 20) DL( 1- 2)
DG ( 16- 21) DL( 1- 2 )
LOCALIZED ALOPECIA: UNDERSIDE LOCALIZED ALOPECIA; UNDERSIDE LOCALIZED ALOPECIA: UNDERSIDE a INCISORS: MISSING/BROKEN CHROMODACRYORRHEA INCISORS: MISSING/BROKEN CHROMODACRYORRHEA INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: BACK LOCALIZED ALOPECIA: BACK a NO ADVERSE FINDINGS NO ADVERSE FINDINGS
DS * DAY OF STUDY DG = DAY OF PRESUMED GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
1
418-008:PAGE C-39
00325
o
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 1) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY
RAT #
8801 8802 8803 8804 8805 8806 8807 8808 8809 8810 8811 8812 8813 8814 8815 8816 8817 8818 8819 8820 8821 8822 8823 8824 8825 8826
1 8 15 22 29 36 42a
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
219. 257. 240. 237. 215. 260 . 236. 247. 216. 253. 234. 251. 227. 255. 228. 239. 220. 254. 232. 239. 231. 237. 232. 244 . 230. 230.
217. 252. 243 . 241. 220. 262 . 243. 248. 226. 255. 238. 254. 226. 260. 227. 251. 213. 284 . 241. 235. 246. 249. 245. 256. 235. 244 .
218. 265. 250. 251 . 230 . 285. 246. 250 . 233 . 261. 248. 272. 246 . 283. 226 . 257. 230. 293. 253 . 242 . 264 . 256 . 249. 275 . 239. 258.
224 . 268. 258. 255. 226 . 270. 253 . 266. 228. 268. 246 . 283 . 248. 286. 233 . 252. 225. 309. 249. 246. 264 . 257. 248. 274 . 250. 250 .
226 . 272. 269. 261. 229. 285. 259. 270. 240. 278. 261. 291. 252 . 297 . 246. 265. 239. 333. 257. 256 . 272. 265. 261. 291. 260 . 263 .
226. 289. 272 . 256. 234 . 296. 264 . 266. 246. 282 . 261. 297. 265. 302. 241. 271. 247. 339. 273. 253. 274 . 271 . 265. 305. 260 . 258.
239. 296. 287. 266. 240. 318. 274 . 275. 249. 283 . 264 . 300. 268. 316. 247. 270. 256. 355. 268. 258. 280 . 267 . 268. 300 . 268. 255 .
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008'.PAGE C-40
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PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 2) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 42a
RAT #
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8827 8828 8829 8830 8831 8832 8833 8834 8835
234. 243 . 223 . 255. 231. 247. 236. 248 . 223.
240. 249. 239. 257. 240. 263. 242. 261. 231.
247. 259. 247. 274 . 243 . 269. 247.. 272 . 238.
246 . 26 8. 250. 278. 250. 280. 248. 275. 236.
254 . 274 . 258. 271. 255. 280. 263 . 286 . 243 .
260. 275. 259. 276. 257 . 285. 267. 303 . 239.
259. 288 . 265. 278 . 262 . 284 . 266 . 294 . 240.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGEC-41
o
o
o
0
JO
vl
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 3) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY RAT tf
1 8 15 DOSAGE GROUP II
22 29 36 42a 0.1 MG/KG/DAY
8836 8837 8838 8839 8840 8841 8842 8843 8844 8845 8846 8847 8848 8849 8850 8851 8852 8853 8854 8855 8856 8857 8858 8859 8860 8861
222 . 253 . 227. 237. 228. 244 . 238. 233 . 221. 239. 224 . 244 . 224. 253 . 229. 249. 226. 239. 236. 245. 225. 249. 231. 246. 234. 242.
223 . 258 . 240 . 235. 224 . 247. 244 . 247 . 228 . 251. 228. 252. 236. 259. 238 . 255. 229. 249. 249. 272. 230. 249. 242 . 241. 242. 255 .
228. 265. 253 . 240 . 237. 257. 247. 250. 237. 257. 233. 263. 252. 274 . 248. 265. 236. 263 . 260. 268. 239. 254 . 243 . 251. 256. 264 .
232 . 272 . 248. 239. 244 . 258 . 258. 257 . 239. 258 . 233 . 264 . 248 . 265. 252 . 266 . 238. 258. 269. 266 . 234 . 254 . 243 . 268. 266 . 262.
240. 289. 256 . 251. 251. 285. 263 . 267. 243. 268 . 241. 272 . 251. 285 . 258 . 280 . 248 . 257. 277. 274 . 238. 268. 255. 265. 280. 270.
241. 285. 267. 256. 265. 290 . 264 . 274 . 253 . 272. 246 . 278. 255. 289. 267. 290. 253. 262. 279. 267. 252. 271. 255. 279. 288. 275.
241. 290. 270. 255. 275. 295. 276. 277. 266. 285. 246. 283 . 250. 293. 275. 290. 257. 260. 275. 278. 246. 274 . 258. 289. 290. 274 .
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGE C-42
n
6 o tU) n 03
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 4) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 42a
RAT U
DOSAGE GROUP II
0.1 MG/KG/DAY
8862 8863 8864 8865 8866 8867 8868 8869 8870
236. 243 . 229. 243 . 235. 236. 223. 252. 238.
252 . 252 . 236. 250. 233 . 246 . 239. 262. 242.
258 . 260 . 238. 263 . 246. 255. 251. 276 . 247.
268. 262 . 249. 264 . 247. 265. 254 . 284 . 255.
269. 258. 251. 269. 253 . 265. 256 . 291. 260 .
284. 267. 252. 279 . 262 . 271. 267. 290. 261.
289. 270 . 256. 278 . 265. 275. 273 . 298. 263 .
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGE C-43
D
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 5) : BODY WEIGHTS - PRECOHABITATION INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 42a
RAT #
DOSAGE GROUP h i
0.4 MG/KG/DAY
8871 8872 8673 8874 8875 8876 8877 8878 8879 8880 8881 8882 8883 8884 8885 8886 8887 8888 8889 8890 8891 8892 8893 8894 8895 8896
212. 254 . 239. 237. 221. 255. 232. 237. 223 . 251. 223. 238. 230. 230 . 231 . 242. 229. 258. 229. 241. 222 . 245. 236 . 253. 223. 248.
224 . 256 . 248. 248. 230. 269. 232 . 247. 232 . 251. 231. 248. 232. 231. 254. 246. 238. 271. 238. 263. 232. 252. 245. 269. 228. 249.
225 . 269. 250 . 245. 239. 275. 236 . 255. 242 . 254 . 248. 260 . 246 . 241. 264. 255. 246. 277. 245. 273 . 241. 260 . 250 . 276 . 229. 261.
220. 274 . 254 . 254. 237. 271. 238. 252. 244 . 268. 254 . 262. 248. 234. 269. 258 . 253. 284 . 248. 275. 238 . 258. 258 . 281. 234 . 260.
233 . 276 . 263. 270. 241. 290. 239. 253 . 252. 267. 256. 277. 261 234 294 . 267, 262. 291. 256 , 291. 246 . 275. 262 295. 237 267
231. 275. 258. 272 . 253 . 294 . 247. 261. 261. 273 . 258. 292 . 265. 233 . 300. 274 . 266 . 295 . 263. 298. 249. 272. 264 . 297. 233 . 276 .
238. 284 . 267. 278. 254 . 297. 248. 260. 275. 275. 265. 294. 262. 240 . 299. 272. 265. 297. 262 . 302 . 254 . 273 . 261. 300. 237. 271.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGE C-44
0330
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 6) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 42a
RAT #
DOSAGE GROUP i n
0.4 MG/KG/DAY
8897 8898 8899 8900 8901 8902 8903 8904 8905
232. 257. 240. 240. 232. 255. 232. 247. 225.
247. 273 . 241. 247. 238. 266. 242. 252. 229.
258. 282 . 252 . 259. 243 . 217. 251. 266 . 226.
263 . 285. 262 . 260 . 239. 265. 249. 274 . 231.
275. 284. 284 . 270. 254 . 282. 262. 282 . 239.
279. 289. 278. 266. 261. 294 . 260. 282. 238.
281. 294 . 283 . 265. 262. 297. 261. 288 . 246.
DAY = DAY OP STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGE C-45
00331
o
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 7) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY RAT tt
1 8 15 DOSAGE GROUP IV
22 29 36 42a 1.6 MG/KG/DAY
8906 8907 8908 8909 8910 8911 8912 8913 8914 8915 8916 8917 8918 8919 8920 8921 8922 8923 8924 8925 8926 8927 8928 8929 8930 8931
220. 259. 243 . 226 . 225. 252. 238. 242. 216. 261. 226 . 248 . 223 . 250. 239. 241. 230. 248 . 243. 242 . 222 . 245. 234 . 245. 229. 254 .
223 . 260. 256 . 226. 234 . 253 . 242 . 245 . 215. 272. 227. 250. 239. 258. 251. 249. 226. 244 . 242. 246. 225. 249. 232 . 254 . 241 . 257.
229. 264 . 252. 237. 243 . 258. 245. 253 . 227. 290. 241. 257. 249. 269. 260. 256 . 234. 254. 250 . 253. 235. 254 . 243 . 254 . 251. 273 .
234 . 265. 250 . 229. 244 . 259. 248. 251. 222 . 309. 235. 260. 242. 262. 259. 259. 226. 239. 243. 254. 240. 256 . 242 . 253 . 255. 272.
233 . 275. 258. 238 . 252. 269. 253. 256. 221 , 302 242 268 252. 292 270 266. 234. 254 257 266 245 267 243 256 257 276
243 . 277 . 258. 243 . 254 . 263. 256. 262. 218. 308 . 245. 270. 257. 291. 267. 265. 234 . 247. 261. 265. 241 . 266. 246 . 255. 260 . 274 .
246. 277. 257. 239. 261. 270. 258. 261. 228. 312 . 252. 274. 254. 299. 272. 268. 231. 256. 261. 270. 243 . 265. 254 . 256 . 259. 288.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
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1
418-008:PAGE C-46
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RAIS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 8) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 42a
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
8932 8933 8934 8935 8938 8937 8938 8939 8940
221. 240. 226. 244 . 240. 251. 231. 241. 248.
228. 244 . 224 . 254 . 251. 264 . 244 . 248. 263.
238. 249. 228. 263 . 255. 264 . 245. 257. 272 .
232. 248. 232. 264. 269. 272. 247. 264 . 289.
241 . 272 . 235. 262. 267 . 278. 250. 272. 293 .
241. 273 . 232 . 266 . 273 . 276 . 219. 275. 302 .
242. 268. 242 . 266 . 277 . 280 . MORIBUND SACRIFICED ON DAY 36 OF STUDY 273 . 304 .
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGE C-47
6
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PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 9) : BODY WEIGHTS PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY RAT ft
1 8 15 DOSAGE GROUP V
22 29 36 42a 3.2 MG/KG/DAY
8941 8942 8943 8944 8945 8946 8947 8948 8949 8950 8951 8952 8953 8954 8955 8956 8957 8958 8959 8960 8961 8962 8963 8964 8965 8966
'
225. 252. 232. 227. 220. 255. 239. 248 . 215. 250. 238. 238. 225. 249. 220. 236. 226. 253. 235. 242. 219. 245. 237. 234. 231. 239.
224 . 249. 227. 230. 222. 267. 237. 244 . 218 . 254 . 248. 236. 224 . 247. 220. 238. 231. 253 . 247. 255. 226. 253. 242 . 238. 232 . 24 5.
225. 256 . 230. 226. 219. 264 . 239. 245 . 213 . 247. 246. 241. 226. 250 . 230. 236. 233 . 250. 252. 264 . 219. 255. 240. 232. 231. 243 .
228 . 253 . 217. 220. 222. 259. 234 . 245 . 216 . 247. 247. 238. 218. 249. 221. 241 . 222. 249. 250. 266 . 226 . 248 . 243. 240 . 234 . 248.
218. 256. 224. 227. 222. 261. 239. 255. 213. 246 . 248 . 232. 226. 252. 226. 229, 229. 252 , 248. 272. 218. 254. 240. 241, 241. 244 .
220. 257. 219. 218. 219255. 236. 247 . 213 . 252 . 244 . 235. 226 . 254 . 222. 232 . 222 . 254. 245. 264 . 219. 250. 237. 238 . 241. 243 .
227. 263 . 214. 224 . 218. 256 . 239. 247 . 211. 261. 244 . 238. 228. 264. 233. 230. 237. 261. 249. 273. 227. 256. 241. 242 . 246. 245.
DAY DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGE C-48
000334
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C23 (PAGE 10) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 42a
RAT ft
DOSAGE GROUP V
3.2 MG/KG/DAY
8967 8968 8969 8970 8971 8972 8973 8974 8975
230. 238. 227. 249. 238. 238. 238. 236. 236 .
235. 235. 231. 268. 250. 235. 239. 241. 240 .
234 . 246. 231. 269. 256. 223 . 238. 234 . 244 .
224. 241. 233 . 279. 258. 220. 235. 237. 242 .
237. 238. 234 . 278 . 265. 221. 240. 230. 241.
242. 230. 226. 246. 266. 216 . 242. 228. 243 .
241. 237. 232. 260. 264 . 219. 243 . 229. 252.
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGE C-49
0C03.7
Cl
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 1) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2 3 4 5
RAT #
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801 P 8802 P 8803 P 8804 P 8805 P 8806 P 8807 P 8808 P 8809 P 8810 P 8811 P 8812 P 8813 P 8814 P 8815 P 8816 P 8817 NP 8818 NP 8819 P 8820 P 8821 P 8822 P 8823 P 8824 P 8825 P
232 .
240.
245.
290.
298.
304 .
274 .
282.
286.
269.
278.
282.
249.
254.
261 .
315.
322.
322.
271.
284.
286.
269.
283 .
282 .
247.
256 .
256 .
283.
288.
293 .
266.
273 .
275.
NO CONFIRMED MATING DATE
269.
283 .
283.
311.
317.
325.
238.
246 .
259.
254.
269.
276.
268.
260.
256.
349.
360.
356.
268 .
274 .
282 .
253.
260.
267.
277.
281.
288 .
265.
269.
277.
272.
273 .
275 .
298.
300.
298.
262 .
271.
279.
243 . 312. 293. 291. 256. 326 . 285. 285. 256. 290. 284 .
285. 320 . 259. 275 . 266 . 364 . 280 . 267. 292 . 276 . 280. 306. 280 .
245. 312. 292. 297. 263 . 331. 290. 282. 266. 297 282.
287. 329. 269. 277. 264 . 370. 290. 272 . 292, 282 . 281. 306. 284 .
244 . 320. 299. 301. 266. 339. 297. 287. 264 . 296. 285.
286. 329. 275 . 281. 268 . 363. 292. 275. 301 . 282 . 277. 305. 281.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6
252 . 321. 299. 299. 268. 340. 296 . 285. 263 . 305. 288.
297. 335. 277. 292 . 270. 372. 293 . 277. 299. 285. 287. 306. 284 .
7
249. 324 . 298. 305. 268. 342. 298. 289. 266. 303. 292.
300 . 340. 278. 295. 271. 378. 300. 279. 302. 288. 283 . 305. 285.
8
253 . 330. 308 . 307. 273 . 346. 304 . 295. 270. 305. 295.
300. 344 . 281. 292 . 271. 378. 299. 283 . 313. 290. 287. 314 . 289.
9
257. 335. 308 . 315. 279. 353. 303 . 287. 276 . 311. 297.
303 . 349. 286 . 299. 269. 380 . 304 . 286 . 307. 295. 293. 316. 294 .
10
261. 338. 309. 319. 281 . 357. 311. 291. 286 . 306. 305.
305. 352 . 302. 310. 269. 377. 309. 291. 313 . 299. 295. 322. 299.
11
262. 319. 323. 283 . 311. 303 .
313 . 310. 353 .
270. 376. 312.
319.
303. 327.
12
267.
321. 328. 290. 322. 310.
315 .
314 . 368.
271. 379. 317.
322. 307. 328.
418-008:PAGE C-50
0C0336
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 2) : MATERNAL BODY WEIGHTS PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2 3 4 5
RAT It
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8826 P 8827 P 8828 P 8829 P 8830 P 8831 P 8832 P 8833 P 8834 P 8835 P
258. 271. 283 . 270. 278. 262. 288. 265. 292. 247.
272 . 275. 290. 277. 281. 263. 285. 277. 296 . 250.
276. 280. 296 . 284 . 287 . 268 . 293. 276. 298. 259.
282 . 284 . 299. 286. 287. 275 . 297. 280 . 305. 262.
284 . 286. 304 . 287. 289. 275 302 283 310 266
288. 288. 300. 290. 292. 276 . 303 . 286 . 317. 270.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6
292 . 292 . 304 . 291. 296 . 280. 310. 290. 314 . 274 .
7
293. 294 . 312. 294. 298. 284 . 309. 286. 317. 280.
8
299. 298. 308. 300. 299. 284. 317. 293 . 323. 280.
9
302 . 304 . 313 . 298. 307. 290. 315. 292. 327. 286 .
10
308. 308. 320. 311. 306. 293 . 323 . 299. 330. 289.
11
311. 312 . 331.
315. 300. 334 . 302. 339. 294 .
12
315. 316. 332.
314. 302 . 334 . 306. 347. 298.
418-008:PAGE C-51
000337
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 3): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18
RAT (t
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801 P 8802 P 8803 P 8804 P 8805 P 8806 P 8807 P 8808 P 8809 P 8810 P 8811 P 8812 P 8813 P 8814 P 8815 P 8816 P 8817 NP 8818 NP 8819 P 8820 P 8821 P 8822 P 8823 P 8824 P 8825 P
270.
320. 328. 293.
324 . 314 .
2*74 .
332. 330. 299.
330. 322 .
280.
339. 341. 306.
334 . 326.
286 .
347. 354 . 310 .
341 . 333 .
294 .
354 . 365. 330.
358 346.
308.
375. 387. 339.
373 . 354.
316.
322.
333.
NO CONFIRMED MATING DATE
320.
326.
336.
369.
374 .
378.
342 .
338. 387.
354
351 404
365.
369. 428.
274 . 381. 329.
276. 375 . 332.
330.
337 .
304 .
307.
330. . 336 .
264 . 376. 337.
342.
312. 340.
262. 382. 356.
351.
322 . 352 .
263 384 370
368
336 368
263. 388. 383.
385.
344. 384.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
19
324 . 387. 393. 350. 388 . 373 .
378.
368. 430.
261 . 368. 390 . 418.
355. 398.
20 21
330 .
400. 412. 368.
394 . 382.
340 .
413. 423. 382.
411. 389.
387.
377. 450 .
400.
396. 465.
259. 353. 413 .
408.
364. 404 .
261. 373. 424.
428.
411.
22
265. 384.
23
264. 375.
24
261. 377.
25 t
260. 378.
418-008:PAGE C-52
OC0338
PROTOCOL, 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 4) : MATERNAL BODY WEIGHTS PRESUMED GESTATION - INDIVIDUAL DATA Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21 22 23 24
RAT
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8826 P 8827 P 8828 P 8829 P 8830 P 8831 P 8832 P 8833 P 8834 P 8835 P
315. 317. 335.
316. 310. 343. 310. 346. 305.
323 . 322. 333 .
322. 310. 349. 312. 350. 308.
330. 328. 343 .
330 . 320. 356. 319. 363 . 316.
336 . 337. 360.
338. 332. 370. 331. 376. 325.
347 . 348 , 376 .
359 348 384 343 398 337
355 . 363. 388.
380 . 357. 402. 365. 410. 346.
362. 378. 406 .
387. 372 . 412. 377. 430 . 362 .
377. 390. 413 .
402. 392 . 429 . 403 . 450 . 377.
384 . 404. 432 .
414 . 403 . 437 . 400. 458. 380.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
25
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 5): MATERNAL BODY WEIGHTS - PRESUMED GESTATION INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2 3 4 5
RAT
DOSAGE GROUP II
0.1 MG/KG/DAY
8836 P 8837 P 8838 P 8839 P 8840 P 8841 P 8842 P 8843 P 8844 P 8845 P 8846 P 8847 P 8848 P 8849 P 8850 NP 8851 P 8852 P 8853 P 8854 P 8855 P 8856 NP 8857 P 8858 P 8859 P 8860 P
237. 282. 268. 256. 272 . 306 . 262. 266. 259. 285. 246. 279. 244 . 294. 268 . 291. 261. 264 . 279. 272.
a 268. 258. 287. 293.
244 . 297. 270. 266. 278. 307. 267. 274. 257. 296. 252. 279. 251. 294. 274 . 296. 264 . 270. 278. 281.
a 273 . 262 . 285. 298.
246. 303 . 276 . 270. 286 . 306. 279. 288 . 266 . 295. 258. 290. 260 . 302. 285. 301. 270 . 277. 280. 282. 252. 279. 264 . 286. 303.
248 . 310 . 280. 267. 284 . 311. 278. 287. 268. 299. 260. 290. 263 . 302. 286. 310. 270. 281. 290. 288. 265. 282. 271. 298 . 308.
252. 317. 284 . 270. 290. 316. 284 292 . 268. 304 . 266. 297. 269. 304 . 286 . 308. 269. 281. 288. 291. 258. 280. 273. 302 . 307.
257 . 318. 287. 277. 293 . 320 . 283 . 294 . 270 . 303 . 263. 295. 270 . 312. 295. 310. 273 . 281. 288. 291 . 258. 280. 274 . 302 . 304 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was not recorded.
6
260. 325. 293 . 280. 296 . 323 . 282. 301. 271. 305. 264. 295. 272. 306. 294 . 315. 279. 285. 299. 295. 256. 279. 277. 310 . 311.
7
258. 325. 295. 284. 299. 324. 280. 297. 267. 309. 268. 303. 279. 304 . 294 . 314. 270. 291. 296. 292. 257. 283. 280. 301. 309.
8
260. 327. 295. 282. 306 . 328. 290 . 298 . 272. 311. 269. 299. 279. 311. 295. 320. 280. 286. 297. 298. 254 . 286. 281. 309. 310.
9
263. 332. 305. 284. 310 . 330. 290. 306 . 280. 309. 272. 309. 284 . 316. 297. 320. 278. 288. 303 . 304. 254 . 290. 284. 310 . 316 .
10
267. 348. 306. 290. 314 . 343 . 303 . 308 . 289. 317. 277. 309. 294 . 320 . 309. 324 . 284 . 294 . 303. 312. 259. 294 . 288. 314 . 319.
11
314 .
318. 346 . 299.
324 . 283 . 316 .
328.
328 . 288. 305. 309. 320.
306. 299.
332.
12
318.
324. 349. 299.
329. 286. 321.
329.
338. 292. 310. 314. 320.
306. 303.
330.
418-008:PAGE C-54
oro3*o
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 6) : MATERNAL BODY WEIGHTS PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2 3 4 5
RAT tf
DOSAGE GROUP II
0.1 MG/KG/DAY
8861 NP 8862 P 8863 P 8864 P 8865 P 8866 P 8867 P 8868 P 8869 P 8870 P
278. 290. 264 . 255. 275. 264 . 272. 270. 291. 263.
282. 298. 273 . 261. 279. 272 . 278 . 280. 294 . 274 .
279. 297 . 280. 265. 286. 275. 282. 283 . 294 . 276.
286. 305. 282. 268. 285. 282. 281. 288 . 304 . 280.
288. 307. 282. 274 . 294. 284. 286. 293 . 305. 281.
293. 309. 286. 274 . 294 . 285. 285. 292. 309. 286 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6
298 . 311. 288 . 276 . 299. 291. 294 . 294 . 315 . 289.
7
301. 318. 287. 277. 297. 292. 293. 296. 318. 293.
a 9 10 11 12
300. 319. 288. 276. 304 . 295. 291. 297. 319. 291.
302. 324 . 296. 280. 306 . 298. 304 . 302. 323 . 295.
319. 330. 300. 281. 304 . 305. 305. 310. 328. 304.
337. 303. 289. 315. 314. 307. 317. 336. 304 .
346 . 310. 293. 314. 317. 317. 322. 341. 303.
418-008:PAGE C-55
TfrCOOO
418-008.PAGE C-56
000342
PROTOCOL 41B-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 7): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21 22 23 24
RAT tt
DOSAGE GROUP II
0.1 MG/KG/DAY
8836 P 8837 P 8838 P 8839 P 8840 P 8841 P 8842 P 8843 P 8844 P 8845 P 8846 P 8847 P 8848 P 8849 P 8850 NP
8851 P 8852 P 8853 P 8854 P 8855 P 8856 NP 8857 P 8858 P 8859 P 8860 P
321.
327. 356. 298.
322.
335. 360. 309.
332. 290 . 321.
332.
336. 295. 311. 322. 328.
312. 305.
335.
337. 295. 324.
343.
346. 299. 319. 326. 332.
315. 313.
341.
332.
345. 366. 319.
340.
354. 377. 338.
363.
377. 378. 344 .
382 .
393 . 393 . 367.
392.
401. 405. 384 .
409.
420. 421. 395.
421.
426 . 433 . 405.
346. 301. 330.
358.
348. 300. 332 . 331. 337.
319. 318 .
349.
354. 313. 338.
370 .
358. 312. 337. 338. 346.
328. 330.
356.
369. 321. 351.
382 .
376. 322. 352 . 354 . 370.
349. 349.
377.
377. 340 . 374 .
396 .
384 . 325. 381. 359. 376.
358. 358.
386 .
385. 347. 382.
411.
395. 341. 393. 378. 388.
373. 374.
404 .
401. 361. 386 .
422 .
413. 352. 405. 402. 403 .
385. 389.
411.
410. 370. 404.
432. 366 . 425. 410. 416.
398. 410 .
427.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
25
418-008:PAGE C-57
000343
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 8) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18
RAT #
DOSAGE GROUP II
0.1 MG/KG/DAY
8861 NP 8862 P 8863 P 8864 P 8865 P 8866 P 8867 P 8868 P 8869 P 8870 P
348. 313. 299. 317. 320. 317. 326. 344 . 304 .
351 . 318. 301 . 320. 323 . 324. 329. 349. 305.
359. 327. 307. 333 . 327. 329. 335. 357. 313.
373 . 331. 319. 339. 341. 339. 342. 368. 326.
382. 349. 329. 356. 356. 352. 357. 385. 341.
400. 370 . 338 . 359. 367. 373 . 376. 399. 343.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
19
402. 379. 349. 370. 388. 382 . 384. 407. 364.
20
423. 398. 364. 381. 401. 393 . 403 . 424. 375.
21
432.
366. 398. 412. 403 . 406. 446. 374.
22
23 299.
24
25
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 9) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2
RAT #
DOSAGE GROUP III
8871 NP 8872 P 0873 P 8874 P 8875 P 8876 P 8877 P 8878 NP 8879 NP 8880 P 8881 P 8882 P 8883 NP 8884 P 8885 P 8886 NP 8887 P 8888 P 8889 P 8890 P 8891 P 8892 P 8893 P 8894 P 8895 P
MATING NOT CONFIRMED
282.
285 .
291.
259.
266 .
268.
281.
281 .
286.
262 .
266 .
265.
294 .
309.
311.
238.
251 .
251.
262 .
264 .
262.
276 .
277 .
270.
274 .
284 .
293.
259.
266.
268.
289.
302 .
299.
251.
261 .
262.
236.
242 .
251.
309.
316.
319.
273 .
278.
276.
266.
269.
276 .
292.
295 .
304 .
286.
286 .
294 .
292.
302 .
308.
262.
264 .
266.
277.
275 .
283 .
265.
268 .
280.
302 .
306 .
307.
234 .
238.
244.
34 0.4 MG/KG/DAY
5
298. 276 . 291. 271. 315. 257. 266 . 265. 296 . 270. 295. 270. 251. 332 . 280. 274 . 306 . 297. 310. 273. 279. 276. 314 . 246.
302. 271. 293 . 266 . 319. 254 . 264 . 261. 301. 273 . 299. 278. 256. 329284. 274. 304 . 298. 309. 272. 279. 278. 309. 244.
307. 278. 296 . 268. 318. 261. 268. 265. 301. 280. 296. 277. 257. 333. 287. 272. 310. 298. 315. 277. 283. 281. 316. 254 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6
301 . 280 . 301 . 271. 321. 265. 275 . 259. 302 . 278. 299. 284. 262 . 336 . 289. 288. 312. 294 . 320. 279. 287. 280 . 318. 256.
7
306 . 282 . 300 . 275. 320 . 264 . 271. 260. 308 . 280. 296. 283. 263. 336. 289. 285. 310. 300. 322. 280. 294. 283. 318. 255.
8
303. 284 . 301. 279. 328. 266 . 273 . 256. 307. 279. 304 . 281. 266 . 346 . 290 . 288. 314 . 296 . 325. 286. 299. 288. 319. 261.
9
310. 290 . 304 . 279. 330. 271 . 277 . 264 . 309. 285 . 302 . 275. 267. 349. 296 . 291. 322. 302. 327. 294 . 303. 289. 322 . 266.
10
310. 303 . 317. 283 . 337. 277. 286 . 264 . 313. 286. 306 . 285. 280. 354 . 308. 299. 328. 303 . 327. 297. 307. 292. 320 . 274 .
ii
315. 315. 293 . 344 .
290. 306.
355 .
306. 331. 301. 312. 301. 333 . 282.
12
i 317. 321. 292. 349.
294 . 314 .
362.
310. 339. 306. 317. 308 . 333. 281.
418-008:PAGE C-58
000344
PROTOCOL 4IB 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295,9)
TABLE C24 (PAGE 10) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 X 2 3 4 5
RAT tt
DOSAGE GROUP III
0.4 MG/KG/DAY
8896 P 8897 P 8898 P 8899 P 8900 P 8901 P 8902 P 8903 NP 8904 NP 8905 P
264. 269. 297. 289. 258. 260. 288. 256. 286 . 251.
268. 281. 299. 288. 266. 266. 298. 254. 284 . 253.
276. 279. 305. 292. 270. 271. 302. 265. 291. 253.
280. 290. 308. 294 . 280. 273 . 303. 271. 294 . 258.
284 . 288. 311. 299. 282. 266. 307. 279. 290. 262 .
289. 302. 311. 304 . 281. 271. 312 . 282 . 287. 265.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
6
289. 299. 314 . 308 . 290. 278. 315. 281. 294. 265.
7
289. 300. 315. 308. 291. 276. 317. 287. 293 . 267.
8
297. 301. 315. 312. 287. 275. 327. 290. 295. 276.
9 10
304 . 308. 319. 314 . 294 . 282. 328. 287. 293. 273.
307. 315. 320. 321. 305. 282. 332. 292. 297. 280.
11 12
310. 323. 327. 327. 309. 300 . 335. 291. 297 . 280.
306. 326. 331. 329. 311. 300. 338. 296. 295. 284.
418-008:PAGE C-59
000345
418-008:PAGE C-60
0C0346
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RAIS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 11): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18
RAT ft
DOSAGE GROUP III
0.4 MG/KG/DAY
8871 NP 8872 P 8873 P 8874 P 8875 P 8876 P 8877 P 8878 NP 8879 NP 8880 P 8881 P 8882 P 8883 NP 8884 P 8885 P 8886 NP 8887 P 8888 P 8889 P 8890 P 8891 P 8892 P 8893 P 8894 P 8895 P
MATING NOT CONFIRMED
325.
331 .
340 .
324 . 296. 351.
330 . 302 . 351.
340. 306. 357.
352.
352. 318 . 367.
372.
363. 331. 382.
389.
388. 342. 380.
301. 320.
370.
300 . 320 .
308. 329.
318. 345.
329. 363.
373 .
383 .
396 .
407.
336. 382.
416.
312. 338. 307. 322 . 303 . 332. 290.
318. 346. 316 . 328 . 314. 342. 294.
319. 351. 327. 332. 321. 338. 305.
333 . 358. 341. 351. 332. 345. 314 .
347. 371. 359. 350. 351. 349. 336.
361. 386. 371. 362. 360. 356. 346.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
19 20 21
410.
393. 357. 396.
425.
408. 370. 399.
430. 410. 411.
359. 398.
364 . 414 .
381. 423 .
435 .
454 .
471.
373. 393 . 388. 371. 378 . 366. 364.
386. 413. 396. 386. 393. 371. 387.
425.
385. 373. 379. 393.
22 380.
23
24
25
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 12) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 IS 16 17 18
RAT It
DOSAGE GROUP III
0.4 MG/KG/DAY
8896 P 8897 P 8898 P 8899 P 8900 P 8901 P 8902 P 8903 NP 8904 NP 8905 P
314 . 323 . 332. 333. 313. 306. 343 . 290. 296. 298.
318. 329. 339. 340. 326 . 308. 351. 295. 301. 301.
325. 340. 350. 345. 333 . 314. 354. 296 . 301. 312.
328. 351 . 353 . 355. 339. 329. 363 . 2BB . 297. 326.
345. 368. 364 . 369. 365. 344 . 380. 292. 298. 341.
356. 378. 382. 377. 372. 352. 402. 292. 298. 359.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
19 20 21 22 23 24 25
370. 391. 386. 390. 379. 363 . 419. 285. 298. 380.
388. 408. 393 . 405. 395. 372. 434 . 285. 297. 391.
407.
409. 380. 427. 283 . 292. 397.
284 . 295.
280. 292 .
276 . 297 .
285. 299.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 13) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2
RAT H
DOSAGE GROUP IV
8906 P 8907 NP 8908 P 8909 P 8910 P 8911 P 8912 P 8913 P 8914 NP 8915 P 8916 P 8917 P 8918 NP 8919 P 8920 P 8921 P 8922 P 8923 NP 8924 P 8925 P 8926 P 8927 P 8928 P 8929 P 8930 P
NO CONFIRMED MATING DATE
275.
282.
270 .
249 .
264.
264 .
241.
251.
257.
264 .
270.
268.
268.
271.
277.
256.
263.
281.
266.
270.
273 .
228.
234 .
232.
310.
324.
328.
243.
250.
259.
276.
286.
283 .
260.
266.
275.
291.
299.
305.
276.
281.
279.
252.
254.
260.
226 .
228.
234.
250.
255.
255.
249.
260.
263.
263.
267.
276.
236.
244 .
243.
262.
271.
279.
250.
254 .
261.
256.
264 .
268.
NO CONFIRMED MATING DATE
34 1.6 MG/KG/Di
270 . 268. 258. 270 . 283 . 264 . 277. 234 . 325. 254 . 282 . 277 . 304 . 282 . 263. 235 . 252. 267. 279. 247 . 283 . 262. 268.
268. 269. 260. 268. 288. 268. 275. 235. 329. 259. 288. 276. 305. 285. 264 . 234 . 256. 272. 290. 249. 287. 264 . 272.
5
274 . 268. 261. 268. 285. 269. 278. 233. 334 . 262. 294 . 274. 313. 285. 264 . 236 . 255. 270. 287. 250. 290 . 262. 275 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
6
276. 274 . 262 . 274. 290 . 275. 279. 237. 335. 265. 291. 279. 316. 287. 277. 240. 258. 273. 288. 251. 289. 263. 277.
7
272. 272 . 264 . 269. 290. 275. 284 . 242. 339. 261. 293 . 279. 328. 287. 278. 241. 254. 270. 297. 253. 286. 268. 283.
8
270. 274 . 266 . 273 . 291. 276 . 285. 239. 342. 271 . 299. 287. 327. 291. 282. 244 . 256. 276 . 292 . 254. 290. 272. 284 .
9
272. 278. 273. 277. 299. 282. 290. 240. 346. 270. 298. 283. 333 . 293 . 280. 246. 259. 276. 294. 258. 298. 275. 286.
10
277. 276 . 279. 283. 308. 295. 293 . 244 . 354. 283 . 314 . 290. 341. 299. 289. 254. 263 . 280. 296. 260. 298. 279. 291.
11
288
295 247
298 349 306 291 262 308 265 301 282 294
12
289.
300. 252.
299. 355. 307. 296. 267. 314. 264. 308. 285. 299.
418-008:PAGE C-62
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 14) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2 3 4 5
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
8931 P 8932 P 8933 NP 8934 P 8935 P 8936 P 8937 P 8938 8939 P 8940 P
288.
291 .
282.
288 .
298.
237 .
247.
250.
251 .
252.
271.
274 .
275.
281 .
282.
234 .
239.
241.
245 .
249.
261 .
266 .
264.
263 .
265.
279.
286.
286.
290.
293.
281.
284 .
287.
288 .
294.
MORIBUND SACRIFICED ON DAY 36 OF STUDY
NO CONFIRMED MATING DATE
298.
304.
308.
302 .
307.
289. 256. 286. 246. 272. 294 . 299.
315.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6
303 . 257. 289. 254 . 271 . 295. 300.
318.
7
296. 260. 297. 257. 277. 299. 297.
322.
89
298. 265. 296. 259. 283 . 298. 306.
308. 267. 298. 262. 277. 303. 301.
322.
319.
10 11 12
304 . 266. 301. 274. 285. 308. 297.
310. 267. 296. 276 . 290. 311. 312.
325. 274 . 284 . 278. 301. 316. 318.
324.
330.
332.
418-008:PAGE C-63
ooo
CO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 15): MATERNAL BODY HEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18
RAT #
DOSAGE GROUP IV
GROUP IV
8906 P 8907 NP 8908 P 8909 P 8910 P 8911 P 8912 P 8913 P 8914 NP 8915 P 8916 P 8917 P 8918 NP 8919 P 8920 P 8921 P 8922 P 8923 NP 8924 P 8925 P 8926 P 8927 P 8928 P 8929 P 8930 P
NO CONFIRMED MATING DATE
292.
296.
302.
312 .
322 .
333 .
299. 245.
308. 239.
318. 240.
330. 240.
343. 240.
351. 236.
302. 357. 309. 300.
285. 365. 316. 300.
276. 374 . 320. 308.
277. 389. 334 . 317.
266.
264 .
264.
260.
312.
316.
324.
270.
273 .
281.
318.
323 .
333 .
293 .
296 .
307.
302.
306 .
319.
NO CONFIRMED MATING DATE
328 . 294 . 341. 316. 326.
273. 412. 346. 336.
263.
338. 306. 363 . 327. 338.
270. 427. 352. 350.
262.
354. 323 . 380 . 340. 355.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL HEIGHTS HERE RECORDED IN GRAMS (G) .
19 20 1.6 MG/KG/DAY
345.
351 .
365. 241.
381 . 238.
276 . 436. 364. 362.
252.
371. 329. 400. 350. 360.
274 . 452 . 376 . 372.
246 .
386. 343 . 424 . 357 . 369.
21
366 .
234 .
270. 389. 390. 242 . 395. 373. 391.
22
238. 271. 248.
23 24
237 .
239.
271 .
275.
246 .
252.
25 t
246. 271. 252.
418-008:PAGE C-64
0C0350
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 16) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
8931 P 8932 P 8933 NP 8934 P 8935 P 8936 P 8937 P 8938 8939 P 8940 P
321.
324.
335.
338.
356.
283 .
287.
298.
312.
326 .
282.
280.
278.
278.
278 .
286.
283 .
295.
313 .
329.
296.
309.
313 .
315.
337.
323.
325.
337.
351.
365.
319.
328.
330.
340 .
346 .
MORIBUND SACRIFICED ON DAY 26 OF STUDY
NO CONFIRMED MATING DATE
338.
336.
349.
365.
382.
376. 341. 280. 341. 349. 377. 360 .
406 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
19
396. 360 . 282. 355. 360. 393 . 374 .
425.
20
408. 377. 277. 369. 373. 404. 388.
434 .
21
413 . 271 .
408. 405.
22 282 .
23 282 .
24 282 .
25 282.
418-008:PAGE C-65
OC 03
f/T
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 17) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0
1
RAT n
DOSAGE GROUP V
2
34 3.2 MG/KG/DAY
5
8941 P 8942 P 8943 P 8944 P 8945 NP 6946 P 8947 P 8948 P 8949 P 8950 P 8951 P 8952 NP 8953 P 8954 P 8955 P 8956 P 8957 NP 8958 P 8959 P 8960 P 8961 P 8962 P 8963 NP 6964 P 8965 P
217. 268. 217 . 219. 221 . 274 . 242. 237. 208 . 262 . 232 . 232. 224 . 249. 216. 233. 218. 260. 258. 264 . 226. 244 . 219. 239. 238.
226 . 260. 218. 222 . 228 . 272. 243. 241. 215. 269. 246. 237. 232. 255. 230. 237. 227. 263. 258. 262 . 236 . 263 . 239. 240 . 241.
219. 274 . 219. 226 . 235. 277 . 248. 234. 214 . 270. 242. 237. 234. 264 . 233 . 236 . 226 . 265. 257. 267. 230. 256 . 245. 245. 241.
224 . 276 . 213 . 224 . 229. 273 . 250 . 229. 219. 269. 238. 238. 234 . 266. 233 . 242 . 226 . 264 . 254 . 268 . 228 . 268. 244 . 241 . 242 .
221 . 279. 216. 227. 233 . 280 . 253. 228. 225. 269. 247. 237. 232. 272. 231. 238. 237. 266 . 259. 270 . 236 . 260 . 252 . 238. 241.
220. 279. 216 . 226 . 228. 278. 255. 233. 226 . 276. 246. 244 . 237. 266. 236 . 245. 231. 259. 261. 274 . 235. 263. 246 . 241. 244 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6
225 . 288. 218. 231. 230. 277. 252. 246. 230. 278. 249. 242. 242 . 272 . 237 . 244 . 236. 283 . 270. 274. 236. 262. 247 . 245 . 246 .
7
228. 286. 218. 232. 234 . 289. 265. 250. 228. 278. 255. 234 . 240 . 276. 235. 243 . 235. 266. 267. 274 . 241. 272 . 252. 250. 252.
8
230. 292. 221. 230 . 231. 285. 266. 253. 232 . 279. 256. 242. 246. 271. 239. 246. 240 . 263 . 262 . 286 . 235. 262. 257. 246. 257.
9
231. 289. 228. 232 . 238. 287. 269. 263 . 231. 283 . 257. 245. 245 . 276. 241. 253 . 244 . 273 . 260. 283 . 240 . 262. 259. 251. 257 .
10
241. 294 . 235. 236. 238 . 293. 287. 268 . 238. 288. 259. 246. 248 . 277. 250. 259. 243. 284 . 270. 291. 242 . 265. 258. 265. 266.
11
301. 236 . 242. 240 . 296 .
240. 297.
243 .
249. 260. 247.
272 . 291. 250 . 266 .
263 .
12
303 . 240. 241. 237. 292 .
240. 299.
244 .
255 . 266. 247.
282. 293. 257. 263.
264 .
418-008:PAGE C-66
000352
PROTOCOL 418-008: COMBINED ORA!. (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 18): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2 3 4 5
RAT It
DOSAGE GROUP V
3.2 MG/KG/DAY
8966 P 8967 P 8968 P 8969 P 8970 P 8971 P 8972 NP 8973 P 8974 P 8975 P
245. 228. 230. 225. 258. 262. 207. 238. 231. 255.
248. 230. 227. 235. 261. 266. 211. 239. 236. 254.
249. 240. 228 . 232. 260. 270. 217. 239. 232. 259.
254 . 235 . 233 . 234 . 268. 270. 214 . 240. 231 . 259.
254. 238. 227. 238. 265. 272. 219. 243 . 230. 259.
259. 246 . 240 . 242. 277 . 279. 223 . 243 . 236. 262.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6
260. 245. 238 . 244 . 276 . 284 . 227. 249. 233. 263 .
7
260. 245. 242. 242. 276. 284 . 224 . 250. 232 . 262.
8
265. 248. 244 . 252 . 280 . 285. 224 . 248. 228 . 267.
9
268. 244. 256. 257. 264 . 298. 229. 246. 235. 270.
10
280. 253. 251. 260. 266. 294. 231. 259. 237. 273.
11 12
264 . 261. 263 . 250 . 301. 228. 264 . 242 . 279.
267. 259. 258 . 255. 306 . 234. 267. 245. 278.
418-008: PAGE C-67
000353
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 19) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18
RAT It
DOSAGE GROUP V
3.2 MG/KG/DAY
8941 P 8942 P 8943 P 8944 P 8945 NP 8946 P 8947 P 8948 P 8949 P 8950 P 8951 P 8952 NP 8953 P 8954 P 8955 P 8956 P 8957 NP 8958 P 8959 P 8960 P 8961 P 8962 P 8963 NP 8964 P 8965 P
307. 243. 242. 230 . 304 .
320. 243 . 249. 231. 311.
327. 250. 256. 230. 318.
333. 264 . 268. 227. 327.
347. 277. 278. 232 . 335.
368. 294. 293 . 234 . 354 .
250. 306.
246.
251. 308.
243 .
257. 312.
240.
269. 319.
239.
280. 332.
242.
299. 340.
276.
256 . 261. 235.
289. 299. 263. 259.
265.
257. 270. 234.
299. 297. 265. 259.
270.
265. 280. 233.
301. 308. 270. 266 .
279.
274 . 288. 239.
282. 325. 285. 276.
298.
283 . 313 . 239.
311. 334. 302. 290.
311.
300. 326. 229.
332. 352. 315. 314.
330.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
19
380 . 307. 304 . 225. 370 .
312. 353 .
242.
314 . 334. 237.
342. 367. 326 . 334 .
347.
20
389. 314 . 314 . 221. 384.
324 . 359.
236 .
321. 346. 237.
353. 381. 340. 345.
359.
21
396. 219.
327. 241.
240. 404 . 351. 364 .
22
223 .
240. 242. 234.
23
222 . 244 . 238.
24
217. 243. 239.
25
227. 243 . 241.
418-008:PAGE C-68
000354
PROTOCOL 410-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C24 (PAGE 20) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18
RAT tf
DOSAGE GROUP V
3.2 MG/KG/DAY
8966 P 8967 P 8968 P 8969 P 8970 P 8971 P 8972 NP 8973 p 8974 p 8975 p
275. 260. 264. 261. 302. 228. 272. 246. 286.
277. 263 . 267. 273 . 311. 228. 274 . 250. 297.
279 . 267. 276 . 285. 315. 224 . 278. 259. 304 .
297. 279. 294 . 294 . 323. 222. 297. 269. 315.
308. 292. 304 . 312. 343. 223 . 310. 288. 330.
329. 300 . 320. 330 . 358. 220. 322 . 306 . 342 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
19
344 . 313 . 346. 344 . 372. 221. 341. 323. 358.
20
350. 317. 344. 357. 384 . 221. 342. 336. 365.
21
344 .
209. 355. 338. 382.
22 215 .
23 214 .
24 218.
25 222 .
418-008:PAGE C-69
OC0355
418-008:PAGE C-70
000356
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C25 (PAGE 1) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1 4 7
RAT #
DOSAGE GROUP I
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8821 8823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
267.
251.
296.
313.
303 .
306.
265.
256.
308.
301.
295.
303.
300.
301.
312 .
331.
292.
310.
339.
338.
NOT PREGNANT
NOT PREGNANT
319.
330.
315.
328.
284 .
292.
300.
315.
290.
285.
302.
300.
308.
310.
288.
310.
276.
263.
318.
331.
293.
296.
328.
332.
264.
286.
262. 322 . 320 . 274 . 306. 296 . 326 . 341. 304 . 337 .
334 . 320. 296. 318. 301. 334 . 313. 315. 289. 334 . 291. 340 . 299.
DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
10 14 21
0 l(VEHICLE) MG/KG/DAY
285. 334. 337 . 284 . 338. 309. 328 356 328 366
276. 345. 352. 305. 341. 342. 308. 336 339. 337
248. 342 . 340 . 327. 345. 335. 336. 363 . 323 . 334 .
349 354 342. 323 341 342. 325 311 320. 312 345 336 . 296 319 330. 314 316 341. 329 347 . ' 315. 321 328 328. 345 313 320. 347 338 333. 316 309 325. 315 306 356. 321 314 336 .
j
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C25 (PAGE 2) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1 4 7 10 14 21
RAT #
DOSAGE GROUP II
0.1 MG/KG/DAY
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865 8866 8867 8868 8869 8870
293. 290 . 326. 284 .a 311. 264 . 298. 318. 320. 274 . 279. 301. 310. 290. 298. 306. 337. 295. 283 . 298. 288. 293 . 282. 330. 291.
312. 301. 325. 298. 306. 279. 289. 312. 339. 279. 296. 317. 318. 299. 308. 305. 344. 296 . 276. 302. 284 . 300 . 287. 330 . 298.
307. 309. 333. 288. 300. 276. 298. 309. 331. 291. 304 . 317. 314. 297. 309. 306 . 333 . 299. 286. 312. 304 . 304 . 295. 332 . 296 .
323. 321. 338. 296 . 330. 289. 302. 327. 342. 308. 322 . 325. 321. 312. 328. 311. 346. 310 . 297. 321 . 304 . 316. 308. 345. 308.
314. 334 . 342. 322. 340. 293 . 282 . 334 . 356. 300. 337. 339. 330. 337. 324. 328. 364. 318. 300. 320. 323. 331. 322. 357. 316.
318 . 335. 337. 317 . 326 . 292. 312. 331. 339. 306. 327. 340 . 337. 336. 310. 333. 351. 319. 313 . 316 . 330. 342. 321. 357. 315.
DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Dam 8842 delivered one additional pup on day 2 of lactation; values for day 1 of lactation excluded from group averages and statistical analyses.
418-008PAGE C-71
000357
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C25 (PAGE 3): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1 4 7
RAT #
DOSAGE GROUP III
8871 8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899 8900 8901 8902 8903 8904 8905
NOT PREGNANT
298.
301.
296 .
305.
272 .
285 .
332.
331.
278 .
267.
276.
252.
354.
344 .
312.
308.
331 .
316.
273 .
278.
299.
295.
274 .
286.
330.
327.
269.
275.
286.
295.
300.
306.
307.
306.
305.
316.
296.
298.
294 .
288.
303.
310.
NOT PREGNANT
NOT PREGNANT
270 .
298.
316. 312 . 290 . 344 . 277. 298 . 358. 308. 303. 283 . 293 . 299. 323 . 282 . 295 . 316. 300 . 313. 306. 297. 310 .
299.
DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
10 14 0.4 MG/KG/DAY
338. 317. 307 . 348 . 300 . 321. 363 . 318. 318. 296 . 312. 318. 335. 294 . 315. 336 . 318. 325 . 326 . 310. 326 .
342. 294 . 314 . 360. 312. 327. 347. 328. 340. 317. 310. 312. 334 . 255. 339. 344 . 318. 321. 337. 311. 349 .
306 .
316.
21
342. 328. 303 . 350 . 321 . 337. 355. 332. 350. 305 . 326. 331. 333 . 302. 316. 346. 325. 330. 347. 324 . 358.
338 .
418-008:PAGE C-72
0C0358
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR-S STUDY NUMBER: 6295.9)
TABLE C25 (PAGE 4): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAY 1 4 7 10 14 21
RAT It
DOSAGE GROUP IV
1.6 MG/KG/DAY
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
269.
258 .
270.
284 .
300.
314.
267.
278 .
287.
304 .
304 .
307.
288.
286.
300 .
313 .
331.
321.
NOT PREGNANT
NOT PREGNANT
357.
346 .
351.
344 .
363.
370.
303 .
298.
297.
308.
318.
326.
292.
278 .
287.
303.
319.
339.
NOT PREGNANT
315.
301 .
305.
313 .
331.
340.
266.
252.
248.
257.
270.
288.
310.
276 .
291.
307.
321.
335.
280.
284 .
290.
309.
336.
331.
308.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
290.
288.
294 .
306.
328 .
336.
318.
311.
311.
320.
330.
327.
276,
277.
273 .
287.
308.
318.
NOT PREGNANT
290,
278.
270.
286.
299.
314.
298.
293 .
293 .
304 .
318.
325.
296.
280.
NO SURVIVING PUPS ON DAY 4 OF LACTATION
313,
295.
314.
317.
329.
356.
MORIBUND SACRIFICED ON DAY 36 OF STUDY
309,
310.
302.
310.
315.
316.
311
323 .
322.
343 .
365.
366.
DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
418-008:PAGE C-73
000359
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C25 (PAGE 5) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
RAT ft
DAY 1
4
DOSAGE GROUP Vr
7
10 14 31.2 MG/KG/DAY
21
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
292.
NO SURVIVING PUPS ON DAY 1 OF LACTATION
250.
NO SURVIVING PUPS ON DAY i OF LACTATION
a NO SURVIVING PUPS ON DAY i OF LACTATION
NOT PREGNANT
315.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
256.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
a NO SURVIVING PUPS ON DAY 1 OF LACTATION
NOT PREGNANT
246.
NO SURVIVING PUPS ON DAY 1 OF LACTATION
272.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
NOT PREGNANT
286 .
NO SURVIVING PUPS ON DAY 2 OF LACTATION
292.
NO SURVIVING PUPS ON DAY 1 OF LACTATION
262.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
268.
NO SURVIVING PUPS ON DAY 1 OF LACTATION
292.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
284 .
NO SURVIVING PUPS ON DAY i OF LACTATION
271.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
243 .
NO SURVIVING PUPS ON DAY 1 OF LACTATION
278.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
301.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
NOT PREGNANT
261.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
257 NO SURVIVING PUPS ON DAY 1 OF LACTATION
266.
NO SURVIVING PUPS ON DAY 1 OF LACTATION
DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was not recorded.
418-008:PAGE C-74
000360
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 1): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS RAT 8
1- 8 8- 15 15- 22 22- 29 29- 36 36> 42a
DOSAGE GROUP ][
0 (VEHICLE) MG/KG/DAY
8801 8602 8803 8804 8805 8806 8807 8808 8809 8810 8811 8812 8813 8814 8815 8816 8817 8818 8819 8820 8821 8822 8823 8824 8825 8826
118. 122. 132. 143. 138. 162 . 127. 139. 134. 133.
b 151. 129. 156. 126. 159. 118. 179. 130. 123 . 142. 128. 128. 150. 148. 120.
111 . 138. 134 . 142. 146 . 171 . 145. 146 . 127. 144 . 131. 146. 136. 170. 169. 130. 132. 177. 131. 134. 142. 124. 129. 163 . 128 . 127.
107 . 115. 140 . 143.
87. 174 . 136. 151. 125. 149. 130. 141. 124 . 150. 133. 126. 124. 180. 125. 131. 138. 128. 128. 155. 145 . 120.
106. 136. 137. 133. 140. 161. 127. 135. 129. 181. 130. 141. 122. 148. 136. 141. 134 . 185. 129. 124. 137. 130. 128. 166. 134. 129.
104 . 141. 127. 142. 119. 154 . 120. 132. 126. 123 . 123 . 142. 131. 153. 116 . 131. 151. 174 . 140. 120. 139. 124 . 121 . 154 . 131. 125.
9B . 124 . 119. 109. 109. 149. 117. Ill . 112. 113 . 105. 114.
99. 129. 121. 133 . 114 . 145 . 103. 110. 115. 103 . 103. 117 . 118. 103 .
DAYS DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value.
418-008:PAGE C-75
000361
418-008:PAGE C-76
000362
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 2) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
RAT ft
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8827 8828 8829 8830 8831 8832 8833 8834 8835
112. 120. 124 . 152. 127. 126 . 130. 131 . 116.
114 . 131. 137. 146. 135. 124. 138. 143 . 122.
110. 130. 132 . 162 . 133. 130. 155. 146 . 138 .
120. 138. 129. 168. 144 . 137. 169. 159. 134 .
116. 135. 133. 153.
b 145. 136. 163. 119.
99. 126. 125. 130. 116. 104 . 119. 128. 109.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value.
*
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 3) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1- 8 8- 15 IS- 22 22- 29 29- 36 36- 42a
RAT n
DOSAGE GROUP II
0 .1 MG/KG/DAY
8836 8837 8838 8839 8840 8841 8842 8843 8844 8845 8846 8847 8848 8849 8850 8851 8852 8853 8854 8855 8856 8857 8858 8859 8860 8861
122 . 128 . 139. 127 . 136 . 131 . 143. 155 . 133 . 139. 127. 140. 140. 143 . 146. 246. 130. 136. 153. 157. 126. 119. 134 . 122. 138. 138.
125. 130. 136. 135. 173 . 147. 145. 160. 136. 144 . 595.b 150. 166. 156. 618. b 145. 127. 144 . 163. 159. 133. 123 . 124 . 136. 618 .b 129.
125. 139. 162. 122 . 152 . 142 . 147, 163. 134. 143. 126. 141. 156. 149. 142. 142. 127. 127. 159. 150. 127. 128. 125. 143 . 160. 119.
124 . 144 . 127. 105. 136. 155. 120. 168. 130. 149. 118. 138. 127. 153 . 128. 149. 131 . 132. 159. 148. 126. 143. 128. 163 . 155. 134 .
110. 132. 136 . 113. 138 . 149. 130 . 115. 138 .
94 . 123. 142. 124 . 151. 132. 143. 124. 127. 149 . 139. 159. 138. 122. 150. 149. 135.
106. 642. b 111.
99. 119. 116. 112. 151. 124. 129.
99. 116.
96. 129. 122. 124. 112.
98. 113. 122. 105. 115. 109. 138. 128. 113.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation. b. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses.
418-008:PAGE C-77
000363
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 4) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
RAT
DOSAGE GROUP II
0 .1 MG/KG/DAY
8862 8863 8864 8865 8866 8867 8868 8869 8870
131. 122. 120. 137. 118. 129. 126. 146. 127.
132. 129. 622 .b 142. 116 . 123 . 123 . 141 . 124 .
136 . 129. 135. 130. 120. 124 . 128. 141. 133.
136. 125. 128. 145. 130. 130. 133. 148 . 128.
140 . 135. 130. 159. 128 . 134 . 139.
C 121.
124 . 111. 122. 123 . 110. 107 . 110. 128. 125.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. c. Spilled feed precluded the calculation of this value.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 5) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS i- a 8- 15 15- 22 22 29 29- 36 36- 42a
RAT tt
DOSAGE GROUP III
0. 4 MG/KG/DAY
8811 8872 8873 8874 8875 8876 8877 8878 8879 8880 8881 8882 8883 8884 8885 8886 8887 8888 8889 8890 8891 8892 8893 8894 8895 8896
126. 141. 154 . 135. 135. 151. 123. 143. 137. 119. 117. 129. 126. 117. 162. 129. 126 . 153. 127. 144. 126. 131. 123. 173. 116. 123.
118. 151. 148 . 136. 138 . 156 . 877.b 144 . 136. 121. 124 . 132 . 139. 123. 157. 131. 138. 155. 620.b 142. 124 . 136. 127. 142. 115. 123.
117. 139. 146. 133 . 129. 144 . 132 . 134 . 137. 130. 121. 141. 132. 114. 164 . 135. 133. 156. 135. 175. 117. 144 . 134. 146. 120. 122.
120. 131. 141 . 131. 120 . 145 .
c 125. 136. 125. 121, 165. 147. 110. 162. 141. 131. 146. 135. 135. 123. 150. 125. 142. 110. 131.
109. 126. 123 . 128. 117. 137. 119. 125. 117. 125. 118. 152 . 133. 116. 162. 134 . 126. 135. 123. 129. 122. 141. 123. 160. 106 . 130.
90 . 118. 122. 110 . 110. 115.
93. 106 . 128. 101. 108. 129. 121. 103 . 131. 112. 104 . 122 . 103 . 135. 103. 116 . 106 . 120. 101. 107.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses. c. Spilled feed precluded the calculation of this value.
418-008: PAGE C-79
000365
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 6) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
RAT It
DOSAGE GROUP III
0 .4 MG/KG/DAY
8897 8898 8899 8900 8901 8902 8903 8904 8905
197 . 158. 134 . 130. 115. 143 . 122. 146 . 111.
523.b 150 . 140. 131. 110.
72. 118. 138. 110.
154. 132. 138. 149. 116. 153. 121. 139. 119.
157 . 121. 158. 145 . 130. 151 . 124 . 143 . 119.
152. 117. 141. 143 . 130. 158. 122. 148. 114 .
124 . 111. 130. 114 . 107. 123 . 104. 128. 113 .
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses.
418-008:PAGE C-80
000366
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C26 (PAGE 7) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
RAT H
DOSAGE GROUP IV
1 .6 MG/KG/DAY
8906 8907 8908 8909 8910 8911 8912 8913 8914 8915 8916 8917 8918 8919 8920 8921 8922 8923 8924 8925 8926 8927 8928 8929 8930 8931
122. 139. 145. 127. 133. 138. 124 . 130. 130. 172. 131. 129. 189. 161. 147. 144 . 105. 129. 123. 122 . 131. 114. 118. 172 . 144 . 139.
137. 142 . 155. 137. 132 . 146 . 130. 136 . 128. 182. 139. 129. 147. 149. 149. 147. 109. 127. 113 . 136. 132 . 119. 121. 140 . 144 . 136 .
133 . 129. 121 . 129. 124 . 142. 124 . 132. 107. 3175.b 129. 128. 147. 131. 139. 145. 110. 110. 105. 135. 127. 125. 121. 149. 135. 128 .
115. 127. 123. 119. 117. 129. 114 . 129. 100. 158. 128. 127. 155. 167. 139. 152. 115. 125. 119. 141. 123. 138. 116. 123. 125. 125.
118. 123. 108. 118. 116. 120. 114 . 117.
98. 138. 132 . 139. 136. 169. 123 . 138.
97. 107. 112. 132. 114 . 128. 107. 123. 138. 139.
100 . 103. 103. 101. 111. 114.
99. 108 .
92. 125. 116. 112. 108. 129. 119. 128 .
92. 94 . 104 . 121. 98. 121. 106. 110. 103. 114 .
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G), a. Last value recorded before cohabitation. b. Value appeared incorrectly recorded and was excluded from group averages and statistical analyses.
418-008:PAGE C-81
000367
418-008:PAGE C-82
000368
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 8) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
RAT #
DOSAGE GROUP IV
1 .6 MG/KG/DAY
8932 8933 8934 8935 8936 8937 8938 8939 8940
130 . 205. 109. 145. 130. 141. 126. 124 . 157.
125. 176. 111. 135. 123. 132. Ill. 123 .
b
116 . 132 . 115. 134. 126. 131. 119. 125. 165.
128. 154. 121. 124 . 123. 137. 116. 124 . 165.
125. 168. 110. 136 . 131. 157.
86. 121. 165.
107 . 164. 101. 110 . 112. 149. MORIBUND SACRIFICED ON DAY 36 OF STUDY 109. 127.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value.
t
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 9) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS RAT #
1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
DOSAGE GROUP V
3 .2 MG/KG/DAY
8941 8942 8943 8944 8945 8946 8947 8948 8949 8950 8951 8952 8953 8954 8955 8956 8957 8958 8959 8960 8961 8962 8963 8964 8965 8966
120 . 114 . 113 . 128 . 126. 145. 128 . 137. 116. 134 . 136. 115. 123. 120. 117. 115 . 122. 127. 132. 147. 102. 139. 126. 116. 114 . 134.
119. 128. 114 . 114 . 125. 139. 114. 134 . 104 . 131. 122. 108. 139. 139. 128. 110. 123 . 195. 124 . 141.
88. 126. 117.
93 . 109. 123.
105. 107.
92 . 106. 113. 120. 105. 128 . 108. 116. 121. 102. 119. 119. 109. 112.
98. 114 . 121. 132.
93. 107. Ill. 106. 109. 117.
93 . 117.
93 . 106. 111. 112. 110 . 131.
90. 124. 111.
98. 122. 121. 108. 109. 114 . 112. 109. 136 .
95. 132. 117. 112. 111. 122.
84 . 102 .
82 . 86 . 107. 103 . 98. 112. 90. 113. 102. 98. 109. 112. 100 . 96. 96. 106 . 94 . 120. 97. 122. 105. 100. 112. 112.
84 . 102.
80. 87. 81. 83. 94 . 102. 69. 109. 92. 86. 99. 117 . 101. 86 . 95. 110. 91. 112. 83. 117. 100. 98 . 104 . 103.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008.PAGE C-83
9C0J0
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C26 (PAGE 10): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
RAT #
DOSAGE GROUP V
3 .2 MG/KG/DAY
8967 8968 8969 8970 8971 8972 8973 8974 8975
118. Ill. 113 . 171. 130. 102. 117. 124 . 122 .
106 . 116 . 110. 150. 132.
91. 103 .
94 . 106 .
87. 107. 114 . 157. 141.
91. 118 . 100. 115.
132. Ill. 120. 136. 140. 102 . 114 . 103 . 111.
108. 87 .
104 . 110. 140.
82 . 103. 108 . 111.
97. 91. 95. 95 . 120. 87. 102. 163 . 99.
DAYS = DAYS OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Last value recorded before cohabitation.
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 1) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2 2 - 3
RAT #
DOSAGE GROUP I
3- 4 4- 5 5- 6 0 (VEHICLE) MG/KG/DAY
8801 P 8802 P 8803 P 8804 P 8805 P 8806 P 8807 P 8808 P 8809 P 8810 P 8811 P 8812 P 8813 P 8814 P 8815 P 8816 P 8817 NP 8818 NP 8819 P 8820 p 8821 p 8822 p 8823 p 8824 p 8825 p
16 . 19.
14 .
21. 28 . 30 .
22. 27. 23 .
24 . 17.
24 .
17 . 21.
20 .
28. 26 . 29.
26. 23. 13 .
24 . 19.
16 .
21. 19. 18.
20. 20. 22.
11. 23. 22.
NO CONFIRMED MATING DATE
24 . 15.
31 .
15. 20. 21.
15. 26. 20.
20. 23. 20 .
7. 12 . 19.
20. 15 . 26.
15. 20 . 21.
19. 22. 23 .
20. 24 . 17.
19. 24 . 20.
14. 19. 22 .
17. 16 . 23.
21. 24 . 26.
24 . 24 . 25. 26 . 24 . 24 . 27. 24 . 20 . 12 . 16 .
21. 23 . 23 . 21. 25. 28. 22. 19. 27. 20 . 17. 19. 16 .
17. 31. 27. 20. 18. 33 . 25. 22 . 21 . 27. 24 .
16. 23. 27. 24 . 22. 18. 20. 24. 22. 21. 18. 18. 27.
17. 32. 21. 29. 22. 25 . 18 . IS. 21. 23. 21.
24. 26. 23. 27. 22. 30. 24 . 20. 16. 21. 19. 18. 22.
P = PREGNANT NP NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6- 7
16. 22. 25. 25. 28. 21. 23. 21. 19. 13 . 27.
22. 29. 22. 25. 29. 29. 24 . 19. 25. 17. 22. 22. 17.
7- 8
18. 26 . 25. 31. 18 . 24 . 26. 22. 23 . 22. 18.
26 . 27. 24 . 22. 20. 30. 32 . 24 . 20. 23. 20. 19. 21.
8- 9
23. 25. 27. 23 . 22. 29. 26. 19. 22 . 21. 23.
19. 25. 27. 26. 24. 26. 21. 22. 28. 22. 23. 24. 24.
9 - 10 10 - 11 11 - 12 12 - 13
15. 17. 21. 16. 27. 22. 26. 27. 25. 25. 28. 26. 27. 25. 17. 24. 22. 27. 18. 25. 26. 24. 18. 20. 29. 26. 21. 17. 25. 19. 24. 26.
22. 26. 21. 24. 30. 30. 30. 27. 24 . 24 . 24. 17. 22. 21. 30. 26. 22. 29. 26. 28. 23. 30. 21. 18. 26. 31. 22. 22. 20. 23. 21. 22. 26. 22. 24. 21. 21.
418-008:PAGE C-85
000371
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 2): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2 2 - 3 3 - 4 4 - 5 5 - 6
RAT
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8826 P 8827 P 8828 P 8829 P 8830 P 8831 P 8832 P 8833 P 8834 P 8835 P
18. 25. 25. 21. 26. 26. 17. 21. 22. 22. 17. 25. 21. 26. 17. 28. 17. 19. 25. 25. 25. 22. 23. 21. 23 . 22. 25. 23. 24. 25. 11. 22. 22. IS. 23. 23. 18. 19. 26. 26. 21. 25. 19. 19. 23. 15. 28. 22. 17. 19. 25. 22. 23. 24 . 18. 26. 24 . 22. 26. 27.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6- 7
30. 25. 23 . 21. 23. 25. 22 . 17. 30. 31.
7- 8
21. 20. 24. 22 . 25. 19. 33. 22. 24. 22.
8- 9
26 . 25. 28. 22. 20. 26. 20. 20 . 27. 24.
9 - 10 10 - 11 11 - 12 12 - 13
27.
20.
23 .
27.
21.
22.
23 .
23.
25. 25. 23. 21.
20.
27. 28. 25. 27.
26. 21. 23. 23.
25. 31. 25. 29.
27. 18. 25. 25.
26. 28. 27. 27.
29. 19. 23 . 30.
418-008:PAGE C-86
000372
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25
RAT tt
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801 P 8802 P 8803 P 8804 P 8805 P 8806 P 8807 P 8808 P 8809 P 8810 P 8811 P 8812 P 8813 P 8814 P 8815 P 8816 P 8817 NP 8818 NP 8819 P 8820 P 8821 P 8822 P 8823 P 8824 P 8825 P
20. 22. 19. 23 .
25 . 25 . 26 . 31 . 25. 23. 28. 29. 22. 16. 19. 24 .
25 . 24 . 20.
23 . 26.
25.
24 . 28.
22. 24 . 23. NO CONFIRMED MATING DATE 26. 24. 23. 28. 24 . 28.
24 .
23 27
19. 16. 17. 16 29. 17. 24. 27 26. 24. 29. 30
24 . 28. 22. 28
17. 21. 22. 22 22. 23. 22. 25
22.
30. 27. 19.
25. 28.
21.
23. 29.
16. 26. 26.
25.
18. 20.
20.
29. 27 . 20.
27. 27.
22.
16. 22.
15. 7.
26.
20.
22. 21.
18.
22. 27. 20.
20 . 22.
20.
19. 26.
15. 9.
25.
18.
20. 16.
20.
24 . 20. 19.
22. 22 .
20.
18. 24 .
20. 18. 21.
26.
21. 12.
13.
13. 16. 15 . 29.
13 . 17. 19. 18.
13. 17.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
418-008.PAGE C-87
000373
418-008.PAGE C-88
000374
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 4): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 20 20 - 21 21 - 22 22
RAT
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8626 P 8827 P 8828 P 8829 P 8830 P 8831 P 8832 P 8833 P 8834 P 8835 P
21. 24 . 25. 23. 19. 19. 20. 17.
23. 19. 21. 25. 22. 23 . 21. 21.
21.
24. -23 .
28.
26.
26 . 19.
24.
24 . 25. 28. 29. 28. 22. 21 . 21.
18. 24. 26. 25
24. 25. 23. 20.
28. 26. 30. 29
27. 22. 26. 23 .
18. 23. 26. 23
25. 25. 23. 20.
24. 25. 28. 26
26. 25. 22. 20.
23. 27. 26. 23
17. 22. 23 . 12.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
23 23 - 24 24
25
PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 5) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2 2 - 3 3 - 4 4 - 5 5 - 6
RAT
DOSAGE GROUP II
0.1 MG/KG/DAY
8836 P 8837 P 8838 P 8839 P 8840 P 8841 P 8842 P 8843 P 8844 P 8845 P 8846 P 8847 P 8848 P 8849 P 8850 NP 8851 P 8852 P 8853 P 8854 P 8855 P 8856 NP 8857 P 8858 P 8859 P 8860 P
19. 17 . 18. 16 . 19. 19.
23. 26. 26. 22. 28. 28.
15 . 16. 23. 20. 17 . 20.
22. 19. 21. 18. 24 . 22.
21. 17. 26 . 25. 22. 23 .
16. 19. 21. 23 . 26. 30.
20. 23 . 18 . 25. 14 . 15.
25. 27. 31. 23. 32. 28.
17. 21. 20. 17. 21. 21.
23. 17. 23. 25. 20. 22.
19.
22 .
23.
24 . 18.
21.
16. 21. 22. 22. 18. 22.
15. 24 . 22. 19. 20. 22.
17. 23 . 22. 21. 22. 26.
23. 27. 25. 26. 26. 24 .
17. 25. 26. 21. 22. 26.
14 . 18. 18. 15. 18. 23.
20. 17. 21. 22. 19. 24 .
11. 25. 25. 16. 26. 27.
14 . 24. 22. 23. 18. 23 .
a a 24. 15. 25. 24 .
16. 18. 22. 19. 21. 18.
11. 23 . 20. 17. 21. 24 .
19. 24 . 31. 21. 32. 30.
18. 25. 23. 19. 23. 23.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Value was not recorded.
6- 7
16 . 24 . 23. 16. 25. 23 . 21. 22 . 21. 21. 23. 24. 21. 20. 23 . 31. 19. 22 . 31. 27. 19. 22. 25. 18. 23.
7- 8
19. 22. 24 . 19. 28. 25. 23. 27. 22. 26. 22. 27. 20. 22. 25. 21. 20. 22. 19. 22. 20. 19. 20. 26. 22 .
8- 9
18. 27. 22. 20. 21. 32. 22. 27. 24. 22. 21. 21. 20. 25. 24 . 24. 18. 18. 25. 24. 19. 22. 23. 27. 24.
9 - 10 10 - 11 11 - 12 12 - 13
17. 21. 23. 16. 26 . 21. 24 . 26. 23 . 24. 24 . 24 . 21. 30. 24 . 32. 24. 23. 28. 26. 18. 25. 24 . 26. 27.
24 .
2B . 27. 21.
27. 24. 26.
25.
22. 19. 24 . 21. 22.
27. 25.
23.
21.
25. 27. 21.
20. 22. 24.
29.
26. 22. 27. 26. 26.
27. 28.
26.
24.
24. 27. 24.
26. 25. 26.
28.
29. 19. 24. 29. 26.
25. 27.
26.
418-008:PAGE C-89
000375
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C27 (PAGE 6) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2 2 - 3 3 - 4 4 - 5 5 - 6 6 - 7 7 - 8 8 - 9 9 - 10 10 - 11 11 - 12 12 - 13
RAT
DOSAGE GROUP II
0.1 MG/KG/DAY
B81 NP 8862 P 8863 P 8864 P 8865 P 8866 P 8867 P 8868 P 8869 P 8870 P
21. 15. 25 . 17. 25. 23. 22.
25. 20 . 29. 24 . 21. 24 . 24.
21. 22. 22 . 21. 18. 20. 21.
20. 21. 24 . 19. 25. 22. 17.
16 . 26 . 20 . 20.
27 . 26.
29.
21. 23 . 18. 25. 23 . 20 . 25.
21. 16. 24 . 21. 17. 23 . 20.
23. 21 . 26. 26. 16 . 19. 22.
11. 23. 25. 20. 25. 23 . 34.
22. 23 . 26. 21. 28. 23 . 20.
23 . 20 . 25. 30. 26 . 30. 24. 20. 25. 21. 23 . 24. 26. 24 . 27. 24. 28. 21. 24. 19. 23. 27. 22. 25. 22. 27. 31. 22. 23 . 28.
28 . 22. 21. 28. 26. 24 . 30 . 23 . 19.
26. 29. 23. 23. 26. 20. 24 . 26. 15.
24. 22. 32. 21. 23. 25. 26. 27. 22.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
418-008:PAGE C-90
000376
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 7): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21
RAT n
DOSAGE GROUP II
0.1 MG/KG/DAY
8836 P 8B37 P 8838 P 8839 P 8840 P 8841 P 8842 P 8843 P 8844 P 8845 P 8846 P 8847 P 8848 P 8849 P 8850 NP 8851 p 8852 p 8853 p 8854 p 8855 p 8856 NP 8857 p 8858 p 8859 P 8860 p
22.
22. 24. 25.
26. 21. 20.
27.
22 . 19. 23. 23. 21.
22. 21.
25 .
21.
24. 28. 26.
26. 21. 21.
29.
19. 16. 23. 23. 25.
20. 23.
26.
27.
27. 22 . 28.
25 . 22 . 23.
24 .
27. 21. 23. 27. 25.
21 . 23.
26 .
26.
28. 18. 25.
26 . 23 . 21.
31 .
23 . 20. 26 . 24 . 26.
24 . 26.
30.
26.
25. 18. 30.
23. 23. 22.
20.
23. 18. 25. 18. 22.
23. 24 .
24.
22.
24 . 19. 24 .
23 . 19. 24.
24 .
23 . 22. 24 . 24. 28.
23. 27.
24 .
22 .
26 . 20. 22 .
24 . 17. 22.
17.
24 . 18. 23. 30. 23 .
21. 24 .
19.
22.
15. 20. 18.
24. 18. 19.
23. 18. 21. 27. 20.
20. 27.
22.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
22 22 - 23 23 - 24 24 - 25
418-008:PAGE C-91
000377
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 8): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25
RAT if
DOSAGE GROUP :II
0.1 MG/KG/DAY
8861 NP 8862 P 8863 P 8864 P 8865 p 8866 p 8867 P 8868 p 8869 p 8870 p
28. 21 . 28. 29. 29. 21,
a 18.
22. 22 . 21. 23. 23 . 23 . 22. 22.
21.
23 . 28.
24 .
29.
26.
20 . 17.
22 . 24 . 30 . 26 . 19. 19. 22. 21.
24. 24 . 21. 24 . 23 . 26. 19. 22.
25. 20 . 24 . 24 . 24 . 24 . 23 . 21.
26. 21 . 23. 26. 25. 16. 19. 15.
21. 24 . 24 . 27. 27. 26 . 21. 18.
16 . 21. 26. 24 . 23 . 24 . 22. 12.
19.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value.
PROTOCOL 416-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 9) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2
2- 3
RAT #
DOSAGE GROUP III
3- 4 4- 5 5- 6 0.4 MG/KG/DAY
8871 NP 8872 P 8873 P 8874 P 8875 P 8876 P 8877 P 8878 NP 8879 NP 8880 P 8881 P 8882 P 8883 NP 8884 P 8885 P 8886 NP 8887 P 8888 P 8889 P 8890 P 8891 P 8892 P 8893 P 8894 P 8895 P
MATING NOT CONFIRMED
21. 26. 24 . 26 . 24 . 20.
16. 18. 22. 21. 23 . 21.
15. 22. 25. 24 . 17. 27.
13 . 20 . 17. 14. 15. 24 .
19. 21. 24 . 21. 22 . 28.
18. 18. 22. 15. 22. 18.
17. 19. 19. 12. 22 . 21.
19. 18. 17.
9. 18. IS.
18. 23. 23. 20. 26. 20.
15. 17. 20. 21. 22 . 21.
19. 20. 15. 18. 17. 20.
17. 17. 24 . 20. 25. 24.
19. 26. 20. 24. 24 . 22.
21. 30. 27. 25. 25. 30.
19. 21. 21. 19. 22 . 21 .
21. 20. 22. 15. 20. 22.
18. 24. 26. 22. 26. 21.
15. 21. 24 . 20. 16. 20.
19. 23. 21. 16. 24 . 22.
15. 20. 22. 18. 23. 23 .
15. 16. 14 . 20. 24 . 25.
19. 23. 20. 19. 22. 21.
22. 24 . 25. 21. 23. 23.
12. 20. 19. 17. 21 . 20.
P PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6- 7
22. 21. 23 . 21. 23. 18. 18. 13. 18. 20. 21. 20. 22. 33 . 18. 17. 23. 20. 16. 23. 23 . 17. 20. 16.
7- 8
20. 20. 24 . 16. 24 . 18. 24 . 10 . 24. 19. 20. 23. 23 . 24. 21. 25. 24 . 14 . 23. 24 . 24 . 19. 25. 20.
8- 9
18. 25. 22. 22 . 26. 21 . 21. 15. 22. 21. 22. 13. 24 . 28. 26. 21. 24 . 13 . 20. 22. 34 . 20. 22. 22.
9 - 10 10 - 11 11 - 12 12 - 13
19. 18. 24. 22.
23.
27. 23. 27. 25.
23 . 18.
23 . 22.
28. 24. 30. 26.
19.
21.
15.
19.
21. 20. 20. 22. 20. 12. 23. 26. 24 .
26.
36. 22. 30. 28. 22.
19.
22.
18 . 15. 17. 17. 23. 18. 24. 23. 27. 23. 24 . 19. 21. 28. 29. 25. 23. 22. 25. 22. 19. 25. 22. 24. 22. 21 . 23 . 23 .
418-008:PAGE C-93
000379
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 10): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2
2- 3 3- 4 4- 5 5- 6
RAT #
DOSAGE GROUP III
0.4 MG/KG/DAY
8896 P 8897 P 8898 P 8899 P 8900 P 8901 P 8902 P 8903 NP 8904 NP 8905 P
12 . 14 . 19. 14 . 18. 19. 20. 12 . 18. 18.
22. 27 . 15. 23 . 24 . 25 . 22. 18. 23 . 21.
20 . 26 . 26 . 23. 29. 23 . 24 . 27. 27. 23 .
14 . 19. 21. 19. 24 . 13 . 19. 22. 17. 20.
24 . 26 . 19. 23 . 25 . 19. 24 . 22 . 21. 21.
20. 23 . 20. 26. 26. 25. 23 . 24 . 24 . 22.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6- 7
27. 27. 23 . 26 . 28 . 20. 21 . 21. 18. 19.
7- 8
20. 24 . 25. 20. 25. 15. 21. 22 . 23 . 20.
8- 9
23. 26. 18. 26. 29. 25. 26 . 21. 17. 18.
9 - 10 10 - 11 11 - 12 12 - 13
26. 22. 22. h i . 24. 25. 29. 24 . 20. 25 . 24 . 23. 30. 19. 26. 25. 31. 27. 22. 23. 18. 28. 26. 26. 28. 19. 25. 27. 26. 21 . 22. 22. 27. 18 . 23 . 22. 23. 17. 21. 21.
418-008:PAGE C-94
000380
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 11) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25
RAT #
DOSAGE GROUP III
0.4 MG/KG/DAY
8871 NP 8872 P 8873 P 8874 P 8875 P 8876 P 8877 P 8878 NP 8879 NP 8880 P 8881 P 8882 P 8883 NP 8884 P 8885 P 8886 NP 8887 P 8888 P 8889 P 8890 P 8891 P 8892 P 8893 P 8894 P 8895 P
MATING NOT CONFIRMED 24.. 23 . 22. 25. 26. 26 . 23 . 20.
24 . 26 . 26 . 24 . 24 . 23. 21. 14 . 21. 18 . 23 . 19. 21. 24 . 21 . 19. 23 . 26 . 24 . 28. 20. 26. 23 . 24 . 19.
16. 22. 22 . 21. 18. 22. 18. 18. 20. 22. 22. 25. 28. 28. 23 . 15.
23 . 26. 27. 28. 22. 25. 27. 24 .
6.
17.
18.
23 .
22.
20. 23. 24 . 21.
21. 24 . 26. 27.
28. 30. 28. 21.
24 . 23 . 27.
26.
29. 24 . 23 . 26.
19. 23 . 23 . 25.
24 . 20 . 21.
22.
22. 22. 20 . 19.
20. 18. 18.
21. 29. 20 . 15.
24. 29. 21 . 16.
2 6 . 29. 25 . 20.
22. 25. 23 . 19.
48.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
418-008PAGE C-95
000381
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 12): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25
RAT #
DOSAGE GROUP :III
0.4 MG/KG/DAY
8896 P 0897 P 8898 P 8899 P 8900 P 8901 P 8902 P 8903 NP 8904 NP 8905 P
20 . 17. 24 . 26 . 18. 21. 22. 22.
23 . 29. 27. 23 . 26. 23 . 27. 27.
22 . 20. 23 . 22. 24 . 18. 16. 16 .
23- 24 . 23. 21. 33. 24 . 21. 13 .
27 . 25. 31 . 32 . 25. 22. 25. 20.
21. 22. 26 . 30. 22. 25. 19. 17.
18. 20. 22. 20 . 27. 27. 20 .
9.
19.
23 . 15.
19.
18 .
16.
li.
12 . 16.
14.
9. 14.
18 . 20 . 22. 17. 21. 22. 20. 13 . 16. 21. 15. 29.
22. 21 . 27. 27. 24 . 2B . 21. 15.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008: COMBINED ORAL (GAVAGEl FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 13): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2 2 - 3 3 - 4 4 - 5 5 - 6
RAT ft
DOSAGE GROUP IV
1.6 MG/KG/DAY
8906 P 8907 NP 8908 P 8909 P 8910 P 8911 P 8912 P 8913 P 8914 NP 8915 P 8916 P 8917 P 8918 NP 8919 P 8920 P 8921 P 8922 P 8923 NP 8924 P 8925 P 8926 P 8927 P 8928 P 8929 P 8930 P
NO CONFIRMED MATING DATE
21. 18. 11 .
22. 16. 19.
17. 23. 20.
20. 20. 19.
18. 24. 21.
20. 16. 20.
19. 22. 21.
IB. 15. 24 .
23. 22. 25.
15. 24 . 19.
20. 22. 19.
20. 29. 21.
23 . 16.
26.
16. 20. 19.
10. 23. 18.
16. 14. 18.
16. 18. 16.
13. 18. 21.
17. 22. 21.
18. 16. 22 .
19. 26. 22.
18. 15. 27.
22. 17. 26 .
NO CONFIRMED MATING DATE
9. 17. 19. 15 . 19. 17 . 20. 18 . 20 . 21 . 22. 24 . 26. 18. 21. 13 . 21. 14 . 19. 20 . 18. 21 . 23 .
22. 20 . 18. 20. 24 . 21. 22. 15. 26 . 22. 25. 29. 26. 19. 45. 16. 13 . 23 . 29. 16. 25. 16. 27 .
20 . 20 . 17. 21. 24. 21. 19. IS. 32. 22. 21. 20. 32 . 20. 26 . 21. 22. 21. 25. 20. 20 . 19. 23.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6- 7
12 . 17. 25. 15. 19. 20. 22 . 16. 21. 17. 19. 21. 26 . 22 . 22 . 15. 11. 13 . 24 . 14. 18. 14 . 17 .
7- 8
14 . 19. 17. 19. 24. 19. 21 . 16. 28. 25. 23. 22. 32. 16 . 19. 18. 21. 23. 24 . 22. 24 . 25. 31.
8- 9
13. 13 . 24. 14. 21. 19. 22 . 19. 19. 19. 20. 23 . 25. 22 . 28. 15. 17.
9. 20. 15. 15. 20. 20.
9 - 10 10 - 11 11 - 12 12 - 13
17. 18. 27. 19. 21. 20. 23 . 19. 24 . 20. 22. 23 . 32. 21 . 21. 16. 19. 20. 21. 18 . 22. 18. 24 .
21.
18. 18.
28. 36. 23 . 22.
20 .
25. 20. 22 . 24 . 29.
25 .
20. 20.
24 . 30 . 22. 27.
18.
22. 18. 27. 20. 22.
25.
23. 16.
24 . 30. 23 . 18.
18.
28. 21. 27. 23. 25.
418-008:PAGE C-97
esjoj
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.91
TABLE C27 (PAGE 14) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - I 1 - 2 2 - 3 3 - 4 4 - 5 5 6
RAT ft
DOSAGE GROUP IV
1.6 MG/KG/DAY
8931 P 8932 P 8933 NP 8934 P 8935 P 8936 P 8937 P 8938 8939 P 8940 P
15. 19. 21. 21. 19.
21. 20. 19. 17. 20.
21 . 27.
20 .
29.
26 ,
21. 18. 19. 21. 20.
20. 16 . 22 . 22. 18.
19. 17. 17. 19. 18.
20. 21. 21. 23 . 24 .
MORIBUND SACRIFICED ON DAY 36 OF STUDY
NO CONFIRMED MATING DATE
24 . 24 . 19. 27. 25.
21. 20. 24 . 19. 25. 20. 23 .
26.
P - PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6- 7
22. 18. 28. 25. 17. 20. 18 .
30 .
7-8
21. 21. 49. 16 . 29. 22. 22 .
20.
8 - 9 9 - 10 10 - 11 11 - 12 12 - 13
24 . 15 . 46 . 27. 13 . 18. 14 .
28.
21. 19. 24 . 19. 24 . 23 . 22 .
20.
22. 18. 23. 22. 27. 22. 18.
27.
24 . 21 . 21. 25. 21. 23. 28 .
30.
24 . 22. 13 . 16 . 29. 25. 26.
25.
418-008:PAGE C-98
000384
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 15) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
8906 P 8907 NP 8908 P 8909 P 8910 P 8911 P 8912 P 8913 P 8914 NP 8915 P 8916 P 8917 P 8918 NP 8919 P 8920 P 8921 P 8922 P 8923 NP 8924 p 8925 p 8926 p 8927 p 8928 p 8929 P 8930 p
NO CONFIRMED MATING DATE
21.
22.
22 . 27 . 20.
25.
21 .
20.
19.
26.
25.
26 .
20.
21.
26.
IB.
8. 13 . 13 . 16. 12. 7. 7. 12. 11. 11 . 12 . 15.
7. 10. 13. 32. 29. 31. 21. 23. 26. 15 24 . 18.
15. 15. 13 .
23 22. 24 . 20 17. 22. 23 26 . 30. 26 20. 25. 28 23 . 30. NO CONFIRMED MATING DATE
12 . 34 . 27. 32.
16 .
24 . 23 . 29. 25. 27.
6. 36. 19. 28.
15.
28. 27. 31. 30. 32 .
16. 21. 25. 34.
2.
28. 16. 30. 16. 16.
20 . 27. 22. 15.
2.
28. 19. 30. 23. 22 .
14 .
24. 27.
7.
20.
18. 23. 24 .
9. 13 . 18. 9. 10 . 15.
17. 12 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
418-008:PAGE C-99
000385
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 16) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 IB - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
8931 P 8932 P 8933 NP 8934 p 8935 P 8936 P 8937 p 8938 8939 p 8940 p
22. 21. 26 . 29. 24 . 24. 23. 22. 23 . 22. 25. 24 . 25 . 24 . 24 . 16. 19. 23 . 23 . a 21. 22. ii. b 40. 17. 12. 20. 24 . 22. 29. 26. 31. 20. 30. 22 . 25. 30. 30. 19. 25. 23 . 21. 26. 26. 25. 19. 22. 15. 22 . 26. 23. 25. 27 . 28. 28. 23. MORIBUND SACRIFICED ON DAY 36 OF' STUDY
NO CONFIRMED MATING DATE 19. 31. 28. 30. 35. 35. 16. 23 .
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value. b. Value was not recorded.
j
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 17): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2 2
3
RAT It
DOSAGE GROUP V
8941 P 8942 P 8943 P 8944 P 8945 NP 8946 p 8947 P 8948 p 8949 p 8950 P 8951 p 8952 NP 8953 p 8954 p 8955 P 8956 P 8957 NP 8958 p 8959 p 8960 p 8961 p 8962 p 8963 NP 8964 P 8965 P
14 . 12.
15 .
10. 15. 18 .
12. 13. 11 .
13. 15. 15 .
18. 16 . 15 .
17. 18.
9.
18. 17. 18.
13. 11.
8.
16. 12. 20.
