Document bBQZE2KGJNKge0531eMD1J093
p
T D
SE
FINAL REPORT
PROTOCOL 418-008
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PERINATAUPOSTNATAL
REPRODUCTION TOXICITY STUDY
IN RATS
AND OF PFOS
SPONSOR'S STUDY NUMBER: 6295.9
FINAL REPORT DATE: 10 JUNE 1999
PROTOCOL 418-008
COMBINED ORAL (GAVAGE) FERTILITY,DEVELOPMENTAL AND PERINATAUPOSTNATAL 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 li. DESCRIPTION OF TEST PROCEDURES A. Conduct ofStudy A.l. Sponsor A.2. TestingFacility A.3. Study Number A.4. Sponsoes Study Number A.5. Purpose oftheStudy A.6. Study Design A.7. RegulatoryCompliance A.8. Ownership ofthe Study A.9. Study Monitor
PAGE 1-1 1-1 1-5 1-10 11-1 11-1 11-1 11-1 11-1 11-1 11-1 11-1 11-2 11-2 11-2
SUBJEC A.10. AlternateStudy Monitor A.11. Study Director A.12. TechnicalPerformance A.13. Report Preparation A. 14. Report Review A. 15. Date ProtocolSigned A. 16. Dates ofTechnicalPerformance A.17. Records Maintained B. Test ArticleInformation B.1. Description B.2. Lot Number B.3. Date Received and Storage Conditions B.4. SpecialHandling Instructions B.5. AnalysisofActivity C. VehicleInformation C. 1. Description C.2. Lot Numbers C.3. Dates Received and Storage Conditions C.4. SpecialHandling Instructions C.5. Analysisof Purity D. Test ArticlePreparation D. 1. Sample Information
PAGE 11-2 11-2 11-2 11-2 11-3 11-3 11-3 11-4 11-4 11-4 11-4 11-5 11-5 11-5 11-5 11-5 11-5 11-5 11-6 11-6 11-6 11-6
SUBJECT D.2. AnalyticaRlesults E. Test System E. 1. Specias E.2. Strain E.3. Supplier(Source) E.4. Sex E.5. RationaleforTest System E.6. Test System Data E.7. Method of Randomization E.8. System of Identification F. Husbandry F.1. Research FacilitRyegistration 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.1 1. Bedding Analysis
PAGE 11-7 11-7 11-7 11-7 11-7 11-7 11-7 11-7 11-8 11-8 11-9 11-9 11-9 11-9 11-10 11-10 11-10 11-10 11-10 11-10 11-11 11-11
SUBJECT
G. Methods
G.l. Dosage Administration
G.2. Assigned Rat Numbers
G.3. RationaleforDosage Selection
G.4. Route ofAdministration
G.5. RationaleforRoute ofAdministration
G.6. Frequency ofAdministration
G.7. Length ofStudy
G.8. Method of Study Performance
G.9. Gross Necropsy
G.10. StatisticAanlalyses 111. RESULTS - Fo GENERATION
MALE RATS
A. ClinicaOlbservations
B. Body Weights and Body Weight Changes
C. Absolute(g/day)and Relative(g/kg/dayF)eed Consumption Values
D. Mating and Fertility
E. Necropsy Observations
F. TerminalBody Weights,Organ Weights and Ratios of Organ Weight toTerminalBody Weight
IV. RESULTS - Fo GENERATION FEMALE RATS
A. ClinicaOlbservations
A.1. Mortality
iv
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
111-1 111-2 111-2
111-3 IV-1 IV-1 IV-1
SUBJECT A.2. ClinicaOlbservations B. Body Weights and Body Weight Changes B.1. Precohabitation B.2. Gestation B.3. Lactation C. Absolute(g/day)and Relative(g/kg/dayF)eed Consumption
Values C. 1. Precohabitation C.2. Gestation C.3. Lactation D. EstrousCycling,Mating and Fertility E. Necropsy Observations F. Caesarean-Sectioningand LifteOrbservations G. NaturalDeliveryand LifteOrbservations H. ClinicaOlbservationsfrom Birthto Day 21 Postpartum and
Necropsy Observations 1. Reflexand PhysicalDevelopment 1.1. SurfaceRighting 1.2. Pinna Unfolding 1.3. Eye Opening 1.4. AcousticStartle 1.5. AirRighting 1.6. PupilConstriction
v
PAGE IV-1 IV-1 IV-1 IV-2 IV-2
IV-3 IV-3 IV-3 IV-3 IV-4 IV-4 IV-4 IV-4
IV-5 IV-6 IV-6 lv-7 IV-7 IV-7 IV-7 IV-8
SUBJECT V. RESULTS - Fl GENERATION MALE AND FEMALE RATS A. Fl Generation Male Rats A.l. Mortalityand ClinicaOlbservations A.2. Body Weights and Body Weight Changes A.3. Absolute (g/day)and Relative(g/kg/dayF)eed Consumption
Values A.4. Sexual Maturation A.5. Passive Avoidance Performance A.6. Watermaze Performance A.7. Mating and Fertility A.8. Necropsy Observations A.9. Terminal Body Weights and Organ Weights and Ratios(%)
ofOrgan Weight toTerminalBody Weight B. Fl Generation Female Rats B.1. Mortalityand ClinicaOlbservations B.2. Maternal Body Weights and Body Weight Changes B.3. MaternalAbsolute(g/day)and Relative(g/kg/dayF)eed
Consumption Values B.4. Sexual Maturation B.5. Passive Avoidance Performance B.6. Watermaze Performance B.7. Mating and Fertility B.8. Necropsy Observations B.9. NaturalDeliveryand LifteOrbservations
vi
PAGE V-1 V-1 V-1 V-2
V-2 V-2 V-3 V-3 V-3 V-3
V-4 V-4 V-4 V-5
V-6 V-7 V-7 V-7 V-7 V-8 V-8
SUBJECT
PAGE
B.10. ClinicalObservationsfrom Birthto 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
Figure2. Body Weights - Fo Generation Female Rats
A-2
Figure3. Body Weights - Fl GenerationMale Rats
A-3
Figure4. Body Weights - Fl GenerationFemale Rats
A4
APPENDIX B - REPORT TABLES - Fo GENERATION MALE RATS
Table Bl. ClinicaOlbservations- Summary - Fo Generation Male Rats B-1
Table B2. Body Weights - Summary - Fo GenerationMale Rats
B-2
Table B3. Body Weight Changes - Summary - Fo GenerationMale Rats B-3
Table B4. AbsoluteFeed Consumption Values (g/day)- Summary -
Fo Generation Male Rats
B-4
Table B5 RelativeFeed Consumption Values (g/kg/day-) Summary -
Fo GenerationMale Rats
B-5
Table B6. Mating and Fertili-tySummary - Fo GenerationMale Rats B-6
Table B7. Necropsy Observations- Summary -Fo Generation Male Rats B-7
Table B8. TerminalBody Weights and Organ Weights - Summary -
Fo GenerationMale Rats
B-8
Table B9. Ratios(%) of Organ Weight toTerminalBody Weight -
Summary - Fo Generation Male Rats
B-9
Table B10. ClinicaOlbservations- IndividuaDlata - Fo Generation
Male Rats
B-10
Table Bl 1. Body Weights - IndividuaDlata - Fo Generation Male Rats B-20
vii
SUBJECT
PAGE
TableB12. Feed ConsumptionValues-IndividuDaaltaFo GeneratioMnaleRats
B-30
TableB13. Matingand Fertil-itIyndividuDaalta- Fo Generation Male Rats
B-40
TableB14. NecropsyObservation-sIndividuDaalta- Fo Generation
Male Rats
B-50
TableB 15. TerminaBlody Weightsand OrganWeightsand Ratios(%) ofOrganWeighttoTerminaBlodyWeight- Individual Data- Fo GeneratioMnaleRats
B-58
APPENDIX C - REPORT TABLES - Fo GENERATION FEMALE RATS
TableCl. ClinicOablservation-sSummary - Fo GeneratioFnemale
Rats
C-1
TableC2. Body Weights- Precohabitat-ioSnummary - Fo Generation
FemaleRats
C-4
Table C3. Body WeightChanges- Precohabitat-ioSnummary -
Fo GeneratioFnemaleRats
C-5
TableC4. MaternaBlodyWeights- Gestatio-nSummary -
Fo GeneratioFnemaleRats
C-6
TableC5. MatemalBody WeightChanges- Gestatio-nSummary -
Fo GeneratioFnemaleRats
C-8
TableC6. MaternaBlody Weights- Lactatio-nSummary -
Fo GeneratioFnemaleRats
C-9
TableC7. MaternaBlody WeightChanges- Lactatio-nSummary Fo GeneratioFnemaleRats
C-10
TableC8. AbsolutFeeed ConsumptionValues(g/day-) Precohabitat-ioSnummary - Fo GeneratioFnemaleRats C-11
TableCg. RelativFeeed ConsumptionValues(g/kg/da-y) Precohabitat-ioSnummary - Fo GeneratioFnemaleRats
C-12
TableC10. MaternaAlbsoluteFeed ConsumptionValues(g/day-) Gestatio-nSummary - Fo GeneratioFnemaleRats
viii
C-13
SUBJECT
PAGE
TableCl 1. MaternaRlelativFeeed ConsumptionValues(g/kg/da-y) Gestatio-nSummary - Fo GeneratioFnemaleRats
C-14
TableC12. MatemalAbsolutFeeed ConsumptionValues(g/day-) Lactatio-nSummary - Fo GeneratioFnemaleRats
C-15
TableC 13. MaternaRlelativFeeed ConsumptionValues(g/kg/da-y) Lactatio-nSummary - Fo GeneratioFnemaleRats
C-16
TableC14. EstrouCsyclingM,atingand Fertil-itSyummary Fo GeneratioFnemaleRats
C-17
TableCl 5. NecropsyObservation-sSummary - Fo Generation FemaleRats
C-19
TableC16. Caesarean-SectionOibnsgervation-sSummary Fo GeneratioFnemaleRats
C-20
TableC17. NaturaDleliverOybservation-sSummary - Fo Generation
FemaleRats
C-21
TableC18. LifteOrbservation(sNaturalDleyliverePdups)- Summary -
Fl GeneratioLnifters
C-22
TableCl 9. ClinicOablservationfsromBirtthoDay 21 Postpartu-m Summary - Fl GeneratioPnups
C-25
TableC20. Reflexand PhysicaDlevelopment- Summary Fl GeneratioLnifters
C-26
TableC21. NecropsyObservation-sSummary - Fl GeneratioPnups C-31
TableC22. ClinicOablservation-sIndividuDaalta- Fo Generation FemaleRats
C-32
TableC23. Body Weights- Precohabitat-ioInndividuDaaltaFo GeneratioFnemaleRats
C-40
TableC24. MaternaBlodyWeights- PresumedGestatio-n IndividuDaalta- Fo GeneratioFnemaleRats
C-50
TableC25. MaternaBlodyWeights- Lactati-onIndividuDaaltaFo Generatio-nFo GeneratioFnemaleRats
C-70
ix
SUBJECT
PAGE
TableC26. Feed ConsumptionValues- Precohabitat-ioInndividual
Data- Fo GeneratioRnats
C-75
TableC27. MaternaFleed ConsumptionValues- PresumedGestatio-n
IndividuDaalta- Fo GeneratioFnemaleRats
C-85
TableC28. MaternaFleed ConsumptionValues- Lactatio-n IndividuDaalta- Fo GeneratioFnemaleRats
C-105
TableC29. EstrousCyclinagnd Days inCohabitati-onIndividuDaalta-
Fo GeneratioFnemaleRats
C-110
TableC30. NecropsyObservation-sIndividuDaalta- Fo Generation
FemaleRats
C-115
TableC31. Caesarean-SectionOibnsgervation-sIndividuDaaltaFo GeneratioFnemaleRats
C-121
TableC32. LifteOrbservation(sCaesaren-DeliveErmebdryos)IndividuDaalta- Fl GeneratioLnifters
C-126
TableC33. EmbryonalVitaSltatus- IndividuDaalta- Fl Generation
Lifters
C-131
TableC34. NaturaDleliverIym,plantatiSointesa,nd Pup Viabiliatnyd Sex - IndividuDaalta- Fo GeneratioFnemaleRats/ Fl GeneratioLnitters
C-136
TableC35. Pup BodyWeightLifteArveragesfromBirtthoDay 21 Postpartu-m IndividuDaalta- Fl GeneratioLnifters
C-141
TableC36. Pup BodyWeightsfromBirtthoDay 21 Postpartu-m IndividuDaalta- Fl GeneratioPnups
C-146
TableC37. Pup VitaSltatusand Sex fromBirtthoDay 21 Postpartu-m
IndividuDaalta- Fl GeneratioPnups
C-176
TableC38. ClinicOablservationfsromBirtthoDay 21 Postpartu-m IndividuDaalta- Fl GeneratioPnups
C-181
TableC39. SurfaceRightin-gIndividuDaalta- Fl GeneratioLniftersC-182
TableC40. PinnaFoldin-g IndividuDaalta- Fl GeneratioLnifters C-193
x
SUBJECT
PAGE
Table C41. Eye Opening - IndividuaDlata - Fl GenerationLifters C-203
Table C42. AcousticStartl-e IndividuaDlata - Fl GenerationLitters C-213
Table C43. AirRighting- IndividuaDlata - Fl Generation Lifters
C-223
Table C44. PupilConstrictio-n IndividuaDlata - Fl GenerationLifters C-233
Table C45. Necropsy Observations- IndividuaDlata - Fl Generation
Pups
C-243
APPENDIX D - REPORT TABLES - Fl GENERATION MALE RATS
Table Dl. ClinicaOlbservations- Summary - Fl GenerationMale
Rats
D-1
Table D2. Body Weights - Summary - Fl GenerationMale Rats
D-3
Table D3. Body Weight Changes - Summary - Fl Generation
Male Rats
D-4
Table D4. AbsoluteFeed Consumption Values (g/day)- Summary -
Fl GenerationMale Rats
D-5
Table D5. RelativeFeed Consumption Values (g/kg/day-) Summary -
Fl GenerationMale Rats
D-6
Table D6. Sexual Maturation- Summary - Fl GenerationMale Rats
D-7
Table D7. PassiveAvoidance Performance - Summary -
Fl GenerationMale Rats
D-8
Table D8. Watermaze Performance - Summary - Fl Generation
Male Rats
D-9
Table Dg. Mating and Fertili-tySummary - Fl GenerationMale Rats D-10
Table D10. Necropsy Observations- Summary - Fl Generation Male Rats
D-1 1
Table Dl 1. TerminalBody Weights and Organ Weights - Summary Fl GenerationMale Rats
D-1 3
xi
SUBJECT
PAGE
TableD12. Ratios(%)ofOrganWeighttoTerminaBlody WeightSummary - Fl GeneratioMnaleRats
D-14
TableD13. ClinicOablservation-sIndividuDaalta- Fl Generation MaleRats
D-15
TableD14. Body Weights- IndividuDaalta- Fl GeneratioMnaleRats D-20
TableD15. Feed ConsumptionValues- IndividuDaalta- Fl Generation
MaleRats
D-26
TableD16. SexualMaturatio-nIndividuDaalta- Fl GeneratioMnale Rats
D-29
TableD17. PassiveAvoidancePerformanc-e IndividuDaalta Fl GeneratioMnaleRats
D-30
TableD18. WatermazePerformanc-e IndividuDaalta- Fl Generation
MaleRats
D-33
TableD19. Matingand Fertil-itIyndividuDaalta- Fl GeneratioMnale
Rats
D-36
TableD20. NecropsyObservation-sIndividuDaalta- Fl Generation
MaleRats
D-39
TableD21. TerminaBlody Weightsand OrganWeightsand Ratios(%)
ofOrganWeighttoTerminalBody Weight- IndividuDaalta-
Fl GeneratioMnaleRats
D-43
APPENDIX E - REPORT TABLES - Fl GENERATION FEMALE RATS
TableEl. ClinicOablservation-sSummary - Fl GeneratioFnemale
Rats
E-1
TableE2. BodyWeights- Precohabitat-ioSnummary - Fl Generation
FemaleRats
E-4
TableE3. Body WeightChanges- Precohabitat-ioSnummary -
Fl GeneratioFnemaleRats
E-5
TableE4. MaternaBlody Weights- Gestatio-nSummary -
Fl GeneratioFnemaleRats
E-6
I xii
SUBJECT
PAGE
Table E5. MaternalBody Weight Changes - Gestation- Summary -
Fl GenerationFemale Rats
E-8
Table E6. MaternalBody Weights - Lactation- Summary -
Fl GenerationFemale Rats
E-9
Table E7. MaternalBody Weight Changes - Lactation- Summary -
Fl GenerationFemale Rats
E-10
Table E8. AbsoluteFeed Consumption Values (g/day)Precohabitatio-n Summary - Fl GenerationFemale Rats
E-1 1
Table E9. RelativeFeed Consumption Values (g/kg/day-) Precohabitatio-n Summary - Fl GenerationFemale Rats E-12
Table E10. MaternalAbsoluteFeed Consumption Values (g/day)Gestation- Summary - Fl GenerationFemale Rats
E-1 3
TableEll. MaternalRelativeFeed Consumption Values (g/kg/day-)
Gestation- Summary - Fl GenerationFemale Rats
E-14
Table E12. MaternalAbsoluteFeed Consumption Values (g/day)-
Lactation- Summary - Fl GenerationFemale Rats
E-15
Table E 13. MaternalRelativeFeed Consumption Values (g/kg/day-)
Lactation- Fl GenerationFemale Rats
E-16
Table E14. Sexual Maturation- Summary - Fl GenerationFemale Rats E-17
Table E 15. Passive Avoidance Performance - Summary -
Fl GenerationFemale Rats
E-18
Table E16. Watermaze Performance- Summary - Fl Generation
Female Rats
E-19
Table E17. Mating and Fertili-tySummary - Fl Generation
Female Rats
E-20
Table E18. Necropsy Observations- Summary - Fl Generation
Female Rats
E-21
Table E19. NaturalDeliveryObservations- Summary - Fl Generation
Female Rats
E-22
xiii
SUBJECT
PAGE
Table E20. LifteOrbservations(NaturallDyeliveredPups) -
Summary - F2 GenerationLitters
E-23
Table E21. ClinicaOlbservationsfrom Birthto Day 21 Postpartum -
Summary - F2 GenerationPups
E-26
Table E22. Necropsy Observations- Summary - F2 GenerationPups E-27
Table E23. ClinicaOlbservations- IndividuaDlata - Fl Generation
Female Rats
E-28
Table E24. Body Weights- Precohabitatio-n IndividuaDlata - Fl
GenerationFemale Rats
E-34
Table E25. Matemal Body Weights - Presumed Gestation- Individual
Data - Fl GenerationFemale Rats
E-37
Table E26. MaternalBody Weights - Lactation- IndividuaDlata -
Fl GenerationFemale Rats
E-43
Table E27. Feed Consumption Values - Precohabitatio-n Individual
Data - Fl GenerationFemale Rats
E-46
Table E28. MaternalFeed Consumption Values - Presumed Gestation-
IndividuaDlata - Fl Generation Female Rats
E-49
Table E29. MaternalFeed Consumption Values - Lactation- Individual
Data - Fl GenerationFemale Rats
E-52
Table E30. Sexual Maturation- IndividuaDlata - Fl Generation
Female Rats
E-55
Table E31. PassiveAvoidance Performance - IndividuaDlata -
Fl GenerationFemale Rats
E-56
Table E32. Watermaze Performance - IndividuaDlata - Fl Generation
Female Rats
E-59
Table E33. Days inCohabitation- IndividuaDlata - Fl Generation
Female Rats
E-62
Table E34. Necropsy Observations- IndividuaDlata - Fl Generation
Female Rats
E-63
xiv
SUBJECT
PAGE
Table E35. NaturalDelivery,ImplantationSites,and Pup Viabilitaynd
Sex - IndividuaDlata - Fl GenerationFemale Rats/
F2 Generation Litters
E-67
Table E36. Pup Body Weight LifteArve.-agesfrom Birthto Day 21
Postpartum- IndividuaDlata - F2 GenerationLitters
E-70
Table E37. Pup Body Weights from Birthto Day 21 Postpartum -
IndividuaDlata - F2 Generation Pups
E-73
Table E38. Pup VitalStatus and Sex from Birthto Day 21 Postpartum -
IndividuaDlata - F2 Generation Pups
E-91
Table E39. ClinicaOlbservationsfrom Birthto Day 21 Postpartum -
IndividuaDlata - F2 GenerationPups
E-94
Table E40. Necropsy Observations- IndividuaDlata - 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 REPORTS
AND RELATIVE HUMIDITY
H-1 to H-9
APPENDIX I- STATEMENT OF THE STUDY DIRECTOR
APPENDIX J - QUALITY ASSURANCE STATEMENT
UNIT FINAL REPORT
J-1 toJ-8
xv
TITLE:
418-008:PAGE 1-1
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
AND PERINATAUPOSTNATAL
REPRODUCTION TOXICITY
STUDY OF PFOS IN RATS
ARGUS RESEARCH LABORATORIES, INC. PROTOCOL NUMBER: 418-008 SPONSOR'S STUDY NUMBER: 6295.9
1. SUMMARY
AND CONCLUSION
A. Methodsa
Text Figure 1 provides a schematic of the study design.
A.I. Fo Generation Rats/Fl Generation Lifters:
One hundred seventy-five male and female Crl:CD(DBR VAF/Plus(D (SpragueDawley) ratswere assigned tofivedosage groups (Groups IthroughV),35 rats per sex per dosage group. The ratswere administeredthe testarticleP,FOS, or the vehicle,0.5% Tween 800, orally(viagavage). The dosages were 0 (Vehicle)0,.1,0.4,1.6and 3.2 mg/kg/day. The male ratswere dosed once dailybeginning42 days beforecohabitatioannd continuingthroughthe day before sacrificeT.he female ratswere dosed once dailybeginning42 days beforecohabitatioannd continuingthroughDG' 9 (ratsassigned toCaesareansectioning)D,G 24 (ratsassigned to naturaldeliverythatdid notdelivera lifter), or DLc 20 (ratsthatdiddelivera lifterT)h.e dosage volume was 5 mukg.
AllFo generationratswere observed forviabilitayt leasttwicedailyduringthe study and forclinicasligns ofeffectsofthe testarticltewicedailyduringthe dosage period.Body weightsand feed consumption values formale ratswere recordedweekly duringthe dosage periodand atsacrificeB.ody weightsfor female ratswere recordedweekly to cohabitationd,ailyduringthe gestation period,on DLs 1,4,7, 10 and 14 (ratsassigned to naturaldeliverya)nd at sacrificeF.eed consumption values were recordedweekly to cohabitationd,aily duringthe gestationperiodand on DLs 1,4, 7, 10 and 14 (ratsassigned to naturaldelivery).
a. Detaileddescriptionosf allprocedures used inthe conduct ofthisstudy are providedinthe appropriatesectionsofthisreportand inAPPENDIX F (PROTOCOL AND AMENDMENTS).
b. DG isused as an abbreviatiofnorday of(presumed) gestation. C. DL isused as an abbreviationforday of lactatioonr day postpartum.
418-008:PAGE1-2
The firsttenfemaleratsperdosagegroupwitha confirmeddateofmatingwere assignedtoCaesarean-sectionoinngDG 10. The remaininfgemaleratswere permittetdonatufaldleylivelritterTsh.ese ratswereevaluatefdorclinical observatiodnusringpartudtiodnu,ratioonfgestatiolni,ftseirzeand pup viability atbirthM.aternablehavioorfthedams was evaluateddailwyhen thepupswere examinedduringthe21-daypostpartupmeriod.
Each liftwears evaluatefdorviabilaitlyeastwiceeachday duringthe21-day postpartupmeriodP.ups ineach liftweerrecountedoncedailyP.hysicasligns inthepupswere recordeodncedailfyor21 dayspostpartumP.up bodyweights and observednursinbgehaviowrere recordedon DLs 1 (birth4),,7,14 and 21. Surfacedghtinrgeflepxi,nnaunfoldinegy,e openinga,coustisctartlresponse and airrightirnegflewxeremonitoreduringthe21-daypostpartupmerioduntil allpupsintheliftreerachedthecriterifoonrthespeciftiecst.Pupilconstriction was evaluateodnceon DL 21. On DL 4,a tableofrandomunitwsas usedto culliftetrosfourmaleand fourfemalepups,wherepossibleO.n DL 21,a table ofrandomunitwsas usedtoselecttwomale and twofemalepupsfromeach liftferromGroups1,11and IIfIorcontinueedvaluation.
Fo generatiomnaleratswere sacrificaefdtecrompletioonfthecohabitation periodand necropsiegdr;osslesionwsere retainedT.he testese,pididymides, prostataend seminalvesicle(switahnd withouftluidw)ereexcisedi,ndividually weighedand retained.
Fo generatiofnemaleratsassignedtoCaesarean-sectionwienrgesacrificoend DG 10 and necropsiepdr;egnancystatuwsas confirmedO.variesand gross lesionwsere retainedT.he ratswere examinedforthenumberand distribution ofcorporaluteaineachovaryand implantatisointesa,nd viablaend nonviable embryos.Embryoswere discardeadfteerxamination.
Fo generatiofnemaleratsassignedtonaturadleliverwyeresacrificoendDL 21 and necropsiedO.variesand grosslesionwsere retainedT.he numberand distributoifoinmplantatisointewsas recorded.
At scheduledsacrifiacfetecrompletioonfthecohabitatipoenriod(maleratsthat siredlifteorfsdams allowetdonaturaldleylivearliftearn)d on DL 21 (female ratsallowedtonaturaldleylivearliftebrl)o,odsamples(approximate4lmyL per ratw)ere collectferdomtheinferivoernacavafromfivemaleand fivefemalerats perdosagegroupand shippedtotheSponsorforpharmacokinetaincalysis.
Pups notselectefdorcontinueedvaluation DL 4 were sacrificaendd necropsiedT.he stomachcontent(smilckurd)were collectferdomallculled pupsfromfiveofthelargesltifteirnsGroups1,11and IIIf,rozenand shippedto theSponsorforanalysis.
418-008:PAGE 1-3
The liverfrom each ratwas excised,weighed, and a sample section(laterallobe) was frozenand shipped to the Sponsor foranalysis.The liversofthe pups from the litterosfthe fivedams inGroups Ithrough IV selectedforpharmacokinetic sample collectiownere excised,pooled per liftefrr,ozenand shipped tothe Sponsor foranalysis.Dams inthe 3.2 mg/kg/day dosage group (Group V) did not have survivingpups on DL 21.
A.2. Fl Generation Rats/F2 Generation Littem:
Only the 0.1and 0.4 mg/kg/day dosage groups were continuedintothe second generationbecause ofthe excessivetoxicitsyeen inthe 1.6and 3.2mg/kg/day Fl generationpups.
There were 150 male and female Fl generationratsinthe threedosage groups (Groups Ithrough 111)2,5 ratsper sex per dosage group. Fl generationmale and female ratswere given appropriatedosages of the testarticloerally (gavage) beginningon DL 22 and continuingthrough the day beforesacrifice.
Beginning at24 days ofage, one male ratand one female ratfrom each lifteirn each dosage group were testedina passiveavoidance paradigm. Female rats were evaluatedforthe age ofvaginalpatency beginningon DL 28. Male rats were evaluatedforthe age ofpreputialseparationbeginningon DL 34. On postpartum day 70, one male ratand one female ratfrom each littewrere evaluatedina water-filleMd-maze. On approximatelyDL 90,ratswithineach dosage group were assigned to cohabitation.
Fl generationmale ratswere sacrificeadftercompletionofthe cohabitation periodand necropsied,as previouslydescribedforthe Fo generationmale rats. AllFl generationfemale ratswere permittedto naturalldyeliverlifterAsl.ldams thatdeliveredlifterwsere sacrificeodn DL 21 and necropsied,as previously describedforthe Fo generationfemale rats.
On DL 21, allF2 generationpups were sacrificeadnd examined forgross lesions.Necropsy procedures were the same as those describedforthe Fl generationpups.
Protoco4l18-008:CombinedOral(Gavage)FertiliDteyv,elopmentandPerinatal/PostnRaetparloductioTnoxicitSytudyofPFOS InRab
MALE
Aodkmgon 1 14 do" L
C..Oon .14 do
PhanyuKaWnek S&nWb Cokcson Sigmup
...
Fo Male Rate Sic6ked
r
y-
35 F, MRatL4)osoge Group Ankv at
To$" F&d*
Period Begin$ Maio Rats
FEMALE
AcdmMW. 14 days
Estmus Evaluation
Illomup.
CoMbiledo" 14.py.6
- -- - - -- - DO 10
ling
Period Ends
C- Sedioning
forMal$ Rats
10/gmup
35 F. Fornals Downg
Rst&#Dosago
Peded
Group Pirin at Begins br
Testing Faeft FoniMe Rea
DOO
DO 10
I@I Possible Delivery (DO 21)
Last POSS"
D"VL"Y (DO 25)
Downs
Polod Ends br Fenuk Rots(DL 20)
Ph@nTdc"o#c sanoo
colock" $*-p
PARTURITION LactatiDoany1 1)
I acrwiw
(DL2t)
Pi GENERATION
DoomgPedod BeginfsorFl GeneratiRoants
.1
CUNIng:
25 "*W and25
107!@ pupworoup d on study
(OL 4)
Matemal MilkCokcU*n (Groups 1.11and V)
xtrLcA AND Smftm RgVft Pkm
Ot@ft.AirR ft.
SR.AL DEVELOPMENT: UnkWW4 Eye 0"@IL Alt,.
- R~. PW4 C.-*~ OL Ift-0 OL 211
BEXUALMATURATION: OL 2 . Vn" Pd@"
OL 39@oft"uM $.W~
I PABSIVE AVOIDANCE: DL 24*1 days I milk &" I
femle pupWAr
Abbreviations:
WATERMM:
OL ?0.1 Nftow h.Al. p.~
DG Day of (Presumed) Gestation OL Day of Lactation
Da"p Prid
CohAbOonj 14 dT
IatPO"be Dolvwy(D021)
LootPatoft D*Mry (DO25)
DL to
0 E&rN@sdiayof mcrw= fw fl mls rats
PARTURITION LactationDay I (OL 1)
Los is Dayof
00$ft Mob an
Femele Rate (DL
F2 GEN RATION
I BACRWICE F Fi DAMW
F2 LffMRS: OL 21
B. Results
418-008:PAGE i-@-;
B.I. Fo Generation Male Rats:
No Fo generation male ratsdied during thisstudy as a resultof treatment with PFOS. Allclinicaolbservations(otherthan normal)were consideredunrelatedto the testarticlaend not signsofcompound toxicity.
Groups administered0.4 mg/kg/day and higherdosages ofthe testarticlhead reduced body weight gains forthe entirestudy.
Absoluteand relativfeeed consumption values were reduced inthe 1.6and 3.2 mg/kg/day dosage groups forthe entireprecohabftatiopneriod.Afterthe cohabitationperiod,absolutefeed consumption valueswere significantly reduced inthe 0.4 and 1.6mg/kg/day dosage groups.
Dosages ofthetestarticlaes high as 3.2 mg/kg/day did notaffectany mating and fertiliptayrameters evaluated.
A significantilnycreasednumber of male ratsinthe 3.2 mg/kg/day dosage group had a lighbtrown or brown livera,n observationattributetdo effectsof PFOS.
The 1.6and 3.2 mg/kg/day dosage groups had significantrleyduced terminal body weights.The absoluteweights ofthe seminal vesicleswithfluidand the prostatewere significantrleyduced inthe 3.2 mg/kg/day dosage group.
B.2. Fo Generation Female Rats/Fl Generation Lifters:
No Fo generationfemale ratsdied duringthisstudy as a resultoftreatmentwith PFOS.
Observationsoflocalizedalopeciawere increasedduringthe precohabitation, gestationand lactatiopneriodsinthe 0.4,1.6and 3.2 mg/kg/day dosage groups.
Groups administered1.6mg/kg/day and higherdosages ofthe testarticlhead significantrleyduced body weight gainsforthe entireprecohabitatiopneriod. The 1.6and 3.2 mg/kg/day dosages of PFOS continuedto reduce body weights and body weightgainsduringgestation.The 3.2 mg/kg/day dosage group had significantrleyduced body weighton DL 1. Body weightgainstended to be reduced inthe 0.4 mg/kg/day dosage group on DLs 1 to4,when significant weight lossoccurredinthe 1.6 mg/kg/day dosage group (the3.2 mg/kg/day dosage group was precludedfrom furtherevaluationbecause allpups died beforeDL 2).
418-008:PAGE1-6
Absoluteand relatifveedconsumptiovnalueswere reducedinthe1.6and 3.2mg/kg/daydosagegroupsduringtheprecohabitatpieorniodT.he 1.6and 3.2mg/kg/daydosagegroupscontinuetdohave reducedabsolutaend relative feedconsumptiovnaluesearlyinthegestatiopneriodA.bsolutaend relative matemalfeedconsumptiovnaluestendedtobe reducedinthe0.4mg/kg/day dosagegroupand were significanrteldyucedinthe1.6mg/kg/dadyosagegroup furtheentirleactatipoenrioda,nd atmostintervawlisthitnhisperiodT.he 3.2mg/kg/daydosagegroupwas precludefdromevaluatiobnecausetherewere no survivinpgupsafteDrL 1.
Dosagesofthetestarticalsehighas 3.2mg/kg/daydidnotaffecetstrous cyclinignthe15 ratsperdosagegroupthatwere evaluatedM.atingand fertility parameterwsereunaffectebdy the3.2mg/kg/daydosageofPFOS.
Allnecropsyobservatiownesreconsidereudnrelatetdotreatment.
Therewere no biologicailmlpyortanotrstatisticsailglnyificdainftferenciensthe liftaevreragesforcorporaluteai,mplantatiovnisa,blembryosornonviable embryosatCaesarean-sectionoinngDG 10.
The duratioonfgestatiownas significanrteldyucedinthe3.2mg/kg/daydosage group,an observatioanssociatewdithpreimplantatlioosns[theaveragenumber ofimplantatisointepserdam was significanrteldyucedr,esultiinnga significantly reducedliftseirze]P.up viabilwiatsy significanrteldyucedinthe1.6and 3.2mg/kg/daydosagegroups.Reflectitnhgeseeffecttsh,eviabilaintdy lactatiionndicewseresignificanrteldyucedinthe1.6and 3.2mg/kg/daydosage groupst,helactatiionndexwas alsosignificanrteldyucedinthe1.6mg/kg/day dosagegroup,as alsoweretheaveragesforsurvivipnugpsinthe1.6mg/kg/day dosagegroupbeginninogn DL 4 postcullianngd,inthe3.2mg/kg/daydosage groupon DL 1.