17 .
21.
18.
17. 14 . 21.
15. 16. 11.
18 . 18.
18.
16. 22. 19.
18. 18. 13 .
13 . 12.
19.
13. 18. 16.
19. 19. 16 .
14. 13. 15.
16. 19. 18 .
12. 18. 17.
28 . 17.
18.
19. 17. 19.
18. 15. 13 .
13. 12. 17.
3- 4 4- 5 S- 6
3.2 MG/KG/DAY
9. 18. 12. 15. 16. 23. 18 . 11. 16. 19. 13. 16. 11. 13. 18. 17. 15. 16. 15. 20. 14 . 21. 15. 16 . 11.
15. 15. 15. 27. 13 . 15. 16. 17. 17. 21. 19. 18. 21. 22. 20. 15. 15. 16. 15. 17. 20. 19. 23 . 14 . 19.
13 . 20.
9. 15. 14 . 17. 16 . 24 . 18. 16 . 18. 14 . 19. 19. 15. 20 . 11 . 25. 22. 21. 10. 14 . 19. 15 . 19.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6- 7
15. 20. 17. 15. 14. 24. 19. 24. 12. 27. 16. 10. IS. 19. 17. 13. 19. 10. 16. 19. 22. 21. 19. 18. 19.
7- 8
14 . 22. 14. 12. 11. 18. 19. 24 . 20. 19. 20. 17 . 20. 17. 18 . 21. 13. 17. 11. 22 . 10. 12. 19. 16. 24 .
8- 9
10. 8.
14 . 14. 17 . 19. 18. 26. 12. 22 . 12. 17 . 14 . 16 . 17. 13 . 22. 17. 12. 21. 20. 20 . 15. 17. 13 .
9 - 10 10 - 11 11 - 12 12 - 13
17.
21. 18. 22. 20.
20. 14. 18. 20.
19. 16. 15. 15. 17 . 15. 15. 17. 18. 20 .
17. 13. 23.
18.
18 . 20. 25. 24. 15.
15. 21. 25 . 23.
16. 9. 20. 17. 18.
14 .
21. 16. 20. 20.
23 . 16. 19. 18.
18. 18. 18.
8.
17.
18. 17. 16. 20. 23. 21. 22. 20. 22. 27. 23. 24 . 16. 14 . 16 . 17. 17.
19. 21. 19. 18.
21.
418-008:PAGE C-101
8C030
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295,9)
TABLE C2 7 (PAGE 18) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 1 1 - 2 2 - 3 3 - 4 4 - 5 5 - 6
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
8966 P 8967 P 8968 P 8969 P 8970 P 8971 P 8972 NP 8973 P 8974 P 8975 P
16. 15 . 18. 18. 19. 20. 16. 20. 11. 16. 18. 17.
7. 16 . 15. 11. 20. 12 . 14 . 18. 13. 20. 19. 16. 23 . 17. 25. 20. 25. 26. 21. 21. 22. 19. 22 . 23 .
8. 17. 18. 10. 22 . 16. 16. 15. 17. 16. 19. 18 . 16. 16. 27. 18. 19. 15. 16. 18. 17. 17. 17. 17.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
6- 7
17. 17. 20. 19. 18. 25. 15. 19. 17. 22 .
7-8
20 . 16. 16 . 17. 25. 22. 17. 13 . 16 . 16.
8 - 9 9 - 10 10 - 11 11 - 12 12 - 13
20. 16 .
18. 19. 19.
20. 17. 19.
25. 14. 18.
16. 10.
8.
24 . 29.
21.
13. 19. 15.
19. 15. 23.
15. 15. 17.
18. 20. 18.
t
24. 26. 18. 15. 21. 18. 12. 31. 18. 25. 14. 18. 20. 25. 18. 15. 18. 19.
418-008PAGE C-102
OC0388
PROTOCOL 418-008 : COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C27 (PAGE 19) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25
RAT )t
DOSAGE GROUP V
3.2 MG/KG/DAY
8941 P 8942 P 8943 P 8944 P 8945 NP 8946 P 8947 P 8948 P 8949 P 8950 P 8951 P 8952 NP 8953 P 8954 P 8955 P 8956 P 8957 NP 8958 P 8959 P 8960 P 8961 P 8962 P 8963 NP 8964 P 8965 P
22 . 24 . 23.
24 . 29.
21.
21 .
22.
15. 19. 19. 22 . 15. 20. 20 . 17.
18. 19. 21. 23 . 20. 22. 21 . 16.
13 . 12 . 12. 17. 14 . 10.
4 . 11. 12. 10 . 10. 14 .
21. 22. 24 . 26 . 26 . 24. 22 . 21.
20 . 18. 21. 24. , 25. 18 . 27 .
22 . 19. 23. 29.
a 21. 23 . 17.
14 . 17. 12. 14 . il. 14 .
9 . 12. 15. 11. 13 . 10.
16. 17. 21. 21 . 23. 23. 16 . 19.
21. 18. 23. 26. 25. 13 . 17.
8. 15. 16. 16.
4 . 9. 13 . 13. 25. 23. 14 . 12.
20. 19. 12. 17 . 21. 15. 21. 19.
19.
24 . 28.
19.
25.
24 .
22.
26.
18. 19. 24 . 26. 20. 20. 22.
13.
15.
19.
20 .
27.
26.
17.
18.
15 . 20. 25. 26. 28. 17. 21.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Wet feed precluded the calculation of this value.
418-008:PAGE C-103
000389
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: G295.9)
TABLE C27 (PAGE 20) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 - 24 24 - 25
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
8966 P 8967 P 8968 P 8969 P 8970 P 8971 P 8972 NP 8973 P 8974 P 8975 P
21. 16. 26 . 23 . 28. 29. 20.
15. 17. 21. 25. 15. 17. 22.
16. 20. 20 . 25. 25. 27. 12. 12 .
24 . 24 . 26 . 28. 28. 22 . 23.
21. 22. 24 . 26 . 28. 27. 27. 14 .
12 . 14 . 11.
11 . 14 . 12 . 15.
0. 12. 15. 10. 11.
19. 21. 25. 25. 24 . 23 . 18 . 20.
14. 16. 20 . 19. 28. 19. 24. 21.
21.
19.
25.
29.
20.
23 .
22.
19.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C28 (PAGE 1) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1 - 4 4 - 7 7 - 1 0 10 - 14a
RAT #
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8821 8823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
52. 106.
88 . 123.
141.
163.
52 . 78.
54 . 159.
56. 91.
92. 127.
c 127.
81. 98.
87. 117.
NOT PREGNANT
NOT PREGNANT
76. 121.
89. 106.
75. 110.
81. 98.
59. 115.
62. 61.
S9. 116.
79 . 107.
54 . 114 .
81. 110.
86. 98.
72. 104 .
102.
140.
125. 142 . 167. 137. 165 . 117. 156 . 155. 132. 155.
146. 130. 135. 116.
b 113 . 145. 131. 149 . 146. 155. 136. 161.
212 . 268. 270.
b 252. 209 . 223 . 255. 229. 218.
234. 206 . 220. 238. 211. 205. 225. 209. 245. 198. 227. 216. 241 .
DAYS = DAYS OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 14 of lactation. b. Spilled feed precluded the calculation of this value. c. Wet feed precluded the calculation of this value.
418-008:PAGE C-105
T6E000
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C28 (PAGE 2) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1 - 4 4 - 7 7 - 10 10 - 14a
RAT if
DOSAGE GROUP II
0.1 MG/KG/DAY
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865 8866 8867 8868 8869 8870
84 . 55. 64 . 72. 62. 82. 64. 51 . 86. 69. 82.
b 98. 63. 74 . 56. 96. 87. 60. 68. 68. 81. 61. 68. 80.
98 . 127. in.
87. 95. 159. 94 . 99. 104 . 120 . 119. 143 . 121. 99. 116. 104 . 130. 118. 103 . 117 . 117. 123. 105. 100. 110.
139. 123. 147. 122. 130. 153. 117. 129. 140 . 146. 132 . 165. 128. 142. 134. 113 . 143. 144 . 140. 135. 109. 116. 142. 132. 142 .
226 . 225. 230 . 210 . 220. 257 . 152. 221 . 244 . 228 . 229 . 262 . 219. 246 . 233 . 244 . 255. 188. 219. 205. 215. 255. 236 . 220. 228.
DAYS = DAYS OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 14 of lactation. b. Spilled feed precluded the calculation of this value.
418-008:PAGE C-106
000392
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C28 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1 - 4 4 7 7 - 10 10 - 14a
RAT H
DOSAGE GROUP III
0.4 MG/KG/DAY
8871 8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899 8900 8901 8902 8903 8904 8905
NOT PREGNANT
80 . 133 .
79. 107.
80. 113 .
67. 100 .
S3 . 96 .
66. 95.
61. 114 .
65 . 101 .
49. 68.
74 . 111.
63. 99.
47 . 115.
52. 72.
71 . 100.
64. 123 .
b 166.
46. 84 .
91 . 169.
62. 126.
63 .
c
59. 84 .
NOT PREGNANT
NOT PREGNANT
95. b
154 . 136 . 126. 125. 125. 164. 120. 127. 123. 136. 133. 146. 102. 138. 156. 161. 120. 135. 145. 127. 143 .
151.
247. 163 . 213 . 183 . 214 . 249. 196. 196. 215. 218. 209. 204. 124 . 206. 269. 266 . 148 . 249. 235. 229. 231.
249.
DAYS = DAYS OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 14 of lactation. b. Spilled feed precluded the calculation of this value. c. Value was not recorded.
418-008.PAGE C-107
000393
418-008:PAGE C-108
000394
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C28 (PAGE 4): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1 - 4 4 - 7 7 - 1 0 10 - 14a
RAT n
DOSAGE GROUP IV
1.6 MG/KG/DAY
8906 8909 8913 8914 8918 8919 8920 6921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
44 .
85.
110 .
202.
71. 98. 121. 200.
57.
104 .
109.
195.
NOT PREGNANT
NOT PREGNANT
54 . 122 . 114 . 204 .
42. 74 . 83 . 150.
50. 109. 131. 209.
NOT PREGNANT
46. 86. 129. 198.
32. 58. 67. 122.
41. 66 . 74 . 117.
65. 95. 120. 203.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
55.
102.
120 .
229.
44 . 66.
83 . 148.
50. 72. 119. 184 .
NOT PREGNANT
36. 68. 111. 190 .
55.
94 . 118.
199.
39. NO SURVIVING PUPS ON DAY 4 OF LACTATION
39. 102. 141. 218.
MORIBUND SACRIFICED ON DAY 36 OF STUDY
43 . 53.
82. 147.
77.
107.
144 .
258.
DAYS = DAYS OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 14 of lactation. b. Spilled feed precluded the calculation of this value.
`
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C28 (PAGE 5) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DAYS 1 - 4 4 - 7 7 - 10 10 - 14a
RAT
DOSAGE GROUP V
3.2 MG/KG/DAY
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NOT PREGNANT NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NOT PREGNANT NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NOT PREGNANT NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY I OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY i OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NOT PREGNANT NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION
DAYS = DAYS OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 14 of lactation.
418-008.PAGE C-109
000395
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C29 (PAGE 1) : ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
RAT #
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801
72
8802
61
8803 8804
-2 -3
8805
6a 7
8806
-i
8807
72
8808
-2
8809
71
8810
71
8811
-4
8812
- 14b
8813
-3
8814
73
8815
-1
8816
-1
8817
5C 7
8818
-3
a. Six or more consecutive days of diestrus observed. b. No confirmed mating date. c. Six or more consecutive days of estrus observed.
RAT ft
8819 8820 B821 8822 8823 8824 8825 8826 8827 8828 8829 8830 8831 8832 8833 8834 8835
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
-3 -1 -2 61 -4 6a 4 8i -4 -7 72 71 -3 -4 6a 3 -1 64 -4
418-008PAGE C-110
000396
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C29 (PAGE 2) : ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA Fo GENERATION FEMALE RATS
RAT It
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
DOSAGE GROUP II
0.1 MG/KG/DAY
8836
-1
8837
-1
8838
-3
8839
71
8840
63 3
8841
-5
8842
-2
8843
71
8844
-1
8845
-3
8846
73
8847
-3
8848
51
8849
74
8850
- 1
8851
74
8852
74
8853
6a 3
a . Six or more consecutive days of diestrus observed.
RAT ft
8854 8855 8856 8857 8858 8859 8860 8861 8862 8863 8864 8865 8866 8867 8868 8869 8870
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
-4 -4 71 -4 -4 -1 -4 -1 63 6a 3 a1 -4 -2 -3 5a 3 -4 71
418-008:PAGE C-111
000397
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C29 (PAGE 3) : ESTROUS CYCLING AND DAYS IN COHABITATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
RAT
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
DOSAGE GROUP III
0.4 MG/KG/DAY
8871
- 14a
8872
-1
8873
-1
8874
-3
8875
-4
8876
-4
8877
61
8878
-1
8879
-1
88B0
-1
8881
64
8882
-4
8883
-1
8884
3c i
8885
74
8886
3b 1
8887
-1
8888
-1
a . Mat ing not confirmed, b. Six or more consecutive days of diestrus observed, c. Six or more consecutive days of estrus observed.
RAT I)
8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899 8900 8901 8902 8903 8904 8905
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
7 6b 5 6b 5b 5 6b 6 7 7
14 1 4 5 1 1 1 4 4 3 4 4 4 i 1 i 1
418-008:PAGE C-112
000398
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C29 (PAGE 4) : ESTROUS CYCLING AND DAYS IN COHABITATION INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
RAT ft
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
DOSAGE GROUP IV
1.6 MG/KG/DAY
8906
6a 14b
8902
-1
8906
71
8909
54
8910
-i
8911
7i
8912
-i
8913
-4
8914
63
8915
61
8916
-1
8917
71
8918
-4
8919
-3
8920
-4
8921
-2
8922
71
8923
-3
a. Six or more consecutive days of diestrus observed. b. No confirmed mating date.
RAT ft
8924 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
-1 61 -3 61 63 63 - 14b -4 -1 4a 2 62 '3 -3 -1 MORIBUND SACRIFICED ON DAY 36 OF STUDY 7 14b -2
418-008:PAGE C-113
66 0J0
418-008:PAGE C-114
000400
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C29 (PAGE S) : ESTROUS CYCLING AND DAYS IN COHABITATION INDIVIDUAL DATA Fo GENERATION FEMALE RATS
RAT # DOSAGE GROUP V
8941 8942 8943 8944 8945 8946 8947 8948 8949 8950 8951 8952 8953 8954 8955 8956 8957 8958
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
3.2 MG/KG/DAY
-1
6 13
-4
74
-2
7 12
81
61
63
-4
61
-2
71
-1
-2
-3
-4
7i
RAT #
8959 8960 8961 8962 8963 8964 8965 8966 8967 8968 8969 8970 8971 8972 8973 8974 8975
PRECOHABITATION ESTROUS STAGES/
28 DAYS
DAYS IN COHABITATION
- 13 -5 74 -2 61 -3 a1 -1 62 74 -2 73 -1 -1 -2 -3 -4
i
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C30 (PAGE 1): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
LIVER WEIGHT (G)
I 0 (VEHICLE)
8801 8802 8803 8804 8805 8806 8807 8808 8809 8810 8811 8812 8813 8814 8815 8816 8817 8818 8819 8820 8821 8822 8823 8824 8825 8826 8827 8828 8829 8830 8831 8832 8833 8834 8835
DL 21 DG 10 DL 21 DL 21 DL 21 DG 10 DL 21 DL 21 DG 10 DG 10 DL 21 DL 21 DL 21 DL 21 DG 10 DG 10 DG 25 DG 25 DL 21 DG 10 DL 21 DG 10 DL 21 DL 21 DG 10 DL 21 DL 21 DL 21 DG 10 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21
P P P P P P P P P P P P P P P P NP NP P P P P P P P P P P P P P P P P P
84 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 90 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 88 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 73 ALL TISSUES APPEARED NORMAL. 69 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 90 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL.
12.59 14.29 14.20
15.65
15.77
DS * DAY OF STUDY DG DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at necropsy.
418-008:PAGE C-115
000401
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C30 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
LIVER WEIGHT (G)
8836 8837 8838 8839 8840 8841 8842 8843 8844 8845 8846 8847 8848 8849 8850 8851 8852 8853 8854 8855 8856 8857 8858 8859 BB60 8861 8862 8863 8864 8865 8866 8867 8868 8869 8870
DG 10 DG 10 DL 21 DG 10 DL 21 DL 21 DL 21 DG 10 DG 10 DL 21 DL 21 DL 21 DG 10 DL 21 DG 10 DL 21 DL 21 DL 21 DL 21 DL 21 DG 10 DL 21 DL 21 DG 10 DL 21 DG 10 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21
P P P P P P P P P P P P P P NP P P P P P NP P P P P NP P P P P P P P P P
52 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL.
85 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL.
DS = DAY OF STUDY DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at necropsy.
14.06 15.15 13.72
15.01 15.18
418-008:PAGE C-116
000402
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C30 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
LIVER WEIGHT (G)
III
0.4
8871
DS 81
NP
80 ALL TISSUES APPEARED NORMAL.
8872
DL 21
P
85 ALL TISSUES APPEARED NORMAL.
8873
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8874
DL 21
P
86 ALL TISSUES APPEARED NORMAL.
8875
DL 21
P
86 ALL TISSUES APPEARED NORMAL.
8876
DL 21
P
87 ALL TISSUES APPEARED NORMAL.
8877
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8878
DG 10
NP
52 ALL TISSUES APPEARED NORMAL.
8879
DG 10
NP
52 ALL TISSUES APPEARED NORMAL.
8880
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8881
DL 21
P
87 ALL TISSUES APPEARED NORMAL.
8882
DL 21
P
87 ALL TISSUES APPEARED NORMAL.
8883
DG 10
NP
52 ALL TISSUES APPEARED NORMAL.
8884
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8885
DL 21
P
86 ALL TISSUES APPEARED NORMAL.
8886
DG 10
NP
52 ALL TISSUES APPEARED NORMAL.
8887
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8888
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8889
DL 21
P
95 ALL TISSUES APPEARED NORMAL.
8890
DL 21
P
84 ALL TISSUES APPEARED NORMAL.
8891
DL 21
P
86 ALL TISSUES APPEARED NORMAL.
8892
DL 21
P
87 ALL TISSUES APPEARED NORMAL.
8893
DL 21
P
84 ALL TISSUES APPEARED NORMAL.
8894
DL 21
P
85 ALL TISSUES APPEARED NORMAL.
8895
DL 21
P
84 ALL TISSUES APPEARED NORMAL.
8896
DL 21
P
86 ALL TISSUES APPEARED NORMAL.
8897
DL 21
P
86 ALL TISSUES APPEARED NORMAL.
8898
DL 21
P
85 ALL TISSUES APPEARED NORMAL.
18.44
15.46 16.06
8899
DL 21
P
86 KIDNEYS: RIGHT, PELVIS, MODERATE DILATION. ALL OTHER TISSUES APPEARED NORMAL.
8900 8901 8902 8903 8904 8905
DL 21 DL 21 DL 21 DG 25 DG 25 DL 21
P P P NP NP P
86 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL. 67 ALL TISSUES APPEARED NORMAL. 67 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL.
17.53 16.54
DS = DAY OF STUDY DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at necropsy.
418-008:PAGE C-117
000403
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C30 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
LIVER WEIGHT (G)
IV
1.6
8906
DL 21
P
86 ALL TISSUES APPEARED NORMAL.
8907
DG 10
NP
52 ALL TISSUES APPEARED NORMAL.
8908
DL 21
P
87 ALL TISSUES APPEARED NORMAL.
8909
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8910
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8911
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8912
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8913
DL 21
P
86 ALL TISSUES APPEARED NORMAL.
8914
DG 25
NP
69 ALL TISSUES APPEARED NORMAL.
8915
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8916
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8917
DG 10
P
52 ALL TISSUES APPEARED NORMAL.
8918
DG 25
NP
70 ALL TISSUES APPEARED NORMAL.
8919
DL 21
P
84
SPLEEN: ADHERED TO ABDOMINAL ADIPOSE TISSUE
17.51
ALL OTHER TISSUES APPEARED NORMAL.
8920 8921 8922 8923 8924 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937
DL 21 DL 21 DG 10 DG 25 DG 10 DL 21 DL 21 DL 21 DL 21 DL 2 DL 21 DL 21 DL 21 DG 25 DL 21 DL 21 DL 4 DL 21
P P P NP P P P P P P P P P NP P P P P
87 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 69 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 83 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL. 82 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 67 ALL TISSUES APPEARED NORMAL. 86 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 82 ALL TISSUES APPEARED NORMAL. 68 ALL TISSUES APPEARED NORMAL. 83 ALL TISSUES APPEARED NORMAL. 85 ALL TISSUES APPEARED NORMAL. 69 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL.
17.39 13.75
16.24 17.31
DS = DAY OF STUDY DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at necropsy.
418-008:PAGE C-118
000404
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C30 (PAGE 5) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
IV (Cont.) 1.6
8938
DS 36
P
35 MORIBUND SACRIFICED ON DAY 36 OF STUDY. ALL TISSUES APPEARED NORMAL.
8939 8940
DL 21 DL 21
P P
87 ALL TISSUES APPEARED NORMAL. 84 ALL TISSUES APPEARED NORMAL.
DS - DAY OF STUDY DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the Individual clinical observations table (Table C22) for external observations confirmed at necropsy.
418-008:PAGE C-119
000405
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C30 (PAGE 6) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
8941 8942 8943 8944 8945 8946 8947 8948 8949 8950 8951 8952 8953 8954 8955 8956 8957 8958 8959 8960 8961 8962 8963 8964 8965 8966 8967 8968 8969 8970 8971 8972 8973 8974 8975
DG 10 DL 1 DL 1 DL 1 DG 25 DL 2 DG 10 DG 10 DL 2 DL 1 DG 10 DG 25 DG 10 DG 10 DL 1 DL 1 DG 25 DG 10 DL 2 DL 1 DL 2 DL 1 DG 10 DL 2 DG 10 DG 10 DL 1 DL 2 DL 1 DL 2 DL 1 DG 25 DL 2 DL 1 DL 1
P P P P NP P P P P P P NP P P P P NP P P P P P NP P P P P P P P P NP P P P
52 ALL TISSUES APPEARED NORMAL. 76 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 68 ALL TISSUES APPEARED NORMAL. 74 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 67 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 64 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 70 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 76 ALL TISSUES APPEARED NORMAL. 68 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 65 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 52 ALL TISSUES APPEARED NORMAL. 63 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 65 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 63 ALL TISSUES APPEARED NORMAL. 67 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 66 ALL TISSUES APPEARED NORMAL. 67 ALL TISSUES APPEARED NORMAL.
DS = DAY OF STUDY DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at necropsy.
418-008:PAGE C-120
000406
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C31 (PAGE 1) : CAESAREAN-SECTIONING OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
VIABLE EMBRYOS NONVIABLE EMBRYOS IMPLANTATION SITES CORPORA LUTEA
RAT #
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
HORN TOTAL
HORN TOTAL
HORN TOTAL
OVARY TOTAL
8802 8806 8809 8810 8815 8816 8620 8822 8825 8829
8 9 17 0 0 0 8 9 17 8 10 18 5 11 16 0 0 0 5 11 16 ii 11 22 8 5 13 0 0 0 8 5 13 8 5 13 6 8 14 0 0 0 6 8 14 10 9 19 4 6 10 2 0 2 6 6 12 7 7' 14 9 4 13 0 0 0 9 4 13 9 5 14 5 9 14 0 0 0 5 9 14 6 9 15 3 1 4 0 0 0 3 1 4 5 6 11 10 3 13 0 0 0 10 3 13 12 8 20 12 1 19 0 0 0 12 7 19 13 7 20
418-008:PAGE C-121
000407
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C31 (PAGE 2) : CAESAREAN-SECTIONING OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
VIABLE: EMBRYOS NONVIABLE: EMBRYOS IMPLANTATION SITES CORPORA LUTEA
RAT H
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
HORN TOTAL
HORN TOTAL
HORN TOTAL
OVARY TOTAL
8836 8837 8839 8843 8844 8848 8850 8856 8859 8861
4480004484S 9 ii 6 17 0 0 0 11 6 17 ii 7 18
9 7 16 0 0 0 9 7 16 ii 9 20 6 9 15 0 0 0 6 9 15 9 9 18 6 8 14 0 0 0 6 8 14 11 8 19 5 7 12 0 0 0 5 7 12 6 10 16 NOT PREGNANT NOT PREGNANT 10 1000 10120 2 NOT PREGNANT
418-008:PAGE C-122
000408
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C31 (PAGE 3) : CAESAREAN-SECTIONING OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
VIABLE EMBRYOS NONVIABLE EMBRYOS IMPLANTATION SITES CORPORA LUTEA
RAT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
HORN TOTAL
HORN TOTAL
HORN TOTAL
OVARY TOTAL
8813 8811 8818 8879 8880 8883 8884 8886 8881 8888
8 1 15 0 0 0 a 7 15 9 7 16 4 9 13 0 0 0 4 9 13 4 9 13 NOT PREGNANT NOT PREGNANT 7 6 13 0 0 0 7 6 13 8 10 18 NOT PREGNANT 1 0 1 0 00 1 0 16 1 7 NOT PREGNANT 9 6 IS 0 0 0 9 6 15 10 8 18 12 4 16 0 0 0 12 4 16 12 5 17
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C31 (PAGE 4): CAESAREAN -SECTIONING OBSERVATIONS - INDIVIDUAL DATA Fo GENERATION FEMALE RATS
DOSAGE GROUP IV
1.6 MG/KG/DAY
VIABLE EMBRYOS NONVIABLE EMBRYOS IMPLANTATION SITES CORPORA LUTEA
RAT U
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
HORN TOTAL
HORN TOTAL
HORN TOTAL
OVARY TOTAL
8907 8908 8910 8911 8912 8915 8916 8917 8922 8924
NOT PREGNANT 4 9 13 0 0 0 4 9 13 4 11 15 10 3 13 0 0 0 10 3 13 13 6 19 9 8 17 0 0 0 9 8 17 10 9 19 9 6 15 0 0 0 9 6 15 9 6 15 10 8 18 1 0 i 11 8 19 ii 12 23 5 6 11 0 0 0 5 6 11 6 7 13 5 6 11 0 0 0 5 6 11 8 9 17 1 6 13 0 0 0 7 6 13 7 6 13 A 0 4 .0 0 0 4 0 4 5 2 7
418-008:PAGE C-124
000410
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C31 (PAGE 5) : CAESAREAN-SECTIONING OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
DOSAGE GROUP V
3.2 MG/KG/DAY
VIABLE EMBRYOS NONVIABLE EMBRYOS IMPLANTATION SITES CORPORA LUTEA
RAT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
HORN TOTAL
HORN TOTAL
HORN TOTAL
OVARY TOTAL
8941 8947 8948 8951 8953 8954 8958 8963 8965 8966
9 7 16 0 0 0 9 7 16 10 9 19
13 3 16 0 0 0 13 3 16 16 4 20
7 6 13 0 0 0 7 6 13 8 8 16
9 4 13 0 0 0 9 4 13 9 6 15
5 a 13 0 0 0 5 8 13 5 8 13
2l
3 0 0 0 2 1 3 6 4 10
6 8 14 0 0 0 6 8 14 8 10 18
NOT PREGNANT
7 8 15 0 0 0 7 8 15 8 8 16
9 6 15 0 0 0 9 6 15 10 9 19
418-008:PAGE C-125
Ti^OO
418-008:PAGE C-126
000412
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C32 (PAGE 1): LITTER OBSERVATIONS (CAESAREAN-DELIVERED EMBRYOS) - INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP I
NUMBER OF LIVE EMBRYOS
RAT ft
TOTAL
8802 8806 8809 8610 8815 8816 8820 8822 8825 8829
17 16 13 14 10 13 14
4 13 19
0 (VEHICLE) MG/KG/DAY
--- - CONCEPTUSES ----NONVIABLE
N N%
17 0 0.0 16 0 0.0 13 0 0.0 14 0 0.0 12 2 16.7 13 0 0.0 14 0 0.0
4 0 0.0 13 0 0.0 19 0 0.0
t
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C32 (PAGE 2): LITTER OBSERVATIONS (CAESAREAN-DELIVERED EMBRYOS) - INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP II
0..1 MG/KG/DAY
NUMBER OF LIVE EMBRYOS
-- CONCEPTUSES ----NONVIABLE
RAT H
TOTAL
N N%
8836 8837 8839 8843 8844 8848 8850 8856 8859 8861
8 17 16 15 14 12 NOT PREGNANT NOT PREGNANT
1 NOT PREGNANT
8 17 16 15 14 12
i
0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0
0 0.0
418-008:PAGE C-127
000413
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C32 (PAGE 3): LITTER OBSERVATIONS (CAESAREAN-DELIVERED EMBRYOS) - INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP III
0 .4 MG/KG/DAY
NUMBER OF LIVE EMBRYOS
-- CONCEPTUSES -.... NONVIABLE
RAT tt
TOTAL
N N%
8873 8877 8678 8879 8880 8883 8884 8886 8887 8888
15 13 NOT PREGNANT NOT PREGNANT 13 NOT PREGNANT
1 NOT PREGNANT IS 16
15 13
13 1
15 16
0 0.0 0 0.0
0 0.0 0 0.0
0 0.0 0 0.0
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C32 (PAGE 4): LITTER OBSERVATIONS (CAESAREAN-DELIVERED EMBRYOS) - INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP IV
NUMBER OF LIVE EMBRYOS
1 .6 MG/KG/DAY
-- CONCEPTUSES ----NONVIABLE
RAT #
TOTAL
N N%
o o
8907 8908 8910 8911 8912 8915 8916 8917 8922 8924
NOT PREGNANT 13 13 17 15 18 11 11 13
4
13 13 17 15 19 11 11 13
4
0 0 0 0.0 0 0.0 1 5.3 0 0.0 0 0.0 0 0.0 0 0.0
o o
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER 1NATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C32 (PAGE 5) : LITTER OBSERVATIONS (CAESAREAN-DELIVERED EMBRYOS) - INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP V
3.2 MG/KG/DAY
NUMBER OF LIVE EMBRYOS
--- CONCEPTUSES ----NONVIABLE
RAT #
TOTAL
N N%
8941 8947 8948 8951 8953 8954 8958 8963 8965 8966
16 16 13 13 13
3 14 NOT PREGNANT 15 15
16 16 13 13 13
3 14
15 15
0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0
0 0.0 0 0.0
418-008:PAGE C-130
000416
4.
PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: G295.9)
TABLE C33 (PAGE 1): EMBRYONAL VITAL STATUS INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
EMBRYO # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT H CLs 8802 8/10 A A A A A A A A / A A A A A A A A A
8806 li/ii A A A A A / A A A A A A A A A A A
8809 8/ 5 A A A A A A A A / A A A A A
8810 10/ 9 A A A A A A / A A A A A A A A
8815 7/ 7 A E E A A A / A A A A A A
8816 9/ 5 A A A A A A A A A / A A A A
8820 6/ 9 A A A A A / A A A A A A A A A
8822 5/ 6 A A A / A
8825 12/ 8 A A A A A A A A A A / A A A
8829 13/ 7 A A A A A A A A A A A A / A A A A A A A
A = VIABLE EMBRYO E = NONVIABLE EMBRYO "/ DENOTES POSITION OF CERVIX CLs = CORPORA LUTEA/OVARY
418-008.PAGE C-131
LTrOOO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C33 (PAGE 2) : EMBRYONAL VITAL STATUS - INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP II
0.1 MG/KG/DAY
EMBRYO It 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
RAT # CLs 8836 4/ 5 A A A A / A A A A
8837 11/ 7 A A A A A A A A A A A / A A A A A A
8839 11/ 9 A A A A A A A A A / A A A A A A A
8843 9/ 9 A A A A A A / A A A A A A A A A 8844 11/ 8 A A A A A A / A A A A A A A A
8848 6/10 A A A A A / A A A A A A A
8850
NOT PREGNANT
8856
NOT PREGNANT
8859 2/ 0 A /
8861
NOT PREGNANT
A = VIABLE EMBRYO E = NONVIABLE EMBRYO "/" DENOTES POSITION OF CERVIX CLs = CORPORA LUTEA/OVARY
418-008:PAGE C-132
sx^oao
PROTOCOL 410-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C33 (PAGE 3) : EMBRYONAL VITAL STATUS - INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP III
0.4 MG/KG/DAY
EMBRYO 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT n CLS 8073 9/ 7 A A A A A A A A / A A A A A A A
8877 4/ 9 A A A A / A A A A A A A A A
8878
NOT PREGNANT
8879
NOT PREGNANT
8880 8/10 A A A A A A A / A A A A A A
8883
NOT PREGNANT
8884 6/ 1 A /
8886
NOT PREGNANT
8887 10/ 8 A A A A A A A A A / A A A A A A
8888 12/ 5 A A A A A A A A A A A A / A A A A
A = VIABLE EMBRYO E = NONVIABLE EMBRYO "/" DENOTES POSITION OF CERVIX CLs = CORPORA LUTEA/OVARY
418-008.PAGE C-133
GVi/OOO
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C33 (PAGE 4): EMBRYONAL VITAL STATUS - INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP IV
1 .6 MG/KG/DAY
EMBRYO #
1234
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT CLs 8907
NOT PREGNANT
8908 4/11 A A A A / A A A A A A A A A
8910 13/ 6 A A A A A A A A A A / A A A
8911 10/ 9 A A A A A A A A A / A A A A A A A A
8912 9/ 6 A A A A A A A A A / A A A A A A
8915 11/12 E A A A A A A A A A A / A A A A A A A A
8916 6 / 7 A A A A A / A A A A A A
8917 8/ 9 A A A A A / A A A A A A
8922 7/ 6 A A A A A A A / A A A A A A
8924 5/ 2 A A A A /
A = VIABLE EMBRYO E = NONVIABLE EMBRYO "/" DENOTES POSITION OF CERVIX CLs = CORPORA LUTEA/OVARY
418-008PAGE C-134
0C0420
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C33 (PAGE 5): EMBRYONAL VITAL STATUS INDIVIDUAL DATA - FI GENERATION LITTERS
DOSAGE GROUP V
3.2 MG/KG/DAY
EMBRYO H 1 2 3 4 5 6 7 B 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT # CLS 8941 10/ 9 A A A A A A A A A / A A A A A A
8947 16/ 4 A A A A A A A A A A A A A / A A
8948 8/ 8 A A A A A A A / A A A A A A
8951 9/ 6 A A A A A A A A A / A A A A
8953 5/ 8 A A A A A / A A A A A A A A
8954 6/ 4 A A / A
8958 8/10 A A A A A A / A A A A A A A A
8963
NOT PREGNANT
8965 8/ 8 A A A A A A A / A A A A A A A A
8966 10/ 9 A A A A A A A A A / A A A A A A
A = VIABLE EMBRYO E = NONVIABLE EMBRYO "/" DENOTES POSITION OF CERVIX CLs = CORPORA LUTEA/OVARY
418-008:PAGE C-135
0C042
h*
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C34 (PAGE 1) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA Fo GENERATION FEMALE RATS/F1 GENERATION LITTERS
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT/ LITTER NUMBER
DURATION OF GESTATION (DAYS) N
LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN
NNN
1 MF
NUMBER OF LIVE PUPS AT
COMPLETION OF DAY POSTPARTUM
4a 4b 7
MF
MF
MF
14 MF
21 MF
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8821 6823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
23 23 23 23 23 23 23
C 22 23 NOT PREGNANT NOT PREGNANT 23 23 22 22 22 23 23 23 22 23 23 23 23
9 12 15 17(1) 13
9 12 17 12 13
1 1 0 0 0 1 0 0 0 0
12 14 12 15 13 14 12 16 15 17 15(1) 13 16
0 0 0 0 0 0 3 0 0 0 0 1 0
10 13 15 17 13 10 12 17 12 13
12 14 12 15 13 14 15 16 15 17 15 17(31 16
63 75 69 4 12 a5 36 66 4 13 39 76
63 7S 69 4 11 B5 36 66 4 13 39 76
53 44 44 44 44 35 44 44 35 44
53 44 44 44 44 35 44 44 35 44
53 44 44 44 44 35 44 44 35 44
53 44 44 44 44 35 44 44 35 44
39 77 75 96 58 59 2 10 11 5 10 5 6 11 86 67 12 4
39 76 75 96 58 59 2 10 11 5 10 5 6 11 86 67 12 4
35 35 44 44 44 44 26 44 44 44 44 44 71
35 35 44 44 44 44 26 44 44 44 44 44 7i
35 35 44 44 44 44 26 44 44 44 44 44 71
35 35 44 44 44 44 26 44 44 44 44 44 7i
M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM. [ 1 = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. a. Number of live pups preculling. b. Number of live pups postculling. c. No confirmed mating date.
TOTAL IMPLAN TATIONS
N
13 15 16 17 14 10 14 18 13 13
14 14 12 16 13 16 16 16 16 17 16 17 16
418-008:PAGE C-136
000422
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C34 (PAGE 2) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA Fo GENERATION FEMALE RATS/FI GENERATION LITTERS
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
RAT/ LITTER NUMBER
DURATION OF GESTATION (DAYS) N
8838 8840 8841 8842c 8845 8846 8847 8849 8851 88S2 8853 8854 8855 8857 8858 8860 8662 8863 8864 8865 8866 8867 8868 8869 8870
22 23 23 23 23 23 23 22 23 23 23 23 23 23 23 23 23 22 23 22 23 23 22 23 23
LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN
NNN
17 19(1) 14 15 13 (1) 15 14 17 15(1) 10 19 14 15 15 10 15 14 16 10 14 16 13 14 16 11
0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 1 0
17 19 14 15 13 15 14 17 15 12(2) 19 14 15 15 11 15 14 16 10 14 16 13 14 17 11
1 MF
10 7 12 6
95 5 10 39 87 95 10 7 59 73 13 6 86 5 10 96 28 78 77 12 4 55 10 4 97 58 86 11 5 56
NUMBER OF LIVE PUPS AT
COMPLETION OF DAY POSTPARTUM
4a 4b 7
MF
MF
MF
14 MF
10 7 12 6
95 5 10 38 87 95 10 6 59 73 13 6 86 5 10 96 28 78 77 12 4 55 10 4 97 58 76 11 5 56
44 44 44 44 35 44 44 44 44 53 44 44 44 44 26 44 44 44 44 44 44 44 44 44 44
44 44 44 44 35 44 44 44 44 53 44 44 44 44 26 44 44 44 44 44 44 44 44 44 44
44 44 44 44 35 44 44 44 44 53 44 44 44 44 26 44 44 44 44 44 44 44 44 44 44
21 MF
44 44 44 44 35 44 44 44 44 53 44 44 44 44 26 44 44 44 44 44 44 44 44 44 44
TOTAL IMPLANTATIONS
N
19 19 14 15 15 16 15 18 16 12 19 15 18 15 13 15 16 16 11 14 16 14 14 17 12
M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM. ( ] NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. a. Number of live pups preculling. b. Number of live pups postculling. c. Dam 8842 delivered one additional pup on day 2 of lactation; values for day 1 postpartum excluded from group averages and
statistical analyses.
418-008:PAGE C-137
000423
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C34 (PAGE 3): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA FO GENERATION FEMALE RATS/FI GENERATION LITTERS
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
RAT/ LITTER NUMBER
DURATION OF GESTATION (DAYS) N
8871 8872 8874c 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 B896d 8897d 8898 8899c 8900 8901 8902 8903 8904 8905
NOT PREGNANT 23 22 22 23 23 23 23 22 23 21 22 23 24 23 22 22 23 22 23 23 23 NOT PREGNANT NOT PREGNANT 22
LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN
NNN
13 15 13
7(1) 14 17 14 14 12 15 12 13
3 17 14 14 12 16 15 13 15
1 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 1 0 1 0 1
14 15 13
7 14 17 16 14 12 15 12 13
3 17 14 14 13 16 16 13 16
19 0 19
1 MF
NUMBER OF LIVE PUPS AT
COMPLETION OF DAY POSTPARTUM
4a 4b 7
MF
MF
MF
14 MF
21 MF
TOTAL IMPLAN TATIONS
N
85 11 4
94 33 59 89 95 95 57 69 66 85 21 98 86 59 84 88 69 58 78
85 11 4
94 33 59 89 95 95 57 69 66 85 21 97 86 59 84 88 68 58 77
44 44 44 33 44 44 53 44 44 44 44 44 2i 44 44 44 44 44 44 35 44
44 53 44 33 44 44 53 44 44 44 44 44 21 44 44 44 44 53 44 35 44
44 53 44 33 44 44 53 44 44 44 44 44 21 44 44 44 44 43 44 35 44
44 53 44 33 44 44 53 44 44 44 44 42 21 44 44 44 44 43 44 35 44
16 17 14
7 15 17 16 14 15 15 14 14
3 17 IS 15 14 18 17 15 16
8 ii
8 10
44
44
4 4. 4 4
19
M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM. a. Number of live pups preculling. b. Number of live pups postculling. c. A sexing error was found prior to weighing on day 7 postpartum,- values for day 4 postpartum postculling were
excluded from group averages and statistical analyses. d. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pups were
arbitrarily distributed between the two dams and values will be included in group averages and statistical analyses.
418-008PAGE C-138
000424
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C34 (PAGE 4) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA FO GENERATION FEMALE RATS/F1 GENERATION LITTERS
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
RAT/ LITTER NUMBER
DURATION OF GESTATION (DAYS) N
LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN
NNN
1 MF
NUMBER OF LIVE PUPS AT
COMPLETION OF DAY POSTPARTUM
4a 4b 7
MF
MF
MF
14 MF
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
C
14 (1) 0
14
85
22
11 0 ii
47
22
12 0 12
57
NOT PREGNANT
NOT PREGNANT
22
16 0 16
10 6
23
9(1) 0
9
62
23
11 2 13
92
NOT PREGNANT
22
12 0 12
2 10
22
12 0 12
39
22
17 0 17
6 11
23
12 0 12
75
23
808
62
G
15(5) 0
15
73
22
11(7) 0
11
4-
22
17 0 17
11 6
NOT PREGNANT
22
13 0 13
76
22
12 0 12
75
23
15(4) 1
16
74
23
9 2 11
54
MORIBUND SACRIFICED ON DAY 36 OF STUDY
C
13 (8) 0
13
32
22
15(1) 1
16
95
64 47 47
10 5 51 82
18 13 35 75 -73 474
64 65 -53
32 85
44 44 44
44 5i 62
17 13 35 44 -53 444
44 44 -53
32 44
44 44 44
44 51 62
17 13 -2 44 -53 444
44 44 53
32 44
44 44 44
44 51 62
16 13 -2 44
--
53 444
44 44 -53
32 44
M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM. a. Number of live pups preculling. b. Number of live pups postculling. c. No confirmed mating date.
21 MF
44 44 44
44 51 62
16 13
-2
44 -53 444
44 44 -53
32 44
TOTAL IMPLAN TATIONS
N
15 11 13
16 13 14
16 15 18 13 15 15 12 17
14 15 16 16
15 16
418-008:PAGE C-139
000425
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C34 (PAGE 5) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA Fo GENERATION FEMALE RATS/F1 GENERATION LITTERS
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
RAT/ LITTER NUMBER
DURATION OF GESTATION (DAYS) N
LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN
NNN
1 MF
NUMBER OF LIVE PUPS AT
COMPLETION OF DAY POSTPARTUM
4a 4b 7
MF
MF
MF
14 MF
21 MF
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
23 22 22 NOT PREGNANT 22 22 22 NOT PREGNANT 22 22 NOT PREGNANT 22 23 22 22 22 22 22 22 22 22 NOT PREGNANT 23 23 22
6(6) 2 (2) 3(3)
0 4 2
9 12
4 (4)
3 0 2
7(7) 2 13 (2) 0
10(2) 4 (4)
11 (1) Kl)
13(3) 0 4 (2) 5(5) 9
13
3 9 3 3 1 8 6 0 2 0
10(9) 1 8(8) 3
12(12) 0
6 6 5
12 12
6
9 13
13 13 14
4 14
9(1) 10
5 11 13
il il 12
_. ---
45 66
--
65
44
--
64
--
82
--
-2
--
54 76
i_
--
__ ---
---
--
..
----------
---
-_ ---
..
---
__ --
__
----------
__
---
__ ---
..
---
..
--
_ ----------
._
-* --
_ ---
.
---
--
.
---------
.
--
---
..
--
--
. --
._
---*----*-
_.
---
M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM. ( ) = NUMBER OF PUPS IN WHICH CANNIBALIZATION AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION OF VIABILITY. a. Number of live pups preculling. b. Number of live pups postculling.
TOTAL IMPLANTATIONS
N
13 11 10
12 12 10
11 13
13 14 14 14 14 12 11 15 12 13
13 12 13
418-008:PAGE C-140
000426
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C35 (PAGE 1) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT/ LITTER NUMBER
DAY 1 MFT
DAY 4a MFT
DAY 4b MFT
DAY 7 MFT
DAY 14 MFT
DAY 21 MFT
8801 8803 8804 8805 8807 8808 8811 8812 8813 . 8814 8817 8818 8819 8821 8823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
7.2 6.7 7.0 6.9 6.8 6.8 7.5 6.6 6.9 5.7 5.3 5.4 7.3 6.9 7.2 7.1 7.0 7.1 7.9 7.5 7.7 7.2 6.7 6.8 7.3 6.6 6.8 8.1 8.0 8.1 NOT PREGNANT NOT PREGNANT 7.5 6.8 7.0 7.1 6.7 6.9 6.6 6.3 6.5 6.0 5.6 5.9 6.4 6.1 6.2 6.3 5.5 5.8 6.8 6.5 6.6 6.6 6.1 6.4 6.4 6.0 6.3 6.2 5.9 6.0 6.3 6.0 6.2 6.7 6.2 6.4 5.8 5.6 5.8
10.1 10.2
9.7 7.2 9.9 9.9 11.4 10.3 10.2 12.5
9.8 10.5
9.0 6.6 9.2 9.6 11.0 9.2 9.5 12.0
10.0 10.3
9.3 6.7 9.6 9.7 11.2 9.4 9.6 12.3
11.0 9.6 9.5 8.2 8.7 8.6 9.2 8.5 8.4 8.3 9.0 9.8 7.9
9.9 10.2 9.4 9.6 9.1 9.3 7.5 7.9 8.4 8.5 7.7 8.0 8.8 8.8 .4 8.5 7.7 8.2 7.9 8.0 8.4 8.8 9.2 9.4 8.2 8.0
10.1 10.0 10.0
7.2 10.0
9.9 11.6 10.3 10.2 12.6
9.8 10.7
9.7 6.8 9.1 9.8 11.4 10.1 9.6 12.0
10.0 10.3
9.8 7.0 9.5 9.8 11.5 10.2 9.8 12.2
11.0 9.8 9.6 8.4 8.6 8.9 9.2 8.8 8.4 8.6 9.3 9.9 8.6
10.6 9.5 9.2 7.9 8.4 8.0 9.0 8.6 8.0 8.4 8.4 9.2 7.7
10.7 9.6 9.4 8.1 8.5 8.5 9.0 8.7 8.2 8.5 8.9 9.6 8.5
15.3 15.3 14.8 10.1 15.5 14.5 17.6 16.2 15.7 20.2
14.9 16.2 14.7
9.3 14.2 14.5 17.1 15.8 14.8 18.8
15.1 15.8 14.7
9.7 14.9 14.5 17.3 16.0 15.2 19.5
17.1 15.9 14.8 13.6 13.9 11.7 14.6 14.6 13.8 14.4 16.6 15.5 14.4
16.5 15.6 14.4 12.6 13.4 11.1 14.4 13.8 13.1 14.5 14.7 14.6 15.0
16.7 15.7 14.6 13.1 13.6 11.4 14.4 14.2 13.4 14.5 15.6 15.1 14.5
31.3 29.8 34.8 27.6 34.0 29.1 35.5 35.4 30.2 39.8
30.1 33.4 32.8 23.9 31.9 28.8 34.0 34.2 29.7 37.7
30.9 31.6 33.8 25.7 33.0 28.9 34.7 34.8 29.9 38.8
46.7 49.8 56.1 46.6 54.3 49.0 58.8 58.0 51.0 64.8
45.8 49.2 53.2 39.4 50.2 48.5 55.2 53.9 49.9 61.0
46.3 49.4 54.7 43.0 52.3 48.7 57.0 56.0 50.3 62.9
35.3 31.3 30.6 28.3 28.9 23.6 33.2 29.9 32.0 30.6 34.0 31.3 32.8
33.9 30.0 29.7 27.5 27.4 22.5 32.2 29.2 31.8 30.7 30.9 29.8 29.7
34.5 30.5 30.1 27.9 28.2 23.0 32.4 29.5 31.9 30.6 32.5 30.6 32.4
54.1 50.9 50.0 45.0 44.0 41.4 52.6 49.9 49.8 50.4 53.8 46.8 50.6
52.3 50.8 49.2 42.2 42.0 39.0 50.8 46.9 48.8 49.7 47.7 43.8 47.0
53.0 50.8 49.6 43.6 43.0 40.2 51.3 48.4 49.2 50.0 50.8 45.2 50.1
M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
m - 0 39Vd:800-8l>
000427
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: G295.9)
TABLE C35 (PAGE 2) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
RAT/
LITTER NUMBER
8838 8840 8841 8842c 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865 8866 8867 8868 8869 8870
DAY 1 M FT
5.9 5.6 5.8 6.4 6.2 6.3 6.5 6.6 6.5 6.8 6.6 6.7 7.0 6.6 6.7 6.4 5.8 6.1 6.6 6.6 6.6 5.7 5.2 5.5 6.3 5.8 6.0 6.5 6.0 6.4 5.9 6.0 5.9 7.1 6.7 6.9 6.6 6.1 6.3 6.4 6.2 6.4 7.6 7.1 7.2 6.6 6.2 6.4 6.8 6.5 6.6 6.0 6.3 6.1 7.2 6.9 7.1 6.2 5.6 6.1 6.2 6.0 6.2 7.7 6.6 7.0 6.4 5.9 6.2 6.6 6.2 6.5 6.8 6.3 6.5
DAY 4a M FT
8.3 7.9 8.8 9.3 10.0 9.1 9.4 7.9 8.5 9.9 7.0 9.5 8.9 8.9 11.0 9.5 9.7 8.8 9.0 8.7 7.5 10.7 9.8 8.8 10.0
7.8 7.5 9.0 8.7 10.0 8.4 9.2 7.3 8.3 9.5 7.6 9.2 8.3 8.2 10.3 8.8 9.4 8.9 8.8 8.3 7.4 9.2 8.8 8.1 9.1
8.1 7.7 8.9 8.9 10.0 8.8 9.3 7.7 8.4 9.8 7.2 9.4 8.5 8.6 10.5 9.2 9.6 8.8 8.9 8.6 7.5 9.8 9.3 8.5 9.5
DAY 4b MFT
8.4 8.3 9.0 9.3 10.0 9.2 9.7 8.1 8.7 9.9 7.9 9.1 8.9 9.0 11.0 9.8 9.7 9.6 9.2 8.7 7.7 11.0 10.3 8.7 10.2
8.0 8.0 9.0 8.7 10.2 8.8 9.3 7.4 8.0 9.5 7.8 9.1 8.6 8.5 10.1 8.9 9.7 8.9 8.8 8.3 7.8 8.6 9.0 8.2 9.3
8.2 8.1 9.0 9.0 10.1 9.0 9.5 7.7 8.4 9.8 7.9 9.1 8.8 8.8 10.4 9.3 9.7 9.3 9.0 8.5 7.7 9.8 9.7 8.5 9.7
DAY 7 M FT
13.9 12.8 14.8 14.5 13.9 14.3 14.8 13.0 13.8 15.1 13.0 15.4 14.6 14.3 17.6 15.8 15.8 15.4 14.1 14.4 11.0 17.5 16.1 13.8 17.3
13.0 12.8 14.6 13.9 14.0 13.4 14.4 12.2 12.4 14.7 12.8 14.7 13.9 13.8 15.8 14.2 15.6 14.1 14.4 13.4 10.9 14.1 14.8 13.2 15.4
13.4 12.8 14.7 14.2 14.0 13.8 14.6 12.6 13.2 15.0 13.0 15.0 14.2 14.0 16.2 15.0 15.7 14.8 14.3 14.0 11.0 15.8 15.4 13.5 16.4
DAY 14 M FT
32.0 29.6 32.5 28.7 29.9 31.5 26.4 29.3 29.8 31.3 28.7 33.2 30.9 31.3 34.2 31.4 35.5 31.3 31.4 31.3 24.0 32.6 35.6 31.3 34.7
31.5 29.9 31.8 28.4 29.9 29.8 25.6 28.1 28.4 31.1 28.8 31.2 28.6 31.2 31.5 29.0 34.3 29.4 31.6 29.7 24.3 29.9 32.8 28.9 32.2
31.8 29.8 32.1 28.5 29.9 30.7 26.0 28.7 29.1 31.2 28.8 32.2 29.8 31.3 32.2 30.2 34.9 30.3 31.5 30.5 24.2 31.2 34.2 30.1 33.4
DAY 21 MFT
51 .3 48.2 48.5 45.2 51.8 49.7 46.0 46.2 50.2 49.6 46.2 49.5 44.8 51.8 55.0 50.0 58.4 46.2 48.8 51.8 39.2 54.5 54.6 50.0 53.7
49.2 47.0 49.0 46.6 50.1 47.2 44.6 44.2 46.2 48.3 46.9 48.0 41.8 51.8 51.2 46.2 56.0 45.4 48.7 49.0 39.3 49.0 51.8 46.8 48.6
50.3 47.6 48. a 45.9 50.8 48.5 45.3 45.2 48.2 49.1 46.6 48.8 43.2 51.8 52.1 48.1 57.2 45.8 48.8 50.4 39.2 51.8 53.2 48.4 51.1
M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
c. Dam 8842 delivered one additional pup on day 2 of lactation; values for day 1 postpartum excluded from group averages and
statistical analyses.
418-Q08:PAGE C-142
000428
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C35 (PAGE 3) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
RAT/ LITTER NUMBER
DAY 1 MFT
DAY 4a M FT
DAY 4b M FT
DAY 7 M FT
DAY 14 M FT
DAY 21 M FT
8871 8872 8874c 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896d 8897d 8898 8899c 8900 8901 8902 8903 8904 8905
NOT PREGNANT 6.2 6.0 6.2 6.0 5.6 5.9 6.7 6.6 6.7 8.7 8.3 8.5 6.3 5.9 6.0 6.9 6.2 6.5 6.8 6.5 6.7 5.7 5.8 5.7 6.7 6.5 6.6 6.2 6.2 6.2 6.6 6.4 6.6 6.5 6.0 6.3 8.2 7.6 8.0 5.4 5.9 5.6 6.3 5.6 6.0 6.7 6.5 6.5 6.7 6.2 6.5 6.2 5.8 6.0 6.5 5.8 6.1 6.7 6.2 6.4 6.4 6.0 6.2 NOT PREGNANT NOT PREGNANT 5.8 5.7 5.8
8.3 8.9 9.4 13.1 8.3 8.9 9.3 7.1 10.0 8.9 9.2 8.2 11.6 7.4 9.0 8.9 9.2 9.1 9.2 9.2 7.9
8.3 8.0 9.6 12.7 7.7 8.2 8.8 7.1 9.8 9.0 9.0 7.7 11.3 7.8 8.2 8.8 8.8 8.6 8.2 8.5 7.7
8.3 8.6 9.5 12.9 7.9 8.5 9.1 7.1 9.9 9.0 9.1 8.0 11.5 7.6 8.6 8.8 9.1 8.8 8.6 8.8 7.8
8.0 7.4 7.7
8.6 9.4 9.6 13.1 8.6 8.9 9.5 7.2 10.2 9.5 9.3 8.5 11.6 7.8 9.4 9.2 9.4 8.8 9.1 9.1 8.0
8.5 8.3 9.6 12.7 7.4 8.8 9.1 7.2 10.1 9.2 8.8 7.6 11.3 8.1 8.6 8.8 8.8 8.8 8.8 8.8 7.6
8.6 9.0 9.6 12.9 8.0 8.8 9.3 7.2 10.2 9.4 9.0 8.1 11.5 7.9 9.0 9.0 9.1 8.8 9.0 8.9 7.8
8.3 7.0 7.6
13.6 15.1 15.1 17.8 14.1 13.2 15.3 12.2 14.6 14.6 14.2 14.1 17.0 12.6 14.2 14.8 14.0 14.2 15.0 10.3 13.6
13.0 13.3 14.8 17.7 12.0 13.4 14.9 11.8 14.2 14.2 13.5 12.6 16.6 12.9 13.4 13.9 13.4 14.2 14.6 11.5 12.4
13.3 14.4 14.9 17.7 13.1 13.3 15.1 12.0 14.4 14.4 13.9 13.4 16.9 12.8 13.8 14.4 13.7 14.2 14.8 11.0 13.0
13.8 12.5 13.2
30.5 29.3 29.8 33.6 30.7 30.2 31.5 26.6 30.6 31.0 28.4 30.4 30.8 29.1 33.4 32.8 26.6 32.3 32.0 24.5 31.8
29.1 27.5 29.6 33.7 27.8 30.4 29.9 25.8 30.2 30.7 27.8 22.5 31.7 28.1 31.8 31.5 25.6 31.8 31.7 26.2 29.7
29.8 28.6 29.7 33.6 29.2 30.3 30.9 26.2 30.4 30.8 28.1 26-4 31.1 28.6 32.6 32.2 26.1 32.1 31.8 256 30.8
33.6 31.2 32.4
51.3 49.1 49.8 57.3 50.0 53.0 51.2 38.4 51.1 48.6 38.8 48.4 46.2 47.0 52.5 46.0 43.4 54.0 52.2 42.7 50.7
49.2 46.8 48.6 55.3 45.0 53.5 50.7 36.8 51.5 47.8 38.5 44.6 44.3 45.8 48.0 46.0 42.4 53.7 51.2 47.0 47.4
50.2 48.2 49.2 56.3 47.5 53.2 51.0 37.6 51.3 48.2 3S.6 47.1 45.5 46.4 50.2 46.0 42.9 53.8 51.8 45.4 49.1
53.1 49.6 51.3
M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
c. A aexing error was found prior to weighing on day 7 postpartum; values for day 4 postpartum postculling were
excluded from group averages and statistical analyses.
d. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pups were
arbitrarily distributed between the two dams and values will be included in group averages and statistical analyses.
418-008:PAGE C-143
000429
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.91
TABLE C35 (PAGE 4): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA FI GENERATION LITTERS
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
RAT/ LITTER NUMBER
DAY 1 M FT
DAY 4a MFT
DAY 4b MFT
DAY 7 M FT
DAY 14 M FT
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
4.9 S.O 4.9 7.5 7.4 7.5 7.6 7.4 7.6 11.9
6.4 6.0 6.1 8.5 8.0 8.2 8.5 8.4 8.4 12.9
5.7 5.6 5.1 8.0 7.8 7.9 8.0 8.1 8.1 11.6
NOT PREGNANT
NOT PREGNANT
5.8 5.4 5.7 7.1 6.5 6.9 7.4 6.7 7.1 11.8
5.9 5.7 5.8 8.4 9.5 8.6 8.4 9.5 8.6 11.3
6.5 6.2 6.4 8.8 8.6 8.7 9.4 8.6 9.2 13.2
NOT PREGNANT
5.4 5.6 5.6 7.8 6.9 7.0 7.8 7.3 1 .4 11.5
5.9 5.6 5.6 6.1 6.1 6.1 6.1 6.1
1 8.5
5.6 6.1 5.9
5.0 4.7 4.8
5.0 4.7 4.8
--
7.1 6.5 6.8 8.6 8.3 8.5 9.1 8.4 8.8 13.2
6.0 6.0 6.0 NO SURVIVING PUPS ON DAY 2 POSTPARTUM
5.1 5.7 5.3 8.1 7.0 7.8 8.5 7.0 7.9 13.0
5.1 --
5.1 7.5 --
7.5 7.5 --
7.5 10.9
5.6 5.3 5.5 5.9 5.4 5.7 6.0 5.4 5.7 9.2
NOT PREGNANT
5.6 5.0 5.3 6.4 5.7 6.1 6.6 5.7 6.2 10.2
5.8 5.4 5.6 6.5 6.5 6.5 6.6 6.7 6.6 10.2
5.4 5.2 5.3 NO SURVIVING PUPS ON DAY 4 POSTPARTUM
7.0 6.6 6.8 8.8 9.0 8.9 8.8 9.0 8.9 12.8
MORIBUND :SACRIFICED ON DAY 36 OF STUDY
5.3 4.9 5.1 8.2 7.8 8.0 8.2 7.8 8.0 11.4
5.8 5.4 5.7 7.6 6.8 7.3 8.6 7.1 7.9 13.8
11.4 12.9 11.8
10.3 13.4 12.2
10.6 8.3 6.3
12.4
10.3
--
8.7
8.5 10.5
11.8
10.7 11.2
11.6 12.9 11.7
11.0 11.6 13.0
10.7 8.4 6.3
12.8
12.0 10.9
9.0
9.3 10.4
12.4
11.1 12.5
26.8 26.2 26.5 27.3 27.1 27.2 24.6 25.0 24.8
27.1 23.8 25.4 22.7 24.4 23.0 26.2 25.2 26.0
26.3 22.7
--
26.6
24.7 19.9 14.6 25.4
24.9 20.6 14.6 26.0
28.8 25.0 27.4
25.3 --
25.3
20.8 20.6 20.7
24.4 21.5 23.0 24.1 24.2 24.2
28.2 26.8 27.7
23.5 22.4 23.1 30.7 25.4 28.0
M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
DAY 21 M FT
42.3 42.3 42.3 42.0 42.8 42.4 40.0 40.8 40.4
46.3 40.8 43.6 40.6 38.0 40.2 44.8 41.6 44.0
37.5 35.8
--
43.4
35.0 32.9 31.2 41.6
35.4 33.6 31.2 42.5
49.2 41.1 46.2
43.2 --
43.2
36.1 35.2 35.6
38.4 34.8 36.6 40.2 39.6 39.9
45.0 42.8 44.2
39.0 37.5 38.4 49.4 41.2 45.3
418-008:PAGE C-144
00043
o
PROTOCOL 418-00B: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C35 (PAGE 5): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION LITTERS
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
RAT/ LITTER NUMBER
DAY 1 MFT
DAY 4a MFT
DAY 4b MFT
DAY 7 MFT
DAY 14 MFT
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NOT PREGNANT 5.6 5.2 5.3 NO SURVIVING PUPS ON DAY 2 OF LACTATION 5.2 4.8 5.0 NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NOT PREGNANT NO SURVIVING PUPS ON DAY 1 OF LACTATION 5.3 5.0 5.2 NO SURVIVING PUPS ON DAY 2 OF LACTATION NOT PREGNANT 5.0 4.8 4.9 NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION 5.0 5.0 5.0 NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION 6.0 6.0 6.0 NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION
5.1 5.1 NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION 5.8 5.7 5.8 NO SURVIVING PUPS ON DAY 2 OF LACTATION 5.8 5.4 5.6 NO SURVIVING PUPS ON DAY 2 OF LACTATION NOT PREGNANT 5.3 --- 5.3 NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION NO SURVIVING PUPS ON DAY 1 OF LACTATION
M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
DAY 21 MFT
418-008:PAGE C-145
000431
PROTOCOL 410-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 1) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 1
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
6.9 7.4 7.2 7.5 7.1 7.0 MS 6.5 6.7 6.8 7.2 5.9 7.7 6.7 7.6 6.4 6.8 MS 7.2 6.4 6.6 6.7 7.0 8.1 7.7 6.9 7.0 7.6 7.5 6.8 6.9 6.8 5.1 6.9 6.2 6.9 6.9 6.8 5.4 5.7 5.8 6.0 5.3 5.4 5.3 4.9 5.7 5.4 5.3 5.3 5.0 5.3 5.3 5.2 FD 1 7.1 6.8 7.0 8.0 7.1 7.6 7.5 7.4 6.8 7.0 6.8 6.4 7.5 7.7 7.1 6.5 6.3 7.1 6.7 7.7 7.2 7.3 FS 7.9 8.3 8.4 8.2 7.4 7.1 7.4 7.3 7.7 7.8 7.6 7.3 7.2 7.3 7.9 6.2 6.6 7.0 6.5 5.7 7.5 6.7 6.9 6.8 6.4 6.7 6.6 6.3 7.2 7.1 7.8 7.1 6.6 5.9 6.3 6.6 7.2 6.8 6.4 6.8 6.5 8.4 8.6 8.2 7.8 7.6 8.3 7.9 8.7 7.9 7.8 8.0 7.9 7.7 NOT PREGNANT
NOT PREGNANT
7.6 7.5 7.4 3.8 6.9 7.5 7.0 7.2 6.8 7.4 7.3 7.8 6.7 6.7 7.1 6.5 6.7 6.4 6.0 6.7 6.1 5.9 6.6 6.3 6.2 5.3 5.1 6.5 6.4 5.8 6.5 6.1 6.4 5.0 6.3 5.9 5.7 4.7 6.3 6.6 6.3 6.5 6.1 6.4 6.1 6.2 6.2 6.0 5.6 6.4 6.3 5.9 6.6 6.5 6.7 6.4 5.4 6.1 5.8 6.0 5.3 5.6 5.3 4.3 5.7 5.8 6.8 6.7 MS 6.4 6.1 6.1 6.3 6.8 6.7 6.9 6.7 6.8 6.4 FS FS 6.0 6.5 6.7 6.8 7.0 6.6 6.8 6.3 6.7 6.5 6.8 5.6 6.3 6.2 6.4 6.0 6.5 6.1 6.2 6.4 6.5 6.0 6.3 6.5 6.8 6.7 6.2 6.1 5.7 6.4 5.7 6.4 6.2 6.0 7.0 5.8 5.6 5.3 6.6 5.7 6.2 5.4 6.2 5.9 6.2 6.0 5.8 5.8 6.7 6.0 5.8 6.6 6.2 6.8 6.1 6.4 6.3 5.9 6.7 5.7 5.6 5.7 6.3 7.1 6.5 6.7 6.4 6.6 7.0 MS 5.4 6.8 6.9 6.4 5.8 5.6 6.2 FU FU UU 6.1 5.8 6.5 5.9 6.2 5.1 6.2 5.1 4.9 5.4 6.1 5.3 6.6 5.8 5.5 5.9
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-146
000432
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 2) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP ft
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER ft
MATERNAL DOSAGE GROUP ii
0.1 MG/KG/DAY
POSTPARTUM DAY 1
8838 8840 8841 8842a 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865 8866 8867 8868 8869 8870
6.2 5.8 6.3 5.9 5.8 6.3 6.3 5.5 5.9 5.3 6.1 5.6 5.3 5.2 5.6 5.7 5.7 6.6 6.3 6.3 6.4 5.8 6.9 6.4 6.6 6.5 6.0 6.3 6.1 6.3 5.5 6.6 6.3 6.6 6.2 FD 1 7.0 6.5 6.6 6.0 6.4 6.0 6.6 6.6 6.5 6.1 6.8 7.1 6.7 6.3 7.0 7.0 6.3 7.2 6.5 7.2 6.7 6.5 6.9 5.7 7.0 6.9 6.5 6.3 7.0 7.2 6.8 6.4 MD 1 6.8 6.9 6.2 6.9 6.6 6.6 6.3 6.4 6.5 6.2 6.3 6.2 6.6 6.1 6.3 6.7 5.8 6.1 6.0 5.8 6.1 5.3 5.4 6.6 6.8 6.4 6.1 6.5 6.7 7.1 7.3 6.4 7.1 6.3 6.3 6.1 7.0 5.9 5.6 5.9 6.0 5.4 5.9 5.5 5.6 5.8 5.6 4.9 5.0 5.3 5.1 5.3 5.0 5.5 6.5 6.8 5.9 5.9 6.2 5.8 5.5 6.1 5.9 5.9 6.2 5.9 5.3 5.9 FD 1 6.5 6.9 7.1 6.2 6.4 6.5 6.2 5.8 5.9 6.3 UU UU 4.3 6.4 6.5 5.5 6.2 5.7 5.7 6.8 5.4 5.5 5.4 6.4 6.6 6.5 6.5 5.3 6.1 6.2 5.7 7.6 6.8 7.3 6.9 6.5 7.3 7.1 7.2 7.0 7.0 6.8 7.1 6.4 6.0 6.3 6.7 6.6 6.8 6.6 6.1 6.6 6.2 5.3 6.0 6.0 6.2 6.4 6.3 6.0 7.2 7.1 6.1 6.3 6.4 6.4 5.9 6.2 6.5 6.2 6.2 5.5 5.8 6.7 6.8 7.6 7.6 MS 7.1 7.4 6.4 6.9 7.9 6.5 6.8 7.8 5.9 6.9 6.2 7.0 6.6 6.8 7.2 5.8 6.4 6.2 6.2 6.1 6.2 6.6 6.3 7.1 6.7 6.7 6.7 6.8 6.5 7.0 6.7 6.4 6.8 6.6 6.6 5.8 6.4 6.7 5.5 6.2 5.8 6.6 6.3 6.7 6.6 5.9 4.6 5.8 5.9 6.4 6.9 6.2 5.6 7.1 7.3 7.0 7.1 7.7 6.8 6.9 6.6 7.2 7.1 6.3 5.8 5.8 6.4 6.1 6.9 6.0 6.2 6.2 6.7 6.0 5.5 5.1 5.9 6.4 6.5 5.5 6.2 6.3 6.4 6.4 6.3 6.2 5.8 6.2 6.1 6.1 5.4 6.2 6.5 8.1 7.2 7.7 7.4 8.0 6.4 7.9 6.8 5.4 6.5 6.7 7.2 5.9 6.6 5.4 5.4 7.0 5.8 7.1 6.8 6.8 5.7 6.6 5.4 5.6 6.2 5.8 6.5 7.1 6.6 6.4 6.5 6.3 6.2 6.7 6.6 7.0 6.6 6.6 6.6 5.8 6.0 5.9 FS 6.9 6.5 6.8 6.9 6.7 6.5 5.5 6.6 6.4 6.5 6.1
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Dam 8842 delivered one additional pup on day 2 of lactation; values for day 1 postpartum excluded from group averages and
statistical analyses.
418-008: PAGE C-147
000433
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 3) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP H 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER II
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
POSTPARTUM DAY 1
8871 8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 889S 8896 8897 8898 8899 8900 8901 8902 8903 8904 8905
NOT PREGNANT 5.4 6.2 6.7 6.0 6.3 6.7 6.0 6.6 MS 6.3 6.1 5.5 6.3 5.9 5.6 5.6 5.7 5.9 5.7 6.5 5.3 6.5 6.6 6.6 5.6 5.8 5.2 5.5 5.9 6.4 6.8 6.7 6.7 7.1 6.4 7.1 6.5 6.5 6.2 6.3 7.2 6.8 8.4 8.5 9.3 MD 1 7.9 9.5 7.6 7.3 6.0 6.4 5.6 6.2 5.6 5.4 5.9 5.3 6.2 6.3 6.0 6.4 6.1 6.3 7.1 6.7 7.1 6.7 7.5 6.9 7.1 6.2 6.3 7.1 6.7 5.4 6.4 4.4 6.5 7.1 7.5 6.8 7.2 6.8 6.0 6.9 6.7 MS 6.4 7.0 6.1 6.8 6.4 6.7 FS 5.4 5.6 5.7 5.6 6.0 6.0 6.1 5.5 5.3 6.0 6.0 5.7 5.7 5.4 6.2 7.2 6.9 6.8 6.3 6.3 6.6 6.5 6.4 6.4 6.8 6.3 6.5 6.2 6.4 6.4 6.5 5.0 5.8 6.4 6.3 6.3 6.2 6.2 6.6 5.8 6.4 6.3 6.5 6.4 6.6 7.7 6.4 6.8 6.0 6.7 6.4 6.6 6.2 7.0 6.3 6.5 6.6 6.5 6.4 6.6 6.1 6.2 5.9 6.1 6.3 5.6 7.9 8.5 7.6 5.8 5.8 6.0 5.8 5.6 3.8 5.8 5.5 5.0 5.9 5.8 6.1 5.6 6.0 5.9 5.5 6.5 6.6 6.2 6.1 5.7 6.1 7.0 6.5 5.8 6.0 4.6 5.4 6.0 5.5 6.5 6.5 6.4 6.9 7.0 6.7 6.3 6.7 6.4 6.6 6.3 6.5 6.4 6.4 6.6 6.5 6.6 6.7 6.8 6.8 6.8 6.6 6.3 6.4 6.4 5.9 FS 6.4 6.1 5.3 5.7 6.1 7.5 6.4 6.3 6.2 5.9 6.6 5.8 6.0 6.3 4.1 5.7 6.8 6.6 6.1 6.4 6.6 6.6 6.2 5.8 5.3 4.9 6.3 6.4 6.0 5.5 5.5 FS 7.1 6.4 6.7 6.6 6.8 6.7 6.2 6.1 5.7 6.1 6.2 6.2 6.5 6.2 6.3 6.4 6.8 6.5 6.5 6.4 5.8 6.0 6.0 6.5 6.0 5.8 6.2 6.1 FS
NOT PREGNANT NOT PREGNANT
5.9 6.2 5.2 5.6 6.1 5.7 5.9 6.0 6.0 5.8 5.5 5.9 6.0 5.4 5.9 5.5
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008iPAGE C-148
000434
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C36 (PAGE 4) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP ft
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER ft
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
POSTPARTUM DAY 1
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 B928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
5.2 5.1 5.6 5.1 4.7 4.4 5.7 6.0 6.2 6.8 6.6 5.0 6.4 5.9 5.4 5.5 5.8 6.3 5.7 5.6 6.0 NOT 1PREGNANT NOT 1PREGNANT 5.8 6.0 6.2 5.7 5.9 6.2 5.8 6.1 5.9 5.9 6.2 5.6 5.7 6.1 7.2 7.3 6.6 6.4 6.8 5.3 6.5 NOT 1PREGNANT 5.5 5.4 5.4 4.7 5.2 5.6 5.8 6.1 5.9 5.6 6.0 5.0 5.7 5.1 6.3 4.8 6.0 5.3 4.9 6.0 5.7 7.1 7.7 7.1 7.2 7.4 7.4 6.0 6.6 5.9 5.9 6.3 6.0 5.5 6.0 6.0 5.0 4.5 4.4 4.8 5.7 5.3 5.4 4.8 5.2 5.0 MD 1 MD 1 MD 1 5.7 5.5 4.6 6.1 5.6 5.7 5.5 NOT PREGNANT 5.8 5.9 5.0 5.6 5.4 5.7 5.7
6.2 6.2 5.3 5.6 6.1 5.7 5.7 5.5 5.1 5.5 5.6 5.8 5.1 5.2 7.8 6.7 6.7 7.2 6.5 MS 6.9 MORIBUND SACRIFICED ON DAY 36 OF STUDY 5.4 4.9 5.6 MD 1 MD 1 4.9 4.9 5.6 6.5 5.6 6.0 6.7 5.3 6.2
3.6 6.7 5.3
5.8 5.3 5.6
5.8 5.2 6.3 6.7 6.0 MD 1 MD 1 6.6
5.0 5.3 5.4 6.4
FD 1 5.6
5.3 6.1 5.7
5.7 FD 1
6.7
6.0 4.8 6.3 6.5
MD 1 MD 1
5.6
5.2 4.7 MS 6.5
FD 1 5.0
5.3 5.3 6.0
5.4
MS
6.0 5.7 5.9 7.0
MD 1 FD 1
5.6
5.4 5.7 MD 1 6.4
FD 1 MD 1
4.1 6.3 5.6
5.5
MS
5.6 6.4 6.1 5.9
5.7 FD 1
5.6
4.9 5.2 5.3 FS
FD 1 5.1
5.0
5.3
5.4
6.1
5.7 6.3 6.1 6.2
5.8
6.0
4.9 5.9 5.2
FD 1 5.3
5.2 FD 1
5.4 5.3 6.2
5.6 6.0 5.5 5.0 4.9 5.0 4.8 5.3 5.1 FD 1 5.8 5.2
5.4
6.2 FD 1
5.3 5.0 5.7
5.5
6.5 4.8 5.1 FS
ALL WEIGHTS WERE RECORDED IN GRAMS (G) . FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-149
000435
PROTOCOL 418 008. COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 5) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP tt
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER tt
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
POSTPARTUM DAY 1
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 89S7 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
MD 1 MD 1 MD 1 MD 1 MS MS MD 1 MS FS NOT PREGNANT
5.4 5.6 5.9 5.1 5.0 5.1 MS FD 1 FD 1 NOT PREGNANT MS MD 1 MD 1 5.5 5.1 5.3 NOT PREGNANT 5.1 5.1 5.2 MD 1 MD 1 MD 1 4.9 4.8 4.9 MS MS MS 5.3 6.0 6.3 MS MS MS MS MS 4.8 5.2 MD 1 MD 1 5.9 5.9 5.7 6.0 5.8 6.1 NOT PREGNANT 5.3 5.2 5.7 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1
MD 1 MS
FD 1
5.3 5.7 FD 1
MD 1 5.7
4.8 MS 5.1 FD 1 6.2 FS 5.4 4.3 6.0 5.5
6.3 MD 1 MD 1
FD 1 MS
FD 1
MS 5.0 FD 1
MD 1 5.0
MD 1 MS 5.2
6.8 FS FD 1 4.3 5.5 6.3
5.1 MS MD 1
FD 1 FD 1
MS 5.2 FS
FS 5.3
MS MS 5.1
5.6 FS FD 1
MS 5.6
5.5 MS MD 1
5.0 4.9
FD 1 5.6
MS MS MS
5.5 FS FS
5.4 5.6
MS FD 1 FD 1
5.3 4.7
FD 1 5.0
4.8 FD 1
4.7
6.1 FS FS
5.9 5.0
5.5 FD 1 FD 1
5.2 4.7
FD 1 4.8
4.9 FS 5.2
6.3 UU FS
5.8 4.9
5.6 FD 1 FD 1
5.0 4.6
5.3
5.0 FS 5.1
MS
FS
5.8 5.5
4.7 FD 1 FD 1
5.3 4.9
4.9 4.5 FS 4 .8 5.7
FS 5.2 FD 1 FS FD 1
FS 4.8
5.1 FD 1
FS FD 1
6.2
5.1
FD 1
FD 1 FS FS FS 6.0
6.4
FS 6.4
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-150
000436
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 6) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
RAT/ LITTER 0
MATERNAL DOSAGEIGROUP1 I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 4 PRECULLING
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8821 8823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
10.2 10.8 10.0 8.3 10.1 10.8 9.0 9.3 9.4 7.5 6.5 7.7
10.2 10.0 9.8 10.0 10.5 9.1 11.3 11.5 11.1 10.2 10.7 10.9 10.4 10.1 10.0 12.6 12.6 12.1 NOT PREGNANT NOT PREGNANT 11.4 10.5 11.1
7.3 6.8 7.7 9.7 9.2 9.7 7.4 8.9 8.8 8.6 8.7 8.3 8.7 7.4 8.8 9.0 9.3 MS 6.2 8.4 7.9 8.6 8.4 8.6 9.6 8.0 7.6 9.8 8.6 9.4 9.8 9.4 9.9 9.3 8.5 8.5
9.8 10.0 10.3
7.0 9.2 10.0 11.9 9.3 9.4 12.5
10.8 6.9 9.0 8.7 9.0 9.0 8.6 9.2 9.2 8.4 9.0 9.6 8.6
9.6 10.1 10.4
7.2 9.5 9.2 10.7 8.3 9.5 12.9
5.4 7.6 9.4 8.7 8.8 9.1 9.3 8.5 8.5 8.5 9.0 10.0 7.7
10.1 11.4
9.9 6.6 10.6 10.3 12.1 9.4 9.8 12.6
10.4 6.6 9.8 7.0 8.2 8.1 8.9 8.2 7.8 7.7 9.5 9.8 9.0
MS 10.7
9.6 5.7 10.1 8.3 11.5 7.4 9.3 12.2
10.8 6.6 9.6 7.1 8.8 6.1 8.4 9.1 8.8 8.4 8.3 MS 8.4
10.1 MS 5.9 6.4 9.9 9.6 11.5 8.4 8.9 12.0
10.6 6.9 9.1 8.6 7.8 7.6 9.4 8.8 8.0 6.8 8.8 9.8 7.8
9.3 9.5 9.7 6.4 9.2 10.0 11.0 9.7 9.5 12.2
10.4 6.4 8.7 8.7 8.6 7.9 7.7 9.1 8.2 7.7 8.7 8.5 7.4
9.9 10.2 10.2
6.9 9.0 FS 9.7 9.0 9.3 11.4
10.2 6.9 9.4 6.7 8.6 8.2 8.8 9.0 8.2 7.7 8.8 9.3 7.8
11.3 9.1 6.8 9.5
11.1 9.9
10.1 12.5
9.9 6.7 9.2 5.9 8.5 8.3 8.9 8.8 7.5 7.6 7.7 9.6 8.1
10.4 9.6 6.3 9.2
11.4 8.5 9.4
12.2
10.7 7.1 9.0 7.8 8.4 7.4 9.1 8.0 7.8 8.1 8.5 9.1 8.2
10.9 7.9 6.7 8.9
9.0
11.9
6.6
8.6 8.7 8.2 8.6 8.7 8.1 7.1 8.3 9.4 4.6
9.5 9.5 6.9 6.5 FM 4 FD 1
9.7 9.3 9.9 10.8
6.9 8.4 7.8 7.6 FS FS 8.0 8.5 9.0 6.7 8.4 8.2 8.1 8.9 8.5 8.7 FD 1 8.6 FU FU UU 8.4 7.0 8.8
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
19
20
418-008:PAGE C-151
000437
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE C36 (PAGE 7) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP H
RAT/ LITTER tf
8838 8640 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 B860 8862 8863 8864 8865 8866 8867 8868 8869 8870
]
3
Al C
r8
S> 10 11 12 13 14 15 16 17 18 19
MATERNAL DOSAGE;GROUP* II
0 .1 MG/KG/DAY
POSTPARTUM DAY Al PRECULLING
7. 1 8 .8 9. 1 9. 3 10 .0 9..0 9..4 8 ,4 8 .7 10 .i 6 .9 8..4 / 8 .9 9..5 10 .6 8..3 9 .4 8 .1 9 .8 9 .0 7 .7 11 .1 10 .4 8 .4 9 .9
8. 6 8 .0 7. 7 9. 4 10. 4 9.,i 9. 8 8..2 8..1 9,.7 6 .6 9..8 8..8 8 .5 11,.5 9,.7 9..5 9..2 8,.5 8 .5 7 .2 11 .2 10 .1 8 .8 10 .3
7. 4 8. 8 8. 7 9. 4 9. 7 9. 3 9. 1 8. 0 8. 7 10. 1 8. 5 8. 8 9. 0 9. 4 MS 10. 0 9. 8 8. 8 8. 5 8. 6 7. 3 9. 8 8. 6 9. 2 10. 2
8. 4 6..7 9. 4 9. 2 9..4 9..0 9..6 7..8 9..4 10..2 7..6 9,.4 9 .1 8 .6 10..9 9..4 10 .0 8 .3 9 .8 8 .8 7 .3 10 .4 10 .5 8 .8 10 .3
8. 2 8. 7 8 .7 9. 3 MD 1 8.,5 8. 6 7..4 7..8 10 .0 7,.2 9. 6 8 .7 8 .6 10..9 10..4 9 .6 8 .3 8..4 8 .5 6 .8 11 .1 8 .4 9 .1 9 .4
8 .3 7 .9 8. 2 9. 2 9. 8 9. 8 9 .1 8 .3 8 .6 9..6 7..8 9..7 8.,i 9..4 9. 7 9. 5 10 .1 8.,9 9..0 8 . .8 7..1 9,.3 10..0 8 .9 9..0
8 .6 8. 3 8 .6 9. 2 10 .8 9. 0 8. 8 7. 2 7 ,.6 9 .6 6 .2 10..4 9 .1 8 .8 9..8 94 9 .6 6..9 8. 6 8 .2 8 .i 8 .7 10 .3 8 .8 8 .0
8. 3 6 .9 9. 6 8. 3 9. 7 8..8 10..1 8. 4 9,.0 9 .5 7,.6 10..0 8 .9 8 .9 10..0 8..3 8 .8 10..1 8 ,7 9 .3 7 .6 8 .9 MD 2 7 .9 9 .4
8 .9 6 .9 9. 4 9. 5 10 .2 9..0 10..1 7.,8 7 .4 9 .0 6 .0 9 .6 8 .3 8 .3 10 .8 8 .6 8 .9 9 .4 8 .9 8 .3 8 .1 7 .8 9 .0 9 .1 9 .8
9. 0 7 .7 9. 7 8 .6 10 .0 7 .8 9. 2 7. 5 9 .1 9..9 5 .3 8 .9 6 .9 8 .8 10 .6 8 .6 9 .2 10 .4 8 .8 9 .3 6 .8 8 .5 8 .2 8 .4 8 .9
7 .7 7 .3 8 .8 8. 7 10 .5 8. 0 9. 6 7. 5 8. 2 uu 7. 8 10. 0 9. 0 7 .3 9. 9 9. 7 10 ,i 8. 8
8..0 7. 6 9. 7 9.,5 9 .0 9. 4
8. 3 8. 4 8. 2 7. 9 9. 4 7. 9 9. 0 7. 0 7. 9 UU 5. 8 8. 1 7. 8 8 .5
8. 9 9. 8 8. 8
8. 6 7..7 10. 5 8. 4 8..2
8. 3 8. 4 8. 9 7 .8 PD 2 9. 1 8. 6 7. 2 8 .6
8.,0 9.,5 8 .4 8 .0
9 .4 9 .3 9 .0
8 .0 8 .3 10 .5 8 .8 7 .3
7. 9 4 .9 9. 3 9. 1
8 .9 9. 4 7..5 8..6
7,.9 9 .2 8 .1 8 .8
8..3 10 .1
9 .2
8 .6 7 .0
8 .8 9 .4
7. 4 7. 6 8. 8 8 .i 7..2 FD 1 7 .4 8 .0 8 .0 8 .8 9 .4
7 .4
7 .6
7. 6 7.6 8. 0 7.9
7..2 FM 4 6 .5 8.4
8 .1 7 .4 7 .8 FS
8.0 FD 1 7.9 7.7
20
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008: PAGE C-152
000438
418-008PAGE C-153
000439
PROTOCOL 418 -008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER; 6295.9)
TABLE C36 (PAGE 8) ; PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP ft
1
2
3
4
5
6
7
8
9 10 11 12
RAT/ LITTER ft
MATERNAL DOSAGE:GROUP III
0 .4 MG/KG/DAY
8871 8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899 8900 8901 8902 8903 8904 8905
NOT !PREGNANT 8.3 7.2 7.9 9.0 8.0 10.0 9.2 10.1 9.4
13.6 12.6 13.0 9.9 8.3 7.9 8.6 9.8 8.8 8.0 10.3 10.0 6.4 7.6 6.9
10.9 9.1 9.8 10.0 8.4 7.1
9.2 9.0 8.7 7.7 8.3 7.9 11.8 11.3 11.3 7.8 7.9 6.4 8.7 9.9 9.4 9.4 8.7 7.8 9.5 9.3 9.3 8.0 10.7 9.0 8.9 9.8 9.0 9.1 9.4 8.9 8.6 7.6 7.6 NOT PREGNANT NOT ]PREGNANT 8.0 7.1 8.6
9.3 9.1 9.5 MD 1 7.0 8.7 9.0 6.8 10.1 9.3 9.2 8.3
7.3 8.4 9.8 9.3 9.8 8.8 8.9 7.6
8.4
9.0 7.4 9.0 12.7 8.5 8.1 9.1 7.0 10.1 9.7 8.9 8.6
7.6 9.0 8.9 9.6 8.9 9.2 8.8 7.9
8.2
8.5 7.9 9.3 14.1 7.6 9.4 9.6 7.3 9.8 8.9 10.0 8.6
7.2 8.2 8.3 8.9 9.4 9.4 9.6 8.1
7.4
7.7 9.6 9.2 11.4 8.0 8.6 9.4 7.6 9.0 8.4 9.3 8.1
7.2 9.1 8.5 9.2 9.1 7.4 7.8 7.8
8.2
8.6 9.2 9.7
7.6 9.3 9.5 7.0 10.3 9.1 9.2 8.5
8.2 9.3 9.3 8.9 8.1 9.1 9.2 6.9
8.2
MS 9.4 9.7
7-7 7.6 MS 7.2 10.0 8.6 8.8 7.9
6.9 8.8 8.6 8.7 9.0 8.2 8.6 7.4
8.4
8.9 9.5 9.8
7.8 8.4 9.1 7.7 10.0 9.3 8.9 7.7
7.5 8.0 8.1 9.3 5.4 9.1 8.7 7.9
7.3
9.4 7.7 8.7 8.5 8.9 10.2
6.7 8.0 8.4 9.3 B .4 8.8 7.2 7.0 9.3 10.0 9.8 9.1 8.3 9.3 7.1 7.9
8.1 7.3 6.9 8.6 9.2 9.0 8.5 8.7 8.3 9.4 8.6 7.7 8.5 7.6 7.7 7.4
8.3 8.2
13 14 15 16 17 18
POSTPARTUM DAY 4 PRECULLING
7.7 7.9 7.0 8.2 8.2 9.7
8.5 7.4 6.0 8.6 7.9 8.9 8.5 8.2 9.4 8.9 FS 6.7 6.8
8.9 9.0 8.8
8.1
8.4 7.2 8.4 7.5 FM 2 8.9 8.0 9.1 9.2 FS 9.6 9.2 8.8 9.0 8.3 7.6 FM 2 FS 9.0 8.0 8.4 FM 3 FS
7.3 7.4 6.9 6.3 7.5 6.6
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
20
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 9) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
MATERNAL DOSAGE;GROUP IV
1 .6 MG/KG/DAY
POSTPARTUM DAY 4 PRECULLING
7.8 6.6 8.2 7.7 7.1 7.6 MD 2 8.6 6.4 9.2 7.7 8.4 7.3 8.3 8.7 8.1 7.2 8.2 MD 3 6.6 8.0 NOT PREGNANT NOT PREGNANT 6.8 7.0 7.6 8.1 6.7 7.4 7.1 8.8 8.7 6.4 8.3 8.0 MD 2 9.5 9.0 10.4 9.5 7.1 6.4 9.5 9.5 NOT 1PREGNANT 7.8 MM 2 4.1 7.7 7.0 8.5 7.0 6.1 MD 3 MD 2 5.0 6.7 6.6 FM 3 4.7 5.0 5.2 MD 3 MD 2 MD 2 5.0 6.1 9.4 9.2 8.6 8.5 9.2 9.3 MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 7.1 8.3 7.1 8.4 8.6 8.5 8.6 7.0 7.9 8.2 7.0 MD 1 MD 1 MD 1 6.3 5.8 5.7 5.9 6.6 4.8 6.4 NOT :PREGNANT 5.8 6.2 6.9 6.2 6.5 7.0 MD 2 7.3 6.2 6.5 6.1 6.0 6.9 MD 4 MD 4 MD 4 MD 4 MD 4 MD 2 MM 2 MD 2 9.9 8.2 8.4 8.8 8.5 MS 9.5 MORIBUND SACRIFICED ON DAY 36 OF STUDY 8.9 7.3 8.4 MD 1 MD 1 7.6 8.0 6.2 7.3 8.5 6.2 8.7 6.4 8.9
MD 2 6.7 8.7
6.8 FM 2
8.6
5.6 FM 3
4.6 8.7 FM 2 MD 1 MD 1 MM 3
6.3 7.1 MD 1 9.3
FD 1 8.5
7.5 8.5 7.6
6.2 FD 1 MD 2
7.1 FD 2
4.7 8.9
MD 1 MD 1 MM 3
5.5 5.7 MS 8.3
FD 1 MD 2
7.9 8.5 7.3
7.3
MS
8.1 FD 2
4.8 7.7
MD 1 FD 1 MD 3
5.5 6.0 MD 1 FM 2
FD 1 MD 1
6.5 8.5 8.1
7.2
MS
FM 2 FD 2
4.3 7.7
7.4 FD 1 MD 2
5.5 6.7 FD 4 FS
FD 1 5.6
7.9
8.7
7.1
8.6
FD 2 FD 2 FM 4
8.4
6.9
4.9
FM 3 7.1
FD 4
FD 1 6.8
FM 3 FD 1
6.2 6.2 8.6
FD 3 FD 3 6.6 FD 1 4.8 5.9
FD 2 FD 3 FD 3 FD 1
8.3 7.0
5.9
FD 2 FD 1
5.9 FD 1
6.2
FM 2
FD 2 FM 3 FD 1
FS
FD 2 FD 3
)
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008: PAGE C-154
000440
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 10) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
POSTPARTUM DAY 4 PRECULLING
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
MD 1 MD 1 MD i MD 1 MS MS MD 1 MS FS
NOT PREGNANT MD 2 MD 2 MD 2 MM 2 MD 2 MD 2
MS FD 1 FD 1 NOT PREGNANT MS MD 1 MD 1 MD 2 MD 2 MD 2 NOT PREGNANT MD 2 MD 2 MD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MS MS MS MM 2 MM 2 MM 2 MS MS MS MS MS FD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MM 2 MM 2 MM 2 NOT PREGNANT MM 2 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1
MD i MS
FD 1
MM 2 MD 2 FD 1
MD 1 MD 2
MD 2 MS
MD 2 FD 1 MM 2
PS FM 2 FD 1 MD 2 MM 2
MD 1 MD 1 MD 1
FD 1 MS
FD 1
MS MD 2 FD 1
MD 1 MD 2
MD 1 MS
MD 2
MD 2 FS
FD 1 FM 1 MD 2 MD 2
MD 1 MS
MD 1
FD 1 FD 1
MS MD 2
FS
FS MD 2
MS MS MM 2
MD 2 FS
FD 1
MS MD 2
MD 1 MS
MD 1
FD 2 FM 2
FD 1 MD 1
MS MS MS
MD 2 FS FS
FD 2 MD 2
MS FD 1 FD 1
FD 2 FM 2
FD 1 FD 2
FD 2 FD 1 FD 2
MD 2 FS FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD i FD 2
FD 2 FS
FD 2
MM 1 UU FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 2
FD 2 FS
FD 2
MS
FS
FD 2 FM 2
FD 1 FD 1 FD 1
FM 2 FD 2
FD 2 FD 2
FS FM 2 FM 2
FS FD 2 FD 1
FS FD 1
FS FD 2
FD 2 FD 1
FS FD 1 FD 2
FD 2
FD 1
FD 1 FS FS FS
FM 1
FD 2
FS FD 1
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008PAGE C-155
000441
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295 9)
TABLE C36 (PAGE 11): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP # 1 2 3 4 S 6 7 8 9 10 11 12 13 14 15 16 17 IB 19
RAT/ LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 4 POSTCULLING
8801 8803 B804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8821 8823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
MC 4 10.8 10.0 8.3 10.1 MC 4
MC 4 9.3 MC 4 7.5 6.5 7.7
MC 4 MC 4 MC 4 10.0 10.5 9.1 11.3 MC 4 11.1 10.2 10.7 10.9 10.4 10.1 10.0 MC 4 12.6 12.1 NOT 1PREGNANT NOT 1PREGNANT 11.4 10.5 11.1 MC 4 9.7 10.1
9.7 9.2 9.7 MC 4 8.9 MC 4
8.6 8.7 8.3 8.7 MC 4 8.8 9.0 9.3 MS MC 4 8.4 MC 4 MC 4 MC 4 MC 4 9.6 MC 4 MC 4 9.8 MC 4 9.4 9.8 MC 4 9.9 9.3 8.5 8.5
9.8 10.0 10.3
7.0 9.2 10.0 11.9 9.3 FC 4 MC 4
10.8 MC 4 MC 4 MC 4 MC 4
9.0 8.6 MC 4 MC 4 8.4 9.0 MC 4 8.6
9.6 MC 4 10.4
7.2 MC 4
9.2 MC 4 FC 4
9.5 12.9
FC 4 9.5
MC 4 8.7 8.8 9.1 9.3
MC 4 8.5 8.5 9.0
10.0 7.7
10.1 11.4
9.9 FC 4 10.6 10.3 12.1 FC 4
9.8 12.6
10.4 9.9
MC 4 MC 4 FC 4
8.1 8.9 MC 4 MC 4 7.7 MC 4 9.8 FC 4
MS MC 4
9.6 FC 4 10.1 FC 4 11.5 FC 4
9.3 MC 4
10.8 MC 4
9.6 7.1 FC 4 FC 4 FC 4 9.1 8.8 8.4 MC 4 MS FC 4
10.1 MS
FC 4 FC 4
9.9 9.6 11.5 FC 4 FC 4 12.0
FC 4 MC 4
9.1 MC 4
7.8 FC 4
9.4 8.8 8.0 FC 4 MC 4 FC 4 FC 4
9.3 FC 4 FC 4 FC 4
9.2 10.0 11.0 FC 4 FC 4 FC 4
FC 4 9.5
FC 4 8.7 8.6
FC 4 FC 4
9.1 MC 4
7.7 FC 4 FC 4 MC 4
9.9 10.2 10.2 FC 4
9.0 FS FC 4 FC 4 9.3 11.4
10.2 9.7 9.4 6.7 8.6 8.2
FC 4 MC 4
8.2 FC 4
8.8 9.3 MC 4
11.3 FC 4 FC 4 FC 4
FC 4 9.9
10.1 12.5
FC 4 FC 4
9.2 FC 4
8.5 8.3 8.9 MC 4 7.5 FC 4 7.7 9.6 MC 4
10.4 9.6 6.3 9.2
11.4 FC 4 FC 4 FC 4
10.7 8.9 9.0 7.8
FC 4 FC 4 FC 4 FC 4
7.8 FC 4
8.5 FC 4
8.2
10.9 FC 4
6.7 8.9
FC 4
11.9
9.4
8.6 FC 4 FC 4
8.6 8.7 8.1 FC 4 FC 4 9.4 MC 4
FC 4 6.9
9.7
FM 2 8.4 7.6 FS 8.0
FC 4 FC 4
8.7 8.6 8.4
9.5 FC 4
FC 4
FC 4
FS 8.5 8.4 FC 4 FD 1 FU MC 4
FM 4 9.9
9.0 8.9 FU 8.8
FD 1 10.8
8.5 UU
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
20
418-008:PAGE C-156
000442
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 12): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP It 1 2 3 4 5 6 7 B 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
POSTPARTUM DAY 4 POSTCULLING
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865 8866 8867 8868 8869 8870
MC 4 MC 4
9.1 9.3 10.0 MC 4 9.4 8.4 8.7 10.1 MC 4 8.4 8.9 9.5 10.6 MC 4 9.4 MC 4 9.8 MC 4 MC 4 11.1 10.4 8.4 9.9
8.6 MC 4 MC 4 MC 4 10.4 MC 4
9.8 8.2 8.1 MC 4 MC 4 MC 4 MC 4 MC 4
11.5 9.7
MC 4 9.2 8.5 8.5 7.2
11.2 10.1
8.8 10.3
MC 4 MC 4
8.7 9.4 9.7 9.3 MC 4 MC 4 8.7 10.1 8.5 8.8 9.0 MC 4 MS MC 4 9.8 MC 4 8.5 8.6 MC 4 MC 4 MC 4 MC 4 10.2
8.4 MC 4 MC 4
9.2 FC 4 MC 4
9.6 MC 4
9.4 10.2 MC 4 MC 4
9.1 MC 4 FC 4 MC 4 MC 4 MC 4
9.8 MC 4
7.3 10.4 10.5 MC 4 10.3
8. 2 8. 7 8. 7 9. 3 MD 1 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 9. 6 8. 7 MC 4 FC 4 10. 4 MC 4 MC 4 MC 4 MC 4 MC 4 11,.1 MC 4 MC 4 MC 4
MC 4 MC 4 MC 4 FC 4 FC 4
9.8 MC 4 MC 4 FC 4
9.6 7.8 9.7 8.1 9.4 9.7 9.5 10.1 MC 4 9.0 MC 4 MC 4 9.3 MC 4 MC 4 9.0
8.6 8.3 MC 4 FC 4 10.8 9.0 MC 4 MC 4 FC 4 9.6 MC 4 MC 4 FC 4 8.8 9.8 9.4 9.6 MC 4 8.6 MC 4 8.1 FC 4 10.3 MC 4 FC 4
MC 4 MC 4 MC 4 FC 4 FC 4
8.8 MC 4
8.4 FC 4
9.5 7.6 MC 4 8.9 MC 4 10.0 FC 4 8.8 10.1 8.7 9.3 MC 4 8.9 MD 2 MC 4 FC 4
MC 4 MC 4
9.4 9.5 10.2 9.0 10.1 MC 4 7.4 9.0 MC 4 FC 4 FC 4 8.3 10.8 8.6 FC 4 MC 4 FC 4 8.3 8.1 7.8 9.0 9.1 9.8
MC 4 7.7 9.7 8.6
10.0 FC 4
9.2 7.5 FC 4 9.9 MC 4 8.9 FC 4 8.8 10.6 8.6 FC 4 10.4 8.8 MC 4 FC 4 8.5 FC 4 8.4 8.9
FC 4 MC 4
8.8 8.7 10.5 FC 4 9.6 7.5 8.2 UU 7.8 10.0 9.0 FC 4 9.9 9.7 10.1 MC 4
8.0 7.6 FC 4 9.5 MC 4 9.4
8.3 8.4 8.2 7.9 9.4 FC 4 9.0 FC 4 7.9 UU MC 4 8.1 FC 4 8.5
FC 4 9.8 8.8
8.6 7.7 FC 4 FC 4 8.2
8.3 8.4 FC 4 FC 4 FD 2 9.1 FC 4 FC 4 8.6
MC 4 9.5 8.4 8.0
FC 4 FC 4
9.0
8.0 8.3 FC 4 8.8 FC 4
7.9 FC 4
9.3 FC 4
8.9 9.4 7.5 FC 4
7.9 FC 4 FC 4
8.8
FC 4 10.1
9.2
8.6 FC 4
8.8 9.4
FC 4 7.6
FC 4 8.1 7.2
FD 1 7.4
FC 4 FC 4
8.8 9.4
FC 4
7.6
FC 4 FC 4
7.2 FC 4
8.1 7.4 7.8
7.6 7.9 FM 4 8.4
FS
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-157
000443
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 13) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP H 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP III
0 .4 MG/KG/DAY
POSTPARTUM DAY 4 POSTCULLING
8871 8872 8874a 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899a 8900 8901 8902 8903 8904 8905
NOT PREGNANT 8.3 MC 4 7.9
MC 4 MC 4 10.0 MC 4 10.1 9.4 13.6 12.6 13.0
9.9 8.3 7.9 MC 4 MC 4 MC 4 MC 4 MC 4 10.0 MC 4 MC 4 MC 4 10.9 MC 4 9.8 10.0 MC 4 MC 4
9.2 9.0 MC 4 MC 4 8.3 MC 4 11.8 11.3 11.3 MC 4 7.9 MC 4 MC 4 9.9 9.4
9.4 8.7 MC 4 9.5 MC 4 9.3 8.0 MC 4 MC 4 8.9 9.8 9.0 9.1 9.4 8.9 8.6 MC 4 7.6 NOT PREGNANT NOT PREGNANT 8.0 MC 4 8.6
9.3 9.1 MC 4 MD 1 MC 4 8.7 MC 4 MC 4 10.1 9.3 MC 4 MC 4
7.3 MC 4
9.8 9.3 9.8 8.8 8.9 7.6
8.4
9.0 MC 4 MC 4 12.7
8.5 8.1 MC 4 7.0 10.1 9.7 8.9 8.6
7.6 9.0 8.9 9.6 8.9 MC 4 MC 4 MC 4
MC 4
MC 4 MC 4
9.3 14.1
7.6 9.4 9.6 7.3 FC 4 8.9 10.0 8.6
MC 4 MC 4 FC 4 MC 4 MC 4 MC 4 MC 4
8.1
MC 4
MC 4 9.6
MC 4 11.4 FC 4 MC 4
9.4 7.6 FC 4 FC 4 FC 4 MC 4
MC 4 9.1
FC 4 MC 4
9.1 FC 4 FC 4 MC 4
8.2
MC 4 MC 4
9.7
FC 4 9.3 9.5 7.0
10.3 FC 4 FC 4
8.5
8.2 MC 4
9.3 MC 4
8.1 9.1 9.2 FC 4
MC 4
MS MC 4 MC 4
FC 4 FC 4
MS MC 4 10.0 FC 4
8.8 7.9
MC 4 8.8 8.6 8.7 9.0
FC 4 8.6 7.4
FC 4
8.9 9.5 9.8
7.8 8.4 9.1 7.7 10.0 9.3 8.9 7.7
7.5 FC 4
8.1 9.3 FC 4 9.1 8.7 7.9
7.3
9.4 7.7 FC 4 8.7 8.5 FC 4 8.9 10.2 9.7
6.7 FC 4 FC 4
7.2 FC 4
9.8 8.3 7.1
FC 4 9.3 8.8 7.0
10.0 9.1 9.3 7.9
FC 4 FC 4 FC 4
6.7
FC 4
FC 4
8.1 FC 4 FC 4
8.5 8.3 8.6 8.5 7.7
FC 4 8.6
FC 4 8.7
FC 4 FC 4 FC 4
7.4
8.4 8.9 9.1 FS FC 4 8.3 FC 4 FC 4
FC 4 FC 4 FC 4
7.9 8.2 8.2
7.4 8.6 9.4 FC 4
FC 4 8.9
8.9 FS
FC 4 8.8
FC 4 8.0
FC 4
8.4 FC 4
FC 4 FC 4 9.0 FC 4 FM 2 FS
FC 4 FM 3 FS
FC 4 6.9 6.3
FC 4 FM 2
7.5
FC 4
FM 3
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. A sexing error was found prior to weighing on day 7 postpartum for litter 8874; values for day 4 postpartum postculling were
excluded from group averages and statistical analyses.
418-008PAGE C-158
0C0444
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 14): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER ft
MATERNAL DOSAGE GROUP IV
i .6 MG/KG/DAY
POSTPARTUM DAY 4 POSTCULLING
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 B940
MC 4 MC 4 8.2 7.7 7.1 7.6 MD 2 8.6 8.4 9.2 7.7 8.4 FC 4 8.3 8.7 8.1 7.2 8.2 MD 3 FC 4 8.0
NOT PREGNANT NOT 1PREGNANT MC 4 MC 4 7.6 8.1 6.7 7.4 MC 4
8.8 8.7 8.4 8.3 8.0 MD 2 9.5 9.0 10.4 9.5 MC 4 MC 4 9.5 9.5 NOT :PREGNANT 7.8 MM 2 FC 4 7.7 7.0 8.5 7.0 6.1 MD 3 MD 2 5.0 6.7 6.6 FM 3 4.7 5.0 5.2 MD 3 MD 2 MD 2 5.0 MC 4 9.4 9.2 8.6 MC 4 9.2 MC 4 MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 MC 4 8.3 MC 4 8.4 8.6 8.5 8.6 7.0 7.9 8.2 7.0 MD 1 MD 1 MD 1 6.3 MC 4 MC 4 MC 4 6.6 4.8 6.4 NOT PREGNANT MC 4 6.2 6.9 MC 4 6.5 7.0 MD 2 7.3 MC 4 MC 4 6.1 6.0 6.9 MD 4 MD 4 MD 4 MD 4 MD 4 MD 2 MM 2 MD 2 9.9 8.2 8.4 8.8 8.5 MS 9.5 MORIBUND SACRIFICED ON DAY 36 OF STUDY 8.9 7.3 8.4 MD 1 MD 1 7.6 8.0 MC 4 MC 4 8.5 MC 4 8.7 MC 4 8.9
MD 2 FC 4
B. 7
MC 4 FM 2
8.6
5.6 FM 3
4.6 8.7 FM 2 MD 1 MD 1 MM 3
6.3 7.1 MD 1 9.3
FD 1 8.5
7.5 8.5 7.6
MC 4 FD 1 MD 2
7.1 FD 2
4.7 8.9
MD 1 MD 1 MM 3
5.5 FC 4
MS 8.3
FD 1 MD 2
7.9 FC 4 FC 4
MC 4
MS
8.1 FD 2
4.8 FC 4
MD 1 FD 1 MD 3
5.5 6.0 MD 1 FM 2
FD 1 MD 1
6.5 7.9 8.5 8.1 FC 4
7.2 7.1
MS 8.6
FM 2 FD 2
4.3 7.7
FD 2 FD 2 FM 4
8.4
7.4 FD 1 MD 2
6.9 4.9
5.5 6.7 FD 4 FS
FM 3 7.1
FD 4
FD 1 FD 1 FC 4 6.8
FM 3
6.2 8.6
FD 3 6.6 4.8
FD 2 FD 3 FD 1
8.3
FD 1
6.2
FD 3 FD 1
5.9 FD 3
7.0
FC 4
FD 2 FD 1
5.9 FD 1
6.2
FM 2
FD 2 FM 3 FD 1
FS
FD 2 FD 3
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN. U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008-.PAGE C-159
000445
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE IS): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP H 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER tt
MATERNAL DOSAGE GROUP V
3 .2 MG/KG/DAY
POSTPARTUM DAY 4 POSTCULLING
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
MD 1 MD 1 MD 1 MD 1 MS MS MD 1 MS FS
NOT PREGNANT MD 2 MD 2 MD 2 MM 2 MD 2 MD 2
MS FD 1 FD 1 NOT PREGNANT MS MD 1 MD 1 MD 2 MD 2 MD 2 NOT PREGNANT MD 2 MD 2 MD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MS MS MS MM 2 MM 2 MM 2 MS MS MS MS MS FD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MM 2 MM 2 MM 2 NOT PREGNANT MM 2 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1
MD 1 MS
FD 1
MM 2 MD 2 FD 1
MD i MD 2
MD 2 MS
MD 2 FD 1 MM 2
FS FM 2 FD 1 MD 2 MM 2
MD 1 MD i MD i
FD 1 MS
FD 1
MS MD 2 FD 1
MD 1 MD 2
MD 1 MS
MD 2
MD 2 FS
FD 1 FM 1 MD 2 MD 2
MD 1 MS
MD 1
FD 1 FD 1
MS MD 2
FS
FS MD 2
MS MS MM 2
MD 2 FS
FD 1
MS MD 2
MD 1 MS
MD 1
FD 2 FM 2
FD 1 MD 1
MS MS MS
MD 2 FS FS
FD 2 MD 2
MS FD 1 FD 1
FD 2 FM 2
FD 1 FD 2
FD 2 FD 1 FD 2
MD 2 FS FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 1 FD 2
FD 2 FS
FD 2
MM 1 UU FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 2
FD 2 FS
FD 2
MS
FS
FD 2 FM 2
FD 1 FD 1 FD 1
FM 2 FD 2
FD 2 FD 2
FS FM 2 FM 2
FS FD 2 FD 1
FS FD 1
FS FD 2
FD 2 FD 1
FS FD 1 FD 2
FD 2
FD 1
FD 1 FS FS FS
FM 1
FD 2
FS FD 1
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008PAGE C-160
000446
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 16): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP (t
12
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 7
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8821 8823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
MC 4 16.1 15.1 17.3 15.2 MC 4 MC 4 14.8 MC 4 10.5 10.1 10.5 MC 4 MC 4 MC 4 15.6 13.5 14.5 17.8 MC 4 17.8 16.1 17.0 15.0 16.0 15.4 15.6 MC 4 20.0 20.3 NOT PREGNANT NOT PREGNANT 16.9 17.5 16.9 MC 4 15.2 16.3 14.8 15.2 15.4 MC 4 14.9 MC 4 14.4 13.8 13.3 10.9 MC 4 11.5 15.1 14.0 MS MC 4 15.0 MC 4 MC 4 MC 4 MC 4 14.6 MC 4 MC 4 16.5 MC 4 16.6 16.0 MC 4 15.1 16.0 14.9 14.4
15.3 -14.6 12.7 MC 4 13.2 15.5
9.3 9.7 16.4 MC 4 13.7 15.0 16.9 MC 4 16.5 FC 4 FC 4 14.6 MC 4 20.0
15.9 MC 4 MC 4 MC 4 MC 4 13.0 14.9 MC 4 MC 4 13.6 16.0 MC 4 14.2
FC 4 16.3 MC 4 10.8 14.1 11.4 14.8 MC 4 13.4 13.7 17.2 15.5 15.0
15.2 15.9 15.5 FC 4 15.3 14.8 17.9 FC 4 15.4 20.3
16.6 16.7 MC 4 MC 4 FC 4 11.0 14.3 MC 4 MC 4 15.7 MC 4 15.5 FC 4
MS MC 4 15.5 FC 4 14.5 FC 4 16.3 FC 4 14.2 MC 4
16.2 MC 4 14.0 14.0 FC 4 FC 4 FC 4 14.1 14.1 14.4 MC 4
MS FC 4
14.9 MS
FC 4 FC 4 15.9 14.2 17.5 FC 4 FC 4 18.0
FC 4 MC 4 14.9 MC 4 12.3 FC 4 14.6 14.7 13.9 FC 4 MC 4 FC 4 FC 4
15.6 FC 4 FC 4 FC 4 14.6 14.7 17.0 FC 4 FC 4 FC 4
FC 4 15.4 FC 4 14.7 13.7 FC 4 FC 4 14.4 MC 4 13.8 FC 4 FC 4 MC 4
14.3 15.4 13.6 FC 4 14.7
FS FC 4 FC 4 15.6 18.8
16.6 14.8 13.5 13.6 14.2 11.4 FC 4 MC 4 13.6 FC 4 14.1 14.9 MC 4
15.4 FC 4 FC 4 FC 4
FC 4 17.0 14.4 19.3
FC 4 FC 4 14.7 FC 4 13.3 10.5 13.9 MC 4 13.6 FC 4 14.2 14.8 MC 4
17.5 14.5 10.3 14.0
17.5 FC 4 FC 4 FC 4
17.0 15.8 14.6 12.8 FC 4 FC 4 FC 4 FC 4 13.0 FC 4 15.0 FC 4 13.9
16.7 FC 4
8.7 13.6
FC 4
19.2
15.1
10.7 FC 4 FC 4 13.7 14.3 12.6 FC 4 FC 4 15.0 MC 4
FC 4 8.6
16.1
FM 2 13.4 11.6
FS 13.6 FC 4 FC 4 15.6 13.7 13.3
15.2 FC 4
FC 4
FC 4
FS 14.7 13.3 FC 4 FD 1
FU MC 4
FM 4 14.9
12.8 14.9
FU 14.0
FD 1 15.4
15.0 uu
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-161
ooo
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 17): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
pup * 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
RAT/ LITTER 0
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
POSTPARTUM DAY 7
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865 8866 8867 8868 8869 8870
MC 4 MC 4 15.7 14.6 13.7 MC 4 14.4 13.0 13.2 14.4 MC 4 16.2 15.0 13.7 17.4 MC 4 16.0 MC 4 15.8 MC 4 MC 4 17.8 16.3 13.0 17.8
13.4 MC 4 MC 4 MC 4 14.6 MC 4 15.5 12.9 13.2 MC 4 MC 4 MC 4 MC 4 MC 4 17.7 16.0 MC 4 14.1 12.5 14.2 10.8 16.9 15.8 14.3 16.9
MC 4 MC 4 14.3 14.3 13.3 13.7 MC 4 MC 4 15.2 15.2 12.3 16.1 14.2 MC 4
MS MC 4 15.5 MC 4 13.7 15.9 MC 4 MC 4 MC 4 MC 4 17.2
13.9 MC 4 MC 4 14.6 FC 4 MC 4 14.8 MC 4 13.8 15.5 MC 4 MC 4 15.2 MC 4 FC 4 MC 4 MC 4 MC 4 14.4 MC 4 11.8 17.6 16.6 MC 4 17.4
13 .8 11. 4 15. 0 14 ,5 MD 1 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 14 .8 13 .9 MC 4 FC 4 16. 2 MC 4 MC 4 MC 4 MC 4 MC 4 17. 6 MC 4 MC 4 MC 4
MC 4 MC 4 MC 4 FC 4 FC 4 13.6 MC 4 MC 4 FC 4 15.6 13.2 14.4 14.1 14.7 15.0 15.4 15.4 MC 4 14.8 MC 4 MC 4 12.3 MC 4 MC 4 15.7
14.5 13.6 MC 4 FC 4 13.8 14.7 MC 4 MC 4 FC 4 14.8 MC 4 MC 4 FC 4 15.1 15.2 15.7 16.4 MC 4 14.2 MC 4 10.6 FC 4 15.8 MC 4 FC 4
MC 4 MC 4 MC 4 FC 4 FC 4 15.1 MC 4 13.6 FC 4 14.4 13.9 MC 4 13.4 MC 4 16.3 FC 4 15.7 16.3 14.4 13.5 MC 4 14.1 MD 2 MC 4 FC 4
MC 4 MC 4 14.4 13.6 13.0 12.4 14.5 MC 4 13.4 14.3 MC 4 FC 4 FC 4 13.8 16.6 15.3 FC 4 MC 4 FC 4 14.2 10.9 15.2 15.2 14.2 15.7
MC 4 12.9 15.6 13.8 14.4 FC 4 14.3 12.4 FC 4 15.5 MC 4 13.0 FC 4 12.9 16.6 13.8 FC 4 16.3 14.4 MC 4 FC 4 14.7 FC 4 13.5 15.3
FC 4 MC 4 15.1 14.4 14.5 FC 4 14.6 12.6 12.6
uu
12.8 15.1 14.6 FC 4 15.1 13.6 14.4 MC 4
14.0 11.7 FC 4 14.5 MC 4 14.8
13.5 13.5 13.5 13.8 14.4 FC 4 14.3 FC 4 12.3
UU
MC 4 16.1 FC 4 14.3
FC 4 16.3 15.1
12.6 9.7
FC 4 FC 4 14.7
12.5 12.6 FC 4 FC 4 FD 2 13.4 FC 4 FC 4 11.5
MC 4 14.5 13.5 14.1
FC 4 FC 4 12.6
13.5 11.4 FC 4 14.3 FC 4
12.4 FC 4 14.3 FC 4
14.1 14.4 11.9 FC 4
12.8 FC 4 FC 4 13.8
FC 4 16.1 14.9
13.7 FC 4
15.0 12.9
FC 4 12.6 FC 4 13.5 12.3 FD 1 12.6 FC 4 FC 4 13.9 15.4
FC 4
12.9
FC 4 FC 4
12.2 FC 4
13.4 10.8 12.2
13.5 12.6 FM 4 13.0
FS
13.5 FC 4
FD 1 13.0
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
20
418-008:PAGE C-162
0C0448
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 18): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM INDIVIDUAL DATA - FI GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
RAT/ LITTER !f
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
POSTPARTUM DAY 7
8871 8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899 8900 8901 8902 8903 8904 8905
NOT PREGNANT 14.1 MC 4 12.7 MC 4 MC 4 15.3 MC 4 16.0 14.8 19.1 17.9 16.3 15.7 13.6 13.4 MC 4 MC 4 MC 4 MC 4 MC 4 15.3 MC 4 MC 4 MC 4 15.2 MC 4 14.9 14.1 MC 4 MC 4 14.0 15.2 MC 4 MC 4 14.0 MC 4 16.1 17.9 16.6 MC 4 12.9 MC 4 MC 4 14.1 13.9 14.5 15.0 MC 4 13.8 MC 4 13.9 12.5 MC 4 MC 4 14.6 14.7 15.8 13.2 8.5 9.2 12.9 MC 4 13.1 NOT PREGNANT NOT PREGNANT 13.5 MC 4 14.8
14.6 14.5 MC 4 MD 1 MC 4 14.0 MC 4 MC 4 14.3 13.5 MC 4 MC 4
12.7 MC 4 15.6 14.2 14.4 15.0 12.5 14.7
14.2
12.9 MC 4 MC 4 17.5 13.7 13.1 MC 4 12.4 14.1 15.2 13.8 13.8
13.0 14.5 14.2 14.2 15.5 MC 4 MC 4 MC 4
MC 4
MC 4 MC 4 14.8 19.8 10.9 13.5 15.7 12.7 FC 4 15.6 14.0 14.2
MC 4 MC 4 FC 4 MC 4 MC 4 MC 4 MC 4 13.6
MC 4
MC 4 16. 1 MC 4 15. 8 FC 4 MC 4 15. 5 11. 9 FC 4 FC 4 FC 4 MC 4
MC 4 14 .4 FC 4 MC 4 13 .9 FC 4 FC 4 MC 4
12 .8
MC 4 MC 4 14.9
FC 4 12.4 14.8 11.9 14.5 FC 4 FC 4 14.3
11.9 MC 4 14.9 MC 4 14.8 14.9 12.4 FC 4
MC 4
MS MC 4 MC 4
FC 4 FC 4
MS MC 4 14.3 FC 4 13.9 11.2
MC 4 12.7 13.7 13.0 14.7 FC 4 12.6 12.3
FC 4
14.0 14.2 14.8
12.5 14.5 14.5 10.7 14.3 13.7 13.9 12.8
12.1 FC 4 14.0 13.1 FC 4 14.5 10.0 12.3
12.6
12.5 15.5 15.5
12.8 FC 4 FC 4 11.8 FC 4 14.3 12.5 13.5
13.2 FC 4 FC 4 14.1 14.9 14.0 10.0 12.3
FC 4
11.9 13.1 14.0
FC 4 13.5 15.7 12.8 13.9 15.1 13.6 13.0
FC 4 13.8 FC 4 13.5 FC 4 FC 4 FC 4 12.9
FC 4
FC 4 FC 4 14 .7
FC 4 FC 4 FC 4 12. 1
FC 4
FC 4
12. 8 13 .2 12..9
FS FC 4 15,.0 FC 4 FC 4
FC 4
13.7 13.7
11.9 12.7 14.6 FC 4
FC 4
FC 4 13.9 FC 4
FC 4 FC 4
FC 4
FC 4
13.1
FC 4 15.0 13.5
13.4
FC 4 FM 2 FM 3 13.3
12.8 FS
FC 4
12.9 FS FS
12.8
ALL WEIGHTS WERE RECORDED IN GRAMS (G) . FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
18 19 ' 20 FC 4 FM 3
418-008:PAGE C-163
000449
PROTOCOL 418-006: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 19) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP It
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER K
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
POSTPARTUM DAY 7
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
MC 4 MC 4 11.9 12.8 11.7 11.2 MD 2 12.0 12.7 13.6 13.3 13.2 FC 4 12.8 12.3 11.6 12.1 10.3 MD 3 FC 4 11.2 NOT 1PREGNANT NOT !PREGNANT
MC 4 MC 4 11.5 12.0 12.3 11.2 MC 4 11.4 11.3 11.2 10.9 11.6 MD 2 13.4 12.7 14.0 12.8 MC 4 MC 4 13.2 13.0 NOT PREGNANT 11.5 MM 2 FC 4 11.9 10.5 8.2 10.6
8.5 MD 3 MD 2 9.3 6.9 8.8 FM 3 MD 5 MD 5 MD 5 MD 3 MD 2 MD 2 6.5 MC 4 13.7 13.0 13.1 MC 4 13.0 MC 4 MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 MC 4 12.6 MC 4 13.1 12.8 13.2 13.3 10.2 11.9 11.9 9.7 MD 1 MD 1 MD 1 10.5 MC 4 MC 4 MC 4 7.8 8.3 10.1 NOT PREGNANT MC 4 9.3 10.7 MC 4 9.9 10.7 MD 2 11.3 MC 4 MC 4 9.6 9.6 10.5 MD 4 MD 4 MD 4 MD 4 MD 4 MD 2 MM 2 MD 2 13.1 12.8 13.0 12.2 13.1 MS 11.9 MORIBUND SACRIFICED ON DAY 36 OF STUDY 11.7 10.2 12.4 MD 1 MD 1 10.9 10.5 MC 4 MC 4 14.2 MC 4 13.2 MC 4 13.8
MD 2 FC 4 12.2
MC 4 FM 2 13.7
12.2 FM 3
6.1 12.8 FM 2 MD 1 MD 1 MM 3
8.1 9.2 MD 1 12.2
FD 1 13.8
12.4 12.6 11.7
MC 4 FD 1 MD 2
11.2 FD 2 FD 5 12.1
MD 1 MD 1 MM 3
8.4 FC 4
MS 11.3
FD 1 MD 2
11. 5 FC 4 FC 4
MC 4
MS
9.,8 FD 2 FM 5 FC 4
MD 1 FD 1 MD 3
8,.1 10,.6 MD 1 FM 2
FD 1 MD 1
11.6 13.1 12.3
11.4
MS
FM 2 FD 2 FM 5 11.4
9.8 FD 1 MD 2
9.5 10.7 FD 4
FS
FD 1 FC 4
10.1
FC 4
11.1
11.9
FD 2 FD 2 FM 4 13.2
9.7
9.5
FM 3 11.5 FD 4
FD 1 9.8
FM 3
9.3 12.4
FD 3 11.3
9.2 FD 2 FD 3 FD 1 13.8
FD 1
9.5
FD 3 FD 1
8.1 FD 3 10.4
FC 4
FD 2 FD 1
8.1 FD 1 10.a
FM 2
FD 2 FM 3 FD 1
FS
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE. S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-164
000450
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 20): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP #
12
3 4 5 6 7 8 9 10 11 12 li 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
POSTPARTUM DAY 7
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
MD 1 MD 1 MD 1 MD 1 MS MS MD 1 MS FS
NOT PREGNANT MD 2 MD 2 MD 2 MM 2 MD 2 MD 2
MS FD 1 FD 1 NOT PREGNANT MS MD 1 MD 1 MD 2 MD 2 MD 2 NOT PREGNANT MD 2 MD 2 MD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MS MS MS MM 2 MM 2 MM 2 MS MS MS MS MS FD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MM 2 MM 2 MM 2 NOT PREGNANT MM 2 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1
MD 1 MS FD 1
MM 2 MD 2 FD i
MD 1 MD 2
MD 2 MS
MD 2 FD 1 MM 2
FS FM 2 FD 1 MD 2 MM 2
MD 1 MD 1 MD 1
FD 1 MS
FD 1
MS MD 2 FD 1
MD 1 MD 2
MD 1 MS
MD 2
MD 2 FS
FD 1 FM 1 MD 2 MD 2
MD 1 MS
MD 1
FD 1 FD 1
MS MD 2
FS
FS MD 2
MS MS MM 2
MD 2 FS
FD 1
MS MD 2
MD 1 MS
MD 1
FD 2 FM 2
FD 1 MD 1
MS MS MS
MD 2 FS FS
FD 2 MD 2
MS FD 1 FD 1
FD 2 FM 2
FD 1 FD 2
FD 2 FD 1 FD 2
MD 2 FS FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 1 FD 2
FD 2 FS
FD 2
MM i UU FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 2
FD 2 FS
FD 2
MS
FS
FD 2 FM 2
FD 1 FD 1 FD 1
FM 2 FD 2
FD 2 FD 2
FS FM 2 FM 2
FS FD 2 FD 1
FS FD 1
FS FD 2
FD 2 FD 1
FS FD 1 FD 2
FD 2
FD 1
FD 1 FS FS FS
FM 1
FD 2
FS FD 1
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-165
000451
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6395.9)
TABLE C36 (PAGE 21): PUP BODY WEIGHTS FROM BIRTH TO DAY 2] POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP u
RAT/ LITTER ft
1 2 3 4 S 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 14
8801 8803 8804 8805 8807 8808 8611 8812 8813 8814 8817 8818 8819 8821 8823 8624 8826 8827 8828 8830 8831 8832 8833 8834 8835
MC 4 30.5 30.8 30.2 26.7 MC 4 MC 4 35.2 MC 4 27.5 28.6 27.4 MC 4 MC 4 MC 4 31.6 28.1 27.6 35.5 MC 4 36.1 35.7 35.8 34.0 30.8 30.2 29.7 MC 4 39.0 40.4 NOT iPREGNANT NOT 1PREGNANT 35.2 36.5 34.3 MC 4 30.8 30.9 31.1 30.0 30.9 MC 4 30.4 MC 4 29.5 27.4 28.9 22.6 MC 4 24.2 33.1 33.2 MS MC 4 29.5 MC 4 MC 4 MC 4 MC 4 32.4 MC 4 MC 4 34.2 MC 4 34.4 31.4 MC 4 30.8 34.6 33.3 33.4
31.7 31.1 34.6 26.8 34.7 29.2 35.4 36.3 FC 4 MC 4
32.1 MC 4 36.3 24.1 MC 4 29.4 MC 4 FC 4 27.4 40.9
34.3 MC 4 MC 4 MC 4 MC 4 25.2 31.8 MC 4 MC 4 28.6 33.0 MC 4 31.9
FC 4 32.1 MC 4 29.9 29.7 22.3 32.0 MC 4 33.0 30.4 34.6 31.2 29.7
31.5 31.1 32.9 FC 4 34.2 29.5 34.9 FC 4 28.3 39.0
MS MC 4 32.7 FC 4 32.7 FC 4 34.2 FC 4 29.9 MC 4
30.6 MS
FC 4 FC 4 34.5 27.6 33.8 FC 4 FC 4 38.8
29.5 FC 4 FC 4 FC 4 31.8 28.2 33.2 FC 4 FC 4 FC 4
30.3 28.6 33.5 FC 4 31.3
FS FC 4 FC 4 32.2 38.0
35.5 FC 4 FC 4 FC 4
FC 4 32.4 30.5 38.1
34.4 31.0 MC 4 MC 4 FC 4 24.1 31.7 MC 4 MC 4 30.8 MC 4 31.9 FC 4
33.4 MC 4 30.3 21.8 FC 4 FC 4 FC 4 30.2 31.2 29.6 MC 4
MS FC 4
FC 4 MC 4 30.2 MC 4 28.1 FC 4 32.0 28.7 32.9 FC 4 MC 4 FC 4 FC 4
FC 4 30.4 FC 4 31.2 28.4 FC 4 FC 4 31.1 MC 4 29.1 FC 4 FC 4 MC 4
34.2 30.9 30.4 21.7 27.3 23.8 FC 4 MC 4 30.8 FC 4 29.4 29.1 MC 4
FC 4 FC 4 29.8 FC 4 26.0 22.6 33.1 MC 4 32.2 FC 4 31.3 30.5 MC 4
34.1 33.0 24.0 31.9
34.6 FC 4 FC 4 FC 4
33.4 29.0 28.4 30.7 FC 4 FC 4 FC 4 FC 4 31.5 FC 4 31.1 FC 4 33.0
35.2 FC 4 23.9 32.5
FC 4
35.8
28.8
28.3 FC 4 FC 4 32.6 27.4 31.6 FC 4 FC 4 29.0 MC 4
FC 4 23.5
35.8
FM 2 29.4 19.5
FS 29.3 FC 4 FC 4 31.7 30.7 31.9
31.9 FC 4 FM 4
FC 4 35.7
FC 4
FS 29.1 31.8 FC 4 FD 1
FU MC 4
31.0
31.4
FU 31.4
FD 1 33.1
32.6 UU
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-166
o
tn
PROTOCOL 41S-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 22) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP ff
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP II
0 .1 MG/KG/DAY
POSTPARTUM DAY 14
8836 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865 8866 8867 8868 8869 8870
MC 4 MC 4 33.2 28.0 30.4 MC 4 26.9 28.3 29.6 31.0 MC 4 33.0 31.5 31.0 33.9 MC 4 34.6 MC 4 31.9 MC 4 MC 4 35.0 34.5 30.6 35.1
32.0 MC 4 MC 4 MC 4 29.7 MC 4 27.4 30.9 27.5 MC 4 MC 4 MC 4 MC 4 MC 4 34.5 28.2 MC 4 31.1 33.5 33.1 25.2 32.9 36.0 29.8 34.2
MC 4 MC 4 31.5 28.5 29.5 33.0 MC 4 MC 4 32.2 31.8 29.2 34.7 29.0 MC 4
MS MC 4 36.3 MC 4 32.0 31.0 MC 4 MC 4 MC 4 MC 4 34.0
30.7 MC 4 MC 4 29.9 FC 4 MC 4 26.7 MC 4 29.9 31.5 MC 4 MC 4 30.5 MC 4 FC 4 MC 4 MC 4 MC 4 28.1 MC 4 22.8 28.0 35.1 MC 4 35.6
32.8 29.3 32.7 28.3 MD 1 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 33.0 32.5 MC 4 FC 4 28.3 MC 4 MC 4 MC 4 MC 4 MC 4 34.3 MC 4 MC 4 MC 4
MC 4 MC 4 MC 4 FC 4 FC 4 31.6 MC 4 MC 4 FC 4 31.0 29.7 32.1 29.8 31.4 32.4 33.3 35.2 MC 4 32.2 MC 4 MC 4 24.1 MC 4 MC 4 31.7
32.7 31.5 MC 4 FC 4 29.6 30.8 MC 4 MC 4 FC 4 31.0 MC 4 MC 4 FC 4 32.6 30.5 35.7 36.0 MC 4 30.7 MC 4 21.6 FC 4 37.0 MC 4 FC 4
MC 4 MC 4 MC 4 FC 4 FC 4 30.7 MC 4 29.4 FC 4 30.3 29.1 MC 4 26.8 MC 4 30.2 FC 4 34.3 28.8 32.5 30.3 MC 4 32.4 MD 2 MC 4 FC 4
MC 4 MC 4 32.5 29.1 30.4 28.2 24.7 MC 4 28.2 31.3 MC 4 FC 4 FC 4 30.3 30.0 31.7 FC 4 MC 4 FC 4 30.7 26.6 32.0 33.3 31.8 32.0
MC 4 31.9 30.9 27.6 28.5 FC 4 24.7 28.7 FC 4 31.7 MC 4 33.6 FC 4 31.7 31.8 29.5 FC 4 32.5 30.9 MC 4 FC 4 31.2 FC 4 33.0 31.4
PC 4 MC 4 30.2 28.9 30.4 FC 4 25.8 26.8 26.5
uu 26.9 32.1 30.0 FC 4 34.0 28.5 34.7 MC 4
28.9 20.5 FC 4 31.7 MC 4 33.5
31.1 25.9 33.3 27.9 30.5 FC 4 25.7 FC 4 30.2
UU MC 4 28.5 FC 4 29.8
FC 4 33.5 32.9
30.8 23.3 FC 4 FC 4 28.4
32.2 28.9 FC 4 FC 4 FD 2 30.4 FC 4 FC 4 28.7
MC 4 30.8 28.0 30.2
FC 4 FC 4 30.4
28.6 26.9 FC 4 32.6 FC 4
29.9 FC 4 32.7 FC 4
30.9 26.4 29.3 FC 4
28.9 FC 4 FC 4 33.1
FC 4 34.7 31.0
30.4 FC 4
33.5 30.8
FC 4 30.2 FC 4 29.7 28.1 FD 1 28.7 FC 4 FC 4 26.2 28.1
FC 4
27.7
FC 4 FC 4
28.1 FC 4
27.9 26.5 28.6
32.8 30.3 FM 4 28.7
FS
30.1 FC 4
FD 1 29.0
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-167
000453
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 23) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
RAT/ LITTER It
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
POSTPARTUM DAY 14
8871 8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899 8900 8901 8902 8903 8904 8905
NOT ]PREGNANT 29.6 MC 4 31.2 MC 4 MC 4 30.4 MC 4 31.5 29.1 34.0 33.2 33.5 29.6 30.6 32.9 MC 4 MC 4 MC 4 MC 4 MC 4 31.6 MC 4 MC 4 MC 4 30.0 MC 4 29.9 31.5 MC 4 MC 4 26.5 28.9 MC 4 MC 4 31.6 MC 4 28.3 33.2 31.7 MC 4 29.5 MC 4 MC 4 34.1 32.6 32.6 32.4 MC 4 27.0 MC 4 26.3 33.8 MC 4 MC 4 33.2 31.7 31.8 22.4 24.2 26.9 33.2 MC 4 31.3 NOT PREGNANT NOT PREGNANT 35.1 MC 4 34.4
31.8 29.4 MC 4 MD 1 MC 4 30.8 MC 4 MC 4 31.0 31.4 MC 4 MC 4
28.8 MC 4 33.6 27.0 33.8 31.2 24.3 30.6
33.2
29.4 MC 4 MC 4 37.6 29.7 29.2 MC 4 27.6 31.5 30.8 28.3 26.0
29.2 34.2 32.6 25.9 29.8 MC 4 MC 4 MC 4
MC 4
MC 4 MC 4 29.3 31.9 26.5 29.9 31.5 27.4 FC 4 30.2 29.8 30.6
MC 4 MC 4 FC 4 MC 4 MC 4 MC 4 MC 4 32.3
MC 4
MC 4 28. 7 MC 4 31. 7 FC 4 MC 4 31..7 25. 4 FC 4 FC 4 FC 4 MC 4
MC 4 MC 4 29.5
FC 4 31.0 29.8 26.0 30.7 FC 4 FC 4 33.3
MC 4 28.8 32,.6 MC 4 FC 4 32.6 MC 4 .MC 4 31..8 MD13 FC 4 31.1 FC 4 23.9 MC 4 FC 4
31 .9 MC 4
MS MC 4 MC 4
FC 4 FC 4
MS MC 4 30.4 FC 4 27.2 16.7
MC 4 31.1 31.2 24.8 32.0 FC 4 28.8 30.9
FC 4
29.5 29.8 30.9
28.5 31.3 28.7 26.2 29.8 30.7 27.6 25.8
29.4 FC 4 31.4 26.6 FC 4 32.8 30.1 29.2
31.8
27.9 28.4 28.0
27.5 FC 4 FC 4 27.7 FC 4 28.9 28.7 27.7
28.3 FC 4 FC 4 26.8 32.9 30.8 24.1 30.3
FC 4
28.1 28.7 29.6
FC 4 31.1 29.7 26.3 29.8 31.2 27.5 19.8
FC 4 33.5 FC 4 24.4 FC 4 FC 4 FC 4 28.4
FC 4
FC 4 FC 4 29. 7
FC 4 FC 4 FC 4 23. 2
FC 4
FC 4
28 ,6 31 .8 30 ,9
FS FC 4 32 .0 FC 4 FC 4
FC 4
31.0 26.7
28.7 29.9 31.2 FC 4
FC 4
FC 4 30.9 FC 4
FC 4 FC 4
FC 4
FC 4
27.0
FC 4 32.7 31.9
26.2
FC 4 FM 2 FM 3 31.6
29.5 FS
FC 4
30.6 FS FS
29.6
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
18 19 20 FC 4 FM 3
418-008:PAGE C-168
000454
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 24): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP ft
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
MATERNAL DOSAGE GROUP IV
1 .6 MG/KG/DAY
POSTPARTUM DAY 14
MC 4 MC 4 26.0 28.3 27.6 25.5 MD 2 27.0 24.6 29.3 28.2 26.8 FC 4 25.7 26.1 22.4 24.3 25.5 MD 3 FC 4 24.6 NOT :PREGNANT NOT !PREGNANT MC 4 MC 4 26.4 26.9 28.3 26.7 MC 4 21.9 22.6 24.4 22.1 22.3 MD 2 24.4 25.8 27.3 26.5 MC 4 MC 4 25.6 26.9 NOT iPREGNANT 26.3 MM 2 FC 4 26.4 21.5 24.2 27.3 22.7 MD 3 MD 2 21.6 21.2 16.8 FM 3 MD 5 MD 5 MD 5 MD 3 MD 2 MD 2 15.5 MC 4 26.9 25.5 28.4 MC 4 25.6 MC 4 MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 MC 4 28.9 MC 4 28.5 30.0 28.3 28.4 27.1 24.0 23.4 26.8 MD 1 MD 1 MD 1 19.4 MC 4 MC 4 MC 4 23.1 23.5 17.3 NOT PREGNANT MC 4 22.9 23.5 MC 4 25.5 25.8 MD 2 21.7 MC 4 MC 4 23.1 25.7 26.0 MD 4 MD 4 MD 4 MD 4 MD 4 MD 2 MM 2 MD 2
28.3 27.2 29.5 27.6 28.6 MS 28.9 MORIBUND SACRIFICED ON DAY 36 OF STUDY 26.1 22.9 21.6 MD I MD 1 23.4 21.5 MC 4 MC 4 29.6 MC 4 33.2 MC 4 29.2
MD 2 FC 4 24.3
MC 4 FM 2 25.4
22.2 FM 3 13.8 25.7 FM 2 MD 1 MD 1 MM 3
23.3 23.5 MD 1 25.7
FD 1 30.8
26.4 27.5 25.2
MC 4 FD 1 MD 2
26.7 FD 2 FD 5 24.9
MD 1 MD 1 MM 3
20.8 FC 4
MS 25.7
FD 1 MD 2
28.1 FC 4 FC 4
MC 4
MS
FD10 FD 2 FM 5 FC 4
MD 1 FD 1 MD 3
21.0 22.7 MD 1 FM 2
FD 1 MD 1
24.4 28.5 26.1
25.9
MS
FM 2 FD 2 FM 5 26.7
24.0 FD 1 MD 2
20.9 26.2 FD 4
FS
FD 1 FC 4
25.7
FC 4
23.1
24.1
FD 2 FD 2 FM 4 24.4
27.7
22.3
FM 3 24.3 FD 4
FD 1 24.0
FM 3
24.2 26.4
FD 3 23.4 21.1 FD 2 FD 3 FD 1 24.3
FD 1
21.9
FD 3 FD 1 19.8 FD 3 23.9
FC 4
FD 2 FD 1 19.2 FD 1 29.4
FM 2
FD 2 FM 3 FD 1
FS
FD 2 FD 3
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008PAGE C-169
000455
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 25) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA FI GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
POSTPARTUM DAY 14
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
MD 1 MD 1 MD 1 MD 1 MS MS MD 1 MS FS
NOT PREGNANT MD 2 MD 2 MD 2 MM 2 MD 2 MD 2
MS FD 1 FD i NOT PREGNANT MS MD 1 MD i MD 2 MD 2 MD 2 NOT PREGNANT MD 2 MD 2 MD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MS MS MS MM 2 MM 2 MM 2 MS MS MS MS MS FD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MM 2 MM 2 MM 2 NOT PREGNANT MM 2 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1
MD 1 MS
FD 1
MM 2 MD 2 FD 1
MD 1 MD 2
MD 2 MS
MD 2 FD i MM 2
FS FM 2 FD 1 MD 2 MM 2
MD 1 MD 1 MD 1
FD 1 MS
FD 1
MS MD 2 FD 1
MD 1 MD 2
MD 1 MS
MD 2
MD 2 FS
FD 1 FM 1 MD 2 MD 2
MD 1 MS
MD 1
FD 1 FD 1
MS MD 2
FS
FS MD 2
MS MS MM 2
MD 2 FS
FD 1
MS MD 2
MD 1 MS
MD 1
FD 2 FM 2
FD 1 MD 1
MS MS MS
MD 2 FS FS
FD 2 MD 2
MS FD 1 FD 1
FD 2 FM 2
FD 1 FD 2
FD 2 FD 1 FD 2
MD 2 FS FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 1 FD 2
FD 2 FS
FD 2
MM 1 UU FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 2
FD 2 FS
FD 2
MS
FS
FD 2 FM 2
FD 1 FD 1 FD 1
FM 2 FD 2
FD 2 FD 2
FS FM 2 FM 2
FS FD 2 FD 1
FS FD 1
FS FD 2
FD 2 FD 1
FS FD 1 FD 2
FD 2
FD 1
FD 1 FS FS FS
FM 1
FD 2
FS FD 1
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-170
000456
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 26) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER II
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 21
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8821 8B23 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
MC 4 47.1 47.4 49.5 43.0 MC 4 MC 4 53.7 MC 4 47.6 47.6 45.9 MC 4 MC 4 MC 4 46.3 53.2 47.6 59.0 MC 4 60.0 58.4 56.3 59.5 52.4 50.3 50.2 MC 4 64.0 68.0 NOT 1PREGNANT NOT IPREGNANT 51.0 56.6 54.7 MC 4 51.9 50.3 48.0 51.0 51.0 MC 4 47.0 MC 4 43.0 43.0 45.0 42.4 MC 4 42.8 53.0 52.1 MS MC 4 54.3 MC 4 MC 4 MC 4 MC 4 48.7 MC 4 MC 4 53.4 MC 4 56.7 47.0 MC 4 47.0 50.0 54.0 51.0
47.0 56.5 55.8 45.4 53.0 48.6 58.0 57.7 FC 4 MC 4
52.3 MC 4 MC 4 MC 4 MC 4 39.5 50.9 MC 4 MC 4 49.9 52.3 MC 4 53.0
45.8 MC 4 55.2 39.6 MC 4 48.1 MC 4 FC 4 52.3 64.0
FC 4 50.4 MC 4 48.0 45.0 40.8 52.2 MC 4 49.0 50.6 52.8 46.0 47.0
46.0 50.0 59.7 FC 4 56.3 47.1 58.0 FC 4 52.0 63.0
52.5 52.6 MC 4 MC 4 FC 4 42.9 52.1 MC 4 MC 4 52.4 MC 4 47.0 FC 4
MS MC 4 51.1 FC 4 55.4 FC 4 56.0 FC 4 50.7 MC 4
50.2 MC 4 50.0 36.0 FC 4 FC 4 FC 4 50.1 50.0 51.0 MC 4
MS FC 4
46.0 MS
FC 4 FC 4 52.5 50.0 55.0 FC 4 FC 4 63.0
FC 4 MC 4 48.0 MC 4 40.0 FC 4 49.6 45.4 51.0 FC 4 MC 4 FC 4 FC 4
47.0 FC 4 FC 4 FC 4 50.1 48.6 54.0 FC 4 FC 4 FC 4
FC 4 49.8 FC 4 49.0 44.0 FC 4 FC 4 49.8 MC 4 50.4 FC 4 FC 4 MC 4
44.3 50.9 52.3 FC 4 50.9
FS FC 4 FC 4 47.8 56.0
52.6 52.8 49.0 46.0 42.0 36.1 FC 4 MC 4 49.0 FC 4 49.6 44.0 MC 4
43.9 FC 4 FC 4 FC 4
FC 4 51.2 46.5 62.0
FC 4 FC 4 51.0 FC 4 42.0 40.7 50.6 MC 4 49.0 FC 4 45.1 43.0 MC 4
46.8 53.3 41.0 49.7
56.0 FC 4 FC 4 FC 4
54.0 49.7 49.0 46.0 FC 4 FC 4 FC 4 FC 4 49.0 FC 4 47.8 FC 4 50.0
55.0 FC 4 37.7 50.3
FC 4
63.0
49.0
44.0 FC 4 FC 4 49.7 50.3 48.0 FC 4 FC 4 43.0 MC 4
FC 4 39.1
56.1
FM 2 33.0 36.2
FS 46.1 FC 4 FC 4 48.4 45.0 49.0
56.3 FC 4
FC 4
FC 4
FS 47.3 49.0 FC 4 FD 1
FU MC 4
FM 4 52.6
43.8 50.2
FU 47.0
FD 1 55.8
47.1 UU
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED)
418-008PAGE C-171
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 27) PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
RAT/ LITTER #
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
POSTPARTUM DAY 21
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865 8866 8867 8868 8869 8870
MC 4 MC 4 48.0 43.6 51.0 MC 4 47.0 44.6 50.0 50.0 MC 4 48.0 45.0 54.0 54.0 MC 4 55.5 MC 4 48.9 MC 4 MC 4 49.0 51.1 48.0 54.7
49.3 MC 4 MC 4 MC 4 51.5 MC 4 44.1 47.3 50.0 MC 4 MC 4 MC 4 MC 4 MC 4 56.0 47.0 MC 4 45.2 52.0 52.0 40.1 56.0 57.3 48.0 53.8
MC 4 MC 4 49.0 46.2 52.8 48.8 MC 4 MC 4 46.0 49.0 43.6 48.0 44.0 MC 4
MS MC 4 58.9 MC 4 48.9 54.0 MC 4 MC 4 MC 4 MC 4 53.1
50.6 MC 4 MC 4 45.1 FC 4 MC 4 44.3 MC 4 55.0 50.0 MC 4 MC 4 45.0 MC 4 FC 4 MC 4 MC 4 MC 4 45.6 MC 4 37.6 57.0 57.0 MC 4 53.2
53 .2 41. 6 48 .0 45. 7 MD 1 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 53 .0 45 .0 MC 4 FC 4 52 .0 MC 4 MC 4 MC 4 MC 4 MC 4 56,.0 MC 4 MC 4 MC 4
MC 4 MC 4 MC 4 FC 4 FC 4 47.6 MC 4 MC 4 FC 4 48.0 47.7 49.0 42.0 51.0 52.0 54.0 59.7 MC 4 50.9 MC 4 MC 4 42.0 MC 4 MC 4 50.4
52.1 51.9 MC 4 FC 4 47.4 48.9 MC 4 MC 4 FC 4 51.0 MC 4 MC 4 FC 4 50.0 48.0 47.0 59.5 MC 4 48.0 MC 4 41.5 FC 4 52.8 MC 4 FC 4
MC 4 MC 4 MC 4 FC 4 FC 4 53.6 MC 4 47.1 FC 4 48.0 46.0 MC 4 40.0 MC 4 53.0 FC 4 54.8 45.6 48.0 51.0 MC 4 50.0 MD 2 MC 4 FC 4
MC 4 MC 4 49.0 45.5 51.6 48.6 48.6 MC 4 41.0 48.0 MC 4 FC 4 FC 4 52.0 50.0 43.0 FC 4 MC 4 FC 4 50.0 37.6 52.0 53.3 53.0 47.3
MC 4 51.3 47.0 45.1 49.9 FC 4 46.7 45.7 FC 4 49.0 MC 4 44.0 FC 4 53.0 54.0 45.0 FC 4 49.6 48.0 MC 4 FC 4 52.0 FC 4 51.0 48.0
FC 4 MC 4 49.0 47.5 50.4 FC 4 44.1 43.3 46.0
UU 47.5 51.0 41.0 FC 4 50.0 48.0 58.2 MC 4
50.0 35.1 FC 4 52.1 MC 4 48.6
47.9 48.0 47.0 48.4 51.4 FC 4 44.0 FC 4 48.0
UU MC 4 50.0 FC 4 50.0
FC 4 55.2 44.4
47.0 42.1 FC 4 FC 4 47.0
50.3 47.7 FC 4 FC 4 FD 2 48.5 FC 4 FC 4 50.0
MC 4 47.0 44.0 50.0
FC 4 FC 4 50.3
51.0 41.5 FC 4 50.1 FC 4
51.5 FC 4 53.0 FC 4
46.9 43.7 44.4 FC 4
46.1 FC 4 FC 4 54.0
FC 4 55.7 45.9
48.0 FC 4
51.5 44.0
FC 4 45.6 FC 4 44.9 44.4 FD 1 48.6 FC 4 FC 4 49.0 42.5
FC 4
51.0
FC 4 FC 4
44.5 FC 4
42.8 38.4 45.0
47.3 47.2 FM 4 46.3
FS
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
19 20 FD 1
46.6
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TABLE C36 (PAGE 28) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM INDIVIDUAL DATA - FI GENERATION PUPS
PUP ft
]
2
3
4
5
6
1t 8
9 10 11 12 13 14 15 16 17 18 19
RAT/ LITTER tf
MATERNAL DOSAGE GROUP III
0. 4 MG/KG/DAY
POSTPARTUM DAY 21
8871 8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896a 8897a 8898 8899 8900 8901 8902 8903 8904 8905
NOT 1PREGNANT 49.9 MC 4 50.8 MC 4 MC 4 48.0 MC 4 51.0 50.0 57.0 58.0 57.0 50.0 50.0 52.0 MC 4 MC 4 MC 4 MC 4 MC 4 52.0 MC 4 MC 4 MC 4 50.9 MC 4 50.9 50.8 MC 4 MC 4 40.0 40.0 MC 4 MC 4 56.1 MC 4 48.6 43.7 44.3 MC 4 50.3 MC 4 MC 4 56.0 52.0 45.0 46.0 MC 4 43.0 MC 4 42.8 51.0 MC 4 MC 4 50.0 50.0 54.0 40.0 41.0 47.0 49.9 MC 4 54.2 NOT PREGNANT NOT PREGNANT 52.4 MC 4 55.0
55.0 50.8 MC 4 MD 1 MC 4 55.0 MC 4 MC 4 51.1 47.7 MC 4 MC 4
48.0 MC 4 48.0 46.1 53.0 55.0 51.0 50.1
54.6
49.4 MC 4 MC 4 55.0 48.0 52.0 MC 4 38.4 51.4 48.3 39.0 49.8
MC 4 MC 4 49.0 59.0 45.0 53.0 49.0 39.0 FC 4 47.4 36.0 35.9
MC 4 50. e MC 4 52 .0 FC 4 MC 4 54 .0 37. 0 FC 4 FC 4 FC 4 MC 4
MC 4 MC 4 49.0
FC 4 52.0 51.0 39.2 51.1 FC 4 FC 4 51.8
46.9 51.0 45.0 41.6 56.0 MC 4 MC 4 MC 4
MC 4 MC 4 FC 4 MC 4 MC 4 MC 4 MC 4 48.6
MC 4 51. 0 FC 4 MC 4 56. 0 FC 4 FC 4 MC 4
42.7 MC 4 48.0 MC 4 MD13 51.0 49.0 FC 4
MC 4 MC 4 50. 5 MC 4
MS MC 4 MC 4
FC 4 FC 4
MS MC 4 52.6 FC 4 38.0 42.0
MC 4 48.0 46.0 40.8 52.0 FC 4 49.0 45.8
FC 4
46.5 46.8 48.0
48.0 51.0 48.0 35.8 49.6 44.8 40.0 47.1
47.2 FC 4 47.0 46.5 FC 4 50.0 45.0 46.8
47.3
49.7 49.1 51.0
45.0 FC 4 FC 4 36.1 FC 4 48.9 37.0 FD17
47.0 FC 4 FC 4 41.0 56.0 52.0 41.0 48.4
FC 4
47.7 48.3 48.0
FC 4 52.0 51.0 40.9 52.7 48.1 39.0 FD16
FC 4 48.0 FC 4 41.5 FC 4 FC 4 FC 4 48.7
FC 4
FC 4 FC 4 48.0
FC 4 FC 4 FC 4 34.5
FC 4
FC 4
45.3 48.0 43.0
FS FC 4 52.0 FC 4 FC 4
FC 4
52.7 46.6
42.0 55.0 53.0 FC 4
FC 4
FC 4 48.0 FC 4
FC 4 FC 4
FC 4
FC 4
45.6
FC 4 50.0 49.6
43.8
FC 4 FM 2 FM 3 50.5
56.0 FS
FC 4
53.0 FS FS
49.2
FC 4 FM 2 51.2
FC 4
FM 3
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pups were
arbitrarily distributed between the two dams and values will be included in group averages and statistical analyses.
20
418-008:PAGE C-173
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TABLE C36 (PAGE 29) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP It
12
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER H
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
POSTPARTUM DAY 21
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
MC 4 MC 4 39.0 41.9 42.5 45.7 MD 2 37.0 46.0 42.0 43.0 43.0 FC 4 44.0 41.0 39.0 44.0 36.0 MD 3 FC 4 41.0 NOT 1PREGNANT NOT 1PREGNANT MC 4 MC 4 48.9 45.0 45.3 46.0 MC 4 42.0 42.0 38.0 42.0 39.0 MD 2 38.0 42.9 46.1 45.5 MC 4 MC 4 45.7 45.3 NOT :PREGNANT 37.5 MM 2 FC 4 36.7 34.3 34.2 37.8 35.8 MD 3 MD 2 34.6 29.4 34.7 FM 3 MD 5 MD 5 MD 5 MD 3 MD 2 MD 2 27.4 MC 4 47.7 40.8 41.0 MC 4 43.9 MC 4 MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 MC 4 48.3 MC 4 47.9 52.4 47.0 50.4 41.0 45.0 45.0 42.0 MD 1 MD 1 MD 1 34.3 MC 4 MC 4 MC 4 38.8 38.9 32.3 NOT PREGNANT MC 4 39.2 38.7 MC 4 38.3 37.3 MD 2 42.0 MC 4 MC 4 42.9 37.1 38.7 MD 4 MD 4 MD 4 MD 4 MD 4 MD 2 MM 2 MD 2 45.1 48.2 41.4 46.2 44.2 MS 46.2 MORIBUND SACRIFICED ON DAY 36 OF STUDY 39.0 37.0 41.0 MD 1 MD 1 37.0 38.0 MC 4 MC 4 50.1 MC 4 50.9 MC 4 46.8
MD 2 FC 4 41.0
MC 4 FM 2 43.6
38.1 FM 3 34.9 42.7 FM 2 MD 1 MD 1 MM 3
33.5 42.5 MD 1 40.6
FD 1 49.6
41.1 43.0 42.0
MC 4 FD 1 MD 2
29.2 FD 2 FD 5 41.1
MD 1 MD 1 MM 3
33.7 FC 4
MS 41.7
FD 1 MD 2
38.7 FC 4 FC 4
MC 4
MS
FD10 FD 2 FM 5 FC 4
MD 1 FD 1 MD 3
36.5 38.6 MD 1 FM 2
FD 1 MD 1
46.8 41.0 39.0
42.7
MS
FM 2 FD 2 FM 5 39.7
46.7 FD 1 MD 2
35.4 37.1 FD 4
FS
FD 1 FC 4
42.5
FC 4
41.5
43.4
FD 2 FD 2 FM 4 42.9
37.6
35.7
FM 3 40.4 FD 4
FD 1 46.5
FM 3
41.0 39.7
FD 3 39.0 37.8 FD 2 FD 3 FD 1 40.9
FD 1
38.2
FD 3 FD 1 33.3 FD 3 38.9
FC 4
FD 2 FD 1 33.8 FD 1 38.7
FM 2
FD 2 FM 3 FD 1
FS
FD 2 FD 3
ALL WEIGHTS WERE RECORDED IN GRAMS (G) . FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008PAGE C-174
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PROTOCOL 418-008: COMBINED ORAL (GAVAGEt FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C36 (PAGE 30) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA FI GENERATION PUPS
PUP U 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP V
3 .2 MG/KG/DAY
POSTPARTUM DAY 21
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
MD 1 MD 1 MD 1 MD 1 MS MS MD 1 MS FS
NOT PREGNANT MD 2 MD 2 MD 2 MM 2 MD 2 MD 2
MS FD 1 FD 1 NOT PREGNANT MS MD 1 MD 1 MD 2 MD 2 MD 2 NOT PREGNANT MD 2 MD 2 MD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MS MS MS MM 2 MM 2 MM 2 MS MS MS MS MS FD 2 MD 1 MD 1 MD 1 MD 2 MD 2 MD 2 MM 2 MM 2 MM 2 NOT PREGNANT MM 2 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 MD 1
MD 1 MS
FD 1
MM 2 MD 2 FD 1
MD 1 MD 2
MD 2 MS
MD 2 FD 1 MM 2
FS FM 2 FD 1 MD 2 MM 2
MD 1 MD 1 MD 1
FD 1 MS
FD 1
MS MD 2 FD 1
MD 1 MD 2
MD 1 MS
MD 2
MD 2 FS
FD 1 FM 1 MD 2 MD 2
MD 1 MS
MD 1
FD 1 FD 1
MS MD 2
FS
FS MD 2
MS MS MM 2
MD 2 FS
FD 1
MS MD 2
MD 1 MS
MD 1
FD 2 FM 2
FD 1 MD 1
MS MS MS
MD 2 FS FS
FD 2 MD 2
MS FD 1 FD 1
FD 2 FM 2
FD 1 FD 2
FD 2 FD 1 FD 2
MD 2 FS FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 1 FD 2
FD 2 FS
FD 2
MM 1 UU FS
FD 2 FM 2
FD 1 FD 1 FD 1
FD 2 FD 2
FD 2
FD 2 FS
FD 2
MS
FS
FD 2 FM 2
FD 1 FD 1 FD 1
FM 2 FD 2
FD 2 FD 2
FS FM 2 FM 2
FS FD 2 FD 1
FS FD 1
FS FD 2
FD 2 FD 1
FS FD 1 FD 2
FD 2
FD 1
FD 1 FS FS FS
FM 1
FD 2
FS FD 1
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-175
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C37 (PAGE 1): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP tf
RAT/ LITTER #
123456 MATERNAL DOSAGE GROUP I
1
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 0 (VEHICLE) MG/KG/DAY
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818 8819 8821 8823 8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
MC 4 M A M A M A M A M A M S F A F A F A M A M A MC 4 M A MC 4 M A MC 4 M S FC 4 F A F A F A F A
MC 4 M A MC 4 M A M A M A F A FC 4 FC 4 F A FC 4 F A FC 4 FC 4 F A M A M A M A M A F A FC 4 FC 4 FC 4 FC 4 FC 4 FC 4 F A F A F A FC 4 FM 4 FD 1
MC 4 MC 4 MC 4 M A MC 4 M A M A M A F A F A FC 4 F A F A M A M A M A F A F A F A FC 4 F A F A F S M A MC 4 M A M A MC 4 M A F A F A F A FC 4 FC 4 F A M A M A M A M A FC 4 FC 4 FC 4 FC 4 FC 4 FC 4 F A FC 4 FC 4 F A FC 4 F A F A M A M A M A FC 4 F A F A F A FC 4 FC 4 F A F A FC 4
MC 4 M A M A MC 4 M A M A MC 4 F A FC 4 F A F A FC 4 F A NOT PREGNANT
NOT PREGNANT
M A M A M A F A FC 4 F A F A FC 4 FC 4 F A FC 4 F A MC 4 M A M A MC 4 M A F A MC 4 MC 4 F A F A FC 4 F A F A FM 2
M A M A M A MC 4 MC 4 MC 4 M A F A FC 4 F A F A F A MC 4 M A MC 4 MC 4 M A MC 4 M A MC 4 M A F A FC 4 F A F A F A FC 4
M A M A M A MC 4 M A FC 4 FC 4 F A F A F A F A FC 4 FC 4 M A MC 4 M A M A M A F A FC 4 FC 4 FC 4 F A F A FC 4 FC 4 F A M A M A M S F A F A F A FC 4 F A FC 4 FC 4 F A FC 4 F A F S F s MC 4 M A MC 4 MC 4 MC 4 MC 4 M A M A M A MC 4 MC 4 FC 4 F A F A F A F A MC 4 MC 4 MC 4 MC 4 M A MC 4 M A M A MC 4 M A F A F A F A FC 4 F A M A MC 4 MC 4 M A M A M A F A FC 4 F A FC 4 FC 4 FC 4 FC 4 FC 4 FC 4 F A F A M A MC 4 M A M A M A MC 4 MC 4 MC 4 FC 4 F A F A F A FC 4 F A FD 1 M A MC 4 M A MC 4 M A M A M s FC 4 FC 4 F A F A FC 4 F A F A F U F U U U M A M A M A M A F A FC 4 FC 4 FC 4 MC 4 MC 4 MC 4 M A MC 4 M A MC 4 M A
FIRST LETTER -- M-MALE, F-FEMALE. U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-176
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C37 (PAGE 2) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP tt 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT/ LITTER ft
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
8838 MC 4 M A MC 4 M A M A MC 4 M A MC 4 MC 4 MC 4 FC 4 F A F A F A FC 4 FC 4 F A 8840 MC 4 MC 4 MC 4 MC 4 M A MC 4 M A MC 4 MC 4 M A MC 4 M A F A FC 4 F A FC 4 F A 8841 M A MC 4 M A MC 4 M A MC 4 MC 4 MC 4 M A F A F A F A FC 4 F A 8842a M A MC 4 M A M A M A FC 4 FC 4 FC 4 F A F A F A F A FC 4 FC 4 FC 4 8845 M A M A M A FC 4 MD 1 FC 4 F A FC 4 F A F A F A F A FD 2 8846 MC 4 MC 4 M A MC 4 MC 4 M A M A M A F A FC 4 FC 4 FC 4 F A F A F A 8847 M A M A MC 4 M A MC 4 MC 4 MC 4 MC 4 M A F A F A F A FC 4 F A 8849 M A M A MC 4 MC 4 MC 4 MC 4 MC 4 M A MC 4 M A F A FC 4 FC 4 F A F A F A FM 4 8851 M A M A M A M A MC 4 FC 4 FC 4 FC 4 F A FC 4 F A F A F A FC 4 FD 1 8852 M A MC 4 M A M A MC 4 M A M A F A F A F A U U U U 8853 MC 4 MC 4 M A MC 4 MC 4 M A MC 4 M A MC 4 MC 4 M A MC 4 MC 4 F A F A FC 4 F A 8854 M A MC 4 M A MC 4 M A M A MC 4 MC 4 FC 4 F A F A F A F A FC 4 8855 M A MC 4 M A M A M A F A FC 4 F A FC 4 FC 4 F A FC 4 F A FC 4 FC 4 8857 M A MC 4 MC 4 MC 4 MC 4 M A M A MC 4 M A F A FC 4 F A F A F A FC 4 8858 M A M A M S FC 4 FC 4 F A F A F A F A F A F A 8860 MC 4 M A MC 4 MC 4 M A M A M A FC 4 F A F A F A FC 4 FC 4 FC 4 F A 8862 M A MC 4 M A MC 4 MC 4 M A M A F A FC 4 FC 4 F A F A FC 4 F A 8863 MC 4 M A MC 4 MC 4 MC 4 MC 4 MC 4 M A MC 4 M A MC 4 M A F A F A F A F A 8864 M A M A M A M A MC 4 F A F A F A FC 4 F A 8865 MC 4 M A M A MC 4 MC 4 MC 4 MC 4 M A M A MC 4 F A F A F A F A 8866 MC 4 M A MC 4 M A MC 4 MC 4 M A MC 4 M A FC 4 F A F A F A FC 4 FC 4 F A 8867 M A M A MC 4 M A M A F A FC 4 F A F A F A FC 4 FC 4 FC 4 8868 M A M A MC 4 M A MC 4 MC 4 M A MD 2 F A FC 4 F A FC 4 F A F A 8869 M A M A MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 M A M A MC 4 F A FC 4 F A F A F A F S 8870 M A M A M A M A MC 4 F A FC 4 FC 4 F A F A F A
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Dam 8842 delivered one additional pup on day 2 of lactation,- values for day 1 postpartum excluded from group averages and
statistical analyses.
418-008:PAGE C-177
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C37 (PAGE 3): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
pup n
12
3 4 5 6 7 B 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT/ LITTER #
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
8871 NOT PREGNANT 8872 M A MC 4 M A M A M A MC 4 MC 4 MC 4 M s F A F A F A FC 4 F A 8874a MC 4 MC 4 M A M A MC 4 MC 4 M A MC 4 MC 4 M A M A F A FC 4 F A F A 8875 MC 4 M A M A MC 4 MC 4 M A MC 4 M A MC 4 F A F A F A F A 8876 M A M A M A MD 1 F A F A F A 8881 M A M A M A MC 4 M A F A FC 4 FC 4 FC 4 F A F A FC 4 FC 4 F A 8882 MC 4 MC 4 MC 4 M A M A M A MC 4 M A FC 4 F A FC 4 F A FC 4 F A FC 4 F A FC 8885 MC 4 MC 4 M A MC 4 MC 4 M A M A M A M S F A FC 4 F A FC 4 F A M A F S 8889 MC 4 MC 4 MC 4 MC 4 M A M A M A M A MC 4 F A F A F A F A FC 4 8890 M A MC 4 M A M A M A FC 4 FC 4 F A F A F A FC 4 F A 8891 M A MC 4 MC 4 M A M A M A FC 4 FC 4 FC 4 F A F A F A FC 4 FC 4 F A 8892 M A M A MC 4 MC 4 M A M A FC 4 FC 4 F A F A F A F A 8893 MC 4 M A MC 4 MC 4 M A M A MC 4 M A F A F A FD17 FD16 FC 4 8894 M A M A F A
8895 MC 4 M A MC 4 M A M A MC 4 MC 4 M A MC 4 F A F A FC 4 F A FC 4 F A FC 4 FM 8896b MC 4 M A M A MC 4 M A MC 4 M A MC 4 F A FC 4 FC 4 F A F A F A 8897b M A M A MC 4 M A M A FC 4 FC 4 F A F A F A FC 4 FC 4 F A FC 4 8898 M A MC 4 M A M A M A MC 4 MC 4 MC 4 F A F A F A F A F S 8899a M A MC 4 MC 4 M A M A MC 4 M A MD13 F A FC 4 F A FC 4 FC 4 FC 4 FC 4 F A 8900 M A M A M A M A MC 4 MC 4 FC 4 F A FC 4 F A F A FC 4 F A FC 4 FM 2 F S 8901 M A M A M A F A MC 4 MC 4 FC 4 F A F A F A F A FC 4 FC 4 8902 M A MC 4 M A M A MC 4 M A MC 4 FC 4 F A F A F A F A FC 4 FC 4 FM 3 F S 8903 NOT PREGNANT
8904 NOT PREGNANT 8905 M A M C 4 M A M A M C 4 M C 4 M A M C 4 F C 4 F A F C 4 F C 4 F C 4 F C 4 F A F A F A F C 4 F M 3
t
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. A sexing error was found prior to weighing the pups on day 7 postpartum; values for day 4 postpartum postculling were excluded
from group averages and statistical analyses. b. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pups were
arbitrarily distributed between the two dams and values will be included in group averages and statistical analyses.
418-008PAGE C-178
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C37 (PAGE 4): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP g 1 2 3 4 5 6 7 8 9 10 11 12 13 14 IS 16 17 18 19 20 21 22 23
RAT/ LITTER tf
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
8906 8909 8913 8914 8918 8919 8920 8921 8923 8925 8926 8927 8928 8929 8930 8931 8932 8933 8934 8935 8936 8937 8938 8939 8940
MC 4 MC 4 M A M A M A M A MD 2 MD 2 F A F A F A F A FM 3 FD 1 M A M A M A M A F A FC 4 F A FC 4 F A FC 4 F A M A M A M A M A MD 3 FC 4 F A F A F A FC 4 F A FC 4
NOT PREGNANT NOT PREGNANT MC 4 MC 4 M A M A M A M A MC 4 MC 4 MC 4 MC 4 F A F A F A F A FC 4 FM 2
M A M A M A M A M A MD 2 F A FM 2 FD 1 M A M A M A MC 4 MC 4 M A M A M A MD 2 M S M S F A F A NOT PREGNANT M A MM 2 FC 4 F A F A F A F A F A F A FD10 FM 2 FD 2 M A MD 3 MD 2 F A F A F A FM 3 FM 3 FD 2 FD 2 FD 2 FD 2 MD 5 MD 5 MD 5 MD 3 MD 2 MD 2 F A F A FD 5 FM 5 FM 5 FM 4 FD 3 FD 3 FD 2 FD 2 FD MC 4 M A M A M A MC 4 M A MC 4 F A F A FC 4 F A F A MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 FM 2 MC 4 M A MC 4 M A M A M A M A MD 1 MD 1 MD 1 F A F A F A FD 1 FD 1 M A M A M A M A MD 1 MD 1 MD 1 MD 1 MD 1 FD 1 FD 1 M A MC 4 MC 4 MC 4 M A M A M A MM 3 MM 3 MD 3 MD 2 F A F A F A F A FM 3 FD NOT PREGNANT MC 4 M A M A MC 4 M A M A MD 2 F A F A F A F A FM 3 FD 2 M A MC 4 MC 4 M A M A M A MD 4 F A FC 4 F A F A F A MD 4 MD 4 MD 4 MD 4 MD 2 MM 2 MD 2 MD 1 M S MD 1 FD 4 FD 4 FD 3 FD 3 FD 1 FD 1 M A M A M A M A M A M S F A F A F A FM 2 F S MORIBUND SACRIFICED ON DAY 36 OF STUDY M A M A M A MD 1 MD 1 F A F A FD 1 FD 1 FD 1 FD 1 FD 1 FD 1 MC 4 MC 4 M A MC 4 M A MC 4 M A M A MD 2 MD 1 FC 4 F A F A F A F A F S
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING -SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008: PAGE C-179
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C37 (PAGE 5) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
PUP tf 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT/ LITTER #
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8942 8943 8944 8945 8946 8949 8950 8952 8955 8956 8957 8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
MD 1 MD i MD i MD 1 FD 1 FD 1 MD 1 M s M s M S M S FD 1 MD I M s F s FD 1 FD 1 NOT !PREGNANT MD 2 MD 2 MD 2 MM 2 M S M S FD 2 FD 2 FD 2 FD 2 FM 2 F S MM 2 MD 2 MD 2 MD 2 MD 2 MD 2 FM 2 FM 2 FD 2 FD 2 FD 2 FD 2
M S FD 1 FD 1 FD 1 FD 1 F S NO T 1PREGNANT
M s MD 1 MD 1 MD 1 MD 1 F S FD 1 FD 1 FD 1 MD 2 MD 2 MD 2 MD 2 MD 2 MD 2 MD 1 FD 2 FD 2 FD 2 FD 2 FD 2 FD I N OT :PREGNANT MD 2 MD 2 MD 2 MD 2 MD 1 M S M S FD 2 FD 2 FD 2 FD 2 FD 1 F S MD 1 MD 1 MD 1 M S M S M S M S FD I F S F S F S F S F S MD 2 MD 2 MD 2 MD 2 MD 2 MM 2 M S FD 2 FD 2 FD 2 FM 2 FD 1 F S
M S M s M S FD 1 MM 2 MM 2 MM 2 MM 2 MD 2 MD 2 MD 2 MD 2 MM 1 M S FM 2 FD 2 FM 1
MS MS MS FS FS FS FS FS UU M S M S FD 2 FM 2 FD 1 FD 1 F S F S F S F S MD 1 MD 1 MD 1 FD 1 FM 1 MD 2 MD 2 MD 2 MD 2 MD 2 M S FD 2 FD 2 FD 2 FD 2 F S MM 2 MM 2 MM 2 MM 2 MD 2 MD 2 MD 2 FM 2 FM 2 FM 2 FD 2 FD 2 FD 2 NOT PREGNANT MM 2 MD 1 MD 1 MD 1 MD 1 MD 1 M S FD 1 FD 1 FD X FD 1 MD 1 MD 1 MD 1 MD 1 M S M S FD 1 FD 1 FD 1 FD 1 F S MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 FD 1 FD 1 FD 1 FD 1 FD 1 FD 1
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE C-180
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C38 (PAGE 1) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
I 0 (VEHICLE)
8819
14 5-21
1/12 PUPS: LEFT HINDPAW, THIRD AND FOURTH DIGITS, MISSING. 1 / 8 PUPS: LEFT HINDPAW, THIRD AND FOURTH DIGITS, MISSING.
8826
14-21
1/ 8 PUPS: TAIL, BENT (2.0 CM FROM BASE).b
II
0.1
8867
7-21
1/8 PUPS: UMBILICAL HERNIA.b
III
0.4
8893
14 -15
2/8 PUPS: HEAD, DOMED.
16 3/7 PUPS: HEAD, DOMED.
17-21
2/6 PUPS: HEAD, DOMED.b
IV
1.6
8925
2- 4
1/ 9 PUPS: PORTION OF TAIL MISSING.
5-10
1/ 8 PUPS: PORTION OF TAIL MISSING.
11-21
1/ 7 PUPS: PORTION OF TAIL MISSING.b
8927
15-21
1/ 2 PUPS: HEAD, DOMED.
V
3.2
8961
1 1/10 PUPS: TAIL MISSING.
8964
1 13/13 PUPS: NOT NURSING, PLACENTA NOT REMOVED.
8968
1 2/ 2 PUPS: NOT NURSING OR NESTING.
8969
1 1/ 3 PUPS: LEFT FORELIMB, CANNIBALIZED.
8970
1 9/ 9 PUPS: NOT NURSING, PLACENTA NOT REMOVED.
a. Tabulation restricted to adverse observations; all other pups appeared normal. b. Observation confirmed at necropsy.
418-008:PAGE C-181
000467
418-008:PAGE C-182
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PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 1): SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
3 4 5 6 7 8 9 10
MATERNAL/LITTER ft
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8819 8821 8823 8824 8828 8827 8828
5/ 9 55.6%
5/12 41.7% 11/15 73.3% 12/16 75.0%
5/13 38.5%
5/ 9 55.6%
4/12 33.3% 11/17 64.7%
6/12 50.0%
8/13 61.5% 10/12 83.3%
6/14 42.8%
2/12 16.7%
4/15 26.7%
2/13 15.4%
5/14 35.7%
6/12 50.0%
1/ 9 11.1%
5/12 41.7%
5/15 33.3%
5/16 31.2%
2/13 15.4%
4/ 9 44.4% 12/12 100.0% 13/17 76.5%
5/12 41.7% 11/13 84.6%
3/12 25.0%
9/13 69.2%
1/12 8.3% 3/15 20.0% 4/13 30.8% 3/14 21.4% 8/12 66.7%
5/ 9 55.6%
4/12 33.3%
3/15 20.0%
2/16 12.5%
7/13 53.8%
6/ 9 66.7%
12/17 70.6%
8/12 66.7% 13/13 100.0%
4/12 33.3% 11/13 84.6%
9/12 75.0%
6/15 40.0%
3/13 23.1%
1/14 7.1% 7/12 58.3%
9/ 9 100.0%
12/12 100.0%
6/15 40.0%
7/15 46.7% 13/13 100.0%
7/ 9 77.8%
11/17 64.7% 12/12 100.0%
10/12 83.3% 10/13 76.9% 12/12 100.0%
8/15 53.3%
1/13 7.7% 3/14 21.4% 12/12 100.0%
5/ 8 62.5%
6/ 8 75.0%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
7/ 8
8/ 8
87.5% 100.0%
8/ 8 100.0%
8/ 8 100.0%
4/ 8 50.0%
3/ 8 37.5%
4/ 8 50.0%
5/ 8 62.5%
1/ 8 12.5%
4/ 8 50.0%
6/ 8 75.0%
4/ 8 50.0%
6/ 8 75.0%
8/ 8 100.0%
6/ a 75.0%
6/ 8 75.0%
6/ 8 75.0%
6/ 8 75.0%
7/ 8 87.5%
7/ 8 87.5%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
11
12
13
418-008:PAGE C-183
000469
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 2) ; SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
3 4 5 6 7 8 9 10 11 12
MATERNAL/LITTER tf
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8830 8831 8832 8833 8834 8835
8/16 50.0%
9/15 60.0%
5/17 29.4%
1/14 7.1% 8/13 61.5% 5/16 31.2%
3/16 18.8%
4/15 26.7%
3/17 17.6%
6/14 42.8%
5/13 38.5%
4/16 25.0%
10/16 62.5%
6/15 40.0%
7/17 41.2%
2/14 14.3%
2/13 15.4%
4/16 25.0%
16/16 100.0%
15/15 100.0%
7/17 41.2%
9/14 64.3%
4/13 30.8%
4/16 25.0%
8/ 8 100.0%
8/ 8 100.0%
5/ 8 62.5%
4/ 8 50.0%
7/ 8 87.5%
8/ 8 100.0%
6/ 8
8/ 8
75.0% 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
13
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 3) : SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
rPARTUM DAY
1
2
3
4
56
7
8
9 10 11 12
ERNAL/LITTER 1)
MATERNAL DOSAGE GROUP II
0 ..1 MG/KG/DAY
8838 8840 8841 8842a 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863
9/17 52.9% 10/18 55.6% 14/14 100.0%
6/14 42.8%
8/12 66.7%
9/15 60.0% 11/14 78.6%
8/17 47.0%
8/14 57.1%
3/10 30.0% 15/19 78.9%
7/14 50.0%
7/15 46.7%
8/15 53.3%
4/10 40.0%
9/15 60.0% 11/14 78.6%
2/16 12.5%
3/17 17.6%
8/18 44.4%
7/15 46.7%
4/11 36.4%
0/15 0.0% 3/14 21.4% 4/17 23.5% 9/14 64.3% 4/10 40.0% 7/19 36.8% 2/14 14.3% 4/15 26.7% 8/15 53.3% 1/10
10.0% 6/15
40.0% 5/14
35.7% 4/16
25.0%
1/17 5.9% 9/18 50.0%
9/17 52.9% 18/18 100.0%
8/ 8 100.0%
9/15 60.0%
7/11 63.6%
3/15 20.0%
5/14 35.7%
9/17 52.9%
0/14 0.0% 4/10 40.0% 11/19 57.9% 1/14 7.1% 8/15 53.3% 2/15 13.3% 7/10 70.0% 5/15 33.3% 3/14 21.4% 6/16 37.5%
10/15 66.7% 11/11 100.0% 13/15 86.7%
9/14 64.3%
5/16 31.2%
8/14 57.1% 10/10 100.0% 11/19 57.9%
5/14 35.7% 12/15 80.0% 15/15 100.0%
9/10 90.0%
6/15 40.0%
8/14 57.1% 13/16 81.2%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
4/ 8 50.0%
8/ 8 100.0%
5/ 8 62.5%
8/ 8 100.0%
8/ 8 1 0 0 .0%
7/ 8 87.5%
7/ 8 87.5%
8/ 8 100.0%
4/ 8 50.0%
7/ 8 87.5%
5/ 8 62.5%
8/ 8 100.0%
3/ 8 37.5%
5/ 8 62.5%
6/ 8 75.0%
5/ 8 62.5%
6/ 8
8/ 8
75.0% 1 0 0 .0%
6/ 8 75.0%
7/ 8 87.5%
7/ 8 87.5%
6/ 8
8/ 8
75.0% 1 0 0 .0%
7/ 8 87.5%
8/ 8
1 0 0 .0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER a. Dam 8842 delivered one additional pup on day 2 of lactation; values for day 1 postpartum excluded from group averages and
statistical analyses.