A dosage-dependenptatteronfreducedpup bodyweightwas evidenitneach groupadministeretdhetestarticlTeh.e 0.1mg/kg/daydosagegrouptendedto havereducedpupweightson DL 4 (prea-nd postcullincgo)m,paredtothe controglroupvalue.The 0.4mg/kg/daydosagegrouptendedtohavereduced pup bodyweightson DLs 1through4 (postcullicnogm)p,aredtothecontrol groupvalue.However,none ofthedifferenciensthe0.1and 0.4mg/kg/day dosagegroupswerestatisticsailglnyificandtmay represenntormalbiological variationTsh.e 1.6mg/kg/daydosagegrouphad significanrteldyucedpup body weightson allweighindgays.The 3.2mglkg/daydosagegrouphad a significanrteldyucedpup bodyweighton DL 1 (nopupssurvivetdosubsequent scheduledweighings).
Clinicanld necropsyobservatioanssociatewdithreducedpup viabilaintdy potentiraelductioinnmaternaclareoccurreidnthe3.2mg/kg/dadyosagegroup.
418-008:PAGE 1-7
Adverse clinicaolbservationsincludethree lifterwsithpups thatwere not nursing(twoofthese litterhsad pups from which the placentahad not been removed, and one had pups thatwere not nested).Apparent maternal cannibalizatiownas alsoevidentinthisdosage group (missingtailinone pup and a cannibalizedforelimbinanotherpup). Itwas not possibleto determine whether these occurredbeforeor afterthese pups had died.
Necropsy observationsinpups thatwere stillboronrfound dead indicatedmany pups withno milkinthe stomach inthe 1.6and 3.2 mg/kg/day dosage group pups. The 3.2 mg/kg/day dosage group also had evidence ofincreased maternalcannibalizatioant necropsy of stillborand found dead pups. Nine of these pups had missinghindlimbsand/orportionofthe tail.
Reversibledelays inreflexand physicaldevelopment thatare highlycorrelated withbody weightoccurredinthe 0.4 and 1.6 mg/kg/day dosage groups. Surface rightinwgas delayed inthe 1.6and 3.2 mg/kg/day dosage groups. The time of development forpinna unfolding,eye opening,acousticstartlereflexand ability to airrightwere delayed inthe 1.6mg/kg/day dosage group (no 3.2 mg/kg/day dosage group pups were evaluatedforthisparameter).Alllivepups inthe 0 (Vehicle)0,.1,0.4and 1.6mg/kg/day dosage groups had the pupilconstriction response when testingwas done on DL 21 (end oflactation).
Upon weaning ofthe lifter(sDL 21),a decisionwas made regardingthe Fl generationpups inthe 1.6 mg/kg/day dosage group. The 1.6mg/kg/day dosage group pups were small (theyhad gained 20% lessweight duringlactatiotnhan the controlpups) and inthe opinionofthe attendinglaboratoryveterinariant,he ratswere notsuitableforfurtherexperimentation.Ithad been determined that the dosage of 1.6mg/kg/day was a levelwhich produced compound toxicity. Continued dosing of 1.6 mg/kg/day most likelwyould not resultinany additional informationand would subjectthe pups to additionadlistress.Therefore, consultatiowniththe Sponsor leadto the decisionnot tocontinuethe 1.6mg/kg/day dosage group Fl generationpups. Only the 0 (Vehicle)0,.1 and 0.4 mg/kg/day dosage group pups were continuedto a second generation.
B.3. Fl Generation Male Rats:
No deaths inthe Fl generationmale ratsat 0.1 and 0.4 mg/kg/day dosages were attributetdo PFOS. Allclinicaolbservationswere consideredunrelatedto the testarticle.
The 0.1 and 0.4 mg/kg/day dosage groups tended toweigh lessthan the control group on day 1 postweaning and generallygained one ortwo grams lessbody weight per week than the controlgroup rats.Reflectintghispatternofweight gain,weight gains inthe 0.1 and 0.4 mg/kg/day dosage groups forthe precohabitatiopneriodwere 98.4% and 97.6% ofthe controlgroup value,
418-008:PAGE 1-8
respectivelyB.ody weight gainsinthe 0.1 and 0.4 mg/kg/day dosage groups for day 1 to terminationwere 98.5% and 96.6% ofthe controlgroup value, respectivelyH.owever, none ofthese body weight gain differenceswere statisticaslilgynificanftrom controlvalues.
Absolutefeed consumption valuesforthe 0.1 and 0.4 mg/kg/day dosage groups were significantrleyduced on postweaning days 1 through 8. Relativefeed consumption values tended to be reduced inthe 0.1 and 0.4 mg/kg/day dosage groups duringthe firswteek of intubatiobnut none were statisticaslilgynificant.
Dosages ofthe testarticlaes highas 0.4 mg/kg/day did not affectthe average day of preputiasleparationinthe Fl generationmale rats.There were no biologicalilmyportantdifferencesinthe valuesforlearning,short-termretention, long-termretentionor response inhibitiointhe Fl generationmale rats,as evaluatedby performance ina passiveavoidance or watermaze performance paradigm.
Dosages ofthe testarticlaes high as 0.4 mg/kg/day did notaffectany mating and fertiliptayrameters evaluatedinthe Fl generationmale rats.
Allnecropsy observationsinthe Fl generationmale ratswere considered unrelatedtothe testarticlbeecause. No statisticaslilgynificandtifferences occurredinthe absoluteor relativvealuesforthe weightsofthe rightor left testiss,eminalvesicles,rightepididymisor prostate.Terminalbody weights tended to be reduced inthe 0.1 and 0.4 mg/kg/day dosage groups but were not statisticaslilgynificanftrom controlvalues.
B.4. Fl Generation Female Rats/F2 Generafion Litters:
No deaths inthe Fl generationfemale ratswere attributetdo PFOS. Alladverse clinicaolbservationsthatoccurredduringthe precohabitation, gestationand lactatiopneriodswere consideredunrelatedto the testarticle.
Body weightstended to be reduced inthe 0.4 mg/kg/day dosage group on day 1 postweaning. Maternalbody weights and body weight gains duringthe gestation periodwere unaffectedby dosages ofthe testarticlaes high as 0.4 mg/kg/day. Significanmtaternalbody weight lossoccurredon DLs 1 to4 inthe 0.4 mg/kg/day dosage group.
The 0.4 mg/kg/day dosage ofthe testarticlweas associatedwitha significant reductioninabsolutefeed consumption and a tendency forreduced relativfeeed consumption on days 1 to 8 postweaning. Absoluteand relativfeeed consumption values duringthe gestationperiodwere unaffectedby dosages of thetestarticlaes high as 0.4 mg/kg/day. The absoluteand relativmeaternal
418-008:PAGE 1-9 REVISED PAG-R_
feed consumption values were reduced duringlactatioinnthe 0.4 mg/kg/day dosage group.
Dosages ofthe testarticlaes high as 0.4 mg/kg/day didnot affectthe average day ofvaginalpatency inthe Fl generationfemale rats.There were no biologicalliymportantdifferencesinthe values forleaming,short-termretention, long-termretentionor response inhib;.tiionnthe Fl generationfemale rats,as evaluatedby performance ina passiveavoidance orwatermaze performance paradigm.
Dosages ofthe testarticlaes high as 0.4 mg/kg/day didnot affectany mating and fertiliptayrameters evaluatedinthe Fl generationfemale rats.
Allnecropsy observationsinthe Fl generationfemale'ratswere considered unrelatedtothe testarticle.
Pregnancy occurredin22 (95.6%),21 (84.0%)and 24 (96.0)ofthe23,25 and 25 female ratsassigned to cohabitatioinnthe 0 (Vehicle)0,.1 and 0.4 mg/kg/day dosage groups,respectivelyA.llpregnant dams deliveredliftersT.he gestation indexwas comparable across the three dosage groups. Viabilitaynd growth of the second generationoffsprin(gF2 pups)to weaning were also unaffectedby the highestdosage tested,0.4 mg/kg/day. There were no toxicologically importantdifferencesfrom the controlgroup values. No clinicaolr necropsy observationsinthe F2 generationpups were attributablteodosages ofthe test articlaes high as 0.4 mg/kg/day
C. Conclusions
418-008:PAGE1-10 REVISED PAGE
On thebasisofthesedata,theFo generatiomnatemaland paternanloobservable-effect-lev(eNlOEL) of PFOS is0.1 mg/kg/day (0.4mg/kg/day and higherdosages caused reductionsinbody weight gainand reduced feed consumption values).
The Fo generationreproductiveNOEL isgreaterthan 3.2 mg/kg/day;no effects on mating,fertiliotryestrouscyclingoccurred.The NOEL forviabiliatnyd growth inthe Fl generationoffspringis0.4 mg/kg/day (1.6mg/kg/day and higherdosages caused preimplantationlossand reductionsinlittesrize,pup viabilitgyr,owth and survival).
The Fl generationmaternaland paternalNOEL of PFOS is0.1 mg/kg/day (0.4mg/kg/day dosage caused reductionsinbody weight gainand reduced feed consumption values).
The Fl generationreproductiveNOEL isgreaterthan a dosage of 0.4 mg/kg/day;no effectson mating or fertiliotcycurred.The NOEL forviability and growth inthe F2 generationoffspringisalso 0.4mg/kg/day. There were no toxicologicalilmyportanteffectson pup survivalor growth atthe highestdosage tested,0.4 mg/kg/day.
-------------
--------------
MildredS. ChristianP,h.D.,Fellow,ATS Date Exec tiveDirectorof Research
M. oberman, Ph.D.,DABT
Date
Directorf Research
----------------
Ray nd G. ork P.D ABT
Date
AssociateDirecto'r R " earch and Study Director
li. DESCRIPTION OF TEST PROCEDURES
418-008:PAGE 11-1
A. Conduct of Siydy:
A.I. SRonso:
3M ToxicologyServices,3M Center,Building220-2E-02,St.Paul, Minnesota 55144-1000
A.2. TestingFacilily:
Argus Research LaboratoriesI,nc.,905 Sheehy Drive,BuildingA, Horsham, Pennsylvania 19044-1297
A.3. Study Number:
418-008
A.4. SRonsor's Study Number:
6295.9
A.S. PurROse of the Study:
The purpose ofthisstudy was totestfortoxiceffects/disturbancreessultinfgrom PFOS treatmentof Crl:CDOBR VAF/Plus(D male and female ratsbefore cohabitatiotnhroughmating,gestationand lactationT.his studywas designed to evaluateICH Harmonised TripartitGeuidelinestages A through F ofthe reproductiveprocess and detecteffectson the estrouscycle,tubaltransport, implantationg,estationp,arturitiolna,ctatioannd matemal behaviorinfemale rats,on the development of the offspringofthe treatedmale and female rats, and permitdetectionoffunctionaelffects(e.g.e,ffectson libidor epididymal sperm maturation)thatmay not be detectedby histologicaelxaminationsof male ratreproductiveorgans. Because manifestationsofeffectsinduced duringthis periodmay be delayed inthe offspringo,bservationswere continuedthrough productionofF2 generationlifters.
A.6. Study Design:
A modificatioonfthe requirementsofU.S. Food and Drug Administratio(nFDA)(') were used as a basisforthe study design.
A.7. Regulatoly COmRiiance:
418-008:PAGE 11-2
The study was conducted incompliance withthe Good LaboratoryPractice (GLP) regulationosfthe U.S. Food and Drug Administratio(nFDA)(')t,he Japanese Ministryof Healthand Welfare(MHW)(')and the European Economic Community (EEC)(4)T.here were no significadnetviationsfrom the GLP regulationtshataffectedthe qualityor integritoyfthe study. QualityAssurance Unitfindingsderivedfrom the inspectionsduringthe conduct ofthisstudy are documented and have been providedtothe Study Directorand the Testing FacilitMyanagement.
A.8. Ownership of the Stud
The Sponsor owns the study. Allraw data,analyses,reportsand allpreserved tissuesare the propertyofthe Sponsor.
A.9. Study Monitor:
Marvin T. Case, D.V.M.,Ph.D.
A.10. AlternateStudy Monito
Andrew M. Seacat, Ph.D.
A.11. Study Director:
Raymond G. York, Ph.D.,DABT (AssociateDirectorof Research)
A.12. Technical Performance:
John F. Barnett,B.S. (DirectorofLaboratoryOperations) KristenlandolaSherer,B.S. (Research Associate/FetaElvaluation) Joseph W. Lech, B.S.(Team Leader - GeneralLaboratory) Sharon Adamski (LaboratoryTechnician)
A.13. R9Rort Preparation
Raymond G. York, Ph.D.,DABT MichelleR. Rzaca, B.S. (StudyCoordinator) HeidiM. Green, M.S. (StudyCoordinator) ErinHagan, B.A.(Data Management Specialist) Karen G. Parker,A.A. (ReportAdministrator)
A.14. Report Review:
418-008:PAGE 11-3
Alan M. Hoberman, Ph.D., DABT (Directorof Research) MildredS. ChristianP,h.D.,Fellow,ATS (ExecutiveDirectorof Research)
A.15. Date Protocol Signed:
21 May 1998
A.16. Dates of TechnicalPerformance:
Fo Generation Male Rats
Rat ArrivalDate
12 MAY 98
Dosage Period(42 days beforecohabitation,
througha 14-day cohabitation
periodand untilsacrifice)
26 MAY 98 - 30 JUL 98
Scheduled Sacrifice
31 JUL 98
Fo GenerationFemale Rats
Rat ArrivalDate
12 MAY 98
Dosage Period- Female Rats Assigned to
Caesarean-Sectioning(42 days before
cohabitatioannd continuingthrough DG a 9) 26 MAY 98 - 17 JUL 98
Dosage Period- Female Rats Assigned to
NaturalDelivery[42 days before
cohabitatiotnhrough DG 24 (ratsthatdid notdelivera lifteorr)DL b 20 (ratsthatdelivered
a lifter)
26 MAY 98 - 30 AUG 98
Dosage Period Estrous
Cycle Evaluation
09 JUN 98 - 06 JUL 98
a. DG isused as an abbreviatiofnorday of (presumed) gestation. b. DL isused as abbreviationforday of lactation.
(Fo GenerationFemale Rats Continued)
418-008:PAGE 1!-4
CohabitationPeriod Male 1 Male 2
DG 10 Caesarean-Sectioning NaturalDeliveryPeriod(DL 1) DG 25 Sacrific(eratsthatdidnot deliver
a lifter) DL 21 Sacrific(edams and pups not selectedforcontinuedstudy)
06 JUL 98 PM - 13 JUL 98 AM 13 JUL 98 PM - 20 JUL 98 AM
17 JUL 98 - 30 JUL 98 28 JUL 98 - 10 AUG 98
01 AUG 98 - 07 AUG 98
17 AUG 98 - 30 AUG 98
Fl GenerationRats
Dosage Period(Male Rats) Dosage Period(Female Rats) PassiveAvoidance Testing Watermaze Testing CohabitationPeriod (initiatwehden approximately90 days ofage) Male 1 Male 2 Male Rats Sacrificed NaturalDeliveryPeriod(DL 1) DL 21 Sacrifice
19 AUG 19 AUG 20 AUG 07 OCT the ratsare
98 - 16 NOV 98 - 27 DEC 98 - 10 SEP 98 - 19 OCT
02 NOV 98 PM - 09 NOV 09 NOV 98 PM - 16 NOV
17 NOV 98 24 NOV 98 - 08 DEC 14 DEC 98 - 28 DEC
98 98 98 98
98 AM 98 AM
98 98
A.17. Records Maintained:
The originarleport,raw data and reservesamples ofthe bulktestarticlaend vehiclecomponents are retainedinthe archivesofArgus Research Laboratories, Inc.Any preserved tissuesare retainedinthe archivesofthe TestingFacilitfyor one year aftermailingthe draftfinalreport,afterwhich timethe Sponsor will decidetheirfinaldispositionA.llunused testarticlseuspensions were discarded atthe TestingFacilityU.nused bulktestarticlweas returnedtothe Study Monitor.
B. Test ArticleInformation:
B.I. Description:
PFOS - an off-whitepowder
B.2. Lot Number:
217 (ExpirationDate: May 2000)
B.3. DateReceivedand StorageConditions:
418-008:PAGEli-I.-I
The testarticlweas receiveodn 20 May 1998,and storedatroom temperature. Prepared suspensions were storedat room temperatureovernight.
B.4. Special Handling Instructions:
Standard safetyprecautions(use ofprotectivcelothingg,loves,dust-mist respiratoarnd safetygoggles)were taken when handlingthe bulktestarticlaend prepared suspensions.
B.5. Analysis of Activily:
Informationregardingthe purityi,dentitys,trengthand compositionofthe test articlieson filewiththe Sponsor.
C. Vehicle Information:
C.l. Description:
0.5% Tween@ 80 inreverseosmosis membrane processed deionizedwater (R.O.deionizedwater).
C.2. Lot Numbers:
M03HO5, K03737, M29477 and L06662
C.3. Dates Received and Storage Conditions:
The Tween@ 80 was receivedfrom J.T.Baker,PhillipsburNge,w Jersey,on 15 August 1997 (LotK03737),22 May 1998 (LotM03HO5), 17 September 1998 (LotM29477), 3 December 1998 (LotM03HO5) and 1 September 1998 (LotL06662),and was storedatroom temperature.R.O. deionizedwater is availablefrom a continuoussource atthe TestingFacilitaynd ismaintained at room temperature. The vehiclewas preparedweekly and storedatroom temperature.
C.4. SROcialHandling Instructions:
418-008:PAGE 11-6
Standard safetyprecautions(use of protectivcelothingg,loves,dust-mist respirators,afetygoggles or safetyglassesand a face-shieldw)ere taken when handlingthe vehicle.
C.S. Analysis of Puft:
Neitherthe Sponsor nor the Study Directorwas aware ofany potential contaminants likeltyobe presentinthe vehiclethatwould interferweiththe resultsof thisstudy.
D. Test ArticlePreRaration:
Suspensions of PFOS were prepared dailyone day priortothe day ofdosing atconcentrationsof0, 0.02,0.08,0.32 and 0.64 mg/mL. The testarticlweas considered 100% pure forthe purpose ofdosage calculations.
D.1 Sample Information:
Sample Type
Size
Date Retained
Shipping/Storage
Conditions
Shipped To
Date Ship
concentration(allevels) 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
VehicleComponent Reserve
Tweene 80
5 mL
R.O. Water
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 syringewas used to withdraw samples from each concentrationduringthefirsatnd sixthweek of dosage administratiofnortheFo generationand duringthefirspand lastweeks ofdosage administratiofnorthe Fl generation.Each sample was dividedintotwo aliquots(2 mL and 3 mL, respectively)O.ne aliquot(2 mL) was shipped foranalysis.The otheraliquot(3 mL) was retainedattheTestingFacilitays a backup.
b. A syringewas used to withdraw samples from thetop,middleand bottom of the highestconcentrationon the firsdtay
of preparation.Each sample was dividedintotwo aliquots(2 mL and 3 mL, respecwely). One aliquot(2 mL) was shipped foranalysis.The otheraliquot(3 mL) was retainedat theTestingFacilitays a backup.
Stabilitdyata forprepared formulationsbracketingthe range of concentrations are on filewiththe Sponsor. The Sponsor confirmeda 48-hour stabilitoyn the testarticlien0.5% Tween@ 80 solutions.
a. See APPENDIX G (DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY), ftem 1.
D.2. AnalyticalResults:
418-008:PAGE 11-7
Resultsofthe concentrationand homogeneity analyseswere not availableatthe time ofthe writingofthisreport.
E. Test System:
E.I. Species:
Rat
E.2. Strain:
Crl:CD(DBR VAF/Plus@ (Sprague-Dawley)
E.3. Supplier(Source):
Charles RiverLaboratories,Inc.,Raleigh,North Carolina
E.4. Sex:
Male and Female
E.S. RationaleforTest System:
The Crl:CDOBR VAF/Plus@ (Sprague-Dawley)ratwas selectedas the Test System because: 1)thisstrainofrathas been demonstrated to be sensitivteo reproductiveand developmental toxinsand has been widelyused throughout industryforreproductiveand developmentaltoxiciteyvaluations2;) historical dataand experienceexistatthe TestingFacility("a)n;d 3) the testarticlies pharmacologicallyactiveinthe speciesand strain.
E.6. Test System Data:
Male Rats
Female Rats
Number of Rats Approximate Date of Birth Approximate Age atArrival Weight (g)on the Day afterArrival 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 arrivalF,o generationratswere assigned to individuahlousing on the basis of computer-generatedrandom units.Afteracclimationm,ale and female rats were selectedforstudy on ttiebasis ofphysicalappearance and body weights recordedduringacclimation.Rats were assigned tofivedosage groups (Groups IthroughV),35 ratsper sex per dosage group,usinga computergenerated (weight-orderedr)andomizationprocedure.
The firstten female ratsper dosage group witha confirmedmating date were assigned to Caesarea n-sectioinng on DG 10. The remaining ratswere permitted to naturallydeliverlitters.
A tableof random unitswas used to assign fiveratsper group to pharmacokineticsample collectioenitheratscheduled sacrificaeftercompletion ofthe cohabitatiopneriod(male ratssiringlitterwsithdams allowed tonaturally delivera lifteorr)on DL 21 (femaleratsallowedto naturalldyelivera lifter).
E.7.b.Fl/F2 Generation Pups
On DL 4, a tableofrandom unitswas used toselectthe pups to be culledand litterwsere reduced toeightpups each. Whenever possible,the same number ofmale and female pups per liftewrere continuedon study.
At weaning ofthe Fl generationpups on DL 21, a tableof random unitswas used toselect25 male and 25 female pups ineach ofGroups 1,11and 111, resultinigna totalof 150 Fl generationrats(75 per sex)chosen forcontinued evaluation.At leastone male pup and one female pup per liftewrere selected. There were no survivingpups inGroup V afterDL 2;pups inGroup IV were not
continuedon the studybecause ofsevere toxiceffectsinthe pups (deathand retardedgrowth)duringlactationT.his decisionwas made inconsultatiownith the study veterinariaannd the Sponsor.
E.B. System of Identification:
E.8.a.Fo Generation
Rats were permanently identifieudsing Monel@ self-piercienagr tags (Gey Band and Tag Co., Inc.,No. MSPT 20101). Male and female ratswere assigned temporary numbers at receiptand given unique permanent identification numbers when assigned tothe study beforeadministratioonfthe firsdtosage of the testarticle.
E.8.b.FI/F2 Generation, Pups and Rats
418-008:PAGE 11-9
Pups were not individualliydentifiedduring lactationa;llparameters were evaluatedinterms ofthe liftebroth beforeand aftercullingon DL 4. At weaning, each Fl generationratselectedforcontinuedobservationwas identifiewditha Monele self-piercinegar tag.
F. Husbandry:
F.I. Research FacililyRegistration:
USDA RegistratioNno. 23-R-099 under the Animal Welfare Act,7 U.S.C. 2131 etseq.
F.2. Study Rooms:
The study rooms were maintainedunder conditionsof positiveairflowrelativteo a hallwayand independentlysuppliedwitha minimum often changes per hour of 100% freshairthathad been passed through99.97% HEPA filtersR.oom temperature and humiditywere monitoredconstantlythroughoutthe study.
Room temperaturewas targetedat 64OF to79OF (180C to 26"C); relative humiditywas targetedat 30% to 70%. See APPENDIX H (TEMPERATURE AND RELATIVE HUMIDITY REPORTS).
F.3. Housing:
Allcage sizesand housingconditionwsere incompliancewiththeGuideforthe Care and Use ofLaboratorAynimals(e).
F.3.a.Fo GenerationRats/FlGenerationLifters
Fo generationratswere individuallhyoused instainlessteelwire-boftomed cages except duringthe cohabitatioannd postpartumperiods.During cohabitatione,ach pairofratswas housed inthe male rat'scage. Beginning no laterthan DG 20, Fo generationfemale ratsassigned to naturaldeliverywere individuallhyoused innestingboxes. Each dam and deliveredliftewrere housed ina common nestingbox duringthe postpartum period.
F.3.b.Fl Generation Rats/F2 Generation Litters
Afterweaning, the Fl generationratswere individualhloyused before cohabitationh,oused inpairs(one male ratper female rat)duringcohabitation, and individuallhyoused aftercohabitationT.he same type of cagingwas used as describedforthe Fo generationrats.Beginning no laterthan DG 20, Fl generationfemale ratswere individualhloyused innestingboxes. Each dam
418-008:PAGE
and deliveredlittewrere housed ina common nestingbox duringthe postpartum period.
F.4. Lighting:
An automatically-controllfelduorescentlighctyclewas maintained at 12-hours light:12-hourdsark,witheach dark periodbeginningat 1900 hours EST.
F.5. Sanitization:
Cage pan linerswere changed approximatelythreetimes each week. Cages were changed approximatelyevery otherweek. Bedding was changed as often as necessary to keep the ratsdry and clean.
F.6. Feed:
Ratswere givenad libituamccesstoCertifieRdodentDietg#5002 (PMI NutritioInnternationaIln,c.,St.Louis,Missouri)inindividuafleeders.
F.7. Feed Analysis:
Analyses were routinelpyerformed by the feed supplier.No contaminants at levelsexceeding the maximum concentrationsforcertifiefdeed or deviations from expected nutritionraelquirementswere detectedby these analyses. Copies ofthe resultsofthe feed analysesare availableinthe raw data.
Neitherthe Study Directornorthe Sponsor was aware ofany agent presentin the feed thatwas known tointerferweiththe resultsof thisstudy.
F.8. Water:
Local water thathad been processed by passage througha reverseosmosis membrane (R.O.water)was availableto the ratsad libitumfrom an automatic wateringaccess system and/orindividuawlater boftles.Chlorinewas added to the processed water as a bacteriostat.
F.9. Water Analysis:
The processed water isanalyzedtwiceannuallyforpossiblechemical contamination(LancasterLaboratoriesI,nc.,Lancaster,Pennsylvania)and monthly forpossiblebacteriaclontamination(AnalyticaLlaboratoriesI,nc., Chalfont,Pennsylvania).Copies ofthe resultsofthe water analysesare availableinthe raw data.
418-008:PAGE 11-11 Neitherthe Study Directornor the Sponsor was aware ofany agent presentin the water thatwas known to interferweiththe resultsofthisstudy.
F.10. Bedding:
Bed-o'cobsO was used as nestingmaterial(The Andersons IndustriaPlroducts Group, Maumee, Ohio).
F.11. Bedding Analysis:
Neitherthe Sponsor nor the Study Directowras aware ofany potential contaminants likeltyo be presentinthe bedding thatwould interferweiththe resultsofthisstudy. Analyses forpossiblecontaminationare conducted annuallyand documented inthe raw data.
G. Methods:
G.l. Dosage Administration:
Dosage Group
1 11 111 IV Iv
Dosage
Concentration Dosage Volume
(mg/kg/day) (mg/ML)
(mL/kg)
0 (Vehicle)
0
5
0.1
0.02
5
0.4
0.08
5
1.6
1
0.32
5
3.2
0.64
5
I-
I
Number ofFo Generation Rats
Per Sex
35 35 35 35
35
Number ofFl Generation Rats
Per Sex
25
25
25
The testarticlewas considered 100% pure forthe purpose of dosage calculations.
G.2. Assigned Rat Numbers:
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Dosage Group
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 Fl GenerationRat Numbers
Male
Female
13101 -13125
13201 -13225
13126 -13150 13151 -13175
a b
13226 -13250 13251 -13275
A B
a. On DL 21, allsurvivinpgups inthe 1.6 mg/kg/daydosage group (Group IV)were sacrificebdecause of severe toxiceffectsinthe pups duringlactation.
b. There were no survivingpups afterDL 2 inthe 3.2 mg/kg/day dosage group (Group V).
G.3. Rationalefor Dosage Selection:
Dosages were selectedby the Sponsor on the basisof previousstudies conducted withthe testarticle.
G.4. Route of Administration:
Oral (gavage)
G.S. Rationale forRoute of Administration:
The oral(gavage) routewas selectedforuse because: 1)incomparison withthe dietaryroute,the exactdosage can be accuratelyadministered;and 2) itisone ofthe possibleroutesof human exposure.
G.6. Freguency of Administration:
The Fo generationmale ratswere given appropriatedosages ofthe testarticle once dailybeginning42 days beforecohabitation(whichcontinuedfora maximum of 14 days) and continuingthroughthe day before sacrifice.
The Fo generationfemale ratswere given the appropriatedosages of the test articlbeeginning42 days beforecohabitation(whichcontinuedfora maximum of 14 days) and continuingthroughDG 9 (ratsassigned to Caesarean-sectioning), DG 24 (ratsassigned to naturaldeliverythatdid not delivera liftero)r,DL 20 (ratsthatdiddelivera lifterT)h.e dosage volume (5 mL/kg) was adjusteddaily on the basis ofthe most recentlyrecordedbody weight and given at approximatelythe same time each daya.
a. See APPENDIX G, item2.
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Dams inthe processofdeliverinpgups were not dosed untilcompletionof parturitioinn,orderto precludepossibledisruptioonfmaternalbehaviorand/or cannibalizatioonfthe pups. Consequently,some dams were notadministered one dailydosage duringthe deliveryperiod.No dam missed more than one dailydosage.
Fl generationmale and female ratswere givenappropriatedosages of the test articloerally(gavage),beginningon day 1 postweaning (DL 22)8and continuing throughthe day beforesacrificeF.2 generationpups were notdirectlgyiventhe testarticleb,ut may have been possiblyexposed tothe testarticldeuring gestation(inuteroexposure)or viamaternalmilkduringthe lactatiopneriod.
G.7. Length of Study:
Approximately7 months
G.8. Method of Study Performance:
G.8.a Fo Generation Rats
AllFo generationratswere observed forviabiliattyleasttwicedailyduringall periodsofthe study. Rats were alsoobserved forgeneralappearance at least once duringthe acclimationperiodand forclinicaolbservationsofeffectsofthe testarticlea,bortionsp,remature deliveriesp,riortoand approximatelyone hour afterdosage and on the day sacrificed.
Body weightsforFo generationmale ratswere recordedat leastonce duringthe acclimationperiod,weekly duringthe dosage periodand at sacrificeF.eed consumption valuesformale ratswere recordedweekly duringthe dosage period.
Body weightsforFo generationfemale ratswere recorded atleastonce during the acclimationperiod,weekly to cohabitationd,ailyduringthe gestationperiod, on DLs 1,4, 7, 10 and 14 (ratsassigned to naturaldeliverya)nd atsacrifice. Feed consumption valueswere recordedweekly tocohabitationd,ailyduringthe gestationperiodand on DLs 1,4, 7, 10 and 14 (ratsassigned to natural delivery).Feed consumption valueswere not recorded afterDL 14,when itwas expected thatthe pups would begin to consume maternalfeed. A tableofrandom unitswas used toselect15 female ratsper dosage group for evaluationofestrouscyclingby examinationofvaginalcytologyfor28 days beforethe startofthe cohabitationperiod.
a. See APPENDIX G, item 3.
"'18-008:PAGE 11-14
Withineach dosage group, consecutiveorderwas used toassign ratsto cohabitationo,ne male ratper female rat.The cohabitationperiodconsistedofa maximum of 14 days. During cohabitationa,llfemale ratswere evaluateddaily untilobservationof spermatozoa ina smear ofthe vaginalcontentsand/or a copulatorypluginsitu(DG 0),followingwhich they were assignedto individual housing. Female ratsthatdid notmate withinthe firssteven days of cohabitatiownere assigned alternatemale ratsthathad mated (withitnhe same dosage group) and remained incohabitationfora maximum ofseven additional days.
The firstten female ratsper dosage group witha confirmedmating date were assigned to Caesarea n-sectioinng on DG 10. The female ratsassigned to Caesarean-sectioningwere examined forthe number and distributiofncorpora lutea,implantatiosnitesand viableand nonviablefetuses.The remainingfemale ratswere permittedto naturalldyeliverliftersT.hese ratswere evaluatedfor clinicaolbservationsduringparturitiodnu,rationofgestation(DG 0 tothe day the firsptup was observed),liftesrize(allpups delivered)and pup viabiliattybirth. Pups thateitherappeared stillboronrthatdied before initieaxlaminationofthe lifterfsorviabiliwteyre examined forvitalstatusat birth.The lungs were removed and immersed inwater. Pups withlungs thatsank were considered stillborpnu;ps withlungsthatfloatedwere consideredlivebornand to have died shortlyafterbirth.Each liftewras subsequentlyexamined dailyforpup viability. Maternalbehaviorofthe dams was evaluateddailywhen the pups were examined duringthe 21-day postpartum period.Observed maternalbehavior was recordedon DLs 1,4, 7, 14 and 21. Variationsfrom expected maternal behaviorwere recorded,ifand when present,on allotherdays ofthe postpartum period.
Fertiliptayrameters were assessed foralldams assigned tonaturaldelivery. These parameters includedthe fertilitnydex(percentageof matingsthat resultedinpregnancies),gestationindex(percentageof pregnanciesthat resultedinthe birthof liveliftersn)u,mber of offsprinpger litte(rlivaend dead pups),number of implantatiosnites,generalconditionofthe dam and lifter duringthe postpartumperiod,viabiliitnydices(percentageofpups born that survived4 and 7 days),and lactatioinndex(percentageof pups born that survived21 days).
G.8.b Fl/F2 Generation Pups - Preweaning Observations
Day 1 of lactatio(npostpartum)was definedas the day of birthand was alsothe firsdtay on which allpups ina liftewrere individuallwyeighed (pup body weights were recordedafterallpups ina littweerre deliveredand groomed by the dam).
Vitalstatusatbirthwas determined forpups thateitherappeared stillboronr that died beforeinitieaxlaminationofthe liftefrorviabilityP.ups thateitherappeared
418-008:PAGE
stillboronr thatdied before initieaxlaminationofthe littefrorviabiliwteyre examined forvitalstatusatbirtha,s previouslydescribed.