13
418-008:PAGE C-184
000470
418-008:PAGE C-185
000471
PROTOCOL 418-008: COMBINED ORAL (GAVAGE1 FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 4): SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
3 4 5 6 7 8 9 10 11 12
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
8864 8865 8866 8867 8868 8869 8870
3/10 30.0%
5/14 35.7%
8/16 50.0%
2/13 15.4%
3/14 21.4% 16/16 100.0%
2/11 18.2%
2/10 20.0%
2/14 14.3%
4/16 25.0%
2/13 15.4%
4/13 30.B\
i/ii 9.1%
1/10 10.0%
7/14 50.0%
5/16 31.2%
4/13 30.8% 10/13 76.9%
6/10 60.0% 14/14 100.0% 12/16 75.0%
9/13 69.2% 13/13 100.0%
7/ 8
8/ 8
87.5% 100.0%
1/ 8 12.5%
7/ 8 87.5%
8/ 8 100.0%
7/ 8 87.5%
7/11 63.6%
6/11
8/ 8
54.5% 100.0%
5/ 8 62.5%
6/ 8
8/ 8
75.0% 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
13
418-008:PAGE C-186
000472
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 5): SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
3 4 5 6 7 8 9 10
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899
4/13 30.8%
2/15 13.3%
5/13 38.5%
2/ 6 33.3%
6/14 42.8%
8/17 47.0% 11/14 78.6%
1/14 7.1% 3/12 25.0% 6/15 40.0% 6/12 50.0% 1/13 7.7% 0/ 3 0.0% 4/17 23.5% 7/14 50.0% 8/14 57.1% 8/12 66.7% 9/16 56.2%
1/13 7.7% 6/14 42.8% 9/13 69.2% 4/ 6 66.7% 4/14 28.6% 8/17 47.0% 4/14 28.6% 6/14 42.8% 4/12 33.3% 5/15 33.3% 5/12 41.7% 6/13 46.2%
0/ 3 0.0% 1/16 6.2% 1/14 7.1% 4/14 28.6% 5/12 41.7% 5/16 31.2%
4/13 30.8%
8/15 53.3%
5/13 38.5%
4/ 6 66.7%
1/14 7.1% 13/17 76.5% 8/14 57.1% 0/14 0.0% 3/12 25.0% 15/15 100.0% 5/12 41.7% 5/13 38.5% 3/ 3 100.0% 4/16 25.0% 2/14 14.3% 1/14 7.1% 8/12 66.7% 6/16 37.5%
10/13 76.9% 15/15 100.0%
6/13 46.2%
6/ 6 100.0%
8/14 57.1% 12/17 70.6%
7/14 50.0%
3/14 21.4% 12/12 100.0%
6/12 50.0%
4/13 30.8%
9/16 56.2%
9/14 64.3% 14/14 100.0%
5/12 41.7%
8/16 50.0%
8/ 8 100.0%
7/ 8 87.5%
6/ 8 75.0%
6/ 8 75.0%
5/ 8 62.5%
4/ 8 50.0%
3/ 8 37.5%
8/ 8 100.0%
4/ 8 50.0%
7/ 8 87.5%
8/ 8 100.0%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
7/ 8 87.5%
4/ 8 50.0%
4/ 8 50.0%
5/ 8 62.5%
8/ 8 100.0%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
7/ 8 87.5%
5/ 8 62.5%
5/ 8 62.5%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
7/8
8/8
87.5% 100.0%
N/N * NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
11
12
13
418-008: PAGE C-187
000473
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 6): SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
1
2
3
4
5
6
7
8
9 10 11 12
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
8900 8901 8902 8905
8/15 53.3%
8/13 61.5%
0/15 0.0% 6/19 31.6%
5/14 35.7%
5/13 38.5%
4/15 26.7%
3/19 15.8%
1/14 7.1% 3/13 23.1% 4/14 28.6% 4/18 22.2%
8/14 57.1%
4/13 30.8%
3/14 21.4%
5/18 27.8%
7/ 8 87.5%
6/ 8 75.0%
7/ 8 87.5%
7/ a 87.5%
5/ 8 62.5%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
5/ 8 62.5%
7/ 8
8/ 8
87.5% 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
13
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 7): SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
3 4 5 6 7 8 9 10 11
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
8906 8909 8913 8919 8920 8921 8925 8926 8927 8928 8929 8930 8931 8932 8934 8935 8936
5/13 38.5%
4/11 36.4%
7/12 58.3%
8/16 50.0%
0/ 8 0.0% 3/11 27.3% 0/12 0.0% 5/12 41.7% 15/17 88.2% 2/12 16.7% 0/ 8 0.0% 1/10 10.0% 0/ 4 0.0% 11/17 64.7% 3/13 23.1% 3/12 25.0% 4/11 36.4%
2/11
2/10
3/10
5/ 8
3/ 8
18.2% 20.0% 30.0% 62.5% 37.5%
1/11
1/11
7/11
3/ 8
5/ 8
9.1%
9.1% 63.6% 37.5% 62.5%
2/12
1/11
8/11
0/ 8
2/ 8
16.7%
9.1% 72.7%
0.0% 25.0%
5/15
3/15
3/15
8/ 8
33.3% 20.0% 20.0% 100.0%
1/ 6
0/ 6
3/ 6
2/ 6
0/ 6
16.7%
0.0% 50.0% 33.3%
0.0%
1/10
3/10
6/10
8/ 8
10.0% 30.0% 60.0% 100.0%
0/ 9
2/ 9
0/ 9
3/ 8
2/ 8
0.0% 22.2%
0.0% 37.5% 25.0%
0/ 7
0/ 4
1/ 4
0/ 4
0/ 4
0.0%
0.0% 25.0%
0.0%
0.0%
2/12
1/ 8
2/ 8
0/ 2
1/ 2
16.7% 12.5% 25.0%
0.0% 50.0%
3/12
1/12
4/12
3/ 8
3/ 8
25.0%
8.3% 33.3% 37.5% 37.5%
NO SURVIVING 1PUPS ON DAY 2 POSTPARTUM
5/ 8 62.5%
7/ 8 87.5%
5/ 8 62.5%
4/ 6 66.7%
8/ 8 100.0%
0/ 4 0.0% 0/ 2 0.0% 4/ 8 50.0%
7/ 8 87.5%
8/ 8 100.0%
6/ 8 75.0%
6/ 6 100.0%
1/ 4 25.0%
0/ 2 0.0% 7/ 8 87.5%
8/ 8 100.0%
5/ 8 62.5%
2/ 4 50.0%
0/ 2 0.0% 8/ 8 100.0%
7/ 8
8/ 8
87.5% 100.0%
1/ 4 25.0%
0/ 2 0.0%
2/ 4 50.0%
1/ 2 50.0%
5/10 50.0%
0/ 4 0.0% 1/16 6.2% 0/11 0.0% 4/12 33.3%
3/ 8 37.5%
2/10 20.0%
0/ 4 0.0%
1/11 9.1% 1/10 10.0% 3/12 25.0% 0/ 6 0.0%
3/10
5/ 8
5/ 8
6/ 8
7/ 8
30.0% 62.5% 62.5% 75.0% 87.5%
0/ 4
0/ 4
1/ 4
1/ 4
2/ 4
0.0%
0.0% 25.0% 25.0% 50.0%
2/11
3/ 8
3/ 8
6/ 8
8/ 8
18.2% 37.5% 37.5% 75.0% 100.0%
1/10
1/ 8
3/ 8
2/ 8
4/ 8
10.0% 12.5% 37.5% 25.0% 50.0%
1/11 9.1%
4/ 8 50.0%
2/ 8 25.0%
2/ 8 25.0%
7/ 8 87.5%
NO SURVIVING 1PUPS ON DAY 4 POSTPARTUM
8/ 8 100.0%
2/ 4 50.0%
8/ 8 100.0%
6/ 8 75.0%
4/ 4 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
12 13
3/ 4 75.0%
0/ 2 0.0%
4/ 4 100.0%
0/ 2 0.0%
418-008:PAGE C-188
000474
418-008PAGE C-189
000475
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 8): SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
1
2
3
4
5
6
7
8
9 10 11 12
MATERNAL/LITTER t1
MATERNAL DOSAGE GROUP IV
1 .6 MG/KG/DAY
8937 8939 8940
2/ 9 22.2%
1/ 5 20.0%
4/14 28.6%
3/ 8 37.5%
2/ 5 40.0%
5/13 38.5%
0/ 8 0.0% 0/ 5 0.0% 4/13 30.8%
4/ 8 50.0%
2/ 5 40.0%
6/13 46.2%
6/ 8 75.0%
1/ 5 20.0%
6/ 8 75.0%
7/ 8 87.5%
3/ S 60.0%
6/ 8 75.0%
8/ 8 100.0%
4/ 5 80.0%
4/ 8 50.0%
3/ 5 60.0%
7/ 8 87.5%
5/ 5 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
13
418-008.PAGE C-190
000476
PROTOCOL 41B-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 9) : SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER h
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
8921
0/2 0.0%
1/2 50.0%
1 /2
50.0%
2/2 100.0%
N/N NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
t
418-008:PAGE C-191
000477
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 10): SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
3456
7 8 9 10 11 12
MATERNAL/LITTER ft
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8942
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8943
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8944
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8946 8949 8950
0/ 9
NO SURVIVING PUPS ON DAY 2 OF LACTATION
0 .0 %
0/12
NO SURVIVING PUPS ON DAY 2 OF LACTATION
0 .0 %
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8955
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8956 8959 8960
2/11
NO SURVIVING PUPS ON DAY 2 OF LACTATION
18.2%
0/ 8
NO SURVIVING PUPS ON DAY 2 OF LACTATION
0 .0 %
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8961 8962
2/10
NO SURVIVING PUPS ON DAY 2 OF LACTATION
2 0 .0 %
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8964 8967
0/10
NO SURVIVING PUPS ON DAY 2 OF LACTATION
0 .0 %
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8968 8969
0/ 2
NO SURVIVING PUPS ON DAY 2 OF LACTATION
0 .0 %
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8970 8971 8973
0/ 9 0.0% 0/13 0.0% 0/ 1 0.0%
NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
13
418-008:PAGE C-192
000478
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C39 (PAGE 11) : SURFACE RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
3 4 5 6 7 8 9 10 11 12
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8974
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION
N/N > NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
13
PROTOCOL 418-OOB: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 1): PINNA UNFOLDING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
2
3
4
5
6
7
MATERNAL/LITTER
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8819 8821 8B23 8824 8826 8827 8828
0/ 9 0.0% 12/12 100.0% 0/15 0.0% 0/16 0.0% 0/13 0.0% 0/ 9 0.0% 9/12 75.0% 17/17 100.0% 0/12 0.0% 13/13 100.0% 0/12 0.0% 0/13 0.0% 0/12 0.0% 0/15 0.0% 0/13 0.0% 0/14 0.0% 0/12 0.0%
4P O CD o 00
\o 1-- 4
9/ 9 100.0%
9/15
3/16
10/13 76.9%
9/ 9 100.0%
12/12 100.0%
12/12 100.0%
11/12 91.7% 13/13 100.0% 12/12 100.0%
5/15 33.3%
1/13 7.7% 5/14 35.7% 12/12 100.0%
15/15 100.0%
15/15 100.0%
13/13 100.0%
12/12 100.0%
15/15 100.0%
13/13 100.0%
14/14 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-193
000479
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 2) : PINNA UNFOLDING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
2
3
4
5
6
7
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8830 8831 8832 8833 8834 8835
0/16 0.0% 0/15 0.0% 0/17 0.0% 0/14
0/13 0.0% 0/16 0.0%
16/16 100.0%
15/15 100.0%
10/17 58.8%
6/14
4/13 30.8%
4/16 25.0%
14/17 82.4% 14/14 100.0% 13/13 100.0% 16/16 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER: WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008PAGE C-194
CD <N
* o o
000480
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 3): PINNA UNFOLDING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
234567
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863
0/17 0.0% 0/18 0.0% 0/12 0.0% 0/15 0.0% 0/11 0.0% 0/15 0.0% 0/14 0.0% 3/17 17.6% 0/14 0.0% 0/10 0.0% 0/19 0.0% 0/14 0.0% 0/15 0.0% 0/15 0.0% 0/10 0.0% 0/15 0.0% 0/14 0.0% 0/16 0.0%
14/17 82.4% 15/18 83.3% 14/14 100.0% 15/15 100.0% 10/11 90.9% 10/15 66.7%
3/14 21.4%
0/17 0.0% 1/14 7.1% 6/10 60.0% 10/19 52.6% 2/14 14.3% 5/15 33.3% 4/15 26.7% 8/10 80.0% 3/15 20.0% 10/14 71.4% 13/16 81.2%
11/17 64.7% 18/18 100.0%
11/11 100.0%
15/15 100.0%
14/14 100.0%
12/16 75.0% 14/14 100.0% 10/10 100.0% 19/19 100.0% 14/14 100.0% 15/15 100.0% 15/15 100.0% 10/10 100.0% 15/15 100.0% 14/14 100.0% 16/16 100.0%
8/ 8 10 0 .0 %
8/ 8
100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-195
0004S1
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 4): PINNA UNFOLDING - INDIVIDUAL DATA FI GENERATION LITTERS
POSTPARTUM DAY
234567
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
8864 8865 8866 8867 8868 8869 8870
0/10 0.0% 0/14 0.0% 0/16 0.0% 8/13 61.5% 0/13 0.0% 0/16 0.0% 0/11
1/10 10.0%
2/14 14.3%
1/16 6.2% 13/13 100.0% 6/13 46.2% 2/16 12.5% 10/11 90.9%
10/10 100.0%
14/14 100.0%
16/16 100.0%
13/13 100.0%
16/16 100.0%
11/11 100.0%
N/N - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-196
O o
000482
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 5): PINNA UNFOLDING INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
234567
MATERNAL/LITTER 0
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896 8897 8898 8899
0/13 0.0% 0/15 0.0% 0/13 0.0% 2/ 6 33.3% 0/14 0.0% 0/17 0.0% 0/14 0.0% 0/14 0.0% 0/12 0.0% 0/15 0.0% 0/12 0.0% 0/13 0.0%
3/ 3 100.0%
0/16 0.0% 0/14 0.0% 0/14 0.0% 0/12 0.0% 0/16 0.0%
1/13 7.7% 5/15 33.3% 11/13 84.6% 6/ 6 100.0% 0/14 0.0% 17/17 100.0% 1/14 7.1% 0/14 0.0% 12/12 100.0% 8/15 53.3% 12/12 100.0% 6/13 46.2%
4/16 25.0%
3/14 21.4%
3/14 21.4%
7/12 58.3%
2/16 12.5%
13/13 100.0%
15/15 100.0%
13/13 100.0%
14/14 100.0%
14/14 100.0%
10/14 71.4%
15/15 100.0%
13/13 100.0%
16/16 100.0%
14/14 100.0%
14/14 100.0%
11/12 91.7% 16/16 100.0%
8/ 8 1 0 0 .0 %
8/ 8 1 00.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-197
000483
PROTOCOL 418 -008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 6): PINNA UNFOLDING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
2
3
4
5
6
7
MATERNAL/LITTER It
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
8900 8901 8902 8905
0/14 0.0% 0/13 0.0% 0/15 0.0% 0/19 0.0%
0/14 0.0% 2/13 15.4% 1/14 7.1% 13/18 72.2%
14/14 100.0%
13/13 100.0%
14/14 100.0%
18/18 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-198
000484
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 7): PINNA UNFOLDING - INDIVIDUAL DATA FI GENERATION LITTERS
POSTPARTUM DAY
2
3
4
5
6
7
MATERNAL/LITTER tt
MATERNAL DOSAGE GROUP IV
1 .6 MG/KG/DAY
8906 8909 8913 8919 8920 8921 8925 8926 8927 8928 8929
0/11
1/10 10/10
0.0% 10.0% 100.0%
0/11
0/11 11/11
0.0%
0.0% 100.0%
0/12
1/11 11/11
0.0%
9.1% 100.0%
0/15
1/15
2/15
8/ 8
0.0%
6.7% 13.3% 100.0%
0/ 6
0/ 6
6/ 6
0.0%
0.0% 100.0%
0/10
5/10 10/10
0.0% 50.0% 100.0%
0/ 9
0/ 9
0/ 9
8/ 8
0.0%
0.0%
0.0% 100.0%
0/ 7
0/ 4
0/ 4
2/ 4
4/ 4
0.0%
0.0%
0.0% 50.0% 100.0%
0/13
0/ 8
0/ 8
0/ 2
1/ 2
0.0%
0.0%
0.0%
0.0% 50.0%
0/12
9/12 12/12
0.0% 75.0% 100.0%
NO SURVIVING PUPS ON DAY 2 POSTPARTUM
2/ 2 100.0%
8930 8931 8932 8934 8935 8936
0/10 0.0% 0/ 4 0.0% 0/17 0.0% 0/11 0.0% 0/12 0.0% 0/ 8 0.0%
0/10 0.0% 0/ 4 0.0% 0/11 0.0% 0/10 0.0% 1/12 8.3% 0/ 6 0.0%
2/10
8/ 8
20.0% 100.0%
0/ 4
4/ 4
0.0% 100.0%
0/11
3/ 8
8/ 8
0.0% 37.5% 100.0%
0/10
2/ 8
2/ 8
8/ 8
0.0% 25.0% 25.0% 100.0%
0/11
5/ 8
8/ 8
0.0% 62.5% 100.0%
NO SURVIVING PUPS ON DAY 4 POSTPARTUM
N/N NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-199
000485
PROTOCOL 418-008; COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 IPAGE 8) : PINNA UNFOLDING INDIVIDUAL DATA FI GENERATION LITTERS
POSTPARTUM DAY
2
3
4
5
6
7
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
8937 8939 8940
0/ 8 o.ot 4/13 30.8% 0/13
O o
0/ 8 0.0% 0/ 5 0.0% 0/13
8/ 8 100.0%
2/ 5 40.0% 11/13 84.6%
5/ 5 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-200
o o
000486
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 9): PINNA UNFOLDING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
2
3
4
5
6
7
MATERNAL/LITTER U
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8942
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8943
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8944
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8946
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8949
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8950
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8955
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8956
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8959
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8960
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8961
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8962
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8964
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8967
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8968
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8969
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8970
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8971
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-201
000487
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C40 (PAGE 10): PINNA UNFOLDING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
2
3
4
5
6
7
MATERNAL/LITTER
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8974
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-202
000488
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 1) : EYE OPENING - INDIVIDUAL DATA FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
IS
16
17
18
MATERNAL/LITTER tt
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8819 8821 8823 8824 8826 8827 8828
0/ 8 0.0% 0/ 8 0 .OV 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
0/ 8 0.0% 4/ 8 50.0% 2/ 8 25.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 2/ 8 25.0% 1/ 8 12.5% 0/ 8 0.0% 3/ 8 37.5% 0/ 8 0.0% 0/ 8 0.0%
1/ 8 12.5%
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
1/ 8 12.5%
8/ 8 100.0%
4/ 8 50.0%
5/ 8 62.5%
2/ 8 25.0%
2/ 8 25.0%
6/ a 75.0%
8/ 8 100.0%
3/ 8 37.5%
8/ 8 100.0%
8/ 8 100.0%
4/ 8 50.0%
5/ 8 62.5%
6/ 8 75.0%
1/ 8 12.5%
4/ 8 50.0%
6/ 8 75.0%
6/ 8
8/ 8
75.0% 100.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
7/ 8 87.5%
7/ 8 87.5%
8/ 8 100.0%
6/ 8 75.0%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-203
000489
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 2) EYE OPENING - INDIVIDUAL DATA FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
15
16
17
18
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8830 8831 8832 8833 8834 8835
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
8/ 8 100.0%
1/ B 12.5%
4/ 8 50.0%
0/ 8 0.0% 2/ 8 25.0% 6/ 8 75.0%
7/ 8 87.5%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
1
418-008:PAGE C-204
000490
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 3): EYE OPENING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
15
MATERNAL/LITTER ft
MATERNAL DOSAGE GROUP II
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863 8864 8865
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% o/ a 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% o/ a 0.0% 0/ 8 0.0% 0/ 8 0.0%
1/ 8 12.5%
0/ 8 0.0%
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 4/ 8 50.0% 0/ 8 0.0%
3/ 8 37.5%
5/ 8 62.5%
1/ 8 12.5%
1/ 8 12.5%
3/ 8 37.5%
2/ 8 25.0%
0/ 8 0.0% 0/ 8
0.0% 3/ 8 37.5% 6/ 8 75.0% 4/ 8 SO .0% 4/ 8 50.0% 0/ 8
0.0% 2/ 8 25.0% 1/ 8 12.5% 8/ 8
100.0% 0/ 8 0.0% 4/ 8
50.0% 7/ 8
87.5% 0/ 8 0.0%
8/ 8 100.0%
8/ 8 100.0%
7/ 8 87.5%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
2/ 8 25.0%
2/ 8 25.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
2/ 8 25.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
8/ a 100.0%
8/ 8 100.0%
16 17 18 0.1 MG/KG/DAY
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-205
000491
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 4) : EYE OPENING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
15
16
17
18
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
8866 8867 8868 8869 8870
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
1/ 8 12.5%
2/ 8 25.0%
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
1/ 8 12.5%
8/ 8 100.0%
2/ 8 25.0%
2/ 8 25.0%
1/ 8 12.5%
4/ 8 50.0%
7/ 8 87.5%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-206
000492
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 5): EYE OPENING INDIVIDUAL DATA FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
IS
16
17
18
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896a 8897a 8898 8899
1/ 8 12.5%
0/ 8 0.0% 0/ 8 0.0% 0/ 6 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 3 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
2/ 8 25.0%
0/ 8 0.0% 0/ 8 0.0% 0/ 6 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
1/ 3 33.3%
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 1/ 7 14.3%
6/ 8 75.0%
0/ 8 0.0% 0/ 8 0.0% 6/ 6 100.0% 0/ 8 0.0% 2/ 8 25.0% 6/ 8 75.0% 0/ 8 0.0% 1/ 8 12.5%
3/ 8 37.5%
3/ a 37.5%
2/ 8 25.0%
3/ 3 100.0%
0/ 8 0.0% 2/ 8 25.0% 2/ 8 25.0% 1/ 8 12.5% 3/ 7 42.8%
8/ 8 100.0%
5/ 8 62.5%
8/ 8 100.0%
2/ 8 25.0%
6/ 8 75.0%
8/ 8 100.0%
5/ 8 62.5%
6/ 8 75.0%
8/ 8 100.0%
7/ 8 87.5%
5/ 8 62.5%
2/ 8 25.0%
8/ 8 100.0%
8/ 8 100.0%
5/ 8 62.5%
7/ 7 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
6/7 85.7%
8/ 8 100.0%
8/ 8 100.0%
6/6 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER a. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pups were
arbitrarily distributed between the two dams and values will be included in group averages and statistical analyses.
418-008:PAGE C-207
000493
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 6): EYE OPENING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
15
16
17
18
MATERNAL/LITTER 0
MATERNAL DOSAGE GROUP h i
0.4 MG/KG/DAY
8900 8901 8902 8905
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
1/ 8 12. 5%
0/ 8 0 . 0% 0/ 8 0 . 0% 0/ 8 0 .0%
1/ 8 12.5%
3/ 8 37.5%
3/ 8 37.5%
2/ 8 25.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-209
000495
PROTOCOL 418-000: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 7) ; EYE OPENING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
15
16
17
18
MATERNAL/LITTER If
MATERNAL DOSAGE GROUP IV
1 .6 MG/KG/DAY
8906 8909 8913 8919 8920 8921 8925 8926 8927 8928 8929
0/ 8
0/ 8
0/ 8
4/ 8
8/ 8
0.0%
0.0%
0.0% 50.0% 100.0%
0/ 8
0/ 8
0/ 8
7/ 8
8/ 8
0.0%
0.0%
0.0% 87.5% 100.0%
0/ 8
0/ 8
2/ 8
8/ 8
0.0%
0.0% 25.0% 100.0%
0/ 8
0/ 8
0/ 8
3/ 8
8/ 8
0.0%
0.0%
0.0% 37.5% 100.0%
0/ 6
0/ 6
0/ 6
0/ 6
1/ 6
0.0%
0.0%
0.0%
0.0% 16.7%
0/ 8
0/ 8
0/ 8
0/ 8
8/ 8
0.0%
0.0%
0.0%
0.0% 100.0%
0/ 7
0/ 7
0/ 7
0/ 7
3/ 7
0.0%
0.0%
0.0%
0.0% 42.8%
0/ 4
0/ 4
0/ 4
0/ 4
1/ 4
0.0%
0.0%
0.0%
0.0% 25.0%
1/ 2
1/ 2
1/ 2
2/ 2
50.0% 50.0% 50.0% 100.0%
0/ 8
0/ 8
2/ 8
3/ 8
8/ 8
0.0%
0.0% 25.0% 37.5% 100.0%
NO SURVIVING PUPS ON DAY 2 POSTPARTUM
6/ 6 100.0%
7/ 7 100.0%
3/ 4 75.0%
4/ 4 100.0%
8930 8931 8932 8934 8935 8936
0/ 8
0/ 8
1/ 8
1/ 8
5/ 8
0.0%
0.0% 12.5% 12.5% 62.5%
0/ 4
0/ 4
3/ 4
4/ 4
0.0%
0.0% 75.0% 100.0%
0/ 8
0/ 8
0/ 8
0/ 8
2/ 8
0.0%
0.0%
0.0%
0.0% 25.0%
0/ 8
0/ 8
0/ 8
0/ 8
2/ 8
0.0%
0.0%
0.0%
0.0% 25.0%
0/ 8
0/ 8
1/ 8
2/ 8
4/ 8
0.0%
0.0% 12.5% 25.0% 50.0%
NO SURVIVING PUPS ON DAY 4 POSTPARTUM
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
1
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 81: EYE OPENING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
15
16
17
18
MATERNAL/LITTER
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
8937 8939 8940
1/ B 12.5%
0/ 5 0.0% 0/ 8 0.0%
2/ 8 25.0%
0/ 5 0.0% 0/ 8 0.0%
1/ 8 12.5%
0/ 5 0.0%
3/ 8 37.5%
4/ 8 50.0%
1/ 5 20.0%
5/ 8 62.5%
8/ 8 100.0%
5/ S 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-210
000496
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 9): EYE OPENING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
15
16
17
18
MATERNAL/LITTER ft
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8942
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8943
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8944
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8946
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8949
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8950
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8955
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8956
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8959
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8960
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8961
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8962
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8964
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8967
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8968
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8969
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8970
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8971
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-211
000497
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C41 (PAGE 10) : EYE OPENING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
12
13
14
15
16
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8974
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-212
000498
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C42 (PAGE 1) : ACOUSTIC STARTLE INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER U
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8819 8821 8823 8824 8826 8827 8828
7/ 8 87.5%
6/ 8 75.0%
8/ 8 100.0%
2/ 8 25.0%
7/ 8 87.5%
6/ 8 75.0%
0/ 8 0.0%
1/ 8 12.5%
8/ 8 100.0%
5/ 8 62.5%
8/ 8 100.0%
7/ 8 87.5%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
1/ 8 12.5%
6/ 8 75.0%
8/ 8 100.0%
5/ 8 62.5%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
5/ 8 62.5%
3/ 8 37.5%
2/ 8 25.0%
8/ 8 100.0%
4/ 8 50.0%
3/ 8 37.5%
7/ 8 87.5%
3/ 8 37.5%
6/ 8 75.0%
7/ 8 87.5%
4/ 8 50.0%
4/ 8 50.0%
3/ 8 37.5%
8/ 8 100.0%
8/ 8 100.0%
3/ 8 37.5%
6/ 8 75.0%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 8 75.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008.PAGE C-213
000499
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C4 2 (PAGE 2) : ACOUSTIC STARTLE - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8830 8831 8832 8833 8834 8835
8/ 8 100.0%
8/ 8 100.0%
V8 87.5%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-214
000500
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C42 (PAGE 3): ACOUSTIC STARTLE INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER A
MATERNAL DOSAGE GROUP II
0 ,1 MG/KG/DAY
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863
7/ 8 87.5%
6/ 8 75.0%
3/ 8 37.5%
7/ 8 87.5%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
3/ 8 37.5%
6/ 8 75.0%
8/ 8 100.0%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
7/ 8 87.5%
7/ 8 87.5%
8/ 8 100.0%
5/ 8 62.5%
7/ 8 87.5%
4/ 8 50.0%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
7/ 8 87.5%
5/ 8 62.5%
8/ 8 100.0%
3/ a 37.5%
5/ 8 62.5%
1/ 8 12.5%
7/ 8 87.5%
6/ 8 75.0%
0/ 8 0.0%
0/ 8 0.0% 1/ 8 12.5% 2/ 8 25.0% 1/ 8 12.5%
7/ 8 87.5%
7/ 8 87.5%
7/ 8 87.5%
5/ 8 62.5%
7/8 87.5%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 8
8/ 8
75.0% 100.0%
7/ 8
8/ 8
87.5% 100.0%
6/8
8/ 8
75.0% 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-215
000501
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C42 (PAGE 4): ACOUSTIC STARTLE - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
8864 8865 8866 8867 8868 8869 8870
5/ 8 62.5%
8/ 8 100.0%
3/ 8 37.5%
8/ 8 100.0%
6/ 8 75.0%
7/ 8 87.5%
6/ 8 75.0%
8/ 8 100.0%
6/ 8 75.0%
4/ 8 50.0%
5/ 8 62.5%
5/ 8 62.5%
8/ 8 100.0%
1/ 8 12.5%
2/ 8 25.0%
4/ 8 50.0%
8/ 8 100.0%
5/ 8 62.5%
5/ 8 62.5%
4/ 8 50.0%
1/ 8 12.5%
5/ 8 62.5%
3/ 8 37.5%
8/ 8 100.0%
8/ 8 100.0%
N/N a NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-216
000502
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C42 (PAGE 5) : ACOUSTIC STARTLE - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER (t
MATERNAL DOSAGE GROUP h i
0..4 MG/KG/DAY
8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896a 8897a 8898 8899
4/ 8 50.0%
4/ 8 50.0%
4/ 8 50.0%
2/ 6 33.3%
6/ 8 75.0%
4/ 8 50.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
4/ 8 50.0%
6/ 8 75.0%
3/ 3 100.0%
5/ 8 62.5%
7/ 8 87.5%
4/ 8 50.0%
5/ 8 62.5%
7/ 7 100.0%
7/ 8 B7.5%
8/ 8 100.0%
4/ 8 50.0%
4/ 6 66.7%
8/ 8 100.0%
3/ 8 37.5%
7/ 8 87.5%
4/ 8 50.0%
5/ 8 62.5%
8/ a 100.0%
7/ 8 87.5%
3/ 8 37.5%
6/ 8 75.0%
6/ 8 75.0%
6/ 8 75.0%
5/ 6 83.3%
4/ 8 50.0%
5/ 8 62.5%
3/ 8 37.5%
8/ 8 100.0%
5/ 8 62.5%
5/ 8 62.5%
3/ 8 37.5%
1/ 8 12.5%
8/ 8 100.0%
4/ 6 66.7%
4/ 8 50.0%
8/ 8 100.0%
6/ 8 75.0%
6/ 8 75.0%
7/ 8 87.5%
0/ 8 0.0%
1/ 8 12.5%
6/ 6 100.0%
4/ 8 50.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
6/8 75.0%
8/ 8 100.0%
8/ 8 100.0%
8/8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER a. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pups were
arbitrarily distributed between the two dams and values will be included in group averages and statistical analyses.
418-008:PAGE C-217
000503
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629b.9)
TABLE C42 (PAGE 6) : ACOUSTIC STARTLE - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP III
0 .4 MG/KG/DAY
8900 8901 8902 8905
5/ 8 62.5%
6/ 8 75.0%
4/ 8 50.0%
6/ 8 75.0%
5/ 8 62.5%
3/ 8 37.5%
8/ 8 100.0%
7/ 8 87.5%
1/ 8 12.5%
3/ 8 37.5%
8/ 8 100.0%
5/ 8 62.5%
4/ 8 50.0%
5/ 8 62.5%
5/ 8 62.5%
4/ 8 50.0%
7/ 8 87.5%
8/ 8 100.0%
5/ 8 62.5%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008: COMBINED ORAL (GAVAGEI FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C42 (PAGE 7) : ACOUSTIC STARTLE - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER
MATERNAL DOSAGE GROUP IV
1 ,.6 MG/KG/DAY
8906 8909 8913 8919 8920 8921 8925 8926 8927 8928 8929
4/ 8
8/ 8
50.0% 100.0%
4/ 8
5/ 8
3/ 8
6/ 8
8/ 8
50.0% 62.5% 37.5% 75.0% 100.0%
4/ 8
4/ 8
5/ 8
4/ 8
6/ 8
50.0% 50.0% 62.5% 50.0% 75.0%
4/ 8
1/ 8
5/ 8
8/ 8
50.0% 12.5% 62.5% 100.0%
3/ 6
3/ 6
3/ 6
2/ 6
4/ 6
50.0% 50.0% 50.0% 33.3% 66.7%
4/ 8
8/ 8
50.0% 100.0%
0/ 7
2/ 7
4/ 7
5/ 7
1/ 7
0.0% 28.6% 57.1% 71.4% 14.3%
1/ 4
0/ 4
1/ 4
0/ 4
4/ 4
25.0%
0.0% 25.0%
0.0% 100.0%
0/ 2
0/ 2
0/ 2
0/ 2
1/ 2
0.0%
0.0%
0.0%
0.0% 50.0%
4/ 8
8/ 8
50.0% 100.0%
NO SURVIVING 1PUPS ON DAY 2 POSTPARTUM
8/ 8 100.0%
3/ 6 50.0%
0/ 7 0.0%
0/ 2 0.0%
4/ 6
6/ 6
66.7% 100.0%
2/ 7
7/ 7
28.6% 100.0%
0/ 2 0.0%
1/ 2 50.0%
1/ 2 50.0%
8930 8931 8932 8934 8935 8936
4/ 8
8/ 8
50.0% 100.0%
1/ 4
0/ 4
2/ 4
2/ 4
4/ 4
25.0%
0.0% 50.0% 50.0% 100.0%
0/ 8
2/ 8
5/ 8
8/ 8
0.0% 25.0% 62.5% 100.0%
2/ 8
3/ 8
5/ 8
5/ 8
1/ 8
25.0% 37.5% 62.5% 62.5% 12.5%
7/ 8
6/ 8
7/ 8
4/ 8
0/ 8
87.5% 75.0% 87.5% 50.0%
0.0%
NO SURVIVING PUPS ON DAY 4 POSTPARTUM
2/ 8 25.0%
8/ 8 100.0%
2/ 8 25.0%
4/ 8
8/ 8
50.0% 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-219
000505
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C42 (PAGE 8): ACOUSTIC STARTLE - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER t1
MATERNAL DOSAGE GROUP IV
1..6 MG/KG/DAY
8937 8939 8940
2/ 8 25.03
1/ 5 20.0%
8/ 8 100.0%
8/ 8 100.0%
0/ 5 0.0%
4/ 5 80.0%
1/ 5 20.0%
3/ 5
5/ 5
60.0% 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-000: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.91
TABLE C42 (PAGE 9): ACOUSTIC STARTLE - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
MATERNAL/LITTER (I
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8942
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8943
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8944
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8946
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8949
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8950
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8955
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8956
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8959
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8960
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8961
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8962
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8964
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8967
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8968
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8969
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8970
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8971
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-221
000507
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C42 (PAGE 10) : ACOUSTIC STARTLE - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
13
14
15
16
IT
18
19
20
21
MATERNAL/LITTER
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8974
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008PAGE C-222
000508
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 1): AIR RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER ft
MATERNAL DOSAGE GROUP1 I
0 (VEHICLE) MG/KG/DAY
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8819 8821 8823 8824 8826 8827 8828
2/ 8 25.0%
4/ 8 50.0%
1/ 8 12.5%
0/ 8 0.0% 3/ 8 37.5% 5/ 8 62.5%
1/ 8 12.5%
6/ 8 75.0%
1/ 8 12.5%
8/ 8 100.0%
1/ a 12.5%
5/ 8 62.5%
1/ 8 12.5%
0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ 8 0.0%
2/ 8 25.0%
5/ 8 62.5%
6/ 8 75.0%
2/ 8 25.0%
6/ 8 75.0%
3/ 8 37.5%
5/ 8 62.5%
6/ 8 75.0%
6/ 8 75.0%
8/ 8 100.0%
3/ 8 37.5%
2/ 8 25.0%
3/ 8 37.5%
0/ 8 0.0% 1/ 8 12.5% 5/ 8 62.5%
5/ 8 62.5%
8/ 8 100.0%
6/ 8 75.0%
3/ 8 37.5%
4/ 8 50.0%
5/ 8 62.5%
8/ 8 100.0%
8/ 8 100.0%
7/ 8 87.5%
8/ 8 100.0%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
5/ 8 62.5%
8/ 8 100.0%
6/ 8 75.0%
4/ 8 50.0%
3/ 8 37.5%
2/ 8 25.0%
1/ 8 12.5%
5/ 8 62.5%
8/ 8 100.0%
7/ 8 87.5%
4/ 8 50.0%
3/ 8 37.5%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
5/8 62.5%
8/ 8 100.0%
8/ 8 100.0%
8/8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008PAGE C-223
000509
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 2) : AIR RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER tt
MATERNAL DOSAGE GROUP i
0 (VEHICLE) MG/KG/DAY
8830 8831 8832 8833 8834 8835
2/ 8 25.0%
0/ 8 0.0% 1/ 8 12.5%
1/ 8 12.5%
1/ 8 12.5%
1/ 8 12.5%
4/ 8 50.0%
3/ 8 37.5%
0/ 8 0.0% 6/ 8 75.0% 3/ 8 37.5%
2/ 8 25.0%
4/ 8 50.0%
4/ 8 50.0%
3/ 8 37.5%
8/ 8 100.0%
4/ 8 50.0%
5/ 8 62.5%
3/ 8 37.5%
3/ 8 37.5%
3/ 8 37.5%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
5/ 8 62.5%
4/ 8 50.0%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
N/N * NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-224
000510
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 3) : AIR RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP II
0 .1 MG/KG/DAY
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 . 8860 8862 8863
1/ 8 12.51
0/ 8 0.01 2/ 8 25.0% 0/ 8 0.01 2/ 8 25.01 1/ 8 12.51 0/ a 0.0% 0/ 8 0.01
1/ 8 12.5%
0/ 8 0.01
1/ 8 12.51
0/ 8 0 .0 % 0/ 8 0.01 3/ 8 37.51 2/ 8 25.01 3/ 8 37.51 0/ 8 0.01 2/ 8 25.0%
6/ 8 75.01
1/ 8 12.51
3/ 8 37.51
2/ B 25.01
0/ 8 0.0% 3/ 8 37.5% 3/ 8 37.5%
5/ 8 62.51
3/ 8 37.51
1/ 8 12.5%
4/ 8 50.0%
1/ 8 12.5%
1/ 8 12.5%
1/ 8 12.5%
3/ 8 37.5%
5/ 8 62.5%
0/ 8 0.0% 5/ 8 62.5%
5/ 8 62.5%
6/ 8 75.0%
2/ 8 25.0%
8/ 8 100.0%
7/ 8 87.5%
8/ 8 100.0%
7/ 8 87.5%
8/ a 100.0%
5/ 8 62.5%
4/ 8 50.0%
5/ 8 62.5%
4/ 8 50.0%
3/ 8 37.5%
3/ 8 37.5%
6/ 8 75.0%
5/ 8 62.5%
5/ 8 62.5%
5/ 8 62.5%
7/ 8 87.5%
7/ 8 87.51
8/ 8 100.01
7/ 8 87.5%
6/ 8 75.0%
6/ 8 75.0%
5/ 8 62.5%
7/ 8 87.5%
6/ 8 75.0%
3/ 8 37.5%
5/ 8 62.5%
5/ 8 62.5%
6/ 8 75.0%
3/ 8 37.5%
5/ 8 62.5%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
S/ 8 62.5%
8/ 8 100.0%
7/ 8 87.5%
6/ 8 75.0%
6/ 8 75.0%
5/ 8 62.5%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-225
000511
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 4) : AIR RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER ft
MATERNAL DOSAGE GROUP ii
0 .1 MG/KG/DAY
8864 8865 8866 8867 8868 8869 8870
0/ 8 0.0%
1/ 8 12.5%
3/ 8 37.5%
3/ 8 37.5%
0/ 8 0.0%
2/ 8 25.0%
0/ 8 0.0%
5/ 8 62.5%
3/ 8 37.5%
1/ 8 12.5%
5/ 8 62.5%
3/ 8 37.5%
2/ 8 25.0%
1/ 8 12.5%
6/ a 75.0%
2/ 8 25.0%
6/ 8 75.0%
6/ 8 75.0%
7/ 8 87 .S%
4/ 8 50.0%
5/ 8 62.5%
8/ 8 100.0%
5/ 8 62.5%
4/ 8 50.0%
7/ 8 87.5%
6/ 8 75.0%
6/ 8 75.0%
8/ 8 100.0%
4/ 8 50.0%
7/ 8 87.5%
3/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
7/ 8 87.5%
8/ 8 100.0%
7/ 8 87.5%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-226
000512
418-008:PAGE C-227
000513
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 5) : AIR RIGHTING INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER tt
MATERNAL DOSAGE GROUP h i
0,.4 MG/KG/DAY
8872 8674 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896a 8897a 8898 8899
2/ 8 25.0%
0/ 8 0.0%
1/ 8 12.5%
2/ 6 33.3%
1/ 8 12.5%
2/ 8 25.0%
2/ 8 25.0%
4/ B 50.0%
1/ 8 12.5%
3/ 8 37.5%
0/ 8 0.0% 0/ 8 0.0% 0/ 3 0.0% 0/ 8 0.0% 0/ 8 0.0%
3/ 8 37.5%
0/ 8 0.0% 1/ 7 14.3%
2/ 8 25.0%
2/ 8 25.0%
0/ 8 0.0% 4/ 6 66.7% 2/ 8 25.0% 5/ 8 62.5% 3/ 8 37.5% 0/ 8 0.0% 5/ 8 62.5% 4/ 8 50.0% 6/ 8 75.0%
1/ 8 12.5%
1/ 3 33.3%
1/ 8 12.5%
3/ 8 37.5%
5/ 8 62.5%
5/ 8 62.5%
3/ 7 42.8%
3/ 8 37.5%
6/ 8 75.0%
3/ 8 37.5%
6/ 6 100.0%
2/ 8 25.0%
5/ 8 62.5%
3/ 8 37.5%
0/ 8 0.0% 4/ 8 50.0% 6/ 8 75.0% 2/ 8 25.0% 2/ 7 28.6% 2/ 3 66.7% 8/ 8 100.0% 3/ 8 37.5% 4/ 8 50.0% 2/ 8 25.0% 5/ 7 71.4%
8/ 8 100.0%
5/ 8 62.5%
7/ 8 87.5%
5/ 8 62.5%
5/ 8 62.5%
8/ 8 100.0%
8/ 8 100.0%
6/ 8 75.0%
6/ 8 75.0%
3/ 8 37.5%
2/ 6 33.3%
3/ 3 100.0%
6/ 8 75.0%
6/ 8 75.0%
5/ 8 62.5%
6/ 7 85.7%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
4/ 6 66.7%
8/ 8 100.0%
8/ 8 100.0%
5/ 8 62.5%
7/ 7 100.0%
6/ 6 100.0%
5/8 62.5%
8/8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER a. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pups were
arbitrarily distributed between the two dams and values will be included in group averages and statistical analyses.
t
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 6) : AIR RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER tt
MATERNAL DOSAGE GROUP III
0 .4 MG/KG/DAY
8900 8901 8902 8905
0/ 8 0.0 0/ 8 o.ot 0/ 8 0.0% 0/ 8 0.0%
2/ 8 25.0%
0/ 8 0.0% 2/ 8 25.0%
3/ 8 37.5%
1/ 8 12.5%
3/ 8 37.5%
4/ 8 50.0%
2/ 8 25.0%
4/ 8 50.0%
5/ 8 62.5%
5/ 8 62.5%
3/ 8 37.5%
8/ 8 100.0%
5/ 8 62.5%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 7) : AIR RIGHTING INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP IV
1 .6 MG/KG/DAY
8906 8909 8913 8919 8920 8921 8925 8926 8927 8928 8929
0/ 8
1/ 8
1/ 8
4/ 8
6/ 8
0.0% 12.5% 12.5% 50.0% 75.0%
1/ 8
0/ 8
3/ 8
4/ 8
8/ 8
12.5%
0.0% 37.5% 50.0% 100.0%
0/ 8 0.0%
1/ 8 12.5%
1/ 8 12.5%
6/ 8 75.0%
4/ 8 50.0%
0/ 8
0/ 8
2/ 8
4/ 8
6/ 8
0.0%
0.0% 25.0% 50.0% 75.0%
0/ 6
0/ 6
1/ 6
1/ 6
3/ 6
0.0%
0.0% 16.7% 16.7% 50.0%
0/ 8
0/ 8
1/ 8
3/ 8
5/ 8
0.0%
0.0% 12.5% 37.5% 62.5%
0/ 7
0/ 7
2/ 7
3/ 7
3/ 7
0.0%
0.0% 28.6% 42.8% 42.8%
0/ 4
0/ 4
0/ 4
0/ 4
2/ 4
0.0%
0.0%
0.0%
0.0% 50.0%
0/ 2
0/ 2
0/ 2
0/ 2
0/ 2
0.0%
0.0%
0.0%
0.0%
0.0%
0/ 8
1/ 8
3/ 8
6/ 8
4/ 8
0.0% 12.5% 37.5% 75.0% 50.0%
NO SURVIVING ]PUPS ON DAY 2 POSTPARTUM
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 6 100.0%
7/ 8 87.5%
4/ 7 57.1%
0/ 4 0.0% 1/ 2 50.0% 8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
7/ 7 100.0%
2/ 4 50.0%
1/ 2 50.0%
2/ 4 50.0%
1/ 2 50.0%
8930 8931 8932 8934 8935 8936
0/ 8
0/ 8
0/ 8
7/ 8
6/ 8
0.0%
0.0%
0.0% 87.5% 75.0%
1/ 4
0/ 4
0/ 4
0/ 4
2/ 4
25.0%
0.0%
0.0%
0.0% 50.0%
0/ 8
0/ 8
2/ 8
3/ 8
5/ 8
0.0%
0.0% 25.0% 37.5% 62.5%
0/ 8
0/ 8
8/ 8
0.0%
0.0% 100.0%
0/ 8
1/ 8
0/ 8
3/ 8
4/ 8
0.0% 12.5%
0.0% 37.5% 50.0%
NO SURVIVING PUPS ON DAY 4 POSTPARTUM
2/ 8 25.0%
2/ 4 50.0%
5/ 8 62.5%
8/ 8 100.0%
4/ 4 100.0%
7/ 8 87.5%
7/ 8
8/ 8
87.5% 100.0%
7/ 8 87.5%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER .
418-008:PAGE C-229
000515
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 8) : AIR RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP IV
1,.6 MG/KG/DAY
8937 B939 8940
0/ 8 0.04 0/ 5 0.0% 2/ 8 25.0%
1/ 8 12.5%
0/ 5 0.0%
0/ 8 0.0%
4/ 8 50.0%
0/ 5 0.0%
2/ 8 25.0%
1/ 8 12.5%
0/ 5 0.0% 5/ 8 62.5%
6/ 8 75.0%
3/ 5 60.0%
5/ 8 62.5%
8/ 8 100.0%
3/ 5 60.0%
8/ 8 100.0%
'5/ 5 100.0%
N/N NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-00B: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 9): AIR RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER #
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8942
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8943
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8944
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8946
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8949
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8950
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8955
NO SURVIVING PUPS ON DAY i OF LACTATION
8956
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8959
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8960
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8961
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8962
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8964
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8967
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8968
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8969
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8970
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8971
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-231
000517
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C43 (PAGE 10): AIR RIGHTING - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
14
15
16
17
18
19
20
21
MATERNAL/LITTER ft
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8974
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008-.PAGE C-232
000S1S
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 1): PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER ft MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8801 8803 8804 8805 B807 8808 8811 8812 8813 8814 8819 8821 8823 8824 8826 8827 8828
8/ 8 100 .0%
8/ 8 100. 0%
8/ 8 100. 0%
8/ 8 100. 0%
8/ 8 100 .0%
8/ 8 100. 0%
8/ 8 100 .0%
8/ 8 100 .0%
8/ 8 100 .0%
8/ 8 100 .0%
8/ 8 100 .0%
8/ 8 100. 0%
8/ 8 100. 0%
8/ 8 100 .0%
8/ 8 100. 0%
8/ 8 100 .04
8/ 8 100 .0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-233
000519
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 2): PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER 8 MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
8830 8831 8832 8833 8834 8835
8/ 8 100. 0%
8/ 8 100 .0%
8/ 8 100. 0%
8/ 8 100. 0%
8/ 8 100. 0%
8/ 8 100. 0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008.PAGE C-234
0005
O
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 3): PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER ft MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858 8860 8862 8863
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
N/N NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-235
000521
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 4): PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER U MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
8864 6865 8866 8867 8868 8869 8870
8/ 8 100 .0%
8/ 8 100. 0%
8/ 8 100 .0%
8/ a 100. 0%
8/ 8 100 .0%
8/ 8 100. 0%
8/ 8 100. 0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-236
000522
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 5): PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER ft MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896a 8897a 8898 8899
8/ 8 100 .ov
8/ 8 100 .0%
8/ 8 100 .0%
6/ 6 100. 0%
8/ 8 100. 0%
8/ 8 100. 0%
8/ 8 100. OV
8/ 8 100. ov
8/ 8 100. OV
8/ 8 100. ov
8/ 8 100. OV
6/ 6 100. OV
3/ 3 100 .0%
8/ 8 100 .OV
8/ 8 100. OV
8/ 8 100. 0%
8/ 8 100 .OV
7/ 7 100. ov
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER a. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pups were
arbitrarily distributed between the two dams and values will be included in group averages and statistical analyses.
418-008: PAG EC-237
000523
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 6) : PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER # MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
8900 8901 8902 8905
8/ 8 100. 04
8/ 8 100 .04
8/ 8 100. 04
8/ 8 100. 04
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 7): PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER # MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
8906 8909 8913 8919 8920 8921 8925 8926 8927 8928 8929
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
6/ 6 100.0%
8/ 8 100.0%
7/ 7 100.0%
4/ 4 100.0%
2/ 2 100.0%
8/ 8 100.0%
NO SURVIVING PUPS ON DAY 2 POSTPARTUM
8930 8931 8932 8934 8935 8936
8/ 8 100.0%
4/ 4 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
NO SURVIVING PUPS ON DAY 4 POSTPARTUM
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-239
00052
PROTOCOL 418-008: COMBINED ORAL (GAVAGEl FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 8) : PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER # MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
8937 8939 8940
8/ 8 100. 0%
5/ 5 100 .0%
8/ 8 100 .0%
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-240
000526
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 9): PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER # MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8942
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8943
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8944
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8946
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8949
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8950
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8955
NO SURVIVING PUPS ON DAY i OF LACTATION
8956
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8959
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8960
NO SURVIVING PUPS ON DAY i OF LACTATION
8961
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8962
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8964
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8967
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8968
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8969
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8970
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8971
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-241
000527
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C44 (PAGE 10): PUPIL CONSTRICTION - INDIVIDUAL DATA - FI GENERATION LITTERS
POSTPARTUM DAY
21
MATERNAL/LITTER It MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8974
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION
N/N = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
418-008:PAGE C-242
000528
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 1): NECROPSY OBSERVATIONS INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
I 0 (VEHICLE)
8B01
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8B03
1 4,21
1 PUP: STILLBORN. ALL PUPS APPEARED NORMAL.
8804
4,21
ALL PUPS APPEARED NORMAL.
8805
1 4,21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
ALL PUPS APPEARED NORMAL.
8807
4,21
ALL PUPS APPEARED NORMAL.
8808
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8811 8812 8813 8814 8819 8821 8823 8824 8826 8827
4,21 4,21 4,21 4,21 4,21 4,21 4,21 4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8828
1 4,21
3 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8830 8831 8832
4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
6ZS000
418-008:PAGE C-243
PROTOCOL 418 006: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 2): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
I (Cont.) 0 (VEHICLE)
8833
1 4,21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL ALL PUPS APPEARED NORMAL.
8834
1 4,21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
ALL PUPS APPEARED NORMAL.
8835
4,21
ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
418-008:PAGE C-244
000530
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
II
0.1
8838
4,21
ALL PUPS APPEARED NORMAL.
8840
1 4,21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8841 8842 8844
4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8845
1 2 4,21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8846 8847 8849
4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8851
1 4,21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8852 8853 8854 8855 8857
4,21 4,21 4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8858
1 4,21
1 PUP: STILLBORN. ALL PUPS APPEARED NORMAL.
8860 8862 8863 8864 8865 8866 8867
4,21 4,21 4,21 4,21 4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
418-008:PAGE C-245
000531
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
II (Cont.) 0.1
8868
2 4,21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8869
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8870
4,21
ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERI NATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 5): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
III
0.4
8872
1
1 PUP: STILLBORN.
4,21
ALL PUPS APPEARED NORMAL.
8874 8875
4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8876
1 21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
ALL PUPS APPEARED NORMAL.
8881 8882
4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8885
1 21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8889 8890 8891
4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8892
4 21
ALL PUPS APPEARED NORMAL. 1 PUP: KIDNEYS, RIGHT. PELVIS, SLIGHT DILATION.
ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS APPEARED NORMAL.
8893
4 16
17
21
ALL PUPS APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: BRAIN, LATERAL VENTRICLES, SEVERE DILATION.
ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: BRAIN, LATERAL VENTRICLES, MODERATE DILATION
ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS APPEARED NORMAL.
8895
4,21
ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
418-008:PAGE C-247
000533
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 6): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
III (Cont.) 0.4
8896 8897
4.21 4.21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8898
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8899
13 4.21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8900
1 4,21
1 PUP: STILLBORN, ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8901
4,21
ALL PUPS APPEARED NORMAL.
8902
1 4,21
1 PUP: STILLBORN ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8905
4,21
ALL PUPS APPEARED NORMAL.
a Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
418-008:PAGE C-248
000534
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 7) : NECROPSY OBSERVATIONS INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
8906
1 4,21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
ALL PUPS APPEARED NORMAL.
8909
4,21
ALL PUPS APPEARED NORMAL.
8913
3 4,21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8919
4,21
ALL PUPS APPEARED NORMAL.
8920
1 2 21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
ALL PUPS APPEARED NORMAL.
8921
1 4,21
1 PUP: STILLBORN. WHOLE BODY EDEMA. ALL OTHER TISSUES APPEARED NORMAL.
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8925
2
10 4,21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL ALL PUPS APPEARED NORMAL.
8926
2 3 21
5 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
ALL PUPS APPEARED NORMAL.
Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
418-008:PAGE C-249
000535
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 8) : NECROPSY OBSERVATIONS INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
IV (Cont.) 1.6
8927
2
3 5
21
4 PUPS: FOUND DEAD. NO MILK IN STOMACH. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 3 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL, 4 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8928
4,21
ALL PUPS APPEARED NORMAL.
8930
1 4,21
4 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8931
1 21
1 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL 6 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL PUPS APPEARED NORMAL.
8932
2
3 4,21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
2 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
418-008:PAGE C-250
000536
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 9) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
IV (Cont.) 16
8934
1 4.21
2 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAIf.
ALL PUPS APPEARED NORMAL.
'
8935
4 4.21
1 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8936
1
2 3 4
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 4 PUPS: FOUND DEAD. NO MILK PRESENT IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 2 PUPS: FOUND DEAD. NO MILK PRESENT IN STOMACH. 2 PUPS: FOUND DEAD. NO MILK PRESENT IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 6 PUPS: FOUND DEAD. NO MILK PRESENT IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8937
1 21
2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8939
1 21
2 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 6 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
8940
1 4,21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
a Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
418-008:PAGE C-251
000537
PROTOCOL 418-006: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 10) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
V
3.2
8942
1
6 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8943
4 PUPS: STILLBORN. 2 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8944
2 PUPS: STILLBORN. 3 PUPS: FOUND DEAD. NO MILK IN STOMACH.
8946
1 2
3 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 7 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8949
2
9 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL.
8950
1
2 PUPS: STILLBORN. 4 PUPS: FOUND DEAD.
8955
1
2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 7 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8956
1
1 PUP: FOUND DEAD. NO MILK IN STOMACH.
BOTH HINDLIMBS, MISSING; PORTION OF TAIL,
MISSING.b
ALL OTHER TISSUES APPEARED NORMAL.
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL.
2 11 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
b. Presumed cannibalized by dam.
418-008:PAGE C-252
000538
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE C45 (PAGE 11) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
V (Cont.) 15
8959
1 2
3 PUPS: 2 PUPS:
a PUPS:
STILLBORN. ALL TISSUES APPEARED NORMAL. FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL. FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
8960
1
9 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 4 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8961
1 2
3 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 8 PUPS : FOUND DEAD. NO MILK IN STOMACH.
PORTION OF TAIL, MISSING, b ALL OTHER TISSUES APPEARED NORMAL.
8962
1
3 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8964
1 2
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 5 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8967
1
8 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL.
8968
1 2
6 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 2 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy. Presumed cannibalized by dam.
418-008:PAGE C-253
00053
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OK PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.91
TABLE C45 (PAGE 12): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
V (Cont.) 2
8969
1
4 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
8970
1 2
2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 9 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8971
2
6 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
8973
1
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. 9 PUPS: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL.
8974
1
3 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 8 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL
8975
1 12 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table C38) for external clinical observations confirmed at necropsy.
418-008:PAGE C-254
000540
APPENDIX D REPORT TABLES - F1 GENERATION MALE RATS
000541
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D1 (PAGE 1): CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II 0 (VEHICLE) 0.1
III 0.4
MAXIMUM POSSIBLE INCIDENCE
2207/ 25 2196/ 25 221S/ 25
FOUND DEAD
2a ,b
1c
0
INCISORS: TOTAL MISALIGNED MISSING/BROKEN
96/ 3 87/ 2 13/ 2
152/ 8 108/ 4
76/ 7
97/ 4 94/ 3 17/ 2
CHROMORHINORRHEA
7/ lb 9/ 4
6/ 4
ABRASION d
0/ 0 61/ 4 32/ 2
CHROMODACRYORRHEA
58/ 1 50/ 4 38/ 1
BASE OF TAIL: LACERATION
0/ 0
0/ 0 11/ 1
SNOUT : SWOLLEN
0/ 0
8/ 2
3/ 1
RED PERIORAL SUBSTANCE
0/ 0
1/ 1
1/ 1
PENIS: RED SUBSTANCE
0/ 0
0/ 0
2/ 1
LOCALIZED ALOPECIA:
TOTAL BACK LIMBS HEAD
6/ 1 0/ 0 6/ 1 0/ 0
66/ 4 16/ 3** 29/ 1 24/ 1
0/ 0 0/ 0 0/ 0 0/ 0
BACK: SCAB
14/ 1
8/ 2
0/ 0
URINE-STAINED ABDOMINAL FUR
0/ 0
4/ 1
0/ 0
SOFT OR LIQUID FECES
0/ 0
1/ 1
0/ 0
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rat 13105 was found dead on day 87 postweaning. b. Rat 13116 was found dead on day 86 postweaning. c. Rat 13138 was found dead on day 66 postweaning. d. Located on the head,corner of left eye, left forelimb or back. " Significantly different from the vehicle control group value (p^O.Ol).
418-008:PAGE D-1
000542
418-008PAGE D-2
000543
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D1 (PAGE 2): CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II 0 (VEHICLE) 0.1
hi
0.4
MAXIMUM POSSIBLE INCIDENCE
2207/ 25 2196/ 25 2215/ 25
FOUND DEAD
2a ,b
1c
0
EARS: SWOLLEN AND PURPLE
9/ 1
0/ 0
0/ 0
RALES
2/ 1
0/ 0
0/ 0
GASPING
1/ 1
0/ 0
0/ 0
EXCESS SALIVATION
1/ 1
0/ 0
0/ 0
EYES: DILATED PUPIL
1/ 1
0/ 0
0/ 0
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rat 13105 was found dead on day 87 postweanlng. b. Rat 13116 was found dead on day 86 postweaning. c. Rat 13138 was found dead on day 66 postweanlng.
i
PROTOCOL 418-008 : COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D2 (PAGE 1): BODY WEIGHTS - SUMMARY FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
BODY WEIGHT (G)
DAY 1 DAY 8
MEAN+S.D. MEAN+S.D .
54.0 + 5.8 101.6 + 10.3
52.1 + 5.3 98.2 + B.l
50.8 + 4.9 [ 23] a
96.4 + 8.5
DAY 15
MEAN+S.D .
161.8 + 13.6
156.2 + 11.6
154.5 + 11.8
DAY 22
MEAN+S.D .
223.7 + 17.1
219.6 + 14.0
216.6 + 15.4
DAY 29
MEAN+S.D .
285.0 + 21.1
279.4 + 17.2
277.2 + 21.0
DAY 36
MEAN+S.D .
338.2 + 25.6
334.7 + 20.9
332.4 + 22.8
DAY 43
MEAN+S.D .
381.1 + 30.3
377.9 + 21.6
373.3 + 26.2
DAY 50
MEAN+S.D .
420.5 + 33.4
414.0 + 25.3
410.6 + 32.9
DAY 57
MEAN+S.D .
448.4 + 34.2
437.0 + 29.5
436.8 + 37.4
DAY 64
MEAN+S.D .
472.2 + 36.9
465.1 + 34.3
462.6 + 44.0
PRECOHABITATION b
TERMINAL BODY WEIGHT d
MEAN+S.D. MEAN+S.D.
508.6 + 42.8
542.0 + 50.9 l. 23] c
499.2 + 39.0 ( 24]1c
533.0 + 43.6 ( 24]1c
494.8 + 51.1 522.3 + 54.6
DAY = DAY POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values that were not recorded. b. Precohabitation body weights were recorded on the day that cohabitation began for the FI generation rats; at that time these
rats were 85 to 97 days of age. c. Excludes values for rats that were found dead. d. Terminal body weights were recorded when the rats were 100 to 112 days of age.
418-008: PAGE D-3
000544
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D3 (PAGE 1): BODY WEIGHT CHANGES - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
BODY WEIGHT CHANGE (G)
DAYS 1 - 8 DAYS 8 - 15
MEAN+S.D . MEAN+S.D.
+47.7 + 5.5 +60.2 + 6.8
+46.1 + 3.9 +58.0 + 5.3
+46.5 + 4.8 [ 23) a
+58.1 + 4.9
DAYS 15 - 22
MEAN+S.D .
+61.8 + 6.2
+63.5 + 4.8
+62.2 + 5.7
DAYS 22 - 29
MEAN+S.D .
+61.4 + 6.5
59.7 + 4.7
+60.6 + 8.0
DAYS 29 - 36
MEAN+S.D .
+53.2 + 10.8
+55.3 + 9.2
+55.2 + 5.0
DAYS 36 - 43
MEAN+S.D .
+42.9 + 8.5
+43.2 + 7.3
+40.9 + 8.9
DAYS 43 - 50
MEAN+S.D .
+39.4 + 6.5
+36.1 + 10.9
+37.3 + 10.2
DAYS 50 - 57
MEAN+S.D .
+27.8 + 8.7
+23.0 + 22.9
+26.3 + 7.2
DAYS 57 - 64
MEAN+S.D .
+23.9 + 8.6
+28.2 + 24.9
+25.8 + 13.9
DAY 1 PRECOHABITATION b
DAY 1 TERMINATION d
MEAN+S.D . MEAN+S.D .
+454.6 + 40.7
+488.0 + 48.6 l 23) C
+447.1 + 36.5 [ 24)lc
+480.9 + 41.2 l 24 )c
+443.5 + 51.4 ( 23]la
+471.2 + 55.3 l 23) a
DAY(S) = DAY(S) POSTWEANING [ ) = NUMBER OF VALUES AVERAGED a. Excludes values that were not recorded. b. Precohabitation body weights were recorded on the day that cohabitation began for the FI generation rats; at that time these
rats were 85 to 97 days of age. c. Excludes values for rats that were found dead. d. Terminal body weights were recorded when the rats were 79 to 91 days of age.
418-008PAGE D-4
000545
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D4 (PAGE 1) : ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - SUMMARY - FI GENERATION MALE RATS
418-008.PAGE D-5
CD
f1--l4
000546
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
RATS TESTED N 25
25
FEED CONSUMPTION (G/DAY)
DAYS 1 - 8
MEAN+S.D .
14.7 + 1.5
1.3*
DAYS 8 - 15
MEAN+S.D .
21.7 + 1.5
22.1 + 2.3
DAYS 15 - 22 DAYS 22 - 29
MEAN+ S .D . MEAN+S.D .
26.0 + 2.2 1 24) a
28.8 + 2.0
25.8 1.4 29.2 + 1.6
DAYS 29 - 36
MEAN+S.D .
30.3 + 3.5
30.0 + 3.1
DAYS 36 - 43
MEAN+S.D .
32.2 + 2.8
32.6 + 2.9
DAYS 43 - 50 DAYS 50 - 57
MEAN+S.D . MEAN+S.D .
32.4 + 3.4 ( 24) a
32.3 + 2.8
33.0 + 3.3 [ :24 ]a
31.7 2.2
DAYS 57 - 64b DAYS 1 - 64b
MEAN+S.D . MEAN+S.D .
30.5 + 2.7 [ 22) a
27.3 + 1.7 ( 221a
30.2 +_ 4.1 27.6 + 1.5
DAYS = DAYS POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Spilled feed precluded the calculation of this value. b. Last value recorded before cohabitation. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p<0.01).
III 0.4
25
13.4 + 2.9** 20.8 3.2 25.4 + 1.7 28.5 + 2.3 29.9 2.3 31.7 + 2.6 31.7 3.1 31.5 +_ 3.1 30.9 +_ 3.2 27.1 + 1.9
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D5 (PAGE 1): RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
RATS TESTED
N
25
25
FEED CONSUMPTION (G/KG/DAY)
DAYS 1 - 8
MEAN+S.D.
189.9 + 17.6
184.9 + 17.8
DAYS 8 - 15
MEAN+S.D .
165.5 + 11.0
174.5 + 16.3
DAYS 15 - 22 DAYS 22 - 29
MEAN+S.D. MEAN+S.D .
135.6 + 7.2 [ 24) b
113.5 + 5.4
137.6 + 7.1 117.1 + 4.6*
DAYS 29 - 36
MEAN+S.D .
97.3 + 8.9
97.7 + 8.1
DAYS 36 - 43
MEAN+S.D .
89.6 + 6.2
91.4 + 6.9
DAYS 43 - 50 DAYS 50 - 57
MEAN+S.D. MEAN+S.D .
80.7 + 5.5 ( 24 ]b
74.5 + 4.6
83.4 + 7.6 [ 24]lb
74.7 + 4.1
DAYS 57 - 64c DAYS 1 - 64c
MEAN+S.D. MEAN+S.D.
67.2 + 4.7 l 22)b
96.2 + 4.1 [ 22] b
67.1 8.4 97.4 + 3.8
DAYS = DAYS POSTWEANING ( ) = NUMBER OF VALUES AVERAGED a. Excludes values that were not recorded. b. Spilled feed precluded the calculation of this value. c. Last value recorded before cohabitation. * Significantly different from the vehicle control group value (p^O.05).
III 0.4
25
183.6 + 38.1 ( 23) a
166.4 23.9 137.3 7.6 115.3 4.8
98.1 + 4.2 90.0 + 6.6 80.9 + 6.0 74.2 +_ 3.8 68.6 + 3.8 96.6 3.6
[ 23 ]b
418-008:PAGE D-6
000547
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D6 (PAGE 1): SEXUAL MATURATION - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
MALE RATS
N 25
25
PREPUTIAL SEPARATION a MEAN+S.D.
45.0 + 2.1
45.7 + 2.3
a. Average day postpartum that the prepuce was observed to be separated.
III 0.4
25
45.1 + 1.8
418-008:PAGE D-7
000548
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D7 (PAGE I) : PASSIVE AVOIDANCE PERFORMANCE SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
MALE RATS
SESSION la
N
23
25
22
TRIALS TO CRITERION LATENCY TRIAL lb LATENCY TRIAL 2b FAILED TO LEARN c
MEANtS.D . MEAN+S.D. MEAN+S.D.
N (%)
4.6 8.9 21.4
0<
+ 1.0 + 5.0 15.8 0 .0)
6.1 7.8 20.1
It
+ 2.9 4.8
+ 19.7 4 .0)
4.8 10.5 23.9
0<
+ 1.1 + 6.0 20.7 0. 0)
SESSION 2a
N
23
24
22
TRIALS TO CRITERION LATENCY TRIAL lb
MEAN+S.D. MEAN+S.D.
3.3 + 2.6 32.8 + 22.2
3.6 + 2.2 28.2 + 23.5
3.5 + 2.7 33.1 22.4
a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c. Number of rats that did not meet the criterion in Session 1 (Learning Phase).
418-008:PAGE D-8
000549
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE D8 (PAGE 1): WATERMAZE PERFORMANCE - SUMMARY - FI GENERATION WALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
MALE RATS
SESSION la
N
23
25
21
TRIALS TO CRITERION ERRORS PER TRIAL LATENCY TRIAL 2b FAILED TO LEARN c
MEAN+S.D. MEAN+S.D. MEAN+S.D.
N (%)
9.1 + 3.1 0.37 + 0.17 11.7 + 7.4
0( 0 . 0)
9.4 + 3.0 0.40 + 0.24 13.7 + 13.9
2 ( 8..0)
9.0 + 3.0 0.43 + 0.22 10.6 + 6.0
0( 0 . 0)
SESSION 2a
N
23
23
21
TRIALS TO CRITERION ERRORS PER TRIAL LATENCY TRIAL lb
MEAN+S.D. MEAN+S.D. MEAN+S.D.
6.4 + 2.6 0.12 + 0.20 10.3 + 8.3
6.3 + 1.9 0.08 + 0.11 9.1 + 6.5
5.5 + 0.9 0.09 + 0.15 10.7 + 6.7
a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c. Number of rats that did not meet the criterion in Session 1 (Learning Phase); Session 2 (Retention Phase) values for these
rats were excluded from group averages and statistical analyses.
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D9 (PAGE 1) : MATING AND FERTILITY - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS IN COHABITATION
N
23a
24b
25
DAYS IN COHABITATION C MEAN+S.D
3.2 + 2.1
3.4 + 1.9
2.6 + 1.5
RATS THAT MATED d
N (%)
20( 87.0)
22( 91.7)
25(100.0)
FERTILITY INDEX e,f
N/N (%)
19/20 ( 95.0)
20/22 ( 90.9)
24/25 ( 96.0)
RATS WITH CONFIRMED
MATING DATES g
N
20
22
25
RATS MATING h DAYS 1-7
N (%)
20(100.0)
22 ( 92.0)
25(100.0)
RATS PREGNANT/RATS IN COHABITATION g
N/N <%)
19/23 ( 82.6)
20/24 ( 83.3)
24/25 ( 96.0)
a. Excludes values for rats that were not assigned to cohabitation because there were no available female rats. b. Excludes values for rat 13138, which was found dead day 66 postweaning. c. Restricted to rats with a confirmed mating date on days 1 to 7 of cohabitation and rats that did not mate. d. Includes only one mating for each male rat. e. Number of pregnancies/number of rats that mated. f. Includes only one pregnancy for each rat that impregnated more than one female rat. g. Includes only one confirmed mating for each male rat. h. Restricted to rats with a confirmed mating date during days 1 to 7 of cohabitation.
418-008PAGE D-10
000551
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE DIO (PAGE 1) : NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS EXAMINED a FOUND DEAD APPEARED NORMAL
N N N
25 2b, c
23
25 Id
21d
25 0
23
ABDOMINAL ADIPOSE TISSUE:
RED WITH FIRM AREAS
N
0
0
1
KIDNEYS:
BILATERAL, LARGE
N
0
0
1
PARENCHYMA, NUMEROUS
FLUID-FILLED CYSTS
N
0
0
1
RIGHT OR LEFT, PELVIS,
SLIGHT DILATION
N
0
2
0
LEFT, PELVIS,
SIX CALCULI
N
0
i
0
TESTES: BILATERAL OR RIGHT, PURPLE AND/OR FLACCID
N
0
3" 0
EPIDIDYMIDES: BILATERAL OR RIGHT, FLACCID
N
0
3** 0
LEFT OR RIGHT, SMALL
N
0
2
0
URETERS:
LEFT, DILATED
N
0
1
0
a. Refer to the individual clinical observations table (Table D13) for external observations confirmed at necropsy. b. Rat 13105 was found dead on day 87 postweaning. c. Rat 13116 was found dead on day 86 postweaning. d. Rat 13138 was found dead on day 66 postweaning. ** Significantly different from the vehicle control group value (p<0.01).
418-008:PAGE D-11
000552
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE DIO (PAGE 2) : NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS EXAMINED a
N
25
25
25
FOUND DEAD
N
2b,c
Id
0
URINARY BLADDER: WALLS, THICKENED AND NUMEROUS CALCULI
N
0
10
THORACIC CAVITY: DARK RED CLOTTED MATERIAL N
lc
0
0
LUNGS: ALL LOBES, DARK RED
N
lb
0
0
EXTERNAL OBSERVATIONS: RED PERINASAL SUBSTANCE
N
lc
0
0
a. Refer to the individual clinical observations table (Table D13) for external observations confirmed at necropsy. b. Rat 13105 was found dead on day 87 postweaning. c. Rat 13116 was found dead on day 86 postweaning. d. Rat 13138 was found dead on day 66 postweaning.
418-008:PAGE D-12
000553
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Dll (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)a
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
23a
24a
25
TERMINAL BODY WEIGHT
MEAN+S .D .
542.0 + 50.9
533.0 + 43.6
522.3 + 54.6
EPIDIDYMIS LEFT
TESTIS LEFT
SEMINAL VESICLES WITH FLUID
SEMINAL VESICLES WITHOUT FLUID
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+ S .D .
0.67 + 0.07 1.77 + 0.16 1.75 + 0.33 1.04 + 0.17
0.65 + 0.06 [ 23] b
1.80 + 0.16 ( 23) b
1.72 + 0.24 ( 22]b
1.05 + 0.19
0.63 + 0.04 1.79 + 0.12
1.62 + 0.20 [ 24 ]b
0.96 + 0.15
EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE
MEAN+S.D. MEAN+S.D. MEAN+S.D.
0.67 + 0.06 1.78 + 0.18 0.93 + 0.19
0.66 + 0.05 ( 21] b
1.79 + 0.15 [ 21] b
0.91 + 0.22
0.64 + 0.04 1.82 + 0.12 0.89 + 0.19
ALL HEIGHTS HERE RECORDED IN GRAMS (G). ( 1 = NUMBER OF VALUES AVERAGED a. Excludes values for rats that were found dead. b. Excludes values for rats that had abnormal organs (weight affected) or organs damaged (weight affected) .
418-008:PAGE D-13
000554
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D12 (PAGE 1): RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT - SUMMARY - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)a
RATS TESTED
N
I 0 (VEHICLE)
25
II 0.1
25
III 0.4
25
INCLUDED IN ANALYSES
N
23a
24a
25
TERMINAL BODY WEIGHT
MEAN+S.D.
542.0 + 50.9
533.0 + 43.6
522.3 + 54.6
EPIDIDYMIS LEFT
TESTIS LEFT
SEMINAL VESICLES WITH FLUID
SEMINAL VESICLES WITHOUT FLUID
MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D .
0.124 + 0.017 0.329 + 0.041 0.325 + 0.068 0.193 + 0.037
0.122 + 0.014 [ 23 ]b
0.332 + 0.043 t 23) b
0.325 + 0.055 t 22}b
0.198 + 0.037
0.121 + 0.014 0.346 + 0.037
0.316 + 0.055 l 24) b
0.184 + 0.032
EPIDIDYMIS RIGHT TESTIS RIGHT PROSTATE
MEAN+S.D . MEAN+S.D . MEAN+S.D .
0.124 + 0.016 0.331 + 0.043 0.172 + 0.035
0.125 + 0.012 ( 21Jb
0.339 + 0.042 [ 21 )b
0.171 + 0.043
0.122 + 0.015 0.351 + 0.037 0.170 + 0.035
ALL WEIGHTS WERE RECORDED IN GRAMS (G)
RATIOS (%) = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
[ ] = NUMBER OF VALUES AVERAGED
a. Excludes values for rats that were found dead.
b. Excludes values for rats that had abnormal organs (weight affected) or organs damaged (weight affected).
418-008:PAGE D-14
000555
*
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D13 (PAGE 1) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT It
DESCRIPTION
13101 13102 13103 13104 13105 13106
13107 13108 13109 13110
13111 13112 13113 13114 13115 13116
13117 13118
13119 13120 13121 13122
13123 13124
13125
DP ( 87 ) DP ( 52- 65) DPI 66 )
DPI 81- 89)
DP ( 32- 33) DPI 34 ) DPI 32- 89) DPI 38- 89)
DPI 67- 72) DPI 79 ) DPI 86 )
DPI 68- 76) DPI 77 )
DPI 55- 87) DPI 80- 85) DPI 86 ) DPI 84- 87)
DPI 81 ) DPI 81 ) DPI 81 ) DPI 81- 82)
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS FOUND DEAD BACK: SCAB (1.0 CM IN DIAMETER) SCAB HEALED NO ADVERSE FINDINGS EARS: SWOLLEN AND PURPLE a NO ADVERSE FINDINGS INCISORS: MISALIGNED INCISORS : REALIGNED CHROMODACRYORRHEA a INCISORS: MISALIGNED a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS CHROMORHINORRHEA CHROMORHINORRHEA FOUND DEAD NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: GROWN IN NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISALIGNED a LOCALIZED ALOPECIA: LIMBS ALOPECIA NO LONGER APPARENT INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS EYES : DILATED PUPIL EXCESS SALIVATION GASPING RALES NO ADVERSE FINDINGS
DP = DAY POSTWEANING a. Observation confirmed at necropsy.
418-008:PAGE D-15
000556
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D13 (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT ft
DESCRIPTION
13126 13127 13128 13129 13130 13131
13132 13133
13134 13135 13136 13137 13138 13139 13140
DP ( 43- 46) DP ( 47 )
DP ( 40- 49) DP ( 50- 51) DP ( 52 ) DP ( 52- 53) DP ( 54 ) DP ( 73- 74) DP ( 73- 75) DP ( 73- 87) DP ( 88 ) DP ( 80 ) DP ( 82- 89)
DP ( 52- 70) DP ( 71 ) DP ( 71- 82) DP ( 83 ) DP ( 80- 89)
DP ( 66 )
NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: GROWN IN NO ADVERSE FINDINGS BACK: ABRASION (1.5 CM X 0.5 CM) BACK: SCAB (0.5 CM IN DIAMETER) SCAB HEALED LOCALIZED ALOPECIA: BACK ALOPECIA NO LONGER APPARENT CHROMORHINORRH EA CHROMODACRYORRHEA INCISORS: MISSING/BROKEN INCISORS : GROWN IN CHROMORHINORRH EA INCISORS : MISALIGNED a NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS ALOPECIA NO LONGER APPARENT LOCALIZED ALOPECIA: BACK ALOPECIA NO LONGER APPARENT LOCALIZED ALOPECIA: LIMBS a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS
DP = DAY POSTWEANING a. Observation confirmed at necropsy.
418-008:PAGE D-16
000557
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D13 (PAGE 3) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT tt
DESCRIPTION
13141
13142
13143 13144
13145 13146
DP ( 32- 34) DP ( 32- 36) DP ( 37 ) DP ( 32- 46) DP ( 2 1 - 41) DPI 42 ) DP ( 51- 64) DP ( 65 ) DPI 62 ) DPI 64- 67) DPI 75- 88) DPI 85- 88) DPI 51 ) DPI 51 ) DPI 51 ) DPI 51- 53) DPI 54 ) DPI 51- 78) DPI 79 ) DPI 81- 88) DPI 19- 22) DPI 39- 50) DPI 51 ) DPI 43 ) DPI 51- 52) DPI 53 ) DPI 65 ) DPI 65- 79) DPI 80 ) DPI 40- 44) DPI 45 ) DPI 21 )
CHROMORHINORRH EA SNOUT: SWOLLEN SWELLING RESOLVED CHROMODACRYORRHEA INCISORS: MISSING/BROKEN INCISORS: GROWN IN INCISORS: MISALIGNED INCISORS: REALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA INCISORS: MISALIGNED a INCISORS: MISSING/BROKEN a CHROMODACRYORRHEA CHROMORHINORRHEA PERIORAL SUBSTANCE SNOUT: SWOLLEN SWELLING RESOLVED INCISORS: MISALIGNED INCISORS: REALIGNED INCISORS: MISALIGNED a URINE-STAINED ABDOMINAL FUR BACK: ABRASION (1.5 CM X 0.5 CM) ABRASION NO LONGER APPARENT CHROMORHINORRHEA LOCALIZED ALOPECIA: BACK ALOPECIA NO LONGER APPARENT CHROMORHINORRHEA INCISORS: MISSING/BROKEN INCISORS: GROWN IN INCISORS: MISSING/BROKEN INCISORS: GROWN IN SOFT OR LIQUID FECES
DP = DAY POSTWEANING a. Observation confirmed at necropsy.
418-008PAGE D-17
000558
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D13 (PAGE 4) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT tt
DESCRIPTION
13147
13148
13149 13150
DP ( 53 ) DP ( 53- 74) DP ( 75 ) DP ( 53- 88) DP ( 60- 73) DP ( 63- 71) DP ( 72 ) DP ( 63- 86) DP ( 87 ) DP ( 78- 88) DP ( 29- 58) DP ( 59 ) DP ( 29- 58) DP ( 51- 58) DP ( 59- 64) DP ( 65 ) DP ( 59- 64) DP ( 65 ) DP ( 4- 9) DP ( 10 )
CHROMODACRYORRHEA INCISORS: MISSING/BROKEN INCISORS: GROWN IN INCISORS: MISALIGNED a CHROMODACRYORRHEA CORNER OF LEFT EYE: ABRASION ABRASION HEALED LOCALIZED ALOPECIA: HEAD ALOPECIA NO LONGER APPARENT CHROMODACRYORRHEA a LEFT SIDE OF BACK: ABRASION (1.0 CM IN DIAMETER) ABRASION HEALED RIGHT SIDE OF BACK: ABRASION (1.5 CM X 1.0 CM) LEFT SIDE OF BACK: ABRASION (0.5 CM IN DIAMETER) BACK: SCAB (0.5 CM IN DIAMETER) SCAB HEALED RIGHT SIDE OF BACK: SCAB (0.5 CM IN DIAMETER) SCAB HEALED INCISORS: MISSING/BROKEN INCISORS: GROWN IN NO ADVERSE FINDINGS
DP = DAY POSTWEANING a. Observation confirmed at necropsy.
418-008:PAGE D-18
000559
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D13 (PAGE 5): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT it
DESCRIPTION
13151 13152 13153 13154
13155
13156 13157 13158 13159
13160 13161 13162 13163 13164 13165 13166 13167 13168 13169 13170 13171 13171
13172
13173 13174
13175
DPI 10- 20) DP ( 62- 91) DP ( 52- 67) DP( 68 ) DP ( 82 ) DP ( 54 ) DP ( 54 ) DP ( 54- 56) DP ( 57 ) DP ( 54- 91) DP ( 54- 91) DP( 78- 91)
DP ( 35- 50) DP ( 51 ) DP ( 64- 89)
DPI 81- 82) DPI 81- 82) DPI 84 ) DPI 69- 70) DPI 78 )
DPI 68- 70) DPI 71 )
NO ADVERSE FINDINGS TAIL: LACERATION (5.0 CM FROM BASE) INCISORS: MISALIGNED a RIGHT SIDE OF HEAD: ABRASION (1.5 CM IN DIAMETER) ABRASION HEALED CHROMORHINORRHEA CHROMORHINORRHEA RED PERIORAL SUBSTANCE SNOUT : SWOLLEN SWELLING RESOLVED CHROMODACRYORRHEA a INCISORS: MISALIGNED a INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LEFT FORELIMB: ABRASION ABRASION NO LONGER APPARENT INCISORS: MISALIGNED a NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED SUBSTANCE: PENIS RED SUBSTANCE: PENIS CHROMORHINORRHEA CHROMORHINORRHEA CHROMORHINORRHEA NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: GROWN IN NO ADVERSE FINDINGS
DP = DAY POSTWEANING a. Observation confirmed at necropsy.
418-008PAGE D-19
000560
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D14 (PAGE 1): BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DAY B 15 22
36 43 50 57 64 71 PRECOHABITATION a
RAT ft
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13101 13102 13103 13104 13105 13106 13107 13108 13109 13110 13111 13112 13113 13114 13115 13116 13117 13118 13119 13120 13121 13122 13123 13124 13125
59. 42. 55. 54 . 54 . 53 . 56. 60. 62. 55. 59. 55. 54 . 64 . 51. 52. 46. 50. 48 . 48. 53. 62. 62. 51. 44 .
105. 84 .
100 . 102. 110. 106 . 108. 110. 110. 103 . 109. 106 . 101 . 121 .
97. 89. 91. 94 . 93 . 92. 95. 120 . 118. 90. 87.
158. 143 . 153 . 168. 173. 166. 167. 170. 170. 156. 174 . 169. 154. IBS. 154 . 143. 164 . 147. 168. 159. 145. 182. 190 . 145. 143.
216 . 209. 216. 232. 240. 236. 233. 232. 234 . 224 . 244 . 234 . 210. 250. 218 . 203 . 213 . 201. 217. 214 . 207. 247. 261. 201. 200.
270 . 274 . 276. 303 . 310 . 308 . 289. 295. 285. 292. 311. 296. 272. 310. 272 . 254 . 272 . 258. 281. 279. 259. 315 . 329. 255. 261.
323. 316. 325. 349. 367. 350. 356. 346. 345. 306. 374 . 355. 318. 366. 330. 307. 330. 308. 339. 338. 311. 374 . 401. 309. 312.
360. 365. 367. 393. 416. 400. 405. 401. 390. 356. 417. 388. 364. 409. 358. 336. 373. 336. 380. 396. 345. 414 . 459. 347. 353.
396 395 398 437 453 441 444 434 426 387 455 430 410 444 390 370 421 376 432 440 388 461 512 382 391
435. 430 . 433. 459. 474 . 457. 475. 470. 459. 422 . 495. 454. 430 . 464 . 401. 399. 443 . 398. 473 . 481. 415. 474 . 541. 410. 417.
458. 449. 455. 486. 504 . 486 . 500 . 472. 490 . 460. 519. 473 . 469. 490. 419. 422 . 472. 420. 505. 500. 433 . 484 . 579. 428. 433 .
478. 473 . 489. 509. 524 . 506. 532. 512 . 523 . 478. 541. 505. 511. 510. 428. 434 . 487. 430. 537. 539. 449. 518. 607. 448. 453.
501 488 515 526 541 526 551 528 521 492 554 511 512 520 434 435 506 448 556 554 457 519 607 452 461
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Precohabitation body weights were recorded on the day cohabitation was begun in the FI generation rats; at that time these rats were 85 to 97 days of age.
418-008:PAGE D-20
000561
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D14 (PAGE 2): BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DAY 78
85
RAT tt
DOSAGE GROUP I
13101 13102 13103 13104 13105 13106 13107 13108 13109 13110 13111 13112 13113 13114 13115 13116 13117 13118 13119 13120 13121 13122 13123 13124 13125
496. 477. 513 . 525. 541. 539. 552 . 541. 533 . 509. 563. 523 . 506. 538. 436. 445. 515. 445. 556. 558. 468. 530. 617. 469. 477.
513 . 503. 535. 544 . 569. 555. 567. 548. 538. 512. 579. 532. 516. 562. 444 . 454 . 528. 456. 577. 587. 485. 554. 640. 434 . 500.
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G).
0 (VEHICLE) MG/KG/DAY
418-008PAGE D-21
000562
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D14 (PAGE 3) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DAY 1
8 15 22 29 36 43 50 57 64 71 PRECOHABITATION a
RAT H
DOSAGE GROUP II
0.1 MG/KG/DAY
13126 13127 13128 13129 13130 13131 13132 13133 13134 13135 13136 13137 13138 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
44 . 54 . 48 . 36 . 54 . 55. 56. 54 . 52. 50. 50. 61. 52. 56. 46. 49. 51. 47. 52. 58. 54. 56. 59. 56. 52.
89. 105 .
93 . '75.
97. 100 . 103.
99. 100 .
96. 92 . 104. 100 . 109. 84 . 89. 100 . 94 . 100. 106 . 99. 102 . 113 . 106 . 100.
143 . 165 . 149. 124 . 152. 162. 155. 156. 160. 155. 150. 156 . 161. 170 . 139. 144 . 163 . 146. 169. 160 . 152. 157. 176 . 174 . 166.
202. 229. 212 . 187. 221. 227. 216. 220 . 229. 223 . 218. 210. 224 . 240. 197. 206. 228. 202 . 244 . 221. 214 . 216 . 236 . 241. 228.
264 . 296 . 264 . 237. 283 . 289. 270. 277. 297. 286. 274 . 270. 281. 300. 256. 260. 296. 260. 304 . 276 . 273. 276 . 301. 305. 289.
308. 342. 317. 295. 347. 347. 323 . 336. 356 . 338. 328. 327. 334 . 354 . 314 . 283 . 366 . 328. 354 . 330. 329. 335. 352. 370. 354 .
344 . 387. 362. 338. 405. 400 . 361. 382 . 403 . 384 . 369. 370. 390. 401. 348. 335. 409. 373. 378. 373 . 374 . 370. 390. 409. 392.
375. 419. 382. 356. 441. 445. 401. 418. 444 . 424 . 410. 398. 450. 440 . 374 . 385. 416 . 415. 417. 404. 417. 407. 429. 442. 441.
401. 446. 399. 365. 473 . 431. 448. 471 . 457. 441. 422. 478. 469. 398. 396. 410. 456. 446 . 411. 437. 448. 443. 453. 471. 454 .
423 . 471 . 410. 385. 512 . 508 . 460 . 472. 509. 489. 463 . 445. 498. 496. 417. 417. 494 . 470. 436 . 460. 475. 461. 494 . 487. 468.
443 . 494 . 435. 412. 542. 546. 501. 502. 536. 517. 490. 467.
b 510. 439. 440. 523. 508. 430. 477. 504 . 474 . 522. 499. 493 .
454 . 510 . 445 . 421. 557. 542 . 513. 509 556 . 528. 505 . 478.
b 529. 450 . 451. 546 . 521. 440. 490 . 520 . 480. 530. 511. 495.
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Precohabitation body weights were recorded on the day cohabitation was begun in the FI generation rats; at that time these
rats were 85 to 97 days of age. b. Rat 13138 was found dead on day 66 postweaning.
418-008:PAGE D-22
92000
418-008:PAGE D-23
000564
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D14 (PAGE 4) : BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DAY 78
85
RAT ft
DOSAGE GROUP !
13126 13127 13128 13129 13130 13131 13132 13133 13134 13135 13136 13137 13138 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
442.
463 .
504 .
523 .
439.
459.
428.
451.
568.
592 .
536 .
571.
511.
535.
516.
532 .
549.
575.
527.
559.
SOI.
524 .
473.
493 .
FOUND DEAD ON
539.
556.
448.
460.
461.
487.
552.
573.
520.
542.
435.
466.
494 .
505.
520.
542 .
489.
503.
533 .
557.
510.
542.
512.
529.
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G).
0.1 MG/KG/DAY
i
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D14 (PAGE 5): BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DAY 1
8 15 22 29 36 43 50 57 64 71 PRECOHABITATION a
RAT #
DOSAGE GROUP III
0.4 MG/KG/DAY
13151 13152 13153 13154 13155 13156 13157 13158 13159 13160 13161 13162 13163 13164 13165 13166 13167 13168 13169 13170 13171 13172 13173 13174 13175
53 . 51. 51. 50. 55. 52. 57. 48. b 43 .b 51. 54 . 47. 50. 47. 51. 49. 48. 46 . 55. 49. 47. 62. 59. 44 . 40.
99. 104 . 101. 103 .
99. 94 . 106 . 91. 81. 97. 96 . 95. 99. 86 . 103 . 92. 91. 95. 98. 94. 90. 112. 115. 92. 77.
155. 160. 168. 167. 151. 146. 164 . 145 . 134. 158 . 152. 159. 162 . 133 . 159. 152 . 145. 152 . 154 . 152 . 148. 172 . 184 . 154 . 134 .
211. 223 . 238. 228. 210. 206. 235. 210 . 190. 217. 206. 233. 226. 189. 220. 209. 211. 219. 212 . 211. 205. 232. 257. 221. 197.
279. 283. 305. 291. 263 . 260. 316. 269. 253 . 280. 253. 305. 286. 244 . 276. 262. 274 . 275. 267. 281. 266 . 298. 326. 275 . 244 .
330 . 337. 356 . 338. 316. 308. 374 . 323 . 306. 334. 306. 372. 344 . 302 . 325. 320. 333. 335. 326. 344 . 316 . 349. 386. 335. 295.
382. 373 . 408. 380. 358. 342. 430. 375 . 358. 382 . 334 . 410. 389. 332. 365. 368. 380. 377. 357. 386 . 348. 384. 412. 380. 322.
418 . 405. 446. 411. 402 . 373. 478. 410. 391. 429. 359. 453 . 412. 362. 420. 406 . 411. 418 . 403. 436. 380. 424 . 470 . 411 . 336.
448. 439. 477 . 440. 412. 398. 517. 435. 425. 462. 375. 479447. 380. 453 . 434 . 437. 438. 424. 459. 404 . 443 . 503 . 440. 352.
465. 464. 488. 461. 436. 412. 554 . 461. 455. 492 . 395. 511. 471. 395. 477. 460. 460. 462. 446. 505. 421. 524 . 525. 463. 362.
498. 495. 514 . 485. 449. 437. 582. 483 . 482. 520. 403. 516. 489. 417. 501. 493. 485. 489. 471. 524. 445. 486 . 568. 484 . 370.
510. 513. 533. 500. 472. 451. 610 . 501. 501. 533 . 404 . 521. 498. 426. 507. 501. 498. 492 . 477. 552. 452. 488. 575. 493 . 362.
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Precohabitation body weights were recorded on the day cohabitation was begun in the FI generation rats; at that time these
rats were 85 to 97 days of age. b. Body weight was recorded on day 2 postweaning and was excluded from group averages and statistical analyses.
418-008:PAGE D-24
000565
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D14 (PAGE 6): BODY WEIGHTS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DAY 78
85
RAT #
DOSAGE GROUP III
13151 13152 13153 13154 13155 13156 13157 13158 13159 13160 13161 13162 13163 13164 13165 13166 13167 13168 13169 13170 13171 13172 13173 13174 13175
500. 504 . 524. 497. 464 . 446. 603 . 496. 503. 538. 415. 534. 498. 421. 501. 504 . 495. 491. 465. 549. 453. 485 . 571.
510. 388.
524 . 533. 546 . 501 . 477. 464 . 627. 506. 520 . 544 . 424 . 549. 533. 438. 519. 520 . 520. 515. 502 . 582 . 465 . 509. 596 . 510.
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
0.4 MG/KG/DAY
418-008PAGE D-25
000566
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR.' S STUDY NUMBER: 6295. 9)
TABLE D15 (PAGE 1): FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS
RAT #
DAYS 1 - 8 8 - 15 15 - 22 22 - 29 29 36 36 - 43 43 - 50 50 - 57 57 - 64a
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13101 13102 13103 13104 13105 13106 13107 13108 13109 13110 13111 13112 13113 13114 13115 13116 13117 13118 13119 13120 13121 13122 13123 13124 13125
103. 75.
113. 102. 121. 106. 118. 110 . 105.
96. 100.
80 . 105. 114. 102.
91. 103 . 101. 100. 100. 101. 116. 113. 102. 100 .
145. 134 . 147. 157. 180. 164. 164 . 155 . 147. 144 . 163 . 157. 148. 160. 145. 132. 151. 145. 148. 145 . 142. 159. 163. 152 . 159.
166. 170 . 181. 192. 215. 212. 187. 185.
b 179. 194. 197. 170. 185. 171. 160. 169. 161. 181. 178. 168. 202. 203. 179. 176.
176 197 194 205 227 217 201 197 198 215 218 218 192 209 194 180 192 179 203 195 188 227 221 203 202
192 . 205 . 205 . 226 . 246 . 228. 232 . 207. 211. 157. 215. 233 . 198. 213 . 199. 188. 194 . 177 . 215. 207. 188. 252. 262. 251. 209.
189. 201. 202. 218. 233 . 221. 231. 217. 219. 204 . 226. 253. 209. 241. 218. 216 . 250. 209. 248. 252 . 217. 250. 269. 223 . 221.
200. 194 .
b 227. 248. 228. 224. 228. 219. 192. 230. 239. 232. 236. 203. 214 . 252. 200. 250. 247. 222. 264 . 281. 184 . 232.
210. 213. 233 . 236 . 255. 231. 230. 232 . 228. 214. 224 . 235. 216. 223 . 191. 206. 227. 182 . 239. 236 . 222. 225. 281. 231. 244 .
200. 197. 217. 216 . 241. 220.
b 168. 225. 226. 234. 220 . 234. 219. 183. 199. 225. 185. 225. 238. 208.
b b 206. 211.
DAYS - DAYS POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value.
418-008:PAGE D-26
000567
PROTOCOL 418-008! COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D15 (PAGE 2) : FEED CONSUMPTION VALUES - INDIVIDUAL DATA - FI GENERATION MALE RATS
DAYS 1 - 8 8 - 1 5 15 - 22 22 - 29 29 36 36 - 4 3 43 - 50 50 - 57 57 - 64a
RAT tt
DOSAGE GROUP II
0.1 MG/KG/DAY
13126 13127 13128 13129 13130 13131 13132 13133 13134 13135 13136 13137 13138 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
89. 98. 92. 81. 94. 94 . 112. 99. 106 . 93. 95. 76. 101. 91. 93. 92. 98. 99. 105. 104 . 104. 100. 104 . 120. 84.
134 . 157. 141. 141. 153 . 151. 145. 151. 149. 146. 139. 204 . 169. 163 . 146 . 140. 190. 146 . 165. 153 . 163 . 165 . 158. 165. 144 .
163 . 190. 175. 172 . 186. 184 . 170. 182. 180. 180 . 175. 167. 186 . 197. 177. 158. 191. 175. 202. 185. 185. 182. 178. 195. 181.
190. 209. 191. 185. 205. 205. 186 . 214 . 215. 212 . 204 . 193. 214 . 218 . 200 . 189. 217. 197. 224 . 203 . 199. 207. 196. 219. 214 .
194 . 219. 213 . 207. 219. 208. 189. 222 . 219. 216 . 201. 207. 215 . 234. 205. 149. 279. 206. 209. 196. 194 . 216 . 194. 222. 219.
195. 215. 208. 203 . 226 . 220. 205. 232. 227. 219. 201. 210 . 246. 239. 249. 218. 284 . 248. 250. 220. 221. 237. 250. 240. 237.
199. 223. 196. 195. 227. 223 . 209. 225. 237. 235. 211. 221. 260. 242. 226. 252. 302. 260.
b 223 . 247. 238. 228. 229. 235.
194 . 219. 203. 192 . 231. 214 . 204 . 226. 229. 237. 211. 211. 253 . 236. 227. 203 . 222 . 247. 225. 229. 234 . 232 . 230. 224 . 224 .
192 . 210 . 192 . 184 . 233 . 218. 202 . 219. 235. 236. 205. 202. 250. 235 . 200. 203 . 101. 236. 210. 212 . 234 . 221. 235. 215. 209.
DAYS = DAYS POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value.
418-008PAGE D-27
000568
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D15 (PAGE 3) : FEED CONSUMPTION VALUES INDIVIDUAL DATA - FI GENERATION MALE RATS
DAYS 1 - 8 8 - 1 5 15 - 22 22 - 29 29 - 36 36 - 43 43 - 50 50 - 57 57 - 64a
RAT #
DOSAGE GROUP III
0.4 MG/KG/DAY
13151 13152 13153 13154 13155 13156 13157 13158 13159 13160 13161 13162 13163 13164 13165 13166 13167 13168 13169 13170 13171 13172 13173 13174 13175
88. 95. 102 . 10B. 103 . 99. 99. 90 . 81. 81. 90. 85. 100. 94 . 19. 95. 98. 92. 94 . 106. 88. 107. 150. 103. 89.
138. 142. 158. 155. 141 . 142. 145. 130. 127. 144 . 141. 150. 174 . 136. 157. 146. 144 . 183. 160. 158.
59. 169. 164 . 151. 138.
165. 178. 198. 189. 168. 170. 183 . 169. 165. 172. 160. 200. 189. 167. 169. 163 . 172. 184 . 172. 185. 189. 186 . 202. 179. 177.
187. 196. 217. 204 . 177. 186. 219. 183 . 178. 200. 177. 230. 215. 184 . 198. 187. 191. 203 . 194 . 212 . 209. 212. 235. 205. 185 .
195. 206. 221. 214 . 197. 207. 233. 208. 202. 222 . 185. 248. 215. 178. 193 . 199. 200. 209. 199. 219. 209. 218. 243 . 212. 203 .
212. 207. 224. 209. 197. 191. 244. 214. 209. 235. 189. 241. 252. 208. 231. 223 . 209. 224 . 236. 242. 247. 219. 228. 247. 210.
275. 191. 218. 223 . 213. 191. 250. 220. 207. 235. 180. 236. 204 . 197. 235. 229. 212. 227. 234. 239. 226. 228. 239. 242. 197.
223 . 209. 219. 215. 189. 197. 256. 226 . 224 . 238. 175. 233 . 239. 188. 239. 217. 220 . 220. 226. 237. 223. 217. 263. 238. 180.
215. 212. 201. 216. 200. 187. 252. 208. 216. 244 . 179. 236 . 227. 180. 234 . 214 . 210. 207. 218. 255. 210. 206. 262. 229. 185 .
DAYS = DAYS POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
418-008:PAGE D-28
000569
418-008:PAGE D-29
000570
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D16 (PAGE 1): SEXUAL MATURATION - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
PREPUTIAL RAT # SEPARATION (DAY)
13101 13102 13103 13104 13105 13106 13107 13108 13109 13110 13111 13112 13113 13114 13115 13116 13117 13118 13119 13120 13121 13122 13123 13124 13125
47 42 43 45 50 46 44 45 47 45 44 44 46 40 43 44 46 46 44 46 44 45 43 47 48
DAY = DAY POSTPARTUM
II 0.1
PREPUTIAL RAT ft SEPARATION (DAY)
13126 13127 13128 13129 13130 13131 13132 13133 13134 13135 13136 13137 13138 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
44 44 46 52 46 44 42 45 46 46 45 46 45 45 46 46 44 52 45 46 48 45 42 46 46
III 0.4
PREPUTIAL RAT It SEPARATION (DAY)
13151 13152 13153 13154 13155 13156 13157 13158 13159 13160 13161 13162 13163 13164 13165 13166 13167 13168 13169 13170 13171 13172 13173 13174 13175
47 43 46 43 47 46 48 45 46 46 47 45 41 44 44 46 44 42 43 48 46 44 44 45 47
i
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D17 (PAGE 1) : PASSIVE AVOIDANCE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
SESSION1 la
SESSION 2a
RAT NUMBER
TRIALS TO CRITERION
LATENCY b TRIAL 1 TRIAL 2
TRIALS TO LATENCY b CRITERION TRIAL 1
13101 13102 13103 13104 13106 13107 13108 13109 13110 13111 13112 13113 13114 13115 13116 13117 13118 13120 13121 13122 13123 13124 13125
6 B 10 5 15 18 4 12 26 5 7 16 4 12 13 5 16 6 5 48 6 9 38 3 22 60 4 8 28 4 2 20 5 10 4 6 16 4 7 21 4 5 28 6 8 11 4 7 32 5 5 23 5 57 6 6 14 4 11 36 3 17 60 7 77
15 25 3 15 3 46 3 34 3 12 3 45 36 3 18 2 60 4 60 3 19 3 27 2 60 38 2 60 2 60 2 60 2 60 37 3 48 32 3 12 3 10
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency wa3 recorded in seconds.
418-008PAGE D-30
000571
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D17 (PAGE 2): PASSIVE AVOIDANCE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
13126 13127 13128 13129 13130 13131 13132 13133d 13134 13135 13136 13137 13138 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
TRIALS TO CRITERION
4 4 4 7 6 9 8 15 3 5 5 10 4 5 4 5 12 4 7 7 3 5 5 8 4
LATENCY b TRIAL 1 TRIAL 2
3 15 6 17 9 17 14 3 6 16 15 3 29 12 6 16 60 14 11 7 21 11 24 25 13 56 4 42 52 6 19 54 4 14 13 60 14 60 48 9 22 9 28
TRIALS TO CRITERION
4 5 3c 4 2 4 3 8 3 13 4 3 3 2 3 3 3 3 2 2 6 3 3 2 3
LATENCY b TRIAL 1
6 11 60 13 60 60 11 25 27 13 60 13
7 60
4 15 24 12 60 60 19
7 8 60 7
SESSION = TEST SESSION a. Sessions I (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c. Maximum interval elapsed after the rat had entered the dark compartment. Shock was delivered and the trial was not counted
towards the criterion. d. Rat did not meet the criterion in Session 1 (Learning Phase); values for Session 2 (Retention Phase) were excluded from group
averages and statistical analyses.
418-008:PAGE D-31
000572
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D17 (PAGE 3): PASSIVE AVOIDANCE PERFORMANCE INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT NUMBER
SESSION la
TRIALS TO CRITERION
LATENCY b TRIAL 1 TRIAL 2
SESSION 2a
TRIALS TO LATENCY b CRITERION TRIAL 1
13151 13152 13153 13154 13156 13157 13158 13160 13161 13162 13163 13164 13165 13166 13168 13169 13170 13171 13172 13173 13174 13175
4 18 56 5 6 10 5 15 5 4 8 10 5 14 60 4 6 30 4 21 16 5 93 4 7 26 7 53 7 15 6 8 24 6 2 13 6 15 13 4 14 12 6 5 52 4 8 13 4 10 55 4 9 10 3 25 60 4 13 45 4 13 4
3 19 15 12
3 17 3 42 3 43 3 19 3 24 2 60 2 60 2 60 3 13 2 60 2 60 38 4 60 3 25 5 9. 34 3 14 3 54 4 60 35
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds.
418-008:PAGE D-32
000573
PROTOCOL 4IB -008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE DIB (PAGE 1) : WATERMAZE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 2
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 1
13101
7
0.28
13
13102
6 0.17 9
13103
7
0.43
19
13104
15
0.27
11
13106
7
0.28
14
13107
8 0.25 5
13108
11
0.18
13
13109
14
0.50
15
13110 10 0.20 6
13111
7
0.43
11
13112 10 0.20 7
13113
7
0.71
38
13114
12
0.42
10
13115
8 0.62 8
13116
7
0.57
18
13117
6 0.17 5
13118
12
0.50
22
13120
6 0.50 6
13121
9
0.44
11
13122 13 0.46 5
13123
6 0.17 6
13124
6 0.17 8
13125 15 0.53 9
5
0.00
11
12 0.33 6
5 0.00 6
5 0.00
6
5 0.00
9
5 0.00
5
5 0.00
5
15
0.33
13
7
0.14
12
5 0.00
5
5 0.00
6
6
0.17
16
5
0.00
11
9
0.33
13
5 0.00
8
5 0.00
5
6
0.83
42
5 0.00
6
9 0.22
7
5 0.00
7
7 0.14
9
5 0.00
5
6
0.33
24
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds.
418-008:PAGE D-33
OOOS74
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE DIB (PAGE 2) : WATERMAZE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 2
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 1
13126 13127 13128 13129c 13130 13131 13132 13133 13134 13135 13136 13137 13138c 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
6 10
9 15 10
7 8 6 9 15 13 6 15 8 12 8 12 10 7 6 10 9 6 12 7
0.17 0.50 0.22 0.60 0.80 0.28 0.25 0.17 0.22 0.80 0.85 0.17 0.93 0.25 0.50 0.25 0.25 0.30 0.28 0.17 0.70 0.33 0.17 0.50 0.28
a 48
7 7 9 12 7 6 5 10 60 9 13 6 16 8 7 7 13 7 39 13 8 7 10
5
0.00
10
5 0.00 7
9 0.11 4
6
0.17
26
5 0.00 4
5 0.00 5
10 0.10 7
5 0.00 6
9 0.22 7
5 0.00 5
5 0.00 9
5 0.00 6
9
0.22
19
10
0.30
32
5
0.00
10
5
0.00
15
8 0.25 7
6
0.17
21
7
0.14
10
5 0.00 5
6
0.17
11
5 0.00 4
5 0.00 5
10 0.30 6
6
0.17
14
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c. Rat did not meet the criterion in Session 1 (Learning Phase); values for Session 2 (Retention Phase) excluded from group
averages and statistical analyses.
418-008:PAGE D-34
000575
418-008:PAGE D-35
000576
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE DIB (PAGE 3) : WATERMAZE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 2
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 1
13151
10
0.50
17
13152
6 0.17 5
13153
7
0.71
31
13154
6
0.33
14
13156 13 0.31 6
13157
9 0.56
7
13158
7
0.26
11
13160
6 0.17 4
13161
14
0.64
10
13162
11
0.45
11
13163
6 0.67 6
13164
9 0.56 9
13165
8
1.12
11
13166
15
0.40
10
13168 14 0.28 5
13169
7
0.28
15
13170
6 0.33 8
13171
8 0.25 4
13172
12
0.42
12
13173
7
0.28
15
13174
9
0.33
12
6
0.17
12
7 0.28 8
5
0.00
10
7
0.28
15
5 0.00 7
5 0.00 5
6
0.50
32
5 0.00 9
8
0.38
10
5
0.00
11
5 0.00 8
5
0.00
10
6
0.17
23
5
0.00
10
5 0.00 6
5 0.00 5
6
0.17
19
5 0.00 6
5 0.00 5
5 0.00 8
5 0.00 5
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds.
'
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D19 (PAGE 1) : MATING AND FERTILITY - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT H
13101 13102 13103 13104 13105 13106 13107 13108a 13108b 13109 13110a 13110b 13111c 13112a 13112b 13113 13114 13115 13116 13117 13118 13119 13120 13121c 13122 13123 13124 13125
DAYS IN COHABITATION
3 4 3 3 7 1 4 2 2 4 2 7
2 1 7 1 4 1 7 1 7 1
1 4 2 2
MATING STATUS
M M M M DID NOT MATE M M M M M M M
M M M M M M DID NOT MATE M DID NOT MATE M
M M M M
MATING DATE
c C
C c
-
c c c c c c c
c c c c c c c c
c c c c
FEMALE PREGNANCY STATUS
P (13202) PI13225) P (13201) P (13213) -(13217) P (13208) N P (13209) P(13218) P (13220) P (13210) P (13216) P (13223)
P (13211) P (13217) P (13224) P (13207) P (13214) P (13204) -(13223) P (13212) -(13220) P (13206)
P (13219) P (13203) P (13215) P (13222)
M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P = PREGNANT NP = NOT PREGNANT a. Result of first cohabitation period, b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat. c. Rat was not assigned to cohabitation because there were no available female rats.
418-008:PAGE D-36
000577
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D19 (PAGE 2): MATING AND FERTILITY - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT tf
DAYS IN COHABITATION
MATING STATUS
MATING DATE
FEMALE PREGNANCY STATUS
13126a 13126b 13126c 13127a 13127b 13128 13129 13130 13131 13132 13133a 13133b 13134 13135 13136 13137 13138d 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
1 6 7 5 X 2 i 3 7 7 2 1 3 2 7 5
6 3 2 2 3 5 3 3 4 1 3 3
M DID NOT MATE DID NOT MATE M M M M M DID NOT MATE M M M M M DID NOT MATE M
M M M M M M M M M M M M
C
-
-
C
C c c c -
c c c c c c
c c c c c c c c c c c c
P (13239) -(13228) -(13245) P (13229) P (13234) P (13242) P (13241) P (13249) -(13234) P (13237) P (13226) N P (13228) P (13238) P (13250) -(13245) P (13227)
P (13230) N P (13243)
P (13233) NPI13244)
P (13246) P (13232) P (13247) P (13240) P (13231) P (13235) P (13248) P (13236)
M = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P = PREGNANT NP = NOT PREGNANT a. Result of first cohabitation period. b. Male rat mated early in the first cohabitation period and was cohabited with a second female rat. c. Male rat mated early in the first cohabitation period and was cohabited with a third female rat. d. Rat 13138 was found dead day 66 postweaning.
418-008:PAGE D-37
000578
PROTOCOL, 418-008 : COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER; 6295.9)
TABLE D19 (PAGE 3): MATING AND FERTILITY - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT #
DAYS IN COHABITATION
MATING STATUS
13151 3 M 13152 1 M 13153 1 M 13154 4 M 13155 2 M 13156 1 M 13157 3 M 13158 4 M 13159 2 M 13160 i M 13161 2 M 13162 1 M 13163 2 M 13164 2 M 13165 7 M 13166 4 M 13167 1 M 13168 5 M 13169 3 M 13170 2 M 13171 4 M 13172 2 M 13173 4 M 13174 3 M 13175 1 M
H = MATED ( ) = FEMALE RAT NUMBER C = CONFIRMED P = PREGNANT NP = NOT PREGNANT
MATING DATE
C C C C C C C C C C C C C C C C C C C C C C C C C
FEMALE PREGNANCY STATUS
P (13257) P (13251) P (13256) P (13270) P (13273) P (13262) P (13266) P (13264) P (13263) P (13265) P (13268) P (13261) P (13259) P (13275) P (13253) P (13252) N P (13274) P (13254) P (13260) P (13271) P (13269) P (13255) P (13267) P (13272) P (13258)
418-008.PAGE D-38
000579
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D20 (PAGE 1): NECROPSY OBSERVATIONS INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
I 0 (VEHICLE)
13101 DP 91 90 ALL TISSUES APPEARED NORMAL.
13102 DP 90 89 ALL TISSUES APPEARED NORMAL.
13103 DP 90 89 ALL TISSUES APPEARED NORMAL.
13104
DP 90
89 ALL TISSUES APPEARED NORMAL.
13105 DP 87 87 FOUND DEAD ON DAY 87 POSTWEANING (ONE HOUR AND 11 MINUTES AFTER DOSAGE). LUNGS : ALL LOBES, DARK RED. ALL OTHER TISSUES APPEARED NORMAL.
13106 DP 90 89 ALL TISSUES APPEARED NORMAL. 13107 DP 90 89 ALL TISSUES APPEARED NORMAL. 13108 DP 89 88 ALL TISSUES APPEARED NORMAL. 13109 DP 89 88 ALL TISSUES APPEARED NORMAL. 13110 DP 89 88 ALL TISSUES APPEARED NORMAL. 13111 DP 89 88 ALL TISSUES APPEARED NORMAL. 13112 DP 89 88 ALL TISSUES APPEARED NORMAL. 13113 DP 89 88 ALL TISSUES APPEARED NORMAL. 13114 DP B8 87 ALL TISSUES APPEARED NORMAL. 13115 DP 88 87 ALL TISSUES APPEARED NORMAL.
13116 DP 86 85 FOUND DEAD ON DAY 86 POSTWEANING (DEATH OCCURRED OVERNIGHT) THORACIC CAVITY: DARK RED CLOTTED MATERIAL. EXTERNAL OBSERVATIONS: RED PERINASAL SUBSTANCE. ALL OTHER TISSUES APPEARED NORMAL.
13117 DP 88 87 ALL TISSUES APPEARED NORMAL. 13118 DP 88 87 ALL TISSUES APPEARED NORMAL. 13119 DP 88 87 ALL TISSUES APPEARED NORMAL. 13120 DP 88 87 ALL TISSUES APPEARED NORMAL. 13121 DP 88 87 ALL TISSUES APPEARED NORMAL. 13122 DP 87 86 ALL TISSUES APPEARED NORMAL. 13123 DP 86 85 ALL TISSUES APPEARED NORMAL. 13124 DP 85 84 ALL TISSUES APPEARED NORMAL. 13125 DP 85 84 ALL TISSUES APPEARED NORMAL.
DP DAY POSTWEANING a. Refer to the individual clinical observations table (Table D13) for external observations confirmed at necropsy.
418-008:PAGE D-39
000580
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D20 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
II 0.1 13126 DP 91 90 ALL TISSUES APPEARED NORMAL.
13127 DP 91 90 ALL TISSUES APPEARED NORMAL. 13128 DP 90 89 ALL TISSUES APPEARED NORMAL. 13129 DP 90 89 ALL TISSUES APPEARED NORMAL. 13130 DP 89 88 ALL TISSUES APPEARED NORMAL. 13131 DP 89 88 ALL TISSUES APPEARED NORMAL. 13132 DP 89 88 ALL TISSUES APPEARED NORMAL. 13133 DP 89 88 ALL TISSUES APPEARED NORMAL.
13134 DP 89 88 TESTES: BILATERAL, PURPLE AND FLACCID. EPIDIDYMIDES: BILATERAL, FLACCID; LEFT, SMALL. KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION. ALL OTHER TISSUES APPEARED NORMAL.
13135 DP 89 88 ALL TISSUES APPEARED NORMAL. 13136 DP 89 88 ALL TISSUES APPEARED NORMAL. 13137 DP 89 88 ALL TISSUES APPEARED NORMAL.
13138
DP 66
65 FOUND DEAD ON DAY 66 POSTWEANING (DEATH OCCURRED OVERNIGHT). ALL TISSUES APPEARED NORMAL.
13139 13140 13141 13142
DP 89 DP 88 DP 88 DP 88
88 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL. 87 ALL TISSUES APPEARED NORMAL.
13143 DP 88 87 KIDNEYS: LEFT, PELVIS, SLIGHT DILATION AND SIX CALCULI (PINPOINT TO 0.2 CM IN DIAMETER). URETERS: LEFT, DILATED. URINARY BLADDER: WALLS, THICKENED AND NUMEROUS CALCULI (PINPOINT TO 0.1 CM IN DIAMETER). ALL OTHER TISSUES APPEARED NORMAL.
13144 DP 88 87 ALL TISSUES APPEARED NORMAL.
DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D13) for external observations confirmed at necropsy.
418-008:PAGE D-40
000581
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D20 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
II (Cont.) 0.1
13145 DP 88 87 TESTES: RIGHT, FLACCID. EPIDIDYMIDES: RIGHT, SMALL AND FLACCID. ALL OTHER TISSUES APPEARED NORMAL.
13146 DP 88 87 ALL TISSUES APPEARED NORMAL. 13147 DP 88 87 ALL TISSUES APPEARED NORMAL.
13148 DP 88 87 TESTES: RIGHT. FLACCID. EPIDIDYMIDES: RIGHT, FLACCID. ALL OTHER TISSUES APPEARED NORMAL.
13149 DP 88 87 ALL TISSUES APPEARED NORMAL. 13150 DP 87 86 ALL TISSUES APPEARED NORMAL.
DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D13) for external observations confirmed at necropsy.
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D20 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF
DOSAGES
NECROPSY ADMINISTERED OBSERVATIONS a
III 0.4 13151 DP 91 90 ALL TISSUES APPEARED NORMAL.
13152 DP 91 90 ALL TISSUES APPEARED NORMAL. 13153 DP 91 90 ALL TISSUES APPEARED NORMAL. 13154 DP 91 90 ALL TISSUES APPEARED NORMAL. 13155 DP 91 90 ALL TISSUES APPEARED NORMAL. 13156 DP 91 90 ALL TISSUES APPEARED NORMAL. 13157 DP 90 89 ALL TISSUES APPEARED NORMAL. 13158 DP 90 89 ALL TISSUES APPEARED NORMAL. 13159 DP 90 89 ALL TISSUES APPEARED NORMAL. 13160 DP 89 88 ALL TISSUES APPEARED NORMAL. 13161 DP 89 88 ALL TISSUES APPEARED NORMAL.
13162 DP 89 88 ABDOMINAL ADIPOSE TISSUE: RED WITH FIRM AREAS. ALL OTHER TISSUES APPEARED NORMAL.
13163 DP 88 87 ALL TISSUES APPEARED NORMAL. 13164 DP 88 87 ALL TISSUES APPEARED NORMAL. 13165 DP 88 87 ALL TISSUES APPEARED NORMAL. 13166 DP 88 87 ALL TISSUES APPEARED NORMAL. 13167 DP 88 87 ALL TISSUES APPEARED NORMAL. 13168 DP 88 87 ALL TISSUES APPEARED NORMAL. 13169 DP 88 87 ALL TISSUES APPEARED NORMAL. 13170 DP 88 87 ALL TISSUES APPEARED NORMAL. 13171 DP 88 87 ALL TISSUES APPEARED NORMAL. 13172 DP 87 86 ALL TISSUES APPEARED NORMAL.
13173 DP 87 86 KIDNEYS: BILATERAL, LARGE (LEFT =4.94 G; RIGHT PARENCHYMA, NUMEROUS FLUID-FILLED CYSTS. ALL OTHER TISSUES APPEARED NORMAL.
13174 DP 87 86 ALL TISSUES APPEARED NORMAL. 13175 DP 79 78 ALL TISSUES APPEARED NORMAL.
DP = DAY POSTWEANING a. Refer to the individual clinical observations table (Table D13) for external observations confirmed at necropsy.
418-008:PAGE D-42
000583
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D21 (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
DOSAGE GROUP I
EPIDIDYMIS LEFT
ABS. REL. W T . % TBW
TESTIS LEFT
ABS. REL. W T . % TBW
0 (VEHICLE) MG/KG/DAY
SEMINAL VESICLES WITH FLUID
ABS. REL. WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. W T . % TBW
TESTIS RIGHT ABS. REL. WT. % TBW
13101 13102 13103 13104 13105a 13106 13107 13108 13109 13110 13111 13112 13113 13114 13115 13116c 13117 13118 13119 13120 13121 13122 13123 13124 13125
553 . 517. 552. 562 . 574 . 568. 596. 561. 548. 527. 584. 534. 523. 570. 448 . 456. 532. 468. 592. 598. 488 . 560. 651. 434 . 500.
0.68 0.74 0.61 0.70 0.67 0.62 0.59 0.54 0.72 0.68 0.77 0.52 0.84b 0.68 0.70 0.67 0.66 0.66 0.63 0.71 0.60 0.62 0.74 0.61 0.70
0.12 0.14 0.11 0.12
--
0.11 0.10 0.10 0.13 0.13 0.13 0.10 0.16 0.12 0.16
--
0.12 0.14 0.11 0.12 0.12 0.11 0.11 0.14 0.14
2.03 1.79 1.76 1.82 1.64 1.77 1.72 1.54 1.75 1.63 2.23 1.63 2.10 1.79 1.81 1.62 1.75 1.70 1.73 1.67 1.71 1.55 1.77 1.64 1.85
0.37 0.35 0.32 0.32
--
0.31 0.29 0.27 0.32 0.31 0.38 0.30 0.40 0.31 0.40
--
0.33 0.36 0.29 0.28 0.35 0.28 0.27 0.38 0.37
1.76 2.09 1.44 1.79 1.85 1.48 2.21 1.53 2.19 1.03 1.81 1.23 1.96 2.35 1.72 1.90 1.73 1.97 1.72 1.38 1.92 1.40 1.88 1.75 1.97
0.32 0.40 0.26 0.32
0.26 0.37 0.27 0.40 0.20 0.31 0.23 0.37 0.41 0.38
--
0.32 0.42 0.29 0.23 0.39 0.25 0.29 0.40 0.39
1.11 1.41 1.17 1.13 0.59 0.93 1.29 0.93 1.34 0.89 1.03 0.81 0.89 1.15 0.89 0.56 0.99 0.96 1.11 0.85 1.07 0.91 0.91 1.22 0.89
0.20 0.27 0.21 0.20 ___
0.16 0.22 0.16 0.24 0.17 0.18 0.15 0.17 0.20 0.20 ___
0.19 0.20 0.19 0.14 0.22 0.16 0.14 0.28 0.18
0.77 0.74 0.60 0.70 0.70 0.67 0.59 0.59 0.60 0.59 0.76 0.69 0.71 0.71 0.62 0.67 0.60 0.64 0.71 0.70 0.67 0.62 0.73 0.67 0.73
0.14 0.14 0.11 0.12
--
0.12 0.10 0.10 0.11 0.11 0.13 0.13 0.14 0.12 0.14
--
0.11 0.14 0.12 0.12 0.14 0.11 0.11 0.15 0.15
2.09 1.85 1.72 1.82 1.68 1.76 1.74 1.53 1.69 1.68 2.31 1.69 2.07 1.83 1.81 1.68 1.77 1.67 1.67 1.77 1.73 1.54 1.68 1.62 1.91
0.38 0.36 0.31 0.32
--
0.31 0.29 0.27 0.31 0.32 0.40 0.32 0.40 0.32 0.40
--
0.33 0.36 0.28 0.30 0.35 0.28 0.26 0.37 0.38
ALL WEIGHTS WERE RECORDEp IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
a. Rat 13105 was found dead day 87 postweaning; values excluded from group averages and statistical analyses.
b. Damaged during processing (weight not affected).
c. Rat 13116 was found dead day 86 postweaning; values excluded from group averages and statistical analyses.
418-008:PAGE D-43
irgSOO^
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D21 (PAGE 2) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA FI GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE
ABS.
REL.
WT. * TBW
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13101 13102 13103 13104 13105a 13106 13107 13108 13109 13110 13111 13112 13113 13114 13115 13116b 13117 13118 13119 13120 13121 13122 13123 13124 13125
553 . 517. 552. 562 . 574 . 568. 596. 561. 548. 527. 584 . 534 . 523 . 570. 448. 456. 532. 468. 592 . 598. 488. 560 . 651. 434 . 500 .
1.11 0.71 0.55 1.04 1.42 0.90 0.96 1.02 0.55 0.75 1.15 0.78 0.94 1.09 0.72 0.99 0.73 1.05 0.93 1.11 0.90 0-93 1.29 1.01 1.13
0.20 0.14 0.10 0.18
--
0.16 0.16 0.18 0.10 0.14 0.20 0.15 0.18 0.19 0.16
--
0.14 0.22 0.16 0.18 0.1B 0.17 0.20 0.23 0.23
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
a. Rat 13105 was found dead day 87 postweaning; values excluded from group averages and statistical analyses.
b. Rat 13116 was found dead day 86 postweaning; values excluded from group averages and statistical analyses.
418-008: PAGE D-44
000585
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D21 (PAGE 3): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
EPIDIDYMIS LEFT
ABS. REL. WT. % TBW
TESTIS LEFT
ABS. REL. WT. % TBW
SEMINAL VESICLES WITH FLUID
ABS. REL. WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. 1 TBW
TESTIS
RIGHT
ABS.
REL.
WT. % TBW
DOSAGE GROUP II
0 .1 MG/KG/DAY
13126 13127 13128 13129 13130 13131 13132 13133 13134 13135 13136 13137 13138b 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
470. 531. 474 . 459. 605. 589. 548 . 547. 588. 570. 527. 501. 502. 571. 465. 490 . 584. 560. 480. 512. 550. 517.
569. 544. 540 .
0.59 0.57 0.64 0.64 0.60 0.67 0.63 0.59 0.30a 0.60 0.70 0.69 0.57 0.68 0.56 0.64 0.74 0.65 0.70 0.60 0.65 0.69 0.79 0.57 0.71
0.12 0.11 0.14 0.14 0.10 0.11 0.11 0.11 0.05a 0.10 0.13 0.14 --
0.12 0.12 0.13 0.13 0.12 0.14 0.12 0.12 0.13 0.14 0.10 0.13
1.74 1 .88 1.72 1.77 1.64 1.74 1.77 1.60 0.98a 1.66 1.78 1.99 1.40 1.83 1.66 1.98 1.80 1.70 1.91 1.99 1.91 1.46 2.03 1.71 2.20
0.37 0.35 0.36 0.38 0.27 0.30 0.32 0.29 0.17a 0.29 0.34 0.40
--
0.32 0.36 0.40 0.31 0.30 0.40 0.39 0.35 0.28 0.36 0.31 0.41
1.64 1.70 2.05 1.74 1.61 1.07 1.40 1.66 1.85 1.88 2.06 1.75 0.86 2.15 1.77 1.72 1.90 1.86c 1.74 1.22c 1.54 1.67 1.64e 1.41 1.86
0.35 0.32 0.43 0.38 0.27 0.18 0.26 0.30 0.31 0.33 0.39 0.35
--
0.38 0.38 0.35 0.32 0.33 0.36 0.24 0.28 0.32 0.29 0.26 0.34
0.91 1.04 1.26 1.13 1.04 0.68 0.81 1.11 1.08 1.40 1.28 0.97 0.44 1.12 1.13 1.01 1.12 1.26 0.81 0.92 1.12 1.10 1.11 0.61 1.20
0.19 0.20 0.26 0.25 0.17 0.12 0.15 0.20 0.18 0.24 0.24 0.19
--
0.20 0.24 0.21 0.19 0.22 0.17 0.18 0.20 0.21 0.20 0.11 0.22
0.65 0.61 0.62 0.65 0.63 0.63 0.64 0.63 0.49a 0.55 0.68 0.70 0.59 0.75 0.58 0.65 0.70 0.70 0.64 0.39d 0.72 0.72 0.4 9f 0.64 0.74
0.14 0.11 0.13 0.14 0.10 0.11 0.12 0.12 0.08a 0.10 0.13 0.14
--
0.13 0.12 0.13 0.12 0.12 0.13 0.08d 0.13 0.14 0.09f 0.12 0.14
1.81 1.87 1.76 1.76 1.60 1.73 1.76 1.84 1.04a 1.61 1.84 1.95 1.46 1.91 1.68 1.88 1.77 1.63 1.85 1.17d 1.93 1.60 1 .32f 1.62 2.21
0.38 0.35 0.37 0.38 0.26 0.29 0.32 0.34 0 .18a 0.28 0.35 0.39 --
0.33 0.36 0.38 0.30 0.29 0.38 0.23d 0.35 0.31 0.23f 0.30 0.41
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) X 100.
a. Rat 13134 had a small and flaccid left epididymis, a flaccid right epididymis and purple and flaccid testes; values excluded
from group averages and statistical analyses. See the individual necropsy observations table (Table D20).
b. Rat 13138 was found dead day 66 postweaning; values excluded from group averages and statistical analyses.
c. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
d. Rat 13145 had a small and flaccid right epididymis and a flaccid right testis; values excluded from group averages and
statistical analyses. See the individual necropsy observations table (Table D20).
e. Damaged during processing (weight not affected).
f. Rat 13148 had a flaccid right epididymis and a flaccid right testis; values excluded from group averages and statistical
analyses. See the individual necropsy observations table (Table D20).
418-008:PAGE D-45
0005S6
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D21 (PAGE 4) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE ABS. REL. WT. % TBW
DOSAGE GROUP II
0 ,1 MG/KG/DAY
13126 13127 13128 13129 13130 13131 13132 13133 13134 13135 13136 13137 13138a 13139 13140 13141 13142 13143 13144 13145 13146 13147 13148 13149 13150
470. 531. 474. 459. 605. 589. 548. 547. 588. 570. 527. 501. 502. 571. 465. 490. 584. 560. 480. 512. 550. 517. 569. 544. 540.
0.67 0.81 0.86 0.55 1.00 0.93 0.58 0.60 1.38 0.89 1.06 0.89 0.83 0.89 0.82 1.04 0.80 0.75 1.14 1.35 0.63 1.18 1.06 0.91 1.01
0.14 0.15 0.18 0.12 0.16 0.16 0.10 0.11 0.23 0.16 0.20 0.18
--
0.16 0.18 0.21 0.14 0.13 0.24 0.26 0.11 0.23 0.19 0.17 0.19
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. \ TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
a. Rat 13138 was found dead day 66 postweaning; values excluded from group averages and statistical analyses.
418-008:PAGE D-46
00059*7
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D21 (PAGE 5): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
DOSAGE GROUP III
EPIDIDYMIS LEFT
ABS. REL. W T . % TBW
TESTIS LEFT
ABS. REL. WT. % TBW
0.4 MG/KG/DAY
SEMINAL VESICLES WITH FLUID
ABS. REL. WT. % TBW
SEMINAL VESICLES WITHOUT FLUID ABS. REL. WT. % TBW
EPIDIDYMIS RIGHT
ABS. REL. WT. % TBW
TESTIS RIGHT ABS. REL. WT. % TBW
13151 13152 13153 13154 13155 13156 13157 13158 13159 13160 13161 13162 13163 13164 13165 13166 13167 13168 13169 13170 13171 13172 13173 13174 13175
532. 549. 571. 526. 477. 469. 644 . 522. 529. 560. 435. 557. 527. 439. 532. 539. 524. 523 . 512. 589. 469. 513 . 606. 519. 394 .
0.64 0.58 0.56 0.71 0.63 0.62 0.65 0.67 0.63 0.60 0.65 0.58 0.71 0.58 0.65 0.60 0.65 0.63 0.63 0.58 0.62 0.67 0.74 0.64 0.59
0.12 0.10 0.10 0.13 0.13 0.13 0.10 0.13 0.12 0.11 0.15 0.10 0.13 0.13 0.12 0.11 0.12 0.12 0.12 0.10 0.13 0.13 0.12 0.12 0.15
1.69 1.75 1.87 1.98 1.82 1.82 1.96 1.81 1.67 1.78 1.85 1.68 1.74 1.52 1.79 1.66 1.81 1.82 1.76 1.67 1.76 1.78 2.12 1.86 1.73
0.32 0.32 0.33 0.38 0.38 0.39 0.30 0.35 0.32 0.32 0.42 0.30 0.33 0.35 0.34 0.31 0.34 0.35 0.34 0.28 0.38 0.35 0.35 0.36 0.44
1.44 1.88 1.48 1.87 1.61 1.7S 1.58 1.14 1.64 1.59 1.64 1.52 1.62 2.14 1.76 1.51 1.59 1.49 1.58 1.81 1.65 1.57 1.32a 1.76 1.36
0.27 0.34 0.26 0.36 0.34 0.37 0.24 0.22 0.31 0.28 0.38 0.27 0.31 0.49 0.33 0.28 0.30 0.28 0.31 0.31 0.35 0.31 0.22 0.34 0.34
0.66 1.06 1.04 1.28 1.06 0.97 0.88 0.85 1.21 0.90 1.01 0.98 1.02 0.99 0.91 1.03 0.86 0.83 1.10 0.92 1.03 0.92 0.87 0.91 0.60
0.12 0.19 0.18 0.24 0.22 0.21 0.14 0.16 0.23 0.16 0.23 0.18 0.19 0.22 0.17 0.19 0.16 0.16 0.21 0.16 0.22 0.18 0.14 0.18 0.15
0.64 0.62 0.56 0.71 0.63 0.60 0.66 0.70 0.67 0.64 0.64 0.59 0.66 0.60 0.60 0.66 0.69 0.65 0.63 0.60 0.69 0.64 0.76 0.64 0.58
0.12 0.11 0.10 0.13 0.13 0.13 0.10 0.13 0.13 0.11 0.15 0.10 0.12 0.14 0.11 0.12 0.13 0.12 0.12 0.10 0.15 0.12 0.12 0.12 0.15
1.78 1.79 1.93 2.01 1.86 1.78 1.94 1.93 1.64 1.81 1.92 1.74 1.74 1.52 1.84 1.82 1.90 1.82 1.76 1.68 1.82 1.85 2.12 1.80 1.69
0.33 0.33 0.34 0.38 0.39 0.38 0.30 0.37 0.31 0.32 0.44 0.31 0.33 0.35 0.34 0.34 0.36 0.35 0.34 0.28 0.39 0.36 0.35 0.35 0.43
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. W T . = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
a. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
418-008:PAGE D-47
000588
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE D21 (PAGE 6): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (I) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT INDIVIDUAL DATA - FI GENERATION MALE RATS
RAT TERMINAL BODY NUMBER WEIGHT
PROSTATE ABS. REL. WT. % TBW
DOSAGE GROUP III
0 .4 MG/KG/DAY
13151 13152 13153 13154 1315S 13156 13151 13158 13159 13160 13161 13162 13163 13164 13165 13166 13167 13168 13169 13170 13171 13172 13173 13174 13175
532. 549. 571. 526. 477. 469. 644 . 522. 529. 560. 435. 557. 527. 439. 532. 539. 524. 523. 512. 589. 469. 513. 606. 519. 394.
1.01 1.41 0.91 0.85 0.80 0.61 1.05 0.83 0.85 1.06 0.83 0.62 0.80 0.93 1.03 0.79 0.97 1.09 0.91 0.76 1.07 0.64 0.96 0.95 0.52
0.19 0.26 0.16 0.16 0.17 0.13 0.16 0.16 0.16 0.19 0.19 0.11 0.15 0.21 0.19 0.15 0.18 0.21 0.18 0.13 0.23 0.12 0.16 0.18 0.13
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL BODY WEIGHT) x 100.
418-008:PAGE D-48
000589
APPENDIX E REPORT TABLES - F1 GENERATION FEMALE RATS
000590
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE El (PAGE 1): CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II 0 (VEHICLE) 0.1
III 0.4
PRECOHABITATION (DAY 1 OF STUDY TO THE DAY OF COHABITATION):
MAXIMUM POSSIBLE INCIDENCE
1721/ ;25 1844/ 25 1840/ 25
SACRIFICED FOUND DEAD
la 0 lb 0
0 0
INCISORS: TOTAL MISALIGNED MISSING/BROKEN
29/ 3 29/ 3 14/ 2
32/ 4
9/ 1 23/ 3
77/ 6 52/ 4 25/ 2
CHROMODACRYORRHEA
5/ i
9/ 1 19/ 3
EARS: SWOLLEN AND PURPLE
8/ 2
4/ 2
0/ 0
LOCALIZED ALOPECIA: '
TOTAL BACK HEAD LIMBS
13/ 2 0/ 0 0/ 0
13/ 2
24/ 2 22/ 2
2/ 1 0/ 0
0/ 0 0/ 0 0/ 0 0/ 0
BACK: ABRASION
0/ 0 10/ 1
0/ 0
BACK: SCAB
0/ 0
1/ 1
0/ 0
URINE-STAINED ABDOMINAL FUR
10/ 2
0/ 0
0/ 0
LEFT HINDPAW: THIRD AND FOURTH DIGITS MISSING
74/ 1
0/ 0
0/ 0
PERIVAGINAL SWELLING
6/ 1
0/ 0
0/ 0
LEFT FOREPAW: SWOLLEN
1/ 1
0/ 0
0/ 0
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION. a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Rat 13221 was found dead on day 28 postweaning.
418-008:PAGE E-1
000591
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE El (PAGE 2): CLINICAL OBSERVATIONS SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I II 0 (VEHICLE) 0.1
hi
0.4
PRESUMED GESTATION: a
MAXIMUM POSSIBLE INCIDENCE
509/ 23 539/ 24 548/ 25
MORTALITY
000
INCISORS: TOTAL MISALIGNED MISSING/BROKEN
66/ 4 62/ 4 21/ 2
90/ 5 77/ 5 41/ 3
142/ 8 123/ 6
22/ 3
CHROMODACRYORRHEA
10/ 2 26/ 1 40/ 3
EARS: SWOLLEN AND PURPLE
44/ 2 15/ 4 23/ 2
RED PERIVAGINAL SUBSTANCE
0/ 0
1/ 1
2/ 2
LOCALIZED ALOPECIA:
TOTAL LIMBS HEAD UNDERSIDE
61/ 3 61/ 3
0/ 0 15/ 1
32/ 3 27/ 2
5/ 1 0/ 0
21/ 2 15/ 1
6/ 1 0/ 0
URINE-STAINED ABDOMINAL FUR CHROMORHINORRHEA SOFT OR LIQUID FECES
0/ 0 14/ 2
0/ 0
0/ 0 1/ 1 1/ 1
1/ 1 0/ 0 0/ 0
LEFT HINDPAW: THIRD AND FOURTH DIGITS MISSING
23/ 1
0/ 0
0/ 0
TAIL: SHEATH MISSING
12/ 1
0/ 0
0/ 0
TIP OF TAIL BLACK
12/ 1
0/ 0
0/ 0
TIP OF TAIL MISSING
10/ 1
0/ 0
0/ 0
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION, a. Restricted to rats with a confirmed mating date.
418-008PAGE E-2
000592
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE El (PAGE 3): CLINICAL OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
LACTATION:
I II 0 (VEHICLE) 0.1
III 0.4
MAXIMUM POSSIBLE INCIDENCE FOUND DEAD
462/ 22 0
441/ 21 0
493/ 24 la
INCISORS: TOTAL MISALIGNED MISSING/BROKEN
65/ 4 44/ 3 42/ 2
43/ 3 42/ 2 34/ 3
116/ 6 116/ 6
18/ 3
RED PERIVAGINAL SUBSTANCE EARS: SWOLLEN AND PURPLE
0/ 0 45/ 3
0/ 0 84/ 4
5/ 5** 42/ 2
CHROMODACRYORRHEA
21/ 1
7/ 1 37/ 2
LOCALIZED ALOPECIA: TOTAL LIMBS UNDERSIDE
63/ 3 63/ 3 21/ 1
42/ 2 42/ 2
0/ 0
21/ 1 21/ 1 13/ 1
CHROMORHINORRHEA
6/ 1
2/ 1
0/ 0
CHEST: ABRASION TIP OF TAIL MISSING LEFT HINDPAW: THIRD AND FOURTH DIGITS MISSING
0/ 0 21/ 1 21/ 1
9/ 1 0/ 0 0/ 0
0/ 0 0/ 0 0/ 0
URINE-STAINED ABDOMINAL FUR
1/ 1
0/ 0
0/ 0
STATISTICAL ANALYSES OF CLINICAL OBSERVATION DATA WERE RESTRICTED TO THE NUMBER OF RATS WITH OBSERVATIONS. MAXIMUM POSSIBLE INCIDENCE = (DAYS X RATS)/NUMBER OF RATS EXAMINED PER GROUP. N/N = TOTAL NUMBER OF OBSERVATIONS/NUMBER OF RATS WITH OBSERVATION, a. Dam 13251 was found dead on day 10 of lactacion. ** Significantly different from the vehicle control group value (p^O.Ol).
418-008:PAGE E-3
000593
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E2 (PAGE 1) : BODY WEIGHTS PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
24a
25
25
BODY WEIGHT (G)
DAY 1
MEAN+S.D .
51.1 + 6.1
50.5 + 4.2
48.7 + 5.1
DAY 8
MEAN+S.D .
91.2 + 9.3
91.8 + 5.2
91.2 + 7.6
DAY 15
MEAN+S.D .
134.5 + 12.5
138.0 + 7.6
134.5 + 9.9
DAY 22
MEAN+S.D .
168.2 + 16.0
173.4 + 9.7
168.5 + 12.4
DAY 29 DAY 36 DAY 43 DAY SO DAY 57 DAY 64 PRECOHABITATION c
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S. D. MEAN+S.D .
194.0 + 21.7 [ 23 Jb
217.4 + 24.9 ( 231b
234.9 + 25.2 [ 23 )b
251.1 + 27.4 [ 23 ]b
259.6 + 29.0 [ 23 ]b
273.2 + 31.4 t 231b
282.8 + 33.6 ( 23 ]b
200.5 + 13.1 226.8 + 15.2 245.1 + 14.6 261.4 + 20.0 272.7 + 20.7 282.7 + 19.6 294.0 + 16.3
193.9 + 16.6 217.8 + 17.4 237.9 + 20,0 251.2 + 20.9 262.7 + 24.4 272.3 + 25.8 280.3 + 26.9
DAY = DAY POSTWEANING ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead day 28 postweaning. c. Precohabitation body weights were recorded on the day that cohabitation began for the FI generation rats; at that time these
rats were 85 to 97 days of age.
418-008PAGE E-4
000594
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E3 (PAGE 1) : BODY WEIGHT CHANGES - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
24a
25
25
BODY WEIGHT CHANGE (G)
DAYS 1 - 8
MEAN+S.D .
+40.0 + 4.2
+41.4 + 2.9
+42.5 + 5.0
DAYS 8 - 15
MEAN+S.D .
+43.3+ 6.3
+46.1 + 4.2
+43.3 + 4.5
DAYS 1 5 - 2 2
MEAN+S.D.
+33.8+ 7.0
+35.5 + 5.2
+34.0 + 6.8
DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64 DAYS 1 - 64 DAY 1 PRECOHABITATION C
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S. D.
MEAN+S.D.
+25.8 + 12.8 [ 23Ja,b
+23.4 + 10.4 [ 23]a,b
+17.5 + 9.2 [ 23]a,b
+16.2 + 6.6 I 23]a,b
+8.5 + 6.8 l 23Ja,b
+13.6 + 7.6 ( 23]a,b
+222.3 + 28.9 [ 23]a,b
+231.9 + 30.7 [ 23]a ,b
+27.0 + 5.8 +26.3 + 5.8 +18.3 + 5.1 +16.3 + 8.0 +11.3 + 9.3 +10.0 + 9.4 +232.2 + 20.3
+243.6 + 17.3
+25.4 + 8.7 +23.8 + 5.7 +20.1 + 7.4 +13.3 + 5.9 +11.6 + 6.9
+9.6 + 7.8 +223.6 + 24.0
+231.6 + 25.1
DAY(S) = DAY(S) POSTWEANING [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead day 28 postweaning. c. Precohabitation body weights were recorded on the day that cohabitation began for the FI generation rats; at that time these
rats were 85 to 97 days of age.
418-008:PAGE E-5
000595
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E4 (PAGE 1) : MATERNAL BODY WEIGHTS GESTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
23a,b
25
25
PREGNANT
N 22
21
24
MATERNAL BODY WEIGHT (G)
DAY 0
MEAN+S.D .
284.4 + 30.8
295.3 + 17.3
279.9 24.8
DAY 1
MEAN+S.D .
291.4 jf 31.1
302.8 + 18.9
288.1 + 25.4
DAY 2
MEAN+S.D .
298.1 + 30.5
308.1 + 19.3
294.5 24.8
DAY 3
MEAN+S.D .
303.1 + 31.0
312.8 + 19.3
297.5 25.9
DAY 4
MEAN+S.D .
305.5 + 31.1
315.3 + 19.1
300.2 + 25.3
DAY 5
MEAN+S.D .
309.2 + 31.2
318.7 + 19.2
304.4 26.5
DAY 6
MEAN+S.D .
313.2 + 32.7
321.6 + 18.7
306.9 + 25.1
DAY 7
MEAN+S.D .
317.4 33.2
322.8 + 19.9
309.0 + 26.0
DAY 8
MEAN+S.D .
321.6 + 32.8
328.0 + 19.9
313.2 f 27.4
DAY 9
MEAN+S.D .
326.2 + 33.0
331.5 + 19.5
317.7 + 26.1
DAY 10
MEAN+S.D.
331.7 + 33.6
336.5 + 20.1
322.3 f 28.2
DAY = DAY OF GESTATION a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 postweaning.
418-008: PAGE E-6
000596
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR1S STUDY NUMBER: 6295.9)
TABLE E4 (PAGE 2) : MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
23a ,b
25
25
PREGNANT
N 22
21
24
MATERNAL BODY WEIGHT (G)
DAY 11
MEAN+S.D .
337.0 + 32.3
341.0 + 21.5
329.0 + 27.1
DAY 12
MEAN+S.D .
342.4 + 34.7
347.2 + 22.9
331.8 + 26.9
DAY 13
MEAN+S.D .
345.6 + 33.8
350.3 + 21.0
336.4 + 28.7
DAY 14
MEAN+S.D .
351.9 + 34.9
354.7 + 21.1
342.3 + 27.3
DAY 15
MEAN+S.D .
358.9 + 35.0
364.0 + 22.3
347.9 + 29.5
DAY 16
MEAN+S.D .
366.2 + 35.0
373.5 + 22.4
358.6 + 29.6
DAY 17
MEAN+S.D .
379.4 + 34.4
385.8 + 25.3
372.3 + 30.2
DAY 18
MEAN+S.D .
394.6 + 32.8
401.6 + 27.4
388.1 + 32.1
DAY 19 DAY 20
MEAN+S.D . MEAN+S.D.
408.3 + 35.6 420.8 + 34.4
414.7 + 27.7 428.0 + 30.3
402.8 + 32.0 417.7 + 34.4
DAY = DAY OF GESTATION a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 postweaning.
418-008:PAGE E-7
000597
td
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E5 (PAGE 1) : MATERNAL BODY WEIGHT CHANGES - GESTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
23a ,b
25
25
PREGNANT
N 22
21
24
MATERNAL BODY WEIGHT CHANGE (G)
DAYS 0 - 7
MEAN+S.D .
+33.0 + 6.9
+27.4 + 9.0
+29.2 + 7.1
DAYS 7 - 10
MEAN+S.D .
+14.3 + 5.0
+13.8 + 6.9
+13.2 + 5.2
DAYS 10 - 14
MEAN+S.D .
+20.2 +_ 5.9
+18.1 + 9.9
+20.0 + 6.2
DAYS 14 - 17
MEAN+S.D .
+27.5 + 13.7
+31.2 + 9.4
+30.0 + 8.6
DAYS 17 - 20
MEAN+S.D .
+41.4 + 11.0
+42.2 + 9.3
+45.4 +^ 9.0
DAYS 0 - 20
MEAN+S.D .
+136.4 + 16.0
+132.7 + 22.7
+137.8 + 16.4
DAYS = DAYS OF GESTATION a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning,- the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 postweaning.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E6 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
23a,,b
25
25
PREGNANT
N 22
21
24
DELIVERED LITTERS
N
22
21
24
MATERNAL BODY WEIGHT (G)
DAY 1
MEAN+S.D .
325.7 + 35.8
334.7 + 16.9
323.4 + 28.4
DAY 4
MEAN+S.D.
328.0 + 33.0
337.5 + 20.9
318.8 + 25.8
DAY 7
MEANtS.D .
331.5 + 31.2
340.2 + 19.1
324.2 + 23.2
DAY 14 DAY 21
MEAN+S.D. MEAN+S.D.
358.9 + 29.2 338.0 + 31.0
368.3 + 21.8 356.0 + 18.4
352.4 + 23.6 ( 23 )c
341.3 + 17.8 [ 23] C
DAY = DAY OF LACTATION ( ) = NUMBER OF VALUES AVERAGED a . Excludes values for rat 13205, b. Excludes values for rat 13221, c. Excludes values for dam 13257,
which was excluded from study on day 7 postweaning; which was found dead on day 28 postweaning. which was found dead on day 10 of lactation.
the sex was
incorrectly identified.
418-008:PAGE E-9
000599
418-008:PAGE E-10
000600
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE E7 (PAGE 1) : MATERNAL BODY WEIGHT CHANGES - LACTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED
N
25
25
25
INCLUDED IN ANALYSES
N
23a, b
25
25
PREGNANT
N 22
21
24
DELIVERED LITTERS
N
22
21
24
MATERNAL BODY WEIGHT CHANGE (G)
DAYS 1 - 4
MEAN+S.D .
+2.3 + 13.6
+2.8 + 10.7
-4.6 + 8-4*
DAYS 4 - 7
MEAN+S.D .
+3.6 + 11.8
+2.7 + 10.7
+5.4 + 8.2
DAYS 7 - 14 DAYS 14 - 21 DAYS 1 - 21
MEAN+S.D. MEAN+S.D. MEAN+S.D.
+27.3 + 12.8 -20.9 + 17.1 +12.3 + 19.1
+28.0 + 15.6 -12.3 + 12.6 +21.3 + 15.3
+30.1 + 10.4 ( 23] c
-11.0 + 17.0 [ 23 ]c
+21.2 + 18.7 [ 23] c
DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 postweaning. c. Excludes values for dam 13257, which was found dead on day 10 of lactation.
* Significantly different from the vehicle control group value (p^O.OS).
)
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE E8 (PAGE 1): ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
24a
25
25
FEED CONSUMPTION (G/DAY)
DAYS 1 - 8
MEAN+S.D .
13.6 + 1.3
13.7 + 1.2
12.6 + 1.7
DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64d DAYS 1 - 64d
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
18.9 + 1.4 [ 23 ]b
20.4 + 2.3 ( 23 Jb
20.5 + 2.8 ( 23) c
20.5 + 2.7 [ 23 ]c
22.4 + 3.8 [ 22]b,c
22.9 + 3.2 ( 22]b,c
23.2 + 3.7 ( 23] c
21.5 + 2.3 t 23 ]c
20.4 + 1.8 ( 23 ]c
19.1 + 1.5
21.2 + 1.6
21.4 + 2.1
21.4 + 2.4
24.4 + 4.0
23.8 + 3.5 { 24] b
23.5 + 3.0
21.9 + 2.0 l 24] b
21.2 + 1.7 l 241b
18.9 + 2.4
20.8 + 1.9 ( 24 ]b
20.8 + 2.0
20.7 + 2.1 ( 24] b
23.6 + 3.9
23.6 + 3.9 [ 24 ]b
22.3 + 2.9
21.5 + 3.0 [ 24] b
20.6 + 1.9 ( 24]b
DAYS = DAYS POSTWEANING [ 3 = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning,- the sex was incorrectly identified. b. Excludes values that were associated with spillage or wet feed. c. Excludes values for rat 13221, which was found dead day 28 postweaning. d. Last value recorded before cohabitation. ` Significantly different from the vehicle control group value (p<0.05).
418-008:PAGE E-11
000601
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E9 (PAGE 1): RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - PRECOHABITATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
24a
25
25
FEED CONSUMPTION (G/KG/DAY)
DAYS 1 - 8
MEAN+S.D .
191.9 +18.7
192.8 + 14.1
180.9 + 23.4
DAYS 8 - 15 DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS 50 - 57 DAYS 57 - 64d DAYS 1 - 64d
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
167.9 + 15.3 [ 23) b
135.9 + 11.0 l 23)b
113.2 + 12.9 [ 23) c
99.9 + 9.6 ( 23 ]C
100.2 + 18.4 ( 22]b,c
95.3 + 13.6 [ 22]b,c
91.5 + 14.7 [ 23 ]C
80.9 + 6.4 ( 23 ]C
109.6 + 8.8 ( 23 ]C
166.7 + 11.4
136.4 + 7.6
114.2 + 6.8
100.3 + 7.8
103.4 + 16.7
93.9 + 11.6 [ 24] b
88.4 + 11.3
79.0 + 6.7 [ 24 ]b
109.2 + 6.6 ( 24 ]b
167.7 + 18.5
137.8 + 11.9 [ 24 ]b
114.6 + 6.8
100.9 + 7.8 ( 241b
104.1 + 18.9
96.8 + 17.6 [ 24 ]b
86.9 + 8.1
80.3 + 9.2 [ 24] b
109.5 + 9.1 [ 24 )b
DAYS = DAYS POSTWEANING ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values that were associated with spillage or wet feed. c. Excludes values for rat 13221, which was found dead day 28 postweaning. d. Last value recorded before cohabitation.
418-008:PAGE E-12
000602
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E10 (PAGE 1): MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - GESTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
1 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
23a,,b
25
25
PREGNANT
N 22
21
24
MATERNAL FEED CONSUMPTION (G/DAY)
DAYS 0 - 7 DAYS 7 - 10
MEAN+S.D. MEAN+S.D .
25.2 + 2.2 27.2 + 3.0
25.0 + 2.6 [ 20) c
26.2 + 4.2
24.0 + 2.4 25.4 + 3.2
DAYS 10 - 14 DAYS 14 - 17
MEAN+S.D. MEAN+S.D .
26.8 + 3.2 27.0 + 3.9
25.6 + 3.1 26.0 + 4.1
25.0 + 2.6 ( 23]c
26.9 + 3.3
DAYS 17 - 20
MEAN+S.D .
25.2 + 3.6
25.0 + 3.6
25.5 + 4.0
DAYS 0 - 20
MEAN+"S.D.
26.2 + 2.4
25.5 + 2.5
25.1 + 2.4
DAYS = DAYS OF GESTATION ( ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 postweaning. c. Excludes values that were associated with spillage.
418-008:PAGE E-13
000603
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE Ell (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - GESTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
23a,b
25
25
PREGNANT
N 22
21
24
MATERNAL FEED CONSUMPTION (G/KG/DAY)
DAYS 0 - 7 DAYS 7 - 10
MEAN+S.D. MEAN+S.D .
83.6 + 5.8 84.1 + 6.9
80.0 + 5.4 I 20] C
79.3 + 10.0
80.9 + 7.4 80.4 + 7.6
DAYS 10 - 14 DAYS 14 - 17
MEAN+S.D. MEAN+S.D .
78.8 + 7 .a 76.7 + 10.2
74.0 + 7.6 70.3 + 10.0
75.8 + 7.1 l 23) c
75.7 + 6.8
DAYS 1 7 - 2 0
MEAN+S.D .
63.1 + 8.2
61.3 + 7.6
64.5 + 8.8
DAYS 0 - 20
MEAN+S.D.
77.8 + 5.6
73.B + 5.0
75.9 + 5.2
DAYS = DAYS OP GESTATION ( ] - NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 postweaning. c. Excludes values that were associated with spillage.
418-008: PAGE E-14
000604
PROTOCOL 41B-00B: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E12 (PAGE 1) : MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - LACTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25 25 25
INCLUDED IN ANALYSES
N
23a,b
25
25
PREGNANT N 22 21 24
DELIVERED LITTERS
N
22
21
24
MATERNAL FEED CONSUMPTION (G/DAY)
DAYS 1 - 4 DAYS 4 - 7
MEAN+S.D. MEAN+S.D.
29.2 + 6.9 36.9 + 4.8
30.1 + 5.7 [ 19) c
39.6 + 7.8
25.2 + 4.7* 35.9 + 6.4
DAYS 7 - 14d DAYS 1 - 14d
MEAN+S.D. MEAN+S.D.
54.0 + 6.1 4 4 .4+ 4.6
57.4 + 7.1 47.1 + 6.2
52.0 + 7.3 [ 23) e
42.2 + 5.5 23) e
DAYS = DAYS OF LACTATION ( ) = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 postweaning. c. Excludes values that were associated with spillage. d. Because it is presumed that the pups begin to consume maternal feed after day 14 of lactation, maternal feed consumption values
were not tabulated on days 14 to 21 of lactation. e. Excludes values for dam 13257, which was found dead on day 10 of lactation.
* Significantly different from the vehicle control group value (p<0.05).
418-008:PAGE E-15
000605
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E13 (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - LACTATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS TESTED N 25
25
25
INCLUDED IN ANALYSES
N
23a,b
25
25
PREGNANT N 22 21 24
DELIVERED LITTERS
N
22
21
24
MATERNAL FEED CONSUMPTION (G/KG/DAY)
DAYS 1 - 4 DAYS 4 - 7
MEAN+S.D. MEAN+S.D .
90.6 + 24.7 113.2 + 20.8
89.0 + 15.0 [ 19) c
117.1 + 22.9
78.9 + 16.0 111.9 + 20.2
DAYS 7 - 14d DAYS 1 - 14d
MEAN+S.D. MEAN+S.D.
157.6 + 21.9 133.4 + 19.9
162.3 + 20.2 136.6 + 17.6
154.1 + 17.7 ( 23]1e
128.8 + 15.1 I 23)e
DAYS = DAYS OF LACTATION [ ] = NUMBER OF VALUES AVERAGED a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 postweaning. c. Excludes values that were associated with spillage. d. Because it is presumed that the pups begin to consume maternal feed after day 14 of lactation, maternal feed consumption values
were not tabulated on days 14 to 21 of lactation. e. Excludes values for dam 13257, which was found dead on day 10 of lactation.
418-008:PAGE E-16
000606
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE El4 (PAGE 1): SEXUAL MATURATION - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
FEMALE RATS N 25 25 25
INCLUDED IN ANALYSES
N
24a
25
25
VAGINA PATENT b
MEAN+S.D.
31.1 + 1.8
31.1 2.0
30.5 + 1.4
a. Excludes values for female rat 13205, which was excluded from study on day 1 postweaning; the sex was incorrectly identified. b. Average day postpartum that the vagina was patent.
418-008.PAGE E-17
000607
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E15 (PAGE 1): PASSIVE AVOIDANCE PERFORMANCE - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
FEMALE RATS
SESSION la
N
22b
25
22
TRIALS TO CRITERION LATENCY TRIAL lc LATENCY TRIAL 2c FAILED TO LEARN d
MEAN+S.D. MEAN+S.D. MEAN+S.D.
N (%)
6.4 8.0 23.2
If
+ 3.1 + 5.0 + 18.1 4 .5)
5.2 7.1 25.6
0(
+ 2.0 + 3.5 + 19.6 0..0)
5.0 11.3 24.1
0(
1.0 + 12.5 + 19.1 0..0)
SESSION 2a
N
21
25
22
TRIALS TO CRITERION LATENCY TRIAL lc
MEAN+S.D. MEAN+S.D.
4.0 + 2.9 26.0 + 21.3
3.3 + 2.7 38.4 + 23.7
2.8 + 1.2* 40.3 + 24.6
a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. Excludes values for rat 13205, which was excluded from study on day 7 postweaning,- the sex was incorrectly identified. c. The latency was recorded in seconds. d. Number of rats that did not meet the criterion in Session 1 (Learning Phase).
* Significantly different from the vehicle control group value (p<0.05).
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E16 (PAGE 1) : WATERMAZE PERFORMANCE - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
FEMALE RATS
SESSION la
N
21
25
21
TRIALS TO CRITERION ERRORS PER TRIAL LATENCY TRIAL 2b FAILED TO LEARN c
MEAN+S.D. MEAN+S.D. MEAN+S.D.
N (%)
11.2 + 2.7 0.S1 + 0.28
12.2 + 7.4 3 ( 14. 3)
9.8 + 2.8 0.40 + 0.18 13.0 + 7.5
3(12. 0)
11.8 + 2.5 0.51 + 0.27
14.5 + 8.2 2 1 9. 5)
SESSION 2a
N
18
22
18d
TRIALS TO CRITERION ERRORS PER TRIAL LATENCY TRIAL lb
MEAN+S.D. MEAN+S.D. MEAN+S.D.
7.3 + 3.2 0.16 + 0.18 14.4 + 12.1
7.5 + 3.0 0.15 + 0.14 10.4 + 5.6
6.3 + 1.8 0.17 + 0.20 10.7 + 3.5
a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c. Number of rats that did not meet the criterion in Session 1 (Learning Phase); Session 2 (Retention Phase) values for these
rats were excluded from group averages and statistical analyses. d. Excludes values for rat 13264, which was not tested during Session 2 (Retention Phase).
418-008:PAGE E-19
603000
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E17 (PAGE 1): MATING AND FERTILITY - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS IN COHABITATION
N
23a,b
25
25
DAYS IN COHABITATION C MEAN+S.D
3.6 t 3.2
3.9 + 2.8
2.6 + 1.5
RATS THAT MATED
N(4)
23(100.0)
24( 96.0)
25(100.0)
FERTILITY INDEX d
N/N <%>
22/23 ( 95.6)
21/24 ( 87.5)
24/25 ( 96.0)
RATS WITH CONFIRMED
MATING DATES
N
23
24
25
RATS MATING e DAYS 1- 7 DAYS 8-14
N (*) N (%)
20( 87.0) 3( 13.0)f
22( 91.7) 2( 8.3)
o o
o
25(100.0)
RATS PREGNANT/RATS IN COHABITATION
N/N (%)
22/23 ( 95.6)
21/25 ( 84.0)
24/25 ( 96.0)
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13121, which was found dead day 28 postweaning. c. Restricted to rats with a confirmed mating date and rats that did not mate. d. Number of pregnancies/number of rats that mated. e. Restricted to rats with a confirmed mating date. f. Includes data for rat 13228; rat was only in cohabitation six days with the first male because there were no available male
rats on day 1 of cohabitation.
000610
A
-- k.
0oi0 0
00
> G) m
m
t1o
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E18 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS EXAMINED a FOUND DEAD
N N
25 lb
25 0
25 lc
SACRIFICED N Id
0
0
APPEARED NORMAL
N
23b, d
25
24
THORACIC CAVITY:
LIGHT ORANGE FLUID
N
0
0
lc
TRACHEA:
WHITE FOAM PRESENT
N
0
0
lc
LUNGS: DARK RED N 0 0 lc
URINARY BLADDER:
ONE CALCULUS
N
2
0
0
WALLS THICKENED
N
1
0
0
KIDNEYS:
BILATERAL OR LEFT, CORTEX
PITTED AND/OR ROUGH
N
2
0
0
RIGHT, PELVIS, ONE CALCULUS N 1 0 0
RIGHT, PELVIS, TAN
GRANULAR MATERIAL
N
1
0
0
a. Refer to the individual clinical observations table(Table E23) b. Rat 13221 was found dead on day 28 postweaning. c. Dam 13257 was found dead on day 10 of lactation. d. Rat 13205 was excluded from study on day 7 postweaning;the sex
for externalobservations confirmed at necropsy. was incorrectly identified.
418-008:PAGE E-21
000611
PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE El9 (PAGE 1) : NATURAL DELIVERY OBSERVATIONS - SUMMARY - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
RATS ASSIGNED TO NATURAL DELIVERY
N
23a,b
25
25
PREGNANT
N (%)
22( 95.6)
21( 84.0)
24( 96.0)
DELIVERED LITTERS
N(%)
22(100.0)
21(100.0)
24(100.0)
DURATION OF GESTATION c MEAN+S.D .
22.9 + 0.5
22.9 + 0.4
22.8 + 0.4
IMPLANTATION SITES
N
PER DELIVERED LITTER MEAN+S.D .
338 15.4 + 2.9
352 16.8 + 2.2
369 15.4 + 2.2
DAMS WITH STILLBORN PUPS N (V)
4{ 18.2)
3( 14.3)
9( 37.5)
DAMS WITH NO LIVEBORN PUPS N
0
0
0
GESTATION INDEX d
% N/N
100.0 22/ 22
100.0 21/ 21
100.0 24/ 24
DAMS WITH ALL PUPS DYING
DAYS 1-4 POSTPARTUM
N
0
0
0
DAMS WITH ALL PUPS DYING
DAYS 5-21 POSTPARTUM
N
0
0
0
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly identified. b. Excludes values for rat 13221, which was found dead on day 28 of study. c. Calculated as the time (in days) elapsed between confirmed mating (arbitrarily defined as day 0) and the time (in days)
the first pup was delivered. d. Number of rats with live offspring/number of pregnant rats.
i
418-008-.PAGE E-22
000612
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PER INATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295. 9)
TABLE E20 (PAGE 1): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
DELIVERED LITTERS WITH
ONE OR MORE LIVEBORN PUPS N
22
21
24
PUPS DELIVERED (TOTAL)
N
MEAN+S.D .
316 14.4 + 3.5
325 15.5 + 2.5
357 14.9 + 2.6
LIVEBORN
MEAN+S.D. N <%)
14.1 + 3.5 310( 98.1)
15.1 + 2.4 318( 97.8)
14.3 + 2.5 344( 96.4)
STILLBORN
MEAN+S.D. N (%)
0.3 + 0.6 6 ( 1.9)
0.3 + 1.1 7( 2.2)
0.5 + 0.9 13( 3.6)
PUPS FOUND DEAD OR PRESUMED CANNIBALIZED
DAY 1 DAYS 2 - 4 DAYS 5- 7 DAYS 8-14 DAYS 15-21
N / N (%) N / N (%) N / N (%) N / N (%) N / N (%)
2/310( 7/3081 0/171( 0/171( 0/171(
0.6) 2.3) 0.0) 0.0) 0.0)
2/3181 2/316 ( 2/1671 1/1651 0/1641
0.6) 0.6) 1.2) 0.6) 0.0)
2/344 ( 11/342(
5/191( 1/178( 0/177(
0.6) 3.2) 2.6) 0.6)a 0.0)a
VIABILITY INDEX b
% N/N
97.1 301/310
98.7 314/318
96.2 331/344
LACTATION INDEX c
% N/N
100.0 171/171
98.2 164/167
96.7 177/183
DAY(S) = DAY(S) POSTPARTUM a. Excludes values for litter 13257; the dam was found dead on day 10 of lactation; eight pups were sacrificed. b. Number of live pups on day 4 (preculling) postpartum/number of liveborn pups on day 1 postpartum. c. Number of live pups on day 21 (weaning) postpartum/number of live pups on day 4 (postculling) postpartum.
418-008:PAGE E-23
000613
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR`S STUDY NUMBER: 6295.9)
TABLE E20 (PAGE 2): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
DELIVERED LITTERS WITH
ONE OR MORE LIVEBORN PUPS
N
22
21
24
SURVIVING PUPS/LITTER a
DAY 1 b
MEAN+S.D.
14.1 + 3.5
15.1 + 2.4
14.3 + 2.5
DAY 4 PRECULLING
MEAN+S.D .
13.7 + 3.3
15.0 + 2.8
13.8 + 2.4
DAY,. 4 POSTCULLING MEAN+S.D .
7.8 + 0.8
8.0 + 0.2
8.0 + 0.2
DAY 7
MEAN+S.D.
7.8 _+ 0.8
7.8 + 0.5
7.8 + 0.7
DAY 14
DAY 21
PERCENT MALE PUPS PER NUMBER OF PUPS SEXED
MEAN+S.D. MEAN+S.D .
7.8 + 0.8 7.8 + 0.8
7.8 + 0.7 7.8 + 0.7
7.7 + 0.8 [ 24]C
7.7 + 0.8 [ 24] c
DAY 1 b
MEAN+S.D .
47.9 + 15.2
52.1 + 10.9
47.0 + 13.3
DAY 4 PRECULLING
MEAN+S.D.
47.9 + 15.1
51.5 + 11.1
46.6 + 13.4
DAY 4 POSTCULLING MEAN+S.D .
47.0 + 10.0
49.6 + 1.6
49.1 + 5.7
DAY 7
MEAN+S.D .
47.0 + 10.0
48.9 + 3.9
48.7 + 6.4
DAY 14 DAY 21
MEAN+S.D . MEAN+S.D.
47.0 + 10.0 47.0 + 10.0
49.2 + 2.6 49.2 + 2.6
48.3 + 6.2 [ 24 )C
48.3 + 6.2 [ 24)C
DAY = DAY POSTPARTUM l ) = NUMBER OF VALUES AVERAGED a. Average number of live pups per litter, including litters with no surviving pups. b. Includes pups born alive, found dead day 1 postpartum. c. Excludes values for litter 13257; the dam was found dead on day 10 of lactation; eight pups were sacrificed.
418-008:PAGE E-24
000614
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E20 (PAGE 3): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
DELIVERED LITTERS WITH
ONE OR MORE LIVEBORN PUPS
N
22
21
24
LIVE LITTER SIZE AT WEIGHING
DAY 1
MEAN+S.D .
14.0 3.5
15.0 2.6
14.2 + 2.5
DAY 4 PRECULLING
MEAN+S.D .
13.7 + 3.3
15.0 + 2.8
13.8 + 2.4
DAY 4 POSTCULLING MEAN+S.D .
7.8 0.8
8.0 + 0.2
7.9 + 0.3
DAY 7
MEAN+S.D .
7.8 + 0.8
7.8 + 0.5
7.8 + 0.7
DAY 14
MEAN+S.D .
DAY 21
MEAN+S.D .
PUP WEIGHT/LITTER (GRAMS)
7.8 + 0.8 7.8 + 0.8
7.8 + 0.7 7.8 + 0.7
7.7 + 0.8 [ 23 )a
7.7 + 0.8 t 23 ]a
DAY 1 DAY 4 PRECULLING DAY 4 POSTCULLING DAY 7 DAY 14 DAY 21
MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D . MEAN+S.D .
6.3 + 0.8 8.7 + 1.6 8.8 f 1.6 14.7 + 2.4 32.0 + 3.5 50.1 + 5.1
6.1 + 0.5 8.2 + 1.0 8.3 + 1.0 13.9 2.2 31.8 + 3.1 49.2 f 5.0
6.2 + 0.5
8.0 + 1.3
8.0 + 1.3
12.8 + 2.6*
28.9+ 4.7** [ 23] a
46.5 + 6.3 ( 23] a
DAY = DAY POSTPARTUM ( ) = NUMBER OF VALUES AVERAGED a. Excludes values for litter 13257; the dam was found dead on day 10 of lactation; eight pups were sacrificed. * Significantly different from the vehicle control group value (p<0.05). ** Significantly different from the vehicle control group value (p<0.01).
418-008:PAGE E-25
000615
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E21 (PAGE 1) : CLINICAL OBSERVATIONS FROM BIRTH TO DAY 21 POSTPARTUM - SUMMARY - F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
LITTERS EXAMINED (N)
22 21 24
TRANSIENT CLINICAL OBSERVATIONS: a
TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS
NOT NURSING OR NESTING
N/N
1/ 1
0/ 0
0/ 0
DECREASED MOTOR ACTIVITY
N/N
1/ 1
0/ 0
0/ 0
COLD TO TOUCH
N/N 1/ 1
0/ 0
0/ 0
PERSISTENT CLINICAL OBSERVATIONS:: a
TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS
TIP OF TAIL MISSING
N/N 21/ 1
0/ 0
1/ 1
UMBILICAL HERNIA
N/N 0/ 0
0/ 0
15/ 1
STATISTICAL ANALYSES WERE RESTRICTED TO THE NUMBER OF LITTERS WITH OBSERVATIONS. N/N = TOTAL FREQUENCY (DAYS X PUPS)/LITTERS WITH OBSERVATIONS a. Tabulation restricted to adverse observations; all other pups appeared normal.
418-008:PAGE E-26
000616
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295/9)
TABLE E22 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
LITTERS EXAMINED (N)
22 21 24
TOTAL PUPS STILLBORN
OR FOUND DEAD a
N9
12
19
STILLBORN
N4
7 12
FOUND DEAD
N5
5
7
NO MILK IN STOMACH b
N (%)
2 ( 40.0)
4( 80.0)
4( 57.1)
PUPS SACRIFICED AND NECROPSIED ON DAYS 4, 10 OR 21 POSTPARTUM a
LITTERS EVALUATED N 22 21 24
PUPS EVALUATED
N 301
311
325
APPEARED NORMAL LITTER INCIDENCE PUP INCIDENCE
N (%) N (%)
21( 9S.4) 300( 99.7)
20( 95.2) 310( 99.7)
24(100.0) 325 (100.0)
LIVER: MEDIAN AND LEFT LATERAL LOBES, TAN RAISED AREA
LITTER INCIDENCE
N (%)
0( 0.0)
PUP INCIDENCE
N(%)
0( 0.0)
1( 4.8) M 0.3)
0( 0.0) 0< 0.0)
BRAIN: HYDROCEPHALY, EXTREME DILATION OF ALL VENTRICLES
LITTER INCIDENCE
N (%)
1( 4.5)
PUP INCIDENCE
N (%)
1( 0.3)
0{ 0.0) 0( 0.0)
0( 0.0) 0( 0.0)
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. b. Analysis restricted to pups found dead and necropsied.