Each liftewras evaluatedforviabilitaytleasttwiceeach day duringthe 21-day postpartumperiod.Pups ineach liftewrere counted once daily.Physicalsigns (includinvgariationfsrom expected nursingbehaviorand gross externalphysical anomalies)inthe pups were recordecionce dailyfor21 days postpartum. Dead pups observed atthese times were removed from the nestingbox. When not precludedby autolysisor cannibalizatiobny the dam, any pup found dead was necropsiedand examined forthe cause of death. Pup body weightswere recordedon DLs 1 (birth4),7, 14 and 21.
Reflexand physicaldevelopment parameters inthe Fl generationpups only were monitoredduringthe 21-day postpartum period.Surfacerightingreflex [abilitoyrightin5 seconds (fromDL 1)],pinna unfolding(fromDL 2),eye opening (fromDL 12),acousticstartlreesponse (fromDL 13) and airrighting reflex(fromDL 14)were monitoreduntialllpups (100%) inthe lifterreached the criteriofnorthe specifitcest.Pupilconstrictiownas evaluatedonce on DL 21; the number ofpups per liftewriththisreflexpresentwas recorded.
G.8.c.Fl Generation Rats - Postweaning Observations
"Postweaning day" observationswere recorded beginningon DL 22. AllFl generationratswere observed forviabiliattyleasttwicedailyduringallperiods ofthe study. Rats were alsoobserved forgeneralappearance at leastonce duringthe acclimationperiodand forclinicaolbservationsofeffectsofthe test articlea,bortions,premature deliveriepsriorto and approximatelyone hour after dosage and on the day sacrificed.
Body weightsforFl generationfemale ratswere recordedweekly duringthe postweaning periodsand at sacrificeF.eed consumption values were recorded weekly except duringcohabitationand at sacrifice.
Body weightsforFl generationfemale ratswere recordedonce weekly to cohabitationd,ailyduringpresumed gestation,on DLs 1,4,7 and 14 (rats assigned to naturaldeliverya)nd atsacrificeF.eed consumption valueswere recordedweekly to cohabitationo,n DGs 0,7, 10, 14, 17 and 20 and DLs 1,4, 7, 10 and 14.
Beginningat24 days ofage, one male ratand one female ratfrom each lifteirn each dosage group were testedforlearning,short-termretentionand long-term retentionina passiveavoidance paradigm. Each ratwas testedon two days, separated by a one-week intervalt;he criteriofnorlearningwas the same for both days oftesting.The passiveavoidance apparatusconsistedofa twocompartment chamber with hinged PlexiglasalDids.One compartment was
418-008:PAGE 11-16
ouffiftewditha brightlightand Plexiglasgfloor.The othercompartment was ouffiftewditha gridfloorto which a brief(1 second) pulseofmildelectriccurrent (1mA) was delivered.The two compartments were separated by a slidindgoor.
Duringeach trialt,he ratwas placed intothe "brightc"ompartment, the sliding door was opened and the lighwtas turnedon. The ratwas allowedto explore the apparatus untilitenteredthe "darw'compartment. The slidingdoor was then immediatelyclosed,the lightwas turned off,and the briefpulse ofcurrentwas deliveredto the gridfloor.The ratwas then removed from the apparatus and placed intoa holdingcage for30 seconds beforethe startofthe nexttrialT.rials were repeateduntitlhe ratremained inthe "brightc"ompartment continuouslyfor 60 seconds on each oftwo consecutivetrial(sthecriteriofnorlearning)or until 15 trialwsere completed. The latencyto enterthe dark compartment or the maximum 60-second intervawlas recordedforeach trial.
Dosage groups were compared on the followingdependent measures: the number oftrialtsothe criterioinnthe firsstession(overalllearningperformance); the latency(inseconds) to enterthe "dark"compartment from the "bright" compartment on tria1l ofthe firsttestsession(activitlyeveland exploratory tendency ina novelenvironment);the latency(inseconds) toenterthe "dark" compartment from the "brightc"ompartment on tria2l inthe firsttestsession (short-terrmetention)t;he number oftrialtsothe criterioinnthe second test session(long-termretention)a;nd the latency(inseconds) to enterthe udark" compartment from the "brightc"ompartment on tria1l inthe second testsession (long-termretention).
On postpartumday 70, one male ratand one female ratfrom each liftewrere evaluatedina water-fillMe-dmaze forovertcoordinations,wimming ability, learningand memory. Each ratwas testedina watertight16-gauge stainless steelmodifiedM-maze. The maze was fillewdithwater to a depth of approximatelynine inches,and the water was monitoredfortemperature (range of21 OC t 1OC). On each testtrialt,he ratwas placed intothe startinpgosition (base ofthe M-maze stem farthesftrom the two arms) and requiredto swim to one ofthe two goals ofthe M-maze, inorderto be removed from the water. On the firsttrialt,he ratwas requiredto enterboth arms ofthe maze before being removed from the water. The initiarlm chosen on tria1l was designatedthe incorrecgtoal duringthe remainingtrialsR.ats thatfailedto make a correctgoal choicewithin60 seconds inany given triawlere guided tothe correctgoal and were then removed from the water. A 15-second intertriianltervasleparated each trialE.ach ratwas requiredto reach a criterioonffiveconsecutiveerrorless trialtsoterminatethe testsession.The maximum number oftrialisnany test sessionwas 15. Latency (measured inseconds) to choose the correctgoal or the maximum 60-second intervawlas recordedforeach triala,s was the number oferrors(incorrectturnsinthe maze) duringeach trial.
418-008:PAGE 11-17
Each ratwas testedtwice.The testsessionswere separated by a one-week intervalt;he correctgoal and the criteriownere the same forboth testsessions. Dosage groups were compared forthe followingdependent measures: the number oftrialtso criterioonn the firsdtay of testingt;he average number of errors(incorrectturnsinthe maze) foreach triaoln the firsdtay oftestingt;he latency(inseconds) to reach the correctgoal on tria2lofthe firsdtay oftesting; the number oftrialtso criterioonn the second day oftestingt;he average number oferrorsforeach triaoln the second day oftestinga;nd the latency(inseconds) toreach the correictgoal on tria1l ofday 2 oftesting.
Female ratswere evaluatedforthe age ofvaginalpatency,beginningon DL 28. Male ratswere evaluatedforthe age of preputialseparation,beginningon DL 34.
On DLs 85 to98, the Fl generationratswithineach dosage group were assigned to cohabitationo,ne male ratper female rat,based on random unit tables,withthe exclusionofsiblingmatings. The cohabitationperiodconsisted of a maximum of 14 days. Female ratswith spermatozoa observed ina smear of the vaginalcontentsand/ora copulatoryplug observed insituwere considered tobe at DG 0 and assigned to individuahlousing. Female ratsthatdid not mate withinthe firs7t days of cohabitatiownere assigned alternatemale ratsfrom the same dosage group thathad mated. Female ratswere allowedto naturally deliverand maintainliftertshrough a 21 -day postpartum period.
These ratswere evaluatedforclinicaolbservationsduringparturitiodnu,rationof gestation(DG 0 tothe day the firsptup was observed),liftesrize(allpups delivered)and pup viabiliattybirth.Pups thateitherappeared stillboronr that died before initieaxlaminationofthe lifterfsorviabiliwteyre examined forvital statusat birth.The lungswere removed and immersed inwater. Pups with lungsthatsank were consideredstillborpnu;ps withlungsthatfloatedwere consideredlivebornand to have died shortlyafterbirth.Each liftewras subsequentlyexamined dailyforpup viabilityM.aternalbehaviorofthe dams was evaluateddailywhen the pups were examined duringthe 21-day postpartum period.Observed maternalbehaviorwas recordedon DLs 1,4, 7, 14 and 21. Variationsfrom expected maternal behaviorwere recorded,ifand when present,on allotherdays ofthe postpartum period. Fertiliptayrameters were assessed foralldams assigned to naturaldelivery. These parameters includedthe fertilitnydex(percentageof matingsthat resultedinpregnancies),gestationindex (percentageofpregnanciesthat resultedinthe birthofliveliftersn)u,mber ofoffspringper lifte(rliveand dead pups),number of implantatiosnites,generalconditionofthe dam and lifter duringthe postpartumperiod,viabiliitnydices(percentageofpups born that survived4 and 7 days),and lactatioinndex(percentageofpups born that survived21 days).
G.9. Gross NecrORW:
418-008:PAGE 11-18
G.9.a Fo Generation Male and Female Rats Assigned to Pharmacokinetic SamRie Collection
At scheduled sacrificaeftercompletion of the cohabitationperiod (male ratsthat siredlifterosfdams allowedto naturalldyelivera liftearn)d on DL 21 (female ratsallowedtonaturalldyelivera liftebrl)ood samples (approximately4 mL per rat)were collectedfrom fiveratsper dosage group from the inferiovrena cava, intoserum separatortubes and centrifugedT.he resultinsgerum (approximately 2 mL) was immediatelyfrozenon dry iceand maintainedfrozen(-700C)until shipment tothe Sponsor foranalysis.The livewras excised,weighed, and a sample section(laterallobe)was frozenand retainedat-700C untilshipment to the Sponsor foranalysis.
The liveorfeach pup from the lifterosfthe fivedams ineach ofGroups Ithrough IVthatwere selectedforpharmacokineticsample collectiownas excised,pooled per littefrr,ozenand retainedat-700C, untilshipment to the Sponsor for
analysis.The dams inthe 3.2 mg/kg/day dosage group (Group V) did not have survivingpups on DL 21.
G.9.b. Fo and Fl Generation Male Rats
Male ratswere sacrificebdy carbon dioxideasphyxiationaftercompletionofthe cohabitatiopneriod,and a gross necropsy ofthe thoracica,bdominal and pelvic viscerawas performed. Gross lesionswere retainedinneutralbuffered 10% formalinforpossiblefutureevaluation.Representativephotographs of gross lesionsare availableinthe raw data. The followingorgans were excised, individualwleyighed and retainedforpossiblehistologiecvaluation:testes, epididymides,prostateand seminal vesicles(withand withoutfiuid)T.he testes were fixedinBouin'ssolutionfor48 to 96 hours and then retainedinneutral buffered10% formalinforpossiblehistopathologicaelvaluation.The remaining organs were retainedinneutralbuffered10% formalin.
G.9.c. Fo Generation Female Rats Assigned to Caesarean-Sectioning
Female ratsassigned toCaesarean-sectioningwere sacrificeodn DG 10,and a gross necropsy of the thoracica,bdominal and pelvicviscerawas performed. Uteriofapparentlynonpregnant ratswere stainedwith 10% ammonium sulfideto confirmthe absence of implantatiosnites(9A)l.lovariesand gross lesionswere
a. A tableof random unitswas used to selectone controlgroup Fo and Fl generationratfrom each sex from which alltissuesexamined at necropsy were retained,inordertoprovidecontroltissuesforpossible histopathologicaelvaluationsofgross lesions.
418-008:PAGE 11-19
retainedinneutralbuffered10% formalinforpossiblefutureevaluation. Representativephotographs of gross lesionsare availableinthe raw data. The ratswere examined forthe number and distributiofn corporaluteaineach ovary and implantationsites,and viableand nonviableembryos. A viable embryo was ovalor crescentshaped, pink,firmand enclosed inan amnioticsac fillewdithclearfluid.A nonviableembryo was amorphous, small,palepinkto tan or deep red to black,softand enclosed inan amnioticsac fillewdithclear, cloudy,or opaque fluid.Embryos were discardedafterexamination.
G.9.d. Fo Generation Female Rats Assigned to Natural Delivelyand Fl Generation Female Rats
At the completionofthe 21 -day postpartum period,alldams thatdeliveredlifters were sacrificeodn DL 21, and a gross necropsy ofthe thoracic,abdominal and pelvicviscerawas performed. The number and distributiofn implantationsites was recorded. Female ratsassigned to naturaldeliverythatdid notdelivera liftewrere sacrificeodn DG 25 and examined forgross lesions.To confirmthe pregnancy status,uterifrom ratsthatappeared nonpregnant were stainedwith 10% ammonium sulfide@9@D.ams withno survivingpups were sacrificedafterthe lastpup was found dead, missingor presumed cannibalized.A gross necropsy ofthe thoracica,bdominal and pelvicviscerawas performed. Allovarieswere retainedinneutralbuffered10% formalinforpossiblefutureevaluation.
Rats thatdiedwere examined forthe cause of death on the day the observation was made. The ratswere examined forgross lesions.Pregnancy statusand uterinecontentswere recorded. Ovarieswere retainedinneutralbuffered10% formalin.
G.9.e. FI/F2 Generation Pups
On DL 21, Fl generationpups notcontinued on study and allF2 generation pups were sacrificeadnd examined forgross lesions.Necropsy procedures were the same as those used forpups culledon DL 4.
Pups thatdied beforeexaminationofthe liftefrorpup viabiliwteyre evaluatedfor vitasltatusat birtha,s describedpreviouslyP.ups found dead were examined for gross lesionsand forthe cause of death. Pups withgross lesionsfound on DLsl to4 were preserved inBouin'ssolution.Gross lesionsfrom pups found on DLs 5 to21 were preserved inneutralbuffered10% formalin.Representative photographs of pup gross lesionsare availableinthe raw data.
Pups not selectedforcontinuedevaluationon DL 4 were sacrificebdy carbon dioxideasphyxiationand examined forgross lesions.Necropsy includeda singlecross-sectionofthe head atthe levelofthe frontaland parietalsutureand examinationof the cross-sectionedhead forapparent hydrocephaly. The
418-008:PAGEil-'4L"
stomach contents(milkcurd)were collectedfrom culledpups from Groups 1,11 and 111.Samples were collectedfrom allpups from fiveofthe largestlifterisn these threedosage groups. Individuaplup samples were combined by litteirnto polypropylenetubes and frozenat-20'C. Aftercompletionof sample collection, samples were shipped (frozenon dry ice)to the Sponsor foranalysis.
G.10. StatisticalAnalyses:
418-008:PAGE 11-21
The followingschematic representsthe statisticanlalyses ofthe data:
jype ofTest'
1. ParametriCb A. BartieftT'esstd
I
Significant at p --0@.05
Nonparametric
Not Significant
1 An-..,siosfVariance
11.Noni2arametricc
A. Kruskal-WalliTsest (:g75%ties)
Sig@ifican@tNot at p.-@0.05
I Dunn's Test
Significant
Significant at p.-@0.05
I Dunneft'sTest
Not Significant B. FishersExactTest (>75% ties)
I11.Test forPrODortionData
Variance Test forHomogeneity ofthe BinomialDistribution
a. Statisticalsliygnificanptrobabilitiaerse reportedas eitherp:50.05orp:50.01. b. Used onlytoanalyze data withhomogeneity of variance. c. Proportiondata are not includedinthiscategory. d. Test forhomogeneity ofvariance.
418-008:PAGE 11-22
Proportiondata were analyzed using theVariance Test forHomogeneity ofthe Binomial Distribution('01.
Continuousdata (e.g.,body weights,body weightchanges and feed consumption data)were analyzed usingBartleftTsest of Homogeneity of Variances(iia)nd theAnalysisofVariance(")w,hen appropriate[i.e.B,artiefts Testwas not significan(tp>0.05)].IftheAnalysisofVariancewas significant (p:gO.05)D,unneft'sTest(")was used to identiftyhe statisticsailgnificancoefthe individuaglroups. Ifthe AnalysisofVariance was not appropriate[i.e.B,artleft's Test was significan(tp,-@0.05t)h]e, Kruskal-WalliTsest(14w)as used (:s75% ties). Incases where the Kruskal-WalliTsest was statisticaslilgynifican(tP!50.05), Dunn's Method of MultipleComparisons(")was used to identiftyhe statistical significancoefthe individuaglroups. Iftherewere greaterthan 75% ties, FisheesExact Test(")was used. Fisher'sExactTest(")was alsoused to evaluatenecropsy data forthe pups which were stillboronr found dead.
Data obtainedatCaesarean-sectioning,naturaldeliveryp,reweaning reflex/physicdaelvelopmental data and postweaning behavioraldata involving discretedata (e.g.,number ofcorpora lutea,number of pups per liftetrr,ialtsoa criterionw)e,re evaluatedby the Kruskal-WalliTsest(1,4a)s described above.
Ill. RESULTS - Fo GENERATION MALE RATS
418-008:PAGE 111-1
A. ClinicalObservations (Summa!y -Table BI: IndividualData Table B10)
No Fo generationmale ratsdied duringthisstudy.
Allclinicaolbservationswere consideredunrelatedto the testarticlbeecause the incidenceswere not dosage-dependent and/orthe observationoccurred inonly one or two rats.These observationsincludedlocalizedalopeciaon the limbs, cornealopacity,dentalproblems (missing,broken or misalignedincisors), abrasionon the neck,hyperactiviteyx,cess salivationc,hromodacryorrhea, swollensnout,chromorhinorrheaand dyspnea.
B. Body Weights and Body Weight Changes (Figure1: Summaries Tables B2 and B3: IndividualData -Table Bl 1)
Groups administered0.4 mg/kg/day and higherdosages ofthe testarticlhead reduced body weight gains. The values were significantrleyduced (p:@0.05or p:@0.01)inthe 0.4 mg/kg/day dosage group on days 56 to 63 ofstudy (DSs 56 to63);inthe 1.6 mg/kg/day dosage group on DSs 29 to 36; and inthe 3.2 mg/kg/day dosage group on DSs 15 to 22, 29 to 36, 36 to 42 and 56 to 63. Reflectingthese effectsofthe testarticleb,ody weight gains were significantly reduced (p.-@0.0f1o)rthe entireprecohabitatiopneriod(DSs 1 to42) inthe 1.6 and 3.2 mg/kg/day dosage groups. The 0.4,1.6and 3.2 mg/kg/day dosage groups had significantrleyduced (p:50.05orp:50.01)body weight gains forthe entirestudy,calculatedfrom DSs 1 to63 orfrom DS 1 to termination.
Body weightswere significantrleyduced (p,-r,0.i0n5t)he 1.6mg/kg/day dosage group on DSs 56, 63 and at studytermination.The 3.2 mg/kg/day dosage group had significantrleyduced (p:50.01b)ody weightson DSs 36, 42, 56, 63 and at study termination.
Body weightsand body weight changes were unaffectedby the 0.1 mg/kg/day dosage ofthe testarticle.
C. Absolute (g/day)and Relative(g/kglday)Feed Consumption Values (Summaries -Tables B4 and B5: IndividualData -Table B121
Relativefeed consumption values were significantrleyduced (p:50.05i)nthe 1.6 and 3.2mg/kg/day dosage groups on DSs 8 to 15. Absolute(g/day)and relativ(eg/kg/day)feed consumption valueswere significantrleyduced (P!@0.01) inthe 3.2 mg/kg/day dosage group on DSs 15 to22, 29 to 36 and 36 to42. As a resultofthese effectsofthe testarticlea,bsoluteand relativfeeed consumption valueswere reduced and/or significantrleyduced inthese two dosage groups for
418-008:PAGE ll!-2
the entireprecohabitatiopneriod(DSs 1 to 42). Afterthe cohabitationperiod (DSs 56 to 63),absolutefeed consumption valueswere significantrleyduced (p-<0.05or p:50.01)inthe 0.4 and 1.6 mg/kg/day dosage groups. Absolute and relativfeeed consumption values were significantrleyduced inthe 3.2 mg/kg/day dosage group duringthisperiod.
Absoluteand relativfeeed consumption were unaffectedby the 0.1 mg/kg/day dosage ofthe testarticle.
I D. Mating and Fertilily(Summary - Table B6: Individual Data -
Table-gj3j
Dosages ofthe testarticlaes high as 3.2 mg/kg/day did not affectany mating and fertiliptayrameters evaluated.Values forthe fertiliatnyd pregnancy indices (number of pregnanciesper number of ratsincohabitatioannd ratsthatmated, respectivelyt)h,e number ofdays to inseminate,the number of ratsthatmated and the number of ratswith confirmedmating dates duringthe firswteek of cohabitatiownere comparable among the fivedosage groups.
E. NecrORSY Observations (Summa!y -Table B7: IndividualData TableDI41
A significantilnycreased(p:50.01n)umber of male ratsinthe 3.2 mg/kg/day dosage group had a lightbrown or brown livera,n observationattributetdo effectsof PFOS. The gross lesionsofthe livewrere consideredrelatedto the testarticlbeecause the incidenceswere dosage-dependent.
One 1.6mg/kg/day dosage group rat(8214)and three3.2 mg/kg/day dosage group rats(8245,8252, 8257) had small,flacciadnd/orpurpletestesa.Allfourof these male ratsmated butdid not impregnatea female rat.One 3.2 mg/kg/day dosage group male rat(8243)had a smallprostatet;hisratimpregnateda female rat.The gross lesionsobserved inthe testesand prostatewere not consideredtestarticle-relataesdthey are common findingsincontrolgroup male ratsand didnot varyfrom HistoricaClontrolincidenceatthe TestingFacilityN.o othermale ratshad gross lesionsof the reproductiveorgans.
Allothernecropsy observationswere consideredunrelatedto the testarticle because: 1)the observationoccurredinonlyone ratina group;or 2) the incidenceswere notdosage-dependent. These observationsincludeda large livera, liverwitha rough surface,constrictepdapillarpyrocess ofthe liverwith
a. In2079 controlgroup ratsfrom 91 studiesconducted at the Testing Facilitfyrom August, 1992 toApril,1999, therewere 21 ratswithsmall, flaccidand/or purpletestes.
418-008:PAGE
pinpointraisedtan areas,opaque lensofthe eye, largekidneys,kidneyswith cystsinthe parenchyma, dilatioonfthe renalpelvisand a largespleen.
F. Terminal Body Weightsi, Organ WeigLhts and Ratios (%) of Organ Weight to Terminal Body Weight (Summaries - Tables B8 and B9: Individual Data -Table Bl E)
The 1.6and 3.2 mg/kg/day dosage groups had significantrleyduced (p!50.05and p:@0.01,respectivelyt)erminalbody weights.The absoluteweightsofthe seminalvesicleswithfluidand the prostatewere significantrleyduced (p:@0.05or p<0.01) inthe 3.2 mg/kg/day dosage group,compared tothe controlgroup. Epididymidesand testesweightsand weightsofthe seminal vesicleswithout fluidwere unaffectedby dosages ofthe testarticlaes highas 3.2 mg/kg/day.
The ratiosofthe weight ofthe leftand righttestestoterminalbody weightswere significantilnycreased(p:50.01i)nthe 3.2 mg/kg/day dosage group,as compared tothe controlgroup values.These observationswere associatedwiththe significantrleyduced (p:gO.01t)erminalbody weights inthisdosage group. The ratiosofthe weightsofthe epididymides,seminalvesiclesand prostatewere generallycomparable among the fivedosage groups.
IV. RESULTS - Fo GENERATION FEMALE RATS
418-008:PAGE IV-1
A. ClinicalObservations (Summa!y -Table Cl. IndividualData Table C22)
A.l. Mortalily
No deaths were attributablteo PFOS. The onlydeath occurred ina 1.6mg/kg/day dosage group rat,an event attributablteo an intubatioanccident.
Female rat8938 inthe 1.6mg/kg/day dosage group was moribund sacrificeodn studyday (DS) 36 afteradministratioonf 35 dailydosages. Adverse clinical observationsincludedchromodacryorrhea and a clearoralexudate on DSs 35 to36, and ptosis,hunched postureand laboredbreathingon DS 36.
Observationsofchromodacryorrhea and ptosiswere confirmedatnecropsy;all othertissuesappeared normal at necropsy. This ratlostbody weight and had
reduced feed consumption on DSs 29 to 36. The clinicaolbservationsindicated thisratwas misintubatedon or about DS 35. AllotherFo generationfemale rats survivedto scheduled sacrifice.
A.2. ClinicaOlbservations
Observationsof localizedalopeciawere increasedduringthe precohabitation, gestationand lactatiopneriodsinthe 0.4,1.6and 3.2 mg/kg/day dosage groups. The incidenceoflocalizedalopeciaatany area was significantilnycreased (p@50.05or p:50.01)inthe 0.4,1.6and 3.2 mg/kg/day dosage groups duringthe gestationperiod.The incidenceoflocalizedalopeciaon the back was significantilnycreased(p@@0.01i)nthe 3.2 mg/kg/day dosage group duringthe lactatiopneriod.
Allotherclinicaolbservationsduringthe precohabitationg,estationand lactation periodswere consideredunrelatedtothe testarticlbeecause: 1)the incidences were not dosage-dependent; and/or2) the observationoccurred inonlyone rat. These observationsincludedchromodacryorrhea and dentalproblems (missing, broken or misalignedincisors)C.learoralexudate,ptosis,hunched postureand laboredbreathingoccurredduringthe precohabitatiopneriodinthe 1.6mg/kg/day ratthatwas moribund sacrificeda,s previouslydescribed.
B. Body Weights and Body Weight Changes ffigure2.Summaries Tables C2 through C7: IndividualData -Tables C23 through C25)
B.I. Precohabitation
Groups administered1.6mg/kg/day and higherdosages ofthe testarticlhead significantrleyduced (p@50.01b)ody weight gainsforthe entireprecohabitation
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period(DSs 1 to42). Duringthisperiod,valueswere significantrleyduced (p,-@0.0i1n)the 1.6mg/kg/day dosage group on DSs 29 to 36; and inthe 3.2 mg/kg/day dosage group on DSs 8 to 15, 22 to 29 and 29 to 36, as compared withthe controlgroup value. Body weightswere significantrleyduced (p.-@0.0i1n)the 3.2 mg/kg/day dosage group on DSs 15,22, 29, 36 and 42, as compared withthe controlgroup values.
Body weightsand body weight gains duringthe precohabitationperiodwere unaffectedby dosages ofthe testarticlaes high as 0.4 mg/kg/day.
B.2. Gestation
The 1.6and 3.2 mg/kg/day dosages of PFOS continuedto reduce body weights and body weight gains duringgestation.Reflectingeffectsthatoccurredduring the precohabitatiopneriod,the 1.6 mg/kg/day dosage group tended toweigh lessand the 3.2 mg/kg/day dosage group weighed significantlleyss(p@50.01) than the controlgroup on day 0 ofgestation(DG 0). Weight gainwas significantrleyduced (p.-@0.0i5n)the 1.6mg/kg/day dosage group on DGs 0 to 7 and then essentiallcyomparable to the controlgroup values atallintervals throughoutthe remainder ofgestationb,eginningwith DGs 10 to 12. Weight gains were significantrleyduced inthe 3.2 mg/kg/day dosage group on DGs 0 to 7 and 10 to 12,afterwhich thisgroup also had weight gains comparable tothe controlgroup. Reflectingthese effectsb,ody weight gainswere significantly reduced (p@gO.01i)nthe 3.2mg/kg/day dosage group forthe entiregestation period(DGs 0 to 20) and body weightswere significantrleyduced (p:gO.05or p!@0.01)inthe 1.6and 3.2 mg/kg/day dosage groups on DGs 3 through 11 and 0 through 20, respectively.
Body weightsand body weight gains duringgestationwere unaffectedby dosages ofthe testarticlaes high as 0.4 mg/kg/day.
B.3. Lactation
The 3.2 mg/kg/day dosage group had significantrleyduced (p:50.01b)ody weight on DL 1,as compared withthe controlgroup value. Body weightgainstended to be reduced inthe 0.4 mg/kg/day dosage group on DLs 1 to4, when significant weight loss(p5O.Ol)occurredinthe 1.6mg/kg/day dosage group (the 3.2 mg/kg/day dosage group was precludedfrom furtherevaluationbecause all pups died beforeDL 2). A significanitncrease(p..@0.0i5n)body weightgain on DLs 10 to 14 inthe 1.6mg/kg/day dosage group was possiblyassociatedwith reduced liftesrizeand associatedwithreduced milkdemand and production.
Body weightsand body weight gains duringlactatiownere unaffectedby the 0.1 mg/kg/day dosage ofthetestarticle.
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C. Absolute (giday)and Relative(glkg/day)Feed ConsUMDtionn Valu s (Summaries -Tables C8 through C13: IndividualData -Tables C26 through C28)
C.I. Precohabitation
Absolute(g/day)and relativ(eg/kg/dayf)eed consumption valueswere reduced inthe 1.6and 3.2mg/kg/daydosage groups duringthe precohabitatiopneriod. These effectswere significa(npt:gO.0o5r p:gO.01)inthe 1.6mg/kg/daydosage group on DSs 22 to29 and 29 to36 (absoluteonly),and inthe 3.2mg/kg/day dosage group atmost tabulatedintervalsR.eflectintgheseeffectosfthetest articlet,he 3.2mg/kg/daydosage group had significantrleyduced (p:@0.01) absoluteand relativfeeed consumption valuesforthe entireprecohabitation period(DSs 1 to42).
Feed consumptionvaluesduringthe precohabitatiopneriodwere unaffectedby dosages of thetestarticlaes highas 0.4mg/kg/day.
C.2. Gestation
The 1.6and 3.2mg/kg/daydosage groups continuedto have reduced absolute and relativfeeed consumptionvaluesearlyinthegestationperiod.Absoluteand relativfeeed consumptionvalueswere significantrleyduced(pf.0.0o5rp:50.01) inthe 1.6mg/kg/daydosage group on DGs 0 to7 (absoluteonly)and 7 to10, and inthe3.2mg/kg/daydosage group on DGs 0 to 7,7 to 10,10 to 12 (absoluteonly).Significantilnycreased(p:@0.0o5r p5O.Ol)feedconsumption valuesoccurredinthe 1.6and 3.2mg/kg/daydosage groups on DGs 15 to 18 (absoluteand relativaen)d DGs 18 to20 (relativoenly),observationisnterrelated withreduced body weightsand the laterstagesofgestationw,hen maternalfeed consumptiontendstoincrease.Despitethe increasesinrelativfeeed consumption values,the 3.2mg/kg/daydosage group had a significantly reduced (p:@0.01a)bsolutefeed consumption valuefortheentiregestation period(DGs 0 to20).
Feed consumption valuesduringgestationwere unaffectedby dosages ofthe testarticlaes highas 0.4mg/kg/day.
C.3. Lactation
Absoluteand relativmeaternalfeed consumption valuestended tobe reduced in the 0.4mg/kg/daydosage group and were significantrleyduced (p5O.Ol)inthe 1.6mg/kg/daydosage group fortheentirelactatiopneriod(DLs 1 to14),and at most intervalwsithinthisperiod.The 3.2mg/kg/day dosage group was precludedfrom evaluationbecause therewere no survivingpups afterDL 1.
418-008:PAGE IV-4
Feed consumption values duringlactatiownere unaffectedby the 0.1 mg/kg/day dosage ofthetestarticle.
D. Estrous Cycling,Mating and Fertilit(ySumma!y -Table C14: IndividualData -Table C29)
Dosages ofthe testarticlaes high as 3.2 mg/kg/day did not affectestrous cycling(number ofestrusstages per 28-days)inthe 15 ratsper dosage group thatwere evaluated.Allfemale ratsmated except one inthe 0.4 mg/kg/day dosage group. The number ofdays incohabitationt,he fertiliatnyd pregnancy indices(number of pregnanciesper number ofratsthatmated and ratsin cohabitationr,espectivelya)n,d the number of ratswith confirmedmatingdates duringthe firsatnd second week ofcohabitatiownere comparable inthe five dosage groups. Pregnancy occurredin33, 32,28, 29 and 30 female ratsin Groups IthroughV, respectively.
E. Necropsy Observations (summa[y -Table C15: IndividualData Table C30)
Allnecropsy observationswere consideredunrelatedtotreatment.One ratin the 0.4 mg/kg/day dosage group had moderate dilatioonfthe pelvisofthe right kidney,an observationthatiscommon inthisspeciesand strain.One ratinthe 1.6mg/kg/day dosage group had adhesion ofabdominal adipose tissueand the spleen. No othergross lesionsoccurredinthe female ratsinthisstudy.
F. Caesarean-Sectioningand LifterObservations (SummaM Table C16: IndividualData -Tables C31 through C33)
Caesarean-sectioningobservationson DG 10 were based on 10 (100%), 7 (70.0%),6 (60.0%),9 (90.0%)and 9 (90.0%)pregnantdams ineach ofthefive respectivedosage groups.
There were no biologicalliymportantor statisticaslilgynificandtifferencesinthe liftearverages forcorporalutea,implantationsv,iableembryos or nonviable embryos. No dam had lifteirnwhich therewere no liveembryos.
G. NaturalDeliveryand LifterObservations (Summaries -Tables C17 and CIB: IndividualData -Tables C34 through C37)
Although 25 presumed pregnant ratsineach dosage group were assigned to naturaldeliveryb,ecause one rat(1.6mg/kg/day dosage group)was moribund sacrificedduringthe premating period(on DS 36),as previouslydescribed,this dosage group had only24 ratsassigned to naturaldelivery.Of these rats,20 to 25 were pregnantand deliveredlifters.
418-008:PAGE iV-17:@
The durationofgestationwas significantrleyduced (p-<0.01i)nthe 3.2 mg/kg/day dosage group, an observationassociatedwithpreimplantatiolnoss[theaverage number ofimplantatiosnitesper dam was significantrleyduced (P-<0.01), resultinigna significantrleyduced (p:50.01)l,iftesrize]and an effectofthe test article.
Pup viabiliwtays significantrleyduced (p-<0.05or p:!@0.01i)nthe 1.6and 3.2 mg/kg/day dosage groups,as describedinthe followinginformation. Althoughthe gestationindex (thepercentageof pregnant ratswith liveoffspring) was comparable across allfivedosage groups,the 1.6 mg/kg/day dosage group had increasednumbers ofpups thatdied orwere presumed cannibalizedon DL 1,and significantilnycreased (p:!@0.0o5rp:!@0.01n)umbers ofpups dead or presumed cannibalizedon DLs 2 to 4 and 5 to 7. The 3.2 mg/kg/day dosage group had postimplantatiolnossevidentas reduced pup viabilitaytbirth[one liftehrad no livebornpups, the number ofdams withstillborpnups was significantilnycreased(p!50.01)t,he liftearverage and number ofstillborpnups were significantilnycreased(p:50.01)a,nd the liftearverage and number of livebornpups were significantrleyduced (p:50.01)a]s, wellas peripartumdeaths [significanutmbers (p@50.05orp:sO.01)ofdead and presumed cannibalized pups on DLs 1 and 2 to 4 (allivebornpups died by DL 2) and significant numbers (p-<0.01o)fdams had allpups dead or presumed cannibalizedon DLs 1 to4]. Reflectingthese effectst,he viabilitiyndexwas significantrleyduced (p:50.01i)nthe 1.6and 3.2 mg/kg/day dosage groups,the lactatioinndexwas alsosignificantrleyduced (p:!@0.0i1n)the 1.6mg/kg/day dosage group, as also were the averages forsurvivingpups (p-<0.05or p-<0.01)inthe 1.6mg/kg/day dosage group beginningon DL 4 postcullinga,nd inthe 3.2 mg/kg/day dosage group on DL 1.