418-008:PAGE E-27
000617
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E23 (PAGE 1) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT tf
DESCRIPTION
13201 13202 13203 13204 13205b 13206
13207 13208
13209
DP ( 77 )
DP ( 23- 24) DP ( 72- 75) DG ( 0- 21) DG ( 5- 21) DL( 1- 21) DL< 1- 21) DP ( 7 ) DP ( 69- 75) DP ( 69- 75) DGl 0- 12) DG( 13 ) DG ( 0- 12) DG ( 13 ) DG ( 18- 21) DL( 1- 21) DP ( 71- 74) DG ( 0- 21) DL( 1- 21) DP ( 9- 16) DP ( 11- 16) DP ( 17 ) DP ( 71 ) DP ( 72 ) DP ( 71- 74) DG( 0- 21) DG ( 7- 21) DG ( 16- 18) DG ( 16- 21) DG ( 16- 21) DL( 1- 21) DL( 1- 21) DL( 1- 21) DL( 1- 21) DL( 20 )
CHROMORHINORRHEA NO ADVERSE FINDINGS URINE-STAINED ABDOMINAL FUR EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE LOCALIZED ALOPECIA: LIMBS EARS: SWOLLEN AND PURPLE a LOCALIZED ALOPECIA: LIMBS a SACRIFICED; THE SEX WAS INCORRECTLY IDENTIFIED INCISORS MISSING/BROKEN INCISORS MISALIGNED INCISORS MISSING/BROKEN INCISORS GROWN IN INCISORS MISALIGNED INCISORS REALIGNED INCISORS MISSING/BROKEN INCISORS MISSING/BROKEN a EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE a URINE-STAINED ABDOMINAL FUR PERIVAGINAL SWELLING SWELLING RESOLVED LEFT FOREPAW : SWOLLEN SWELLING RESOLVED LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: UNDERSIDE CHROMORHINORRHEA CHROMODACRYORRHEA INCISORS MISALIGNED CHROMODACRYORRHEA a INCISORS MISALIGNED a LOCALIZED ALOPECIA: LIMBS a LOCALIZED ALOPECIA: UNDERSIDE URINE-STAINED ABDOMINAL FUR NO ADVERSE FINDINGS
DP = DAY POSTWEANING DG = DAY OF GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy. b. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008:PAGE E-28
8T3000
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E23 (PAGE 2) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT n
DESCRIPTION
13210
13211
13212 13213 13214 13215 13216
13217
13218 13219 13220
13221 13222 13223 13224 13225
DP ( 62- 77) DP ( 76- 77) DG ( 0- 2) DG ( 0- 20) DG ( 4 ) DG ( 17- 20) DL ( 1- 21) DL( 1- 21) DP ( 1- 75) DG ( 0- 22) DL ( 1- 21)
DPI 65- 74) DG( 0- 21) DL ( 1- 21) DP ( 65- 71) DP ( 72 ) DP ( 65- 80) DPI 69- 73) DP ( 79 ) DG ( 0- 21) DL ( 1- 2) DL( 3 )
DG ( 0- 11) DG ( 0- 11) DG ( 12- 21) DL ( 1- 21) DP ( 28 )
DL ( 19- 21) DG ( 5 ) DG ( 12- 21) DL ( 1- 6)
INCISORS MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA INCISORS MISALIGNED CHROMODACRYORRHEA INCISORS MISSING/BROKEN INCISORS MISSING/BROKEN a INCISORS MISALIGNED a LEFT HINDPAW: THIRD AND FOURTH DIGITS MISSING LEFT HINDPAW: THIRD AND FOURTH DIGITS MISSING LEFT HINDPAW: THIRD AND FOURTH DIGITS MISSING NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS LOCALIZED ALOPECIA: LIMBS a INCISORS MISSING/BROKEN INCISORS GROWN IN INCISORS MISALIGNED CHROMODACRYORRHEA CHROMORHINORRHEA INCISORS MISALIGNED INCISORS MISALIGNED INCISORS REALIGNED NO ADVERSE FINDINGS NO ADVERSE FINDINGS TAIL: SHEATH MISSING TIP OF TAIL BLACK TIP OF TAIL MISSING TIP OF TAIL MISSING a FOUND DEAD NO ADVERSE FINDINGS NO ADVERSE FINDINGS EARS: SWOLLEN AND PURPLE a CHROMORHINORRHEA CHROMORHINORRHEA CHROMORHINORRHEA
DP DAY POSTWEANING DG = DAY OF GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
418-008:PAGE E-29
000619
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E23 (PAGE 3): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT (t
DESCRIPTION
13226 13227 13228
13229 13230 13231 13232
13233 13234
13235 13236 13237 13238
13239 13240 13241 13242
DG ( 10 24) DG ( 25 ) DG( 11 24) DG ( 25 )
DG ( 2- 20) DL( 1- 21)
DP ( 72 - 78) DG ( 0 ) DG ( 0- 3) DG ( 4 ) DG ( 9 ) DG ( 9- 21) DG ( 9- 21) DL( 1- 21) DL( 1- 21) DL( 15 - 16)
DP ( 73 - 81) DG ( 0- 21) DG ( 19 ) DL( 1- 21) DL< 5- 11) DG ( 22 )
DL( 13 - 21) DP ( 75 - 76) DG ( 0- 21) DL ( 1- 21) DL( 10 - 21)
NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS MISALIGNED INCISORS REALIGNED . INCISORS MISSING/BROKEN INCISORS GROWN IN NO ADVERSE FINDINGS EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE NO ADVERSE FINDINGS INCISORS MISSING/BROKEN INCISORS GROWN IN INCISORS MISSING/BROKEN INCISORS GROWN IN CHROMORHINORRHEA INCISORS MISSING/BROKEN INCISORS MISALIGNED INCISORS MISSING/BROKEN INCISORS MISALIGNED a CHROMORHINORRHEA NO ADVERSE FINDINGS EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE SOFT OR LIQUID FECES EARS: SWOLLEN AND PURPLE CHROMODACRYORRHEA RED PERIVAGINAL SUBSTANCE NO ADVERSE FINDINGS CHEST: ABRASION (0.5 CM INCISORS MISALIGNED INCISORS MISALIGNED INCISORS MISALIGNED a INCISORS MISSING/BROKEN NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS NO ADVERSE FINDINGS
DP = DAY POSTWEANING DG = DAY OF GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
418-008:PAGE E-30
000620
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E23 (PAGE 4): CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
RAT #
DESCRIPTION
13243 13244
13245 13246
13247 13248
13249 13250
DP ( 65- 75) DP ( 65- 75) DG ( 0- 25) DG ( 0- 25) DPI 38- 47) DP ( 38- 48) DPI 49 ) DPI 48 ) DP ( 49 ) DP ( 72- 74) DG( 0- 4) DG ( 5 ) DP ( 51- 59) DP ( 60 ) DP ( 38- 48) DP ( 49 ) DP ( 72- 75) DG ( 0- 21) DG ( 10- 21) DL( 1- 21) DL( 1- 21)
DG ( 2 ) DG ( 3 ) DG( 2- 11) DG ( 12 ) DG( 7- 21) DG( 10- 21) DL( 1- 21) DL( 1- 21) DL( 21 )
DP { 50- 60) DP ( 61 )
CHROMODACRYORRHEA INCISORS: MISALIGNED CHROMODACRYORRHEA a INCISORS: MISALIGNED a BACK: ABRASION (0.3 CM IN DIAMETER) LOCALIZED ALOPECIA: BACK ALOPECIA NO LONGER APPARENT BACK: SCAB (0.3 CM IN DIAMETER) SCAB NO LONGER APPARENT LOCALIZED ALOPECIA: HEAD LOCALIZED ALOPECIA: HEAD ALOPECIA NO LONGER APPARENT INCISORS: MISSING/BROKEN INCISORS: GROWN IN LOCALIZED ALOPECIA: BACK ALOPECIA NO LONGER APPARENT EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE LOCALIZED ALOPECIA: LIMBS EARS: SWOLLEN AND PURPLE a LOCALIZED ALOPECIA: LIMBS NO ADVERSE FINDINGS INCISORS: MISALIGNED INCISORS: REALIGNED INCISORS: MISSING/BROKEN INCISORS: GROWN IN LOCALIZED ALOPECIA: LIMBS EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE a LOCALIZED ALOPECIA: LIMBS a INCISORS: MISSING/BROKEN a NO ADVERSE FINDINGS INCISORS: MISSING/BROKEN INCISORS: GROWN IN
DP = DAY POSTWEANING DG = DAY OF GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
418-008:PAGE E-31
000621
PROTOCOL. 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERI NATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E23 (PAGE 5) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT ft
DESCRIPTION
13251 13252
13253 13254 13255 13256 13257 13258 13259 13260
13261
13262 13263 13264 13265
DG ( 4- 20) DL( 1- 20) DL ( 21 ) DG ( 1- 15) DG ( 16 ) DP( 49- 53) DP ( 54- 55) DP ( 48- 67) DP ( 68 ) DL ( 1 ) DL ( 10 )
DG ( 11- 21) DL ( 1- 21) DG ( 6- 9) DG ( 10 ) DG ( 10- 21) DL( 1- 21) DG ( 3- 5) DG ( 3- 21) DL ( 1- 12) DL ( 13 )
DL ( 1 ) DP ( 55- 73) DG ( 0- 21) DG ( 7- 21) DG ( 8- 21) DG ( 21 ) DL ( 1- 5) DL ( 1- 21) DL ( 1- 21) DL ( 9- 21) DL ( 10- 20) DL ( 19- 21)
NO ADVERSE FINDINGS INCISORS MISALIGNED INCISORS MISALIGNED INCISORS REALIGNED INCISORS MISSING/BROKEN INCISORS GROWN IN INCISORS MISSING/BROKEN INCISORS GROWN IN INCISORS MISSING/BROKEN INCISORS GROWN IN RED PERIVAGINAL SUBSTANCE FOUND DEAD NO ADVERSE FINDINGS EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE a INCISORS MISSING/BROKEN INCISORS GROWN IN EARS: SWOLLEN AND PURPLE EARS: SWOLLEN AND PURPLE a INCISORS MISSING/BROKEN INCISORS MISALIGNED INCISORS MISALIGNED INCISORS REALIGNED NO ADVERSE FINDINGS NO ADVERSE FINDINGS RED PERIVAGINAL SUBSTANCE
INCISORS MISALIGNED INCISORS MISALIGNED LOCALIZED ALOPECIA: LIMBS CHROMODACRYORRHEA RED PERIVAGINAL SUBSTANCE CHROMODACRYORRHEA INCISORS : MISALIGNED a LOCALIZED ALOPECIA: LIMBS a LOCALIZED ALOPECIA: UNDERSIDE a CHROMODACRYORRHEA INCISORS MISSING/BROKEN a
DP = DAY POSTWEANING DG = DAY OF GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
418-008:PAGE E-32
000622
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E23 (PAGE 6) : CLINICAL OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
RAT
DESCRIPTION
13266 13267 13268
13269 13270
13271
13272 13273 13274 13275
DP ( 71- 74) DP ( 72- 74) DG ( 0- 2) DG ( 0- 20) DG ( 3- 8) DG ( 9 ) DG ( 4 ) DL( 1- 21) DL( 20- 21) DL ( 1 ) DP ( 62- 76) DP ( 65- 72) DG ( 0- 21) DL ( 1 ) DL ( 1- 21) DL ( 9- 21) DP ( 56- 74) DP ( 58- 61) DP ( 69- 74) DG ( 0- 21) DG ( 0- 21) DL ( 1- 21) DL ( 1- 21) DP ( 74 ) DG ( 0 ) DG ( 21 )
DL ( 1 )
NO ADVERSE FINDINGS NO ADVERSE FINDINGS INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA INCISORS: MISALIGNED LOCALIZED ALOPECIA: HEAD ALOPECIA NO LONGER APPARENT CHROMODACRYORRHEA INCISORS : MISALIGNED a INCISORS: MISSING/BROKEN a RED PERIVAGINAL SUBSTANCE INCISORS: MISALIGNED CHROMODACRYORRHEA INCISORS: MISALIGNED RED PERIVAGINAL SUBSTANCE INCISORS: MISALIGNED a INCISORS: MISSING/BROKEN a INCISORS: MISALIGNED CHROMODACRYORRHEA CHROMODACRYORRHEA CHROMODACRYORRHEA INCISORS : MISALIGNED CHROMODACRYORRHEA a INCISORS: MISALIGNED a URINE-STAINED ABDOMINAL FUR URINE-STAINED ABDOMINAL FUR RED PERIVAGINAL SUBSTANCE NO ADVERSE FINDINGS RED PERIVAGINAL SUBSTANCE
DP = DAY POSTWEANING DG = DAY OF GESTATION DL = DAY OF LACTATION a. Observation confirmed at necropsy.
418-008:PAGE E-33
000623
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE E24 (PAGE 1): BODY WEIGHTS - PRECOHABITATION INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 43 50 57 64 71 PRECOHABITATION a
RAT ft
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13201 13202 13203 13204 13205b 13206 13207 13206 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
53 . 46 . 45. 53 .
55. 61. 57 . 54 . 50. 54 . 56. 50. 64 . 49. 45. 44 . 51. 46 . 49. 57. 59. 42 . 43 . 44 .
95 . 86 .
11 .
91.
101 . 107.
96 . 94 . 90. 92 . 95. 94 . 109. 83. 78. 80. 93 . 85 . 82 . 100. 105. 81. 81. 87.
138. 122 . 114 . 137.
145 . 154 . 139. 125 . 138. 140. 146 . 141. 152. 121. 117. 136. 139. 130 . 120. 142 . 158. 112. 128. 134 .
170 . 143 . 142 . 168 .
188 . 184 . 165 . 151. 170 . 182 . 177 . 189. 187 . 148. 154 . 174 . 173 . 164 . 154 . 170. 198. 141 . 177. 169.
188 . 166 . 165. 194 .
217 . 186. 171. 204 .
233 . 211 . 203 . 228.
245. 220 . 217. 234 .
226 .
249.
262
272.
229.
257.
276 .
289.
229.
228.
257
287.
167.
188.
200
215.
200.
224 .
254
262.
180.
211 .
244
257.
208.
217 .
234
250.
222.
247 .
257
278.
202.
238 .
260
274 .
169.
190.
202
221.
184 .
207.
223
247 .
199.
237.
251
266.
181 .
214 .
217
235.
182.
204 .
220
238.
182.
214 .
212
237.
FOUND DEAD ON DAY 28 IPOSTWEANING
228.
268 .
277
307.
166.
186 .
200
212.
203 .
235.
264
285.
192.
208.
218
227.
261. 233. 222. 236.
270 . 307. 293 . 227. 280 . 284 . 251 . 282. 284 . 228. 256. 272 . 249. 243 . 239 .
317. 215. 291. 230.
271. 253 . 236. 243 .
298. 320. 297 . 239. 298. 298. 278. 303 . 290. 242. 272. 289. 261. 248. 243 .
327. 224 . 320. 233 .
279. 261. 238. 257.
307. 340. 324 . 249. 301 . 310 . 278. 317. 309. 238. 272 . 291. 262 . 261. 246 .
338. c c c
289. 268 . 245. 260.
303 . 336. 314 . 252 . 290 . 317. 287. 317. 303 . 244 . 283 . 294 . 273 . 257. 241.
332. 224 . 329. 240 .
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Precohabitation body weights were recorded on the day cohabitation was begun in the FI generation rats; at that time these
rats were 85 to 97 days of age. b. Rat 13205 was excluded from study on day 7 postweaning,- the sex was incorrectly identified. c. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 64 postweaning
was the last day on which the youngest rats (in this group) had a body weight value recorded.
418-008: PAGE E-34
000624
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E24 (PAGE 2) : BODY WEIGHTS PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 43 50 57 64 71 PRECOHABITATION a
RAT #
DOSAGE GROUP II
0.1 MG/KG/DAY
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
52. 52 . 44 . 41 . 55. 50. 53 . 51. 48 . 42 . 51. 57. 53. 54 . 50. 50. 50. 43. 57. 53. 50. 52. 52. 52 . 50.
87. 91. 88. 78. 96 . 94 . 95. 92. 88. 82 . 96. 99. 94. 100. 90. 86. 90. 88. 97. 98 . 90. 93. 95. 94 . 95 .
129. 135. 130. 116 . 141. 141. 136. 146 . 139. 128. 142 . 150. 142 . 147. 139. 128. 133. 141. 139. 142. 134 . 136 . 145. 146 . 144 .
161. 162. 155. 154. 177. 180. 170. 178 . 180. 164 . 177. 180. 170 . 191. 181. 166 . 170. 178. 177. 189. 164 . 171. 180. 183 . 178 .
188. 184 . 180 . 172 . 202. 214 . 195. 207. 215. 191. 198. 206. 193. 222 . 208. 195. 198. 220. 192. 215 . 184 . 202 . 206. 216 . 209.
210. 208. 200. 200. 226 . 244 . 214 . 238. 252. 222. 224 . 227. 214 . 236 . 236. 222 . 227. 254 . 216. 244 . 211. 240 . 226 . 238. 240 .
229. 226 . 224 . 217. 245. 264 . 229. 271. 266. 245. 238. 246. 232. 250. 251 . 237. 248. 265. 241. 259. 231. 258 . 251. 246 . 258.
236. 238. 226. 225 . 256 . 284 . 244 . 288. 283 . 266 . 262 . 262. 245. 288. 269. 248. 258. 285. 259. 275. 242. 282. 261. 260 . 293 .
253 . 254 . 244 . 246. 266 . 286 . 246 . 317 . 299. 282 . 276. 258. 256. 284 . 267 . 260. 278 . 287. 259. 300. 252. 284 . 279. 271. 314 .
261. 266. 254. 245. 272. 305. 266 . 302. 309. 301. 275. 272. 264 . 289. 280. 280. 282. 308. 278 . 294 . 271. 302. 278. 286. 328 .
269. 279 . 257 . 263 . 287. 314 . 280. 318. 330. 315 . 296 . 277. 289. 305. 284 . 289. 301 . 307. 293 . 312 . 267. 303 . 293. 282 . 326.
274 . 283. 267. 269. 286 . 312 . 277. 319. 319. 317. 292. 285. 286. 298. 289. 288 . 307. 310. 280. 308. 276. 314 . 299. 287. 309.
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Precohabitation body weights were recorded on the day cohabitation was begun in the FI generation rats; at that time these
rats were 85 to 97 days of age.
418-008:PAGE E-35
000625
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E24 (PAGE 3) : BODY WEIGHTS - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAY 1
8 15 22 29 36 43 50 57 64 71 PRECOHABITATION a
RAT ft
DOSAGE GROUP III
0.4 MG/KG/DAY
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
46 . 43 . 42 . 47. 46. 46 . 50. 52. 50. 49. 53 . 51. 48. 45 . 52. 47. 48 . 46. 58. 50 . 47. 62. 57. 42 . 40 .
102. 83. 91. 92. 90. 88. 92. 95. 93. 86. 87. 92. 90. 83. 97. 82. 86 . 89. 97. 93. 90.
115. 102.
86. 78.
153 . 128 . 137. 138 . 133 . 124 . 139. 133. 133 . 130. 131. 136. 142 . 122 . 143 . 123 . 126 . 130. 136 . 139. 124 . 165 . 143 . 129. 125 .
187. 175. 162 . 168. 172. 153 . 187. 173 . 163 . 162. 162 . 177. 179. 150 . 179. 163 . 153 . 162 . 159. 165. 152 . 203 . 173 . 165. 168.
220 . 183 . 193 . 172 . 197. 189. 224 . 200. 190 . 199. 192. 197. 204. 173 . 201. 188. 172 . 185. 173. 199. 169. 236. 204 . 185. 203 .
246 . 209 . 203 . 194 . 214 . 207. 254 . 220. 212 . 231. 212. 224 . 228. 203 . 229. 212 . 201. 207. 195. 235. 194 . 255. 231. 210 . 218.
266 . 227. 230 . 211 . 246. 228. 288 . 249. 234 . 252 . 233 . 250 . 245 . 208. 260 . 236 . 214 . 216 . 212. 243 . 218 . 270. 244 . 231 . 236.
279. 244 . 228. 223 . 258. 247. 301. 257. 247. 266. 249. 264 . 250. 230 . 283. 249. 231. 230. 230. 258. 229. 293. 253. 234. 246.
301. 255 . 241 . 233 . 280. 251. 316. 265. 252 . 267. 259. 284 . 263 . 230. 300. 269 . 240 . 236 . 240 . 273 . 235. 308. 267 . 257 . 246 .
312. 257. 252. 233. 2B6 . 275. 340. 275. 266. 284 . 264 . 284. 268. 236. 307. 284 . 253 . 243 . 265. 277. 244 . 310 . 285. 252 . 255.
323 . 274. 262 . 252. 291. 281. 344 . 283 . 272. 299. 266 . 300. 264 . 246. 291 . 284 . 256. 250. 280. 276. 247. 311. 294 . 276 .
b
325. 270. 255. 252. 303 . 279. 353. 287. 277. 296 . 270 . 293 . 275. 242 . 302. 294 . 257. 242 . 279 . 284 . 246 . 313. 292 . 266 . 255 .
1
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Precohabitation body weights were recorded on the day cohabitation was begun in the FI generation rats; at that time these rats were 85 to 97 days of age.
b. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 64 postweaning was the last day on which the youngest rats (in this group) had a body weight value recorded.
418-008: PAGE E-36
000626
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E25 (PAGE 1) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0 1 2 3 4 5 6 7 8
RAT ft
DOSAGE GROUP I
0 [CLE) MG/KG/DAY
13201 P 13202 P 13203 P 13204 P 13205a 13206 P 13207 P 13208 P 13209 NP 13210 p 13211 p 13212 P 13213 p 13214 P 13215 p 13216 p 13217 p 13218 p 13219 p 13220 p 13221 13222 13223 13224 13225
284 . 265. 250 . 257.
298. 274 . 256 . 246 .
298 . 281. 267. 270.
304 284 275 275
307.
304 .
312.
321
324.
330.
340.
344
308.
314 .
316.
331
259.
264 .
263 .
268
294 .
306.
305.
312
304.
315.
323.
322
288.
296.
301.
309
317.
325.
332.
339
301.
309.
318.
323
243.
248.
250.
257
283.
290.
297.
299
309.
316.
318.
324
273.
275.
282 .
283
252 .
258.
266 .
270
246.
261.
268.
273.
FOUND DEAD ON DAY 28 POSTWEANING
336.
338.
351.
352
253.
266.
265 .
265
329.
341.
345.
350.
234.
244 .
253 .
256
308. 285. 273. 280.
321. 358 329 269 315 330. 308. 345. 322 . 260 . 302. 326. 286. 270. 279.
348. 267, 349, 260.
311. 292. 277. 285.
326. 357. 332. 274. 311. 335. 309. 349. 332. 261. 306. 327. 291. 275. 282.
352. 271. 358. 263 .
308. 297. 279. 287.
334 . 365. 341. 272. 323 . 347. 316. 351. 330. 260. 305. 334 . 298. 277. 285.
359. 273 . 356. 266 .
308. 301. 283 . 294 .
341. 371. 343 . 273 . 326. 349. 314 . 357. 336. 265. 312. 340. 300. 277. 290.
365. 279. 363. 270.
316. 303 . 286 . 300.
345. 377. 346 . 281. 329. 353. 327. 365. 346. 276. 312. 340. 306. 284 . 288 .
364. 280. 360. 273 .
P = PREGNANT
1 = NOT PREGNANT (VALUES EXCLUDI
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
9
319. 312. 291. 299.
345. 381. 344 . 280. 337. 362. 333. 368. 347. 279. 324. 342. 313. 288. 292.
373. 282. 367. 278.
10
327. 321. 300. 307.
355. 381. 360. 278. 339. 361. 333 . 376 . 356 . 281. 329. 348. 320. 295. 293 .
379. 284. 373. 280 .
11
328. 326. 307. 316 .
355. 385. 360. 283 . 352. 374. 343. 376. 361. 291. 334 . 349. 329. 303. 297.
378. 290. 377. 283.
12
332. 332. 300. 319.
364. 394. 366. 278. 356. 379. 347. 391. 368 . 293 . 338. 359. 334. 307. 304 .
387. 291. 382. 290.
418-008:PAGE E-37
000627
PROTOCOL 41B-00B: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E25i (PAGE 2): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18 19 20 21
RAT
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13201 P 13202 P 13203 P 13204 P 13205a 13206 P 13207 P 13208 P 13209 NP 13210 P 13211 P 13212 P 13213 P 13214 P 13215 P 13216 P 13217 P 13218 P 13219 P 13220 P 13221 13222 P 13223 P 13224 P 13225 P
339. 340. 300. 324 .
342 . 340 . 306. 338.
346. 350. 320. 345.
353 .
363 . 328. 354.
370.
375.
387.
390.
392 .
406 .
416.
416 .
366.
377.
379.
373.
276.
280.
284.
280.
360.
367.
372.
393.
385.
388 .
391.
394 .
354.
361.
370.
372.
386.
393 .
403.
415.
362.
370 .
382.
390.
300.
303.
312.
327.
342.
347.
350.
354 .
362.
362.
376.
384 .
340.
346 .
352.
356.
313.
317.
322.
325.
302 .
312.
314.
322.
FOUND DEAD ON DAY 28 POSTWEANING
392.
398.
408.
418.
298.
303.
311.
316.
386 .
397 .
392 .
408.
290.
294 .
298.
306 .
372 . 375. 348. 366 .
399 443 362 276 410 406 390 433 407 343 366 392 369 342 337
434 334 396 323
389. 394 . 353 . 381.
412. 447. 390. 273 . 416. 420. 404 . 445. 422. 362. 389. 407. 386. 363. 351.
443 . 352. 424 . 332.
398. 408. 358. 397.
427. 476. 404 . 277 . 432. 424 . 414 . 464 . 430. 379. 407. 422. 405. 375. 358.
455. 362. 444 . 343.
418. 424 . 369. 406 .
432. 496. 423 . 274. 453 . 424. 433. 472. 446. 389. 417. 439. 411. 393. 378.
453. 379. 446 . 356.
431.
355. 422.
428. 498. 403 . 275.
431. 442. 477. 462 . 398 . 433. 458. 431. 402. 396.
465. 396. 477. 361.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OP PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
22
279 . 439.
23 282.
24 25
278 .
278.
418-008: PAGE E-38
000628
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E25 (PAGE 3) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0
1
RAT It
DOSAGE GROUP II
2
34 0.1 MG/KG/DAY
5
13226 P 13227 P 13228 NP 13229 p 13230 p 13231 p 13232 P 13233 p 13234 p 13235 p 13236 p 13237 p 13238 p 13239 p 13240 p 13241 p 13242 P 13243 NP 13244 NP 13245 NP 13246 P 13247 P 13248 P 13249 P 13250 P
270.
273 .
280.
288.
293 .
300 .
284 .
291.
297.
259.
278.
281.
286.
294 .
299.
311.
326.
327.
290.
298.
297.
316.
328.
334.
334.
345.
356.
314.
311.
318.
295.
308 .
314.
292.
299.
304.
282.
284 .
290.
299.
301.
312.
292.
300.
306.
290.
288.
298.
301.
312 .
321.
305.
314.
317.
297.
286 .
280.
MATING NOT CONFIRMED
280.
283.
286.
307.
314.
313.
302.
312.
311.
279.
283 .
289.
315.
330.
334.
282. 304. 300. 289. 304. 329. 301. 334 . 366. 324. 323. 303 . 296. 312. 310. 299. 326. 321. 289.
295. 324. 316. 297. 334.
286 . 309. 303. 289. 307. 340. 302. 338. 360. 328. 323 . 308. 296. 314 . 312. 304 . 333. 321. 290.
297. 326. 318. 296 . 335.
289. 309. 308. 298. 309. 337. 302. 340. 374 . 331. 318 . 309. 306. 318. 321. 306. 330. 326. 288.
304. 331. 322 . 301. 337.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
6
294. 314 . 312. 296. 316. 338. 310. 332. 377. 335. 330. 318. 307. 325. 315. 309. 332. 321. 288 .
303. 329. 328. 304 . 341.
7
294 . 318. 319. 298. 321. 345. 309. 319. 383. 342. 327. 315. 308 . 328 . 322. 312 . 332. 327. 295.
303. 332. 319. 306 . 345.
8
298 . 325. 321. 300. 324. 345. 318. 332. 386 . 346. 330. 318. 315. 329. 328 . 318. 342. 332. 300.
305. 336. 331. 310. 353.
9
305. 328. 320. 304. 334. 345. 314. 345. 386. 351. 338. 317. 321. 332. 335. 318. 343. 332. 298.
312. 346. 326. 311. 351.
10 11 12
306 . 330. 320. 311. 338. 355. 317. 350. 388. 359. 345. 310. 324 . 340. 338. 325. 350. 336. 291.
318. 352. 338. 320. 353 .
319. 338. 316 . 311. 345. 362. 316. 362. 390. 360. 338. 303. 326. 346. 351. 329. 358. 340. 301.
320. 358. 347. 324. 358.
324. 337. 320. 314 . 346. 368. 332. 360. 406. 380 . 354. 315. 334. 342. 357. 332. 364 . 342. 287.
324. 360. 349. 327. 366.
418-008:PAGE E-39
000629
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E25 (PAGE 4) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA FI GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13
14
RAT #
DOSAGE GROUP II
15
16 17 0.1 MG/KG/DAY
18
13226 P 13227 P 13228 NP 13229 P 13230 P 13231 P 13232 P 13233 P 13234 P 13235 P 13236 P 13237 P 13238 P 13239 P 13240 P 13241 P 13242 P 13243 NP 13244 NP 13245 NP 13246 P 13247 P 13248 P 13249 P 13250 P
327.
333.
336 .
341.
345.
359.
321.
308.
300 .
325.
331.
340 .
346.
353 .
367.
364 .
371.
377.
324 .
330.
338.
369.
370.
383 .
410.
418.
432.
338.
341.
349.
361.
360.
371.
325.
335.
346.
347.
342 .
350.
352.
364 .
370.
368.
359.
370.
336.
347.
355.
367.
373.
388.
352.
342.
347 .
288.
291.
298 .
MATING NOT CONFIRMED
335.
330.
340.
361.
363 .
371.
358.
368.
369.
334 .
341.
350 .
368.
374.
383.
350. 374. 297. 347. 366. 395. 350. 397. 435. 351. 386. 356. 365. 367. 380. 366. 399. 340. 302.
345. 383 . 377. 360. 395.
362. 374 . 304 . 355. 379. 410. 355. 410 . 454 . 356 . 403 . 370. 377. 369. 396. 379. 418. 334 . 309.
360. 397. 391. 380. 408.
381. 391. 304. 368. 390 . 426. 363. 422. 468. 360. 424 . 390. 391. 384 . 414 . 397. 442 . 339. 316.
371. 420. 410. 401. 421.
P = PREGNANT NP - NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
19
394. 401. 298. 383. 403 . 439. 378 . 436. 483. 371. 438. 407. 411. 405. 424 . 413 . 461. 332. 317.
382. 420. 422. 403. 435.
20
403 . 413. 301 . 379. 416 . 455. 393. 443 . 507. 385. 466. 422. 430 . 419. 448 . 420. 463 . 332. 317.
397. 432. 436. 417. 445.
21
416. 428. 305. 407.
480. 408. 459. 524. 397. 488. 442. 448. 425. 457. 425. 478. 324. 320.
414 . 448. 458. 440. 464 .
22 303.
406.
320. 326.
23 294.
325. 321.
24 289.
324. 319.
25 294 .
320. 317.
418-008:PAGE E-40
000630
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E25 (PAGE 5) : MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
PREGNANCY STATUS DAY 0
12
RAT ft
DOSAGE GROUP III
13251 P 13252 P 13253 P 13254 P 13255 P 13256 P 13257 P 13258 P 13259 P 13260 P 13261 P 13262 P 13263 P 13264 P 13265 P 13266 P 13267 P 13268 P 13269 P 13270 P 13271 P 13272 P 13273 P 13274 NP 13275 P
321. 276. 266. 261. 294. 277. 350. 282. 269. 293. 261. 292. 272. 243. 299. 282. 255. 250. 277. 290. 254. 314. 286. 272. 253.
326. 290 . 273 . 268. 305. 289. 355. 294 . 282. 311. 250. 299. 279. 252. 304 . 300. 266 . 254 . 283. 296 . 265. 321. 290. 274 . 262 .
329. 290 . 276. 278. 305. 298. 360. 300. 282. 310. 280. 308. 285. 256. 315. 302. 272. 261. 296. 306. 257. 332. 299. 286 . 272.
4
0.4 MG/KG/DAY
334 . 297. 279. 282. 303 . 302. 363. 304 . 287. 318. 277. 312. 286. 260. 324. 308. 272. 259. 294 . 310 . 261. 336. 299. 287. 274 .
339. 297. 284 . 283. 309. 305. 364. 308. 290. 323. 275. 313. 294 . 261. 323. 311. 271. 265. 288. 316. 272. 330. 309. 286. 276.
5
343. 302. 288. 285. 311. 309. 370. 311. 294. 335. 289. 318. 293. 265. 330. 314. 275. 260. 294 . 314. 273. 338. 312. 286. 282.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
6
342. 306. 293 . 293. 311. 310. 370. 314. 292. 331. 287 . 314. 300. 270. 326. 315. 277. 268. 298. 322. 275. 347. 315. 290. 289.
7
343. 309. 299. 293. 311. 312. 375. 318. 295. 339. 290. 318. 298. 273 . 335. 321. 280. 269. 294. 319. 277. 348. 313 . 293 . 288.
8
351. 310. 304 . 300. 317. 314 . 384 . 322. 304 . 345. 290. 319. 302. 271. 328. 326. 286. 271. 298. 326. 278. 356. 322. 296. 293 .
9
357. 314 . 311. 304 . 322. 317. 383. 325. 306. 348. 298. 329. 311. 280. 337. 329. 283 . 277. 300. 328. 285. 355. 324 . 299. 301.
10
365. 316. 313. 311. 329. 324 . 389. 330. 308. 354. 300. 331. 316. 279. 339. 337. 285. 280. 304. 338. 285. 363. 338. 301. 301.
11
366. 327. 322. 315. 328. 328. 399. 337. 312. 363. 309. 340. 321. 286. 348. 342. 294. 291. 309. 338. 298. 367. 341. 308. 314.
12
370. 327. 323. 314. 337. 328. 400. 343. 315. 367. 316. 343. 329. 292. 348. 340. 301. 286. 309. 341. 306. 372. 338. 313. 319.
418-008:PAGE E-41
000631
418-008:PAGE E-42
000632
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295,9)
TABLE E25 (PAGE 6): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
PREGNANCY STATUS DAY 13 14 15 16 17 18
RAT #
DOSAGE GROUP III
0.4 MG/KG/DAY
13251 P 13252 P 13253 P 13254 P 13255 P 13256 P 13257 P 13258 P 13259 P 13260 P 13261 P 13262 P 13263 P 13264 P 13265 P 13266 P 13267 P 13268 P 13269 P 13270 P 13271 P 13272 P 13273 P 13274 NP 13275 P
373. 327. 332. 318. 339. 336. 411. 348. 320. 374. 316. 346. 330. 293. 360. 342. 298. 291. 320. 348. 311. 380. 342. 312. 320.
383. 329. 342. 325. 342. 339. 408. 356. 325. 372. 324. 354. 340. 296. 366. 345. 304 . 304 . 321. 357. 318. 384 . 351. 314. 331.
398. 338. 343. 334. 354 . 340. 419. 360. 331. 377. 330. 365. 340. 304 . 370. 353. 314. 306 . 326. 359. 308. 394 . 356. 320. 330.
401. 349. 355. 349. 366 . 350. 431. 369. 335. 384 . 340. 370. 349. 318. 382. 360. 323 . 317. 346. 378. 313. 412. 365. 315. 345.
413. 359. 373. 356. 383. 357. 444 . 380. 349. 405. 356. 374 . 362. 330. 392. 380. 345. 326. 362. 399. 328. 426. 379. 311. 355.
426. 365. 386. 371. 402. 374 . 468. 402. 362. 423 . 371. 393. 380. 344 . 401. 402. 354. 342. 372. 399. 352. 455. 399. 303. 372.
P = PREGNANT NP = NOT PREGNANT' (VALUES EXCLUDED FROM AVERAGES) DAY = DAY OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G).
19
447. 372. 406. 384. 419. 391. 473 . 417 . 386 . 432. 391. 405 . 388. 358. 415. 412. 363. 351. 390 . 425. 363. 467. 420. 305. 391.
20
462. 391. 424 . 407. 432. 409. 497. 435. 399. 457. 409. 417. 384. 374 . 422. 426. 383. 366. 401. 437. 369. 488. 434 . 308. 401.
21
475.
427.
447. 418. 515. 447. 404 . 468. 422. 427. 404 . 390. 420. 447.
412. 445. 385. 512. 454 . 293 . 419.
22 431.
288.
23 297.
24 295 .
25
290.
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE E26 (PAGE 1) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAY 1 4 7 14 21
RAT #
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13201 13202 13203 13204 13205a 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
310. 325 . 275. 303 .
303 . 314 . 282. 299.
330. 328. 284 299
380. 364 . 318. 317.
361.
366 .
368
374 .
352.
365.
375
402.
300 .
345.
321
372.
NOT PREGNANT
365.
354.
364
388.
373 .
367.
361
374 .
336.
327.
348
365.
374 .
380.
378
409.
331.
340.
340
371.
294.
299.
292
332.
307.
321.
317
361.
334 .
338.
351
363.
334 .
338.
327
371.
292.
282.
292
317.
276.
288.
308
329.
FOUND DEAD ON DAY 28 :POSTWEANING
382.
369.
372
386.
285.
301.
304
330.
377.
361.
351
366.
279.
276.
284
306.
346. 329. 283 . 298.
366. 374 . 345.
368. 351. 351. 370. 348. 276. 332 . 361. 338. 326. 322.
380. 289. 372 . 311.
DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008PAGE E-43
000633
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E26 (PAGE 2): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAY 1 4 7
RAT #
DOSAGE GROUP II
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
316. ' 314 .
335.
324.
NOT PREGNANT
312.
301.
349.
344.
362.
363.
313 .
313.
353.
357.
371.
382.
327.
314.
335.
356.
337.
360.
333.
347.
314.
317.
352.
336.
324 .
323.
347.
356.
NOT PREGNANT
NOT PREGNANT
NOT PREGNANT
315.
328.
337.
348.
324.
331.
326.
324.
347.
350.
325. 323.
312. 340. 365. 325. 362. 394 . 330. 364. 357. 334. 328. 340. 334. 328.
327. 343. 347. 325. 342.
DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
14 21
0.1 MG/KG/DAY
339. 342.
347. 327 .
335. 361. 375. 355. 415. 409. 355. 379. 366. 384. 373. 351. 358. 388.
332 . 355. 370. 350. 401. 388. 345. 363. 378. 349. 343 . 350 . 350. 363.
344. 372. 396. 366. 371.
336. 338. 371. 358 . 362.
418-008:PAGE E-44
000634
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E26 (PAGE 3) : MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAY 1 4 1 14 21
RAT ft
DOSAGE GROUP III
0.4 MG/KG/DAY
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
378.
362 .
322.
314 .
319.
315.
304 .
312 .
304 .
303.
322.
327.
399.
381.
333.
328.
327.
309.
332.
338.
306 .
316.
344.
325.
305.
300.
282.
277.
355.
345.
310.
308.
284.
277.
284 .
277.
312.
311.
339.
336.
296.
295.
348.
354.
326.
326.
NOT PREGNANT
331.
315.
370. 323 . 314 . 316. 308. 339. 368. 336. 330. 348. 311. 327. 312. 288. 332. 316. 278. 286. 315. 340. 316. 358. 332.
317.
393 . 338. 356. 344. 339. 366.
a 349. 356. 398. 322. 361. 340. 321. 360. 350. 321. 315. 334. 362. 354. 398. 380.
348.
376. 331. 342. 326. 356. 349.
334 . 354 . 363. 325. 342. 327. 317. 328. 342. 316. 332. 341. 364. 340. 379. 319.
348.
DAY = DAY OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G) . a. Dam 13257 was found dead on day 10 of lactation.
418-008:PAGE E-45
000635
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E27 (PAGE 1): FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAYS 1 - 8 8 - 1 5 1 5 - 2 2 2 2 - 2 9 2 9 - 3 6 3 6 - 4 3 43 50 50 - 57 57 - 64a
RAT tf
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13201 13202 13203 13204 13205b 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
102. 88. 68.
105.
102. 96 . 94 . 95. 91. 89. 90.
102. 107.
93. 87. 79. 104 . 93 . 97. 99. 105. 97. 93 . 107.
133 . 107. 119. 134 .
135. 131. 134 . 121. 139. 129. 128. 144 . 139.
d 125. 121. 146. 133 . 134. 131. 146. 129. 139. 153 .
141. 100. 123 . 140.
144 . C
143. 121. 154 . 150. 153. 172. 144 . 123. 142. 142. 152. 142 . 140. 141. 171. 136. 159. 161 .
134 . 117. 135. 136 .
139. 122. 117. 135 .
140. 127 . 127. 160 .
144 .
131. 145. 144 .
160 .
170 ,
147.
146 .
161.
157.
161.
164.
172 .
138,
133 .
172.
122 .
107
119.
133 .
162 .
170
d 206 .
84 . 169
172 .
166.
148 .
149
142.
136 .
169.
152
158.
170.
139.
138
166.
d
120 .
112
142 .
148 .
146.
132
165.
169.
145.
144
160.
157.
139.
152
211.
191.
143.
126
168.
173 .
148.
148
236 .
209.
FOUND DEAD ON DAY 28 POSTWEANING
165.
173
169.
166.
142 .
142
139.
133 .
158. ' 166
174 .
180.
153 .
146
143 .
150.
142. 142. 145. 234 .
150. 170. 173 . 133 . 230. 173 . 147. 169. 166. 129. 147. 153 . 143. 155. 167.
177. 154 . 184. 164.
143 . 140 142 154
166 157 139 123 177 164 174 161 152 134 152 148 141 142 147
166 124 182 131
DAYS = DAYS POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified. c. Wet feed precluded the calculation of this value. d. Spilled feed precluded the calculation of this value.
418-008: PAGE E ^ 6
000636
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E27 (PAGE 2) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAYS 1 - 8 8 - 1 5 1 5 - 2 2 2 2 - 2 5 29 36 36 - 43 43 - 50 50 - 57 57 - 64a
RAT tt
DOSAGE GROUP II
0.1 MG/KG/DAY
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
81 . 94 . 87 . 86 . 98 . 87. 93 . 96. 94 . 88 . 92. 101 . 105. 111. 104 . 84 . 96 . 101 . 99. 105. 89. 103. 98 113 . 96 .
111 . 133 . 132 . 123. 134 . 124 . 119. 144 . 136 . 126. 129. 136. 145. 154 . 141 . 115. 143 . 142. 127 . 145 . 132 . 147. 133 . 145 . 138 .
131. 135. 130. 140. 1S3 . 141 . 139. 157. 157. 141. 140. 142. 147. 168. 160 . 139. 154 . 164 . 141. 167. 146. 159. 163. 156 . 149.
133 . 134 . 132 . 127 . 149 . 148 . 138. 168 . 167. 150. 136 . 141 . 147. 175. 160. 144 . 153 . 174 . 132 . 162 . 136 . 167 . 148 . 164 . 160 .
131. 139. 136 . 142. 146 . 154 . 128. 167. 175. 151. 135. 137. 147. 175. 159. 134 . 147. 169. 129. 150. 135. 179. 159. 147. 182 .
128. 135. 149. 196. 149. 154 . 135. 193. 179. 165. 142. 137. 155. 166. 184 . 191. 185. 200. 156 . 223. 226. 191. 213. 153. 162.
126. 142 . 139. 133 . 152. 160. 133 . 179. 175. 172 . 159. 150 . 177. 205. 175. 175. 166. 181. 151. 192 . 211. 217.
b 155. 175.
138. 154 . 155. 149. 174 . 155. 146 . 191. 202. 170. 155. 218. 193 . 167. 156 . 146. 161 . 168 . 157. 174 . 160. 178 . 181. 152 . 123 .
127. 147. 154 . 137. 149. 138. 138. 157. 182. 167. 136. 134 . 156. 147. 160. 153 . 154 . 158 . 228. 153 . 171. 181. 165. 157. 166 .
DAYS = DAYS POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value.
418-008: PAGE E-47
000637
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E27 (PAGE 3) : FEED CONSUMPTION VALUES - PRECOHABITATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
RAT K
DAYS 1 8 8 - 1 5 15 DOSAGE GROUP III
22 22 - 29 29 - 36 36 -4 3 43 0.4 MG/KG/DAY
50 50 - 57 57 - 64a
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
87. 79. 95. 95. 94 . 87. 69. 80. 85. 94 . 89. 100. 97. 87. 78. 85. 88. 82. 107. 102. 90. 114 . 65. 97. 64 .
139. 121 . 140 . 154 . 136 . 113 . 124 . 103 . 125. 124. 116. 136. 136. 113. 132. 121. 113. 135. 136. 144 . 161. 148. 177. 134 . 130.
158. 124 . 145. 149. 151. 125. 161. 137. 137. 146 . 130 . 149. 156. 128. 146. 139. 126. 146. 145. 151. 175. 167.
b 148 . 156 .
159. 130. 145 . 128. 152. 136 . 164 . 143 . 133 . 161 . 138. 146. 153. 126 . 155. 137. 132. 145. 134 . 155. 120 . 164 . 156. 152. 173 .
157. 136. 129. 124 . 140. 131. 172. 147. 132. 169. 132. 146. 143 . 130 . 153 . 131. 131. 139. 162. 159. 139. 167.
b 156 . 157.
151 . 140. 136 . 128 . 170 . 130 . 175. 155. 146 . 170. 146 . 155 . 189. 142 . 194 . 182 . 143 . 154 . 245. 210. 194. 180. 164. 182 . 155.
161 . 141 . 129 . 132 . 170. 139. 184 . 150 . 133 . 170. 145. 169.
b 148 . 193 . 188. 172. 163. 240. 166 . 138. 170. 178. 221. 162 .
169. 138. 128 . 142. 175 . 128 . 191. 144 . 138 . 164 . 141. 173 . 149. 137. 186. 171. 148. 150. 177. 179. 144 . 188. 164 . 166. 122.
164 . 141 134 127 148. 138 181 151 143 162 134 143 140 127 161 158 137 142 196 197 112 168. 164 150
C
DAYS = DAYS POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation. b. Spilled feed precluded the calculation of this value. c. Value was not recorded.
418-008: PAGE E ^ 8
8C9000
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E28 (PAGE 1): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 7 7 - 10 10 - 14 14 - 17 17 - 2 0 20 - 25
RAT ft
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13201 P 13202 P 13203 P 13204 P 13205a 13206 P 13207 P 13208 P 13209 NP 13210 P 13211 P 13212 P 13213 P 13214 P 13215 P 13216 P 13217 P 13218 P 13219 P 13220 P 13221 13222 P 13223 P 13224 P 13225 P
161. 161. 172. 169.
12 .
80. 74 . 82.
88. 106.
92. 113.
71. 90 . 78. 86.
178.
87 . 114.
97 .
201.
93. 108.
90.
170.
77. 103.
71.
133. 58. 74. 57 .
188.
88. 133. 101.
199.
94. 131.
93.
175.
86. 111.
98.
208.
98 . 116.
94 .
167.
83 . 100.
80.
147.
72. 104.
96.
176. 80. 98. 72.
175.
84 . 98.
74 .
169.
80. 110.
80.
166. 75. 98. 80.
184 .
80. 107.
71.
FOUND DEAD ON DAY 28 POSTWEANING
194 .
86 . 121.
102.
163 .
55.
86.
70.
199.
89. 127.
63.
166. 80. 99. 78.
66. 73 . 54. 72.
94. 87. 67. 42. 86. 81. 92. 81. 58. 84. 76. 71. 79. 82. 67.
89. 74. 67. 66.
76.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL HEIGHTS WERE RECORDED IN GRAMS (G). a. Rat 13205 was excluded from study on day 7 po3tweaning; the sex was incorrectly identified.
418-008:PAGE E-49
000639
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E28 (PAGE 2) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 7 7 - 10 10 - 14 14 - 17 17 - 20 20 - 25
RAT
DOSAGE GROUP II
0.1 MG/KG/DAY
13226 P 13227 P 13228 HP 13229 p 13230 p 13231 p 13232 p 13233 p 13234 p 13235 p 13236 p 13237 p 13238 p 13239 p 13240 p 13241 P 13242 p 13243 NP 13244 NP 13245 NP 13246 P 13247 P 13248 P 13249 P 13250 P
156.
74 . 107.
172.
73 . 101.
181.
83 . 83 .
158.
65. 105.
171.
82. 104 .
166 .
75.
97.
156.
63 . 92.
167.
74 . 107.
219.
105.
128.
179. 91. 72.
184. 80. 92.
158. 46. 88.
163.
81. 103 .
181.
86. 104 .
194 .
92. 120.
157. 193.
72. 93. 85. 114 .
166.
74. 105.
147. 66. 62.
MATING NOT CONFIRMED
180.
74 . 94 .
193.
89. 113.
a 85. 115.
153. 68. 95.
199.
93. 108.
82. 64. 36 . 72 . 66 . 81. 60. 92. 86 . 45. 84 . 77. 92. 65. 87 . 81. 95. 65. 67.
75. 91. 80. 84 . 80.
79. 62. 46. 71. 69. 71. 61. 83. 89. 43 . 76. 91. 87. 75. 83. 78. 85. 42. 64 .
72. 75. 76. 74. 77 .
70.
62. 101.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Spilled feed precluded the calculation of this value.
418-008:PAGE E-50
000640
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E28 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
PREGNANCY STATUS DAYS 0 - 7 7 - 1 0 10 - 14 14 - 17 17 - 20 20 - 25
RAT #
DOSAGE GROUP III
0.4 MG/KG/DAY
13251 P 13252 P 13253 P 13254 P 13255 P 13256 P 13257 P 13258 P 13259 P 13260 P 13261 P 13262 P 13263 P 13264 P 13265 P 13266 P 13267 P 13268 P 13269 P 13270 P 13271 P 13272 P 13273 P 13274 NP 13275 P
161. 163. 179. 181. 146 . 164. 180. 172. 145. 200. 141. 163. 170. 156. 172 . m. 146. 141. 178. 197. 154 . 191. 182. 181 . 176.
82. 71. 86. 75. 70. 68. 86. 81. 68. 98. 67. 75. 78. 68. 76. 77 . 58. 71. 72. 80. 60. 86. 93. 77. 81.
102 . 90.
126. 104 .
89. 86. 114. 109. 89.
a 91. 99. 103. 88. 114 . 94. 91. 96. 97. 114 . 96. 108. 100 . 106. 104 .
89. 68. 73 . 72. 78. 70. 91. 82. 75. 96. 76. 83. 76. 76. 104. 80. 75. 72. 94. 95. 67 . 88. 81. 85. 77.
87. 54 . 91. 81. 74 . 79. 87. 90 . 73. 82. 81. 81. 53. 61. 102. 70 . 58. 70. 81. 68. 75. 77. 85. 68. 77.
72.
P = PREGNANT NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES) DAYS = DAYS OF PRESUMED GESTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G)a. Spilled feed precluded the calculation of this value.
418-008:PAGE E-51
000641
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E29 (PAGE 1): MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAYS 1 - 4 4 - 7 7 - 1 0 10 - 14a
RAT ft
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13201 13202 13203 13204 13205b 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
73. 68. 100. 83.
119. 108. 114 .
92.
161. 163 . 135. 145.
260. 263. 225. 217.
65. 100. 134. 189.
87. 120. 166. 235.
102 .
87 . 134.
238.
NOT PREGNANT
142.
113 .
158.
249.
60. 79. 113. 172 .
74. 112. 158. 225.
85. 112. 159. 229.
85.
123 .
157.
259.
98. 122. 163. 242 .
106.
125.
183 .
268.
89.
124 .
164.
231.
105.
103 .
143.
228.
55. 105. 155. 228.
85. 133. 162. 263 .
FOUND DEAD ON DAY 28 POSTWEANING
67. 110. 139. 230 .
Ill.
128.
163.
121.
73. 87. 133. 205.
112.
118.
137.
225.
DAYS = DAYS OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 14 of lactation. b. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008:PAGE E-52
000642
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E29 (PAGE 2) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAYS 1 - 4 4 - 7 7 - 10 10 - 14a
RAT tt
DOSAGE GROUP II
0.1 MG/KG/DAY
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
72 . 110.
67. 102.
NOT PREGNANT
86 . 113.
63 . 98.
109.
145.
76 . 135.
104 .
123 .
90. 127.
69. 105.
108 .
127.
116.
120.
114 .
134.
82 . 134.
87 . 88.
b 103.
112 .
112 .
NOT PREGNANT
NOT PREGNANT
NOT PREGNANT
100 123.
78. 93.
b 197.
84 . 105.
98 104 .
152. 138.
151. 145. 165. 144 . 159. 159. 134. 161. 154. 179.
49. 308. 138. 180.
174. 121. 184 . 144 . 147.
245. 231 .
255. 221. 262. 252. 266. 247. 222. 250. 245. 274 . 308. 228 . 221. 279.
242 . 178 . 260 . 208 . 215 .
DAYS = DAYS OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 14 of lactation. b. Spilled feed precluded the calculation of this value.
418-008:PAGE E-53
000643
418-008:PAGE E-54
000644
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E29 (PAGE 3) : MATERNAL FEED CONSUMPTION VALUES - LACTATION - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DAYS 1 - 4 4 - 1 7 - 10 10 - 14a
RAT #
DOSAGE GROUP III
0.4 MG/KG/DAY
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
75. 110 .
67. 92.
73 .
101.
56. 160.
65. 103.
93 . 128.
65. 100 .
88. 120.
89. 113 .
95 . 115.
82. 82.
36 . 77.
89. 117.
82 . 113 .
65. 72 .
67. 96.
68. 88.
62. 99.
98. 111.
77 .
128.
79. 110.
80 . 134 .
86. 112 .
NOT PREGNANT
74 . 101.
159. 122. 157. 114. 118. 169.
b 152 . 156 . 180. 108 . 103 . 123 . 138. 119. 147. 132. 147. 107. 161. 135. 177. 163 .
132.
240 . 201 . 248. 188 . 198 . 259.
b 255. 216 . 267. 143 . 208 . 226 . 224 . 188. 198 . 210 . 220 . 259. 246 . 235. 283 . 252.
203 .
DAYS B DAYS OF LACTATION ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. It is presumed that the pups begin to consume the maternal feed after day 14 of lactation. b. Dam 13257 was found dead on day 10 of lactation.
(
PROTOCOL 4IB -008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E30 (PAGE 1) : SEXUAL MATURATION - INDIVIDUAL DATA FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
I 0 (VEHICLE)
II 0.1
III 0.4
VAGINAL RAT # PATENCY (DAY)
VAGINAL RAT tf PATENCY (DAY)
VAGINAL RAT # PATENCY (DAY)
13201 13202 13203 13204 13205 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
30 30 31 32
a 31 30 30 30 30 32 30 32 28 29 31 31 34 30 33 30 29 34 35 34
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
36 34 31 32 31 33 32 31 30 34 28 29 29 32 30 34 31 28 31 30 30 29 30 30 33
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
30 30 30 30 30 32 29 29 32 31 31 29 30 33 31 30 28 33 30 30 31 32 29 29 33
DAY = DAY POSTPARTUM a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008:PAGE E-55
000645
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E31 (PAGE 1): PASSIVE AVOIDANCE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO CRITERION
LATENCY b TRIAL 1 TRIAL 2
TRIALS TO LATENCY b CRITERION TRIAL 1
13201 13202 13203 13204 13205c 13206 13207 13208 13210 13211 13212 13213 13214d 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224
4 4 4 9
6 5 11 5 6 4 4 15 5 5 8 10 5 10 4 4 4 10
4 18 10 57
9 45 59
14 19 68 2 15
20 60 2 27 7 32
18 49 10 13 12 13
89 48 58 3 10 34 9 31 8 20 12 51 44
38 3 59 3 51 69
2 60 3 23 15 12 3 31 4 60 2 60 3 33 12 60 3 15 3 40 55 34 95 33 3 31 35 39 3 22
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified. d. Rat did not meet the criterion in Session 1 (Learning Phase); values for Session 2 (Retention Phase) were excluded from group
averages and statistical analyses.
418-008:PAGE E-56
9^9000
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E31 (PAGE 2): PASSIVE AVOIDANCE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO CRITERION
LATENCY b TRIAL 1 TRIAL 2
TRIALS TO LATENCY b CRITERION TRIAL 1
13226
5 10 60
13221 6 5 21
13228
11
7 35
13229 6 7 3
13230 5 8 33
13231 4 7 17
13232
4 13 30
13233 4 6 21
13234
4 10 9
13235 4 3 9
13236
li
58
13237 S 7 5
13238 4 5 18
13239 7 3 11
13240
4 11 60c
13241 4 4 31
13242
5 14 9
13243 3 6 60
13244 4 5 39
13245
4 14 8
13246 4 6 25
13247 5 3 12
13248 7 2 3
13249 5 5 60
13250
4 12 52
2 60 3 22 8 60 3 12 15 1 2 60 3a 3n 38 3 36 2 60 3 16 2 60
3 59 3 19 2 60 2 60 3 13 3 11 3 23 2 60 2 60 2 60 2 60 4 60
SESSION = TEST ;SESSION a . Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c . Maximum interval elapsed after the rat had entered the dark compartment. Shock was delivered and the trial was not counted
towards the criterion.
418-008:PAGE E-57
000647
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E31 (PAGE 3): PASSIVE AVOIDANCE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO CRITERION
LATENCY b TRIAL 1 TRIAL 2
TRIALS TO LATENCY b CRITERION TRIAL 1
13251 13252 13254 13255 13256 13258 13259 13260 13261 13262 13263 13264 13265 13266 13268 13269 13270 13271 13272 13273 13274 13275
5 4 60 5 13 60 4 16 14 4 4 52 5 24 60 4 10 20 4 17 35 4 12 26 6 5 21 6 10 6 6 4 45 4 6 26 5 10 11 5 21 16 7 23 5 2 11 5 69 6 3 17 4 88 5 99 7 60 11 5 3 10
2 60 39 3 10 39 2 60 2 60 3 38 2 60 2 60 2 60 2 60 3 57 3 58 4 13 4 12 2 60 2 60 74 2 60 2 60 34 3 12
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds.
418-008:PAGE E-58
000648
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E32 (PAGE 1): WATERMAZE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 2
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 1
13201 13202 13203c 13204 13206 13207 13208 13210 13211 13212 13213 13214 13215 13216 13217c 13218 13219 13220 13222 13223 13224c
14 13 15 13 11 14
9 9 9 11 9 6 11 9 15 8 8 11 13 13 15
0.57 0.92 0.53 1.23 0.27 0.43 0.33 0.33 0.33 0.82 0.89 0.17 0.45 0.33 0.33 0.25 0.25 0.36 0.85 0.54 0.53
16 14 11 22 18 14
5 5 11 14 34 7 5 6 5 9 7 7 23 11 13
6
0.17
15
10
0.20
18
8
0.25
11
5 0.00 9
5 0.00 6
10
0.50
45
5
0.00
14
7 0.43 4
14
0.21
19
6
0.17
11
5 0.00 7
5 0.00 9
5 0.00 4
5 0.00 7
7
0.43
13
7 0.14
9
11 0.18 7
5 0.00 5
15
0.53
39
6
0.33
31
5 0.00 5
SESSION TEST SESSION a. Sessions 1 (Learning phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c. Rat did not meet the criterion in Session 1 (Learning Phase); values for Session 2 (Retention Phase) excluded from group
averages and statistical analyses.
418-008:PAGE E-59
000643
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E32 (PAGE 2) : WATERMAZE PERFORMANCE - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP II
0.1 MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 2
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 1
13226 13227 13228 13229 13230c 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242c 13243 13244c 13245 13246 13247 13248 13249 13250
12 8
10 7
15 11
8 6 8 6 10 8 8 ii ii 12 15 6 15 12 10 7 6 10 12
0.50 0.25 0.30 0.57 0.67 0.45 0.25 0.17 0.62 0.17 0.20 0.50 0.38 0.54 0.27 0.58 0.27 0.17 0.67 0.50 0.30 0.28 0.17 0.60 0.67
20 6 6
16 13 10
7 12 20
7 10 18 11 15
8 18
6 11 15 41
6 14
5 11 18
13
0.46
10
13
0.23
19
6
0.17
11
10 0.20 7
15
0.67
21
7 0.14 6
6
0.33
23
5 0.00
7
10 0.30 8
5 0.00
6
5 0.00
7
7 0.14
8
15
0.47
23
9 0.11
5
5 0.00
6
6
0.17
11
6
0.50
31
10
0.20
14
8
0.38
14
5 0.00
8
6
0.17
18
7 0.14
9
5 0.00
4
6
0.17
12
5 0.00
6
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. C. Rat did not meet the criterion in Session 1 (Learning Phase); values for Session 2 (Retention Phase) excluded from group
averages and statistical analyses.
418-008:PAGE E-60
000650
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RAIS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E32 (PAGE 3) : WATERMA7.E PERFORMANCE - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP III
0.4 MG/KG/DAY
SESSION la
SESSION 2a
RAT NUMBER
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY b TRIAL 2
TRIALS TO ERRORS/ CRITERION TRIAL
LATENCY TRIAL 1
13251 13252 13254C 13255 13256 13258 13259 13260C 13261 13262 13263 13264 13265 13266 13268 13269 13270 13271 13272 13273 13274
8 15 15 12 14 10 12 15 12 10 11 11
9 9 14 12 14 6 11 13 15
0.38 0.60 0.93 0.25 0.57 0,20 0.42 1.27 0.42 0.50 0.54 0.73 0.22 0.56 0.50 0.50 0.36 0.17 0.18 0.77 0.60
20 7
17 13
8 10
8 37 18
8 17 25 13 10 30
9 16
5 5 14 14
5 0.00 9
5 0.00 9
6
0.17
13
12
0.33
12
6
0.33
17
5 0.00 6
6
0.17
11
11
0.27
35
5
0.00
10
5 0.00 7
6
0.17
17
dd
d
7 0.28 8
9
0.11
10
7
0.43
12
5 0.00 8
6
0.17
15
7 0.71 7
5 0.00 8
5
0.00
10
8
0.38
16
SESSION = TEST SESSION a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week interval. b. The latency was recorded in seconds. c. Rat did not meet the criterion in Session 1 (Learning Phase); values for Session 2 (Retention Phase) excluded from group
averages and statistical analyses. d. Values were not recorded.
418-008:PAGE E-61
000651
418-008:PAGE E-62
000652
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E33 (PAGE 1) : DAYS IN COHABITATION INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
1 0 (VEHICLE)
II 0.1
III 0.4
DAYS IN RAT tf COHABITATION
DAYS IN RAT # COHABITATION
DAYS IN RAT ft COHABITATION
13201 13202 13203 13204 13205 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
3 3 4
l
b 1 1 1 4 4 2 1 3 4 2 2 8 2 1 9 d 2 14 7 4
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 .13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
2 5 7a 5 6 4 5 2 8 1 3 7 3 1 3 1 2 3 2 14c 3 3 3 3 2
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
1 4 7 s 2 1 3 1 2 3 1 1 2 4 1 3 4 2 4 4 2 3 2 1 2
a. The first cohabitation consisted of six days and mating occurred during the second cohabitation. b. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified. c. Mating not confirmed. d. Rat 13221 was found dead on day 28 postweaning.
|
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E34 (PAGE 1): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
I 0 (VEHICLE)
13201 13202
DL 21 DL 21
p P
119 ALL TISSUES APPEARED NORMAL. 117 ALL TISSUES APPEARED NORMAL.
13203
DL 21
P
120 KIDNEYS: LEFT, CORTEX, ROUGH AND PITTED; RIGHT, PELVIS, ONE CALCULUS (1.0 CM X 0.5 CM X 0.5 CM). URINARY BLADDER: ONE CALCULUS (0.75 CM X 0.50 CM X 0.30 CM). ALL OTHER TISSUES APPEARED NORMAL.
13204
DL 21
p
118 ALL TISSUES APPEARED NORMAL.
13205b
DP 7
-
7 SACRIFICED ON DAY 7 POSTWEANING. ALL TISSUES APPEARED NORMAL.
13206 13207
DL 21 DL 21
P p
118 ALL TISSUES APPEARED NORMAL. 117 ALL TISSUES APPEARED NORMAL.
13206
DL 21
P
117 KIDNEYS: BILATERAL, CORTEX, PITTED; PELVIS, TAN, GRANULAR MATERIAL. URINARY BLADDER: WALLS THICKENED, ONE CALCULUS, (1.0 CM IN DIAMETER). ALL OTHER TISSUES APPEARED NORMAL.
13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220
DG 25 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21
NP p P P P P P p P P p P
102 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 116 ALL TISSUES APPEARED NORMAL. 117 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 115 ALL TISSUES APPEARED NORMAL. 115 ALL TISSUES APPEARED NORMAL. 121 ALL TISSUES APPEARED NORMAL. 115 ALL TISSUES APPEARED NORMAL. 114 ALL TISSUES APPEARED NORMAL. 122 ALL TISSUES APPEARED NORMAL.
DP = DAY POSTWEANING DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table E23) for external observations confirmed at necropsy. b. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008:PAGE E-63
000653
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E34 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OP PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
I (Cont.) 0 (VEHICLE)
13221
DP 28
-
2 1 FOUND DEAD ON DAY 28 POSTWEANING. ALL TISSUES APPEARED NORMAL.
13222 13223 13224 13225
DL 21 DL 21 DL 21 DL 21
p p P P
113 ALL TISSUES APPEARED NORMAL. 125 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 115 ALL TISSUES APPEARED NORMAL.
DP DAY POSTWEANING DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table E23) for external observations confirmed at necropsy.
418-008:PAGE E-64
000654
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E34 (PAGE 3): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
II
0.1
13226
DL 21
P
119 ALL TISSUES APPEARED NORMAL.
13227
DL 21
P
122 ALL TISSUES APPEARED NORMAL.
13228
DG 25
NP
108 ALL TISSUES APPEARED NORMAL.
13229
DL 21
P
121 ALL TISSUES APPEARED NORMAL.
13230
DL 21
p
119 ALL TISSUES APPEARED NORMAL.
13231
DL 21
P
119 ALL TISSUES APPEARED NORMAL.
13232
DL 21
P
119 ALL TISSUES APPEARED NORMAL.
13233
DL 21
p
117 ALL TISSUES APPEARED NORMAL.
13234
DL 21
P
122 ALL TISSUES APPEARED NORMAL.
13235
DL 21
P
117 ALL TISSUES APPEARED NORMAL.
13236
DL 21
p
118 ALL TISSUES APPEARED NORMAL.
13237
DL 21
p
121 ALL TISSUES APPEARED NORMAL.
13238
DL 21
p
118 ALL TISSUES APPEARED NORMAL.
13239
DL 21
p
116 ALL TISSUES APPEARED NORMAL.
13240
DL 21
p
117 ALL TISSUES APPEARED NORMAL.
13241
DL 21
p
114 ALL TISSUES APPEARED NORMAL.
13242
DL 21
P
117 ALL TISSUES APPEARED NORMAL.
13243
DG 25
NP
100 ALL TISSUES APPEARED NORMAL.
13244
DG 25
NP
100 ALL TISSUES APPEARED NORMAL.
13245
DP 112
NP
112 ALL TISSUES APPEARED NORMAL.
13246
DL 21
P
116 ALL TISSUES APPEARED NORMAL.
13247
DL 21
P
117 ALL TISSUES APPEARED NORMAL.
13248
DL 21
P
116 ALL TISSUES APPEARED NORMAL.
13249
DL 21
P
117 ALL TISSUES APPEARED NORMAL.
13250
DL 21
P
115 ALL TISSUES APPEARED NORMAL.
DP = DAY POSTWEANING DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table E23) for external observations confirmed at necropsy.
418-008:PAGE E-65
00065
01
PROTOCOL 418008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6.\'95.9)
TABLE E34 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - FI GENERATION FEMALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY)
RAT NUMBER
DAY OF PREGNANCY DOSAGES NECROPSY STATUS ADMINISTERED OBSERVATIONS a
III
13251
DL 21
P
118 ALL TISSUES APPEARED NORMAL.
13252
DL 21
P
119 ALL TISSUES APPEARED NORMAL.
13253
DL 21
P
124 ALL TISSUES APPEARED NORMAL.
13254
DL 21
P
120 ALL TISSUES APPEARED NORMAL.
13255
DL 21
P
119 ALL TISSUES APPEARED NORMAL.
13256
DL 21
P
118 ALL TISSUES APPEARED NORMAL.
13257
DL 10
P
106 FOUND DEAD ON DAY 10 OF LACTATION (DEATH OCCURRED OVERNIGHT). THORACIC CAVITY: CONTAINED 2 ML OF LIGHT ORANGE FLUID, TRACHEA: WHITE FOAM. LUNGS: DARK RED IN COLOR. ALL OTHER TISSUES APPEARED NORMAL.
13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DL 21 DG 25 DL 21
P P P P P P P P P P P P P P P P NP P
117 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 116 ALL TISSUES APPEARED NORMAL. 115 ALL TISSUES APPEARED NORMAL. 116 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 115 ALL TISSUES APPEARED NORMAL. 116 ALL TISSUES APPEARED NORMAL. 116 ALL TISSUES APPEARED NORMAL. 114 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 118 ALL TISSUES APPEARED NORMAL. 115 ALL TISSUES APPEARED NORMAL. 115 ALL TISSUES APPEARED NORMAL. 114 ALL TISSUES APPEARED NORMAL.
96 ALL TISSUES APPEARED NORMAL. 106 ALL TISSUES APPEARED NORMAL.
DP = DAY POSTWEANING DG = DAY OF (PRESUMED) GESTATION DL = DAY OF LACTATION P = PREGNANT NP = NOT PREGNANT a. Refer to the individual clinical observations table (Table E23) for external observations confirmed at necropsy.
418-008:PAGE E-66
000656
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E35 (PAGE 1): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA FI GENERATION FEMALE RATS/F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
RAT/ LITTER NUMBER
DURATION OF GESTATION (DAYS) N
LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN
NNN
13201 13202 13203 13204 13205c 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
23
14 (1) 2
16
22 15 1 16
23 16 0 16
23 18 0 18
23 6 0 6
22 19 0 19
23 13 0 13
NOT PREGNANT
22 17 0 17
24 5 0 5
23 14 0 14
23 15 0 15
22
16(1) 2
18
23 14 0 14
23 15 0 15
23 17 0 17
23 14 0 14
23 15 0 15
23 17 0 17
FOUND DEAD DAY 28 POSTWEANING
23 9 1 10
23 14 0 14
23 15 0 15
23 12 0 12
1 MF
76 69 88 10 8
33 13 6
76
10 7 32 68 1 14 96 3 11 B7 98 95 87 7 10
27 59 87 75
NUMBER OF LIVE PUPS AT
COMPLETION OF DAY POSTPARTUM
4a 4b 7
MF
MF
MF
14 MF
76 69 86 88
44 44 44 44
44 44 44 44
44 44 44 44
33 13 6
66
33 44 44
33 44 44
33 44 44
97 32 6a 1 14 96 3 11 87 98 95 86 7 10
44 32 44 i7 44 35 44 44 44 44 44
44 32 44 i7 44 35 44 44 44 44 44
44 32 44 i7 44 35 44 44 44 44 44
27 59 87 75
26 44 44 44
26 44 44 44
26 44 44 44
M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM. a. Number of live pups preculling. b. Number of live pups postculling. c. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
21 MF
44 44 44 44
33 44 44
44 32 44 i7 44 35 44 44 44 44 44
26 44 44 44
TOTAL IMPLANTATIONS
N
17 16 17 18
10 19 16
18 7
14 16 18 14 15 18 14 15 17
il 16 17 15
418-008:PAGE E-67
000657
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E35 (PAGE 2) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA FI GENERATION FEMALE RATS/F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
RAT/ LITTER NUMBER
DURATION OF GESTATION (DAYS) N
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
23 23 NOT PREGNANT 23 22 23 23 22 23 24 23 23 23 23 23 22 23 NOT PREGNANT NOT PREGNANT NOT PREGNANT
23 23 23 23 23
LITTER DELIVERED LIVE STILL TOTAL BORN BORN BORN
NNN
11 1 12 13 0 13
15 13 17 13 16 14 10 (2) 21 14 16 15 16 16 17
0 0 0 0 0 5 0 0 0 0 0 0 0 0
15 13 17 13 16 19 10 21 14 16 15 16 16 17
15 0 15 16 0 16 17 1 18 16 0 16 17 0 17
1 MF
65 85
96 94 6 ii 76 88 86 44 10 ii 77 79 10 5 88 97 98
NUMBER OF LIVE PUPS AT
COMPLETION OF DAY POSTPARTUM
4a 4b 7
MF
MF
MF
14 MF
65 85
44 44
44 44
44 44
96 94 6 11 76 88 85 34 10 11 77 79 10 5 88 97 98
44 44 44 44 44 44 34 44 44 44 44 44 44 44
44 44 44 44 44 44 34 44 44 44 44 44 44 44
44 44 44 44 44 44 34 44 44 44 44 44 44 44
5 10 5 11 89 79 12 5
5 10 S 11 89 79 12 5
44 44 44 44 44
44 24 44 44 44
44 23 44 44 44
M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM. a. Number of live pupa preculling. b. Number of live pups postculling.
21 MF
44 44
44 44 44 44 44 44 34 44 44 44 44 44 44 44
44 23 44 44 44
TOTAL IMPLAN TATIONS
N
14 14
16 13 20 13 18 20 17 21 14 18 17 17 16 18
16 17 18 17 18
418-008:PAGE E-68
000658
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E35 (PAGE 3) : NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL DATA FI GENERATION FEMALE RATS/F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
RAT/ LITTER NUMBER
DURATION OF GESTATION (DAYS) N
LITTER DELIVERED LIVE STILL- TOTAL BORN BORN BORN
NNN
1 MF
NUMBER OF LIVE PUPS AT
COMPLETION OF DAY POSTPARTUM
4a 4b 7
MF
MF
MF
14 MF
21 MF
13251 13252 13253 13254 13255 13256 13257c 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
23 22 23 22 23 23 23 23 23 23 23 22 22 23 23 23 22 22 23 23 23 23 23 NOT PREGNANT 22
13 15 15 17 14 14 15 15 13(1) 18(1) 14 11 15 16
7 18 17 13 14 15 10 16 16
13
0 0 0 0 4 1 0 0 0 0 0 1 0 0 0 0 0 1 0 1 1 2 1
1
13 15 15 17 18 15 15 15 13 IB 14 12 15 16
7 18 17 14 14 16 11 18 17
14
76 B7 78 6 11 86 59 69 69 93 B9 4 10 65 96 79 25 7 11 5 12 76 10 4 78 46 ii 5 6 10
58
7e 87 77 37 86 58 69 69 93 79 4 10 65 96 79 25 6 11 5 12 76 10 4 78 46 11 5 6 10
58
44 44 44 35 44 44 44 44 53 44 44 44 44 44 25 44 44 44 44 44 44 44 44
44
44 44 44 35 34 44 44 44 53 44 23 43 44 44 25 44 44 44 44 44 44 44 44
44
44 44 44 35 34 44
--
44 53 44 23 33 44 44 25 44 44 44 44 44 44 44 44
44
44 44 44 35 34 44
--
44 53 44 23 33 44 44 25 44 44 44 44 44 44 44 44
44
M = MALE F = FEMALE ( ) = NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM. a. Number of live pupa preculling. b. Number of live pups postculling. c. Dam 13257 was found dead on day 10 of lactation; eight pups were sacrificed on day 10 postpartum.
TOTAL IMPLAN TATIONS
N
14 16 16 17 18 15 IS 16 13 18 14 13 16 16
9 18 18 14 15 16 12 18 17
15
418-008PAGE E-69
000659
PROTOCOL 418-008; COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E36 (PAGE 1) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP
0 (VEHICLE) MG/KG/DAY
RAT/ LITTER NUMBER
DAY 1 MFT
DAY 4a M FT
DAY 4b M FT
DAY 7 M FT
DAY 14 M FT
13201 13202 13203 13204 13205c 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
6.6 6.5 6.5 5.7 5.5 5.6 4.8 4.4 4.6 5.4 5.2 5.3
8.9 8.9 8.9 8.3 7.7 8.0 6.2 6.1 6.2 6.9 6.4 6.7
6.5 6.5 6.5 10.2 10.0 10.1 5.9 5.8 5.9 8.0 8.0 8.0 6.1 6.0 6.1 9.1 8.8 8.9 NOT PREGNANT 5.5 5.6 5.6 6.9 6.8 6.9 9.0 8.8 8.9 14.4 14.5 14.5 6.2 6.1 6.1 8.6 8.7 8.6 6.8 6.8 6.8 8.7 7.8 7.8 6.3 6.0 6.2 8.9 8.4 8.7 7.2 6.6 6.8 9.5 9.1 9.2 6.7 6.5 6.6 8.9 8.7 8.8 6.9 6.3 6.6 8.7 7.8 8.3 6.5 6.2 6.4 9.4 8.9 9.2 6.4 6.1 6.3 8.4 8.1 8.2 6.0 5.7 5.9 7.6 7.6 7.6 FOUND DEAD ON DAY 28 POSTWEANING 7.2 7.0 7.0 10.6 10.2 10.3 6.8 6.2 6.4 9.8 9.0 9.3 6.8 6.4 6.6 8.8 8.4 8.6 6.4 5.9 6.2 9.2 8.1 8.7
8.8 8.9 8.8 8.3 7.7 8.0 6.2 6.0 6.1 7.2 6.6 6.9
10.2 10.0 10.1 8.2 8.1 8.1 9.4 8.9 9.1
7.0 14.4
9.0 8.7 9.2 9.5 9.1 9.4 9.8 8.4 7.8
6.8 14.5
8.6 7.6 8.2 9.1 8.9 8.2 9.1 8.1 7.7
6.9 14.5
8.8 7.7 8.8 9.2 9.0 8.8 9.4 8.3 7.8
10.6 9.7 8.8 9.2
10.4 9.0 8.5 8.3
10.4 9.4 8.6 8.8
14.8 15.0
9.7 11.6
14.9 14.2
9.4 11.0
14.8 14.6
9.5 11.3
17.1 16.7 16.9 14.6 14.2 14.4 14.5 13.9 14.2
10.8 22.1 15.8 14.9 16.2 16.6 15.8 15.9 16.4 13.5 13.8
10.5 21.4 15.2 13.4 14.4 15.8 15.4 14.7 15.6 12.8 13.4
10.6 21.8 15.4 13.6 15.3 16.1 15.6 15.3 16.0 13.1 13.6
16.8 16.2 14.1 15.0
16.4 15.7 13.6 13.6
16.4 16.0 13.9 14.3
34.3 35.1 24.5 27.6
33.3 34.4 23.5 26.3
33.8 34.8 24.0 26.9
37.5 36.4 37.0 33.1 31.0 32.0 30.6 29.9 30.2
27.2 40.0 32.9 33.3 36.1 34.9 33.6 34.7 33.7 30.2 31.9
25.4 38.2 31.6 30.4 33.1 33.0 33.0 33.1 32.0 29.0 30.3
26.3 39.3 32.2 30.8 34.6 33.7 33.3 33.9 32.9 29.6 31.1
34.8 34.0 30.3 31.6
33.7 33.2 28.8 30.2
34.0 33.6 29.6 30.9
M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM
ALL WEIGHTS WERE RECORDED IN GRAMS (G) .
MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
c. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
DAY 21 M FT
55.0 52.9 38.4 43.0
52.8 50.6 37.5 41.4
53.9 51.7 37.9 42.2
61.5 59.2 60.3 49.6 46.8 48.2 49.5 49.0 49.2
43.2 59.6 53.0 49.0 54.3 53.6 54.7 51.8 55.8 51.7 50.0
41.3 56.0 51.4 45.0 48.9 50.7 54.9 50.4 52.6 50.4 48.8
42.3 58.2 52.2 45.5 51.6 51.8 54.8 51.1 54.2 51.0 49.4
48.9 53.0 50.5 50.1
48.3 50.3 47.4 47.2
48.5 51.6 48.9 48.7
418-008:PAGE E-70
000660
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E36 (PAGE 2) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
RAT/
LITTER NUMBER
DAY 1 MFT
DAY 4a M FT
DAY 4b M FT
DAY 7 M FT
DAY 14 M FT
DAY 21 MFT
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
7.1 6.7 6.9 6.2 6.0 6.1 NOT PREGNANT 6.2 5.7 6.0 6.0 5.6 5.9 6.5 6.2 6.3 6.7 6.7 6.7 6.1 5.5 5.8 6.1 6.3 6.2 5.4 4.8 5.1 6.6 5.9 6.2 7.3 6.8 7.0 6.7 6.4 6.5 5.4 5.3 5.4 6.5 6.3 6.4 5.6 5.3 5.5 6.9 6.2 6.5 NOT PREGNANT NOT PREGNANT NOT PREGNANT 6.4 6.0 6.1 6.3 5.9 6.0 6.3 6.2 6.2 6.6 6.1 6.3 5.9 5.6 5.8
8.6 8.2 8.4 8.9 8.9 8.9
8.8 8.4 8.6 15.4 14.8 15.1 32.8 32.8 32.8 51.9 53.3 52.6 8.6 8.9 8.8 15.0 15.2 15.1 31.9 32.4 32.2 51.5 52.7 52.1
7.3 6.6 7.0 7.5 6.6 7.1 11.3 9.8 10.6 30.5 26.8 28.6 47.1 42.2 44.7 7.0 6.6 6.9 7.1 6.6 6.9 11.7 11.0 11.4 26.7 25.7 26.2 39.2 39.1 39.1 9.8 8.9 9.2 9.6 9.5 9.6 17.4 17.2 17.3 37.2 36.3 36.7 57.0 54.2 55.6 9.3 9.2 9.3 9.4 9.2 9.2 16.2 15.9 16.1 33.8 33.9 33.9 54.4 53.7 54.0 8.9 8.0 8.4 8.8 8.7 8.8 14.4 14.4 14.4 33.4 32.4 32.9 50.3 48.3 49.3 9.8 9.3 9.6 10.1 9.4 9.8 16.6 16.3 16.4 33.6 33.5 33.6 54.0 52.4 53.2 8.8 7.8 8.3 8.8 7.8 8.3 14.1 12.5 13.2 31.7 29.9 30.7 50.1 47.9 48.8 8.2 7.3 7.7 7.7 7.8 7.7 13.2 13.2 13.2 32.0 31.9 32.0 46.9 46.4 46.6 8.9 8.3 8.6 9.0 8.6 8.8 12.5 13.0 12.7 32.5 32.4 32.5 52.6 51.8 52.2 9.6 9.3 9.4 9.6 9.3 9.5 17.2 16.8 17.0 37.3 36.8 37.0 57.3 56.4 56.8 8.5 8.3 8.4 8.5 8.3 8.4 15.8 15.4 15.6 36.7 35.8 36.2 55.8 54.6 55.2 8.2 7.8 8.0 8.5 7.6 8.0 14.0 12.6 13.3 30.2 28.9 29.6 46.2 45.6 45.9 6.6 .2 6.4 7.0 5.9 6.4 11.3 9.3 10.3 28.1 25.2 26.6 42.8 46.0 44.4 9.4 8.8 9.1 9.7 9.5 9.6 16.6 15.7 16.2 36.6 35.1 35.9 56.0 54.5 55.3
8.1 7.6 7.7 6.6 6.3 6.4 6.9 6.9 6.9 9.1 8.6 8.9 7.9 7.3 7.8
8.1 7.6 7.8 14.1 13.3 13.7 31.8 30.5 31.2 50.4 48.2 49.3 6.8 6.3 6.5 10.0 10.3 10.2 28.0 28.1 28.0 45.2 45.5 45.4 7.2 7.0 7.1 12.7 11.3 12.0 31.0 29.5 30.2 45.0 43.2 44.2 9.1 8.8 9.0 15.3 15.5 15.4 31.1 31.0 31.1 43.8 43.5 43.7 8.1 7.4 7.8 14.2 13.3 13.7 30.6 28.8 29.8 46.4 43.0 44.7
M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
418-008:PAGE E-71
000661
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE E36 (PAGE 3) : PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM INDIVIDUAL DATA - F2 GENERATION LITTERS
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
RAT/ LITTER NUMBER
DAY 1 M FT
DAY 4a M FT
DAY 4b M FT
DAY 7 M FT
DAY 14 M FT
DAY 21 M FT
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
6.6 6.5 6.6 5.2 4.9 5.1 6.1 5.6 5.9 5.8 5.2 5.4 6.4 6.3 6.4 6.8 6.4 6.5 7.6 6.8 7.1 7.0 6.7 6.8 6.5 6.5 6.5 6.2 6.0 6.1 7.1 6.7 6.8 6.0 5.4 5.7 6.0 5.6 5.9 6.1 5.8 6.0 6.6 6.2 6.3 6.3 6.1 6.2 5.9 5.6 5.7 5.8 5.5 5.6 6.9 6.6 6.8 6.4 6.1 6.2 7.3 6.6 6.9 6.9 6.6 6.8 6.5 6.2 6.3 NOT PREGNANT 5.6 5.5 5.5
9.7 6.5 8.4 5.3 7.2 9.5 10.2 9.6 8.6 8.9 6.9 7.4 8.9 7.8 10.7 7.1 6.3 6.0 8.9 8.6 9.6 8.6 8.6
7.8
9.4 9.6 6.2 6.4 7.9 8.2 4.8 4.9 7.1 7.2 8.8 9.0 9.0 9.5 9.3 9.4 8.7 8.6 8.1 8.5 6.4 6.6 6.4 6.9 8.0 8.5 7.4 7.6 9.9 10.1 6.6 6.8 5.8 6.0 7.1 6.5 8.8 8.9 8.2 8.4 8.7 9.1 8.5 8.6 8.0 8.2
7.5 7.6
10.1 6.6 8.4 5.3 7.4 9.7
10.5 9.8 8.6 8.6 6.9 7.2 9.0 7.9
10.7 7.4 6.3 7.0 9.2 8.6 9.6 8.6 8.5
7.9
9.6 9.8 6.3 6.4 7.6 8.0 4.9 5.0 7.4 7.4 8.8 9.3 9.0 9.8 9.1 9.5 8.7 8.6 8.0 8.3 6.7 6.8 6.4 6.8 8.0 8.5 7.6 7.8 9.9 10.1 7.0 7.2 6.0 6.1 7.1 7.1 8.8 9.0 8.0 8.3 8.8 9.2 8.4 8.5 8.1 8.3
7.4 7.6
17.2 10.7 14.0
6.5 10.7 16.8 16.7 15.4 14.0 13.4
9.9 12.1 15.0 13.2 16.0 11.8
8.2 10.7 13.6 14.3 15.2 15.7 13.7
15.6 10.6 12.5
5.6 10.3 15.2 15.0 14.8 14.0 12.6
9.2 11.1 13.0 12.4 14.3 11.4
7.9 11.0 13.7 13.1 14.2 15.4 13.2
16.4 10.6 13.3
6.0 10.5 16.0 15.9 15.1 14.0 13.0
9.5 11.7 14.0 12.8 14.8 11.6
8.1 10.8 13.7 13.7 14.7 15.5 13.4
13.2 12.2 12.7
36.6 25.1 32.4 17.7 25.1 35.8
c 34.1 31.1 33.1 25.0 30.6 30.4 28.1 32.2 26.6 22.7 26.4 28.1 31.8 33.0 37.7 32.1
34.0 24.5 29.1 14.9 23.3 33.6
c 33.1 30.4 31.5 23.6 28.1 27.3 26.7 29.7 25.6 22.2 27.1 29.0 30.1 31.3 36.3 31.5
35.3 24.8 30.7 16.0 24.1 34.7
c 33.6 30.8 32.3 24.2 29.4 28.9 27.4 30.4 26.1 22.4 26.8 28.6 31.0 32.1 37.0 31.8
27.6 26.1 26.9
60.2 39.0 50.4 35.1 42.7 56.1
c 56.0 51.5 51.0 42.3 50.8 47.1 44 .X 46.4 43.4 39.0 43.0 46.1 50.3 53.6 59.0 49.4
53.3 38.0 46.2 30.9 41.6 53.1
c 52.5 50.3 48.1 39.6 48.6 42.6 43.4 42.7 41.2 38.9 41.8 46.7 48.7 49.6 55.4 47.9
56.8 38.5 48.3 32.4 42.0 54.6
c 54.2 51.0 49.6 40.7 49.7 44.8 43.8 43.8 42.3 39.0 42.4 46.4 49.5 51.6 57.2 48.6
43.2 41.5 42.3
M = MALE F = FEMALE T = TOTAL (SUM OF PUP WEIGHTS/NUMBER OF LIVE PUPS) DAY = DAY POSTPARTUM
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
MEAN LITTER WEIGHTS INCLUDE ONLY WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
c. Dam 13257 was found dead on day 10 of lactation; eight pups were sacrificed on day 10 postpartum.