A dosage-dependent patternofreduced pup body weight was evidentineach group administeredthe testarticleT.he 1.6mg/kg/day dosage group had significantrleyduced WO.01) pup body weightson allweighingdays. The 3.2 mg/kg/day dosage group had a significantrleyduced (p!@0.01p)up body weighton DL 1 (no pups survivedtosubsequent scheduled weighings).
The percentageof male pups was comparable across allfivedosage groups.
H. ClinicalObservations from Birthto Day 21 Postpartum and NecroRsy Observations (Summaries -Tables C19 and C211 IndividualData -Tables C38 and C45)
Adverse clinicaalnd necropsy observationsassociatedwithreduced pup viability and potentiarleductioninmaternalcare occurred inthe 3.2 mg/kg/day dosage group. Adverse clinicaolbservationsincludethree(p:!@0.0l1i)fterwsithpups that were not nursing(twoofthese lifterhsad pups from which the placentahad not been removed, and one had pups thatwere not nested).Apparent maternal
418-008:PAGE IV-6
cannibalizatiownas alsoevidentinthisdosage group (missingtailinone pup and a cannibalizedforelimbinanotherpup),which may have occurredafter these pups died.
Necropsy observationsinpups thatwere stillboronr found dead included significanitncreases(p-<0.05orp-<0.01)inthe numbers of pups withno milkin the stomach inthe 1.6and 3.2 mg/kg/day dosage group pups. No pups (p<-0.01) inthe 0.1 mg/kg/day dosage group had thisobservation,as compared withtwo controlgroup pups. The 3.2 mg/kg/day dosage group alsohad evidence of increasedmaternalcannibalizatioant necropsy of stillborand found dead pups. Nine ofthese pups had missing hindlimbsand/orportionofthe tail.
Allotherclinicaalnd necropsy observationsinthe Fl generationpups were consideredunrelatedtothe testarticlbeecause: 1)the incidenceswere not dosage-dependent;or 2)the observationoccurredinonlyone lifterC.linical observationsincludeda domed head, portionofthe tailmissing,umbilicalhernia, missingdigitsand bent tail.One 1.6mg/kg/day dosage group stillborpnup had anasarca (edema ofthe entirebody). Necropsy on DL 21 revealedtwo 0.4 mg/kg/day dosage group liftermatewsithmoderate or severe dilatioonfthe lateravlentricleosfthe brain,and one pup from a differen0t.4 mg/kg/day dosage group liftewrithslightdilatioonfthe renalpelvis.
1. Reflex and Physical Development Data - Tables C39 through C")
(Summary
- Table C20: Individual
Reversible delays in reflex and physical development that are highly correlated withbody weight(',"o)ccurredinthe 0.4 and 1.6 mg/kg/day dosage groups,as described below.
I.I. Surface Righift
Surface rightinwgas delayed inthe 1.6and 3.2 mg/kg/day dosage groups,as describedbelow. The percentage of pups thatcouldsurfacerightwas significantrleyduced (p.-@0.0o5rp:sO.01)inthe 1.6mg/kglday dosage group on DLs 3,4, 5,6, 7,8 and 10,and inthe 3.2 mg/kg/day dosage group on DL 1,after which therewere no survivingpups inthisdosage group. The average day that atleast50% ofthe pups ina dosage group had the abilittyosurfacerightwas significantilnycreased(p:50.05i)nthe 1.6 mg/kg/day dosage group. Allsurviving pups ultimatelayttainedthe abilittyosurfaceright.
The abilittyosurfacerightwas unaffectedby the 0.4 mg/kg/day dosage of the testarticle.
1.2. Pinna Unfolding
418-008:PAGE IV-7
Pinna unfoldingwas delayed inthe 0.1,0.4 and 1.6mg/kg/day dosage groups (no 3.2 mg/kg/day dosage group pups were evaluatedforthisparameter).The effectwas transient(evidenton onlyone day) inthe 0.1 and 0.4 mg/kg/day dosage groups,and consideredofno toxicologicailmportance [thepercentages ofpups per liftewrithpinna unfoldingwere significantrleyduced (p@@0.05or p:!@0.01i)nthe 0.1 and 0.4 mg/kg/day dosage groups on DL 3 only].The percentageof pups withan unfoldedpinnawas significantrleyduced (P<0.01)on DLs 3,4 and 5) inthe 1.6 mg/kg/day dosage group,and the average day thatat least50% ofthe pups ina dosage group had an unfoldedpinna was significantly increased(p@50.01i)nthisdosage group. Allsurvivingpups ultimatelhyad unfoldedpinnae.
1.3. Eye Openi!ig
Eye opening was delayed inthe 0.1,0.4 and 1.6mg/kg/day dosage groups (no 3.2 mg/kg/day dosage group pups were evaluatedforthisparameter).The effectwas transien(tevidenton onlyone day) inthe 0.1 and 0.4 mg/kg/day dosage groups,and consideredofno toxicologicailmportance[thepercentages of pups per liftewrithopen eye lidswere significantrleyduced (P:50.05i)nthe 0.1 and 0.4 mg/kg/day dosage groups on DL 14 only].The percentageof pups with at leastone open eye was significantrleyduced (p:50.01i)nthe 1.6mg/kg/day dosage group on DLs 14, 15 and 16. The day thatat least50% ofthe pups had at leastone open eye was significantilnycreased(p@@0.01i)nthe 0.4 and 1.6mg/kg/day dosage groups. Allpups had open eyelidsby DL 21, when pupil constrictiownas tested.
1.4. Acoustic Startle
The time ofdevelopment ofthe acousticstartlreeflexwas delayed (p:@0.05or p:50.01)inthe 1.6 mg/kg/day dosage group; no 3.2 mg/kg/day dosage group pups survivedto be testedforthisreflex.The percentage ofpups inthe 1.6 mg/kg/day dosage group withthisreflexwas significantrleyduced (p:50.05or p:!@0.01o)n DLs 13, 14, 16, 17, 18, 19 and 20, resultinigna tendency foran increaseinthe average day thatat least50% ofthe pups had the acousticstartle reflex'.
The development ofthe acousticstartlreeflexwas unaffectedby the 0.1 and 0.4 mg/kg/day dosages ofthe testarticle.
I.S. Air Righting
The abilittyoairrightwas delayed (p:50.01i)nthe 0.4 and 1.6 mg/kg/day dosage groups;no 3.2 mg/kg/day dosage group pups survivedtobe testedforthis
418-008:PAGE IV-8
reflex.The effectwas transientand not oftoxicologicailmportanceinthe 0.4mg/kg/day dosage group, occurringonlyon DL 16. The percentage ofpups inthe 1.6mg/kg/day dosage group thatairrightedwas significantrleyduced (p:50.01o)n DLs 14 through21, resultinigna significanitncrease(P-<0.01i)nthe day thatat least50% ofthe pups could airright.
1.6. PURII Constrictioki
All live pups in the 0 (Vehicle),0.1, 0.4 and 1.6 mg/kg/day dosage groups had the pupilconstrictiornesponse presenton DL 21.
418-008:PAGE \/-l V. RESULTS - Fl GENERATION MALE AND FEMALE RATS
A. Fl Generation Male Rats
A.l. Mortaillyand ClinicalObservations (SummaOL- Table DI: Individual Data -Table DI
A.l.a.Mortality
No deathsintheFl generationmale ratswere attributetdoPFOS. Two control group ratswere found dead on days 86 and 87 postweaning. These deaths were attributetdo intubationerrors.One 0.1 mg/kg/day dosage group ratwas found dead on day 66 postweaning;thisdeath was consideredunrelatedto the. testarticlbeecause itwas a single,nondosage-dependent effect.Observations forthese ratsthatdied are providedbelow.
Controlgroup male rat13105 was found dead on day 87 postweaning,one and 11 minutesafterthe 87th dailydosage. No otheradverse clinical observationsoccurredinthisrat,and itsbody weight gains and feed consumption values were comparable tootherratsinthisdosage group. Necropsy ofthe ratrevealedthatalllung lobeswere dark red,which in associationwiththe time death occurred,iscompatiblewithan intubation accident.
hour
Controlgroup male rat13116 was found dead on day 86 postweaning,afterit had been administered85 dailydosages. Additionaladverse clinical observationsinthisratwere limitedtochromorhinorrhea(days 67 to72 and 79 postweaning).Body weightgainsand feed consumption valuesinthisrat were comparable to those ofotherratsinthisdosage group. Necropsy ofthe rat revealeddark red clottedmaterial(presumed to be blood)inthe thoraciccavity and a red perinasalsubstance,observationscompatiblewithan intubation accident.
Male rat13138 (0.1mg/kg/day dosage group)was found dead on day 66 postweaning,afterithad been administered65 dailydosages. No otheradverse clinicaolbservationsoccurredinthisrat,and itsbody weight gains and feed consumption valueswere comparable to those ofotherratsinthisdosage group. Alltissuesappeared normal atnecropsy.
A.l.b.ClinicaOlbservations
Alladverse clinicaolbservationswere considered unrelatedto the testarticle because: 1)the incidenceswere not dosage-dependent;and/or2) the observationoccurredinonly one ortwo rats.A significanitncrease(p:50.01i)n the incidenceof localizedalopeciaon the back inthe 0.1 mg/kg/day dosage
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group was not consideredtreatment-relatebdecause the value was not dosagedependent. No otherstatisticaslilgynificanitncreasesinan adverse clinical observationoccurred. Additionaladverse clinicasligns observed and considered unrelatedtothe testarticliencludeddentalproblems (missing,broken and/or misalignedincisors)c,hromorhinorrhea,abrasionon the head, near the eye, forelimbor back, chromodacryorrhea,laceratioantthe base ofthe taila, swollen snout,a red perioralsubstance,a red substance on penis,localizedalopeciaon the back,limbsand/or head, a scab on the back, urine-staineadbdominal fur, softor liquifdeces,swollenand purpleears,rales,gasping,excess salivation and dilatedpupils.
A.2. Body Weights and Body Weight Changes (Figure 2: Summaries Tables D2 and D3: IndividualData -Table D14)
The 0.1 and 0.4 mg/kg/day dosage groups tended to weigh lessthan the control group on day 1 postweaning and generallygained one ortwo grams lessbody weight per week than the controlgroup rats,withthe exceptionofdays 71 to 78, when these groups had significanrteductions(p:50.05orp:50.01)inbody weight gains,as compared withthe controlgroup value. Reflectingthispatternof weight gain,weight gains inthe 0.1and 0.4 mg/kg/day dosage groups forthe precohabitatiopneriod(day 1 postweaning to precohabitationw)ere 98.4% and 97.6% ofthe controlgroup value,respectivelyB.ody weight gains inthe 0.1 and 0.4 mg/kg/day dosage groups forday 1 to terminationwere 98.5% and 96.6% of the controlgroup value,respectively.
A.3. Absolute (giday)and Relative(g/kg/day)Feed Consumption Values (Summaries -Tables D4 and D5: IndividualData -Table Dl )
Absolute(g/day)feed consumption values were significantrleyduced (p:@0.05 and p:50.01,respectivelya)nd relativ(eg/kg/day)feed tended to be reduced in the 0.1 and 0.4 mg/kg/day dosage groups duringthefirswteek of intubation (days 1 to 8 postweaning),as compared tothe controlgroup values. These observationscommonly occur and were associatedwiththe tendency for reduced body weight inthese two dosage groups on day 1 postweaning. A significanitncrease(p:50.05i)nthe relativfeeed consumption valueinthe 0.1 mg/kg/day dosage group on days 22 to 29 postweaning was considered unrelatedtothe testarticlbeecause the valuewas notdosage-dependent. No otherstatisticalsliygnificandtifferencesoccurredinthe feed consumption values forthisportionofthe study.
A.4. Sexual Maturation(Summary -Table D6: IndividualData -Table Pj6j
Dosages ofthe testarticlaes highas 0.4 mg/kg/day did notaffectthe average day of preputiasleparationinthe Fl generationmale rats.No significant differenceosccurredamong the threedosage groups.
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A.S. Passive Avoidance Performance (Summary -Table D7: Individual Data -Table D17)
There were no biologicalliymportantdifferencesinthe valuesforlearning,shortterm retentionl,ong-termretentionor response inhibitiointhe Fl generation male rats,as evaluatedby performance ina passiveavoidance paradigm. No statisticaslilgynificandtifferencesoccurredinthe number oftrialtsocriterion, triallatenciesor numbers of ratsthatfailedto learn.
A.6. Watermaze Performance (Summary -Table D8: IndividualData Table D18)
No biologicalliymportantdosage-dependent differencesoccurredinwatermaze performance ofthe Fl generationmale ratsregardingleaming,short-term retentionl,ong-termretentionor response inhibitionN.o statisticalsliygnificant differenceosccurredinthe number oftrialtso criteriotnr,iallatenciesor numbers ofratsthatfailedto learn.
A.7. Mating and Fertilil(ySummary -Table D9: IndividualData Table D19)
Dosages ofthe testarticlaes highas 0.4 mg/kg/day did not affectany mating and fertiliptayrametersevaluatedinthe Fl generationmale rats.Values forthe fertiliatnyd pregnancy indices(number ofpregnanciesper number of ratsthat mated and ratsincohabitationr,espectivelyt)h,e number ofdays to inseminate, the number of ratsthatmated and the number of ratswithconfirmedmating dates duringthe firswteek ofcohabitationwere comparable among the three dosage groups. Of the male ratsassigned tocohabitation8,2.6%, 83.3% and 96.0% impregnated the cohortfemale rat.
A.8. NecrORsY Observations (Summa[y -Table D10: IndividualData Table D20)
Allnecropsy observationsinthe Fl generationmale ratswere considered unrelatedto the testarticlbeecause: 1)the incidenceswere not dosagedependent; and/or2) the observationcommonly occurs inthisstrainof rat.
Gross lesionsof male reproductiveorgans includedflaccids,malland/or purple testesand epididymidesinthreeWO.01) 0.1mg/kg/day dosage group male rats (13134,13145, 13148),each ofwhich sireda lifterT)h.ese observationswere consideredunrelatedtothe testarticlbeecause: 1)the incidenceswere not dosage-dependent; and 2) thesefindingsare known to be geneticallmyediated and common inthisratstrain.No othergross lesionoccurredat a statistically significanitncidence.
418-008:PAGE V-4
Additionalnecropsy observationsconsideredunrelatedtothe testarticle includedred abdominal adipose tissuewithfirmareas (one 0.4 mg/kg/day dosage group male rat;13162),and urinarytractlesions,as describedinthe followinginformation.One 0.1 mg/kg/day dosage group male rat(13143) had a dilatedureter;anotherratinthisdosage group (13134) had slightdilatioonfthe renalpelvis.One 0.4 mg/kg/day dosage group male rat(13173)had large kidneyswith numerous fluid-filclyesdtsinthe parenchyma; the lefktidney had slightdilatioonfthe pelvis,inwhich therewere sixcalculia,nd thickenedurinary bladderwallsassociatedwiththe presence of numerous calculi.Necropsy observationsinthe controlgroup ratsthatdied as the resultof an intubationerror were describedpreviously.
A.9. Terminal Body Weights and Organ Weights and Ratios (%) of Orcian Weight to Terminal Body Weight (Summaries -Tables Dl I and Di 2: IndividualData -Table D21)
No statisticalsliygnificandtifferencesoccurredinthe absoluteor relativ(etobody weight)valuesfortheweights ofthe rightor leftestiss,eminal vesicles(withand withoutfluid)r,ightepididymisor prostate.Terminalbody weightstended to be reduced inthe 0.1 and 0.4 mg/kg/day dosage groups;the terminalbody weights inthe 0.1 and 0.4 mg/kg/day dosage groups were 98.3% and 96.4%, respectivelyo,fthe controlgroup value.
B. Fl Generation Female Rats
B.I. Mortalilyand ClinicalObservations-(Summary -Table Elm Individual Data - Tables E23)
B.I.a.Mortalily
No deaths inthe Fl generationfemale ratswere attributetdo PFOS. One controlgroup ratwas sacrificeodn day 7 postweaning,because itwas a male rat thathad been incorrectliydentifieads a female rat.One controlgroup ratwas found dead on day 28 postweaning;no cause ofdeath was identifiefdorthisrat. One ratinthe 0.4 mg/kg/day dosage group was found dead on day 10 of lactatio(nDL 10) as the resultof an intubatioanccident.Observationsforthese ratsare provided below.
No gross lesionswere revealedby necropsy ofcontrolgroup rat13205 on day 7 postweaning.
The controlgroup female rat(13221)thatwas found dead on day 28 postweaning,afterithad been administered27 dailydosages did not have any otheradverse clinicaolbservations,and itsbody weight gains and feed
418-008:PAGE V-5
consumptionvalueswere comparable tootherratsinthisdosage group. All tissuesappeared normalat necropsy.
Female rat13257 (0.4mg/kg/day dosage group)was found dead on the morning ofDL 10,afterithad been administereda totalof 106 dailydosages. No other adverse clinicaolbservationsoccurredinthisrat,althoughitlostweighton DLs 1 to7. Itsfeed consumptionvalueswere unremarkable.Thisratdelivered15 livebornpups,ofwhich seven were culledon DL 4 and eightwere sacrificeadfter thedeath ofthedam. Necropsy ofthedam revealedgrosslesionscompatible withan intubatioanccident(whitefoam inthetrachea,approximately2 mL ofa lighotrange fluiidnthethoracicavitya,nd dark redlungs).
B.I.b.ClinicalObservations
A red perivaginaslubstanceoccurredinone and two dams inthe 0.1 and 0.4mg/kg/daydosage groups,respectivelyo,n days 21 or 22 ofgestationa,nd redperivaginaslubstancewas alsoobserved on DL 1 infive(p:50.01d)ams in the0.4 mg/kg/daydosage group. These observationsprobablywere associated withparturitiorna,therthan an effectofthetestarticlea,nd didnotappear to adverselyaffecthe healthofthe dams ortheiroffspringN.o otheradverse clinicaolbservationoccurredat a statisticaslilgynificainntcidence.
Allotheradverse clinicaolbservationsthatoccurredduringthe precohabitation, gestationand lactatiopneriodswere consideredunrelatedtothe testarticle because: 1)theincidenceswere notdosage-dependent;2)theobservation occurredinonlyone ortwo rats;and/or3)theobservationiscommon inthe laboratoreynvironment.These observationsincludeddentalproblems (misalignedm,issingand/orbroken teeth)c,hromodacryorrhea,swollenand purpleears,localizeadlopeciaon the back,head, limbsand/orunderside, abrasionor scab on the back,urine-staineadbdominalfur,missinghindpaw digitsp,erivaginaslwellings,wollenforepaw,chromorhinorrheas,oftor liquid feces,missingtailsheath,tipoftailblackor missingand abrasionon the chest.
B.2. Maternal Body Weights and Body Weight Changes (Figure4: Summaries -Tables E2 through E7: IndividualData -Tables E24 through E26)
B.2.a.Precohabitation
Body weightstended to be reduced inthe 0.4mg/kg/daydosage group on day 1 postweaning.No statisticaslilgynificaonrtdosage-dependentdifferenceisn precohabitatiobnody weightgainsorbody weightsoccurredinthe Fl generation female ratsduringtheprecohabitatiopneriod.
B.2.b.Gestation
418-008:PAGE V-6
Maternal body weights and body weight gainsduringthe gestationperiodwere unaffectedby dosages ofthe testarticlaes highas 0.4 mg/kg/day. Allvalues were comparable among the three dosage groups and didnot significantdliyffer.
B.2.c.Lactation
Significan(tp:@0.05m)aternalbody weight lossoccurredon DLs 1 to4 inthe 0.4 mg/kg/day dosage group, as compared tothe controlgroup value,after which body weight gains were greaterthan,orweight losslessthan the control group values.
Maternalbody weightsand body weight gainsduringthe lactatiopneriodwere unaffectedby the 0.1 mg/kg/day dosage ofthetestarticle.
B.3. Maternal Absolute (g/day)and Relativeig/kg/day)Feed Consumption Values (Summaries - Tables E8 through E13, IndividualData Tables E27 through E29)
B.3.a.Precohabitation
The 0.4 mg/kg/day dosage ofthe testarticlweas associatedwitha significant reduction(p:50.05i)nabsolute(g/day)feedconsumption and a tendency for reduced relativ(eg/kg/day)feed consumption on days 1 to 8 postweaning, observationsthatwere associatedwiththe tendency forsmallerbody weight in thisgroup on day 1 postweaning. Absoluteand relativfeeed consumption values forthe remainder ofthe precohabitatiopneriodwere comparable and did not significantdliyffearmong the threedosage groups.
B.3.b.Gestation
Absoluteand relativfeeed consumption valuesduringthe gestationperiodwere unaffectedby dosages ofthe testarticlaes highas 0.4 mg/kg/day. Allvalues were comparable among the threedosage groups and did not significantdliyffer.
B.3.c.Lactation
The absolutematernalfeed consumption value was significantrleyduced (p:!@0.0o5n) DLs 1 to 4 inthe 0.4 mg/kg/day dosage group, as compared tothe controlgroup value. The relativfeeed consumption value was also reduced, however notsignificant(lpy>0.05).These observationswere associatedwiththe significanwteight lossthatoccurred inthisgroup on DLs 1 to4 and attributetdo the testarticle.
418-008:PAGE V-7
Absolute and relativfeeed consumption values duringthe lactatiopneriodwere unaffectedby the 0.1 mg/kg/day dosage ofthetestarticle.
B.4. Sexual Maturation (SummaEy - Table E14: IndividualData Tabie_glOj
Dosages ofthe testarticlaes highas 0.4 mg/kg/day didnot affectthe average day ofvaginalpatency inthe Fl generationfemale rats.No significant differencesoccurred among the threedosage groups.
B.5. Passive Avoidance Performance (Summa[y -Table E15: Individual Data -Table E311
There were no biologicalliymportantdifferencesinthe values forlearning,shortterm retentionl,ong-termretentionorresponse inhibitiointhe Fl generation female rats,as evaluatedby performance ina passiveavoidance paradigm. No statisticaslilgynificandtifferenceosccurredinthe trialatenciesor numbers of ratsthatfailedto learn.
The number oftrialtsocriteriownas significantrleyduced (p:@0.05f)orthe female ratsinthe 0.4 mg/kg/day dosage group,as compared tothe controlgroup value. This observationwas not consideredan effectofthe testarticlbeecause an increaseinthe number oftrialtsocriterionr,atherthan a decrease,would be expected as an indicatioonftoxicity.
B.6. Watermaze Performance (Summary -Table E16: IndividualData Table 512 1
No biologicalliymportantdosage-dependent differencesoccurredinwatermaze performance ofthe Fl generationfemale ratsregardinglearning,short-term retentionl,ong-termretentionor response inhibitionN.o statisticaslilgynificant differencesoccurred inthe number oftrialtso criteriont,riallatenciesor numbers of ratsthatfailedto learn.
B.7. Mating and Fertilil(ySumma!y -Table E17a IndividualData Table RU3
Dosages ofthe testarticlaes highas 0.4 mg/kg/day did notaffectany mating and fertiliptayrameters evaluatedinthe Fl generationfemale rats.Values for the number of days incohabitationt,he number ofratsthatmated, the fertility and pregnancy indices(number of pregnanciesper number ofratsthatmated and ratsincohabitationr,espectivelya)n,d the number ofratswithconfirmed mating dates duringthe firsatnd second week of cohabitationwere comparable among the threedosage groups.
418-008:PAGE V-8 REVISED PAGE
B.8. Necropsy Observations (Summary- Table E18; IndividualData Table E34)
Allnecropsy observationsinthe Fl generationfemale ratswere considered unrelatedto the testarticlbeecause: 1)the observationsoccurredinratsinthe controlgroup; and 2) the observationcommonly occurs inthisstrainof rat. These observationsincludedrough and/orpittedcortexofthe kidneyswith calculinthe kidneyand/orurinarybladderof two controlgroup rats.One of these ratsalsohad a tan granularmaterialinthe renalcortexand thickened wallsofthe udnary bladder. Necropsy observationsforthe 0.4 mg/kg/day dosage group dam thatdied as the resultof an intubatioenrrorwere described previously.
B.9. Natural Deliveryand LitterObservations (Su"mmaries -Tables E19 and E20: IndividualData -Tables E35 through E38)
Pregnancy occurred in22 (95.6%),21 (84.0%) and 24 (96.0%) ofthe 23, 25 and 25 female ratsassigned to cohabitatioinnthe 0 (Vehicle)0,.1 and 0.4 mg/kg/day dosage groups,respectivelyA.llpregnantdams deliveredlittersT.he gestation index(thepercentageof pregnant ratswithliveoffspringw)as comparable across thethreedosage groups.
The viabiliotfythe second generationoffspring(F2 pups) was unaffectedat the highestdosage tested,0.4 mg/kg/day. Small increasesinthe number of dams withstillborpnups and inthe number of pup deaths afterDL 2 inthe 0.4 mg/kg/day dosage group were not toxicologicalilmyportantbecause: 1)the valueswere not significantdliyfferenftrom the controlgroup values;2) the average forliveliftesrizesdeliveredand survivingto DL 21 were greaterthan or comparable to the controlgroup values;and 3) neitherthe viabiliotrylactation indicesforthe 0.4 mg/kg/day dosage group remarkably differefdrom the control group values.
Pup body weightsofthe second generationoffspring(F2 pups)were unaffected atthe highestdosage tested,0.4 mg/kg/day. Small reductionsinpup body weightsinthe 0.1 and 0.4 mg/kg/day dosage groups were nottoxicologically importantbecause: 1)the smalldifferencesbetween the pup body weightsfor the controland 0.1 mg/kg/day dosage groups were not statisticaslilgynificant and were associatedwiththe largerliveliftesrizesofthe 0.1 mg/kg/day dosage group on DLsl through4, as compared withthe controlgroup values,and the random selectionofpups forcontinuedobservationson DL 4; 2)the small reductionsinpup body weightsinthe 0.4 mg/kg/day dosage group were associatedwitha minimallylargerliveliftesrizeat birth(DL 1)and on DL 4 precullinga,s compared withthe controlgroup values,and the random selection of pups forcontinuedobservationon DL 4; the statisticalsliygnificanrteductions
418-008:PAGE V-9 REVISED PAGE
(p-<0.05and p-<0.01,respectivelyp)resenton DLs 7 and 14,as compared to the controlgroup values,were transientand disappeared by DL 21.
Administrationofthe testarticlaetdosages as high as 0.4 mg/kg/day did not adverselyaffectany otherparameter evaluatedat naturaldeliveryor duringthe 21 -day lactatiopneriod(durationof gestation,averages forimplantationasnd live littesrizes,numbers ofdams withallpups dyingduringlactationv,iabiliatnyd lactatioinndices,survivingpups per littearnd pup sex ratios).
B.10. ClinicalObservations from Birthto Day 21 Postpartum and Necropsy Observations (Summaries -Tables E21 and E22; IndividualData -Tables E39 and E40)
No clinicaolr necropsy observationswere attributablteodosages ofthe test articlaes high as 0.4 mg/kg/day because: 1)the incidenceswere notdosagedependent; and/or2) the observationoccurred inonlyone ortwo pups. These clinicaolbservationsincludedone controlgroup pup thatwas not nestingor nursing,had decreased motor activitaynd was coldto the touch,one pup in each ofthe controland 0.4 mg/kg/day dosage groups thathad a missingtipof tailand one 0.4 mg/kg/day dosage group pup thathad an umbilicalhernia.
No milkinstomach occurred in2,4 and 4 pups thatwere found dead inthe three respectivedosage groups. One controlgroup pup had hydrocephalyand one 0.1 mg/kg/day dosage group pup had a raisedtan area on the median and left lateralobesof the liverat necropsy on DL 21.
REFERENCES
418-008:PAGE V-10
1. Study Design as Modificatioonf: U.S. Food and Drug Administration (1994). InternationCaolnference on Harmonisation;Guidelineon detectionoftoxicittyo reproductionformedicinalproducts.Federal Register,September 22, 1994, Vol.59, No. 183.
2. U.S. Food and Drug Administration.Good LaboratoryPractice Regulations;FinalRule. 21 CFR Part58.
3. Japanese Ministroyf Healthand Welfare (1997).Good Laboratory PracticeStandard forSafetyStudieson Drugs, MHW Ordinance Number 21, March 26, 1997.
4. European Economic Community (1989).Councildecisionon 28 July 1989 on the acceptance by the European Economic Community ofan OECD decision/recommendationon compliance withprincipleosfgood laboratorypractice.OfficiaJlournalofthe European Communities: Legislation3.2 (No.L 315;28 October):1-17.
5. ChristianM,.S. and Voytek,P.E.(1982).InVivo Reproductiveand MutagenicityTests. EnvironmentalProtectionAgency, Washington, D.C. NationalTechnicalInformationService,U.S. Department ofCommerce, SpringfieldV,A 22161.
6. ChristianM,.S. (1984).Reproductivetoxicitaynd teratologeyvaluationsof naltrexone(Proceedingsof NaltrexoneSymposium, New York Academy of Sciences,November 7, 1983),J.Clin.Psychiat.45(9):7-10.
7. Lang, P.L.(1988).Embryo and FetalDevelopmentalToxicity(Teratology) ControlData inthe Charles RiverCrl:CD7BR Rat. Charles River LaboratoriesI,nc.W,ilmington,MA 01887-0630. (Data base providedby Argus Research LaboratoriesI,nc.)
B. Institutoef LaboratoryAnimal Resources (1996). Guide forthe Care and Use of LaboratoryAnimals. NationalAcademy Press,Washington, D.C.
9. Salewski,E. (1964).Ftirbemethodezum makroskopischen Nachweis von lmplantationssteliaemn Uterusder Rafte.Arch.Pathol.Exp. Pharmakol. 247:367.
10. Snedecor, G.W. and Cochran,W.G. (1967).Variancetestfor homogeneity ofthe binomialdistributioSnt.atisticMaelthods, 6th Edition, Iowa State UniversitPyress,Ames, pp. 240-241.
418-008:PAGE V-1I
ii. Sokal,R.R.and Rohff,F.J.(1969).Bartlettt'esstof homogeneity of variances.Biometry,W.H. Freeman and Co.,San Francisco, pp. 370-371.
12. Snedecor, G.W. and Cochran,W.G. (1967).AnalysisofVariance. StatisticMaelthods, 6th Edition,Iowa StateUniversityPress,Ames, pp. 258-275.
13. Dunnett,C.W. (1955).A multiplecomparison procedure forcomparing severaltreatmentswitha control.J.Amer. Stat.Assoc. 50:1096-1121.
14. Sokal,R.R. and Rohlf,F.J.(1969).Kruskal-WalliTsest. Biometry, W.H. Freeman and Co.,San Francisco,pp. 388-389.
15. Dunn, O.J.(1964).Multiplecomparisons usingrank sums. Technometrics6(3):241-252.
16. Siegel,S. (1956). NonparametricStatisticfsorthe BehavioralSciences, McGraw-Hill,New York,pp. 96-104.
17. Lochry,E.A.,Hoberman, A.M. and ChristianM,.S. (1984).Positive correlatioonf pup body weight withothercommonly used developmental landmarks. Teratology29(2):44A.
I
APPENDIX A REPORT FIGURES
575 550 525 500 X 475 450 425 400 375
BODY WEIGHTS
Fo GENERATION MALE RATS Figure 1
-X----- X x-
-
-
T
T
15
22
29
@6
4ia
49
5b
63
c
DAY OF STUDY
a. Last valuerecordedbeforecohabitation. b. Firstvaluerecorded aftercohabitation. c. Terminalbody weight.
BODY WEIGHTS
Fo GENERATION FEMALE RATS Figure2
400
380
360 -
340
(9320 -
300
280
260240
x-Xx
220
IT5
36--@@a
DAY OF STUDY
-,1-, f T- 10 11 12 DAY OF GESTATION
1 11
1 f --T--f
14 15 16 17 18 19 20-
lO 1'4@l
DAY OF LACTATION
a. Lastvalue recordedbeforecohabitation.
600 500 400 F1: 300 200 100 -
0
BODY WEIGHTS
Fl GENERATION MALE MTS Figure3
22
3f6- -@3
-@O
67
a[
DAY POSTWEANING
a. Precohabitatiobnody weights. b. Terminalbody weights.
BODY WEIGHTS
Fl GENERATION FEMALE RATS Figure4
425
375 -
325
275 Fx
225 -
4Z
in-
1-@F
175 -
125 -
75 -
25 5 29 43 @O 57 4 a
DAY POSTWEANING
10 11 12 13 14 15 16 i'@ I'8 @9 20
4
DAY OF GESTATION
DAY OF LACTATI
a. Precohabitatiobnody weight,
I
APPENDIX B REPORT TABLES - Fo GENERATION
MALE RATS
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PPOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE BI (PAGE 1): CLINICAL OBSERVATIONS
SUMMARY
Fo GENERATION
MALE RATS
I - - ------------ ----- --DOSAGE GROUP DOSAGE (MG/KG/DAY) ------ --- -----------------------MAXIMUM POSSIBLE INCIDENCE
MORTALITY
---------------- - ----- --- ----------------
----
-----------
1 0 (VEHICLE) - ----------------------
11
IV
0.1
0.4
1.6
------------------------------
2345/ 35 2345/ 35 2345/ 35 2345/ 35 23
-
0
0
0
0
LOCALIZED ALOPECIA:
LIMBS
102/ 4
S4/ 2
37/ 2
100/ 4
LEFT EYE: CORNEAL OPACITY
0/ 0
0/ 0
0/ 0
0/ 0
INCISORS:
TOTAL MISSING/BROKEN MISALIGNED
78/ 3 45/ 3 51/ 1
2/ 1 2/ 1 0/ 0
102/ 4 68/ 4 80/ 2
66/ 2 19/ 1 47/ 1
NECK: ABRASION
0/ 0
0/ 0
0/ 0
0/ 0
HYPERACTIVITY
0/ 0
0/ 0
0/ 0
0/ 0
EXCESS SALIVATION
0/ 0
0/ 0
0/ 0
0/ 0
CHROMODACRYORRHEA
24/ 1
0/ 0
34/ 2
41/ 1
SNOUT:
SWOLLEN
0/ 0
0/ 0
27/ 1
43/ 1
CHROMORHINORRHEA
0/ 0
1/ 1
0/ 0
4/ 1
DYSPNEA
0/ 0
0/ 0
0/ 0
4/ 1
--------------------------------------------------------------------------------------------------------------
STATISTICAL
ANALYSES OF CLINICAL OBSERVATION
DATA
MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER
NIN = TOTAL NUMBER OF OBSERVATIONS/NUMBER
OF RATS
WERE RESTRICTED OF RATS EXAMINED WITH OBSERVATION.