418-008:PAGE E-72
000662
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 1): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP ft
RAT/ LITTER #
12 3 4 5 MATERNAL DOSAGE GROUP I
6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 1
13201 13202 13203 13204 13205a 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
6.7 7.0 6.2 6.5 6.8 6.4 6.5 7.2 6.7 6.9 6.3 6.0 5.9 FD 1 FS FS 6.3 5.4 5.7 5.8 5.4 5.7 5.8 5.2 5.9 5.6 5.5 5.8 5.3 5.4 5.3 FS 4.5 4.7 4.7 4.8 5.1 4.9 4.6 4.7 3.6 4.4 4.4 4.2 4.8 4.8 4.6 4.1 4.9 5.5 5.6 5.6 5.5 5.1 5.8 5.6 5.5 5.4 5.5 4.7 5.2 4.9 5.6 4.9 5.4
6.6 6.7 6.1 6.6 6.7 6.3 5.7 6.3 5.5 6.2 5.6 6.2 5.9 5.8 5.8 5.6 5.6 5.8 6.6 5.7 6.1 5.7 5.8 6.1 5.8 5.5 6.3 6.5 6.0 6.6 5.9 5.7 6.4 6.5 5.8 5.8 NOT PREGNANT
5.1 5.9 5.5 5.9 5.7 5.6 4.7 5.5 5.6 5.7 5.6 5.7 5.3 5.4 5.6 5.8 5.9 9.3 8.5 9.2 9.0 8.6 5.3 6.2 6.3 5.7 6.7 7.0 5.9 6.1 6.1 6.4 6.1 6.4 6.0 5.8 6.8 7.0 6.3 6.9 6.9 6.0 7.1 6.4 6.6 7.1 6.9 6.9 6.9 6.9 6.6 6.4 6.3 5.6 5.9 6.4 6.1 6.8 6.7 6.8 MD 1 MS MS 5.7 6.8 5.3 6.1 5.8 7.5 7.1 7.1 6.5 7.2 6.4 6.6 6.5 6.8 6.5 6.7 6.3 6.7 6.8 7.1 6.6 6.6 6.8 6.8 6.5 6.7 6.5 6.9 6.3 6.7 6.9 5.9 6.6 6.4 7.4 7.2 7.0 6.4 6.8 6.7 7.1 6.7 7.1 6.7 5.9 5.7 6.3 6.4 6.3 6.5 6.6 6.5 6.9 6.1 7.0 6.5 4.9 6.7 6.9 6.9 5.7 6.3 6.0 6.6 6.2 6.8 6.5 6.3 6.5 6.0 6.4 6.6 6.2 6.4 6.3 5.9 6.0 6.4 5.8 5.8 6.0 5.9 6.2 5.9 6.4 5.8 6.2 5.8 5.7 5.5 5.6 5.7 5.9 5.5 S .5 6.0 6.1 FOUND DEAD ON DAY 28 POSTWEANING
7.4 6.9 MS 6.8 6.1 7.7 7.4 7.0 6.5 7.3 7.0 6.7 6.4 6.8 7.1 6.5 6.3 5.8 6.4 6.4 6.3 6.2 6.0 6.1 7.0 6.8 7.0 6.5 6.8 7.2 6.1 6.6 6.4 6.7 6.0 6.9 6.3 6.6 6.1 6.1 6.7 6.1 6.5 7.0 6.4 6.3 5.7 6.0 5.4 6.1 6.1
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008:PAGE E-73
000S63
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 2): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP u 1 2 3 21 22 23
4
56 v
7B
9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER ft
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
POSTPARTUM1 DAY 1
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236
13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
7.0 7.1 6.8 6.9 7.8 7.1 MS 6.9 6.2 6.9 7.0 6.4 5.9 5.3 5.4 6.4 6.5 6.5 7.1 6.2 6.2 5.7 6.1 6.1 5.7 NOT PREGNANT 6.5 6.4 7.0 5.9 5.6 6.3 6.6 6.0 5.8 5.7 6.5 5.9 5.1 5.3 5.6 6.3 5.8 6.0 5.9 5.8 6.0 6.1 6.0 5.9 5.5 5.7 5.7 5.6 6.3 6.4 6.5 6.3 7.2 6.5 6.3 6.3 6.7 6.7 5.5 5.7 6.4 6.6 5.9 6.7 5.6 6.5 6.7 6.3 7.0 6.7 7.1 6.7 6.9 6.4 6.7 7.0 6.9 6.5 6.7 5.7 5.9 6.2 5.9 5.8 6.2 6.3 5.4 6.1 5.1 4.9 5.9 5.8 5.9 5.2 6.6 5.7 5.5 6.6 6.4 6.2 5.6 6.2 MS MS MS 6.7 6.3 6.1 5.5 6.9 6.2 FS FS 5.1 6.1 6.2 4.4 MD 1 MD 1 4.3 5.1 4.6 5.3 7.0 6.9 6.6 6.7 6.7 5.8 6.6 5.7 6.8 6.8 5.8 5.7 5.8 6.1 5.9 6.5 6.1 6.1 6.2 5.6 5.5 7.4 7.6 7.5 6.8 7.2 6.8 7.7 6.6 6.4 6.9 6.9 6.2 7.3 7.0 6.4 6.6 7.1 6.5 6.4 6.8 7.1 6.4 6.4 6.4 6.6 6.3 6.2 6.4 6.4 6.1 5.7 5.0 5.3 5.2 5.8 5.1 5.5 5.8 5.2 5.9 5.2 4.9 6.3 5.0 5.2 6.5 6.0 6.6 7.2 5.3 6.4 6.6 7.1 5.9 6.6 6.3 6.6 6.5 6.2 6.2 5.8 5.1 5.7 5.6 6.1 5.3 5.3 5.4 5.6 6.0 5.1 5.2 5.2 5.5 5.1 5.7 5.6 6.9 8.3 6.3 6.0 6.5 6.7 8.2 6.4 6.5 6.5 6.2 6.2 6.7 6.7 5.4 5.5 6.3 NOT PREGNANT NOT PREGNANT NOT PREGNANT 6.6 6.7 6.5 6.2 6.1 6.2 5.6 6.3 5.4 5.8 6.0 6.1 6.1 6.0 6.3 6.0 6.7 6.3 6.3 6.0 6.3 6.1 5.3 5.7 6.0 6.1 6.0 6.0 6.3 6.1 5.4 7.1 6.1 6.6 6.4 5.9 5.0 6.6 7.0 6.4 6.4 5.7 6.2 5.7 6.1 6.6 6.0 6.3 FS 6.6 6.7 6.3 6.3 6.7 6.5 6.8 6.0 6.5 6.3 6.0 6.4 6.0 6.3 5.8 5.9 5.8 5.9 6.3 6.0 5.8 5.9 6.0 5.6 5.9 6.0 5.8 5.8 5.7 5.7 5.7 5.2 5.8
ALL WEIGHTS WERE RECORDED IN GRAMS (G) . FIRST LETTER -- M-MALE, F-FEMALE, U -SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE E-74
000664
PROTOCOL 410-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 3) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP #
RAT/ LITTER U
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
POSTPARTUM DAY 1
6.6 6.0 7.0 6.7 6.7 6.4 7.0 6.6 6.5 6.5 6.3 6.3 6.8 5.0 5.0 5.4 5.3 5.3 5.0 5.6 5.2 4.7 4.9 5.1 4.9 5.2 4.8 4.8 5.7 6.6 6.1 5.3 6.6 5.9 6.7 6.0 4.7 6.4 5.9 6.4 5.2 5.0 5.4 5.6 6.2 5.5 6.2 6.2 5.4 4.1 5.7 5.4 5.6 5.1 5.6 5.3 5.2 5.3 5.3 4.9 6.3 6.0 6.1 6.8 6.6 6.8 6.9 MS 5.9 6.1 6.1 6.0 6.4 6.8 6.2 FS FS FS 7.3 7.1 5.8 6.9 7.1 MS 6.0 5.8 6.6 6.8 6.4 6.4 6.9 6.1 6.3 7.7 7.8 7.2 8.0 7.2 7.5 6.9 6.7 7.0 6.6 7.3 6.5 6.6 7.1 6.8 6.8 7.2 7.1 7.2 6.8 7.1 6.4 6.6 6.5 6.8 7.2 6.4 6.6 7.2 6.7 6.9 6.2 6.8 6.5 6.5 6.9 6.2 6.0 6.5 MD 1 6.5 6.3 6.7 6.1 6.6 6.2 6.5 6.2 6.2 6.0 6.2 MD 1 6.2 6.1 5.8 6.4 5.5 6.2 6.3 5.5 6.3 7.1 7.5 7.1 6.8 6.9 6.6 6.6 7.3 6.5 6.3 6.5 6.6 6.1 7.4 5.5 5.8 6.5 6.1 5.6 6.4 5.3 5.0 5.5 5.4 5.8 FS
6.2 6.1 5.8 6.0 5.9 5.9 6.2 5.9 6.4 5.5 6.1 5.2 5.5 5.6 5.6 6.1 6.2 6.5 5.7 5.7 6.2 6.6 6.1 5.8 5.7 5.6 5.8 5.8 6.1 6.0 5.4 6.9 6.4 7.0 6.3 7.0 6.7 3.9
6.8 6.3 6.1 6.9 6.0 5.8 6.3 5.5 6.6 5.6 6.3 6.2 5.7 7.3 6.2 6.0 5.4 5.9 5.8 6.2 5.7 5.6 6.0 5.5 5.4 6.2 5.6 5.2 5.9 5.5 5.8 5.7 5.7 5.9 5.1 6.0 5.8 5.0 5.8 6.0 5.9 5.9 5.7 5.3 5.8 5.3 5.4 5.5 FS 6.3 6.9 6.7 6.6 7.6 6.8 7.3 6.8 7.1 6.6 6.6 6.5 6.5 6.8
6.2 6.0 6.6 6.7 6.5 6.5 6.6 6.2 6.4 6.1 5.6 5.8 6.1 6.3 6.1 US 7.7 7.1 7.3 7.2 MS 7.1 6.3 6.6 6.7 6.3 6.7
7.7 6.5 7.9 6.3 7.3 7.7 6.5 6.3 6.0 6.3 7.8 MS MS 7.0 6.0 6.3 6.0 7.5 6.8 6.5 6.5 6.5 6.6 6.2 MS 6.5 6.4 6.4 6.5 6.9 5.4 6.3 5.8 5.2 6.1
NOT PREGNANT
5.7 5.3 5.5 5.6 6.0 MS 5.3 5.3 5.4 5.5 5.8 5.5 5.6 5.6
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-foALE, P-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
20
418-008:PAGE E-75
000665
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 4) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP # 1 2 3 4 5 6
10 11 12 13 14 15 16 17 16 19 20
RAT/ LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 41 PRECULLING
13201 13202 13203 13204 13205a 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
8.9 8.3 9.2 8.9 9.5 8.8 9.0 8.9 8.2 9.0 8.5 9.3 9.3 FD 1 FS PS 7.8 8.5 8.0 7.9 8.9 8.7 8.6 7.5 7.1 7.6 7.5 7.6 8.1 7.6 8.1 FS 6.5 6.2 5.7 6.7 6.6 6.1 6.2 5.9 5.3 6 .1 6.1 6.4 5.9 6.6 FM 3 FM 2 7.2 7.5 6.9 7.0 5.2 6.7 7.0 7.7 MD 4 MM 2 6.4 5.7 6 .7 6.8 6.1 6.3 6.9 6.7
10.7 10.1 9.9 9.6 10.4 10.1
7.4 8.6 7.5 7.8 8.3 7.8 8.3 9.3 8.9 8 . 2 6.5 7.4 9.0 9.6 9.7 9.2 9.3 8.0 MD 2 8.3 8.9 8.9 7.2 9.8 NOT PREGNANT
8 . 2 8.0 8.0 8.3 7.3 8.0
7.1 6.6 7.1 6.8 7.0 6.5 7.3 7.0 7.1 MD 2 6.4 6.9 7.2 6.8 6.7 7.0 6.4 13.8 14.9 14.6 14.6 14.4
9.5 9.2 8.0 8.5 7.5 8.7 8.8 8.7 9.6 7.3 8.0 7.4 7.1 8.1 9.8 9.4 7.9 8.5 9.6 9.6 8.1 9.3 9.4 9.7 9.6 8.8 9.0 9.1 9.5 8.2 8.0 8.3 9.7 8.4 9.2 7.9 9.5 8.2 9.5 8.7 8.2 9.1 9.9 9.8 10.1 9.0 9.9 10.0 9.1
8 . 8 9.2 8.4
8.5
8 .3 7.6 7 .7
7.4 6.5
8.4 MD 1 MS MS 7.1 8.3 8.4 9.3 9.2 8.3
9.1 9. 5 9.0 9.4 9.0 9.2
9.1 8 . 9 8.2 9.0 9.2 8 . 0 8.3
8.2 8 . 5 8.3 7.3 8.6 8.0 8.6 6.1 7.3
7.1 7. 9 8.8 9.4 8.8
8.4 8.4 8.5 8.8 8.3 8.4 8 . 2
7.8 B.O 8.3 8.3 8.1
FM 2
7.8 6.9 7.5 7.7 7.6 7.8 8.1 8.0 7.8 7.7 6.9 7.4 7.2
7.4 7.6 8.0
FOUND DEAD ON DAY 28 POSTWEANING
10.7 10.6 MS 10.9 10.0 11.2 11 3 9.0
10.1 10.3 9.2 9.6 9.7 9.3 8 7 8.6 9.6 8.3 7.7 9.3 9.3 9.1 8 6 8.2 9.7 9.0 9.3 9.3 8.7 9.4 9.0 8.2
9.5 10.2 8 . 6 8.8 8.3 7.7 8.0 8.7 9.1 8.7 7.3
ALL WEIGHTS WERE RECORDED IN GRAMS (G) . FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008:PAGE E-76
999000
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 5): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP tt
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
21 22 23
RAT/ LITTER It
13226 1322T 13228 13229 13230 13231 13232 13233 13234 13235 13236
13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
POSTPARTUM DAY 4 PRECULLING
8.0 8.0 8.4 9.1 9.1 8.7 MS 7.8 9.0 7.2 8.1 8.9 9.5 9.2 10.0 9.4 8.5 7.6 8.9 7.9 8.9 9.4 8.5 9.2 8.6 NOT PREGNANT
7.3 7.3 7.2 7.7 6.6 7.0 7.4 8.0 7.0 6.8 6.9 5.6 7.0 7.2 6.2 7.3 7.1 7.5 6.6 6.6 7.5 6.7 6.8 7.1 6.1 7.0 6.5 7.0 10.1 10.1 10.1 9.3 9.9 9.3 8.0 8.6 9.6 9.8 9.5 7.6 9.9 10.2 7.2 8.8 8.8 9.1 9.4 9.6 9.6 9.4 9.0 9.3 9.0 9.7 9.2 9.3 9.0 9.3 8.1 8.5 8.3 8.7 9.1 9.9 8.6 9.8 8.1 8.2 9.2 8.7 6.8 7.3 7.0 8.8 8.7 10.8 10.2 9.0 9.7 10.4 9.7 9.5 MS MS MS 8.5 8.8 9.3 10.3 9.5 FM 4 FS FS 7.5 8.7 10.3 MD 2 MD 1 MD 1 6.9 8.1 7.6 8.8 8.4 8.3 9.4 8.3 8.5 8.2 6.7 7.2 8.7 8.4 8.3 7.4 7.9 7.2 7.1 6.1 6.2 7.5 7.9 7.6 7.2 8.6 8.2 7.8 9.6 9.5 9.3 9.5 8.4 8.3 9.6 7.6 7.8 8.0 8.6 10.1 9.3 10.2 9.7 9.5 9.2 9.2 9.3 8.5 9.9 9.2 8.8 9.7 9.6 8.9 10.2 9.3 a.4 8.7 8.9 8.9 8.5 7.7 8.5 8.6 7.8 9.6 8.0 7.7 8.0 8.0 8.4 6.8 8.7 8.9 8.2 B .8 8.4 7.4 7.3 7.6 8.1 7.4 8.5 7.5 7.9 7.9 7.0 6.7 7.1 5.8 7.1 7.1 6.1 6.4 6.6 6.4 6.6 4.9 6.0 6.4 6.5 6.3 9.1 9.1 9.4 9.1 10.5 8.1 9.2 9.1 11.2 9.7 9.1 7.1 8.2 8.4 10.1 9.4 8.7 NOT PREGNANT
NOT PREGNANT
NOT PREGNANT
8.1 8.3 7.4 8.6 8.2 7.6 7.4 7.1 8.1 7.7 7.8 7.8 7.5 7.6 7.0 6.2 6.9 6.1 6.5 7.4 6.6 6.4 6.5 6.6 5.5 6.5 5.8 6.6 6.5 5.6 6.3 7.1 4.6 6.8 7.8 8.2 7.2 6.7 6.6 6.9 6.7 7.0 7.6 6.9 7.3 6.5 7.4 6.1 FS 9.2 9.0 9.3 8.8 9.1 9.1 9.4 8.2 8.7 8.3 8.8 8.3 9.5 9.2 8.4 8.5 7.7 8.0 7.8 7.1 8.1 8.0 8.0 8.1 7.9 8.5 8.0 8.1 7.4 7.9 7.1 7.2 7.0
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE E-77
000667
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 629S.9)
TABLE E37 (PAGE 6) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 IS 16 17 18
RAT/ LITTER #
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
POSTPARTUM DAY 4 PRECULLING
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
10.1 9.5 9.9 10.7 8.8 10.3 8.8 9.7 9.7 9.1 8.9 9.6 9.3
6.3 6.3 6.5 6.8 6.2 6.4 6.4 7.3 6.4 6.2 5.4 6.1 6.7 5.9 6.5 9.2 8.8 8.3 7.0 8.8 9.0 7.5 8.2 9.1 6.8 9.1 9.0 6.9 6.4 FM 2 4.8 5.2 5.9 MD 4 MM 3 MM 3 4.0 3.9 5.3 4.7 5.0 5.7 4.9 FD 4 FM 4 FD 3 FD 3 7.3 7.1 7.1 7.6 6.9 7.1 8.0 MS 6.9 7.3 6.3 8.4 6.6 7.1 7.1 FS FS FS 9.4 8.5 10.4 10.0 9.0 MS B .6 8.6 9.2 9.1 8.4 9.0 8.0 9.1 FM 3
10.5 9.3 9.8 10.5 9.8 11.2 8.3 9.6 9.0 8.7 9.2 9.3 8.6 9.1 9.3 9.8 9.2 9.6 9.2 10.4 9.4 10.1 9.2 9.5 8.7 9.5 9.5 9.2 9.4 8.6 8.0 8.9 8.6 8.8 8.5 8.4 8.4 9.2 8.7 MD 1 8.5 9.1 8.4
9.0 9.6 9.5 8.5 8.9 8.9 8.2 MM 2 MD 1 8.0 8.8 8.0 8.0 8.1 7.9 8.5 8.2 7.5 7.5 6.9 6.5 6.7 6.4 5.8 6.3 6.1 6.5 7.3 6.2 6.8 6.8 6.0
6.8 8.4 7.8 6.2 7.0 8.0 7.3 6.8 6.0 6.2 5.9 FS
8.6 9.0 8.8 9.0 9.1 9.2 8.4 9.2 8.5 7.8 8.5 7.3 8.3 8.0 8.0
8.6 8.4 7.4 7.0 7.6 8.3 7.5 8.0 7.5 6.2 7.7 7.3 7.4 7.9 7.8 7.3
11.2 10.2 10.9 11.8 9.7 11.6 5.6
7.1 7.9 7.5 6.5 7.2 6.5 MM 3 6.8 6.7 7.7 5.9 6.7 7.0 6.5 6.1 5.7 6.9 7.0 6.2 6.3 6.1 6.5 6.3 4.8 6.3 6.3 6.0 5.5 6.1 6.0 5.8 5.9 5.7 5.9 5.6
6.7 6.8 7.6 7.4 5.9
.2 7.1 7.1 7.1 7.2 7.1 7.2 7.0 FS
8.2 8.7 8.5 8.7 9.5 10.2 9.3 8.2 8.2 9.9 8.4 8.6 8.4 9.6
9.0 8.5 8.1 7.8 8.6 9.4 9.1 8.5 7.8 8.6 8.6 7.8 7.5 8.2 8.6 US
9.4 9.3 9.7 10.2 MS 9.4 8.8 8.5 8.4 8.7 8.3
8.1 8.9 8.5 9.6 9.2 8.1 8.3 9.5 9.1 8.1 7.7 MS MS 8.7 9.4 7.8 8.5 8.0
8.9 7.8 8.6 8.6 8.6 9.2 MS 8.1 8.0 8.3 6.5 8.6 7.8 7.5 8.3 8.6 8.4
NOT PREGNANT
7.4 8.2 7.7 8.7 7.2 MS 7.7 7.5 7.0 7.6 7.2 7.7 7.6 8.0
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
19
20
418-008:PAGE E-78
893000
PROTOCOL 410-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 7): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA F2 GENERATION PUPS
PUP ft
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
RAT/ LITTER tt
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 4 POSTCULLING
13201 13202 13203 13204 13205a 13206 13207 1320B 13209 13210 13211 13212 13213 13214 13215 13216 13217 13210 13219 13220 13221 13222 13223 13224 13225
0.9 8.3 MC 4 MC 4 MC 4 8.8 9.0 8.9 FC 4 9.0 8.5 9.3 FC 4 FD 1 FS FS MC 4 8.5 8.0 7.9 8.9 MC 4 8.6 FC 4 7.1 7.6 7.5 FC 4 FC 4 FC 4 FC 4 FS MC 4 MC 4 MC 4 6.7 MC 4 6.1 6.2 5.9 5.3 6.1 FC 4 FC 4 5.9 6.6 FM 3 FM 2
7.2 MC 4 MC 4 MC 4 MC 4 6.7 7.0 7.7 MD 4 MM 2 FC 4 FC 4 6.7 FC 4 6.1 FC 4 6.9 6.7
10.7 10.1 9.9 9.6 10.4 10.1 MC 4 8.6 7.5 7.8 MC 4 MC 4
9.0 9.6 9.7 MC 4 9.3 MC 4 NOT PREGNANT MC 4 MC 4 MC 4 MC 4 7.0 6.5 13.8 14.9 14.6 14.6 14.4 9.5 9.2 MC 4 8.5 MC 4 8.7 8.7 FC 4 7.3 8.0 7.4 FC 4 MC 4 9.4 MC 4 MC 4 9.6 9.6 9.3 9.4 9.7 FC 4 8.8 FC 4 9.5 MC 4 8.0 MC 4 9.7 MC 4 MC 4 9.5 MC 4 9.5 MC 4 MC 4 MC 4 MC 4 10.1 MC 4 MC 4 10.0 8.4 MC 4 MC 4 8.8 8.3 MC 4 MC 4 MC 4 MC 4 7.7 7.6 7.8 FOUND DEAD ON DAY 28 iPOSTWEANING 10.7 10.6 MS 10.9 10.0 11.2 MC 4 10.3 9.2 9.6 9.7 FC 4 9.6 MC 4 7.7 MC 4 MC 4 9.1 MC 4 MC 4 9.3 9.3 MC 4 9.4
MC 4 MD 2
7.3
8.8 8.1 MC 4 9.1 9.2 9.1 9.1 8.2 8.1
11.3 FC 4
8.6 9.0
MC 4 8.3
7.0
FC 4 FC 4 MC 4
8.9 MC 4
9.3 9.8 MC 4 FC 4
FC 4 8.6
MC 4 8.2
8.9 8.9
MC 4
FC 4 FC 4
8.4 FC 4
9.1 MC 4 MC 4
7.8 7.8
9.6 FC 4 FC 4
8.4
MC 4 8.9
MD 2
FC 4 8.3
MD 1 9.5
FC 4 8.5
FC 4 FC 4
7.7
9.3 FC 4 FC 4
7.9
MC 4 FC 4
6.4
9.2 7.6 MS FC 4 FC 4 FC 4 8.8 8.3 FC 4
FC 4 8.3 8.7
MC 4 FC 4
6.9
8.4 FC 4
MS FC 4
9.0 FC 4
9.4 8.3 FC 4
10.2 FC 4 FC 4
MC 4 9.4
7.2
8.0 FC 4
7.1 9.0 9.2 8.6 8.8 8.1 FC 4
8.6 8.0
FC 4
6.8
FC 4 FC 4
8.3 FC 4 FC 4 FC 4
9.4 FC 4
7.9
8.8 8.7
80
FC 4
6.5 FC 4
8.3 8.6 FM 2 7.4
9.1
8.0 FC 4
9.3 FC 4 FC 4
8.3 FC 4
FC 4 7.3
FC 4
FC 4 8.3
8.0
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008 PAGE E-79
000669
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 8) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP tt
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
21 22 23
RAT/ LITTER ft
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236
MATERNAL DOSAGE GROUP II
0 .1 MG/KG/DAY
POSTPARTUM DAY 4 POSTCULLING
MC 4 MC 4 8.4 MC 4 MC 4 10.0
NOT PREGNANT MC 4 MC 4 MC 4 MC 4 7.1 7.5 MC 4 10.1 MC 4
9.1 9.4 9.6 MC 4 MC 4 8.3 MC 4 10.8 MC 4
7.5 8.7 10.3 MC 4 8.3 MC 4
9.1 9.1 8.7 MS MC 4 MC 4 7.6 8.9
7.7 6.6 9.3 MC 4 8.7 MC 4 MD 2 MC 4
MC 4 MC 4
9.9 MC 4 MC 4 MC 4 MD 1 MC 4
MC 4 MC 4
9.3 MC 4 MC 4 10.4 MD 1 MC 4
7.4 MC 4 FC 4
9.3 8.6 9.7 6.9 6.7
7.8 7.9
8.0 MC 4 FC 4
9.0 9.8 9.5 8.1 7.2
9.0 FC 4 FC 4 9.4
7.0 7.1 9.6 FC 4 FC 4 MS 7.6 8.7
6.8 6.1 FC 4 FC 4 8.2 MS 8.8 MC 4
8.1 8.5
FC 4 7.0 9.5 9.3 9.2 MS
8.3
8.9 9.2
5.6 6.5 FC 4 9.0 8.7 8.5
FC 4
8.6
7.0 7.0 FC 4 9.3 FC 4 FC 4
7.9
7.2
10.2
FC 4 9.3
FC 4
FC 4 FC 4
FC 4 10.3
FC 4
FC 4
8.8 9.5
FC 4
8.8
FM 4 FC 4
FS FC 4
FS FC 4
--
7.6
13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
8.6 8.2 MC 4 10.1 MC 4 MC 4
9.3 8.4 MC 4 8.4 MC 4 MC 4 7.0 6.7 MC 4 9.1 9.1 9.4 NOT PREGNANT NOT PREGNANT NOT PREGNANT 8.1 8.3 7.4 6.2 6.9 MC 4 7.1 MC 4 6.8 MC 4 MC 4 9.3 7.7 MC 4 MC 4
9.6 9.7 MC 4 8.9 MC 4 MC 4
8.6 6.5 MC 4 8.8 MC 4
9.5 9.5 MC 4 8.2 7.1 MC 4
MC 4 7.4 8.2 9.1
MC 4
MC 4 MC 4 MC 4 MC 4
7.1 MC 4
FC 4 6.6
MC 4 9.1
MC 4
MC 4 9.2
MC 4 8.4
MC 4 MC 4
7.4 FC 4
6.7 MC 4 MC 4
8.4 FC 4 MC 4 MC 4 MC 4 MC 4
FC 4 FC 4 MC 4
8.2 8.1
FC 4 8.5 8.6 7.3
MC 4 11.2
8.1 FC 4
6.9 FC 4 MC 4
9.6 9.9 7.8 7.6 FC 4 9.7
FC 4 FC 4 FC 4 FC 4
8.5
FC 4 9.2 9.6
FC 4 FC 4 FC 4
FC 4 FC 4
7.0 FC 4 MC 4
FC 4 FC 4 FC 4
7.4 4.9 FC 4
7.8 FC 4 FC 4 FC 4
8.1
8.0 FC 4
7.7 FC 4
6.0 FC 4
FC 4 6.6
FC 4 9.5 7.4
8.6 9.6 8.0 FC 4 6.4 FC 4
FC 4 FC 4 FC 4
9.2 7.9
FC 4 8.0 7.9
FC 4 10.1
7.0 5.6 6.5 8.4 7.1
FC 4
FC 4 6.3 9.4
6.3 7.4 FC 4 7.2
8.7
FC 4 FC 4
FS
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE E-80
000670
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 9) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP (t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
RAT/ LITTER #
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
POSTPARTUM DAY 4 POSTCULLING
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
MC 4 9.5 9.9 MC 4 MC 4 6.5
9.2 MC 4 8.3 4.8 5.2 5.9 MC 4 MC 4 MC 4 9.4 MC 4 10.4 10.5 MC 4 MC 4 9.8 MC 4 9.6 MC 4 8.9 8.6 9.0 MC 4 MC 4 7.5 6.9 6.5 MC 4 MC 4 7.8 8.6 MC 4 MC 4 8.6 8.4 MC 4 11.2 10.2 10.9 7.1 7.9 7.5 6.2 6.3 6.1 6.7 6.8 MC 4 MC 4 8.7 MC 4 9.0 MC 4 MC 4 9-4 9.3 9.7 MC 4 8.9 MC 4 8.9 7.8 8.6 NOT PREGNANT 7.4 8.2 MC 4
10.7 MC 4 MC 4 MD 4
7.6 10.0 10.5 MC 4 MC 4
8.5 6.7 6.2 9.0 7.0 11.8 MC 4 6.5 7.4 8.7 7.8 10.2 MC 4 MC 4
8.7
MC 4 6.2 8.8
MM 3 MC 4
9.0 9.8 10.4 8.5 MC 4 FC 4 7.0 9.1 MC 4 9.7 7.2 MC 4 MC 4 MC 4 8.6 MS MC 4 8.6
7.2
10.3 6.4
MC 4 MM 3
7.1 MS 11.2 9.4 MC 4 8.9 FC 4 8.0 9.2 MC 4 11.6 MC 4 FC 4 MC 4 MC 4 MC 4 9.4 MC 4 MC 4
MC 4 MC 4
7.5 4.0 8.0 FC 4 FC 4 FC 4 8.4 8.2 FC 4 7.3 MC 4 7.5 5.6 MM 3 FC 4 7.1 9.3 9.1 8.8 8.3 MS
MS FC 4
9.7 7.3 8.2 FC 4 MS FC 4 FC 4 9.2 MC 4 MM 2 FC 4 FC 4 MC 4 8.0
FC 4 6.3 7.1
MC 4 8.5
FC 4 MC 4
8.1
7.5
9.7 FC 4 FC 4 FC 4
6.9 9.2 9.0 FC 4 8.7 MD 1 6.5 6.0 MC 4 7.5
FC 4 6.0 7.1
MC 4 FC 4
8.4 9.1 FC 4
7.0
FC 4 FC 4
6.8 4.7 7.3 FC 4 FC 4 FC 4 MD 1 8.0 7.3 6.2 FC 4 FC 4
FC 4 FC 4 FC 4
5.0 FC 4 FC 4 FC 4
9.5 8.5 FC 4 6.2 5.9 8.5 7.7
7.7 FC 4
7.2 9.9 FC 4 8.7 8.1 8.3
FC 4 6.1 7.1 8.4
FC 4 FC 4 MC 4 FC 4
7.6 FC 4
9.6 6.1 9.0 5.7 8.4 9.0 9.3 FC 4 9.1 8.0 6.8 FS 7.3 FC 4
FC 4 FC 4 FC 4
8.6 7.8
MS FC 4
FC 4
9.3 6.7 FC 4 4.9 6.6 8.0 8.6 9.2 8.4 8.0 FC 4
FC 4 FC 4
7.0 FC 4 FC 4
8.4 7.5
MS 7.8
7.6
5.9 6.4 FD 4 FC 4 9.1 9.1 FC 4
FC 4 FC 4
8.0 FC 4
FC 4 FC 4
FS 9.6 8.2
FC 4 FC 4
FC 4
6.5 FM 2 FM 4
7.1 FM 3 FC 4
8.6
7.9
8.0 FC 4
6.1 FC 4
FC 4
9.4 8.3
FD 3 FS
FC 4
7.3 FC 4 FC 4
us 7.8 FC 4
FD 3 FS
FC 4
FC 4 5.6
8.5 FC 4
FS FC 4
7.0 8.0
ALL WEIGHTS WERE RECORDED IN GRAMS (G) . FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
20
418-008:PAGE E-81
000671
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 10) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
RAT/ LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 7
13201 13202 13203 13204 13205a 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
14.8 MC 4 MC 4 10.4
14.5 15.0 MC 4 MC 4
MC 4 15.5 MC 4 MC 4
MC 4 15.5
9.5 MC 4
MC 4 14.2 MC 4 MC 4
14.9 MC 4 10.7 11.9
14.8 13.7
9.4 11.6
15.1 FC 4
9.3 12.6
FC 4 15.6 10.5 MD 4
14.4 14.0
9.4 MM 2
15.3 13.7 FC 4 FC 4
14.9 FC 4 FC 4 FC 4
FC 4 FC 4
8.2 11.0
FD 1 FC 4
9.3 FC 4
FS FC 4 FM 3 11.4
FS FS FM 2 FC 4
11.3
10.2
17.6 17.1 16.5 15.9 16.8 17.3 MC 4 13.1 16.1 15.2 MC 4 MC 4 14.7 14.6 14.0 MC 4 14.8 MC 4
NOT PREGNANT MC 4 MC 4 MC 4 MC 4 11.2 9.6 21.5 22.5 22.3 22.1 20.6 16.0 16.2 MC 4 15.3 MC 4 15.5 14.9 FC 4 14.8 14.4 14.2 FC 4 MC 4 15.0 MC 4 MC 4 16.6 16.8 16.5 17.2 16.1 FC 4 15.7 FC 4 16.6 MC 4 14.1 MC 4 16.1 MC 4 MC 4 16.2 MC 4 16.0 MC 4 MC 4 MC 4 MC 4 16.7 MC 4 MC 4 15.4 14.1 MC 4 MC 4 13.2 13.4 MC 4 MC 4 MC 4 MC 4 13.6 13.2 14.7
FOUND DEAD ON DAY 28 POSTWEANING 16.7 16.8 MS 16.4 16.0 17.5 MC 4 17.3 17.4 16.0 14.2 FC 4 16.2 MC 4 15.0 MC 4 MC 4 11.7 MC 4 MC 4 14.9 15.0 MC 4 14.8
MC 4 MD 2
10.9
15.1 11.8 MC 4 16.3 16.4 15.5 16.9 13.2 13.7
17.3 FC 4 13.5 15.1
MC 4 13.2
11.3
FC 4 FC 4 MC 4 15.7 MC 4 16.0 16.5 MC 4 FC 4
FC 4 15.7 MC 4 13.7
13.8 MC 4 MC 4 MC 4 MC 4 13.7 14.1 FC 4 FC 4 14.7
MC 4 MD 2 10.2 11.4 10.8
FC 4 FC 4 16.3 FC 4 15.8 MC 4 MC 4 12.6 12.5
FC 4 12.3 MD 1 15.0 FC 4 14.9 FC 4 FC 4 13.9
15.8 12.3
MS FC 4 FC 4 FC 4 15.1 13.1 FC 4
15.6 FC 4
MS FC 4 16.3 FC 4 15.2 13.2 FC 4
14.1 FC 4 14.5 16.2 14.1 15.7 15.7 12.2 FC 4
14.6 FC 4 FC 4 13.3
16.3 FC 4 FC 4 13.1
FC 4 13.9 14.2
15.3 FC 4 FC 4
16.9 13.4
FC 4
9.7
FC 4 FC 4 12.7 FC 4 FC 4 FC 4 16.2 FC 4 13.4
15.0 13.3
14.2
FC 4
13.7 FC 4 15.4 14.8 FM 2 13.7
14.0
13.8 FC 4
16.4 FC 4 FC 4
13.9 FC 4
FC 4 13.3 FC 4
FC 4 14.0
14.9
ALL WEIGHTS WERE RECORDED IN GRAMS (G) . FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
20
418-008:PAGE E-82
000672
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 11) ; PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM INDIVIDUAL DATA - F2 GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT/ LITTER tt
MATERNAL DOSAGE GROUP II
0. 1 MG/KG/DAY
POSTPARTUM DAY 7
13226 13221 13228 13229 13230 13231 13232 13233 13234 13235 13236
13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
MC 4 MC 4 15.5 MC 4 MC 4 n .3
NOT PREGNANT MC 4 MC 4 MC 4 MC 4 10.7 11.9 MC 4 17.2 MC 4 16.1 15.9 16.2 MC 4 MC 4 15.5 MC 4 17.7 MC 4 16.1 12.2 14.0 MC 4 13.9 MC 4 13.0 14.0 10.9 MC 4 16.3 MC 4 MC 4 14.7 16.6 MC 4 14.6 MC 4 MC 4 12.3 11.1 MC 4 16.5 15.8 15.6
NOT PREGNANT NOT PREGNANT NOT PREGNANT 14.0 15.0 13.5 10.5 9.4 MC 4 13.3 MC 4 11.1 MC 4 MC 4 15.5 14.0 MC 4 MC 4
16.0 MC 4
11.1 12.1 17.3 MC 4 14.0 MC 4 MD 2 MC 4
13.1 17.2 MC 4 14.3 MC 4 MC 4
13.9 MD 7 MC 4 14.5 MC 4
14.5 MC 4
MC 4 MC 4 17.4 MC 4 MC 4 MC 4 MD 1 MC 4
12.0 17.9 MC 4 13.1 10.9 MC 4
MC 4 MD 6 14.3 15.9 MC 4
15. 7 14 .0
MC 4 MC 4 17. 8 MC 4 MC 4 15. 2 MD 1 MC 4
MC 4 MC 4 MC 4 MC 4 10. 9 MC 4
FC 4 9.,9
MC 4 15..2 MC 4
MS 15.2
11.9 MC 4 FC 4 16.8 13.6 17.4 13.2 12.7
MC 4 17.4 MC 4 13.9 MC 4 MC 4
13.3 FC 4 12.1 MC 4 MC 4
14.6 15.2 13.6 FC 4
10.6 MC 4 FC 4 16.3 14.7 15.9 13.4 14.5
11.6 12.2 17.8 FC 4 FC 4
MS 11.2 `11.8
12.8 FC 4 MC 4 MC 4 MC 4 MC 4
FC 4 17.5 16.2 13.3 MC 4 18.7
FC 4 FC 4 MC 4 16.5 15.4
13.9 FC 4 11.1 FC 4 MC 4
FC 4 14.9
10.8 11.9 FC 4 FC 4 13.7
MS 12.2 MC 4
12.9 16.4 15.6 11.5 FC 4 15.9
FC 4 FC 4 FC 4 FC 4 14.0
13.8 16.0
FC 4 11.5 16.5 15.9 14.6
MS
13.9
FC 4 16.6 17.4 FC 4 FC 4 FC 4
FC 4 FC 4 11.4 FC 4 MC 4
15.8 15.3
10.9 10.9 FC 4 16.1 15.0 15.4
FC 4
FC 4 FC 4 FC 4 12.6
8.9 FC 4
14.2 FC 4 FC 4 FC 4 13.3
14.6
7.4 9.6 FC 4 15.3 FC 4 FC 4
12.5
14.3 FC 4 14.8 FC 4 10.3 FC 4
FC 4 11.5 FC 4 14.8 13.6
10.2
17.0
FC 4 16.6
FC 4
11.8 16.6 15.1 FC 4
7.8 FC 4
FC 4 FC 4 FC 4 15.3 12.7
FC 4
FC 4
FC 4 15.5
FC 4
FC 4 14.5 13.1 FC 4 14.5
11.8 10.4 il.i 15.4 13.8
FC 4 14.5 17.8 FC 4
FC 4 FC 4 10.2 16.0
9.3 11.6 FC 4 13.0
17.5 FM 4 FC 4
16.4
FC 4 FC 4
FS FC 4
FS
FS FC 4
13.5
ALL WEIGHTS WERE RECORDED IN GRAMS (G) . FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE E-83
000673
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER.- 6295.9)
TABLE E37 (PAGE 12) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP #
RAT/ LITTER tt
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
MATERNAL DOSAGE GROUP III
0 .4 MG/KG/DAY
POSTPARTUM DAY 7
MC 4 17.4 18.3 MC 4 MC 4 11.9 15.6 MC 4 14.6
5.6 8.1 5. B MC 4 MC 4 MC 4 18.0 MC 4 16.7 16.9 MC 4 MC 4 16.3 MC 4 15.3 MC 4 14.6 14.2 13.8 MC 4 MC 4 10.7 9.1 MD 7 MC 4 MC 4 9.5 15.3 MC 4 MC 4 14.5 11.2 MC 4 15.5 16.5 8.5 12.1 11.7 11.2
8.8 7.5 8.2 10.6 10.3 MC 4 MC 4 14.3 MC 4 13.6 MC 4 MC 4 16.1 14.3 15.3 MC 4 14.8 MC 4 12.7 13.6 13.7 NOT PREGNANT 12.3 12.9 MC 4
17.1 MC 4 MC 4 MD 4 11.4 16.7 16.5 MC 4 MC 4 12.8 MD 6 12.0 14.8 12.8 17.1 MC 4
8.5 11.1 14.5 13.7 15.2 MC 4 MC 4
13.4
MC 4 10.5 12.8 MM 3 MC 4 15.9 15.8 14.9 13.3 MC 4 FC 4 13.2 14.7 MC 4 15.1 12.0 MC 4 MC 4 MC 4 14.8
MS MC 4 14.7
14.1
16.2 10.4 MC 4 MM 3 10.1
MS 17.6 15.3 MC 4 13.8 FC 4 13.8 15.2 MC 4 16.7 MC 4 FC 4 MC 4 MC 4 MC 4 14.2 MC 4 MC 4
MS
MC 4 MC 4 13.1
5.6 10.6 FC 4 FC 4 FC 4 14.2 13.2 FC 4 12.7 MC 4 14.1 14.2 MM 3 FC 4 10.9 12.9 15.1 14.0 15.0
MS
FC 4
16.5 10.0 15.4 FC 4
MS FC 4 FC 4 15.1 MC 4 MM 2 FC 4 FC 4 MC 4 11.9
FC 4 7.9
11.3 MC 4 12.6 FC 4 MC 4 12.5
12.7
15.2 FC 4 FC 4 FC 4 MD 5 13.9 16.0 FC 4 13.6 MD 1 10.2
9.9 MC 4 12.9
FC 4 8.3
10.9 MC 4 FC 4 14.1 16.0 FC 4
11.3
FC 4 FC 4 10.9
4.8 10.5 FC 4 FC 4 FC 4 MD 1 13.4
8.3 10.6 FC 4 FC 4
10.4 FC 4 10.7 12.9 FC 4 14.3 16.9 13.4
12.2
FC 4 FC 4 FC 4
4.4 FC 4 FC 4 FC 4 14.9 13.3 FC 4
9.1 FD 5 12.7 12.0
FC 4 6.9
11.0 13.0 FC 4 FC 4 MC 4 FC 4
FC 4
14.3 10.7 10.2
6.1 10.0 15.9 15.4 FC 4 13.6 12.4 FD 6
FS 12.9 FC 4
FC 4 FC 4 FC 4 12.5 12.8
MS FC 4
FC 4
16.3 10.3 FC 4
7.2 9.2 15.0 14.0 15.1 15.0 12.3 FC 4
FC 4 FC 4
11.5 FC 4 FC 4 13.6 13.3
MS 13.5
12.5
9.9 13.5 FD 4 FC 4 16.0 14.7 FC 4
FC 4 FC 4
12.3 FC 4
FC 4 FC 4
FS 15.6 13.8
FC 4 FC 4
FC 4
11.3 FM 2 FM 4 11.6 FM 3 FC 4 14.0
12.5
14.1 FC 4
12.5 FC 4
FC 4
17.3 13.4
FD 3 FS
FC 4
13.0 FC 4 FC 4
US 13.9 FC 4
FD 3 FS
FC 4
FC 4 8.6
15.7 FC 4
FS FC 4 11.0 14.6
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
19
20
418-008:PAGE E-84
000674
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 13): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP ft 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
RAT/ LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DA.Y 14
13201 13202 13203 13204 13205a 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
33.3 MC 4 MC 4 28.7
35.6 34.9 MC 4 MC 4
MC 4 35.8 MC 4 MC 4
MC 4 34.8 26.8 MC 4
MC 4 35.0 MC 4 MC 4
34.2 MC 4 23.2 25.4
34.2 35.9 23.8 27.8
34.2 FC 4 24.1 28.3
FC 4 34.5 23.4 MD 4
32.8 33.4 21.8 MM 2
33.5 33.8 FC 4 FC 4
32.6 FC 4 FC 4 FC 4
FC 4 FC 4 26.0 27.1
FD 1 FC 4 22.8 FC 4
FS FC 4 FM 3 24.4
FS FS FM 2 FC 4
25.9
27.8
38.8 36.8 36.9 37.7 35.4 36.1 MC 4 35.6 34.1 30.9 MC 4 MC 4 31.1 30.3 30.4 MC 4 30.5 MC 4
NOT PREGNANT MC 4 MC 4 MC 4 MC 4 27.4 26.4 39.9 40.5 39.6 40.5 35.9 33.6 31.8 MC 4 34.1 MC 4 32.1 33.3 FC 4 28.7 30.3 33.3 FC 4 MC 4 36.7 MC 4 MC 4 36.2 34.7 34.4 34.3 36.0 FC 4 34.2 FC 4 33.4 MC 4 32.2 MC 4 34.8 MC 4 MC 4 34.9 MC 4 34.2 MC 4 MC 4 MC 4 MC 4 33.5 MC 4 MC 4 33.9 29.3 MC 4 MC 4 30.0 31.4 MC 4 MC 4 MC 4 MC 4 33.3 31.7 30..9
FOUND DEAD ON DAY 28 1POSTWEANING 34.5 35.2 MS 31.6 35.2 33.3 MC 4 35.3 35.1 31.5 34.0 FC 4 27.2 MC 4 32.0 MC 4 MC 4 30.1 MC 4 MC 4 32.5 31.1 MC 4 31.6
MC 4 MC 4 31.7 MD 2 29.5 32.1
26.7 28.3 MC 4
32.5 31.2 MC 4 33.1 34.0 34.4 34.1 29.9 31.8
FC 4 FC 4 MC 4 33.1 MC 4 35.4 33.3 MC 4 FC 4
FC 4 FC 4 36.9 FC 4 32.5 MC 4 MC 4 28.1 30.3
33.9 FC 4 32.0 31.0
FC 4 34.1 MC 4 30.1
33.6 FC 4 FC 4 29.7
MC 4 29.7
MD 2
FC 4 28.3 MD 1 32.8 FC 4 35.0 FC 4 FC 4 31.6
34.8 FC 4 FC 4 30.2
MC 4 FC 4
26.6
31.5 32.7
MS FC 4 FC 4 FC 4 34.0 28.8 FC 4
FC 4 29.5 30.9
MC 4 FC 4
25.8
32.7 FC 4
MS FC 4 35.1 FC 4 32.8 28.6 FC 4
32.7 FC 4 FC 4
MC 4 28.2
23.8
29.7 FC 4 29.7 31.6 32.7 33.3 30.9 30.3 FC 4
33.3 27.9
FC 4
25.3
FC 4 FC 4 33.9 FC 4 FC 4 FC 4 30.5 FC 4 28.3
32.5 29.4
32.1
FC 4
28.3 FC 4 31.5 30.3 FM 2 31.0
28.5
29.6 FC 4
36.1 FC 4 FC 4
30.3 FC 4
FC 4 33.7 FC 4
FC 4 32.7
32.0
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
20
418-008:PAGE E-85
000675
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 14): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT/ LITTER #
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236
13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
MATERNAL DOSAGE GROUP II
0. 1 MG/KG/DAY
POSTPARTUM DAY 14
MC 4 MC 4 33.9 MC 4 MC 4 29.5
NOT PREGNANT MC 4 MC 4 MC 4 MC 4 27.8 25.8 MC 4 37.8 MC 4 33.3 34.2 34.4 MC 4 MC 4 34.8 MC 4 35.8 MC 4 29.0 31.6 34.4 MC 4 32.1 MC 4 32.9 31.9 35.3 MC 4 37.8 MC 4 MC 4 37.7 36.4 MC 4 30.3 MC 4 MC 4 28.2 27.6 MC 4 35.7 35.9 36.0
NOT PREGNANT NOT PREGNANT NOT PREGNANT 30.8 32.7 32.3 28.6 27.4 MC 4 31.8 MC 4 29.2 MC 4 MC 4 31.2 30.2 MC 4 MC 4
33.6 MC 4
30.1 27.5 36.9 MC 4 33.2 MC 4 MD 2 MC 4
29.8 38.0 MC 4 31.2 MC 4 MC 4
31.3 MD 7 MC 4 30.6 MC 4
32.0 31 .5 MC 4 31. 6
MC 4 MC 4 36.6 MC 4 MC 4 MC 4 MD 1 MC 4
MC 4 MC 4 37. 4 MC 4 MC 4 33. 3 MD 1 MC 4
33.1 37.4 MC 4 31.2 26.7 MC 4
MC 4 MC 4 MC 4 MC 4 29. 8 MC 4
MC 4 MD 6 33.7 31.3 MC 4
FC 4 27 .1 MC 4 31..4 MC 4
MS 35.1
31.7 MC 4 FC 4 33.5 32.7 33.4 31.1 34.2
MC 4 36.1 MC 4 28.0 MC 4 MC 4
30.0 FC 4 29.1 MC 4 MC 4
32.5 31.5
28.8 MC 4 FC 4 32.8 32.9 32.0 31.6 32.1
32.7 FC 4 MC 4 MC 4 MC 4 MC 4
FC 4 FC 4 MC 4 30.9 30.8
33.4 FC 4 FC 4 33.5
31.3 25.6 35.8 FC 4 FC 4
MS 27.8 29.7
21.2 25.8 FC 4 FC 4 32.8
MS 29.2 MC 4
FC 4 37.2 37.4 29.6 MC 4 38.9
31.0 37.8 35.3 28.5 FC 4 36.0
31.7 FC 4 29.7 FC 4 MC 4
FC 4 FC 4 FC 4 FC 4 30.4
33.6 30.9
FC 4 26.2 35.6 34.1 31.8
MS
31.0
FC 4 36.6 38.1 FC 4 FC 4 FC 4
FC 4 FC 4 29.3 FC 4 MC 4
31.9 34.2
28.6 24.1 FC 4 33.6 33.1 32.1
FC 4
FC 4 FC 4 FC 4 30.1 26.2 FC 4
28.5 FC 4 FC 4 FC 4 31.2
31.0
28.3 26.8 FC 4 35.0 FC 4 FC 4
30.8
32.0 FC 4 34.6 FC 4 27.7 FC 4
FC 4 25.6 FC 4 32.4 29.8
29.2
37.7
FC 4 35.3
FC 4
34.1 35.4 35.2 FC 4 23.0 FC 4
FC 4 FC 4 FC 4 30.2 28.5
FC 4
FC 4
FC 4 35.4
FC 4
FC 4 35.1 27.5 FC 4 35.4
31.9 31.5 29.8 30.7 29.8
FC 4 32.0 31.1 FC 4
FC 4 FC 4 23.9 33.1
FD10 29.2 FC 4 27.3
36.0 FM 4 FC 4
36.0
FC 4 FC 4
FS FC 4
FS
FS FC 4
L 32.8
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE E-86 000676
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 15): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
RAT/ LITTER #
MATERNAL DOSAGE GROUP III
0 .4 MG/KG/DAY
POSTPARTUM DAY 14
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
MC 4 36.1 37.6 36.6 MC 4 36.0 MC 4 36.2 30.9 FC 4 FC 4 32.9 36.2 MC 4 MC 4 24.8 MC 4 23.3 27.1 MC 4 25.3 FC 4 FC 4 FC 4 24.6 23.0 24.7 29.1 MC 4 30.6 MC 4 35.5 MC 4 34.3 25.4 FC 4 33.3 FC 4 25.5 FC 4 32.1 21.2 17.0 14.9 MD 4 MM 3 MM 3 16.9 FC 4 FC 4 19.0 11.2 16.3 11.3 FD 4 MC 4 MC 4 MC 4 24.3 MC 4 24.9 26.1 MS MD 5 24.5 FC 4 21.1 24.4 FC 4 37.9 MC 4 34.6 35.5 35.2 MS FC 4 FC 4 33.9 FC 4 FC 4 33.8 34.3 32.3 FOUND DEAD ON DAY 10 OF LACTATION; EIGHT PUPS WERE SACRIFICED ON DAY 10 POSTPARTUM 34.2 MC 4 35.9 MC 4 33.3 33.1 FC 4 33.9 FC 4 FC 4 33.6 FC 4 32.4 FC 4 MC 4 31.2 30.4 MC 4 31.0 MC 4 32.4 MC 4 30.7 MD 1 30.4 29.7 31.0 32.3 MC 4 MC 4 34.0 MC 4 33.4 32.8 MM 2 MD 1 32.7 FC 4 30.4 31.4 FC 4 24.5 25.6 MD 7 MD 6 FC 4 FC 4 FC 4 FC 4 24.5 21.8 24.5 FD 6 FC 4 FC 4 MC 4 MC 4 29.4 30.6 31.8 MM 9 30.3 FC 4 26.9 27.1 FD 5 FS 29.5 MC 4 MC 4 30.3 31.2 30.8 MC 4 MC 4 MC 4 FC 4 27.9 28.2 FC 4 26.0 26.7 30.4 MC 4 29.8 MC 4 MC 4 25.4 28.9 26.4 FC 4 26.9 FC 4 FC 4 FC 4 32.6 31.9 30.9 32.2 33.3 20.6 31.7 26.1 25.8 28.1 MC 4 26.3 MC 4 MM 3 FC 4 FC 4 27.5 FC 4 FC 4 25.2 FC 4 20.1 23.0 23.5 24.1 MC 4 FC 4 FC 4 24.0 18.9 FC 4 22.8 FC 4 FC 4 FC 4 26.6 26.2 MC 4 25.4 MC 4 MC 4 27.S 27.2 27.3 26.7 27.2 FC 4 FC 4 FS MC 4 27.5 MC 4 27.1 MC 4 MC 4 28.4 MC 4 MC 4 29.3 31.3 28.8 26.8 29.3 32.6 MC 4 MC 4 30.4 31.2 MC 4 33.2 29.1 FC 4 FC 4 FC 4 29.2 30.9 31.2 32.7 31.6 31.1 36.5 MS 31.4 32.1 FC 4 32.0 29.7 FC 4 MC 4 35.5 MC 4 MC 4 MC 4 MC 4 40.8 MC 4 39.7 34.8 MC 4 MS MS FC 4 30.9 32.2 32.6 MC 4 32.8 MC 4 MS 32.4 FC 4 31.1 FC 4 FC 4 32.2 FC 4
NOT PREGNANT
27.4 28.2 MC 4 27.2 27.6 MS FC 4 27.1 25.0 26.3 FC 4 FC 4 26.1 FC 4
25.8 FM 2 FM 4 23.3 FM 3
32.4
31.6
27.2 FC 4
25.1 FC 4
FC 4
34.5 30.2
FD 3 FS
FC 4
24.7 FC 4 FC 4
US 40.8 FC 4
FD 3 FS
FC 4
FC 4 23.1
36.4 FC 4
FS FC 4 24.6 33.5
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
20
Ir*v
9
O O O
418-008-.PAGE E-87
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 16) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP tt
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19
RAT/ LITTER U
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 21
13201 13202 13203 13204 13205a 13206 13207 13208 13209 13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221 13222 13223 13224 13225
55.1 MC 4 MC 4 44.8
52.9 53.8 MC 4 MC 4
MC 4 52.4 MC 4 MC 4
MC 4 53.2 38.6 MC 4
MC 4 52.1 MC 4 MC 4
57.1 MC 4 41.3 42.6
55.1 49.4 37.3 44.9
54.8 FC 4 36.4 39.9
FC 4 52.8 39.8 MD 4
51.1 49.3 36.1 MM 2
54.2 50.8 FC 4 FC 4
51.2 FC 4 FC 4 FC 4
FC 4 FC 4 35.9 43.4
FD 1 FC 4 38.1 FC 4
FS FC 4 FM 3 37.7
FS FS FM 2 FC 4
43.0
41.4
60.2 62.7 61.5 59.0 61.2 57.4 MC 4 47.8 52.5 50.6 MC 4 MC 4 50.4 48.4 47.8 MC 4 51.4 MC 4
NOT PREGNANT MC 4 MC 4 MC 4 MC 4 44.7 43.5 58.0 62.0 58.9 58.7 53.2 53.2 51.0 MC 4 52.2 MC 4 55.6 49.0 FC 4 47.1 42.0 48.0 FC 4 MC 4 55.4 MC 4 MC 4 55.0 53.9 53.0 54.9 52.9 FC 4 49.2 FC 4 58.4 MC 4 50.2 MC 4 54.3 MC 4 MC 4 51.2 MC 4 52.7 MC 4 MC 4 MC 4 MC 4 55.0 MC 4 MC 4 53.6 50.5 MC 4 MC 4 51.7 54.0 MC 4 MC 4 MC 4 MC 4 52.8 48.9 48.9
FOUND DEAD ON DAY 28 1POSTWEANING 47.7 50.1 MS 48.1 47.2 51.3 MC 4 52.2 55.0 49.6 55.1 FC 4 51.7 MC 4 52.3 MC 4 MC 4 49.2 MC 4 MC 4 49.4 48.9 MC 4 53.0
MC 4 MD 2
42.3
48.4 41.6 MC 4 54.0 55.8 50.1 56.1 50.6 49.2
48.7 FC 4 48.7 49.1
MC 4 53.0
42.5
FC 4 FC 4 MC 4 50.3 MC 4 53.1 58.5 MC 4 FC 4
FC 4 51.1 MC 4 48.0
47.4 50.0
MC 4
FC 4 FC 4 52.9 FC 4 52.6 MC 4 MC 4 50.5 51.5
51.0 FC 4 FC 4 47.9
MC 4 MC 4 46.4 FC 4
MD 2 41.6
FC 4 43.9 MD 1 52.0 FC 4 51.5 FC 4 FC 4 51.2
53.9 46.1
MS FC 4 FC 4 FC 4 56.2 48.2 FC 4
43.7 FC 4 FC 4 45.9
FC 4 48.9 47.1
MC 4 MC 4 FC 4 46.5
38.2 42.4
52.2 FC 4
MS FC 4 55.3 FC 4 51.1 52.9 FC 4
51.1 FC 4 44.2 48.0 52.9 44.9 53.7 49.9 FC 4
50.8 51.2 FC 4 47.1 FC 4
FC 4
42.9
FC 4 FC 4 47.2 FC 4 FC 4 FC 4 49.5 FC 4 44.6
48.1 47.1
44.2
FC 4
46.4 FC 4 58.8 51.1 FM 2 48.1
46.4
48.5 FC 4
54.9 FC 4 FC 4
47.3 FC 4
FC 4 54.3 FC 4
FC 4 49.3
47.0
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
20
418-008:PAGE E-88
000678
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 17) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP tt
1
2
3
4
5
7
8
9 10 11 12 13 14 15 16 17 18 19 20
21 22 23
RAT/ LITTER #
MATERNAL DOSAGE GROUP II
0 .1 MG/KG/DAY
POSTPARTUM DAY 21
13226 13227 13228 13229 13230 13231 13232 13233 13234 1323S 13236
13237 13238 13239 13240 13241 13242 13243 13244 13245 13246 13247 13248 13249 13250
MC 4 MC 4 52.6 MC 4 MC 4 49.2
NOT PREGNANT MC 4 MC 4 MC 4 MC 4 39.8 37.3 MC 4 58.6 MC 4 53.3 55.9 54.3 MC 4 MC 4 51.3 MC 4 54.2 MC 4 51.3 53.2 45.8 MC 4 50.6 MC 4 44.4 49.9 53.6 MC 4 59.4 MC 4 MC 4 54.4 57.4 MC 4 41.9 MC 4 MC 4 45.4 43.8 MC 4 54.3 53.4 59.2
NOT PREGNANT NOT PREGNANT NOT PREGNANT 51.1 50.0 51.3 46.0 44.5 MC 4 42.8 MC 4 46.9 MC 4 MC 4 44.4 46.2 MC 4 MC 4
52.5 MC 4
47.8 38.7 58.1 MC 4 50.2 MC 4 MD 2 MC 4
57.6 58.0 MC 4 47.0 MC 4 MC 4
49.0 MD 7 MC 4 44.8 MC 4
52.5 MC 4
MC 4 MC 4 58.0 MC 4 MC 4 MC 4 MD 1 MC 4
49.1 55.6 MC 4 49.5 40.5 MC 4
MC 4 MD 6 44.3 43.4 MC 4
50. 1 51 .0
MC 4 MC 4 53 .5 MC 4 MC 4 53 .4 MD 1 MC 4
MC 4 MC 4 MC 4 MC 4 41. 6 MC 4
FC 4 49. 5 MC 4 42 .7 MC 4
MS 54.6
46.7 MC 4 FC 4 54.0 49.7 51.0 48.9 46.7
MC 4 56.1 MC 4 46.3 MC 4 MC 4
46.3 FC 4 46.2 MC 4 MC 4
55.7 51.3
45.7 MC 4 FC 4 55.4 49.9 57.5 46.7 46.2
54.2 FC 4 MC 4 MC 4 MC 4 MC 4
FC 4 FC 4 MC 4 45.8 47.0
54.0 FC 4 52.6 FC 4 54.6 50.3
48.2 40.9 51.7 FC 4 FC 4
MS 52.3 44.1
33.8 37.0 FC 4 FC 4 47.6
MS 43.8 MC 4
FC 4 39.6 53.8 53.8 51.4
MS
44.4
FC 4 55.4 56.6 41.9 MC 4 57.3
52.2 58.0 54.8 44.3 FC 4 52.3
FC 4 57.3 59.3 FC 4 FC 4 FC 4
48.4 FC 4 43.9 FC 4 MC 4
FC 4 FC 4 FC 4 FC 4 45.2
FC 4 FC 4 43.1 FC 4 MC 4
51.0 54.4
44.4 40.4 FC 4 52.8 47.3 49.7
FC 4
FC 4 FC 4 FC 4 49.5 42.7 FC 4
50.4 FC 4 FC 4 FC 4 47.4
51.6
45.7 39.3 FC 4 52.7 FC 4 FC 4
47.2
49.5 FC 4 52.9 FC 4 49.5 FC 4
FC 4 43.3 FC 4 43.1 42.7
45.0
54.2
FC 4 56.4
FC 4
51.4 54.9 54.4 FC 4 47.0 FC 4
FC 4 FC 4 FC 4 43.0 42.8
FC 4
FC 4
FC 4 50.6
FC 4
FC 4 51.8 46.8 FC 4 54.8
47.7 43.6 43.8 42.2 43.2
FC 4 46.9 52.8 FC 4
FC 4 FC 4 44.8 53.4
FD10 42.2 FC 4 43.4
57.1 FM 4 FC 4
57.4
FC 4 FC 4
FS FC 4
FS
FS FC 4
49.4
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE E-89
000679
PROTOCOL 416 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E37 (PAGE 18) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA F2 GENERATION PUPS
PUP # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
RAT/ LITTER tt
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
POSTPARTUM DAY 21
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274 13275
MC 4 63.7 S9.6 60.2 MC 4 57.5 MC 4 46.9 50.9 FC 4 FC 4 55.7 59.6 MC 4 MC 4 39.5 MC 4 36.7 41.2 MC 4 38.5 FC 4 FC 4 FC 4 37.3 38.4 36.7 53.2 MC 4 53.8 MC 4 48.7 MC 4 46.0 53.2 FC 4 41.2 FC 4 51.1 FC 4 39.5 39.3 32.0 34.0 MD 4 MM 3 MM 3 32.2 FC 4 FC 4 32.9 27.5 35.8 25.9 FD 4 MC 4 MC 4 MC 4 43.3 MC 4 41.4 43.3 MS MD 5 42.5 FC 4 42.8 42.2 FC 4 53.9 MC 4 54.9 56.3 59.3 MS FC 4 FC 4 51.7 FC 4 FC 4 54.8 51.8 54.2 FOUND DEAD ON DAY 10 OF LACTATION; EIGHT PUPS WERE SACRIFICED ON DAY 10 POSTPARTUM 55.2 MC 4 54.9 MC 4 55.0 58.9 FC 4 53.7 FC 4 FC 4 49.5 FC 4 53.5 FC 4 MC 4 51.7 52.7 MC 4 49.4 MC 4 53.1 MC 4 50.7 MD 1 50.1 50.1 50.6 51.4 MC 4 MC 4 52.0 MC 4 49.3 51.5 MM 2 MD 1 47.9 FC 4 48.0 46.6 FC 4 41.6 43.0 MD 7 MD 6 FC 4 FC 4 FC 4 FC 4 40.6 40.2 37.9 FD 6 FC 4 PC 4 MC 4 MC 4 49.7 53.3 49.3 MM 9 46.7 FC 4 48.1 51.0 FD 5 FS 47.0 MC 4 MC 4 48.0 46.2 47.1 MC 4 MC 4 MC 4 FC 4 43.2 43.0 FC 4 40.7 44.2 39.5 MC 4 46.6 MC 4 MC 4 46.1 41.7 44.5 FC 4 42.8 FC 4 FC 4 FC 4 48.1 44.8 47.0 45.2 46.3 44.0 31.0 44.9 41.0 43.7 MC 4 44.2 MC 4 MM 3 FC 4 FC 4 40.2 FC 4 FC 4 40.4 FC 4 35.4 40.3 40.6 39.7 MC 4 FC 4 FC 4 39.9 38.9 FC 4 41.7 FC 4 FC 4 FC 4 44.0 45.4 MC 4 40.8 MC 4 MC 4 41.9 42.1 39.2 43.2 42.7 FC 4 FC 4 FS MC 4 48.0 MC 4 46.1 MC 4 MC 4 45.1 MC 4 MC 4 45.2 49.3 46.8 42.2 48.5 48.3 MC 4 MC 4 53.2 50.8 MC 4 49.0 45.9 FC 4 FC 4 FC 4 52.2 48.7 47.9 55.0 49.0 49.2 61.1 MS 51.0 48.6 FC 4 49.5 49.4 FC 4 MC 4 63.1 MC 4 MC 4 MC 4 MC 4 62.5 MC 4 55.0 S5.3 MC 4 MS MS FC 4 49.8 47.5 50.5 MC 4 49.7 MC 4 MS 50.8 FC 4 46.0 FC 4 FC 4 44.8 FC 4
NOT PREGNANT
43.4 42.9 MC 4 42.6 43.7 MS FC 4 41.5 41.9 41.5 FC 4 FC 4 41.0 FC 4
39.4 FM 2 FM 4 38.7 FM 3
53.3
49.8
43.6 FC 4
42.6 FC 4
FC 4
51.7 49.9
FD 3 FS
FC 4
44.6 FC 4 FC 4
US 62.3 FC 4
FD 3 FS
FC 4
FC 4 35.2
52.9 FC 4
FS FC 4 41.5 54.6
ALL WEIGHTS WERE RECORDED IN GRAMS (G). FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
19
20
418-008:PAGE E-90
ooosso
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY. DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E38 (PAGE 1) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
PUP ft 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT/ LITTER #
MATERNAL DOSAGE GROUP I
0 (VEHICLE) MG/KG/DAY
13201 M A M A MC 4 MC 4 MC 4 M A M A F A FC 4 F A F A F A FC 4 FD 1 F S F S 13202 MC 4 M A M A M A M A MC 4 F A FC 4 F A F A F A FC 4 FC 4 FC 4 FC 4 F S 13203 MC 4 MC 4 MC 4 M A MC 4 M A M A M A F A F A FC 4 FC 4 F A F A FM 3 FM 2 13204 M A MC 4 MC 4 MC 4 MC 4 M A M A M A MD 4 MM 2 FC 4 FC 4 F A FC 4 F A FC 4 F A F A 13205a
13206 M A M A M A F A F A F A 13207 MC 4 M A M A M A MC 4 MC 4 MC 4 MC 4 M A MC 4 MC 4 MC 4 MC 4 FC 4 F A F A F A FC 4 13208 M A M A M A MC 4 M A MC 4 MD 2 F A F A F A FC 4 FC 4 F A 13209 NOT PREGNANT 13210 MC 4 MC 4 MC 4 MC 4 M A M A M A M A MC 4 MD 2 F A F A F A F A FC 4 FC 4 FC 4 13211 M A M A M A F A F A 13212 M A M A MC 4 M A MC 4 M A F A FC 4 FC 4 FC 4 F A F A F A FC 4 13213 M A FC 4 F A F A F A FC 4 F A FC 4 FC 4 F A F A FC 4 FC 4 FC 4 F A 13214 MC 4 M A MC 4 MC 4 M A M A MC 4 MC 4 M A MD 1 M s M S F A F A FC 4 F A FC 4 F A 13215 M A M A M A FC 4 F A FC 4 F A F A FC 4 F A FC 4 FC 4 F A FC 4 13216 M A MC 4 M A MC 4 M A MC 4 M A MC 4 F A FC 4 FC 4 F A F A FC 4 F A 13217 MC 4 M A MC 4 M A MC 4 MC 4 M A M A MC 4 F A FC 4 FC 4 F A FC 4 F A FC 4 F A 13218 MC 4 MC 4 M A MC 4 MC 4 M A M A M A MC 4 FC 4 F A F A F A F A 13219 M A MC 4 MC 4 M A M A MC 4 M A MC 4 F A FC 4 F A F A F A FC 4 FM 2 13220 MC 4 MC 4 MC 4 M A M A M A M A FC 4 F A F A FC 4 FC 4 FC 4 F A F A FC 4 FC 4 13221 FOUND DEAD ON DAY 28 !POSTWEANING
13222 M A M A M S F A F A F A F A FC 4 F A F A 13223 MC 4 M A M A M A M A FC 4 FC 4 F A FC 4 FC 4 FC 4 F A F A F A 13224 M A MC 4 M A MC 4 MC 4 M A M A MC 4 FC 4 FC 4 F A FC 4 F A F A F A 13225 MC 4 MC 4 M A M A MC 4 M A M A F A F A F A F A FC 4
FA
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
418-008PAGE E-91
TS3000
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E38 (PAGE 2): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA F2 GENERATION PUPS
PUP It 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
RAT/ LITTER #
MATERNAL DOSAGE GROUP II
0.1 MG/KG/DAY
13226 13227 13228 13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243 13244 13245 1?246 13247 13248 13249 13250
MC 4 MC 4 M A M A M A M A M S F A F A FC 4 F A F A
MC 4 MC 4 M A MC 4 MC 4 M A M A M A FC 4 F A F A F A F A NOT PREGNANT
MC 4 MC 4 MC 4 M A MC 4 MC 4 M A M A M A F A FC 4 F A F A F A FC 4 MC 4 M A M A M A MC 4 MC 4 MC 4 MC 4 M A F A F A F A F A MC 4 M A MC 4 M A M A M A FC 4 FC 4 F A FC 4 F A FC 4 FC 4 F A FC 4 FC 4 F A
M A M A M A MC 4 MC 4 MC 4 M A F A FC 4 FC 4 F A F A F A MC 4 MC 4 M A M A MC 4 MC 4 M A M A FC 4 F A F A F A FC 4 FC 4 FC 4 F A MC 4 M A MC 4 MC 4 MC 4 M A M A M A M S M S M S F A FC 4 F A F A F A FM 4 F S F S
M A M A M A MD 2 MD 1 MD 1 F A F A F A F A MC 4 M A MC 4 MC 4 MC 4 MC 4 M A M A M A MC 4 F A FC 4 F A FC 4 FC 4 FC 4 FC 4 FC 4 FC 4
M A M A MC 4 M A M A MC 4 MC 4 F A FC 4 F A FC 4 FC 4 F A F A M A MC 4 MC 4 M A M A MC 4 M A FC 4 F A F A F A FC 4 FC 4 F A FC 4 FC 4 M A M A MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 M A M A F A FC 4 F A F A F A M A MC 4 MC 4 M A M A MC 4 M A MC 4 F A F A FC 4 F A FC 4 FC 4 F A FC 4 M A M A MC 4 MC 4 M A M A MC 4 MC 4 MC 4 FC 4 FC 4 F A F A F A FC 4 F A M A M A M A MC 4 MC 4 MC 4 MC 4 MC 4 M A F A FC 4 FC 4 FC 4 FC 4 F A F A F A
NOT PREGNANT NOT PREGNANT
NOT PREGNANT M A M A M A M A MC 4 FC 4 F A FC 4 F A FC 4 FC 4 F A FC 4 FC 4 F A M A M A MC 4 MD 7 MD 6 F A FC 4 FC 4 FC 4 FC 4 FC 4 FC 4 F A FC 4 F A FD10 M A MC 4 M A MC 4 M A MC 4 M A MC 4 F A FC 4 F A FC 4 FC 4 FC 4 F A F A FC 4 MC 4 MC 4 M A M A M A M A MC 4 F A FC 4 FC 4 FC 4 FC 4 F A F A F A FC 4 M A MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 M A MC 4 M A MC 4 M A F A F A F A F A FC 4
FA
FA
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED) NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
418-008:PAGE E-92
000632
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E38 (PAGE 3) : PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM INDIVIDUAL DATA - F2 GENERATION PUPS
PUP # 1 2
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
RAT/ LITTER ft
MATERNAL DOSAGE GROUP III
0.4 MG/KG/DAY
13251 MC 4 M A M A M A MC 4 M A M C 4 F A F A F C 4 F C 4 F A F A
13252 MC 4 MC 4 M A M C 4 M A M A M C 4 M A F C 4 F C 4 F C 4
FA FA FA FA
13253 M A M C 4 M A MC 4 M A M C 4 M A F A F C 4 F A F C 4 F A F C 4 F A F M 2
13254 M A M A M A MD 4 MM 3 MM 3 F A F C 4 F C 4 F A F A F A F A F D 4 F M 4 F D 3 F D 3
13255 MC 4 MC 4 MC 4 M A MC 4 M A M A M S M D 5 F A F C 4 F A F A F C 4 F A F S F S F S
13256 M A M C 4 M A M A M A M S F C 4 F C 4
FAFC4FC4 FA FAFAFM3
13257a MX10 MC 4 MC 4 MX10 MX10 MX10 FC 4 FC 4 FX10 FC 4 FC 4 FX10 FX10 FX10 FC 4
13258 M A MC 4 M A MC 4 M A M A FC 4 F A FC 4 FC 4 F A FC 4 F A FC 4 F A
13259 MC 4 M A M A MC 4 M A MC 4 M A MC 4 M A MD 1 F A F A F A
13260 M A MC 4 MC 4 M A MC 4 M A M A MM 2 MD 1 F A FC 4 F A F A FC 4 F A FC 4 FC 4 FC 4
13261 M A M A MD 7 MD 6 FC 4 FC 4 FC 4 FC 4 F A F A F A FD 6 FC 4 FC 4
13262 MC 4 MC 4 M A M A M A MM 9 F A FC 4 F A F A FD 5 F S
13263 M A MC 4 MC 4 M A M A M A MC 4 MC 4 MC 4 FC 4 F A F A FC 4 F A F A
13264 M A M A MC 4 M A MC 4 MC 4 M A F A F A FC 4 F A FC 4 FC 4 FC 4 FC 4 F A
13265 M A M A F A F A F A F A F A
13266 M A M A M A MC 4 M A MC 4 MM 3 FC 4 FC 4 F A FC 4 FC 4 F A FC 4 F A FC 4 FC 4 F A
13267 M A M A M A M A MC 4 FC 4 FC 4 F A F A FC 4 F A FC 4 FC 4 FC 4 FC 4 FC 4 F A
13268 M A M A MC 4 M A MC 4 MC 4 M A F A F A F A F A FC 4 FC 4 F S
13269 MC 4 M A MC 4 M A MC 4 MC 4 M A MC 4 MC 4 M A F A F A F A F A
13270 M A MC 4 MC 4 M A M A MC 4 M A F A FC 4 FC 4 FC 4 F A F A F A FC 4 U S
13271 M A M A M A M A M S F A F A FC 4 F A F A FC 4
13272 MC 4 M A MC 4 MC 4 MC 4 MC 4 M A MC 4 M A M A MC 4 M S M S FC 4 F A F A F A F A
13273 M A M A M A MC 4 M A MC 4 M S F A FC 4 F A FC 4 FC 4 P A FC 4 F A FC 4 FC 4
13274 NOT PREGNANT
13275 M A M A MC 4 M A M A M S FC 4 F A F A F A FC 4 FC 4 F A FC 4
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE SECOND LETTER -- A-ALIVE, S-STILLBORN, U-UNCERTAIN, D-DIED, C-CULLED, M-MISSING (PRESUMED CANNIBALIZED), X-SACRIFICED NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED. a. Dam 13257 was found dead on day 10 of lactation; eight pups were sacrificed on day 10 postpartum.
23
418-0Q8:PAGE E-93
000683
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E39 (PAGE 1): CLINICAL OBSERVATIONS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
I 0 (VEHICLE)
13208
1 1/13 PUPS: COLD TO TOUCH, DECREASED MOTOR ACTIVITY, NOT NESTING OR NURSING.
13211
1-21
1/ 5 PUPS: TIP OF TAIL MISSING.b
II 0.1 -
'
III
0.4
13251
7-21
1/ 8 PUPS: UMBILICAL HERNIA.b
13258
21 1/ 8 PUPS: TIP OF TAIL MISSING.b
a. Tabulation restricted to adverse observations; all other pups appeared normal. b. Observation confirmed at necropsy.
418-008:PAGE E-94
000684
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E40 (PAGE 1): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
I 0 (VEHICLE)
13201
1 4,21
2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13202
1 4 21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL. 1 PUP: BRAIN, HYDROCEPHALY, EXTREME DILATION OF ALL VENTRICLES. ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS APPEARED NORMAL.
13203
4,21
ALL PUPS APPEARED NORMAL.
13204
4 21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL OTHER PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13206 13207
21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13208
2 4.21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13210
2 4,21
1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13211 13212 13213
21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13214
1 4,21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
2 PUPS: STILLBORN. ALL PUPS APPEARED NORMAL.
13215
4,21
ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table E39) for external clinical observations confirmed at necropsy.
418-008PAGE E-95
000685
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E40 (PAGE 2) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
I (Cont.) 0 (VEHICLE)
13216 13217 13218 13219 13220
4,21 4,21 4,21 4.21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13222
1 4,21
1 PUP: STILLBORN ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13223 13224 13225
4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table E39) for external clinical observations confirmed at necropsy.
418-008:PAGE E-96
000686
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POST NATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E40 (PAGE 3) : NECROPSY OBSERVATIONS - INDIVIDUAL DATA F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
13226
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13221 13229 13230 13231 13232 13233
4,21 4,21 4,21 4,21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13234
1 4,21
5 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL ALL PUPS APPEARED NORMAL.
13235
1
2 21
2 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
1 PUP: FOUND DEAD. ALL PUPS APPEARED NORMAL
13236 13237 13238 13239 13240 13241 13242 13246
4, 21 4,21 4,21 4,21 4,21 4,21 4,21 4,21
ALL PUPS APPEARED NORMAL ALL PUPS APPEARED NORMAL ALL PUPS APPEARED NORMAL ALL PUPS APPEARED NORMAL ALL PUPS APPEARED NORMAL ALL PUPS APPEARED NORMAL ALL PUPS APPEARED NORMAL ALL PUPS APPEARED NORMAL
13247
4 6 7
10
21
ALL PUPS APPEARED NORMAL 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. 1 PUP: LIVER, MEDIAN AND LEFT LATERAL LOBES, TAN
RAISED AREAS (0.1 CM X 0.1 CM AND 0.5 CM X 0.5 CM). ALL OTHER TISSUES APPEARED NORMAL. ALL OTHER PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table E39) for external clinical observations confirmed at necropsy.
418-008:PAGE E-97
89000
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E40 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
II (Cont.) 0.1
13248
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13249 13250
4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table E39) for external clinical observations confirmed at necropsy.
(
418-008:PAGE E-98
000688
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E40 (PAGE 5): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
III
0.4
13251
4,21
ALL PUPS APPEARED NORMAL.
13252
4,21
ALL PUPS APPEARED NORMAL.
13253
4,21
ALL PUPS APPEARED NORMAL.
13254
3 4 21
2 PUPS: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
2 PUPS: FOUND DEAD. ALL OTHER PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13255
1 4 5 21
4 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL. 1 PUP: FOUND DEAD. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13256
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13257b 13258
4,10 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13259
1 4,21
1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL OTHER TISSUES APPEARED NORMAL.
ALL PUPS APPEARED NORMAL.
13260
1 4,21
1 PUP: FOUND DEAD. ALL PUPS APPEARED NORMAL.
13261
4 6 7
21
ALL PUPS APPEARED NORMAL. 2 PUPS: FOUND DEAD. ALL TISSUES APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH.
ALL OTHER TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table E39) for external clinical observations confirmed at necropsy.
b. Dam 13257 was found dead on day 10 of lactation; eight pups were sacrificed on day 10 postpartum.
418-008:PAGE E-99
000S9
PROTOCOL 418 008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
TABLE E40 (PAGE 6); NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PUPS
MATERNAL DOSAGE GROUP MATERNAL DOSAGE (MG/KG/DAY)
LITTER NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
III (Cont.) 0.4
13262
1 4 5 21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL. 1 PUP: FOUND DEAD. NO MILK IN STOMACH. ALL PUPS APPEARED NORMAL.
13263 13264 13265 13266 13267
4.21 4,21
21 4,21 4,21
ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13268
1 4.21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13269
4,21
ALL PUPS APPEARED NORMAL.
13270
1 4.21
1 PUP: STILLBORN. ALL PUPS APPEARED NORMAL.
13271
1 4.21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13272
1 4.21
2 PUPS: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13273
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
13275
1 4,21
1 PUP: STILLBORN. ALL TISSUES APPEARED NORMAL. ALL PUPS APPEARED NORMAL.
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. Refer to the individual pup clinical observations table (Table E39) for external clinical observations confirmed at necropsy.
418-008:PAGE E-100
000690
APPENDIX F PROTOCOL AND AMENDMENTS
000691
418-008:PAGE F-1
A r g u s R esearch Laboratories, Inc. 905 Sheehy Drive, Bu ilding A
Horsham, Pennsylvania 19044 T: (215)443-8710 F: (215)443-8587
PROTOCOL 418-008
SPONSOR'S STUDY NUMBER: 6295.9
STUDY TITLE:
Combined Oral (Gavage) Fertility, Developmental and Perinatal/Postnatal Reproduction Toxicity Study of PFOS in Rats.
PURPOSE:
The purpose of this study is to test for toxic effects/ disturbances resulting from PFOS treatment of Crl:CDBR VAF/Plus male and female rats before cohabitation through mating, gestation and lactation. This study evaluates ICH Harmonised Tripartite Guideline stages A through F of the reproductive process and should detect effects on the estrous cycle, tubal transport, implantation, gestation, parturition, lactation and maternal behavior in female rats, on the development of the offspring of the treated male and female rats, and permit detection of functional effects (e.g., effects on libido or epididymal sperm maturation) that may not be detected by histological examinations of male rat reproductive organs. Because manifestations of effects induced during this period may be delayed in the offspring, observations will be continued through production of F2 generation litters.
TESTING FACILITY:
Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A Horsham, Pennsylvania 19044-1297 Telephone: (215) 443-8710 Telefax: (215)443-8587
STUDY DIRECTOR:
Raymond G. York, Ph.D., DABT Associate Director of Research
SPONSOR:
3M Toxicology Services 3M Center, Building 220-2E-02 St. Paul, Minnesota 55144-1000
000692
/ 418-008.PAGE F-2
Protocol 418-008 Page 2
STUDY MONITOR:
Marvin T. Case, D.V.M., Ph.D. Telephone: (612) 733-5180 Telefax: (612) 733-1773
ALTERNATE STUDY MONITOR:
Andrew M. Seacat, Ph.D. Telephone: (612) 575-3161 Telefax: (612) 733-1773
REGULATORY CITATIONS:
Study Design as Modification of: U.S. Food and Drug Administration (1994). International Conference on Harmonisation; Guideline on detection of toxicity to reproduction for medicinal products. F ederal R egister, September 22, 1994, Vol. 59, No. 183.
U.S. Food and Drug Administration. Good Laboratory Practice Regulations; Final Rule. 21 CFR Part 58.
Japanese Ministry of Health and Welfare (1997). G ood Laboratory P ractice S tandard fo r S afety S tudies on Drugs, MHW Ordinance Number 21, March 26, 1997.
European Economic Community (1989). C ouncil decision on 28 J u ly 1989 on the
acceptance b y the European E conom ic C om m unity o f an O ECD decision/recom -
m endation on com pliance with principles o f goo d la b o ra to ry practice. Official Journal of the European Communities: Legislation. 32 (No. L 315; 28 October): 1-17.
REGULATORY COMPLIANCE:
This study will be conducted in compliance with the Good Laboratory Practice (GLP) regulations cited above.
All changes or revisions of this protocol shall be documented, signed by the Study Director and the Sponsor, dated and maintained with the protocol.
The Quality Assurance Unit (QAU) will audit the protocol, the raw data and the report, and will inspect critical phases of the study in accordance with the Standard Operating Procedures of Argus Research Laboratories, Inc.
The final report will include a statement signed by the Study Director that the report accurately reflects the raw data obtained during the performance of the study and that all applicable GLP regulations were followed in the conduct of the study. Should significant deviations from GLP regulations occur, each will be described in detail, together with how the deviation might affect the quality or integrity of the study.
000693
418-008:PAGE F-3
Protocol 418-008 Page 3
STUDY SCHEDULE:
See ATTACHMENT 1 to the protocol.
TEST ARTICLE AND VEHICLE:
Identification:
Test Article:
Name: Physical Description: Lot/Batch Number: Specific Gravity: Purity: Expiration Date:
PFOS. Light-colored powder. 217.
- 0.6. 98.9%. May, 2000.
Information on the identity, composition, strength and purity of the test article is on file with the Sponsor.
Vehicle:
0.5% Tween 80 in Reversed Osmosis Membrane Processed Deionized Water (R.O. Deionized Water). Supplier and lot identification of Tween 80 to be documented in the raw data.
Neither the Sponsor nor the Study Director is aware of any potential contaminants likely to be present in the vehicle that would interfere with the results of this study. Therefore, no analyses other than those mentioned in this protocol will be conducted.
Safety Precautions:
Gloves, mask, appropriate eye protection and a uniform/lab coat are to be worn during formulation preparation and dosage administration. The Material Safety Data Sheet (MSDS) is attached to the protocol (ATTACHMENT 2).
Storage:
Bulk Test Article: Vehicle Components: Prepared Vehicle: Prepared Formulations:
Room temperature. Room temperature. Room temperature. Frozen (-20C).
All test article shipments to the Testing Facility should be addressed to the attention of Julian Gulbinski, Manager of Formulations, at the previously cited address and telephone number.
000694
418-008:PAGE F-4
Protocol 418-008 Page 4
Shipments should include information concerning storage conditions and shipping cartons should be labeled appropriately. The recipient should be notified in advance of shipment. FORMULATION: Frequency of Preparation: Formulations (suspensions) will be prepared daily at the Testing Facility. Detailed preparation procedures are attached to this protocol (ATTACHMENT 3). Adjustment for Purity: The test article will be considered 100% pure for the purpose of dosage calculations. Testing Facility Reserve Samples: The Sponsor will reserve a sample (1 g) of each lot of the bulk test article used during the course of this study. The Testing Facility will reserve a sample (5 mL) of each lot of the vehicle components used during the course of this study. Samples will be stored under the previously cited conditions. ANALYSES: Samples additional to those described below may be taken if deemed necessary during the course of the study. Bulk Test Article Sampling: No analyses of the bulk test article will be conducted during the course of this study. Information on the stability of the bulk test article is on file with the Sponsor. Analyses of Prepared Formulations: Stability: Stability data for prepared formulations bracketing the range of concentrations and conditions of this study are on file with the Sponsor and will not be determined during the conduct of this study. Suspensions will be prepared daily at the Testing Facility.
000695
418-008:PAGE F-5
Protocol 418-008 Page 5
Homogeneity Analyses:
Homogeneity of the test article in prepared suspensions will be verified during the course of this study. A syringe will be used to withdraw samples (5 mL each) from the top, middle and bottom of the highest concentration on the first day of preparation. Each sample (5 mL) will be divided into two aliquots, one of 2 mL and one of 3 mL. One aliquot (2 mL) will be shipped for analysis; the other aliquot (3 mL) will be retained at the Testing Facility as a backup sample. Backup samples will be stored under the previously cited conditions and discarded at the Testing Facility upon the request of the Sponsor.
Concentration Analyses:
Concentration of the prepared test article suspensions will be verified during the course of this study. A syringe will be used to withdraw samples (5 mL each) from each concentration during the first and sixth week of dosage administration. Each sample (5 mL each) will be divided into two aliquots, one of 2 mL and one of 3 mL. One aliquot (2 mL) will be shipped for analysis; the other aliquot (3 mL) will be retained at the Testing Facility as a backup sample. Backup samples will be stored under the previously cited conditions and discarded at the Testing Facility upon the request of the Sponsor.
Shipping Instructions:
Samples to be analyzed will be shipped (frozen on dry ice) to:
Kris J. Hansen, Ph.D. 3M Environmental Technology and Safety Services 935 Bush Avenue Building 2-3E-09 St. Paul, Minnesota 55133-3331 Telephone: (612) 778-6018 Telefax: (612)778-6176
Both the recipient and the Study Monitor will be notified in advance of sample shipment.
DISPOSITION:
Prepared formulations will be discarded at the Testing Facility. All remaining bulk test article will be returned to the Study Monitor at the previously cited address.
000696
418-008:PAGE F-6
Protocol 418-008 Page 6
TEST SYSTEM:
Soecies/Strain and Reason for Selection:
The Crl:CDBR VAF/Plus (Sprague-Dawiey) rat was selected as the Test System because: 1) this strain of rat has been demonstrated to be sensitive to reproductive and developmental toxins and has been widely used throughout industry for reproductive and developmental toxicity evaluations; 2) historical data and experience exist at the Testing Facility0'3'; and 3) the test article is pharmacologically active in the species and strain.
Number:
Initial population acclimated: 195 virgin male and 205 virgin female rats. Population selected for study: 175 male rats (35 per dosage group) and 175 female
rats (35 per dosage group).
Ten mated female rats will be assigned to Caesarean-sectioning on day 10 of presumed gestation; the remaining female rats will be permitted to deliver litters.
250 F1 generation pups (25 per sex per dosage group) will be selected at weaning on day 21 postpartum for continued postnatal observation.
Body Weight and Aae:
Male rats will be ordered to weigh from 300 g to 325 g each at receipt, at which time they will be expected to be at least 60 days of age. Female rats will be ordered to weigh from 200 g to 225 g each at receipt, at which time they will be expected to be at least 60 days of age. Actual body weights will be recorded the day after receipt and will be documented in the raw data. The weight ranges will be included in the final report.
Sex:
Both Fo and F1 generation male and female rats will be evaluated. Only Fo generation male and female rats will be given the test article.
Source:
Charles River Laboratories, Inc., Raleigh, North Carolina.
The rats will be shipped in filtered cartons by air freight and/or truck from Charles River Laboratories, Inc., to the Testing Facility.
000G97
418-008:PAGE F-7
Protocol 418-008 Page 7
Identification:
Fo Generation:
Rats are permanently identified using Monel self-piercing ear tags (Gey Band and Tag Co., Inc., No. MSPT 20101). Male and female rats are assigned temporary numbers at receipt and given unique permanent identification numbers when assigned to the study before administration of the first dosage of the test article.
F1/F2 Generations:
Pups will not be individually identified during lactation; all parameters will be evaluated in terms of the litter. At weaning, each rat selected for continued observation will be identified with a Monel self-piercing ear tag.
ANIMAL HUSBANDRY:
All cage sizes and housing conditions are in compliance with the G uide fo r the Care and Use o f Lab orato ry A nim als(4).
Housing.
Fo Generation Rats/F1 Generation Litters:
Fo generation rats will be individually housed in stainless steel wire-bottomed cages except during the cohabitation and postpartum periods. During cohabitation, each pair of rats will be housed in the male rat's cage. Beginning no later than day 20 of presumed gestation, Fo generation female rats assigned to natural delivery will be individually housed in nesting boxes. Each dam and delivered litter will be housed in a common nesting box during the postpartum period.
F1 Generation Rats/F2 Generation Litters:
After weaning, the F1 generation rats will be individually housed before cohabitation, housed in pairs (one male rat per female rat) during cohabitation, and individually housed after cohabitation. The same type of caging will be used as described for the Fo generation rats. Beginning no later than day 20 of presumed gestation, F1 generation female rats will be individually housed in nesting boxes. Each dam and delivered litter will be housed in a common nesting box during the postpartum period.
000698
418-008: PAGE F-8
Protocol 418-008 Page 8
Nesting Material:
Bedding material (bed-o'cobs) will be supplied to female rats assigned to natural delivery.
Bedding will be changed as often as necessary to keep the animals dry and clean. Analyses for possible contamination are conducted annually and documented in the raw data.
Room Air. Temperature and Humidity:
The animal room is independently supplied with at least ten changes per hour of 100% fresh air that has been passed through 99.97% HEPA filters (Airo Clean room). Room temperature will be maintained at 64F (18C) to 79F (26C) and monitored constantly. Room humidity will also be monitored constantly and maintained at 30% to 70%.
L ig h t:
An automatically controlled 12-hour light:12-hour dark fluorescent light cycle will be maintained. Each dark period will begin at 1900 hours EST.
Diet:
Rats will be given Certified Rodent Diet #5002 (PMI Nutrition International) available ad libitum from individual feeders.
Water:
Water will be available ad libitum from individual bottles attached to the cages or from an automatic watering access system. All water will be from a local source and passed through a reverse osmosis membrane before use. Chlorine will be added to the processed water as a bacteriostat; processed water is expected to contain no more than 1.2 ppm chlorine at the time of analysis. Water is analyzed monthly for possible bacterial contamination and twice annually for possible chemical contamination.
Contaminants:
Neither the Sponsor nor the Study Director is aware of any potential contaminants likely to be present in the certified diet, the drinking water or the nesting material at levels that would interfere with the results of this study. Therefore, no analyses other than those routinely performed by the feed supplier or those mentioned in this protocol will be conducted.
000699
418-008PAGE F-9
Protocol 418-008 Page 9
RANDOMIZATION AND COHABITATION:
Fo Generation:
Upon arrival, rats will be assigned to individual housing on the basis of computergenerated random units. After acclimation, male and female rats will be selected for study on the basis of physical appearance and body weights recorded during acclimation. The rats will be assigned to dosage groups based on computer-generated (weight-ordered) randomization procedures.
Within each dosage group, consecutive order will be used to assign rats to cohabitation, one male rat per female rat. The cohabitation period will consist of a maximum of 14 days. Female rats with spermatozoa observed in a smear of the vaginal contents and/or a copulatory plug observed in situ will be considered to be at day 0 of presumed gestation and assigned to individual housing. Female rats not mated within the first 7 days of cohabitation will be assigned alternate male rats that have mated (same dosage group) and will remain in cohabitation for a maximum of seven additional days.
The first ten female rats per dosage group with a confirmed date of mating will be assigned to Caesarean-sectioning on day 10 of presumed gestation. The remaining female rats will be permitted to naturally deliver litters.
A table of random units will be used to assign five rats per group to a pharmacokinetic sample collection at scheduled sacrifice after completion of the cohabitation period (male rats siring litters with dams allowed to naturally deliver a litter) or on day 21 postpartum (female rats allowed to naturally deliver litters).
F1/F2 G eneration Puds:
Day 1 of lactation (postpartum) is defined as the day of birth and is also the first day on which all pups in a litter are individually weighed (pup body weights will be recorded after all pups in a litter are delivered and groomed by the dam).
On day 4 postpartum, a table of random units will be used to select pups to be culled, and litters will be reduced to eight pups each. Whenever possible, the same number of male and female pups per litter will be continued on study.
At weaning of the F1 generation pups on day 21 postpartum, a table of random units will be used to select 25 male and 25 female pups per group, resulting in a total of 250 F1 generation rats (125 per sex) chosen for continued evaluation. At least one male pup and one female pup per litter, when possible, will be selected.
000700
418-008:PAGE F-10
Protocol 418-008 Page 10
ADMINISTRATION: Route and Reason for Choice:
The oral (gavage) route was selected for use because: 1) in comparison with the dietary route, the exact dosage can be accurately administered; and 2) it is one of the possible routes of human exposure.
Method and Frequency:
Dosages will be adjusted for the most recently recorded body weight and given at approximately the same time each day. Fo Generation Male Rats:
Male rats will be given the test article once daily beginning 28 days before cohabitation (maximum 14 days) and continuing through the day before sacrifice. Male rats will be sacrificed after completion of the cohabitation period. Fo Generation Female Rats:
Female rats will be given the test article once daily beginning 28 days before cohabitation (maximum of 14 days) and continuing through day 9 of presumed gestation (rats assigned to Caesarean-sectioning), day 24 of presumed gestation (rats assigned to natural delivery that do not deliver a litter) or day 20 postpartum (rats that deliver a litter). F1 Generation:
F1 generation pups will not be directly given the test article, but may be possibly exposed to the test article during maternal gestation (in utero exposure) or via maternal milk during the lactation period.
Rationale for Dosage Selection:
Dosages will be selected by the Sponsor on the basis of previous studies conducted with the test article.
000701
418-008PAGE F-11
Dosage Levels. Concentrations and Volumes:
Protocol 418-008 Page 11
Number
Dosage
Dosage of Rats Dosage
Volume
Group Per Sex (mg/kg/day) Concentration (mg/mL) (mUkg)
Argus Batch Number
I 35 0 (Vehicle)
II 35
0.1
III 35
0.4
IV 35
1.6
35 3.2
0 0.02 0.05 0.32 0.64
5 B-416-008-A(Day.Month.Year) 5 B-416-008-B(Day.Month.Year) 5 B-418-008-C(Day.Month.Year) 5 B-418-006-D(Day.Month.Year) 5 B-418-008-E(Day.Month.Year)
The test article will be considered 100% pure for the purpose of dosage calculations.
TESTS. ANALYSES AND MEASUREMENTS - Fo GENERATION:
Viability - Male and Female Rats:
All Periods:
At least twice daily.