TO THE NUMBER PER GROUP.
OF RATS WITH OBSERVATIONS.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/PO5;rNATAL
REPRODUCTION
TOXIC
TABLE 82 (PAGE 1): BODY WEIGHTS - SUMMARY - Fo GENERATION MALE RATS
-------------
----------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ----------------------------
RATS TESTED
- ---
- --N
------
---------
I
ii
0 (VEHICLE)
0.1
----- ------------------------
35
35
------ ----
III 0.4 ---- -- ----
35
----------
-- -----
IV 1.6 ----- ------
35
BODY WEIGHT (G)
DAY
1
MEAN+S.D
388.9 + 22.0
390.1 + 25.7
389.8 + 23.6
390.8 + 16.4
DAY
8
MEAN+S.D
417.2 + 25.8
419.8 + 24.9
417.1 + 24.0
414.8 + 21.6
DAY 15
MEAN+S.D
441.0 + 30.1
441.1 + 28.4
438.1 + 28.4
437.2 + 25.2
DAY 22
MEA.N+S.D
459.1 + 36.3
460.8 + 32.1
456.4 + 32.1
449.6 + 30.9
DAY 29
MEAN+S.D
471.3 + 41.9
476.7 + 36.5
472.1 + 34.3
463.5 + 29.4
DAY 36
MEAN+S.D
488.4 + 42.4
488.5 + 36.4
482.3 + 36.1
472.1 + 30.4
DAY 42a
MEAN+S.D
501.7 + 45.3
503.1 + 40.8
494.8 + 34.0
484.2 + 33.8
DAY 49
MEAN+S.D
509.8 + 46.2
513.2 + 42.3
501.2 + 33.6
492.5 + 35.2
DAY 56b
MEAN+S.D
520.2 + 48.8
518.6 + 45.0
507.9 + 37.2
496.9 + 36.5
DAY 63
MEAN+S.D
538.0 + 52.1
535.2 + 48.6
520.2 + 39.7
510.9 + 39.4
TERMINAL BODY
WEIGHT
MEAN+S.D
542.6 + 52.3
539.3 + 49.2
522.6 + 43.2
512.8 + 40.5
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
a. Last value recorded before cohabitation.
b. First value recorded after cohabitation.
Significantly Significantly
different different
from the vehicle control group value from the vehicle control group value
(p@0.05). (p@0.01@.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVEI,OPMENTAL STUDY N[IMBER: 6295.9)
AND PERINATAL/POSTNAIAL
REPRODUCTION
TOXICT
TABLE B3 (PAGE 1): BODY WEIGHT CHANGES - SUMMARY - Fo GENERATION MALE RATS
DOSAGE GROUP DOSAGE (MG/KG/DAY) - ----------------RATS TESTED
-------
BODY WEIGHT CHANGE (G)
---------- -
I
0 (VEHICLE) ------ -- ---------- - -----
N
35
-- --- -------------
ii
I-II---
0.1
04
------ ----------------
35
35
------------I-V----
1.6 -----------------
-----
35
DAYS
1
8
MEAN+S.D.
+28.2 + 16.1
+29.7 + 11.4
+27. 3 + 12.7
+23.9 + 8.4
DAYS
8
15
MEAN+S.D.
+23.8 + 7.8
+21.3 + 6.6
+21.0 + 7.4
+22.5 + 6.8
DAYS 15
22
MEAN+S.D.
+18.1 + 9.3
+19.8 + 7.8
+18.3 + 8.1
+12.3 + 16.6
DAYS 22
29
MEAN+S.D.
+12.2 + 17.2
+15.9 + 7.5
+15.7 + 6.5
+13.9 + 8.8
DAYS 29
36
MEAN+S.D.
+17.1 + 15.7
+11.8 + 5.6
+10.2 + 5.7
+8.6 + 7.4**
DAYS 36
42a
MEAN+S.D.
+13.3 + 7.8
+14.6 + 6.9
+12.4 + 12@l
+12.1 + 7.2
DAYS
1
42a
MEAN+S.D.
+112.8 + 33.7
4113.0 + 25.8
+105.0 + 24.6
+93.4 + 22.4**
DAYS 56b- 63
DAYS
1 - 63
MEAN+S.D. MEAN+S.D.
+17.7 + 5.8 +149.0 + 40.3
+16.6 + 7.2 +145.1 + 33.6
+12.2 + 8.8* +130.3 + 30.8*
+14.0 + 6.6 +120.0 + 28.9**
DAY
1-
TERMINATION
MEAN+S.D.
+153.6 + 41.5
+149.2 + 34.5
+132.8
------------------------------------------------------------------------------------
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@0.01).
+ 34.0*
+121.9 + 30.2**
---------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NIJMBER: 6291,.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B4 (PAGE 1): ABSOLUTE FEED CONSUMPTION
VALUES (G/DAY) - SUMMARY - Fo GENERATION
MALE RATS
DOSAGE GROUP
DOSAGE (MG/KG/DAY)
------ -------- ----------------
PATS TESTED
N
0 (VEHICLE@ - -------- ------ ---------
35
FEED CONSUMPTION
(G/DAY)
-------- ----- ------
ii
III
0.1
0.4
-----------------------
35
35
-- ----- ---- --------
IV 1.6 -----------------------
35
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 15
22
DAYS 22
29
MEAN+S.D. MEAN+S.D. MEAN+S.D.
27.0 + 2.8
27.8 + 3.4 1 34)a
28.0 + 3.6
27.0 + 2.2 t 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.o
26.3 + 2.8 I 34]a
26.8 + 2.4
DAYS 29
36
DAYS 36 42b
DAYS 1 42b
MEAN+S.D.
MEAN+S.D. MEAN+S.D.
29.5 + 3.7
27.8 + 3.2 27.8 + 2.8
29.2 + 2.4 [ 34]a
27.4 + 2.3
27.8 + 2.1
28.7 + 2.4 [ 34]a
27.0 + 2.9
27.4 + 1,9
27.8 + 2.6
[ 33)a 26.6 + 3.7
26.6 + 2.0*
DAYS 56c- 63
MEAN+S.D.
28.0 + 2.7 1 34)a
27.6 + 2.4
26.6 + 2.2*
25.8 + 2.3*
--------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF STUDY
( I = 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@S0.01).
PROTOCOL 418-008:
COMBINED ORAI, (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENI'AL
STUDY NUMBER
629,..91
AND PERINATAI,/POST14ATAL
REPRODUCTION
TOXIC,
TABLE BS (PAGE 1): RELATIVE FEED CONSUMPTION
VALUES (G/KG/DAY) - SUMMARY - Fo GENERATION
MALE RATS
--------- ---DOSAGE GROUP DOSAGE (MG/KG/DAY) -- ----------------------RATS TESTED
---N
------ -- I
0 (VEHICLE) ------------------
35
- --- - ----------- -- ---- - ---------------- ----
ii 0.1 ----- -- --------------
III
0.4 -----
IV
1.6 -----------------------
35
35
35
FEED CONSUMPTION
(G/KG/DAY)
DAYS 1
8
MEAN+S.D.
65.8 + 5.4
6S.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 4.4 t 34]a
60.2 + 6.7
62.8 + 3.6 f 34)a
61.9 + 4.8
60.9 + 3.6
62.7 + 3.9 61.4 + 4.9 60.2 + 4.0
60.9 + 3.3*
59.2 + 5.2 [ 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 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
52.4 + 3.4
51.7 + 3.3
51.2 + 3.3
[ 34]a
-------------------------------- ------------------------------------------------------------------------------
DAYS = DAYS OF STUDY
I ) = 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).
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
AND PERINATAL/POSTNATAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
621.05.9)
REPRODUCTION
TOXICI
TABLE B6 (PAGE 1): MATING AND FERTILITY - SUMMARY - Fo GENERATION MALE RATS
--- - --- ------------------------------------------
DOSAGE GROUP
I
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
---------------------------------------------------------
RATS IN COHABITATION
N
35
------------ --- ---- -----------------
III
IV
0.1
0.4
1.6
--- -------------------- -------- -- -------------- -
35
35
34a
DAYS IN COHABITATION
b
MEAN+S.D
2.7 + [ 341
1.8
2.6 + 1.3
2.5 + 1.8
2.1 + 1.2 [ 31)
RATS THAT MATED c
N(%)
35(100.0)
35(100.0)
33( 94.3)
34(100.0)
FERTILITY INDEX d,e
NIN
33/35 94.3)
32/35 91.4)
27/33 81.8)
29/34 85.3)
RATS WITH CONFIRMED
MATING DATES f
N
34
35
33
31
RATS MATING g DAYS 1-7
N(%)
34(100.0)
35(100.0)
33(100.0)
31(100.0)
RATS PREGNANT/RATS
IN
COHABITATION
f
NIN
33/35
32/35
27/35
29/34
(t)
94.3)
91.4)
77.1)
85.3)
----------------------------------------------------------------------------------------------------------------
[ I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 8238, which was not assigned to cohabitation
because there were no available
female
b. Restricted to rats with a confirmed mating date on days 1 to 7 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.
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUD-I- NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE 87 (PAGE 1): NECROPSY OBSERVATIONS
SUMMARY - Fo GENERATION
MALE RATS
------- ------ --- -----------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) -------------- ---------------
PATS EXAMINED a
N
- ----------- --------------- ------- -- ------ -- ---- ---------
I 0 (VEHICLE)
ii 0.1
III 0.4
IV 1.6
-- ------ -- -- --------------------------------------------------------
35
35
35
3S
MORTALITY
N
0
0
0
APPEARED
NORMAL
N
33
35
34
32
TESTES:
BILATERAL,
SMALL, PURPLE
AND/OR FLACCID
N
0
0
0
1
LIVER:
LIGHT BROWN OR BROWN
N
0
0
0
0
LARGE
N
1
0
0
ROUGH SURFACE
N
0
0
0
PAPILLARY
PROCESS,
CONSTRICTED
AND NUMEROUS
TAN, RAISED AREAS
N
0
0
0
1
PROSTATE: SMALL
N
1
0
0
EYES:
LEFT, LENS OPAQUE
N
0
0
0
0
KIDNEYS:
BILATERAL,
LARGE
N
1
0
0
1
PARENCHYMA,
CONTAINED
MULTIPLE, PALE, FLUID-
FILLED CYSTS
N
0
0
0
1
RIGHT, PELVIS, SLIGHT
DILATION
N
0
0
1
SPLEEN:
LARGE
N
1
0
0
---------------------------------------------------------------------------------------------------
- -----------
a. Refer to the individual clinical observations table (Table B10) for external observations confirmed at necr
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NTIMBER: 6295.9)
AND PERINATALIPOSTNATAL
REPRODUCTION
TOXIC
TABLE BB (PAGE 1) : TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - Fo GENERATION MALE RATS
-------- ------ ------------ ------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) --------------------------------------
RATS TESTED
N
TERMINAL BODY WEIGHT
MEAN+S.D.
------------ - ---------- ----------------
I
ii
0 (VEHICLE)
0.1
------------ -----------------------------
35
35
--
III 0.4 --
35
542.6 + 52.3
539.3 + 49.2
522.6 +
-------------- --------
IV
1.6 -----------------------
43.2
35 512.8 +
40 .5
EPIDIDYMIS
LEFT
MEAN+S.D.
0.70 + 0.08
0.72 + 0.08
0.70 + 0.06
0.70 + 0.07
TESTIS LEFT
SEMINAL VESICLES WITH FLUID
SEMINAL WITHOUT
VESICLES FLUID
EPIDIDYMIS
RIGHT
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
1.72 + 0.19 [ 33)b
2.07 + 0.34
0.99 + 0.23 0.72 + 0.08
1.76 + 0.14 2.11 + 0.32 1.01 + 0.21 0.74 + 0.07
1.72 + 0.15
1.97 + 0.33 f 34]b
0.95 + 0.18 0.72 + 0.06
1.74 + 0.13 i 34]b
2.01 + 0.35 ( 34)b
0.98 + 0.17
0.70 + 0.08
TESTIS RIGHT
MEAN+S.D.
1.75 + 0.16
1.75 + 0.15
1.71 + 0.16
1.74 + 0.14
PROSTATE
MEAN+S.D.
1.18 + 0.27 1 34]b
1.28 + 0.28
1.15 + 0.31
[ 34]b 1.13 + 0.29
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
[ I = 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 ORAI, (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295,9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE S9 (PAGE 1): RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT
SUMMARY - Fo GENERATION
MALE RATS
---------- -
DOSAGE GROUP DOSAGE (MG/KG/DAY) ----------------- -RATS TESTED
------------ - -
-- -----------N
--- --- --------------
--- ---- -- -- -----------
I
IT
III
0 (VEHICLE)
0.1
0.4
--------- --------------------------------------------
35
35
35
-- ----------IV
1.6 ---- ------------
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.
0.131 + 0.018
0.134 + 0.016
0.134 + 0.016
0.136 + 0.016
TESTIS LEFT
SEMINAL VESICLES WITH FLUID
SEMINAL WITHOUT
VESICLES FLUID
MEAN+S.D. MEAN+S.D. MEAN+S.D.
0.319 + 0.043
0.382 + 0.062 I 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 [ 34]b
0.182 + 0.035
0.339 + 0.032 [ 34)b
0.394 + 0.068 [ 34)b
0.192 + 0.035
EPIDIDYMIS
RIGHT
MEAN+S.D.
0.134 + 0.018
0.138 + 0.016
0.137 + 0.015
0.137 + 0.016
TESTIS RIGHT
MEAN+S.D.
0.324 + 0.038
0.327 + 0.038
0.328 + 0.034
0.340 + 0.035
PROSTATE
MEAN+S.D.
0.218 + 0.053
0.239 + 0.057
0.220 + 0.062
1 34]b 0.219 + 0.054
( i4lb
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS ( I = NUMBER OF VALUES AVERAGED
(G).
RATIOS (It) = (ORGAN WEIGHT/TERMINAL
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) FERIILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STIIDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B10 (PAGE 1): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fa GENERATION
MALE RATS
---------- ---- -------------------- -- - -- --- -------------- --
---------- ------------ ---
DOSAGE GROIIP 1
0 (VEHICLE) MG/K(;/DAY
----------------- ---------------------------- - -- -------------- --- ---- ---------------- ----------------
RAT #
DESCRIPTION
----------------- ---------------------------- I --- --------------- ------------------------------------------
8101
Dq( 16- 23)
INCISORS:
MISSING/BROKEN
DS(
24
INCISORS:
GROWN IN
8102
NO ADVERSE FINDINGS
8103
NO ADVERSE FINDINGS
8104
DS( S- 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
silo
NO ADVERSE FINDINGS
Bill
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( S6- 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
8125
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PF(1!3 IN RAI'S (SPONSOR'S
E7ERTIIITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINAI-AL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B10 (PAGE 2): CLINICAI, OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION MALE RATS
------------------ DOSAGE GROUP 1
------------------ I RAT #
---------------------
8126 8127 8128 8129
--- -- ------------- ---- ------ ----------- --------
------------------- - - ------
------
0 (VEHICLE) MG/KG/DAY ------------ --- ---------------------------
----------------------- ------
DESCRIPTION ------ -------------------- ---------------------------- ------------------------------
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
8130
NO ADVERSE FINDINGS
8131
NO ADVERSE FINDINGS
8132
NO ADVERSE FINDINGS
8133
DS( 17 67)
LOCALIZED
ALOPECIA:
LIMBS a
8134
NO ADVERSE FINDINGS
8135
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. Observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL STUDY NUMiil-:R: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIt'
TABLE BIO (PAGE 3): CLINICAL OBSERVATIONS
- INDIVII)IJAI, DATA - Fo GENERATION MALE RATS
--- ------------- ----- -- --- -- -------------------
------------------------ --------------------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
----------------------- -- ------ -------------------
----------------------------------------------------
RAT #
DESCRIPTION
----------------------- -- --------------------------
------------------------------------------------------
8136
NO ADVERSE FINDINGS
8137
NO ADVERSE FINDINGS
8138
NO ADVERSE FINDINGS
8139
NO ADVERSE FINDINGS
8140
NO ADVERSE FINDINGS
8141
NO ADVERSE FINDINGS
8142
DS( 16- 67)
LOCALIZED
ALOPECIA:
LIMBS a
8143
NO ADVERSE FINDINGS
8144
NO ADVERSE FINDINGS
8145
NO ADVERSE FINDINGS
8146
DS( 66- 67)
LOCALIZED ALOPECIA:
LIMBS a
8147
NO ADVERSE FINDINGS
8148
NO ADVERSE FINDINGS
8149
NO ADVERSE FINDINGS
8150
NO ADVERSE FINDINGS
8151
NO ADVERSE FINDINGS
8152
NO ADVERSE FINDINGS
8153
NO ADVERSE FINDINGS
8154
NO ADVERSE FINDINGS
8155
NO ADVERSE FINDINGS
8156
NO ADVERSE FINDINGS
8157
NO ADVERSE FINDINGS
8158
NO ADVERSE FINDINGS
8159
NO ADVERSE FINDINGS
8160
NO ADVERSE FINDINGS
8161
DS( 66- 67)
INCISORS:
MISSING/BROKEN
a
8162
NO ADVERSE FINDINGS
8163
NO ADVERSE FINDINGS
8164
NO ADVERSE FINDINGS
8165
NO ADVERSE FINDINGS
--------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. Observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6:195.9)
AND PERINATAL/POS'l-NATAL
REPRODUCTION
TOXIC
TABLE B10 (PAGE 4): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA
Fo GENERATION
MALE RATS
-----
--------------- --------
DOSAGE GROUP 11 ------------------------
PAT #
------------------ -- -
0.1 MG/KG/DAY --------------- ---------------
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.
-------------------------------------------------------------------
------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXIC
TABLE BIO (PAGE 5): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
MALE RATS
-- ---------------- -
--------------------- ----- ----------------------------- - -----------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------------------------------------------- -- -------------------------------------------------------
RAT # --------------------------
DESCRIPTION ---------------------------------------------------------
-------------------------
8171
DS( 9- 16)
INCISORS:
MISSING/BROKEN
DS(
17 )
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 8174 8175
NO ADVERSE NO ADVERSE NO ADVERSE
FINDINGS FINDINGS FINDINGS
8176
NO ADVERSE FINDINGS
8177
NO ADVERSE FINDINGS
8178
NO ADVERSE FINDINGS
8179
NO ADVERSE FINDINGS
8180 8181
NO ADVERSE NO ADVERSE
FINDINGS 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
B187
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
8196
NO ADVERSE FINDINGS
8197
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B10 (PACE 6): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION MALE RATS
------ -------------------------- --- -- ----- ----------------- ------ -------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
--------------------------------- ---- ------------------------------- --- -------------------
PAT #
DESCRIPTION
----------------------------------------------------------------------------------------------
8198
NO ADVERSE FINDINGS
8199
NO ADVERSE FINDINGS
8200
NO ADVERSE FINDINGS
8201
NO ADVERSE FINDINGS
6202
NO ADVERSE FINDINGS
8203
DS( 7- 12)
INCISORS:
MISSING/BROKEN
DS(
13
INCISORS:
GROWN IN
8204
NO ADVERSE FINDINGS
8205
NO ADVERSE FINDINGS
----------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. Observation confirmed at necropsy.
-- -------------------------------------------
----------------
PROTOCOL 418-008:
COMBINED ORAL rAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (!IIONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE BIO (PAGE 7): CLINICAL OB.@ERVATIONS - INDIVIDUAL DATA
Fo GENERATION
MALE RATS
-------
-- -------------------- -
DOSAGE GROUP IV ------------------------ -
RAT # ---------------------------
8206 8207 8208 8209 8210 8211 8212 8213 8214 8215 8216 8217 8218 8219 8220 8221 8222 8223 8224
DS( 25- 67)
DS( 14- 67) DS( 66- 67)
DS(
17
-- ---------- --------- -
------------- --------- - - -------------- -
1.6 MG/KG/DAY ----------------------- --- --------------- ------------------------------
DESCRIPTION ----------------------- --------------------------------------------------
NO ADVERSE LOCALIZED NO ADVERSE NO ADVERSE
FINDINGS ALOPECIA:
FINDINGS FINDINGS
LIMBS a
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
LOCALIZED
ALOPECIA:
LIMBS a
NO ADVERSE NO ADVERSE
FINDINGS FINDINGS
LOCALIZED ALOPECIA: NO ADVERSE FINDINGS
LIMBS a
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS 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
8232
NO ADVERSE FINDINGS
8233
NO ADVERSE FINDINGS
8234
NO ADVERSE FINDINGS
8235
NO ADVERSE FINDINGS
----------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. observation confirmed at necropsy.
PROTOCOI, 418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONc;OR'S STUDY NUMBER:
6295.91
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE Bl') (PAGE 8): CLINICAL OBSERVA'I'IONS - INDIVIDUAL DATA - Fo GENERATION
MALE RATS
----------------
------------------------- -- ---------------- -------
----------------
DO.'AGE GROUP IV
1.6 MG/KG/DAY
-------- --- ------------------------- ------------------------
---- ------------------- -----------------
RAr #
DESCRIPTION
--------- ----------------------------- I ------------------------- ----------------------------------------------
8236
NO ADVERSE FINDINGS
6237 8238
DS( 13- 31)
NO ADVERSE INCISORS:
FINDINGS MISSING/BROKEN
8239
DS(
32
INCISORS: NO ADVERSE
GROWN IN FINDINGS
8240
DS(
67
LOCALIZED ALOPECIA:
LIMBS a
--------- ------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. Observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGS) PFOS IN RAI'S (SPONSOR'S
FERTIIITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI
TABLE B10 (PACE 9): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION MALE PATS
-- ------ ------------------DOSAGE GROUP V
---------- -------------------
-I ----------- -- ---- ------ -------- ----------------3.2 MG/KG/DAY
-------------------------------------------------------
----------------
- ---------------------
RAT # ------------------------------
DESCRIPTION ------------------------------------------------------------------------------
8241 8242 8243 8244 8245 8246 8247 8248 8249 8250 8251 8252 8253
DS( 66- 67)
DS(
54
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
HYPERACTIVITY
LIMBS a
8254 8255 8256 8257 825B 8259 8260
8261 8262 8263 8264 8265 8266
DS(
54
DS( 34- 67)
DS( 65- 67) DS( 32- 43)
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
INCISORS!
MISSING/BROKEN
CM)a
DS(
44
INCISORS:
GROWN IN
8267
NO ADVERSE FINDINGS
--------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL Sl'tll)YNUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B10 (PAGE 10): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION MALE RATS
---------------- -------------------- -------
DOSAGE GROUP V
3.2 MG/KG/DA@'
------------------------------------ - -------
-------------------------------------------------------------------------------------------
------
RAT #
DESCRIPTION
---------------------------------------------------------------------------------------------------------
-----
8268
NO ADVERSE FINDINGS
8269
DS(
67
LOCALIZED
ALOPECIA:
LIMBS a
8270
NO ADVERSE FINDINGS
8271
NO ADVERSE FINDINGS
8272
NO ADVERSE FINDINGS
8273
NO ADVERSE FINDINGS
8274
NO ADVERSE FINDINGS
8275
NO ADVERSE FINDINGS
--------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. Observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STTJDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE Bll (PAGE 1): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
- ------------------- -----------------------
------- -----------------
-- -------------------- ---- ---
DAY
1
8
15
22
----------------------------------------------
29
36
42a
49
56
-----------------------------
63b -----------------------------
---
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
----------------------------------------------
--------------------------- ---------------------------------
8101
354.
371.
363.
377.
385.
392.
398.
411.
409.
420.
8102
434.
477.
508.
549.
566.
591.
613.
628.
637.
659.
8103
400.
428.
450.
462.
485.
485.
513.
519.
526.
551.
8104
393.
390.
416,
437.
366.
452.
478.
480.
483.
496.
8105
362.
383.
410.
422.
432.
452.
476.
474.
477.
492.
8106
410.
468.
505.
546.
532.
586.
606.
622.
643.
661.
8107
394.
409.
440.
453.
476.
466.
491.
502.
510.
523.
8108
386.
400.
422.
438.
439.
443.
454.
470.
478.
494.
8109
361.
387.
412.
430.
435.
449.
459.
470.
476.
488.
8110
412.
440.
467.
495.
514.
529.
528.
553.
567.
589.
Bill
391.
427.
453.
461.
493.
504.
501.
512.
513.
537.
8112
394.
425.
451.
476.
486.
498.
504.
499.
525.
537.
8113
365.
382.
402.
420.
430.
439.
447.
453.
461.
471.
8114
410.
436.
454.
473.
486.
495.
507.
520.
525.
551.
oils
380.
397.
416.
434,
450.
463.
467.
481.
491.
502.
8116
400.
432.
458.
478.
505.
516.
526.
535.
546.'
561.
8117
380.
398.
412.
429.
438.
451.
466.
458.
484.
498.
8118
414.
439.
465.
495.
516.
541.
564.
562.
573.
596.
8119
391.
416.
437.
454.
454.
470.
492.
498.
516@
524.
8120
395.
421.
456.
466.
483.
504.
516.
528.
526.
552.
8121
359.
377.
407.
425.
432.
433.
443.
451,
462.
481.
8122
418.
446.
467.
488.
501.
507.
520.
532.
548.
561.
8123
391.
414.
436.
453.
477.
494.
498.
sio.
521.
539.
8124
411.
442.
467.
494.
503.
506.
529.
531.
542.
567.
8125
373.
401.
423.
442.
462.
470.
484.
486.
495.
513.
8126
321.
417.
453.
476.
491.
505.
518.
527.
550.
566.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN CRAMS (G).
a. Last value recorded before cohabitation.
b. First value recorded after cohabitation.
PROTOCOL 418-008:
COMBINED ORAL PFOS IN RATS
(GAVAGE) (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NIIMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE Bll (PACE 2): BODY WEIGHTS - INDIVIDUAL DAI'A - Fo GENERATION MALE RATS
--------------------- -- --- ----------------- -- - --------------------------- -- ----------------- -- -- -
DAY
1
8
is
22
29
36
42a
49
56
------------------------------------------------- - ---------------------------
63b ----------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------------------------------------------
-----------------------------
8127
393.
418.
446.
461.
480.
502.
515.
523.
525.
550.
8128
407.
453.
473.
495.
531.
549.
569.
577.
595.
624.
8129
377.
413.
438.
450.
458.
472.
488.
502.
518.
534.
8130
399.
427.
453.
479.
492.
sio.
525.
522.
538.
557.
8131
381.
402.
424.
426.
446.
466.
479.
488.
500.
511.
8132
397.
419.
437.
431.
443.
481.
497.
503.
520.
538.
8133
364.
376.
389.
394.
411.
425.
424.
436.
434.
446.
8134
398.
440.
465.
477.
500.
518.
536.
545.
551.
580.
8135
398.
430.
460.
484.
499.
511.
530.
536.
544.
561.
--------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE Bll (PAGE 3): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE PATS
----- ---------------------- -
----- -------------------
DAY
1
8
15
22
29
36
-42-a------49-------5-6------63b --------------------------
-------- ------------------- ------------------------------ - ---------------------- --------------------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------- ----------------------------------------------------------------------------------
8136
353.
365,
372.
384.
378.
393.
396.
401.
409.
408.
8137
433.
472.
497.
525.
547.
556.
578.
584.
600.
615.
8138
383.
410.
422.
453.
461.
474.
492.
491.
507.
515.
8139
385.
409.
426.
444.
468.
466.
478.
485.
489.
504.
8140
367.
390.
409.
422.
435.
452.
466.
476.
478.
491.
8141
418.
461@
490.
521.
536.
539.
563.
574.
583.
597.
8142
379.
404.
423.
436.
449.
465.
467.
478.
476.
493.
8143
390.
425
450.
467.
472.
482.
496.
508.
508.
528.
8144
357.
390.
404.
423.
433.
435.
448.
452.
453.
457.
8145
408.
434.
456.
467.
487.
496.
512.
524.
520.
524.
8146
404.
436.
4S9.
483.
508.
522.
537.
550.
542.
559.
8147
398.
427.
452.
465.
486.
492.
507.
521.
522.
538.
8148
373.
398.
417.
426.
431.
437.
447.
458.
463.
474.
8149
416.
446.
460.
483.
498.
511.
513.
531.
532.
556.
8150
384.
410.
431.
456.
474.
489.
500.
515.
526.
544.
8151
400.
436.
456.
467.
477.
479.
492.
509.
509.
525.
8152
379.
412.
435.
462.
475.
494.
504.
517.
526.
546.
8153
414.
444.
480.
512.
540.
549.
567.
572.
594.
612.
8154
391.
424.
452.
471.
486.
494.
500.
515.
525.
539.
8155
374.
412.
430.
454.
472.
489.
504.
504.
500.
522.
8156
430.
466.
500.
530.
550.
567.
594.
603.
622.
648.
8157
388.
408.
423.
447.
472.
486.
509.
508.
519.
543.
8158
375.
402.
422.
445.
4SO.
460.
474.
484.
490.
518.
8159
402.
423.
447.
474.
479.
495.
502.
512.
517.
538.
8160
290.
368.
396.
420.
439.
450.
455.
464.
467.
486.
8161
404.
431.
452.
469.
485.
491.
508.
514.
519.
533.
---------------------------------------------------------------------------------------------------------------
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE Bll (PAGE 4): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
-------- --
--------------- - - ---------- ----- ----- ---- -- ----------------- ------------------
DAY
1
a
15
22
29
36
42a
49
56
63b
-------- --- --------------------- ----- -------------------------------------------------
------------------
RAT 4
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8162
378.
392.
410.
426.
435.
450.
467.
474.
476.
497.
8163
404.
426.
456
481.
507.
520.
549.
556.
557.
580.
8164
381.
390.
413.
434.
450.
467.
482.
492.
498.
522.
8165
406.
437.
462.
479.
499.
509.
529.
546.
552.
571.
8166
387.
425.
444.
443.
466.
477.
501.
517.
523.
534,
8167
407.
447.
456.
469.
487.
511.
527.
537.
550.
572.
8168
379.
408.
424.
433.
450.
466.
471.
476.
477.
486.
8169
404.
426.
443.
460.
483.
502.
518.
531.
S32.
536.
8170
412.
438.
469.
499.
521.
534.
556.
582.
590.
621.
--------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE Bll (PAGE 5): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
------------ ----
DAY
-1-------8------1-5-------22--
--- ------- ---- ---- ------------
29
36
42a
49
56
----- --------------------63b
---------------------------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8171
354.
366.
375.
379.
387.
390.
402.
409.
416.
418.
8172
437.
480.
517.
543.
565.
578.
528.
542.
575.
566.
8173
394.
422.
436.
456.
467.
474.
485.
494.
489.
486.
8174
396.
421.
443.
462.
478.
486.
503.
498.
516.
522.
8175
360.
384.
392.
398.
410.
42S.
448.
458.
462.
482.
8176
408.
448.
478.
Soo.
Sil.
523.
544.
542.
549.
573.
8177
385.
411.
424.
446.
467.
468.
491.
501.
511.
528.
8178
392.
418.
445.
469.
484.
491.
503.
511.
515.
530.
8179
361.
385.
416.
436.
453.
454.
470.
475.
472.
489.
8180
408.
427.
452.
476.
485.
492.
511.
522.
528.
535.
8181
396.
423.
438.
459.
468.
479.
490.
490.
483.
490.
8182
399.
417.
437.
464.
472.
482.
499.
502,
514.
532.
8183
373.
386.
412.
430.
435.
444.
448.
452.
460.
468.
8184
417.
448.
477.
508.
533.
546.
559.
574.
588.
604.
8185
382.
407.
415.
433.
443.
456.
461.
474.
471.
491.
8186
408.
429.
451.
460.
466.
466.
467.
477.
482.
488.
8187
377.
406.
431.
446.
455.
473.
485.
499.
507.
515.
8188
404.
430.
455.
477.
496.
507.
521.
519.
536.
534.
8189
379.
391.
406.
433.
451.
449.
465.
474.
475.
486.
8190
404.
422.
447.
463.
475.
482.
493.
499.
506.
528.
8191
380.
401.
427.
447.
470.
482.
490.
497.
499.
521.
8192
406.
437.
4S6.
477.
490.
500.
514.
513.
515.
534.
8193
389.
415.
439.
466.
481.
486.
Sil.
518.
526.
546.
8194
389.
405.
428.
434.
465.
477.
489.
505.
S22.
536.
8195
298.
378.
400.
424.
434.
444.
458.
468.
479.
491.
8196
408.
436.
463.
481.
502.
513.
530.
535.
551.
577.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
b. First value recorded after cohabitation.
PROTOCOL 41R-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
SI'UDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE Bll (PAGE 6): BODY WEIGHTS
INDIVIDUAL
DATA - Fo GENERATION
MALE RATS
----- - -------- ----------
-- ---------- ---------------- -- ------------ ---- ------------------
DAY
1
8
is
22
29
36
42a
49
56
63b
------------ ---------- ----------- --- -- ---------- --------------------------------------------------------
RAT # ------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------- ---- -------------------------------------------------------------------
8197
389.
428.
442.
467.
484.
502.
518.
516.
516.
518.
8198
399.
422.
444.
453.
467.
484.
494.
499.
501.
518.
8199
386.
416.
440.
466.
465.
502.
518.
514.
513.
539.
8200
409.
448.
482.
509.
529.
538.
549.
553.
571.
583.
8201
384.
405.
413.
413.
437.
446.
460.
467.
466.
469.
8202
417.
465.
485.
487.
sis.
540.
563.
574.
576.
601.
8203
374.
404.
417.
424.
445.
459.
478.
489.
491.
498.
8204
397.
406.
422.
438.
447.
463 . 474.
474.
484.
490.
8205
385.
412.
430.
451.
472.
481.
499.
510.
513.
520.
--------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE Bll (PAGE 7): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION MALE RATS
---------------- - ----------------------------- --------- --------------- ----------- --- ------------ -----
DAY
1
8
15
22
29
36
42a
49
56
63b
---------------------------------------------------------- I-----------------------------------------------------
RAT #
DOSAGE GROUP IV
-------------------------------------
1.6 MG/KG/DAY -------------------------------------------------------------------------
8206
354.
361.
303.
395.
407.
417.
428.
428.
433.
444.
8207
428.
463.
496.
506.
523.
524.
539.
546.
563.
576.
8208
384.
409.
430.
453.
463.
464.
479.
488.
508.
520.
8209
399.
427.
446.
465.
472.
485.
498.
506.
517.
531.
8210
364.
376.
394.
408.
413.
419.
434.
442.
455.
464.
8211
402.
426.
454.
474.
486.
486.
500.
507.
514.
S32.
8212
387.
420.
436.
446.
462.
470.
480.
502.
491.
514.
8213
392.
411.
429.
446.
453.
460.
468.
512.
493.
499.
8214
375.
393.
412.
424.
435.
444.
460.
463.
474.
486.
8215
422.
448.
477.
491.
495.
502.
532.
538.
535.
551.
8216
387.
412.
437.
464.
471.
487.
510.
S14.
520.
547.
8217
398.
428.
450.
472.
484.
492.
503.
511.
518.
531.
8218
363.
383.
402.
423.
438.
435.
439.
443.
448.
460.
8219
403.
436.
456.
473.
485.
498.
504.
sis.
517.
538.
8220
395.
421.
437.
451.
467.
475.
492.
490.
493.
496.
8221
402.
433.
461.
471.
482.
489.
501.
502.
514.
535.
8222
379.
406.
423.
446.
454.
470.
473.
472.
465.
482.
8223
405.
432.
453.
471.
497.
524.
540.
554.
567.
579.
8224
385.
415.
437.
367.
408.
438.
461-
477.
486.
494.
8225
400.
402.
437.
462.
473.
484.
495.
508.
518.
534.
8226
380.
407.
429.
444.
459.
472.
478.
490.
494.
SOS.
8227
405.
438.
468.
478.
497.
508.
528.
530.
538.
562.
8228
373.
385.
394.
392.
405.
402.
412,
415.
416.
419.
8229
408.
428.
456.
478.
495.
494.
510.
512.
517.
534.
8230
382.
396.
418.
431.
446.
458.
466.
468.
462.
488.
8231
405.
434.
466.
484.
487.
491.
494.
498.
495.
512.
---------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE Bll (PAGE 8): BODY WEIGHTS
INDIVIDUAL DATA - Fo GENERATION
MALE RATS
------------- - ----------
- --------
----------
DAY
1
8
is
------------------------------------
RAT N
DOSAGE GROUP IV
22
29
36
42a - 4-9 -- --5-6------63-b --- -- -- --------------
- --- --------- ----------------------------- ---------------------------
1.6 MG/KG/DAY
------------------------------------ --------------------------- ---------------------------------------------
8232
390.
411.
437.
438,
450.
459.
471.
487.
485.
501.
8233
397.
422.
452.
471.
488.
494.
501.
505.
515.
523.
8234 8235
376. 397.
402. 435.
428. 441.
449. 469.
466. 486.
468. 498.
470. 512.
481. 526.
493. 526.
512. 538.
8236
373.
392.
405.
401.
440.
452.
455.
460.
463.
481.
8237
406.
443.
478.
478.
503.
523.
554.
567.
567.
589.
8238
380.
400.
421.
421.
433.
438.
440.
454.
450.
458.
8239
406.
418.
439.
447.
442.
442.
448.
449.
451.
456.
8240
378.
404.
422.
447.
457.
462.
474.
477.
490.
491.
---------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE Bll (PAGE 9): BODY WEIGHTS - INDIVIDUAL DATA - Fo GENERATION
MALE RATS
-- ---------- ----- -- -- ------ -- ----- ----- - -- - ------------ ------- -----------
- ------------------
DAY -------------------
1
8
is
22
29
36
42a
49
56
63b
-- -- ------------------------------------------------- -- --------- I ---------------------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
--- --------------- ------------ ------------------- ---------------------------------------------------------
8241
354.
380.
392.
393.
396.
391.
394.
395.
393.
400.
8242
439.
477.
507.
528.
553.
554.
559.
572.
566.
578.
8243
390.
415.
441.
458.
466.
470.
486.
482.
483.
513.
8244
395.
410.
426.
445.
456.
462.
469.
473.
473.
482.
8245
366.
378.
400.
413.
421.
422.
436.
437.
444.
451.
8246
410.
432.
448.
474.
480.
497.
500.
497.
508.
515.
8247
377.
404.
425.
426.
425.
421.
429.
425.
427.
430.
8248
388.
420.
434 . 453.
451.
459.
472.
482.
481.
447.
8249
367.
388.
396.
406.
413.
408.
417.
418.
421.
431.
8250
40S.
431.
450.
463.
476.
476.
477.
481.
478.
496.
8251
384.
402.
422.
438.
445.
444.
453.
456.
466.
447.
8252
391.
41S.
434.
446.
449.
451.
458.
468.
470.
474.
8253
359.
375.
398.
421.
432.
436.
435.
436.
436.
448.
8254
415.
438.
461.
480.
491.
494.
500.
502.
500@
511.
8255
390.
413.
444.
461.
469.
478.
473.
467.
476.
490.
8256
398.
417.
439.
449.
453.
447.
443.
451.
442.
462.
8257
378.
393.
403.
411.
409.
415.
416.
414.
420.
425.
8258
405.
439.
460.
481.
486.
490.
485.
492.
497.
498.
8259
388.
407.
428.
438.
438.
432.
440.
434.
433.
432.
8260
413.
439.
463.
491.
504.
517.
527.
516.
521.
555.
8261
370.
394 . 408.
425.
424.
431.
435.
437.
445.
453.
8262
409.
425.
434.
448.
447.
445.
450.
450.
457.
466.
8263
379.
408.
439.
465.
483 . 492.
500.
498.
511.
520.
8264
403.
436.
461.
486.
502.
493.
505.
503.
510.
516.
8265
374.
397.
406.
395.
410.
414.
413.
413.
424.
423.
8266
401.
429.
450.
440.
452.
464.
466.
474.
477.
488.
---------------------------------------------------------------------------------------------------------------
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AN[) PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE Bll (PACE 10): BODY WEIGHTS @ INDIVIDUAL DATA - Fo GENERATION MALE RATS
---------- ---------I ------- ----------- ---- -
DAY
1
8
------------------------------
15
22
-------------
RAT #
DOSAGE GROUP V
---------------------------------------- ----
29-------36----- 42-a--- 4-9---- --------------- --
3.2 MG/KG/DAY ------------------------
----5-6-------63-b----------- ---- --------------------------------------------------
-----------------------------------------
8267
375.
395.
410.
403.
414.
415.
423.
422.
430.
432.
8268
410.
448.
484.
498.
516.
517.
531.
528.
534.
544.
8269
382.
415.
440.
453.
470.
479.
493.
494.
498.
507.
8270
403.
428.
456.
457.
479.
481.
500.
491.
492.
498.
8271
386.
410.
432.
432.
456.
474.
483.
489.
495.
510.
8272
405.
439.
470.
464.
494.
493.
512.
512.
S20.
529.
8273
379.
399.
435.
432.
440.
442.
456.
460.
455.
458.
8274
400.
423.
443.
453.
460.
467.
477.
481.
491.
497.
8275
400.
427.
452.
454.
472.
488.
497.
480.
487.
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
PFOS IN PATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B12 (PACE 1): FEED CONSUMPTION
VALUES - INDIVIDUAL DATA - Fo GENERATION
MALE RATS
------ ------------------ --------------- ----------- -I --------------- ----------------------------
DAYS
I- 8 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
------------------------------------ - --------------------------- --------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8101
158.
147.
149.
165.
isi.
130.
158.
8102 8103 8104 8105 8106
229. 173. 164. 168. 226.
232. 174. 164. 184. 229.
253. 183. 173. 187. 254.
233. 185. 108. 179. 202.
254. 189. 228. 195. 279.
193. 160. 182. 172. 213.
232. 190.
c 192. 242.
8107
180.
188.
193.
190.
197.
153.
183.
8108
167.
178.
183.
188.
169.
146.
184.
8109
148.
159.
171.
162.
168.
145.
166.
8110
181.
188.
201.
208.
213.
154.
215.
Bill 8112 8113
189. 206. 160.
189. 219. 168.
202. 224. 176.
213. 231. 174.
222. 230. 177.
146. 175. 146.
194. 211. 168.
8114
185.
182.
195.
190.
201.
160.
206.
8115
172.
185.
191.
200.
196.
147.
190.
8116
186.
193.
199.
199.
201.
160.
192.
8117
170.
177.
185.
175.
186.
156.
188.
8118
208.
213.
222.
224.
230.
198.
216.
8119 8120
184. 179.
190. 178.
194. 191.
176. 184.
196. 197.
174. 169.
195. 191.
8121
166.
181.
201.
184.
186.
144.
179.
8122
197.
193.
203.
193.
208.
167.
200.
8123
199.
193.
197.
207.
212.
162.
195.
8124
208.
192.
205.
185.
196.
173.
187.
8125
169.
171.
178,
183.
182.
150.
172.
8126
212.
204.
201.
193.
196.
159.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B12 (PAGE 2): FEED CONSUMPTION
VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
------------------------------------------ ------ --------------------------------- ---I--------------------- -
DAYS
I- 6 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
---------------------- ------------------- - ------- ---------------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
-------------------------------------- -------------------------------------------- --------------------------
8127
191.
194.
191.
189.
196.
170.
200.
8128
222.
204.
228.
231.
235.
196.
225.
8129
207.
204.
203.
202.
210.
174.
200.
8130
192.
199.
201.
205.
223.
189.
202.
8131
189.
206.
169.
243.
237.
191.
214.
8132
177.
180.
c
213.
233.
176.
203.
8133
155.
158.
131.
195.
182.
142.
159.
8134
199.
206.
185.
226.
234.
184.
211.
8135
199.
211.
198.
225.
228.
183.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI
TABLE B12 (PAGE 3): FEED CONSUMPTION
VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
----------- -- -------------------------- ---------- -------- ----------- ----------- ----------- ----------
DAYS
I- 8 8- 15 IS- 22
-------------------------------------------
RAT #
DOSAGE GROUP 11
----------------- -----------------------
22- 29 29 36 36- 42a 56b- 63 ---------- ---------------------------------------- I ---
0.1 MG/KG/DAY -------------------------------------------------------
--------------------
8136 8137 8138 8139 8140 8141 8142 0143 8144 8145 8146 8147 8148 8149 8150 8151 8152 6153 8154 8155 8156 8157 8158 8159 8160 8161
149. 205. 168. 169. 166. 217. 171. 200. 182. 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.
lB6. 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.
200. 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.
PROTOCOL 418-008:
COMBINED ORAL ((3AVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295,9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXIC
TABLE B12 (PAGE 4); FEED CONSUMPTION VALUES - INDIVIDUAL DATA
Po GENERATION
MALE RATS
---------- ------------------------
- --------- ----- ------- ---------------------------- ----------- --
DAYS
I- 8 8- 15 15- 22 22- 29 29 36 36- 42a 56b- 63
----------------------------------- --- ------------------------- -------------------------------------------
RAT #
DOSAGE GROUP 11
-----------------------------------
0.1 MG/KG/DAY ----------------------------- ----------------------
--------------------
8162 8163 8164
16B. 198. 174.
175. 208. 180.
174. 226. 182.
176. 212. 180.
179. 234. 198.
152. 183. 150.
181. 212. 196.
8165
205.
205.
211.
212.
220.
183.
207.
8166
194.
193.
147.
219.
221.
169.
194.
8167
196.
198.
189.
238.
223.
177.
212.
8168
183.
173.
151.
194.
195.
151.
177.
8169
187.
175.
172.
220.
227.
182.
197.
8170
189.
197.
201.
213.
220.
185.
214.
----------------------------------------------------------------------------------------------------------------
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B12 (PAGE 5): FEED CONSUMPTION
VALUES - INDIVIDUAL DATA - Fo GENERATION
MALE RATS
-- --------------------------------- - --------------- ------ ----------- -- ----- --------- -----------------
DAYS
I- 8 8- 15 IS- 22 22- 29 29- 36 36- 42a 56b- 63
------ -------------------------- -- - ------------------------------------------- --------------------- ------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
------------------------------------ -------------------------------------------- -- --------------------------
8171 8172 8173 8174 8175
8176 8177 8178 8179 8180 8181 8182
155. 218. 190. 176. 168. 205. 180. 192. 202. 177. 186.
185.
156. 221. 176. 180. 168. 214. 174.
196. 208. 188. 170. 195.
162. 228. 186. 191. 168. 218. 194. 200. 193. 199. 192. 217.
159. 213. 185. 186. 167. 205. 191. 192. 202. 194. 184. 207.
156. 217. 186. 197.
c 214. 182. 205. 204. 191. 192. 215.
132. 96.
155. 153. 159. 182. 162. 154. 160. 163. 160. 180.
153. 177. 160. 183. 186. 205. 187. 178. 175. 176. 165. 207.
8183 8184 8185
169. 210. 174.
180. 214. 161.
190. 223. 195.
183. 222. 201.
181. 227. 191.
150. 171. 174.
182. 194. 188.
8186 8187 8188 8189 8190 8191
196. 182. 193. 178. 193. 192.
191. 193. 192. 181. 193. 187.
182. 192. 197. 198. 192. 209.
171. 197. 206. 191. 188. 202.
192. 210. 208. 198. 201. 202.
144. 160. 164. 164. 158. 172.
175. 186. 177. 178. 188. 201.
8192 8193 8194 8195 8196
188. 182. 166. 200. 195.
189. 190. 177. 192. 205.
198. 206. 174. 194. 203.
195. 194. 184. 192. 198.
202. 211. 191. 187. 190.
159. 184. 159. 160. 178.
186. 199. 188. 101. 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.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
MD PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B12 (PAGE 6): FEED CONSUMPTION
VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
------------- --------------- ---- ----------------------
DAYS
I- 8 8 15 15- 22 22- 29 29- 36 36 -4-2-a---56-b-----6-3---------- --
--------- --------------- - -- ------------------------ ----------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------- -----------------------------------------------------
---- -----------------------------------------------------
8197
193.
178.
8198 8199 8200 0201
181. 180. 198. 180.
186. 198. 218. 164.
8202
227.
216.
8203
183.
172.
8204
177.
171.
8205
187.
177.
----------------------------------
192.
185.
195.
161.
170.
185.
173.
198.
161.
175.
204.
207.
209.
164.
208.
227.
226.
234.
172.
216.
135.
198.
180.
148.
177.
162.
226.
245.
208.
217.
162.
218.
207.
164.
183.
167.
193.
192.
157.
179.
195.
208.
220.
174.
204.
---------------------------------------------------------------------------
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAb/POSTNATAL
REPRODUCTION
TOXICIT
TABLE B12 (PAGE 7): FEED CONSUMPTION VALUES - INDIVIDUAL DATA
Fo GENERATION
MALE RATS
--------- ----------------------- ------------------------------- ---------- ------------------
DAYS
1- 0 8- 15 15- 22 22- 29 29- 36 36- 42a 56b- 63
-----------------------------------------------------------------------------------------------
-------------------------------
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
----------------------------------------------------------------------------------------------------------------
8206
152.
164.
166.
167.
167.
137.
166.
8207
191.
193.
196.
186.
186.
155.
188.
8208
184.
179.
194.
185.
c
153.
180.
8209
178.
172.
180.
178.
188.
155.
184.
8210
153.
163.
168.
167.
48.d
127.
146.
8211
200.
204.
207.
195.
182.
161.
180.
8212
196.
190.
197.
193.
201.
144,
185.
8213
171.
171.
176.
176.
178.
144.
178.
8214
173.
166.
176.
176.
182.
150.
174.
8215
217.
199.
185.
182.
211.
171.
189.
8216
187.
177.
187.
188.
185.
161.
202.
8217
185.
192.
197.
198.
192.
172.
185.
8218
167.
165.
186.
162.
173.
138.
153.
8219
191.
172.
193.
177.
201.
146.
190.
8220
189.
177.
190.
188.
197.
150.
170.
8221
190.
182.
184.
185.
193.
159.
183.
8222
183.
177.
186.
176.
188.
145.
149.
8223
200.
193.
189.
212.
228.
254.
203.
8224
197.
191.
b
154.
202.
189.
199.
8225
163.
183.
199.
195.
168.
167.
186.
8226
186.
179.
189.
188.
192.
161.
180.
8227
201.
193.
204.
196.
221.
181.
198.
8228
158.
157.
155.
163.
171.
134.
157.
8229
213.
210.
228.
219.
229.
176.
210.
8230
173.
181.
182.
183.
194.
158.
189.
8231
210.
194.
188.
197.
205.
157.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B12 (PAGE 8): FEED CONSUMPTION
VALUES
INDIVIDUAL DATA - Fo GENERATION MALE RATS
-------------- -------------------------------
DAYS
I- 8 8- 15 15- 22 22-
----------------------------------------------
RAT #
DOSAGE GROUP IV
- --------------------
29 29- 36 36- 42a 56b ----------------------- I
1.6 MG/KG/DAY
--------------------------63 -----------------------------
- --------------
----------------------------------------------------------------------------------------------------
8232 8233 8234 8235 8236 8237 8238
157. 204. 174. 198. 174.
202. 183.
205. 193. 173. 163. 166. 201. 181.
194. 199. 188. 210. 125.
156. 148.
198. 193. 185. 213. 217. 223. 200.
227. 201. 167. 212. 203. 231. 184.
183. 156. 163. 161. 148. 185. 149.
194. 169. 185. 183. 182. 207. 167.
---------
8239 8240
177. 195.
170. 177.
161. 185.
172. 197.
175. 196.
143. 161.
169. 184.
---------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
b. First value recorded after cohabitation.
PROTOCOL 416-008:
COMBINED ORAL (GAVACE@ PPOS IN RATS (SPONSOR'S
FERTIIITY, DEVELOPMENTAL STUDY NTJMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B12 (PAGE 9): FEED CONSUMPTION
VALUES - INDIVIDUAL DATA - Fo GENERATION MALE RATS
--------------- ----------------- ---------------- -------------- ---- --------------------- -------------- --
DAYS
I- 8 8- 15
--------------- -----------------
15- 22 22- 29 29- 36 36- 42a 56b- 63 -- -------------------------------------------------------------------------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8241
173.
168.
158.
189.
138.
117.
142.
8242 8243
236. 202.
220. 198.
227. 198.
210. 190.
207. c
170. 155.
199. 177.
8244 8245
177. 160.
181. 170.
180. 176.
182. 166.
179. 168.
142. 138.
169. IS7.
8246
194.
181.
197.
200.
209.
154.
177.
8247
183.
171.
166.
151.
147.
128.
150.
8248
185.
176.
194.
166.
179.
149.
135.
8249
161.
153.
158.
150.
153.
122.
141.
8250
188.
181.
183.
182.
188.
140.
170.
8251
186.
169.
199.
185.
172.
148.
163.
8252
187.
171.
178.
205.
195.
162.
160.
8253 8254
167. 190.
164. 184.
175. 188.
167. 186.
184. 189.
127. 147.
155. 167.
8255
182.
178.
191.
177.
191.
137.
175.
82S6
188.
174.
187.
173.
181.
132.
164.
8257
166.
162.
154.
Ise.
156.
125.
149.
8258
208.
196.
201.
184.
185.
140.
176.
8259
179.
174.
186.
176.
172.
144.
148.
8260
193.
178.
186.
181.
192.
152.
162.
8261
182.
165.
181.
153.
169.
144.
154.
8262
179.
160.
176.
166.
164.
129.
157.
8263
190.
186.
213.
204.
201.
164.
186.
8264
219.
202.
204.
200.
171.
149.
204.
8265
178.
162.
115.
180.
157.
140.
141.
8266
182.
181.
138.
188.
177.
144.
169.
---------------------------------------------------------------------------------------------------------------
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 precluded the calculation of this value.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAI,
STUDY NUMBSR:
6295.9)
AND PtRINATAL/POSTNATAL
REPRODUCTION
TOXICLT
TABLE B12 (PAGE 10); FEED CONSUMPTION
VALUES - INDIVIDUAL DATA
Fo GENERATION
MALE RATS
------ -------------- --------------
DAYS
I- 8 8- 15 15- 22
------------------------------------------
22- -2-9----29- -3-6 --3-6--- 42-a 5-6-b----6-3---------- ------ -- --- ---------------------- ----------- ----------------------------------------------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
----------------- ------------------------ ------------- -------- ----------------------------------------------
8267
172.
173.
130.
184.
165.
136.
156.
8268
215.
223.
189.
219.
203.
160.
185.
8269 8270
171. 190.
164. 194.
173. 166.
184. 204.
183. 201.
147. 155.
162. 174.
8271
207.
199.
153.
208.
202.
160.
182.
8272
196.
190.
149.
201.
188.
156.
192.
8273
192.
194.
148.
194.
175.
153.
158.
8274
198.
189.
187.
199.
184.
157.
172.
8275
189.
186.
151.
205.
184.
151.
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 PFOS IN RATS
(GAVAGE) (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE 813 (PAGE 1): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
-------- --------- ---- -- - --------- - ------ ------- --------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
-------------------- ---------------------- -------- ----------------
-- --- ------- 11 ---------- --------------------- I ---- ----------
DAYS IN
FEMALE PREGNANCY
RAT
COHABITATION
MATING STATUS
MATING DATE
STATUS
---------------------------------------------------- ---------------- ----------------------------------------
8101
2
m
c
P(8801)
8102
1
m
c
P(8802)
8103
2
m
c
P(8803)
8104
3
m
c
P(8804)
8105
7
m
c
P(8805)
8106
1
m
c
P(8806)
8107
2
m
c
P(8807)
8108
2
m
c
P(BOOB)
8109
1
m
c
P(8809)
8110a
1
m
c
P(8810)
8110b
7
DID NOT MATE
-(8812)
8111
4
m
c
P(8811)
8112
7
m
NC
P(8812)
8113
3
m
c
P(8813)
8114
3
m
c
P(8814)
8115
1
m
c
P(8815)
8116
1
m
c
P(8616)
8117
7
m
c
NP(8817)
8118
3
m
c
NP(8818)
8119
3
m
c
P(8819)
8120
1
m
c
P(8820)
6121
2
m
c
P(8821)
8122
1
m
c
P(8822)
8123
4
m
c
P(8823)
8124
4
m
c
P(8824)
8125
1
m
c
P(882S)
8126
4
m
c
P(8826)
8127
7
m
c
P(8827)
8128
2
m
c
P(8828)
6129
1
m
c
P(8829)
8130
3
m
c
P(8830)
--------------------------------------------------------------------------------------------------------------
M = MATED
( ) = FEMALE RAT NUMBER
C = CONFIRMED P = PREGNANT
NC
NOT CONFIRMED
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.
PROTOCOL 418-008:
COMBINED ORAI, (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDN' NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B13 (PAGE 2): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
- - -------------- -------
DOSAGE GROUP 1
0 -(VEH-I-C-LE)---M-G-/-K-G/-D-A-Y ----------- -------------- -------------- ---- -------- ---
---------------------------- - ------------------- ---------------------- - -------------------------------
DAYS IN
RAT
COHABITATION
MATING
------------------------------ I - ---------------
FEMALE PREGNANCY
STATUS
MATING DATE
STATUS
---- --------------------------------------------------------
8131
4
m
c
8132
3
m
c
8133
1
m
c
8134
4
m
c
8135
4
m
c
----------------------------------------------------------------------------
P(8831) P(8832) P(8833) P(8834) P(8835) ---------------------------------
M = MATED C = CONFIRMED P = PREGNANT
( ) = FEMALE RAT NUMBER
NC
NOT CONFIRMED
P
NOT PREGNANT
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE B13 (PAGE 3): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
---------
------------ ----------
--- - ----------- ---- - - ------------ - - ---------- ---
DOSAGE GROUP 11
0.1 MG/KG/D-A-Y------
------------------------------------ --------------------------------------- I - ----------------------- ---------
DAYS IN
RAT
COHABITATION
------------------------------------
FEMALE PREGNANCY
MATING STATUS
MATING DATE
STATUS
-------------------------------------- --------------------- --------------
8136 8137
1
m
c
P(8836)
1
m
c
P(8837)
8138
3
m
c
P(8838)
8139
1
m
c
P(8839)
8140
3
m
c
P(8840)
8141
5
m
c
P(8841)
8142
2
m
c
P(8842)
8143
1
m
c
P(8843)
8144
1
m
c
P(8844)
8145
3
m
c
P(8645)
8146 8147
3
m
c
P(8846)
3
m
c
P(8847)
8148
1
m
c
P(8848)
8149
4
m
c
P(8849)
8150
1
m
c
NP(8850)
oisi
4
m
c
P(8851)
8152
4
m
c
P(8852)
8153
3
m
c
P(8853)
8154
4
m
c
P(6854)
8155 8156
4
m
c
P(8855)
1
m
c
NP(8856)
8157
4
m
c
P(8857)
8158
4
m
c
P(8858)
8159 8160 8161 8162
1
m
c
P(8859)
4
m
c
P(8860)
1
m
c
NP(8861)
3
m
c
P(8662)
8163
3
m
c
P(8863)
8164
1
m
c
P(8864)
816S
4
m
c
P(6865)
-----------------------------------------------------------------------------------------------------------------
M = MATED
( ) = FEMALE PAT NUMBER
C = CONFIRMED
NC
NOT CONFIRMED
P = PREGNANT
P
NOT PREGNANT
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B]3 (PAGE 4): MATING AND FERTILITY
INDIVIDUAL
DATA - Fo GENERATION
MALE RATS
-- ----------- --- ---------
DOSAGE GROUP Il
0.1 MG/KG/DAY
--------------- ------------ -- ------------
------------------- -- ------------------ ----
DAYS IN
RAT
COHABITATION
MATING STATUS
MATING DATE
---------------------------- -------------------- ----- -- ------------------ ----
8166
2
8167
3
8168
3
8169
4
8170
1
----------------------------
m
c
m
c
m
c
m
c
m
c
------------------------------------------------------
M = MATED
( ) = FEMALE RAT NUMBER
C = CONFIRMED
NC
NOT CONFIRMED
P = PREGNANT
P
NOT PREGNANT
--------------- -
-------------------- -----
FEMALE PREGNANCY STATUS
- --------------- - ------
P(8866) P(8867) P(8868) P(8869) P(8870) ---------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI
TABLE B13 (PAGE 5): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
----------- ------- -----------
------
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------- -------------------------------------
----- ---------
-----------
----- -----------------------
- ---------------------------------------------------
DAYS IN
RAT
COHABITATION
MATING STATUS
-------------------------------------------------------
MATING DATE -----------------------
FEMALE PREGNANCY
STATUS ------ -----------------------
8171 8172 8173 8174 8175 8176
7
DID NOT MATE
-(8871)
1
m
c
P(8872)
1
m
c
P(8873)
3
m
c
P(8874)
4
m
c
P(8875)
4
m
c
P(8876)
8177
1
m
c
P(8877)
8178
1
m
c
NP(8878)
8179
1
m
c
NP(8879)
8180a
1
m
c
P(8880)
8180b
7
m
8181
4
m
8182
4
m
8183
1
m
c
P(8889)
c
P(8881)
c
P(8882)
c
NP(8883)
8184
1
m
c
P(8884)
8185
4
m
c
P(8885)
8186
1
m
c
NP(8886)
8187
1
m
c
P(8887)
8188
1
m
c
P(8888)
8189
7
DID NOT MATE
-(8889)
8190
1
m
c
P(8890)
8191
4
m
c
P(8891)
8192
5
m
c
P(8892)
8193
1
m
c
P(8893)
8194
1
m
c
P(8894)
8195
1
m
c
P(8895)
8196
4
m
c
P(8896)
8197
4
m
c
P(8897)
8198
3
m
c
P(8898)
8199
4
m
c
P(8899)
8200a
4
m
c
P(8900)
8200b
7
DID NOT MATE
-(8871)
-------------------------------------------------------------------------------------------------------------
M = MATED C = CONFIRMED P = PREGNANT
( ) = FEMALE RAT NUMBER NC = NOT CONFIRMED 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.
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B13 (PAGE 6): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
----------
----------------------- --- -----------------
------------------ -----------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------- -------------------------- ------------------------ --- ------------------------------------------
DAYS IN
FEMALE PREGNANCY
RAT
COHABITATION
MATING STATUS
MATING DATE
STATUS
------------------------------------------------------------------- ------------------------------------------
8201
4
m
c
P(8901)
8202
1
m
c
P(8902)
8203
1
m
c
NP(8903)
8204
1
m
c
NP(8904)
8205
1
m
c
P(8905)
--------------------------------------------------------------------------------------------------------------
M = MATED C = CONFIRMED P = PREGNANT
( ) = FEMALE PAT NUMBER
NC
NOT CONFIRMED
P
NOT PREGNANT
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICIT
TABLE B13 (PAGE 7): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
-----------------------------------------------------------------------------------------------------------------
DOSAGE GROUP IV
1.6 MG/KG/DAY
----------------------------------------------------------------------------------------------------------------
DAYS IN
FEMALE PREGNANCY
RAT
COHABITATION
MATING STATUS
MATING DATE
STATUS
----------------------------------------------------------------------------------------------------------------
8206
7
m
NC
P(8906)
8207a
I
m
c
NP(8907)
8207b
7
DID NOT MATE
-(8930)
8208a
1
m
c
P(8908)
8208b
7
DID NOT MATE
-(8906)
8209
4
m
c
P(8909)
8210
1
m
c
P(8910)
8211 8212
1
m
c
P(8911)
1
m
c
P(8912)
8213a
4
m
c
P(8913)
8213b
7
DID NOT MATE
-(8939)
8214
3
m
c
NP(8914)
8215
1
m
c
P(8915)
8216
1
m
c
P(8916)
8217
1
m
c
P(8917)
8218
4
m
c
NP(8918)
8219
3
m
c
P(8919)
8220
4
m
c
P(8920)
8221
2
m
c
P(8921)
8222
1
m
c
P(8922)
8223
3
m
c
NP(8923)
8224
1
m
c
P(8924)
8225
1
m
c
P(892S)
8226
3
m
c
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
NP(8933)
8234
2
m
c
P(8934)
8235
3
m
c
P(8935)
---------------------------------------------------------------------------------------------------------- --
M = MATED
( ) = FEMALE RAT NUMBER
C = CONFIRMED P = PREGNANT
NC NOT CONFIRMED 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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B13 (PAGE 8): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
- - -------------- -------------------- - - ---------- -- -------- --- ---------------------------- -----------
DOSAGE GROUP IV
1.6 MG/KG/DAY
---------------------- -- I -------------------------------------------------------------------------------------
DAYS IN
FEMALE PREGNANCY
RAT
COHABITATION
MATING STATUS
MATING DATE
STATUS
---------------------------------------------------------------------------------------------------------------
8236
3
m
c
P(8936)
8237
1
m
c
P(8937)
8238a
8239
7
m
NC
P(8939)
8240
2
m
c
P(8940)
---------------------------------------------------------------------------------------------------------------
M = MATED
( ) = FEMALE RAT NUMBER
C = CONFIRMED P = PREGNANT
NC
NOT CONFIRMED
P
NOT PREGNANT
a. Rat 8238 was not assigned to cohabitation because there were no available female rats.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STIIDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B13 (PACE 9): MATING AND FERTILITY
INDIVIDUAL DATA - Fo GENERATION
MALE PATS
--- ------------- -- -- -- ------ -----
---
--- --------- - ------ --- ------------ -- -------
DOSAGE GROUP V
3.2 MG/KG/DAY
----------------------- - ----------------- ----
--------------------- ------------------------------------
DAYS IN
RAT
COHABITATION
MATING
------------------------------------------------
FEMALE PREGNANCY
STATUS
MATING DATE
STATUS
- ----------------------------------------------------------
8241 8242
1
m
c
P(8941)
7
DID NOT MATE
-(8942)
8243a
4
m
c
P(8943)
8243b
7
m
c
P(8959)
8244
4
m
c
P(8944)
824S
2
m
c
NP(8945)
8246 8247 8248 8249 8250
7
DID NOT MATE
-(8946)
1
m
c
P(8947)
1
m
c
P(8948)
3
m
c
P(8949)
4
m
c
P(8950)
8251
1
m
c
P(8951)
8252
2
m
c
NP(8952)
8253
1
m
c
P(8953)
6254 6255 8256 8257
1
m
c
P(8954)
2
m
c
P(8955)
3
m
c
P(8956)
4
m
c
NP(8957)
8258
1
m
c
P(8958)
8259
7
DID NOT MATE
-(8959)
8260
5
m
c
P(8960)
8261
4
m
c
P(8961)
8262
2
m
c
P(8962)
8263
1
m
c
NP(8963)
8264
3
m
c
P(8964)
8265
1
m
c
P(8965)
8266
1
m
c
P(8966)
8267
2
m
c
P(8967)
8268
4
m
c
P(8968)
8269
2
m
c
P(8969)
8270
3
m
c
P(8970)
--------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B13 (PAGE 10): MATING AND FERTILITY - INDIVIDUAL DATA - Fo GENERATION MALE RATS
------------------- --- - -- ------------
DOSAGE GROUP V
3.2 MG/KG/DAY
--- ----- ------------ - -------- - - ---------- -----
-------- ---- --------------
----------------------------------- -- ---------------------------------------
DAYS IN
FEMALE PREGNANCY
RAT
COHABITATION
MATING STATUS
MATING DATE
STATUS
------------------------ ---- - ----- ----------- --------------------- ---------------------------------------
8271
1
m
c
P(8971)
8272a
1
m
c
NP(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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILII-Y, DEVELOPMENTAL STUI)Y NTJMSER: 6295.9)
AND PERINAI'AL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B14 (PAGE 1): NECROPSY OBSERVATIONS
INDIVIDUAL DATA - Fo GENERATION
MALE RATS
DOSAGE---G-R-O-UP------ ---DOSAGE (MG/KG/DAY) -----------------------
I 0 (VEHICLE)
---- -R-A-T ---------DA-Y--OF
NUMBER
NECROPSY
- -- -----------------
8101 8102
DS 67 DS 67
--------------------
DOSAGES
ADMINISTERED
OBSERVATIONS
----------------------
66
ALL TISSUES
66
ALL TISSUES
--------------------
a -------------------
APPEARED APPEARED
NORMAL. NORMAL.
8103
DS 67
66
PROSTATE:
SMALL.
ALL OTHER TISSUES APPEARED NORMAL.