Clinical Observations and/or General Appearance - Male and Female Rats:
Acclimation Period:
At least once.
Dosage Period:
Twice daily. Prior to dosage administration and once approximately one hour postdosage.
Maternal Behavior:
Days 1,4, 7, 14 and 21 postpartum. Any observed abnormal behavior will be recorded daily.
Clinical observations may be recorded more frequently than cited above, if deemed appropriate by the Study Director and/or Study Monitor.
Body Weights - Male Rats:
Acclimation Period:
At least once.
Dosage Period:
Weekly.
Sacrifice:
Terminal weight.
000702
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Protocol 418-008 Page 12
Body Weights - Female Rats:
Acclimation Period:
At least once.
Dosage Period:
Weekly to cohabitation. Daily during presumed gestation and on Days 1, 4, 7 and 14 postpartum (rats assigned to natural delivery).
Sacrifice:
Terminal weight.
Feed Consumption Values - Male Rats (recorded and tabulated):
Dosage Period:
Weekly.
Feed Consumption Values - Female Rats (recorded and tabulated):
Dosage Period:
Weekly to cohabitation. Daily during presumed gestation. Days 1,4, 7 and 14 postpartum (rats assigned to natural delivery).
Feed consumption not tabulated after day 14 postpartum, when it is expected that pups will begin to consume maternal feed.
Feed Consumption Values - Male and Female Rats:
Feed consumption values may be recorded more frequently than cited above if it is necessary to replenish the feed. During cohabitation, when two rats occupy the same cage with one feed jar, replenishment of the feed jars will be documented. Individual values will not be recorded or tabulated.
Estrous Cycling and Mating:
A table of random units will be used to select 15 female rats per group for evaluation of estrous cycling by examination of vaginal cytology for 14 days before the start of the cohabitation period.
During cohabitation, all female rats will be evaluated daily until spermatozoa are observed in a smear of the vaginal contents and/or a copulatory plug is observed
in situ.
Duration o f Gestation:
The duration of gestation is calculated from day 0 of presumed gestation to the day the first pup is observed.
000703
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Protocol 418-008 Page 13
Fertility Parameters;
Fertility Index (percentage of matings that result in pregnancies).
Gestation Index (percentage of pregnancies that result in birth of live litters).
Number of offspring per litter (live and dead pups).
Number of implantation sites.
General condition of dam and litter during the postpartum period.
Viability Indices (percentage of pups bom that survive 4 and 7 days).
Lactation Index (percentage of pups bom that survive 21 days).
Caesarean-Sectioning Observations:
Rats will be Caesarean-sectioned on day 10 of presumed gestation. Placentae that appear abnormal (size, color or shape) will be noted in the raw data. The rats will be examined for number and distribution of:
Corpora Lutea.
Implantation Sites.
Viable and Nonviable Embryos. (A viable embryo is oval or crescent shaped, pink, firm and enclosed in an amniotic sac filled with clear fluid. A nonviable embryo is amorphous, small, pale pink to tan or deep red to black, soft and enclosed in an amniotic sac filled with clear, cloudy, or opaque fluid.)
Natural Delivery:
Female rats will be evaluated for:
Clinical Observations During Parturition.
Duration of Gestation (day 0 of presumed gestation to the time the first pup is observed).
Length of Parturition (time of delivery of last pup minus the time of delivery of the first pup divided by N-1 pups in each litter).
Litter Size (defined as all pups delivered).
000704
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Protocol 418-008 Page 14
Pup Viability at Birth.
METHOD OF SACRIFICE - Fo GENERATION:
Rats will be sacrificed by carbon dioxide asphyxiation. Embryos will be discarded after examination.
NECROPSY - Fo GENERATION:
Gross lesions will be retained in neutral buffered 10% formalin for possible future evaluation (a table of random units will be used to select one control group rat of each sex from which all tissues examined at necropsy will be retained, in order to provide control tissues for any possible histopathological evaluations of gross lesions). Unless specifically cited below, all other tissues will be discarded.
Male and Female Rats Assigned to Pharmacokinetic Sample Collection:
At scheduled sacrifice after completion of the cohabitation period (male rats siring litters with dams allowed to naturally deliver a litter) and on day 21 postpartum (female rats allowed to naturally deliver a litter), five rats per group will be assigned to a pharmacokinetic sample collection. In addition to the appropriate evaluations described below, blood samples (approximately 4 mL per rat) will be collected from the inferior vena cava into serum separator tubes and centrifuged. The resulting serum (approximately 2 mL) will be immediately frozen on dry ice and maintained frozen (-70 C) until shipment to the Sponsor for analysis. The liver will be excised, weighed, and a sample section (lateral lobe) will be frozen and retained at -70C until shipment to the Sponsor for analysis.
After completion of sample collection, serum and liver section (lateral lobe) samples wilt be shipped (frozen on dry ice) to Kris J. Hansen, Ph.D., at the previously cited address for analysis. Both the recipient and the Study Monitor will be notified in advance of sample shipment.
Scheduled Sacrifice of Male Rats:
After completion of the cohabitation period, male rats will be sacrificed and a gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. The following organs will be excised and weighed and retained for possible histologic evaluation: testes, epididymides, prostate and seminal vesicles (weighed with and without fluid). The testes will be fixed in Bouin's solution for 48 to 96 hours and then retained in neutral buffered 10% formalin for possible histopathological evaluation. The remaining organs will be retained in neutral buffered 10% formalin.
000705
418-008: PAGE F-15
Protocol 418-008 P age 15
Scheduled Sacrifice - Female Rats Assigned to Caesarean-Sectioning:
On day 10 of presumed gestation, female rats will be sacrificed, Caesarean-sectioned, and a gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. Uteri of apparently nonpregnant rats will be stained with 10% ammonium sulfide to confirm the absence of implantation sites15'. Uteri of nonpregnant rats and all ovaries will be retained in neutral buffered 10% formalin for possible future evaluation.
Scheduled Sacrifice - Female Rats Assigned to Natural Delivery:
Rats that do not deliver a litter will be sacrificed on day 25 of presumed gestation and examined for gross lesions. Uteri will be stained with 10% ammonium sulfide to confirm the absence of implantation sites'5'.
After completion of the 21-day postpartum period, female rats will be sacrificed, and a gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. The number and distribution of implantation sites will be recorded.
Dams w ith No Surviving Pups:
Dams with no surviving pups will be sacrificed after the last pup is found dead, missing or presumed cannibalized. A gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. Postpartum data for these dams will be excluded from summary tables.
Rats Found Dead or Moribund:
Rats that die or are sacrificed because of moribund condition or abortion will be examined for the cause of death or moribund condition on the day the observation is made. The rats will be examined for gross lesions. Testes, epididymides, prostate and seminal vesicles of male rats will be excised and individual organ weights will be recorded (seminal vesicles weighed with and without fluid). The testes will be fixed in Bouin's solution for 48 to 96 hours and then retained in neutral buffered 10% formalin. The remaining organs will be retained in neutral buffered 10% formalin. Pregnancy status and uterine contents of female rats will be recorded. Aborted fetuses and/or delivered pups will be examined to the extent possible. Ovaries will be retained in neutral buffered 10% formalin. Uteri of apparently nonpregnant rats will be stained with 10% ammonium sulfide to confirm the absence of implantation sites'5'.
000706
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_ Protocol 418-008 Page 16
TESTS. ANALYSES AND MEASUREMENTS - F1 GENERATION:
Viability:
Preweaning Period:
Litters will be observed for dead pups at least twice daily. The pups in each litter will be counted once daily.
Postweaning Period:
Twice daily.
Clinical Observations and/or Generai Appearance:
Preweaning Period:
Once daily.
Postweaning Period:
Once weekly.
Maternal Behavior:
Days 1, 4, 7, 14 and 21 postpartum. Any observed abnormal behavior will be recorded daily.
Clinical observations may be recorded more frequently than cited above, if deemed appropriate by the Study Director and/or the Study Monitor.
Body Weights:
Preweaning Period:
Days 1 (birth), 4, 7, 14 and 21 postpartum.
Postweaning Period:
Weekly.
Presumed Gestation Period: Days 0, 7, 10, 14, 17 and 20 (female rats only).
Lactation Period:
Days 1, 4, 7, 10 and 14 (female rats only).
Sacrifice:
Terminal weight.
Feed Consumption Values (recorded and tabulated):
Preweaning Period:
Not recorded.
Postweaning Period:
Weekly except during cohabitation.
Presumed Gestation Period: Days 0, 7, 10, 14, 17 and 20 (female rats only).
Lactation Period:
Days 1, 4, 7, 10 and 14 (female rats only).
000707
/ 418-008:PAGE F-17
Protocol 418-008 Page 17
Feed consumption values may be recorded more frequently if it is necessary to replenish the feed. During cohabitation, when two rats occupy the same cage with one feed jar, values will be documented when feed jars are filled. These intervals will not be tabulated.
Preweanina Developmental Observations:
The number of pups meeting the criterion is recorded on each day of testing. Testing continues until the day the criterion is attained by all pups in the litter.
Surface Righting Reflex (ability to right in 5 seconds): From day 1 postpartum.
Pinna Unfolding: From day 2 postpartum.
Eye Opening: From day 12 postpartum.
Acoustic Startle Response: From day 13 postpartum.
Air Righting Reflex: From day 14 postpartum.
Pupil constriction is evaluated once, on day 21 postpartum.
Postweanina Developmental Observations:
Sexual Maturation:
Female rats will be evaluated for the age of vaginal patency, beginning on day 28 postpartum. Male rats will be evaluated for the age of preputial separation, beginning on day 39 postpartum.
Passive Avoidance Testing:
Beginning at 24 1 day postpartum, one male rat and one female rat from each litter, where possible, will be evaluated in a passive avoidance test for learning, short-term retention and long-term retention.
The passive avoidance apparatus consists of a two-compartment chamber with hinged Plexiglas lids. One compartment is fitted with a bright light and Plexiglas floor. The other compartment is fitted with a grid floor to which a brief (1 sec) pulse of mild electric current (1 mA) can be delivered. The two compartments are separated by a sliding door. On each test trial, the rat is placed into the "bright" compartment, the sliding door is opened and the light is turned on. The rat is allowed to explore the apparatus until it enters the "dark" compartment. The sliding door is then immediately dosed, the light is turned off and the brief pulse of current is delivered to the grid floor. The rat is then removed from the apparatus and placed into a holding cage for 30 seconds before the start of the next trial. Trials are repeated until the rat remains in the "bright"
000708
418-008:PAGE F-18
Protocol 418-008 P age 18
compartment for 60 seconds on two consecutive trials (the criterion for learning) or until 15 trials have been completed. The latency to enter the dark compartment or the maximum 60-second interval is recorded for each trial.
Each rat is tested twice. The test sessions are separated by a one-week interval, and the criterion is the same for both days of testing.
Dosage groups are compared for the following dependent measures:
The number of trials to the criterion in the first session-this measure will be used to compare groups for overall learning performance.
The latency (in seconds) to enter the "dark" compartment from the "bright" compartment on trial 1 in the first test session-this measure will be used to compare groups for activity levels and exploratory tendencies in a novel environment.
The latency (in seconds) to enter the "dark" compartment from the "bright" compartment on trial 2 in the first test session-this measure will be used to compare groups for short-term retention.
The number of trials to the criterion in the second test session-this measure will be used to compare groups for long-term retention.
The latency (in seconds) to enter the "dark" compartment from the "bright" compartment on trial 1 in the second session-this value is another indication of long-term retention.
Watermaze Testing:
Beginning at approximately 70 days postpartum, one male rat and one female rat from each litter will be evaluated in a water-filled M-maze for overt coordination, swimming ability, learning and memory.
Each rat is tested in a watertight 16-gauge stainless steel modified M-maze. The maze is filled with water to a depth of approximately nine inches, and the water is monitored for temperature (range of 21 C 1C).
On each test trial, the rat will be placed into the starting position (base of the M-maze stem farthest from the two arms) and required to swim to one of the two goals of the M-maze, in order to be removed from the water. On the first trial, the rat is required to enter both arms of the maze before being removed from the water. The initial arm chosen on trial 1 is designated the incorrect goal during the remaining trials. Rats that fail to make a correct goal choice within 60 seconds in any given trial are guided to the correct goal and are then removed from the water. A 15-second intertrial interval will separate each trial. Each rat is required to reach a criterion of five consecutive errorless trials to terminate the test session. The maximum number of trials in any test
000709
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Protocol 418-008 Page 19
session is 15. Latency (measured in seconds) to choose the correct goal or the maximum 60-second interval is recorded for each trial, as is the number of errors (incorrect turns in the maze) during each trial.
Each rat is tested twice. The test sessions are separated by a one-week interval, and the correct goal and the criterion are the same for both test sessions.
Dosage groups are compared for the following dependent measures:
The number of trials to criterion on the first day of testing-this measure will be used to compare groups for overall learning performance.
The average number of errors (incorrect turns in the maze) for each trial on the first day of testing-this measure will also be used to compare groups for overall learning performance.
The latency (in seconds) to reach the correct goal on trial 2 of the first day of testing-this measure will be used to compare groups for short-term retention.
The number of trials to criterion on the second day of testing-this measure will be used to compare groups for long-term retention.
The average number of errors for each trial on the second day of testing-this measure will also be used to compare groups for long-term retention.
The latency (in seconds) to reach the correct goal on trial 1 of day 2 of testing-this is another indicator of long-term retention.
Reproductive Capacity:
At approximately 90 days of age, the F1 generation rats within each dosage group will be assigned to cohabitation, one male rat per female rat, based on computer-generated random units or random unit tables, with the exclusion of sibling matings. The cohabitation period will consist of a maximum of 14 days. Female rats with spermatozoa observed in a smear of the vaginal contents and/or a copulatory plug observed in situ will be considered to be at day 0 of presumed gestation and assigned to individual housing. Female rats that do not mate within the first 7 days of cohabitation will be assigned alternate male rats from the same dosage group that have mated. Female rats will be allowed to naturally deliver and maintain litters through a 21-day postpartum period.
Mating Performance:
As cited above for Fo generation rats.
000710
418-008.PAGE F-20
Protocol 418-008 Page 20
Duration of Gestation:
As cited above for Fo generation rats.
Fertility Parameters:
As cited above for Fo generation rats.
F2 Generation Litter Data:
Viability, clinical observations and body weights for F2 generation pups will be recorded as cited above for F1 generation litters.
METHOD OF SACRIFICE - F1 GENERATION RATS/F2 GENERATION PUPS:
As previously cited for Fo generation rats.
NECROPSY - F1 GENERATION RATS:
Gross lesions will be retained in neutral buffered 10% formalin for possible future evaluation (a table of random units will be used to select one control group rat of each sex from which all tissues examined at necropsy will be retained, in order to provide control tissues for any possible histopathological evaluations of gross lesions). Unless specifically cited below, all other tissues will be discarded.
Scheduled Sacrifice - F1 Generation Male Rats:
Rats will be sacrificed after completion of the 14-day cohabitation period. A gross necropsy of the thoracic, abdominal and pelvic visceral will be performed. Testes and epididymides of male rats will be excised and individual organ weights will be recorded. The epididymides will be retained in neutral buffered 10% formalin. The testes will be fixed in Bouin's solution for 48 to 96 hours and then retained in neutral buffered 10% formalin.
Scheduled Sacrifice - F1 Generation Female Rats:
Female rats will be sacrificed after completion of the 21-day postpartum period. The number and distribution of implantation sites will be recorded. Rats that do not deliver a litter will be sacrificed on day 25 of presumed gestation and uteri will be stained with 10% ammonium sulfide to confirm the absence of implantation sites(5). A gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. Female rats without a confirmed mating date that do not deliver a litter will be sacrificed on an estimated day 25 of presumed gestation.
000711
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Protocol 418-008 Page 21
F1 Generation Rats Found Dead or Moribund:
Rats that die or are sacrificed because of moribund condition or abortion will be examined for the cause of death or moribund condition on the day the observation is made. The rats will be examined for gross lesions. Testes, epididymides, prostate and seminal vesicles of male rats will be excised and individual organ weights will be recorded (seminal vesicles weighed with and without fluid). The testes will be fixed in Bouin's solution for 48 to 96 hours and then retained in neutral buffered 10% formalin. The remaining organs will be retained in neutral buffered 10% formalin. Pregnancy status and uterine contents of female rats will be recorded. Aborted fetuses and/or delivered pups will be examined to the extent possible. Ovaries will be retained in neutral buffered 10% formalin. Uteri of apparently nonpregnant rats will be stained with 10% ammonium sulfide to confirm the absence of implantation sites<5).
F1 Generation Dams with No Surviving Puds:
Dams with no surviving pups will be sacrificed after the last pup is found dead, missing or presumed cannibalized. A gross necropsy of the thoracic, abdominal and pelvic viscera will be performed. Postpartum data for these dams will be excluded from summary tables.
F1/F2 Generation Pups Found Dead on Day 1 Postpartum:
Pups that die before examination of the litter for pup viability will be evaluated for vital status at birth. The lungs will be removed and immersed in water. Pups with lungs that sink will be identified as stillborn; pups with lungs that float will be identified as livebom, and to have died shortly after birth. Pups with gross lesions will be preserved in Bouin's solution for possible future evaluation. Should postmortem autolysis preclude these evaluations, it will be noted in the necropsy data.
F1/F2 Generation Pups Found Dead or Moribund on Davs 2to 21 Postpartum:
Pups found dead or sacrificed due to moribund condition will be examined for gross lesions and for the cause of the moribund condition or death. Pups with gross lesions found on days 2 to 4 postpartum will be preserved in Bouin's solution for possible future evaluation; gross lesions of pups found on days 5 to 21 postpartum will be preserved in neutral buffered 10% formalin. Should postmortem autolysis preclude these evaluations it will be noted in the necropsy data.
000712
418-008PAG E F-22
Protocol 418-008 Page 22
F1/F2 Generation Pups Not Selected for Continued Observation:
F1 and F2 generation pups culled on day 4 postpartum will be sacrificed and examined for gross lesions; pups with gross lesions will be preserved in Bouin's solution. Necropsy will include a single cross-section of the head at the level of the frontal-parietal suture and examination of the cross-sectioned brain for apparent hydrocephaly. All F1 generation pups culled on day 21 postpartum will be sacrificed and examined for gross lesions; gross lesions will be preserved in neutral buffered 10% formalin. Necropsy will include a single cross-section of the head at the level of the frontal-parietal suture and examination of the cross-sectioned brain for apparent hydrocephaly.
Scheduled Sacrifice - F2 Generation Puds:
On day 21 postpartum, pups will be sacrificed and examined for gross lesions. Necropsy will include a single cross-section of the head at the level of the frontal-parietal suture and examination of the cross-sectioned brain for apparent hydrocephaly.
000713
418-008:PAGE F-23
Protocol 418-008 Page 23
PROPOSED STATISTICAL METHODS*6-12:
Averages and percentages will be calculated. Litter values will be used where appropriate. Additional procedures and/or analyses may be performed, if appropriate.
Type of Test*
I. Parametric6
II. Nonparametricc
A. Bartlett's Test6
A. Kruskal-Wallis Test (s;75% ties)
Significant at ps0.05 Not Significant
Significant at p *0.05 Not Significant
Nonparametric
Analysis of Variance
Dunn's Test
Significant at psiO.05
Not Significant B. Fisher's Exact Test (>75% ties)
Dunnett's Test
II- Test for Proportion Data
Variance Test for Homogeneity of the Binomial Distribution
a. Statistically significant probabilities are reported as either p<;0.05 or psO.01. b. Used only to analyze data with homogeneity of variance. c. Proportion data are not included in this category. d. Test for homogeneity of variance.
000714
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Protocol 418-008 Page 24
DATA ACQUISITION. VERIFICATION AND STORAGE:
Data will be hand- and/or computer-recorded. Records will be reviewed by the Study Director and/or appropriate management personnel within 21 days after generation. All original records will be stored in the archives of the Testing Facility. All original data will be bound and indexed. A copy of all raw data will be supplied to the Sponsor upon request. Preserved tissues will be stored at the Testing Facility at no charge for one year after mailing of the draft final report, after which time the Sponsor will be contacted to determine the disposition of these materials.
RECORDS TO BE MAINTAINED:
Protocol and Amendments. Test Article, Vehicle and/or Reagent Receipt, Preparation and Use. Animal Acquisition. Randomization Schedules. Mating History. Treatment (if prescribed by Staff Veterinarian). General Comments. Clinical Observations and/or General Appearance. Blood Sample Collection, Processing and Shipment. Body Weights. Feed Consumption Values. Caesarean-Sectioning Observations. Natural Delivery Observations. Litter Observations. Reflex and Physical Development and Behavioral Observations - F1 Generation Pups. Gross Necropsy Observations. Organ Weights (if required). Photographs (if required). Study Maintenance (room and environmental records). Feed, Water and Bedding Analyses. Packing and/or Shipment Lists.
KEY PERSONNEL:
Executive Director of Research: Mildred S. Christian, Ph.D., ATS Director of Research: Alan M. Hoberman, Ph.D., DABT Associate Director of Research and Study Director: Raymond G. York, Ph.D., DABT Director of Laboratory Operations: John F. Barnett, B.S. Manager of Study Coordination: Valerie A. Sharper, M.S. Manager of Animal Operations and Member, Institutional Animal Care and Use Committee: Dena C. Lebo, V.M.D. Manager of Regulatory Compliance: Kathleen A. Moran, M.S. Consultant, Veterinary Pathology: W. Ray Brown, D.V.M., Ph.D., ACVP
000715
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Protocol 418-008 Page 25
FINAL REPORT:
A comprehensive draft final report will be prepared on completion of the study and will be finalized following consultation with the Sponsor. The report will include the following:
Summary and Conclusion. Experimental Design and Method. Evaluation of Test Results. Appendices: Figures, Summary and Individual Tables Summarizing the Above Data, Protocol and Associated Amendments and Deviations, Study Director's GLP Compliance Statement, Reports of Supporting Data (if appropriate) and QAU Statement.
INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE STATEMENT:
The procedures described in this protocol have been reviewed by the Testing Facility's Institutional Animal Care and Use Committee. All procedures described in this protocol that involve study animals will be conducted in a manner to avoid or minimize discomfort, distress or pain to the animals. The Sponsor's signature below documents the fact that information concerning the necessity for conducting this study and the fact that this is not an unnecessarily duplicative study may be obtained from the Sponsor. No alternative (in vitro) procedures were available for meeting the stated purposes of the study.
000716
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Protocol 418-008 Page 26
REFERENCES:
1. Christian, M.S. and Voytek, P.E. (1982). In Vivo R eproductive and M utagenicity Tests. Environmental Protection Agency, Washington, D.C. National Technical Information Service, U.S. Department of Commerce, Springfield, VA 22161.
2. Christian, M.S. (1984). Reproductive toxicity and teratology evaluations of naltrexone (Proceedings of Naltrexone Symposium, New York Academy of Sciences, November 7, 1983), J. Clin. Psychiat. 45(9):7-10.
3. Lang, P.L. (1988). Em bryo and F etal D evelopm ental T oxicity (Teratology) C ontrol D ata in the C harles R ive r Cr1:CDBR R a t Charles River Laboratories, Inc., Wilmington, MA 01887-0630. (Data base provided by Argus Research Laboratories, Inc.)
4. Institute of Laboratory Animal Resources (1996). G uide fo r the Care and Use o f Laboratory Anim als. National Academy Press, Washington, D.C.
5. Salewski, E. (1964). Firbemethode zum makroskopischen Nachweis von Implantationsstellen am Uterus der Ratte. Arch. Pathol. Exp. Pharmakol. 247:367.
6. Snedecor, G.W. and Cochran, W.G. (1967). Variance test for homogeneity of the binomial distribution. S tatistical M ethods, 6th Edition, Iowa State University Press, Ames, pp. 240-241.
7. Sokal, R.R. and Rohlf, F.J. (1969). Bartlett's test of homogeneity of variances. Biom etry, W.H. Freeman and Co., San Francisco, pp. 370-371.
8. Snedecor, G.W. and Cochran, W.G. (1967). Analysis of Variance. S tatistical M ethods, 6th Edition, Iowa State University Press, Ames, pp. 258-275.
9. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc. 50:1096-1129.
10. Sokal, R.R. and Rohlf, F.J. (1969). Kruskal-Wallis Test. Biom etry, W.H. Freeman and Co., San Francisco, pp. 388-389.
11. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6(3):241-252.
12. Siegel, S. (1956). N onparam etric S tatistics fo r the B e h a vio ra l Sciences, McGraw-Hill, New York, pp. 96-104.
000717
PROTOCOL APPROVAL: FOR THE TESTING FACILITY
George E. Dearlove, Associate Director of Research
418-008PAGE F-27
Protocol 418-008 Page 27
212 A >* / } --
&
.
Date
Z , / - *lrH[ -Vjr Date
J 2 LA t W O i .
irbara J. Patte B.A. Chairperson, Institi ional Animal Care and Use Committee
Date
FOR THE SPONSOR
Marvin T. Case, D.V.M., Ph.D. Study Monitor
2a Aw i cL 3 .r
Date
OGO'
^}
418-008:PAGE F-28
ATTACHMENT 1 STUDY SCHEDULE
000719
ATTACHMENT 1
418-008PAGE F-29
Protocol 418-008 Page 1 of 2
SCHEDULE'
12 MAY 98 26 MAY 98
26 MAY 98-15 JUL 98
26 MAY 98 -19 AUG 98
09 JUN 98 - 22 JUN 98 22 JUN 98 PM - 29 JUN 98 AM 29 JUN 98 PM - 06 JUL 98 AM
23 JUN 98 06 JUL 98 20 JUL 98
Animal Receipt - Acclimation Begins (Fo generation rats).
Start of Dosage Period - Fo Generation Male Rats (28 days before cohabitation and continuing through a 14-day cohabitation period until sacrifice after successful mating has been determined).
Dosage Period - Female Rats Assigned to Caesarean-Sectioning (28 days before cohabitation and continuing through day 09 of presumed gestation). Dosage Period - Female Rats Assigned to Natural Delivery [28 days before cohabitation through day 24 of presumed gestation (rats that do not deliver a litter) or day 20 postpartum (rats that deliver a litter)].
Dosage Period Estrous Cycle Evaluation.
Cohabitation Period (Maximum of 14 days). Male 1 (07 days) Male 2 (07 days)
First Possible Day 0 of Presumed Gestation. Last Possible Day 0 of Presumed Gestation.
Fo Generation Male Rats Sacrificed after Completion of the Cohabitation Period (Earliest possible date).
a. The study initiation date is the day the Study Director signs the protocol.
000720
ATTACHMENT 1
418-008:PAGE F-30
Protocol 418-008 Page 2 of 2
03 JUL 98 16 JUL 98 14 JUL 98 31 JUL 98 18JUL 98 31 JUL 98 03 AUG 98 20 AUG 98 04 AUG 98 19 OCT 98-02 NOV 98
16 NOV 98
10 NOV 98-27 NOV 98 30 NOV 98-17 DEC 98
06 APR 99
First Possible Day 10 of Presumed Gestation Caesarean-sectioning. Last Possible Day 10 of Presumed Gestation Caesarean-section ing.
First Possible Delivery (Day 21 of presumed gestation). Last Possible Delivery (Day 25 of presumed gestation).
First Possible Day 25 of Presumed Gestation Female Sacrifice. Last Possible Day 25 of Presumed Gestation Female Sacrifice.
First Possible Day 21 Weaning (Dams and F1 generation pups not selected for continued observation sacrificed). Last Possible Day 21 Weaning.
F1 Generation Postweaning Observations Begin (Details of tests cited in protocol).
F1 Generation Cohabitation Period (Initiated when rats are approximately 90 days of age approximate initial date).
F1 Generation Male Rats Sacrificed after Completion of Cohabitation Period Approximate Earliest Possible Date.
Delivery Period - F1 Generation Dams/F2 Generation Litters (Approximate dates).
Sacrifice of F1 Generation Dams and F2 Generation Litters on Day 21 Postpartum (Approximate dates).
Draft Final Report.
000721
418-008: PAGE F-31
ATTACHMENT 2 MATERIAL SAFETY DATA SHEET
000722
418-008: PAGE F-32
M ATERIAL SAFETY DATA SHEET
3M 3M C e n te r S t . P a u l, M in n e sota 55144-1000
1-800-364-3577 o r (612)
737-6501
(24 h o u rs)
C o p y rig h t, 1998, M in n e sota M in in g and M an u factu rin g Coapany. A l l r ig h t s re se rv e d . C opying a n d /o r dow nloading o f t h is . i n f o r a a t i o n f o r th e p u rp o se o f p r o p e r ly u t i l i z i n g 3M p r o d u c ts i s allow ed p ro vid e d th a t: 1) the in f o r a a t io n i s co p ie d in f u l l w ith no ch an ge s u n le s s
p r io r a g re e a e n t i s o b ta in e d f r o a 3M, and 2) n e ith e r the copy nor the o r ig in a l i s re so ld o r otherw ise
d is trib u te d w ith the in te n tio n o f e arn in g a p r o fit thereon.
D I V I S I O N : 3M C H E M IC A L S
TRADE NAME:
F C -9 5 FLUORAD B ran d F lu o r o c h e m ic a l S u r f a c t a n t
ID NUMBER/ U. P .C .:
98-0207-0103-7 00-51135-09054-1 98-0207-0104-5
98-0211-0888-5 00-51135-09362-7 98-0211-3916-1
ZF-0002-1044-1
...
ISSU E D : Jan u ary 29, 1998
SUPERSEDES: November 05, 1997
DOCUMENT: 1 0 -3 7 9 6 -9
00-51135-09055-8 0 0 -5 1 1 3 5 -0 2 3 1 1 -2
1 . INGREDIENT
C . A . S . NO.
PERCENT
P O T A S S IU M PERFLUOROALKYL SU L F O N A T E ........ P O T A S S IU M PERFLUORO ALKYL S U L F O N A T E ........ P O T A S S IU M PERFLUOROALKYL SU L F O N A T E ........ P O T A S S IU M PERFLUOROALKYL SU L F O N A T E ........ P O T A S S IU M PER FLU O RO ALKYL SU L F O N A T E ........
2795-39-3 3871-99-6 29420-49-3 6 0 2 7 0 -5 5 -5 3872-25-1
82 3 3 2 1
- 86 -8 -7 -6 -3
2. PHYSICAL DATA
B O IL IN G P O I N T : .......... VAPOR P R E S S U R E : ........ VAPOR D E N S I T Y : .......... EVAPORATION R A T E :. . . S O L U B IL IT Y IN WATER: SP E C IF IC G R A V IT Y :...
PERCENT V O L A T IL E :. . . P H : ...............................
V I S C O S I T Y : .................. M E L T IN G P O I N T : ..........
N/A N/A N/A N/A slig h t ca. 0 .6 Water1
(B u lk) 0% 7-8
(0.1% Aqueous) N/D N/D
APPEARANCE AND ODOR: L ig h t c o lo re d , fr e e flo w in g powder.
A b b r e v ia tio n s : N/D - Not Determ ined N/A - Not A p p lic a b le CA - A p p ro xim ately O O O V 2 3
USDS: F C -9 5 FLUORAD B rand F lu o r o c h e a ic a l S u r f a c t a n t January 29, 1998
3 . F IR E AND EXPLO SIO N HAZARD DATA
418-008:PAGE F-33
PAGE 2
FLA SH P O I N T : ................................... None
FLAMMABLE L IM IT S -
L E L : .... N /A
FLAMMABLE L IM IT S -
U E L : .... N /A
A U T O IG N IT IO N T E M P E R A T U R E :.......... N /A
EX T IN G U ISH IN G M EDIA: M ater, Carbon d io x id e , Dry c h e a ic a l, Foaa
SP E C IA L F IR E FIG H TIN G PROCEDURES: Hear f u l l p ro te ctiv e c lo th in g , in c lu d in g h elae t, se lf-c o n ta in e d , p o s i t iv e p r e s su r e o r p r e s s u r e demand b r e a th in g a p p a r a tu s, bunker and p a n ts, bands around a n as, w a ist and le g s , fa c e mask, and p ro te c tiv e co v e rin g fo r exposed are as o f the head.
coat
UNUSUAL F IR E AND EXPLOSION HAZARDS: See Hazardous D ecom position se c tio n f o r p ro d u cts o f com bustion.
4 . R EA C T IV IT Y DATA
ST A B IL IT Y : S ta b le
IN C O M P A T IB IL IT Y - M A T E R IA L S /C O N D IT IO N S TO A V O ID : Not a p p lica b le .
HAZARDOUS POLYMERIZATION: H azardo u s p o ly m e r iz a tio n w i l l not o c c u r.
HAZARDOUS DECOMPOSITION PRODUCTS: Carbon M onoxide and Carbon D io x id e , O xid e s o f S u lfu r , Hydrogen F lu o rid e , T oxic V apors, Gases or P a r tic u la te s .
5. ENVIRONMENTAL INFORMATION
S P IL L RESPONSE: O bserve p re c a u tio n s from o th e r s e c t io n s . Vacuum, use wet sw eeping compound o r w a te r to a v o id d u s t in g . CAUTION! A vacuum c le a n e r c o u ld be an i g n i t io n so u rc e . C le a n up re s id u e w ith w ate r. P la c e in an approved m etal co n ta in e r. S e a l the co n ta in e r.
RECOMMENDED D ISP O SA L: Do not r e le a se to w aterw ays o r sew er. Do n o t use in p ro d u c ts or p ro ce sse s th a t cou ld r e s u lt in a q u a tic c o n c e n tra tio n s gre a te r than 1/10 o f the lo w e st EC50 o r LC50 c o n c e n tr a tio n . In c in e r a te in an in d u s t r ia l o r com m ercial f a c i l i t y in the presence o f a co m b u stib le m a te ria l. Com bustion p ro d u cts w i l l in c lu d e HF. D is p o s a l a lt e r n a t iv e : D isp o se o f w aste product in a f a c i l i t y perm itted to
A b b r e v ia t io n s : N/D - Not D eterm ined N /A - Not A p p lic a b le CA - A p p ro x im a te ly
000724
HSDS: F C -9 5 FLUORAD Brand F lu o r o c h e m ic a l S u r f a c t a n t January 29, 1998
5. ENVIRONMENTAL INFORMATION (continued)
418-008:PAGE F-34
PAGE 3
accept c h e n ic a l w aste.
ENVIRONMENTAL DATA: 9 6 -H r. A q u a tic F ish LC50, Fathead M innow (Pim ephales p ro a e la s)= 3 8 mg/1, B l u e g i l l S u n fish (L e p o m is * a c r o c h ir u s )-6 8 a g /1 , Rainbow T r o u t(S a ln o g a i r d n e r i ) - 1 1 m g/1; 4 8 -H r . EC50, D a p h n ia M agna = 50 a g / 1 ; COD=.004 g / g ; B0020 = N il.
REGULATORY INFORMATION: V o la t ile O rga n ic Coapounds: N/A. VOC L e ss H20 & Exempt S o lv e n ts : N/A.
Sin ce re g u la tio n s vary, co n su lt a p p lic a b le re g u la tio n s or a u th o ritie s b e fo re d is p o s a l. U .S. EPA H azardous W aste Number = None (N ot U .S . EPA H azardous).
T h is prod uct com p lie s w ith the ch em ical r e g is t r a t io n requirem ents o f TSCA, EIN EC S, CDSL, A IC S , M IT I and K orea.
EPCRA HAZARD C LA SS: F IR E HAZARD: No PRESSURE: No R E A C T IV IT Y : No ACUTE: Y e s CHRONIC: Y e s
6. SUGGESTED F IR ST A ID
EYE CONTACT: Im m e d ia te ly f l u s h e ye s w ith l a r g e am oun ts o f w a te r f o r a t l e a s t 15 m in u te s. Get im m ediate m e d ical a tte n t io n .
S K IN CONTACT: Im m ed iately f lu s h sk in w ith la rg e am ounts o f w ater. con tam in ated c lo t h in g . I f i r r i t a t i o n p e r s is t s , c a l l con tam in ated c lo t h in g be fore reu se.
Remove a p h y sicia n .
Mash
IN H A L A T IO N : I f sig n s/sy m p to m s o ccu r, remove p e rso n t o f r e s h a ir . I f sign s/sym p tom s con tin u e, c a ll a p h y sic ia n .
IF SWALLOWED: D r in k two g la s s e s o f w a te r. C a l l a p h y s ic ia n .
7. PRECAUTIONARY INFORMATION
EYE PROTECTION: A v o id eye c o n ta c t. Wear vented g o g g le s .
A b b r e v ia t io n s : N /D - Not D eterm ined N /A - Not A p p lic a b le CA - A p p ro x im a te ly
000725
MSOS: F C -9 5 FLUORAO Brand F lu o r o c h e a ic a l S u r f a c t a n t January 29, 1998
418-008: PAGE F-35
PAGE 4
7 . PRECAUTIONARY INFORMATION
(continu ed)
S K IN PROTECTION: A v o id s k in c o n t a c t . H ear a p p r o p r ia t e g lo v e s when h a n d lin g t h i s M a t e r ia l. A p a ir o f g lo v e s Made from th e f o llo w in g M a t e r ia l( s ) are recom aended: b u t y l rubber. Use one o r nore o f th e fo llo w in g p e rso n a l p ro te c tio n ite n s a s n e ce ssa ry to preve n t s k in c o n ta c t: head c o v e rin g , c o v e r a lls . P ro te c tiv e garm ents (o th e r than g lo v e s) should be nade of e it h e r o f the fo llo w in g m a te r ia ls : p o ly e th y le n e /p o ly v in ylid e n e ch lo rid e (Saranex).
RECOMMENDED V EN TILA TIO N : Use w ith a p p ro p ria te lo c a l exhaust v e n t ila t io n . Use in a w e llv e n tila te d are a. Provide s u ff ic ie n t v e n t ila t io n to m ain tain e m is s io n s below recommended e xp osu re l i m i t s . I f e x h a u st v e n t ila t io n i s not adequate, use a p p ro p riate r e s p ir a to r y p ro te c tio n .
RESPIRA TO RY PROTECTION: A v o id b re a th in g o f d u st. S e le c t one o f th e f o llo w in g NIOSH approved r e s p ir a t o r s based on a irb o rn e c o n c e n tr a tio n o f c o n ta m in a n ts and in a c c o rd a n c e w ith OSHA r e g u la t io n s : h a lf-m a s k d u s t and m is t r e s p ir a t o r , h alf-m ask su p p lie d a ir re sp ira to r, f u ll- f a c e dust and m ist re sp ira to r, f u ll- f a c e su p p lie d a ir re sp ira to r.
PREVEN TIO N OF ACCID EN TA L IN G E ST IO N : Do n o t e a t , d r in k o r smoke when u s in g a re a s th o ro u g h ly w ith soap and w ater. before e atin g.
t h is p rod u ct. Nash exposed Nash hands a fte r h an dlin g
and
RECOMMENDED STORAGE: Keep c o n t a in e r d ry . Keep c o n ta in e r c lo s e d when n o t in use.
F IR E AND EXPLOSION AVOIDANCE: Nonflam m able.
OTHER PRECAUTIONARY INFORMATION: No sm o k in g: Sm okin g w h ile u s in g t h i s p ro d u c t can r e s u l t in c o n ta m in a tio n o f th e to b a c c o a n d /o r smoke and le a d to th e fo rm a tio n o f th e h azard ou s d e co m p o sitio n p ro d u c ts m entioned in s e c t io n 4 o f t h is MSDS.
HM IS HAZARD RATIN G S: HEALTH: 2 FLAM M ABILITY: 0 R E A C T IV IT Y : 0 PERSONAL PROTECTION: X (Se e p r e c a u t io n s , s e c t io n 7 .)
EXPOSURE L IM IT S
IN G REDIENT
VALUE UNIT
TYPE AUTH S K IN
PO TA SSIU M PERFLUOROALKYL SU L F O N A T E ... 0.1 MG/ M3 POTASSIUM PERFLUOROALKYL SU LFO N ATE... 0.1 M G/M3 POTASSIUM PERFLUOROALKYL SU LFO N A TE... 0.1 MG/M3 POTASSIUM PERFLUOROALKYL SU LFO N A TE... 0.1 MG/M3
TNA THA TNA TNA
3M 3M 3M 3M
Y Y Y Y
A b b r e v ia t io n s : N/D - Not Determ ined N/A - Not A p p lic a b le CA - A p p ro x im ately
000726
418-008:PAGE F-36
USDS: F C -9 5 FLUORAO Brand F lu o r o c h e a ic a l S u r f a c t a n t January 29, 1998
EXPOSURE L IM IT S
(continu ed)
PAGE 5
IN G REDIENT
VALUE UNIT
TYPE AUTH S K IN *
PO TASSIU M PERFLUOROALKYL SU LF O N A T E ... 0.1 MG/M3
TWA
3M
Y
* S K IN NOTATION: L is t e d s u b s ta n c e s in d ic a t e d w ith 'Y ' un de r S K IN r e f e r to the p o te n tia l c o n trib u tio n to the o v e r a ll exposure by the cutaneous route in c lu d in g nucous eembrane and eye, e it h e r by a irb o rn e o r , more p a r t ic u la r ly , by d ir e c t co n ta ct w ith the su b stan ce . V e h ic le s can a lt e r s k in a b so rp tio n .
SOURCE OF EXPOSURE L IM IT DATA:
- 3M:
3M Recommended E x p o su re G u id e lin e s
8. HEALTH HAZARD DATA
EYE CONTACT: M ild Eye Ir r it a t io n : sign s/sym p tom s can in c lu d e red n e ss, s w e llin g , p ain , and te a rin g .
S K IN CONTACT: M ild S k in Ir r it a t io n (a ft e r prolonged or repeated c o n ta c t): sign s/sym ptom s can in c lu d e redness, sw e llin g , and it c h in g .
May be a b so rb e d th ro u g h th e s k in and p e r s i s t in th e body f o r an extended tim e.
IN H A L A T IO N : May be h a rm fu l i f in h a le d .
May be a b so rb e d by i n h a l a t io n and p e r s i s t in th e body f o r an extended tim e .
S i n g l e o v e re x p o s u re , a bo ve recommended g u i d e l i n e s , may c a u s e :
Ir r it a t io n (upper r e s p ir a t o r y ): sign s/sym p tom s can in c lu d e so re n e ss o f the nose and th ro a t, cou ghin g and sn e e z in g.
I F SWALLOWED: In g e stio n i s not a lik e ly route o f exposure to th is product.
I l l n e s s may r e s u l t fro m a s i n g l e s w a llo w in g o f a m o d e ra te q u a n t i t y o f t h is m a te ria l.
May be h a rm fu l i f sw a llo w e d .
M UTAGENICITY: M u ta g e n ic ity a ssa y s in d ic a te the product i s not m utagenic.
A b b r e v ia t io n s : N/D - Not D eterm ined N/A - Not A p p lic a b le CA - A p p ro x im ate ly
_0 0 7 2 7
USDS: F C -9 5 FLUORAD Brand F lu o ro c h e m ic a l S u r f a c t a n t January 29, 1998
418-008:PAGE F-37
PAGE 6
6 . HEALTH HAZARD DATA
(continu ed)
REPRODUCTIVE/DEVELOPMENTAL T O X IN S: N o t te r a t o g e n ic in the r a t a t o r a l d o se s below a a t e r n a lly t o x ic le v e ls.
OTHER HEALTH HAZARD INFORMATION: T h is p ro d u c t i s n o t known to c o n ta in any su b sta n c e s r e g u la te d under C a lifo r n ia P ro p o sitio n 65.
A P ro du ct T o x ic it y Sunmary Sheet i s a v a ila b le .
SE C T IO N CHANGE DATES
H E A D IN G
SECTIO N CHANGED S IN C E November 05, 1997 IS S U E
A b b r e v ia t io n s : N /D - Not D eterm ined N/A - N ot A p p lic a b le CA - A p p ro x im a te ly
The in fo rm a tio n in t h is M a te r ia l S a fe ty D ata Sh eet (MSDS) i s b e lie ve d to be c o r r e c t a s o f t h e d a t e i s s u e d . 3M MAKES NO W A R R A N T IE S, E X P R E S S E D OR IM P L IE D , IN C L U D IN G , BUT NOT L IM IT E D TO, ANY IM P L IE D WARRANTY OF M E R C H A N T A B IL IT Y OR F IT N E S S FOR A P A R T IC U L A R PURPOSE OR COURSE OF PERFORMANCE OR USAGE OF TR A D E. U s e r i s r e s p o n s i b l e f o r d e t e r m i n i n g w h e th e r th e 3M p r o d u c t i s f i t f o r a p a r t i c u l a r p u rp o se and s u i t a b l e f o r u s e r ` s method o f use o r a p p lic a t io n . G ive n th e v a r ie t y o f f a c t o r s th a t c a n a f f e c t th e u s e and a p p l i c a t i o n o f a 3M p r o d u c t , som e o f w h ic h a r e u n iq u e ly w ith in th e u s e r 's know ledge and c o n t r o l, i t i s e s s e n t ia l th a t t h e u s e r e v a l u a t e t h e 3M p r o d u c t t o d e t e r m in e w h e th e r i t i s f i t f o r a p a r t ic u la r p urp ose and s u it a b le f o r u s e r 's method o f use o r a p p lic a t io n .
3M p r o v id e s i n f o r m a t i o n i n e l e c t r o n i c fo rm a s a s e r v i c e t o i t s c u s t o m e r s . Due t o th e rem ote p o s s i b i l i t y t h a t e le c t r o n ic t r a n s f e r may have r e s u lt e d i n e r r o r s , o m i s s i o n s o r a l t e r a t i o n s i n t h i s i n f o r m a t i o n , 3M m akes no re p re se n ta tio n s a s to i t s com pleteness or a ccu racy . In a d d itio n , in f o r m a t io n o b t a in e d fro m a d a t a b a s e may n o t be a s c u r r e n t a s th e in f o r m a t io n i n th e MSDS a v a il a b l e d i r e c t l y fro m 3M.
000728
418-008:PAGE F-38
ATTACHMENT 3 TEST ARTICLE PREPARATION PROCEDURE
000729
/
418-008:PAGE F-39
ATTACHMENTS
Protocol 418-008
Version: 418-008i2iJdA Y98} Page 1 of 3
TEST ARTICLE PREPARATION PROCEDURE
Test Article:
PFOS.
Vehicle:
0.5% Tween 80 in R.O. Deionized Water.
A. Purpose: The purpose of this procedure is to provide a method for the preparation of dosage suspensions of PFOS and the control article for oral administration to rats on Argus Study 418-008.
B. General Information:
1. All suspension containers will be labeled and color coded. Each label will specify the protocol number, test article identification, Argus batch number, concentration, dosage level, preparation date, expiration date and storage conditions.
2. Suspensions will be prepared:
X Daily
__ Weekly
__For___ days of use
3. Suspensions will be prepared at a final dosage volume of 5 mL/kg.
4. Safety:
X Gloves, lab coat, goggles or safety glasses and faceshield X Dust-Mist Respirator __ Half-Face Respirator __ Full-Face Respirator/Positive Pressure Hood __ Tyvek Suit/Apron
5. Dosage solutions adjusted for Free base and % Purity.
__ Yes
X No (Calculations based on 100%)
___ Free Base __ Purity
6. Sampling requirements: Cited in protocol.
7. Storage: Cited in protocol.
000730
418-008:PAGE F-40
ATTACHMENT 3
Protocol 418-008 Version: 418-008 (21 MAY 98)
Page 2 of 3
TEST ARTICLE PREPARATION PROCEDURE
NOTE:
Test article will be prepared as a serial dilution from the high dosage to the low dosage. Stir bars are to be added to the containers; mixing should occur during sampling and/or dosage administration.
C. Preparation of the Control Group:
1. Add the required amount of vehicle to an appropriate vessel. (See TEST ARTICLE CALCULATIONS for exact quantities.)
D. Test Article Solution Preparation:
1. To prepare the 0.64-mg/mL, (group V) solution, add 160 mg of test article into an appropriately sized, labeled container.
2. Q. S. to 250 mL with the vehicle and mix by inversion.
3. Add a stir bar and heat the preparation to 80 C in a water bath for approximately 30 minutes (or until the test article has dissolved).
4. Remove the solution from the water bath, and slowly spin over night while the solution equilibrates to room temperature.
5. To prepare group IV, (the 0.32-mg/mL solution), add 100 mL of group V solution to an appropriately labeled container, then q.s. to 200 mL with vehicle. Add a stir bar and mix until uniform.
6. To prepare group III, (the 0.08-mg/mL solution), add 50 mL of group IV solution to an appropriately labeled container, then q.s. to 200 mL with vehicle. Add a stir bar and mix until uniform.
000731
418-008:PAGE F-41
ATTACHMENT 3
Protocol 418-008 Version: 418-008 (21 MAY 981
Page 3 of 3
TEST ARTICLE PREPARATION PROCEDURE
7. To prepare group II, (the 0.02-mg/mL solution), add 50 mL of group III solution to an appropriately labeled container, then q.s. to 200 mL with vehicle. Add a stir bar and mix until uniform.
Written by:
Approved b
Date:
_ <)R.C
Clarification: >^N o y Yes (See attached clarification form.)
Initial/Date : R C
000732
418-008: PAGE F ^2
ARGUS
TEST ARTICLE/SUBSTANCE PREPARATION PROCEDURE CLARIFICATION
Protocol : H
VorIon:
( n .* * * .111)
Data of
Preparation
Clarification_____ Stap #__________________________ Clarification
* 't jy s
2 OO ^ , 2 e - f U e h <c ! r / s a d d ec-\
C c n 't ' ) 0 * e.it 10
(/? 7/ / S 'U r
/?/-</ <7
Study Director
Data
Study Diractor
Date
Reviewed by: CD rc ? 7 / ' r / v s
Study Diractor
Date
Data :
1^
08.15.97 TASPPM-01-02
c 00733
418-008:PAGE F-43
A rg u s Research Laboratories, Inc. 905 Sheehy Drive, Building A
H orsham , Pen nsylvan ia 19044 T: (215) 443-8710 F: (215) 443-8587
PROTOCOL 418-008 COMBINED ORAL(GAVAGE) FERTILITY, DEVELOPMENTAL
AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS SPONSOR'S STUDY NUMBER: 6295.9 Amendment 1 - June 2, 1998
1. Storage (page 3 of the protocol): [Effective Date: May 26, 1998] Prepared formulations will be stored at room temperature overnight, rather than frozen. Reason for Change: This change was made to clarify the protocol and facilitate dose formulation preparation.
2. Freouencv of Preparation (page 4 of the protocol): [Effective Date: May 26, 1998] The vehicle (0.5% Tween 80 in R.O. Deionized Water) will be prepared weekly by adding 15 mLs of Tween 80 to 2985 mL of R.O. Deionized Water. Reason for Change: This change was made to clarify the protocol and facilitate dose formulation preparation.
3. Stability (page 4 of the protocol): [Effective Date: May 27, 1998] The Sponsor has confirmed a 48-hour stability on the test article in 0.5% Tween 80 solutions. This allows for preparations to be made one day prior to the day of dose administration. Due to the lengthy
000734
418-008:PAGE F-44
Protocol 418-008 Amendment 1 Page 2
preparation procedure, dose solutions may be made one day prior to the day of dosing.
Reason for Change:
This change was made to clarify the protocol and facilitate dose formulation preparation.
_L 7bsi, -f
Alan M. Hoberman, Ph.D., DABT Date Director of Research
Raymond G. York, Ph.D.,/DABT Associate Director of Research and Study Director
Date
Dena C. Lebo, V.M.D.
Date
Member, Institutional Animal Care
and Use Committee
Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date
000735
418-008:PAGE F-45
A rg u s Research Laboratories, Inc. 90S Sheehy Drive, Building A
Horsham, Pennsylvania 19044 T: (215) 443-8710 F: (215) 443-8587
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS SPONSOR'S STUDY NUMBER: 6295.9 Amendment 2 - June 11, 1998
1. Body Weights - Female Rats (page 12 of the protocol): [Effective Date: May 26, 1998] Body weights and feed consumption values will also be collected on Fo generation females on postpartum day 10. Reason for Change: This information was added to the protocol to match data collection on F1 generation females.
2. Scheduled Sacrifice of Male Rats (page 14 of the protocol): [Effective Date: May 26, 1998] At scheduled sacrifice of Fo male rats, all organs will be weighed individually. Reason for Change: This change clarifies the protocol.
3. Scheduled Sacrifice - Female Rats Assigned to Caesarean-Sectioning (page 15 of the protocol): [Effective Date: May 26, 1998] Uteri of non-pregnant rats will not be retained.
000736
418-008:PAGE F-46
Protocol 418-008 Amendment 2 Page 2
Reason for Change:
This change was made at the request of the Sponsor.
4. Scheduled Sacrifice - F1 Generation Male Rats (page 20 of the protocol):
[Effective Date: May 26, 1998] Seminal vesicles (with and without fluids) and prostates, will be weighed at scheduled sacrifice of all F1 generation male rats.
Reason for Change:
This information was added to the protocol to match data collection on Fo generation males.
Alan M. Hoberman, Ph.D., DABT Date Director of Research
Raymond G. York, Associate Director o and Study Director
, DABT search
Dena C. Lebo, V.M.D.
Date
Member, Institutional Animal Care
and Use Committee
Marvin T. Case, D.V.M., Ph.D. Study Monitor
U t?
Date
000737
418-008.PAGE F-47
A rg u s Research Laboratories, Inc. 905 Sheehy Drive, Building A
Horsham , Pennsylvania 19044 T: (215) 443-8710 F: (215) 443-8587
PROTOCOL 418-008 COMBINED ORAL(GAVAGE) FERTILITY, DEVELOPMENTAL
AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS SPONSOR'S STUDY NUMBER: 6295.9 Amendment 3 - June 25, 1998
1. Administration. Method and Frequency (Page 10 of the protocol): [Effective Date: June 19, 1998] Due to a programming error in dosage calculation the dosage period will be extended for an additional 2 weeks and the cohabitation period will occur two weeks later than originally scheduled. The error in dosage calculations caused the male rats to receive approximately 89% to 90% of the targeted dosage and female rats to receive approximately 95% to 99% of the targeted dosage. This occurred for six of the seven days in the second and third weeks and two days of the fourth week of the dosage period. Reason for Change: This change was made to ensure that all rats receive the correct dosage before cohabitation.
000738
418-008:PAGE F-48
Protocol 418-008 Amendment 3 Page 2
Schedule (Attachment 1 of the protocol):
SCHEDULE
12 MAY 98
Animal Receipt - Acclimation Begins (Fo generation rats).
26 MAY 98
26 MAY 98 - 29 JUL 98
26 MAY 98 - 02 SEP 98
09 JUN 98 - 06 JUL 98 06 JUL 98 PM -13 JUL 98 AM 13 JUL 98 PM - 20 JUL 98 AM
07 JUL 98 20 JUL 98 03 AUG 98
17 JUL 98 30 JUL 98
Start of Dosage Period - Fo Generation Male Rats (42 days before cohabitation and continuing through a 14-day cohabitation period until sacrifice after successful mating has been determined).
Dosage Period - Female Rats Assigned to Caesarean-Sectioning (42 days before cohabitation and continuing through day 09 of presumed gestation).
Dosage Period - Female Rats Assigned to Natural Delivery [42 days before cohabitation through day 24 of presumed gestation (rats that do not deliver a litter) or day 20 postpartum (rats that deliver a litter)].
Dosage Period Estrous Cycle Evaluation.
Cohabitation Period (Maximum of 14 days). Male 1 (07 days) Male 2 (07 days)
First Possible Day 0 of Presumed Gestation. Last Possible Day 0 of Presumed Gestation.
Fo Generation Male Rats Sacrificed after Completion of the Cohabitation Period (Earliest possible date).
First Possible Day 10 of Presumed Gestation Caesarean-section ing. Last Possible Day 10 of Presumed Gestation Caesarean-sectioning.
000739
418-008:PAGE F-49
Protocol 418-008 Amendment 3 Page 3
28 JUL 98 14 AUG 98 01 AUG 98 14 AUG 98 17 AUG 98 03 SEP 98 18 AUG 98 02 NOV 98-16 NOV 98
30 NOV 98
24 NOV 98-11 DEC 98 14 DEC 98 - 31 DEC 98
06 APR 99
First Possible Delivery (Day 21 of presumed gestation). Last Possible Delivery (Day 25 of presumed gestation).
First Possible Day 25 of Presumed Gestation Female Sacrifice. Last Possible Day 25 of Presumed Gestation Female Sacrifice.
First Possible Day 21 Weaning (Dams and F1 generation pups not selected for continued observation sacrificed). Last Possible Day 21 Weaning.
F1 Generation Postweaning Observations Begin (Details of tests cited in protocol).
F1 Generation Cohabitation Period (Initiated when rats are approximately 90 days of age approximate initial date).
F1 Generation Male Rats Sacrificed after Completion of Cohabitation Period Approximate Earliest Possible Date.
Delivery Period - F1 Generation Dams/F2 Generation Litters (Approximate dates).
Sacrifice of F1 Generation Dams and F2 Generation Litters on Day 21 Postpartum (Approximate dates).
Draft Final
000740
418-008:PAGE F-50
Protocol 418-008 Amendment 3 Page 4
Reason for Change:
This schedule was changed due to the extension of the dosing period by two weeks and the cohabitation period occurring two weeks later than scheduled.
Alan M. Hoberman, Ph.D., DABT Date Director of Research
zS -3U v
Raymond G. Y. h.D., DABT Date Associate Directi f Research and Study Director
^ 5 \ J . 9F
Dena C. Lebo, V.M.D.
Date
Member, Institutional Animal Care
and Use Committee
Marvin T. Case, D.V.M., Ph.D. Date Study Monitor
000741
GPrimedica
418-008:PAGE F-51
Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A Horsham, PA 19044 Telephone: (215) 443-8710 Telefax: (215) 443-8587
PROTOCOL 418-008
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS.
SPONSOR'S STUDY NUMBER: 6295.9
Amendment 4 - July 14, 1998
1. Test Article Preparation Procedure (Version 29 JUN 98 of Attachment 3 to the protocol):
[Effective Date: June 29, 1998] The volume of the test article solutions prepared each day will be increased. The new Test Article Preparation Procedure is attached to this amendment.
Reason for Change:
It is necessary to increase the volume of the test article solutions prepared each dajdbecause of the increasing body weights of the rats.
'^/G eorge E. Dearloveyn.D., DABT Date RaymoHd G. York, PH)JJ., DABT
Associate Director of Research
Associate Director of Research
Study Director
(Barbara J. P on, B.A.
Date Marvin T. Case, D.V.M., Ph.D.
Chairperson, titutional Animal Care Study Monitor
and Use Comr ittee
Date
000742
418-008:PAGE F-52
ATTACHMENTS
Protocol 418-008 Version: 418-008 129 JUN 98)
Page 1 of 3
TEST ARTICLE PREPARATION PROCEDURE
Test Article:
PFOS.
Vehicle:
0.5% Tween 80 in R.O. Deionized Water.
A. Purpose: The purpose of this procedure is to provide a method for the preparation of dosage suspensions of PFOS and the control article for oral administration to rats on Argus Study 418-008.
B. General Information:
1. All suspension containers will be labeled and color coded. Each label will specify the protocol number, test article identification, Argus batch number, concentration, dosage level, preparation date, expiration date and storage conditions.
2. Suspensions will be prepared:
X Daily
__ Weekly
__For____days of use
3. Suspensions will be prepared at a final dosage volume of 5 mUkg.
4. Safety: X Gloves, lab coat, goggles or safety glasses and faceshield X Dust-Mist Respirator __ Half-Face Respirator __ Full-Face Respirator/Positive Pressure Hood __ Tyvek Suit/Apron
5. Dosage solutions adjusted for Free base and % Purity.
__ Yes
X No (Calculations based on 100%)
___ Free Base ___ Purity
6. Sampling requirements: Cited in protocol.
7. Storage: Cited in protocol.
000743
418-008:PAGE F-53
ATTACHMENTS
Protocol 418-008 Version: 418-008 (29 JUN 981
Page 2 of 3
TEST ARTICLE PREPARATION PROCEDURE
NOTE:
Test article will be prepared as a serial dilution from the high dosage to the low dosage. Stir bars are to be added to the containers; mixing should occur during sampling and/or dosage administration.
C. Preparation of the Control Group:
1. Add the required amount of vehicle to an appropriate vessel. (See TEST ARTICLE CALCULATIONS for exact quantities.)
D. Test Article Solution Preparation:
1. To prepare the 0.64-mg/mL, (group V) solution, add 224 mg of test article into an appropriately sized, labeled container.
2. Q. S. to 350 mL with the vehicle.
3. Add a stir bar and heat the preparation to 80 C in a water bath for approximately 30 minutes (or until the test article has dissolved).
4. Remove the solution from the water bath, and spin while the solution equilibrates to room temperature.
5. To prepare group IV, (the 0.32-mg/mL solution), add 150 mL of group V solution to an appropriately labeled container, then q.s. to 300 mL with vehicle. Add a stir bar and mix until uniform.
6. To prepare group III, (the 0.08-mg/mL solution), add 65 mL of group IV solution to an appropriately labeled container, then q.s. to 260 mL with vehicle. Add a stir bar and mix until uniform.
000744
418-Q08PAGE F-54
ATTACHMENT 3
Protocol 418-008 Version: 418-008 (29 JUN 981
Page 3 of 3
TEST ARTICLE PREPARATION PROCEDURE
7. To prepare group II, (the 0.02-mg/mL solution), add 50 mL of group III solution to an appropriately labeled container, then q.s. to 200 mL with vehicle. Add a stir bar and mix until uniform.
000745
OPrimedica
418-008:PAGE F-55
Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A Horsham, PA 19044 Telephone: (215) 443-8710 Telefax: (215) 443-8587
PROTOCOL 418-008
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS.
SPONSOR'S STUDY NUMBER: 6295.9
Amendment 5 - July 17, 1998
1. Concentration Analyses (page 5 of the protocol):
Samples (5 mL each) from each concentration will be taken during the first and last week of the F1 dosage administration to verify concentrations of the prepared test article formulations.
Reason for Change:
This change was made because dosage administration was extended to include the F1 generation male and female rats.
2. Sex (page 6 of the protocol):
The F1 generation male and female pups will be given the test article or vehicle.
Reason for Change:
These changes were made at the request of the Sponsor in order to provide information about the effects of the test article on the second generation.
3. Method and Frequency (page 10 of the protocol):
The F1 generation male and female pups will be administered the test article orally (gavage) on day 1 postweaning through the day before sacrifice. F2 generation pups will not be directly given the test article, but may be possibly exposed to the test article during maternal gestation (in utero exposure) or via maternal milk during the lactation period.
000746
418-008:PAGE F-56
Protocol 418-008 Amendment 5 Page 2
Reason for Change:
These changes were made at the request of the Sponsor and follow the method of exposure to Fo generation.
Dosage Levels. Concentrations and Volumes (page 11 of the protocol):
Dosage Group
Number ofFo
Generation Rats
Per Sex
1 35 II 35 III 35 IV 35 V 35
Number of F1
Generation Rats Per Sex
Dosage (mg/kg/day)
25 0 (Vehicle) 25 0.1 25 0.4 25 1.6 25 3.2
Concentration (mg/mL)
0 0.02 0.08 0.32 0.64
Dosage Volume (mUkg)
Argus Batch Number
5 B-418-008-A(Day.Month.Year) 5 B-418-008-B(Dav.Month.Year) 5 B-418-008-C(Day.Month.Year) 5 B-418-008-D(Day.Month.Year) 5 B-418-008-E(Dav.Month.Year)
Reason for Change:
This change was made because dosage administration was extended to include the F1 generation male and female rats.
Tests. Analyses and Measurements - F1 Generation (page 16 of the protocol):
Clinical Observations and/or General Appearance:
Preweaning Period:
Once daily.
Dosage Period:
Twice daily. Prior to dosage administration and once approximately one hour postdosage.
Maternal Behavior:
Days 1, 4, 7 , 1 4 and 21 postpartum. Any observed abnormal behavior will be recorded daily
000747
418-008-.PAGE F-57
Protocol 418-008 Amendment 5 Page 3
Body Weights - Male:
Preweaning Period:
Days 1 (birth), 4, 7, 14 and 21 postpartum.
Dosage Period:
Weekly.
Sacrifice:
Terminal weight.
Body Weights - Female:
Preweaning Period:
Days 1 (birth), 4, 7,14 and 21 postpartum.
Dosage Period:
Weekly to cohabitation. Daily during presumed gestation and on Days 1, 4, 7 and 14 postpartum (rats assigned to natural delivery).
Sacrifice:
Terminal weight.
Reason for Change:
These changes were made because dosage administration was extended to include the F1 generation male and female rats.
F1/F2 Generation Puds Not Selected for Continued Observation (page 22 of the protocol):
On day 4 postpartum, the stomach contents (milk curd) will be collected from culled pups from Groups I, II and V (or highest dosage group available). Samples will be collected from all pups from four to five of the largest litters in these three dosage groups. Individual pup samples will be combined by litter into polypropylene tubes and frozen at -20 C. After completion of sample collection, samples will be shipped (frozen on dry ice) to Kris J. Hansen, Ph.D. at 3M Environmental Technology and Safety Services, 935 Bush Avenue, Building 2-3E-09,, St. Paul, Minnesota 55133-3331 for analysis. Both the recipient and the Study Monitor will be notified in advance of sample shipment.
000748
418-008:PAGE F-58
Protocol 418-008 Amendment 5 Page 4
Reason for Change: Collection of milk samples were requested by the Sponsor to determine if the test article is reaching the pups via lactation.
.'frG o t^ e E. Dearlove/Pj.D.t DABT Date Associate Director orResearch
Raymond G. York.^h.D., DABT Associate Director of Research Study Director
Date
C- ^
TA
Barbara J. Patterson,~B.A.
?>
Date
Chairperson, Institutional Animal Care
and Use Committee
Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date
000749
OPrimedica
418-008:PAGE F-59
Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A Horsham, PA 19044 Telephone: (215) 443-871C Telefax: (215) 443-8587
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS
SPONSOR'S STUDY NUMBER: 6295.9 Amendment 6 - 1 3 August 1998
1. Necropsy (page 20 of the protocol):
On postpartum day 21, the 1.6 mg/kg/day dosage group (Group IV) dams and litters will be sacrificed.
Reason for Change:
Group IV was terminated at weaning because of the severe pup toxicity during lactation (mortality and reduced body weights and delayed development).
2. Male and Female Rats Assigned to Pharmacokinetic Sample Collection (page 14 of the protocol):
On postpartum Day 21, the livers of the pups from five litters in each of the remaining groups will be excised, pooled per litter, frozen and retained at -70C until shipment to the Sponsor. Reason for Change:
This change was made at the request of the Sponsor for possible analysis.
3. Scheduled Sacrifice - Female Rats Assigned to Natural Delivery and Dams with No Surviving P u ps (page 15 of the protocol):
Ovaries will be retained in neutral buffered 10% formalin.
000750
418-008PAGE F-60
Reason for Change: This change was made to clarify the protoo
Amendment 6 Page 2
Seorg^ E. Dearlove, Ph.D., DABT Date Associate Director of Research
j-V ) BarbaraKl/^atterson.iB/A.
Date
0 Chairperson, Institutional Animal Care
and Use Committee
y u y sg .
nd G. York, Associate Director
Director
T C ^~
f
Marvin T. Case, D.V.M., Ph.D. Study Monitor
18
Date
Date
000751
OPrimedica
418-008:PAGE F-61
Argus Research Laboratories, Inc. 90S Sheehy Drive, Building A Horsham, PA 19044 Telephone: (215) 443-8710 Telefax: (215) 443-8587
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS
SPONSOR'S STUDY NUMBER: 6295.9 Amendment 7 - 2 4 November 1998
1. Natural Delivery (page 13 of the protocol): The Length of Parturition (time of delivery of last pup minus the time of delivery of the first pup divided by N-1 pups in each litter) will not be calculated. Reason for Change: A litter watch was not required by the Sponsor.
'V\l.
Zi**#'
^orgefc. Dearlove, Ph.D., DABT Date Associate Director of Research
Raiyyrrtpo^i LddG. Y<ork, P Associate Director of Study Director
A
., DABT arch
Date
ne J V / / C t f ?
Dena C. Lebo, V.M.D.
Date
Chairperson, Institutional Animal Care
and Use Committee
7~dL
Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date
CCQ75Z
GPrimedica
418-008: PAGE F-62
Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A Horsham, PA 19044 Telephone: (215)443-8710 Telefax: (215) 443-8587
PROTOCOL 418-008
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATALVPOSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS
SPONSOR'S STUDY NUMBER: 6295.9
Amendment 8 - 1 8 May 1999
1. Concentration Analyses (page 5 of the protocol):
The concentration samples were sent to the Sponsor. Sample analyses will be conducted at the discretion of the Sponsor and no report will be sent to the Testing Facility.
Reason for Change:
This change was made at the request of the Sponsor to clarify the protocol.
2. Male and Female Rats Assigned to Pharmacokinetic Sample Collection (page 14 of the protocol):
The liver and serum samples were sent to the Sponsor. Samples will be analyzed at the discretion of the Sponsor.
Reason for Change:
This change was made at the request of the Sponsor to clarify the protocol.
3. F1/F2 Generation Puds Not Selected for Continued Observation (page 22 and Amendment 5 of the protocol):
The stomach contents of these pups were sent to the Sponsor for analysis. Stomach contents will be analyzed at the discretion of the Sponsor.
000753
418-008: PAGE F-63
Reason for Change:
Protocol 418-008 Amendment 8 Page 2
This change was made at the request of the Sponsor to clarify the protocol.
L.
L G^orgj E. Dearlove, Ph.D., DABT Date Associate Director of Research
Raymond G. York,
DABT
Associate Director of search
Study Director
Date
IbLSLzz.
ena C. Lebo, V.M.D.
Date
Chairperson, Institutional Animal Care
and Use Committee
Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date
APPENDIX G DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING
PROCEDURES OF THE TESTING FACILITY
000755
418-008:PAGE G-1
DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY
On 8 August 1998, the 5 mL concentration sample was not taken during the first week of dosage administration for the F1 generation rats. This deviation did not adversely affect the outcome or interpretation of the study because sufficient data were collected to accurately evaluate this parameter.
On 3 to 8 June 1998 [study days (DSs) 9 to 14], 10 to 15 June 1998 (DSs 16 to 21), 17 June 1998 (DS 23) and 18 June 1998 (DS 24), all Fo generation male and female rats were dosed with the dosage volumes based on body weights recorded on DS 1 (26 May 1998), rather than on weekly body weights. As a result of this error, male rats were administered approximately 89% to 90% of the targeted dosages and female rats were administered approximately 95% to 99% of the targeted dosages. This deviation did not adversely affect the outcome or interpretation of the study because the precohabitation dosage period was extended for an additional two weeks to ensure that all rats were administered the correct dosages before cohabitation.
On 21 August 1998 (postweaning day 1), F1 generation male rats 13158 and 13159 in the 0.4 mg/kg/day dosage group were neither weighed nor dosed. The dosage volume for the rest of the week was based on the postweaning day 2 body weight. This deviation did not adversely affect the outcome or interpretation of the study because a sufficient number of postweaning day 1 body weights were collected to evaluate this parameter, and the dosage volumes were based on the day 2 postweaning weight were presumed to be very similar to dosage volumes based on the day 1 postweaning weight.
All deviations ace*documented in the raw data.
Raymond G. York/Ph.D., DABT Associate DirectorVof^research and Study Director
Date
000756
APPENDIX H TEMPERATURE AND RELATIVE HUMIDITY REPORTS
000757
418-008: PAGE H-1
ARGUS
Temperature and Relative Humidity Report Location: Room 17
Protocol Number 418-008
Range of Dates: 12-May-1998 12:00 to 12-Jun-1998 09:46
Target Range: Species: Rat
Total Number of Days: Total Number of Hours: Total Number o f Data Points:
Temperature 64*F to 79' F
32 741.5 742
Relative Hum idity 30% to 70%
32 741.5 742
Mean ( SD):
Maximum: Median: M inim um :
Number o f Points in Range (%): Number o f Points High (%): Number o f Points Low (%):
69.6 (1.1) 46.2 ( 3.9)
71.9 61.2 69.7 46.5 66.4 37.9
742 (100.0) 742 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
Report Generated: 04-Sep-1998 at 13:18
COMMENTS:
REVIEWED BY:
DATE: ? / / / ? /
Cumulative by Location (v04.01.97)
000758
ARGUS
418-008:PAGE H-2
Temperature and Relative Humidity Report Location: Room 03
Protocol Number 418-008
Range of Dates: 12-Jun-1998 09:46 to 21-Sep-1998 13:40
Target Range: Species: R at
Total Number o f Days: Total Number o f Hours: Total Number o f Data Points:
Temperature
6 4 *F to 7 9*F
102 2427.74
2423
Relative H um idity
3 0 % to 7 0 %
102 2427.74
2423
Mean (1 SD):
Maximum: Median: M inim um :
Number o f Points in Range (%): Number o f Points High (%): Number o f Points L o w (% ):
69.0
75.3 69.1 62.0
2405 0 18
( 2.0)
(99.3) (0.0) (0.7)
61.6
72.3 63.1 45.7
2404 19 0
( 4 .8 )
(99.2) (0.8) (0.0)
Report Generated: 31-M ar-1 999 at 09:02
COMMENTS:
REVIEWED BY:
DATE: V ~M-
Cumulative by Location (v04.01.97)
000759
ARGUS
418-008PAG E H-3
Temperature and Relative Humidity Report Location: Room 05
Protocol Number: 418-008
Range of Oates: 27-Jul-1998 12:50 to 28-Dec-1998 08:29
Target Range: Species: Rat
Total Number o f Days: Total Number o f Hours: Total Number o f Data Points:
Temperature 64*F to 79*F
155 3691.26
3677
Relative Hum idity 30% to 70%
155 3691.26
3677
Mean ( SD):
Maximum: Median: M inim um :
Number o f Points in Range (%): Number o f Points High (%): Number o f Points Low (%):
69.3
82.7 69.7 64.6
3661 16 0
(1.8)
(99.6) (0.4) (0.0)
56.3
71.3 58.1 34.3
3667 10 0
( 6.7)
(99.7) (0.3) (0.0)
Report Generated: 31-Mar-1999 at 09:22
COMMENTS:
REVIEWED BY:
DATE:
Cumulative by Location (v04.01.97)
000760
ARGUS
418-008:PAGE H-4
Temperature and Relative Humidity Report Location: Room 35-37
Protocol Number 418-008
Range of Dates: 21-Sep-1998 13:40 to 28-Dec-1998 08:29
Target Range: Species: Rat
Total Number o f Days: Total Number o f Hours: Total Number o f Data Points:
Temperature 64*F to 79*F
99 2346.52
2336
Relative Humidity 30% to 70%
99 2346.52
2336
Mean ( SD):
Maximum: Median: M inim um :
Number o f Points in Range (%): Number o f Points High (%): Number o f Points Low (%):
69.7
73.0 69.7 67.8
2336 0 0
( 0.7)
(100.0) (0.0) (0.0)
52.5
69.5 51.7 23.6
2332 0 4
(4.0)
(99.8) (0.0) (0.2)
Report Generated: 31-Mar-1999 at 09:52
COMMENTS:
REVIEWED BY: y
I'
tr- (
DATE: 3
Cumulative by Location (v04.01.97)
000761
418-008:PAGE H-5
ARGUS
Temperature Deviations Report Location: Room 03
Protocol Number 418-008
Range of Dates: 12-Jun-1998 09:46 to 21-Sep-1998 13:40
Temperature Target Range: Species: Rat
Date
17-Jun-1998 17-Jun-1998 17-Jun-1998 17-Jun-1998 17-Jun-1998 28-Jun-1998 28-Jun-1998 0 8-Jul-l 998 08-JuH 998 08-JuH 998 0 9 -J U -1 9 9 8 09-JuH 998 09-JuH 998 0 9 -J u l-1 9 9 8 09-JuH 998 0 9 -J u l-1 9 9 8 0 9 -J u l-1 9 9 8
Time
03:00 04:00 05:00 06:00 07:00 06:00 07:00 21:00 22:00 23:00 00:00 01:00 02:00 03:00 04:00 05:00 06:00
Temp.
63.9 L 63.5 L 63.2 L 62.9 L 62.7 L 63.9 L 63.7 L 63.6 L 63.2 L 62.8 L 62.6 L 62.5 L 62.3 L 62.2 L 62.1 L 62.0 L 62.0 L
64F to 79F
Date Time
0& -Jul-1998 07:00
Temp.
62.4 L
H = Value out o f range - High L = Value out o f range - Low Temp. * Temperature *F
Report Generated: 31-Mar-1999 at 09:09
T h e se d eviations did not adve rse ly affect the ou tcom e or interpretation of the study. T h e follow ing d e v ia tio n s) im pacted on the ou tcom e o f the study a s described:
Deviations by Location (v04.01.97)
000762
418-008:PAGE H-6
ARGUS
Relative Humidity Deviations Report Location: Room 03
Protocol Number 418-008
Range of Dates: 12-Jun-1998 09:46 to 21-Sep-1998 13:40
Humidity Target Range: Species: Rat
Date
26-Jun-1998 26-Jun-1998 09-Jul-1998
09-JuM 998 09-JuM 998 21-UM998 24-Jul-1998 16-Aug-1998
16-Aug-1998 18-Aug-1998
24-Aug-1998 25-Aug-1998
27-Aug-1998 30-Aug-1998 31-Aug-1998 15-Sep-1998 16-Sep-1998
Time
11:00
12:00 08:00 11:00 12:00 12:00 10:00 17:00
19:00 01:00 15:00 17:00 15:00 13:00 11:00 21:00 14:00
R.H.
70.7 H
71.0 H 70.1 H 70.2 H 70.6 H 70.2 H 70.1 H 72.0 H 71 .OH
70.2 H 70.3 H 70.6 H 72.3 H 70.6 H 71.2 H 70.2 H 72.1 H
30% to 70% Date Time
H * Value out o f range - High L = Value out o f range - Low R.H. = Relative Hum idity (%)
Report Generated: 31-Mar-1999 at 09:15
These deviations did not adversely affect the outcome or interpretation of the study. The following deviation(s) impacted on the outcome ofthe study as described:
Deviations by Location (v04.01.97)
00076
418-008PAGE H-7
ARGUS
Temperature Deviations Report Location: Room 05
Protocol Number 418-008
Range of Dates: 27-Jul-1998 12:50 to 28-Dec-1998 08:29
Temperature Target Range: Species: Rat
Date
19-Sep-1998 19-Sep-1998 19-Sep-1998
19-Sep-1998 19-Sep-1998
19-Sep-1998 19-Sep-1998 19-Sep-1998 20-Sep-1998 20-Sep-1998 20-Sep-1998 20-Sep-1998 20-Sep-1998 20-Sep-1998
20-Sep-1998 20-Sep-1998
Time
16:00 17:00 18:00 19:00 20:00 21:00 22:00 23:00 00:00 01:00 02:00 03:00 04:00 05:00 06:00 07:00
Temp.
80.8 H 81.7 H 82.4 H
82.7 H 82.4 H
82.1 H 81.9 H 81.8 H 81.6 H 81.5 H 81.3 H
81.2 H 81.1 H 81.0 H 81.1 H 81.1 H
64F to 79F
Date Time Temp.
H = Value out o f range - High L = Value out o f range - Low Temp. = Temperature F
Report Generated: 31-Mar-1999 at 09:36
These deviations did not adversely affect the outcome or interpretation of the study. The following deviations) impacted on the outcome of the study as described:
Deviations by Location (v04.01.97)
000764
418-008.PAGE H-8
ARGUS
Relative Humidity Deviations Report Location: Room 05
Protocol Number 418-008
Range of Dates: 27-Jul-1998 12:50 to 28-Dec-1998 08:29
Humidity Target Range: Species: Rat
Date
26-Sep*1998 26-Sep-1998 26*Sep-1998 30-Sep*1998 09-Oct-1998
14-Oct-1998 14-Oct-1998 03-NOV-1998
07-Dec-1998
Time
14:00 16:00 19:00 17:00 02:00
07:00 11:00 16:00 08:00
R.H.
70.7 H
70.1 H 70.1 H 70.1 H 70.5 H 70.4 H 70.1 H 70.3 H 71.3 H
30% to 70% Date Time
H = Value out of range - High L = Value out of range - Low R.H. * Relative Humidity (%)
Report Generated: 31-Mar-1999 at 09:45
j ^ T hese deviations did not adversely affectthe outcome or interpretation ofthe sti __ The following deviations) impacted on the outcome ofthe study as described:
Deviations by Location (v04.01.97)
000765
418-008:PAGE H-9
ARGUS
Relative Humidity Deviations Report Location: Room 35*37
Protocol Number 418*008
Range of Dates: 21-Sep-1998 13:40 to 28-Dec-1998 08:29
Humidity Target Range: Species: Rat
Date
23-Sep'1998 23-Sep-1998 23-Sep-1998 23-Sep-1998
Time
10:00 11:00 12:00
13:00
R.H.
29.3 L 27.3 L 28.2 L 23.6 L
30% to 70% Date Time R.H.
H * Value out of range - High L = Value out of range - Low R.H. = Relative Hum idity (%)
Report Generated: 31-Mar-1999 at 10:12
These deviations did not adversely affect the outcome or interpretation of the study. The following deviations) impacted on the outcome of the study as described:
Deviations by Location (v04.01.97)
000766
APPENDIX I STATEMENT OF THE STUDY DIRECTOR
000767
418-008PAGE 1-1
Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A
Horsham, Pennsylvania 19044
T: (215) 443-8710 F: (215) 443-8587
PROTOCOL 418-008: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS SPONSOR'S STUDY NUMBER: 6295.9
STATEMENT OF THE STUDY DIRECTOR
This final report accurately reflects the raw data obtained during the performance of the study. No deviations from the U.S. Food and Drug Administration (FDA) Good Laboratory Practice Regulations: Final Rule3, the Japanese Ministry of Health and Welfare (MHW) G o o d L a b o ra to ry P ra c tic e S ta n d a rd fo r S a fe ty S tu d ie s on D ru g sb and the European Economic Community (EEC) C o u n c il d e c is io n o n 2 8 J u ly 1989 on th e a c c e p ta n c e b y th e E u ro p e a n
E co n o m ic C o m m u n ity o f an O E C D d e c is io n /re c o m m e n d a tio n o n c o m p lia n ce w ith
p rin c ip le s o f g o o d la b o ra to ry p ra c tic e 0 occurred that affected the quality or integrity of the study.
Associate Director of Research and Study Director i Argus Research Laboratories, Ine.
a. U.S. Food and Drug Administration. Good Laboratory Practice Regulations: Final Rule. 21 CFR Part 58.
b. Japanese Ministry of Health and Welfare (1997). G o o d L a b o ra to ry P ra c tic e S ta n d a rd fo r S a fe ty S tu d ie s on D ru g s, MHW Ordinance Number 21, March 26, 1997.
c. European Economic Community (1989). C o u n c il d e cisio n on 2 8 J u ly
1989 on th e a c ce p ta n ce b y th e E u ro p e a n E co n o m ic C o m m u n ity o f an O E C D d e c is io n /re c o m m e n d a tio n o n c o m p lia n c e w ith p rin c ip le s o f g o o d
la b o ra to ry p ra c tic e . Official Journal of the European Communities: Legislation. 32(No. L 315; 28 October): 1-17.
0QQ7S8
APPENDIX J QUALITY ASSURANCE UNIT FINAL REPORT STATEMENT
000769
GPrimedica
418-008:PAGE J-1
Argus Research Laboratories, Inc. 905 Sheehy Drive, Building A Horsham, PA 19044 Telephone: (215) 443-8710 Telefax: (215)443-8587
QUALITY ASSURANCE UNIT FINAL REPORT STATEMENT
Study Director: Raymond G. York, Ph.D., DABT
Executive Director of Research: Mildred S. Christian, Ph.D., Fellow, ATS
Protocol 418-008:
Combined Oral (Gavage) Fertility, Developmental and Perinatal/Postnatal Reproduction Toxicity Study of PFOS in Rats Sponsor's Study Number: 6295.9
The draft protocol for this study was audited for adherence to U.S. Food and Drug Administration (FDA) Good Laboratory Practice Regulations, Japanese Ministry of Health and Welfare (MHW); Good Laboratory Practice Standard for Safety Studies on Drugs, and European Economic Community (1989) council decision on 28 July 1989 on the acceptance by the European Economic Community of an OECD decision/recommendation on compliance with principles of good laboratory practice on 13 MAY 98.
Critical phases of this study were inspected 24 times; study information and raw data were audited six times (see tables 1 and 2 for dates and phases/data).
The draft final report and the raw data for this study were compared and audited for accuracy, for adherence to protocol requirements, and for adherence to U.S. Food and Drug Administration (FDA) Good Laboratory Practice Regulations, Japanese Ministry of Health and Welfare (MHW); Good Laboratory Practice Standard for Safety Studies on Drugs, and European Economic Community (1989) council decision on 28 July 1989 on the acceptance by the European Economic Community of an OECD decision/recommendation on compliance with principles of good laboratory practice between 05 DEC 98 and 29 APR 99, and for revisions requested by the Sponsor 18 MAY 99, 7 JUN 99, 9 JUN 99, and for finalization on 10 JUN 99.
000770
418-008:PAGE J-2
This study was conducted according to U.S. Food and Drug Administration (FDA) Good Laboratory Practice Regulations, Japanese Ministry of Health and Welfare (MHW); Good Laboratory Practice Standard for Safety Studies on Drugs, and European Economic Community (1989) council decision on 28 July 1989 on the acceptance by the European Economic Community of an OECD decision/recommendation on compliance with principles of good laboratory practice.
Quality Assurance Manager
L - /0JILA :( C1
Heather L. RaDtJttino, M.S. Quality Assurance Supervisor and Principal Auditor
Date
000771
TABLE 1 CRITICAL PHASES INSPECTED
418-008: PAGE J-3
Test Article Administration - Gavaae Dates of inspection: 28 MAY 98, 02 JUN 98, 03 SEP 98 Dates results reported to the Study Director and Management: 15 JUN 98, 15 JUN 98, 18 SEP 98
Estrous Cycle Evaluation Date of inspection: 11 JUN 98 Date results reported to the Study Director and Management: 11 JUN 98
Cohabitation
Dates of inspection: 08 JUL 98, 04 NOV 98
Dates results reported to the Study Director and Management: 14 JUL 98, 12 NOV 98
Scheduled Sacrifice - Day 10 Date of inspection: 17 JUL 98 Date results reported to the Study Director and Management: 03 AUG 98
Test Article Preparation
Dates of inspection: 29 JUL 98, 16 SEP 98
Dates results reported to the Study Director and Management: 14 AUG 98, 24 SEP 98
Natural Delivery
Dates of inspection: 31 JUL 98, 25 NOV 98
Dates results reported to the Study Director and Management: 14 AUG 98, 02 DEC 98
Blood Collection
000772
418-008:PAGE J-4 Dates of inspection: 31 JUL 98, 18 AUG 98 Dates results reported to the Study Director and Management:
14 AUG 98, 21 AUG 98
Physical and Reflex Development - Surface Righting. Pinna Unfolding. Eve Opening. Auditory Startle. Air Righting. Pupil ConstrictionSexual Maturation Dates of inspection: 31 JUL 98, 13 AUG 98, 18 AUG 98, 28 AUG 98, 11 SEP 98 Dates results reported to the Study Director and Management: 14 AUG 98, 03 SEP 98, 08 SEP 98, 11 SEP 98, 12 SEP 98
Male Necropsy Date of inspection: 31 JUL 98 Date results reported to the Study Director and Management: 14 AUG 98
Necropsy - Dam and Litter Sacrifice Dates of inspection: 18 AUG 98, 15 DEC 98 Dates results reported to the Study Director and Management: 21 AUG 98, 18 DEC 98
Dav 21 Weaning Date of inspection: 18 AUG 98 Date results reported to the Study Director and Management: 08 SEP 98
Behavioral Testing - Passive Avoidance. Watermaze. Dates of inspection: 25 AUG 98, 08 OCT 98 Dates results reported to the Study Director and Management: 12 SEP 98, 12 OCT 98
000773
418-008PAGE J-5 TABLE 2 RAW DATA AUDIT(S) The following study information and raw data were audited on 29 SEP 98, 01 OCT 98, 04 OCT 98 TO 05 OCT 98: Protocol. Protocol amendments. List of personnel and computer operator codes. Error codes and codes for clinical sigh observations. Animal receipt, randomization, physical examination and acclimation. In-life transaction record. Feed consumption. Necropsy. Organ weights. Tissue packing lists. Edit requests. Deviations. Data review page/pages. Blood collection data and packing lists. Key for testing facility computer backup record abbreviations.
The results of this audit were reported to the Study Director and Management on 06 OCT 98.
000774
418-008.PAGE J-6
The following study information and raw data were audited on 06 OCT 98, 12 OCT 98, 02 NOV 98 TO 06 NOV 98:
Animal receipt, randomization, physical examination and acclimation. In-life transaction record. Feed consumption. Estrus cycle evaluation. Cohabitation. Caesarean-sectioning. Maternal gross observations Natural delivery observations. Litter observations. Pup body weights and status. Table of random units. Necropsy. Tissue packing lists. General comments. Reflex and physical development. Study maintenance records. Temperature and relative humidity reports. Feed, water and bedding analyses. Edit requests. Data review page. Blood collection data and packing lists. Pup stomach contents.
The results of this audit were reported to the Study Director and Management on 08 NOV 98.
418-008:PAGE J-7
The following study information and raw data were audited on 08 NOV 98 to 09 NOV 98:
Vehicle receipt, preparation and use. Test article receipt, preparation and use. Test article packing lists. The results of this audit were reported to the Study Director and Management on 12 NOV 98.
The following study information and raw data were audited on 26 JAN 99 to 28 JAN 99:
In-life transaction record. Feed consumption. Passive avoidance. Watermaze. Genealogy chart. Necropsy. Organ weights. Tissue packing lists. Sexual Maturation. Edit request. The results of this audit were reported to the Study Director and Management on 28 JAN 99.
000776
418-008PAGE J-8
The following study information and raw data were audited on 28 JAN 99 to 01 FEB 99:
In-life transaction record. Feed consumption. Cohabitation. Natural delivery observations. Litter observations. Pup body weights and status. Passive avoidance. Watermaze. Table of random units. Necropsy. Tissue packing lists. General comments. Sexual maturation. Study maintenance records. Temperature and relative humidity reports. Feed, water and bedding analyses. Edit requests. Dosage volumes. Data review pages.
The results of this audit were reported to the Study Director and Management on 01 FEB 99.
The following study information and raw data were audited on 25 JAN 99:
Vehicle receipt, preparation and use. Test article receipt, preparation and use. Test article packing lists.
The results of this audit were reported to the Study Director and Management on 28 JAN 99.
c ro T 'rr