8104 8105 8106 8107 8108 8109 8110 8111 8112 8113 8114 8115 8116 8117 8118 8119 8120 8121 8122 8123
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8124
DS 67
66
LIVER: LARGE (49.71 G).
KIDNEYS:
BILATERAL, LARGE (LEFT
4.37 G; RI
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 8128
DS 67
66
ALL TISSUES APPEARED
NORMAL.
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 B10) for external observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI
TABLE B14 (PAGE 2): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION MALE RATS
- --------------------- - ----------------- - -
----------------------
DOSAGE GROUP
RAT
DAY OF
DOSAGES
DOSAGE (MG/KG/DAY)
NUMBER
NECROPSY
-----------------------------------------------
ADMINISTERED
OBSERVATIONS
- - ------------------------
I (Cont.)
0 (VEHICLE)
---------------------- --
a --------------------------------
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 B10) for external observations confirmed at ne
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI
TABLE B14 (PAGE 3): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION MALE RATS
-------------------
---- -- --- ------ - ----
DOSAGE GROUP
RAT
DAY OF
DOSA-GES ---- -- --------- -- ------ ------- ---- -- -----
DOSAGE ----
(MG/KG/DAY)
NUMBER
NECROPSY
ADMINISTERED
OBSERVATIONS
a
---------------- - -------- --- ---------------- -----------------------------------------------------
ii
0.1
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 8150 8151 8152 8153 8154 8155
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
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 B10) for external observations confirmed at nf
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B14 (PACE 4): NECROPSY OBSERVATIONS
- INIIIVIDUAL DATA - Fo GENERATION MABE RATS
---------------- ------------ - -------------- -
I - ---------------- ---- - ------------------ -
DOSAGE GROUP
RAT
DAY OF
DOSAGES
DOSAGE (MG/KG/DAY)
NUMBER
NECROPSY
ADMINISTERED
OBSERVATIONS
a
---------------- ------------ I ---------------- -- - ------------------- ---------------------------
III
0.4
8171
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 8176
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8177 8178 8179 8180
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
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 8187
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8188 8189
DS 67
66
ALL TISSUES APPEARED
NORMAL.
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.
8202
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8203
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8204
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8205
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 nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PPOS IN RATS (SPONSOR'S S'R[JDY NI]MBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B14 (PAGE 5): NECROPSY OBSERVATIONS
INDIVIDUAL DATA - Fo GENERATION
MALE RATS
-- ------------------------- -- -------------
DOSAGE GROUP
RAT
DAY OF
DOSAGE (MG/KG/DAY)
NUMBER
NECROPSY
---------------------- ---------------------- --
IV 1.6
8206 8207
DS 67 DS 67
------------------- -
DOSAGES
ADMINISTERED
OBSERVATIONS
- ----------------------
------------------------
- -----
a ----------------------- --------
66
ALL TISSUES APPEARED NORMAL.
66
ALL TISSUES APPEARED NORMAL.
8208
DS 67
66
LIVER:
PAPILLARY PROCESS, CONSTRICTED
AND NUM
AREAS, (PINPOINT).
ALL OTHER TISSUES APPEARED
NORMAL.
8209 8210 8211 8212 8213
DS 67
66
ALL TISSUES APPEARED NORMAL.
DS 67
66
ALL TISSUES APPEARED NORMAL.
DS 67
66
ALL TISSUES APPEARED NORMAL.
DS 67
66
ALL TISSUES APPEARED NORMAL.
DS 67
66
ALL TISSUES APPEARED NORMAL.
8214
DS 67
66
TESTES:
BILATERAL,
SMALL, PURPLE AND FLACCID.
ALL OTHER TISSUES APPEARED NORMAL.
8215 8216 8217 8218 8219 8220 8221 8222 8223 8224 8225 8226 8227 8228 8229 8230
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8231
DS 67
66
LIVER: LARGE (28.83 G), ROUGH SURFACE.
KIDNEYS:
BILATERAL, LARGE (LEFT: 4.23 G; RIGH
PARENCHYMA,
MULTIPLE
PALE, FLUID-FILLED
CYSTS
TO 0.1 CM IN DIAMETER).
ALL OTHER TISSUES APPEARED
NORMAL.
----------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. Refer to the individual clinical observations table (Table BIO) for external observations confirmed at necr
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B14 (PAGE 6): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION MALE RATS
-------------- -------------------- ----------------- --- - --------------------
DOSAGE GROUP
RAT
DOSAGE (MG/KG/DAY)
NUMBER
---------------------------------------
DAY OF
DOSAGES
NECROPSY
ADMINISTERED
OBSERVATIONS
a
------------ ---------------------------
----------
------------ --
------------------------------
IV (Cont.)
1.6
8232
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8233
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8234
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8235
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8236
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8237
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8238
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8239
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8240
DS 67
66
ALL TISSUES APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. Refer to the individual clinical observations table (Table Blo) for external observations confirmed at nec
PROTOCOL 418-008;
COMBINED ORAI, (GAVAGE) PFOS IN RAI'S (SPONSOR'S
FERTILITY, DEVELOPMENTAL STUDY NIJMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B14 (PAGE 7): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
MALE RATS
------------ ----- ---------
---------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ------------ -----
-----
RAT
DAY OF
NUMBER
NECROPSY
----- ----------------
v
3.2
6241
DS 67
8242
DS 67
- ------ ----------- ----- ------------------- --
DOSAGES
ADMINISTERED
OBSERVATIONS
a
- -------------------------- ----------------------
---------
-----
66
ALL TISSUES APPEARED NORMAL.
66
ALL TISSUES APPEARED NORMAL.
8243
DS 67
66
PROSTATE: ALL OTHER
SMALL. 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 8247
8248 B249 8250 8251
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8252
DS 67
66
TESTES:
BILATERAL, SMALL AND FLACCID.
ALL OTHER TISSUES APPEARED
NORMAL.
8253 8254 8255 8256
DS 67
66
ALL TISSUES APPEARED NORMAL.
DS 67
66
ALL TISSUES APPEARED NORMAL.
DS 67
66
ALL TISSUES APPEARED NORMAL.
DS 67
66
ALL TISSUES APPEARED NORMAI,.
8257
DS 67
66
EYES: LEFT, LENS OPAQUE. b
TESTES:
BILATERAL,
SMALL, PURPLE AND FLACCID.
ALL OTHER TISSUES APPEARED NORMAL.
8256
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8259
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8260
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8261
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8262
DS 67
66
ALL TISSUES APPEARED
NORMAL.
8263
DS 67
66
ALL TISSUES APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
a. Refer to the individual clinical observations table (Table B10) for external observations b. Confirms a clinical observation (corneal opacity).
confirmed at necr
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B14 (PAGE 8): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
MALE RATS
-----DOSAGE DOSAGE
------- ---------- -------
GROUP (MG/KG/DAY)
--------
RAT
NUMBER ---------------- --
V (Cont.) 3.2
8264
------- ------ -------- --------- - ----- ------ -----------
DAY OF
DOSAGES
NECROPSY
ADMINISTERED
OBSERVATIONS
a
----------------------------------- I -- --------------------------
-----
DS 67
66
LIVER: LIGHT BROWN.
ALL OTHER TISSUES APPEARED NORMAL.
8265 8266
DS 67
66
ALL TISSUES APPEARED
NORMAL.
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 B10) for external observations confirmed at nec
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B15 (PAGE
1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS
INDIVIDUAL
DATA
Fo GENERATION
MALE RATS
(t) OF ORGAN WEIGHT TO TERMINAL
BODY
--------- - ----------------------- --- ------------------- --- ---------------- --------------- ----------
EPIDIDYMIS
LEFT
RAT
TERMINAL
BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
TBW
---------- - -----------------------------
TESTIS
SEMINAL
LEFT
WITH
ABS.
REL.
ABS.
WT.
t TBW
WT.
-----------------------
VESICLES
SEMINAL
FLUID
WITHOUT
REL.
ABS.
TBW
WT.
----------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
------------ ------------------------------ ----------------------------------------
VESICLES
EPIDIDYMIS
FLUID
RIGHT
REL.
ABS.
REL.
96 TBW
WT.
t TBW
-----------------------
--------------------------
8101
428.
0.67
0.16
1.47
0.34
2.00
0.47
1.17
0.27
0.69
0.16
8102
664.
0.82
0.12
1.79
0.27
2.11
0.32
0.73
0.11
0.85
0.13
8103
563.
0.72
0.13
1.55
0.28
1.83
0.32
0.82
0.14
0.71
0.13
8104
492.
0.69
0.14
1.54
0.31
1.53
0.31
0.79
0.16
0.71
0.14
8105
502.
0.58
0.12
1.49
0.30
1.86
0.37
0.86
0.17
0.63
0.12
8106
674.
0.64
0.09
1.85
0.27
2.96
0.44
1.44
0.21
0.60
0.09
8107
526.
0.75
0.14
1.67
0.32
2.51
0.48
1.17
0.22
0.76
0.14
8108
499.
0.52
0.10
1.65
0.33
1.90
0.38
1.01
0.20
0.59
0.12
8109
490.
0.68
0.14
1.73
0.35
2.22
0.45
1.21
0.25
0.70
0.14
8110
588.
0.61
0.10
1.69
0.29
1.85
0.31
0.50
0.08
0.61
0.10
Bill
538.
0.58
0.11
1.63
0.30
1.69
0.31
0.82
0.15
0.57
0.10
8112
535.
0.73
0.14
1.78
0.33
2.23
0.42
0.70
0.13
0.80
0.15
8113
478.
0.74
0.15
1.61
0.34
2.25
0.47
1.12
0.23
0.76
0.16
8114
544.
0.66
0.12
1.81
0.33
2.13a
0.39a
1.47
0.27
0.70
0.13
8115
508.
0.73
0.14
1.63
0.32
2.02
0.40
0.94
0.18
0.76
0.15
8116
565.
0.69
0.12
1.79
0.32
1.81
0.32
0.97
0.17
0.73
0.13
8117
506.
0.75
0.15
1.96
0.39
1.67a
0.33a
1.26
0.25
0.79
0.16
8118
606.
0.67
0.11
1.65
0.27
2.16
0.36
1.14
0.19
0.72
0.12
8119
530.
0.75
0.14
1.98
0.37
2.39
0.45
1.09
0.20
0.78
0.15
8120
556.
0.64
0.12
1.58
0.28
2.02
0.36
1.11
0.20
0.63
0.11
8121
486.
0.68
0.14
1.83
0.38
2.07
0.42
0.83
0.17
0.68
0.14
8122
ssi.
0.76
0.14
1.95
0.35
2.37
0.43
1.14
0.21
0.63
0.11
8123
549.
o@81
0.15
1.77
0.32
2.03
0.37
0.73
0.13
0.77
0.14
8124
562.
0.85
0.15
1.98
0.35
2.99
0.53
1.54
0.27
0.90
0.16
8125
521.
0.81
0.16
1.97
0.38
2.09
0.40
0.98
0.19
0.80
0.15
8126
573.
0.78
0.14
1.90
0.33
2.15
0.38
0.87
0.15
0.76
0.13
8127
554.
0.84
0.15
1.80
0.32
2.04
0.37
1.03
0.18
0.75
0.14
8128
631.
0.75
0.12
1.83
0.29
2.17
0.34
1.00
0.16
0.80
0.13
8129
543.
0.67
0.12
1.83
0.34
2.09
0.38
1.11
0.20
0.77
0.14
8130
572.
0.67
0.12
1.66
0.29
2.13
0.37
0.89
0.16
0.73
0.13
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. t TBW = (ORGAN WEIGHT/TERMINAL
B
a. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B15 (PAGE
2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS
INDIVIDUAL
DATA - Fo GENERATION
MALE RATS
(t) OF ORGAN WEIGHT TO TERMINAL
BODY
------- ------- ------------------------------------------------------------------ -- -------------------------
EPIDIDYMIS
TESTIS
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
LEFT
RAT
TERMINAL BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
t TBW
------------------------------------------
LEFT
WITH FLUID
WITHOUT FLUID
RIGHT
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
WT.
TBW
WT.
t TBW
WT.
t TBW
WT.
TBW
-------------------------------------------------------------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8131
524.
0.73
0.14
1.74
0.33
1.74
0.33
0.68
0.13
0.72
0.1
8132
542.
0.63
0.12
1.00
0.18
2.21
0.41
1.08
0.20
0.70
0.1
8133
450.
0.73
0.16
1.81
0.40
1.59
0.35
0.81
0.18
0.73
0.1
8134
582.
0.59
0.10
1.57
0.27
1.35
0.23
0.72
0.12
0.62
0.1
8135
558.
0.74
0.13
1.89
0.34
1.96
0.35
1.01
0.18
0.82
0.1
--------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT.
ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B15 (PAGE
3): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL
INDIVIDUAL
DATA - Fo GENERATION
MALE RATS
BODY
---- --------------- ------ ---- -- -------- -
------------------
--- ------------------- --
PROSTATE
RAT
TERMINAL
BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
TBW
--------------------------- ---- ------------- ----11 ---- --------------------
----------------------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------- -----------------------------------------------------------
-----
8101
428.
0.67
0.16
8102
664.
1.37
0.21
8103
563.
0.44a
0.08a
8104
492.
0.96
0.20
8105
502.
1.19
0.24
8106
674.
1.00
0.15
8107
526.
0.85
0.16
8108
499.
0.62
0.12
8109
490.
1.16
0.24
silo
588.
1.22
0.21
8111
538.
1.34
0.25
8112
535.
0.93
0.17
8113
478.
1.47
0.31
8114
544.
0.81
0.15
8115
508.
1.24
0.24
olig
565.
1.15
0.20
8117
506.
1.62
0.32
8118
606.
1.10
0.18
8119
530.
1.60
0.30
8120
5S6.
0.90
0.16
8121
486.
1.31
0.27
8122
551.
1.09
0.20
8123
549.
1.00
0.18
8124
562.
0.94
0.17
8125
521.
1.23
0.24
8126
573.
1.68
0.29
8127
554.
1.47
0.26
8128
631.
0.95
0.15
8129
543.
1.39
0.26
8130
572.
1.40
0.24
----------------------------------------------------------------------------------------------------------
----
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
a. Rat 8103 had a small prostate; values excluded from group averages
necropsy observations table (Table B14).
REL. i TSW = (ORGAN WEIGHT/TERMINAL
and statistical analyses.
See the indi
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXICI
TABLE B15 (PAGE 4): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (t) OF ORGAN WEIGHT TO TERMINAL BODY
INDIVIDUAL
DATA
Fo GENERATION
MALE RATS
------- --------------- -------------- --- ------------------- ----------------- -----------------------------
PROSTATE
RAT
TERMINAL BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
% TBW
----------------------------------------
-------------------------------------------------------------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
------------------------------------------------------------
--------------------------------------------------
8131
524.
1.60a
0.30a
8132
542.
1.21
0.22
8133
450.
1.24
0.28
8134
582.
1.19
0.20
813S
558.
1.13
0.20
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN
a. Damaged during processing (weight not affected).
WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER!
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B15 (PACE 5): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (t) OF ORGAN WEIGHT TO TERMINAL BODY
INDIVIDUAL
DATA - Fo GENERATION
MALE RATS
----------- ---------------------- - ----------- -- ---------- ----- ------ ------ --------------------- --
EPIDIDYMIS
TESTIS
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
LEFT
LEFT
WITH FLUID
WITHOUT FLUID
RIGHT
RAT
TERMINAL BODY
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
% TBW
WT.
t TBW
WT.
t TBW
WT.
t TBW
WT.
TBW
----------------------------------------------------- ----------------------------------------------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8136
41S.
0.58
0.14
1.43
0.34
1.63
0.39
0.59
0.14
0.59
0.1
8137
617.
0.75
0.12
1.91
0.31
2.38
0.38
1.24
0.20
0.73
0.1
8138
524.
0.70
0.13
1.69
0.32
1.31
0.25
0.78
0.15
0.80
0.1
8139
503.
0.72
0.14
2.04
0.40
2.22
0.44
0.95
0.19
0.75
0.1
8140
502.
0.75
0.15
1.69
0.34
2.19
0.44
0.73
0.14
0.72
0.1
8141
610.
0.90
0.15
1.95
0.32
2.71
0.44
1.17
0.19
0.85
0.1
8142
498.
0.65
0.13
1.72
0.34
1.99
0.40
0.99
0.20
0.71
0.1
8143
538.
0.84
0.16
1.96
0.36
1.80
0.33
0.79
0.15
0.81
0.1
8144
455.
0.70
0.15
1.72
0.38
2.13
0.47
0.81
0.18
0.77
0.1
8145
528.
0.56
0.11
1.78
0.34
1.92
0.36
1.07
0.20
0.57
0.1
8146
562.
0.77
0.14
1.82
0.32
2.34
0.42
1.19
0.21
0.80
0.1
8147
540.
0.70
0.13
1.70
0.31
2.24
0.41
1.22
0.22
0.73
0.1
8148
480.
0.64
0.13
1.68
0.35
2.10
0.44
0.86
0.18
0.67
0.1
8149
561.
0.60
0.11
1.54
0.27
2.36
0.42
1.25
0.22
0.72
0.1
8150
546.
0.68
0.12
1.57
0.29
2.00
0.37
1,15
0.21
0.72
0.1
8151
525.
0.76
0.14
1.98
0.38
2.36
0.45
1.31
0.25
0.75
0.1
8152
547.
0.62
0.11
1.54
0.28
2.25
0.41
1.14
0.21
0.62
0.1
8153
615.
0.62
0.10
1.70
0.28
2.24
0.36
0.94
0.15
0.71
0.1
8154
535.
0.84
0.16
1.88
0.35
2.33
0.44
1.01
0.19
0.83
0.1
8155
529.
0.60
0.11
1.7B
0.34
2.16
0.41
1.35
0.26
0.60
0.1
8156
663.
0.74
0.11
1.81
0.27
2.34
0.35
0.81
0.12
0.71
0.1
8157
532.
0.76
0.14
1.75
0.33
1.87
0.35
1.01
0.19
0.78
0.1
8158
519.
0.76
0.15
1.76
0.34
2.05
0.39
1.12
0.22
0.73
0.1
8159
539.
0.83
0.15
1.61
0.30
1.60
0.30
0.73
0.14
0.79
0.1
8160
493.
0.72
0.15
1.76
0.36
2.14
0.43
0.97
0.20
0.78
0.1
8161
533.
0.69
0.13
1.83
0.34
2.12
0.40
1.08
0.20
0.64
0.1
8162
494.
0.80
0.16
1.87
0.38
1.67
0.34
0.82
0.16
0.76
0.1
8163
582.
0.74
0.13
1.69
0.29
2.94
0.50
1.38
0.24
0.67
0.1
8164
536.
0.73
0.14
1.73
0.32
1.78
0.33
0.81
0.15
0.75
0.1
8165
576.
0.74
0.13
1.76
0.30
2.03
0.35
1.04
0.18
0.83
0.1
--------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B15 (PAGE
6): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS
INDIVIDUAL
DATA - Fo GENERATION
MALE RATS
(%) OF ORGAN WEIGHT TO TERMINAI. BODY
------ -------------------- -- ---- ----------- ---- -- --------------- ---------- -----------------------
EPIDIDYMIS
TESTIS
LEFT
LEFT
RAT
TERMINAL
BODY
ABS.
REL.
ARS.
REL.
NUMBER
WEIGHT
WT.
t TBW
WT.
% TBW
--------------------------- -------------------------- --
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
WITH FLUID
WITHOUT FLUID
RIGHT
ABS.
REL.
ABS.
REL.
ABS.
REL.
WT.
t TBW
WT.
% TBW
WT.
TBW
----------------------------------------------------
DOSAGE GROUP 11 ---------------------------
0.1 MG/KG/DAY -------------------------- -------------------------------------------------------
8166
539.
0 80
0.15
1.67
0.31
2.30
0.43
1.29
0.24
0.81
0.1
8167
578.
0.79
0.14
1.99
0.34
2.61
0.45
1.28
0.22
0.85
0.1
8168
500.
0.66
0.13
1.70
0.34
2.01
0.40
0.67
0.13
0.73
0.1
8169
538.
0.70
0.13
1.67
0.31
1.78
0.33
0.88
0.16
0.75
0.1
8170
624.
0.71
0.11
1.88
0.30
1.90
0.30
0.88
0.14
0.75
0.1
--------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418-008:
COMBINED ORAL PFOS IN RATS
(GAVAGE) (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B15 (PAGE
7): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL
INDIVIDUAL
DATA - Fo GENERATION
MALE RATS
BODY
------ ----------------------------------- ---- - ------------ -----------------------------
PROSTATE
RAT
TERMINAL BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
% TBW
--------------------------------------------------------------------------------------------
---- I ---------------------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------------------------------------------------------------------
8136 8137 8138 8139 8140 8141 8142 8143 8144 8145 8146
415. 617. 524. 503. 502. 610. 498. 538. 455. 528. 562.
1.17 0.94 1.06 1.35 1.27 1.47 1.27 1.10 0.97 0.73 1.37
0.28 0.15 0.20 0.27 0.25 0.24 0.26 0.20 0.21 0.14 0.24
8147
540.
1.45
0.27
8148
480.
1.45
0.30
8149 8150 8151 8152 8153 8154 8155 8156 8157 8158 8159 8160
561. 546. 525. 547.
615. 535. 529. 663. 532. 519. 539. 493.
0.84 1.31 1.23 1.54 0.74 1.29
1.50 1.19 1.31 0.85 1.61 1.33
0.15 0.24 0.23 0.28 0.12 0.24 0.28 0.18 0.25 0.16
0.30 0.27
8161 8162
533. 494.
1,74 1.26
0.33 0.26
8163
582.
1.00
0.17
8164
536.
1,64
0.30
8165
576.
1.56
0.27
---------------------------------------------------------------------------------------------
----------------- --------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418-008:
COMBINED ORAL (GAVA@3E) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B15 (PAGE 8): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY INDIVIDUAL DATA - Fo GENERATION MALE RATS
------------------------------------------------------------------------------------------ --------------------
PROSTATE
PAT
TERMINAL BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
TBW
--------------------------------------
------------------------------------------------------------------------
DOSAGE GROUP Il
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8166
539.
1.33
0.25
8167
578.
1.77
0.31
8168
500.
1.79
0.36
8169
538.
1.04
0.19
8170
624.
1.30
0.21
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. t TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS ISPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B15 (PAGE
9): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL
INDIVIDUAL
DATA
Fo GENERATION
MALE RATS
BODY
-------- ---- ------------- ----- ----------- ---------------------------- -------------------------- ---------
EPIDIDYMIS
TESTIS
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
LEFT
LEFT
WITH FLUID
WITHOUT FLUID
RIGHT
RAT
TERMINAL BODY
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
TBW
WT.
TBW
WT.
% TSW
WT.
TBW
WT.
!i 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
8172 8173 8174 8175
596. 492. 526. 481.
0.73 0.63 0.78 0.72
0.12 0.13 0.15 0.15
1.75 1.86 1.99 1.69
0.29 0.38 0.38 0.35
1.86 2.10 2.39 2.22
0.31 0.43 0.4S 0.46
1.09 1.03 0.94 1.04
0.18 0.21 0.18 0.22
0.80 0.69 0.81 0.77
0.13 0.14 0.15 0.16
8176
581.
0.71
0.12
1.79
0.31
1.86
0.32
0.91
0.16
0.71
0.12
8177
535.
0.71
0.13
1.88
0.35
1.66
0.31
0.80
0.15
0.75
0.14
8178
530.
0.74
0.14
1.90
0.36
1.50
0.28
0.77
0.14
0.71
0.13
8179
486.
0.61
0.12
1.57
0.32
1.20
0.25
0.60a
0.12a
0.59
0.12
8180
545.
0.69
0.13
1.58
0.29
2.24
0.41
1.11
0.20
0.72
0.13
Biel
483.
0.72
0.15
1.67
0.34
1.40
0.29
0.79
0.16
0.64
0.13
8182
538.
0.76
0.14
1.60
0.30
1.95
0.36
1.05
0.20
0.72
0.13
8183 8184 8185
471. 606. 460.
0.63 0.79 0.66
0.13 0.13 0.14
1.55 1.92 1.73
0.33 0.32 0.38
2.02 1.82b 1.83
0.43 0.30b 0.40
1.00 1.01 O.B4
0.21 0.17 0.18
0.68 0.74 0.67
0.14 0.12 0.14
8186
492.
0.79a
0.16a
1.97
0.40
2.40
0.49
1.23
0.25
0.80
0.16
8187
512.
0.65
0.13
1.46
0.28
2.21
0.43
1.24
0.24
0.81
0.16
8188
535.
0.64
0.12
1.39
0.26
1.91
0.36
0.70
0.13
0.66
0.12
8189
489.
0.67
0.14
1.87
0.38
1.92
0.39
0.80
0.16
0.68
0.14
8190
525.
0.64
0.12
1.80
0.34
2.16
0.41
1.25
0.24
0.70
0.13
8191
518.
0.70
0.14
1.78
0.34
1.98
0.38
0.89
0.17
0.74
0.14
8192
533.
0.76
0.14
1.83
0.34
2.44
0.46
1.13
0.21
0.83
0.16
8193
557.
0.73
0.13
1.77
0.32
2.19
0.39
0.91
0.16
0.79
0.14
8194
544.
0.55
0.10
1.49
0.27
2.08
0.38
0.77
0.14
0.61
0.11
8195
500.
0.68
0.14
1.74
0.35
1.81
0.36
1.07
0.21
0.68
0.14
8196
585.
0.69
0.12
1.75
0.30
1.68
0.29
0.82
0.14
0.75
0.13
8197
507.
0.70
0.14
1.63
0.32
2.21
0.44
1.00
0.20
0.72
0.14
8198
512.
0.64
0.12
1.57
0.31
2.34
0.46
1.09
0.21
0.66
0.13
8199
553.
0.77
0.14
1.83
0.33
1.98
0.36
1.02
0.18
0.79
0.14
8200
590.
0.76
0.13
1.82
0.31
2.70
0.46
1.37
0.23
0.76
0.13
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN
a. Damaged during processing (weight not affected).
WEIGHT.
REL. t TBW = (ORGAN WEIGHT/TERMINAL
b. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE 815 IPAGE 10):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA - Fo GENERATION
WEIGHTS AND RATIOS MALE RATS
(%) OF ORGAN WEIGHT TO TERMINAL
BODY W
----------- --------------------- -- --------- ------ --- ------- -------------- -----------------------------
EPIDIDYMIS
TESTIS
LEFT
LEFT
RAT
TERMINAL
BODY
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
TBW
WT.
t TBW
------------ ---------------------- -------------------
---
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
WITH FLUID
WITHOUT FLUID
RIGHT
ABS.
REL.
ABS.
REL.
ABS.
REL.
WT.
TBW
WT.
TBW
WT.
TBW
I ---------------------------------------------------
DOSAGE GROUP Ill
0.4 MG/KG/DAY
----------- ----------------------------------------------------------------------------------------------------
8201
472.
0.65
0.14
1.49
0.32
2.27
0.48
0.98
0.21
0.61
0.13
8202
605.
0.61
0.10
1.77
0.29
1.52
0.25
0.73
0.12
0.68
0.11
8203
498.
0.70
0.14
1.64
0.33
1.85
0.37
1.00
0.20
0.68
0.14
8204
494.
0.68
0.14
1.92
0.39
1.46
0.30
0.73
0.15
0.70
0.14
8205
515.
0.71
0.14
1.56
0.30
1.82
0.35
0.84
0.16
0.79
0.15
-----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. t TBW = (ORGAN WEIGHT/TERMINAL
B
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS TN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B15 (PAGE 11):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA - Fo GENERATION
WEIGHTS AND MALE RATS
RATIOS
(%) OF ORGAN WEIGHT
TO TERMINAL
BODY
--- ------------ -------
-----------
----------------- - -
--------------
PROSTATE
RAT
TERMINAL
BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
t TBW
----------------------------- --------------- -------------------------------------------------------- -------
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------------------------------------------------
8171 8172 8173 8174
426. 596. 492. 526.
1.01 0.56 1.57 1.74
0.24 0.09 0.32 0.33
------------------------------------------------ ---------
8175
4Bl.
0.69
0.14
8176
SBI.
0.59
0.10
8177 8178 8179 8180
535. 530. 486. 545.
1.40 0.97 0.90 1.01
0.26 0.18 0.18 0.18
Biel
483.
0.99
0.20
8182
538.
1.44
0.27
8183
471.
0.56
0.12
8184
606.
1.14
0.19
8185
460.
1.30
0.28
8186 8187
492. 512.
0.86 1.24
0.17 0.24
8188 8189 8190
535. 489. 525.
1.24 1.50 1.31
0.23 0.31 0.25
8191 8192
518. 533.
1.43 1.27
0.28 0.24
8193
557.
1.41
0.25
8194
544.
1.27
0.23
8195 8196
500. 585.
1.27 1.52
0.25 0.26
8197
507.
1.35
0.27
8198
512.
1.38
0.27
8199
553.
1.48
0.27
8200
590.
0.69
0.12
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B15 (PAGE 12):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA - Po GENERATION
WEIGHTS AND MALE RATS
RATIOS
(%) OF ORGAN WEIGHT TO TERMINAL
BODY
------- ------------------------------------------- ---------------------------------- ------------------- ----
PROSTATE
PAT
TERMINAL BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
-----------------------------
TBW --------------------------------------------------------------------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8201
472.
1.20
0.25
8202
605.
1.07
0.18
8203
498.
0.65
0.13
8204
494.
1.10
0.22
B205
515.
1.11
0.22
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RA7'S (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICII
TABLE B15 (PAGE 13):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA - Fo GENERATION
WEIGHTS AND MALE RATS
RATIOS
(%) OF ORGAN WEIGHT TO TERMINAL
BODY V
-------- --------------------- - ----- -- -------------------------------------- ------------- ----------------
EPIDIDYMIS
TESTIS
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
LEFT
LEFT
WITH FLUID
WITHOUT FLUID
RIGHT
RAT
TERMINAL BODY
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
t TBW
WT.
t TBW
WT.
% TBW
WT.
TBW
WT.
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
8207
572.
0.69
0.12
1.77
0.31
1.42
0.25
0.78
0.14
0.75
0.13
8208
519.
0.70
0.13
1.68
0.32
2.42
0.47
1.12
0.22
0.71
0.14
8209
540.
0.76
0.14
1.85
0.34
1.66
0.31
0.82
0.15
0.77
0.14
8210
459.
0.64
0.14
1.68
0.37
1.76a
0.38a
1.00
0.22
0.68
0.15
8211
540.
0.80
0.15
1.68
0.31
1.89
0.35
0.62
0.11
0.82
0.15
8212
502.
0.70
0.14
1.74
0.35
2.16
0.43
1.00
0.20
0.70
0.14
8213
503.
0.67
0.13
1.78
0.35
2.65
0.53
1.18
0.23
0.81
0.16
8214
496.
0.45
0.09
o.80b
0.16b
2.51
0.51
1.32
0.27
0.45
0.09
8215
548.
0.68
0.12
1.81
0.33
1.90
0.35
1.03
0.19
0.71
0.13
8216
546.
0.75
0.14
1.66
0.30
2.08
0.38
1.03
0.19
0.71
0.13
8217
537.
0.70
0.13
1.63
0.30
1.96
0.36
1.05
0.20
0.71
0.13
8218
460.
0.65
0.14
1.29
0.28
2.32
0.50
0.96
0.21
0.62
0.13
8219
533.
0.64
0.12
1.83
0.34
2.51
0.47
1.19
0.22
0.64
0.12
8220
508.
0.68
0.13
1.91
0.38
1.89
0.37
0.91
0.18
0.65
0.13
8221
533.
0.80
0.15
1.77
0.33
2.34
0.44
0.77
0.14
0.71
0.13
8222
477.
0.63
0.13
1.48
0.31
1.81
0.38
0.79
0.16
0.69
0.14
8223
588.
0.77
0.13
1.92
0.33
2.73
0.46
1.44
0.24
0.78
0.13
8224
494.
0.64
0.13
1.81
0.37
1.94
0.39
0.94
0.19
0.65
0.13
8225
537.
0.72
0.13
1.83
0.34
2.23
0.42
1.12
0.21
0.79
0.15
8226
503.
0.79
0.16
1.87
0.37
2.05
0.41
1.04
0.21
0.75
0.15
8227
563.
0.73
0.13
1.70
0.30
1.53
0.27
0.82
0.14
0.79
0.14
8228
418.
0.66
0.16
1.76
0.42
1.83
0.44
0.95
0.23
0.64
0.15
8229
540.
0.71
0.13
1.75
0.32
1.87
0.35
0.90
0.17
0.64
0.12
8230
492.
0.77
0.16
1.75
0.36
1.96
0.40
1.04
0.21
0.78
0.16
8231
519.
0.75
0.14
2.00
0.38
2.00
0.38
0.85
0.16
0.81
0.16
8232
500.
0.73
0.15
1.79
0.36
2.16
0.43
0.98
0.20
0.73
0.15
8233
523.
0.64
0.12
1.64
0.31
1.85
0.35
0.95
0.18
0.64
0.12
8234
520.
0.62
0.12
1.74
0.33
1.71c
0.33c
1.07
0.20
0.63
0.12
8235
541.
0.80
0.15
1.76
0.32
1.97
0.36
0.97
0.18
0.85
0.16
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT.
a. Damaged during processing (weight not affected).
= ORGAN
WEIGHT.
REL. t TBW = (ORGAN WEIGHT/TERMINAL
B
b. Rat 8214 had small, purple and flaccid testes; values excluded from group averages and statistical analyses
individual necropsy observations table (Table B14).
C. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE B15 (PAGE 14):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA - Fo GENERATION
WEIGHTS AND MALE RATS
RATIOS
(%) OF ORGAN WEIGHT TO TERMINAL
BODY
-- -------------------------------- I ----------------------- ---------------------------------------------------
EPIDIDYMIS
TESTIS
LEFT
LEFT
RAT
TERMINAL
BODY
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
% TBW
WT.
t TBW
-----------------------------------------------------------
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
WITH FLUID
WITHOUT FLUID
RIGHT
ABS.
REL.
ABS.
REL.
ABS.
REL.
WT.
!k TBW
WT.
TBW
WT.
t TBW
--------------------------------------------------
DOSAGE GROUP IV
1.6 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8236
489.
0.68
0.14
1.75
0.36
1.94
0.40
1.18
0.24
0.70
0.14
8237
596.
0.70
0.12
1.77
0.30
2.47
0.41
1.22
0.20
0.68
0.1
8238
460.
0.85
0.18
1.76
0.38
1.34
0.29
0.76
0.16
0.72
0.1
8239
455.
0.63
0.14
1.60
0.35
1.40
0.31
0.96
0.22
0.60
0.1
8240
495.
0.66
0.13
1.65
0.33
1.68
0.34
0.74
0.15
0.66
0.1
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. t TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODIICTION TOXICI
TABLE B15 (PAGE 15):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA
Fo GENERATION
WEIGHTS AND MALE RATS
RATIOS
(%) OF ORGAN WEIGHT TO TERMINAL
BODY
--------- --- -- ------------
-----------
-- ------------------- --- --------
PROSTATE
RAT
TERMINAL
BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
t TBW
-------- ------------------------------
----------------------------
-- I -------------------------- ------------
DOSAGE GROUP IV ----------------------
8206 6207 8208
442. 572. 519.
1.6 MG/KG/DAY ------------------
1.07 1.38 1.04
0.24 0.24 0.20
---------------------------
-----------------------------
--- --------
8209
540.
1.36
0.25
8210
459.
0.93
0.20
8211
540.
1.43
0.26
8212 8213
502. 503.
1.39 1.51
0.28 0.30
8214 8215 8216
496. 548. 546.
0.66 0.84 1.59
0.13 0.15 0.29
8217
537.
0.95
0.18
8218
460.
0.98
0.21
8219
533.
0.66
0.12
8220
508.
1.16
0.23
8221
533.
0.81
0.15
8222 8223 8224 8225 8226
477. 588. 494. 537. 503.
1.02 1.38
1.56 0.89 0.87
0.21 0.23 0.32 0.16 0.17
8227 8228 8229
S63. 418. 540.
1.00 0.80 1.06
0.18 0.19 0.20
8230
492.
1.17
0.24
8231
S19.
1.13
0.22
8232 8233
500. S23.
1.58 1.22
0.32 0.23
8234
520.
1.07
0.20
8235
541.
1.61
0.30
--------------------------------------------------------------------------------------------------
------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. t TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B15 (PAGE 16):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA - Fo GENERATION
WEIGHTS AND RATIOS MALE RATS
(t) OF ORGAN WEIGHT TO TERMINAL
BODY
-------------------------- - ---------------
---- ------------ ------- - - -------------- ---------
PROSTATE
RAT NUMBER
TERMINAL WEIGHT
BODY
ABS. WT.
REL. t TBW
---------------------------- - ---------------------------------------------------- ---------------------------
DOSAGE GROUP IV
1.6 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8236
489.
0.76
0.16
8237
596.
1.60
0.27
8238
460.
1.22
0.26
8239
455.
0.62
0.14
8240
495.
1.17
0.24
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B15 (PAGE 17):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA - Fo GENERATION
WEIGHTS AND RATIOS MALE RATS
(%) OF ORGAN WEIGHT TO TERMINAL
BODY
-- -------------------- -- -------------------------- --- -- ---- -- ---------------------------------------
EPLDIDYMIS
TESTIS
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
LEFT
LEFT
WITH FLUID
WITHOUT FLUID
RIGHT
RAT
TERMINAL
BODY
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
t TBW
WT.
% TBW
WT.
TBW
WT.
% TBW
WT.
% TBW
---------------------------------------------------------------------------------------------------------------
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
8242
578.
0.76
0.13
1.85
0.32
1.67
0.29
0.97a
0.17a
0.82
0.14
8243
516.
0.73a
0.14a
1.87
0.36
1.98
0.38
1.09
0.21
0.73
0.14
8244
486.
0.65
0.13
1.67
0.34
1.73
0.36
0.88
0.18
0.61
0.12
8245
454,
0.69
0.15
0.59b
0.13b
1.78
0.39
0.93
0.20
0.67
0.15
8246
517.
0.62
0.12
1.32
0.26
1.74
0.34
0.97
0.19
0.64
0.12
8247
428.
0.73
0.17
2.01
0.47
1.92
0.45
0.91
0.21
0.72
0.17
8248
467.
0.68
0.14
1.66
0.36
1.99
0.43
1.29
0.28
0.74
0.16
8249
437.
0.58
0.13
1.57
0.36
1.94
0.44
1.28
0.29
0.61
0.14
8250
496.
0.72
0.14
2.05
0.41
1.98
0.40
0.88
0.18
0.76
0.15
8251
457.
0.56
0.12
1.82
0.40
1.58
0.34
0.68
0.15
0.57
0.12
8252
469.
0.49
0.10
0.85b
0.18b
1.19
0.25
0.50
0.11
0.47
0.10
8253
441.
0.67
0.15
1.68
0.38
1.37
0.31
1.02
0.23
0.64
0.14
8254
506.
0.63
0.12
1.84
0.36
1.98
0.39
0.87
0.17
0.64
0.13
8255
492.
0.63
0.13
1.76
0.36
2.09
0.42
1.13
0.23
0.73
0.15
8256
436.
0.70
0.16
1.81
0.42
1.11
0.25
0.83
0.19
0.65
0.15
8257
425.
0.61
0.14
0.94c
0.22c
1.61
0.38
0.64
0.15
0.62
0.14
8258
506.
0.63
0.12
1.96
0.39
1.79
0.35
0.84
0.17
0.68
0.13
8259
440.
0.65
0.15
1.60
0.36
1.47
0.33
0.77
0.18
0.60
0.14
8260
545.
0.65
0.12
1.80
0.33
1.87
0.34
0.93
0.17
0.71
0.13
8261
453.
0.69
0.15
1.61
0.36
1.95
0.43
0.95
0.21
0.(i5
0.14
8262
464.
0.70
0.15
2.04
0.44
1.62
0.35
0.61
0.17
0.76
0.16
8263
530.
0.73
0.14
1.71
0.32
1.70
0.32
0.90
0.17
0.77
0.14
8264
506.
0.71
0.14
1.85
0.36
2.16
0.43
1.06
0.21
0.74
0.15
8265
422.
0.66
0.16
1.74
0.41
1.33
0.32
0.62
0.15
0.69
0.16
8266
498.
0.68
0.14
1.71
0.34
1.99
0.40
1.11
0.22
0.70
0.14
8267
438.
0.68
0.16
1.25
0.28
1.40
0.32
0.73
0.17
0.69
0.16
8268
541.
0.79
0.15
2.19
0.40
1.64
0.30
0.85
0.16
0.77
0.14
8269
514.
0.65
0.13
1.65
0.32
1.20
0.23
0.69
0.13
0.68
0.13
8270
507.
0.72
0.14
1.93
0.38
1.54
0.30
0.77
0.15
0.66
0.13
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS a. Damaged
WERE RECORDED IN GRAMS (G).
ASS. WT. = ORGAN
during processing (weight not affected).
WEIGHT.
REL.'% TBW = (ORGAN WEIGHT/TERMINAL
b. Rat had small and flaccid testes; values excluded from group averages and statistical analyses. necropsy observations table (Table B14).
See the i
c. Rat 8257 had a small, purple and flaccid left testis; values excluded from group averages and statistical individual necropsy observations table (Table B14).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE B15 (PAGE 18):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA
Fo GENERATION
WEIGHTS AND RATIOS MALE RATS
(%) OF ORGAN WEIGHT TO TERMINAL
BODY
------------ ------ ------------------
--------------------------------- --------------------- ------------
EPIDIDYMIS
TESTIS
SEMINAL VESICLES
SEMINAL VESICLES
LEFT
LEFT
WITH FLUID
WITHOUT FLUID
RAT NUMBER
TERMINAL WEIGHT
BODY
ABS. WT.
REL. t TBW
ABS. WT.
REL. t TBW
ABS. WT.
REL. TBW
ABS. WT.
REL. 't TBW
--------------------------------------------------------------------------------------------------
EPIDIDYMIS
RIGHT
ABS.
REL.
WT.
t TBW
---------
DOSAGE GROUP V
3.2 MG/KG/DAY
--------------------------------------------------------------------------------------------------
------------
8271
SOS.
0.72
0.14
2.08
0.41
1.88a
0.37a
1.01
0.20
0.78
0.15
8272
534.
0.73
0.14
1.92
0.36
2.49
0.47
1.40
0.26
0.78
0.15
8273
457.
0.77
0.17
1.79
0.39
1.75
0.38
0.95
0.21
0.78
0.17
8274
493.
0.64
0.13
1.62
0.33
1.98
0.40
1.04
0.21
0.60
0.12
8275
511.
0.80
0.16
2.24
0.44
1.92
0.38
0.80
0.16
0.84
0.16
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS a. Damaged
WERE RECORDED IN GRAMS (G).
ABS.
during processing (weight affected);
WT. = ORGAN WEIGHT.
REL. t TBW
values excluded from group averages
= (ORGAN WEIGHT/TERMINAL and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE B15 (PAGE 19):
TERMINAL BODY WEIGHTS AND ORGAN
INDIVIDUAL
DATA - Fo GENERATION
WEIGHTS AND RATIOS MALE RATS
(t) OF ORGAN WEIGHT TO TERMINAL
BODY
----------------------------------------------------- ----------------------- ------------------------------- -
PROSTATE
RAT
TERMINAL
BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
t 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
404. 578.
516. 486. 454. 517. 428. 467. 437. 496. 457. 469.
441. S06. 492. 436.
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
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
8257
425.
1.13
0.26
8258 8259 8260 8261
8262 8263
506. 440. 545. 453. .464. 530.
1.25 0.91 0.45 1.20 1.04 1.22
0.25 0.21 0.08 0.26 0.22 0.23
8264 8265
506. 422.
1.38 0.68
0.27 0.16
8266 8267
498. 438.
1.08 1.11
0.22 0.25
8268
541.
1.28
0.24
8269
514.
1.26
0.24
8270
507.
0.94
0.18
--------------------------------------------------------------
------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN
a. Damaged during processing (weight not affected).
WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
b. Rat 8243 had a small prostate; values excluded from group averages and statistical analyses. necropsy observations table (Table B14).
See the indi
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE BIS (PAGE 20):
TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS INDIVIDUAL DATA - Fo GENERATION MALE RATS
(t) OF ORGAN WEIGHT TO TERMINAL
BODY
--------------------------------------------------------------------------------------------------------------
PROSTATE
RAT
TERMINAL BODY
ABS.
REL.
NUM13ER
WEIGHT
WT.
TBW
---------------------------------------------------------------------------------------------------------------
DOSAGE GROUP V
3.2 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8271 8272 0273 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. t TBW = (ORGAN WEIGHT/TERMINAL
APPENDIX C REPORT TABLES - Fo GENERATION
FEMALE RATS
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE Cl (PAGE 1): CLINICAL OBSERVATIONS
- SUMMARY - Fo GENERATION FEMALE RATS
- -1 ------------------DOSAGE GROUP DOSAGE (MG/KG/DAY) ----- --PRECOHABITATION------(-DA-Y---1 --OF---S-TU-D-Y
- - -- - -------- ---- - -------T-O--TH-E--D-A-Y--O-F---CO-H-A-B-IT-A-T-I-ON-)-:--------
- ----------1
0 (VEHICLE)
----11 0.1
----------- ---------
---------------------
111
IV
0.4
1.6
---------------------
MAXIMUM POSSIBLE INCIDENCE
1470/ 35 1470/ 35 1470/ 35 1464/ 35 14
MORIBUND SACRIFICED
0
0
0
la
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
CHROMODACRYORRHEA
16/ 1
2/ 1
0/ 0
2/ la
INCISORS:
MISSING/BROKEN
0/ 0
47/ 2
11/ 1
0/ 0
CLEAR ORAL EXUDATE
0/ 0
0/ 0
0/ 0
2/ la
PTOSIS
0/ 0
0/ 0
0/ 0
1/ la
HUNCHED POSTURE
0/ 0
0/ 0
0/ 0
1/ la
LABORED BREATHING
0/ 0
0/ 0
0/ 0
1/ la
--------------------------------------------------------------------------------------------------------------
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.
NIN = 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) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE Cl (PAGE 2): CLINICAL OBSERVATIONS
- SUMMARY - Fo GENERATION FEMALE RATS
-------------------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY)
---------------------------------
PRESUMED GESTATION:
a
---
- -- -------------- -------- -------------------
--------
I
ii
III
0 (VEHICLE) 0.1
0.4
-----------------------------------------------
----------
IV 1.6 -- - ----------
MAXIMUM POSSIBLE INCIDENCE
649/ 34
660/ 35
647/ 34
S81/ 31
6
MORTALITY
0
0
0
0
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** 38/ 3
7/ 1 0/ 0
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
CHROMODACRYORRHEA
4/ 2
0/ 0
0/ 0
0/ 0
---------------------------------------------------------------------------------------------
----------------
STATISTICAL
ANALYSES OF CLINICAL OBSERVATION
DATA WERE RESTRICTED
MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER
OF RATS EXAMINED
MIN m 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
Significantly different from the vehicle control group value
TO THE NUMBER PER GROUP.
(p<O.OS). (p<0.01).
OF RATS WITH OBSERVATIONS.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXICI
TABLE Cl (PAGE 3): CLINICAL OBSERVATIONS
- SUMMARY - Fo GENERATION FEMALE RATS
---- --------------------
DOSAGE GROUP DOSAGE (MG/KG/DAY) -------- ------------------------LACTATION:
- ------------------ -
------------- --------- -------------------
I
ii
III
IV
0 (VEHICLE)
0.1
0.4
1.6
- -------------------- - - - ---------------I ------ --- ------------------
MAXIMUM POSSIBLE INCIDENCE
483/ 23
525/ 25
462/ 22
384/ 20 - 3
MORTALITY
0
0
0
0
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
65/ 4 0/ 0
21/ 1 65/ 4
0/ 0
65/ 5 21/ 1
1/ 1 43/ 3
0/ 0
INCISORS:
TOTAL
0/ 0
21/ 1
0/ 0
0/ 0
MISSING/BROKEN
0/ 0
21/ 1
0/ 0
0/ 0
MISALIGNED
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.
NIN = TOTAL NUMBER OF OBSERVATIONS/NUMBER
OF RATS WITH OBSERVATION.
Significantly different from the vehicle control group value (p<0.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
I,OXICII
TABLE C2 (PAGE 1): BODY WEIGHTS - PRECOHABITATION
---
-1.@ --- ----------- ---- ------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) --- -------------------------
I
0 (VEHICLE) ---------- -------
RATS TESTED
N
35
SUMMARY - Fo GENERATION
FEMALE RATS
--- ------- ---- -------- -- ----------- --- ------
ii
III
IV
0.1
0.4
1.6
- ---------------------------------------------
------
35
35
35
BODY WEIGHT (G)
DAY
I
DAY
8
DAY 15
MEAN+S.D MEAN+S.D MEAN+S.D
237.2 + 12.2 243.8 + 14.5 253.6 + 17.3
236.4 +
9.4
243.8 + 11.3
252.4 + 11.8
237.1 + 11.8 245.7 + 13.5 251.9 + 15.5
238.4 + 11.7 243.9 + 13.6 251.5 + 13.6
DAY 22
MEAN+S.D
256.2 + 19.0
255.4 + 12.4
255.8 + 15.9
252.1 + 17.8
DAY 29
MEAN+S.D
265.2 + 20.4
263.0 + 14.1
265.3 + 18.2
259.2 + 18.0
DAY 36
MEAN+S.D
269.5 + 22.9
268.7 + 13.5
268.8 + 19.3
259.5 + 19.9
DAY 42a
MEAN+S.D
274.4 + 24.1
272.4 + 15.1
271.6 + 18.8
263.6 + 19.1
1 34]b ----------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
[ I = 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).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUI)Y NUMNER:
6295.9)
AND IIERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C3 (PAGE 1): BODY WEIGHT CHANGES - PRECOliABITATION
- SUMMARY - Fo GENERATION
FEMALE RATS
---------------------------- --- ------------ - ---
DOSAGE GROUP
I
DOSAR.E (MG/KG/DAY)
0 (VEHICLE)
--------------------------------------------- - -----
RATS TESTED
N
35
- ----------------
ii 0.1 ------------------
35
------- I ------------------
-------
III
IV
0.4
1.6
- --------------------------- --------
35
35
BODY WEIGHT CHANGE (G)
DAYS
1
8
MEAN+S.D.
+6.6 + 7.3
+7.5 + 6.4
+8.6 + 5.7
+5.5 + 5.7
DAYS
8
15
MEAN+S.D.
+9.8 + 6.3
+8.5 + 4.5
+6.2 + 10.6
+7.6 + 4.5
DAYS 15
22
MEAN+S.D.
+2.6 + 6.7
+3.0 + 5.7
+3.9 + 9.0
+0.6 + 7.0
DAYS 22
29
MEAN+S.D.
+9.0 + 5.6
+7.6 + 6.3
+9.5 + 6.6
+7.0 + 7.0
DAYS 29
36
MEAN+S.D.
+4.3 + 6.0
+5.8 + 5.1
+3.4 + 5.2
+0.3 + 6.7**
DAYS 36
42a
MEAN+S.D.
+4.8 + 6.8
+3.7 + 4.8
+2.8 + 4.1
42.9 + 4.5
DAYS
I
42a
MEAN+S.D.
+37.1 + 15.8
+36.0 + 10.5
+34.5 + 12.9
1 34]b +25.0 + 11.9**
( 34)b ---------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF STUDY
( I = NUM13ER 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).
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE C4 (PAGE 1): MATERNAL BODY WEIGHTS - GESTATION
SUMMARY - Fo GENERATION
FEMALE RATS
--------------- ----- -I ---------------- ----------------------- -
------------------------ --------------
DOSAGE GROUP
I
ii
III
IV
DOSAGE (MG/KG/DAY)
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
(G)
DAY
0
MEAN+S.D.
270.2 + 18.9
271.0 + 15.9
272.7 + 20.0
262.0 + 21.0
DAY
I
MEAN+S.D.
277.1 + 18.2
276.5 + 15.4
278.2 + 20.4
268.8 + 21.5
DAY
2
MEAN+S.D.
281.8 + 17.2
281.4 + 14.6
282.6 + 20.3
272.2 + 21.0
DAY
3
MEAN+S.D.
284.3 + 18.3
285.0 + 16.0
286.2 + 20.9
273.0 + 20.1*
DAY
4
MEAN+S.D.
287.9 + 18.1
288.1 + 15.9
286.8 + 21.4
276.3 + 21.3*
DAY
5
MEAN+S.D.
290.4 + 19.1
289.5 + 15.8
290.6 + 20.9
277.8 + 22.4*
DAY
6
MEAN+S.D.
293.5 + 18.5
293.1 + 16.5
293.1 + 20.4
280.9 + 21.9*
DAY
7
MEAN+S.D.
295.5 + 19.2
293.7 + 16.7
294.3 + 20.4
282.5 + 23.0*
DAY
8
MEAN+S.D.
299.3 + 19.7
296.1 + 17.0
297.5 + 21.0
285.4 + 22.2*
DAY
9
MEAN+S.D.
302.7 + 19.7
300.3 + 17.1
301.@ + 20.9
288.0 + 22.5**
DAY 10
MEAN+S.D.
307.8 + 19.3
305.8 + 18.0
306.2 + 20.0
293.5 + 22.7*
----------------------------------------------------------------------------------------------------------------
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.
Significantly different from the vehicle control group value (p@S0.05).
Significantly different from the vehicle control group value (plO.01).
PROTOCOI, 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERIILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C4 (PAGE 2): MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - Fo GENERATION
FEMALE RATS
-- ----------------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY)
--------------------------------
RATS TESTED
N
-------------- -----------------------------------------------
ii
III
IV
0 (VEHICLE)
0.1
0.4
1.6
-----------------------------------------------------------------------------
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
MEAN+S.D.
312.5 + 19.2
313.5 + 15.9
313.4 + 19.5
298.5 + 21.4*
DAY 12 DAY 13 DAY 14
MEAN+S.D. MEAN+S.D. MEAN+S.D.
317.0 + 20.0 320.2 + 19.8 325.0 + 20.0
317.2 + 16.S 320.4 + 16.7 325.4 + 17.0
316.7 + 20.6 320.6 + 19.4 326.2 + 19.7
303.6 + 22.6 306.9 + 21.3 311.2 + 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 DAY 18 DAY 19
MEAN+S.D. MEAN+S.D. MEAN+S.D.
356.3 + 23.5 370.9 + 25.9 383.5 + 26.0
357.6 + 18.2 371.0 + 19.9 383.1 + 18.6
358.4 + 18.5 370.6 + 19.7 384.5 + 19.7
345.4 + 24.9 359.7 + 26.4 373.2 + 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 8930, 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 (p@0.05).
significantly different from the vehicle control group value (p@0-01).
PROTOCOL 418-008:
COMBINED ORAI, (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICIT
TABLE C5 (PAGE 1): MATERNAL BODY WEIGHT CHANGES
GESTATION - SUMMARY - Fo GENERATION
FEMALE RATS
-------------------
DOSAGE GROUP DOSAGE (MG/KG/DAY) -------------------RATS TESTED
--------
--------- N
----------------
I 0 (VEHICLE) - ---------------
35
---------- I
-------------------------------------- ----
ii
III
IV
0.1
0.4
1.6
---------------------------------- --------------------
35
35
34a
-----
PREGNANT
N
33
32
28
29
INCLUDED IN ANALYSES
N
32b
32
28
26b
14ATERNAL 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
MEAN+S.D. MEAN+S.D.
+10.2 + 3.4 [ 22)c
+15.3 + 4.2
+10.3 + 4.6 ( 25)c
+15.5 + 4.7
+8.8 + 4.1 ( 22)c
+16.4 + 5.5
+10.5 + 5.5 [ 17]c
+16.6 + 4.8
DAYS 15
18
MEAN+S.D.
[ 22]c +38.7 + 7.8
[ 25)C +38.2 + 7.4
[ 22]c +37.4 + 8.8
1 17]C +39.5 + 8.0
( 22)c
I 25)c
( 22]c
[ 17]C
DAYS 18
20
MEAN+S.D.
+25.5 + 6.8
+26.S + 5.5
+27.2 + 7.4
+26.4 + 7.4
[ 22)c
( 25]c
[ 22]c
( 17)c
DAYS
0
20
MEAN+S.D.
+125.1 + 15.9
+123.8 + 13.3
+121.9 + 20.2
+123.1 + 18.3
( 22]c
[ 25)C
[ 22)c
I 17]C
----------------------------------------------- ----------------------------------------------------------------
DAYS = DAYS OF GESTATION
C I = 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 (p:so.05).
Significantly different from the vehicle control group value (p.SO.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
PERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
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
------------- -1 ----------
I
ii
0 (VEHICLE)
0.1
----------------------------
--------------------------------------------
III
IV
0.4
1.6
--------------------------------------------
25
25
25
24a
PREGNANT
N
23
25
22
20
DELIVERED LITTERS
N
23
25
22
20
MATERNAL BODY WEIGHT (G)
DAY
1
DAY
4
MEAN+S.D. MEAN+S.D.
298.3 + 19.4 303.8 + 24.0
299.0 + 18.0 [ 24]b
304.0 + 17.9
298.0 + 23.2 299.4 + 21.3
297.8 + 21.6 290.7 + 22.5
DAY
7
MEAN+S.D.
311.8 + 21.3
306.0 + 14.9
305.5 + 18.9
( IS]d 294.7 + 22.7
DAY 10
MEAN+S.D.
325.1 + 20.7
318.0 + 15.3
320.3 + 16.6
( 18]d 306.4 + 20.2*
DAY 14
MEAN+S.D.
327.0 + 19.6
326.5 + 19.5
324.0 + 22.4
[ 18)d 321.4 + 22.2
DAY 21
MEAN+S.D.
331.2 + 21.3
326.4 + 14.9
331.8 + 16.1
[ IB)d 329.4 + 20.4
( 18]d ---------------------------------------------------------------------------------------------------------------
DAY = DAY 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 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).
PROTOCOL 418-008:
COMBINED ORAL ((;AVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SIIONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXIC
TABLE C7 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - LACTATION - SUMMARY - Fo GENERATION
FEMALE RATS
----- - ------------ --------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ----- -------------------------- --
RATS ASSIGNED TO
NATURAL DELIVERY
N
- ------- -- -------------- ---------- - -
I
ii
0 (VEHICLE)
0.1
-------------- -------------- ----------- ---
25
25
------- -- - -------------
III
IV
0.4
1.6
-----------------------------
25
24a
PREGNANT
N
23
25
22
20
DELIVERED
LITTERS
N
23
25
22
20
INCLUDED IN ANALYSES
N
23
25
22
lab
14ATERNAL BODY WEIGHT CHANGE (G)
DAYS DAYS
1- 4 4- 7
MEAN+S.D. MEAN+S.D.
+5.5 + 11.0 +8.0 + 10.8
+5.3 + 8.4 I 24]C
+2.0 + 7.6
+1.4 + 11.1 +6.1 + 11.5
-6.7 + 11.0* +4.0 + 7.9
DAYS
7 - 10
MFAN+S.D.
+13.3 + 17.4
+12.0 + 6.0
+14.8 + 5.9
+11.7 + 6.4
DAYS 10 - 14
MEAN+S.D.
+1.9 + 18.4
+8.5 + 10.7
+3.6 + 15.2
+15.0 + 6.4*
DAYS 14 - 21
MEAN+S.D.
+4.1 + 19.4
-0.1 + 10.0
+7.8 + 15.2
+8.0 + 9.3
DAYS
1 - 21
MEAN+S.D.
+32.8 + 19.7
+27.8 + 12.3
+33.8 + 17.8
+32.0 + 14.6
[ 24]C --------------------------------------------------------------------------------------------------------------
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 values for dam 8842, 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@0.01).
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERTNATAL/POSTNATAL
REPRODUCTION
TOXICII
TABLE CB (PAGE 1): ABSOLUTE FEED CONSUMPTION
VALUES (G/DAY) - PRECO"ABITATION
- SUMMARY - Fo GENERATION
FEMA
---- - ------ ----- ------------- ------------ -----------
DOSAGE DOSAGE
GROUP (MG/KG/DAY)
I 0 (VEHICLE)
---- ------------------------------------------------------
PATS TESTED
N
35
-- -- ---- ---- --------------
ii
III
0.1
0.4
------------------------------
35
35
-------- - IV
1.6 --------- -- -
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
19.7 + 3.0
19.3 + 2.3 ( 34]a
18.4 + 1.8
DAYS 22
29
MEAN+S.D.
20.0 + 2.5
19.5 + 2.0
19.3 + 2.0
I 34]a 18.5 + 2.2**
DAYS 29
36
MEAN+S.D.
19.2 + 2.2
19.1 + 2.0
f 34]a 18.6 + 2.0
18.0 + 2.7*
1 34)a
( 34]a
DAYS 36
42b
MEAN+S.D.
19.3 + 2.0
19.4 + 2.0
18.9 + 1.8
18.7 + 2.5
DAYS
I 42b
MEAN+S.D.
19.5 + 1.9
t 34)a 19.6 + 1.5
19.1 + 1.7
[ 34]c 18.9 + 2.1
[ 34]a
[ 34]c
----------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF STUDY
[ I = 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).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE C9 (PAGE 1): RELATIVE FEED CONSUMPTION
VALUES (G/KG/DAY) - PRECOHABITATION
- SUMMARY - Fo GENERATION F
------------------------------ -------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) --------------------------------------
RATS TESTED
N
--- - ---- ------ --------------------------- ------------ -- -
I
ii
III
IV
0 (VEHICLE)
0.1
0.4
1.6
----- ----- ------ - ----------------------------------------------
35
35
35
35
-------
FEED CONSUMPTION
(G/KG/DAY)
DAYS 1
8
MEAN+S.D.
79.7 + 7.2
81.5 + 11.5
80.0 + 9.2
81.6 + 11.8
[ 34]a
DAYS
8
15
DAYS 15 22
MEAN+S.D.
MEAN+S.D.
79.8 + 7.8
75.7 + 7.6
79.8 + 8.5
f 31]a 77.6 + 6.9
75.5 + 8.0
[ 32)a 76.3 + 6.1
78.1 + 8.1
I 34)a 73.3 + 5.8
DAYS 22 29
MEAN+S.D.
76.6 + 7.1
75.4 + 5.7
73.8 + 5.9
1 34]a 72.4 + 6.3**
DAYS 29 36 DAYS 36 -.42b
MEAN+S.D. MEAN+S.D.
71.5 + 5.2 1 34]a
71.0 + 5.9
72.0 + 6.9 [ 34]a
71.9 + 5.8
( 34]a 69.6 + 4.7
69.9 + 4.7
69.0 + 7.5 71.2 + 7.4
DAYS I - 42b
MEAN+S.D.
75.7 + 4.5
( 34]a 76.5 + 4.4
74.3 + 4.3
I 34]C 74.5 + 6.0
[ 34]a
I 34]C
---------------------------------------------------------------------------------------------------------------
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).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE CIO (PAGE 1): MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - GESTATION - SUMMARY - Fo GENERATION
-------- -- -- -------------------------- ----- ----
----- -- -- ---------------------------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) --------------------------------
1
11
111
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.
21.6 + 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
MEAN+S.D.
24.2 + 3.0
24.3 + 2.5
22.9 + 3.2
23.6 + 3.4
DAYS 12
15
MEAN+S.D.
( 22)c 23.8 + 2.4
[ 25)C 23.6 + 2.1
( 2i]c 22.8 + 2.5
( 17]c 23.4 + 2.8
[ 22]c
( 25]C
[ 22]C
[ 17]c
DAYS 15 - 18
MEAN+S.D.
24.8 + 2.8
24.4 + 2.3
24.2 + 1.9
26.6 + 2.9*
t 22]c
[ 25]c
( 22]c
( 17)c
DAYS 18 - 20
MEAN+S.D.
22.2 + 2.6
22.4 + 2.3
22.9 + 2.5
23.6 + 3.3
DAYS
0 - 20
MEAN+S.D.
[ 22)C 23.0 + 1.9
[ 24)c,d 22.9 + 1.2
( 22]c 22.4 + 2.0
t 17]C 22.8 + 2.2
1 22]C
[ 24]c,d
t 22)C
( 17]C
--------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF GESTATION
( I = 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 d. Excludes values that were associated with spillage or wet feed.
on day 10 of gestation.
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE Cll (PAGE 1) : MATERNAL RELATIVE FEED CONSUMPTION
VALUES (G/KG/DAY) - GESTATION
- SUMMARY - Fo GENERAT
-----------------------DOSAGE GROUP DOSAGE (MG/KG/DAY)
-----------------------RATS TESTED
----- -- --------- ---------------------------------- -----------------------------
1
11
0 (VEHICLE)
0.1
----- ------------- --------------- --------
N
35
35
111
IV
0.4
1.6
----------------------------------------
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
74.6 + 5.9
DAYS
7
10
MEAN+S.D.
77.7 + 5.4
78.0 + 5.4
75.3 + 9.2
72.8 + 7.4*
DAYS 10
12
MEAN+S.D.
77.2 + 6.3
77.8 + 7.3
73.2 + 9.7
78.7 + 7.4
DAYS 12
15
MEAN+S.D.
[ 22]c 73.5 + 5.6
t 25]c 72.8 + 5.4
I 22)c 70.4 + 6.6
( 17]c 75.4 + 6.2
DAYS 15
18
MEA.N+S.D.
1 22)C 70.7 + 6.1
[ 25]c 69.4 + 6.3
( 22]c 69.0 + 5.7
[ 17]c 78.5 + 5.8**
DAYS 18
20
MEAN+S.D.
[ 22]c 58.1 + 6.1
t 25)c 58.7 + 6.1
[ 22)c 59.7 + 6.7
( 17]c 63.4 + 8.0*
DAYS
0
20
MEAN+S.D.
t 22)c 72.7 + 4.3
i 24]c,d 72.4 + 2.9
( 2i]c 70.5 + 5.3
I 17)C 74.8 + 4.4
f 22)c
I 24]c,d
( 22)c
[ 17]C
---------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF GESTATION
t I = 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 rate that were assigned to Caesarean-sectioning
on day 10 of gestation.
d. Excludes values that 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@0.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTII,ITY, DEVELOPMENTAL
ST11r)Y NUMBER:
6295.9)
AND PF.RINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C12 (PAGE 1): MATERNAL ABSOLUTE FEED CONSUMPTION VALUES (G/DAY)
LACTATION - SUMMARY - Fo GENERATION
----------------- - -----------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) --------------------------------
RATS ASSIGNED TO
NATURAL DELIVERY
N
-------------
------------------
I
ii
0 (VEHICLE)
0.1
-----------
-------------------
25
25
--- -- ----------------------
---
III
0.4 -------------------------
25
- ------IV
1.6 - ---------
24a
PREGNANT
N
23
25
22
20
DELIVERED LITTERS
N
23
25
22
20
INCLUDED IN ANALYSES
N
23
25
22
18b
MATERNAL
FEED
CONSUMPTION
(G/DAY)
DAYS
1- 4
MEAN+s@D.
25.4 + 6.9
24.0 + 4.4
22.0 + 4.5
16.7 + 4.0**
DAYS
4- 7
MEAN+S.D.
1 22)c 37.5 + 7.5
[ 23]c,d 37.6 + 5.4
[ 21]C 36.3 + 8.7
28.9 + 6.6**
DAYS
7 - 10
MEAN+S.D.
47.2 + 5.2 f 22]c
44.8 + 4.4
( 20)c 45.3 + 5.1
36.6 + 7.6**
DAYS 10 - 14e
MEAN+S.D.
56.9 + 5.1 [ 22]c
56.7 + 5.8
53.6 + 9.2
46.8 + 9.2**
DAYS
I - 14e
MEAN+S.D.
43.4 + 5.4 [ 22]c
42.5 + 4.5 [ 24]d
41.0 + 6.9
33.4 + 6.5**
---------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF LACTATION
I 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 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 fe
were not tabulated on days 14 to 21 of lactation.
Significantly different from the vehicle control group value (pliO.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERI'ILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C13 (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION
VALUES (G/KG/DAY) - LACTATION
- SUMMARY - Po GENERATI
------------------------------ ------ ---- - --------------------- ----- --------------------- - --
DOSAGE GROUP
I
ii
III
IV
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
1.6
------------------------------------- ---------------------------------------------------------------------- --
RATS ASSIGNED TO
NATURAL DELIVERY
N
25
25
25
24a
PREGNANT
N
23
25
22
20
DELIVERED
LITTERS
N
23
25
22
20
INCLUDED IN ANALYSES
N
23
25
22
18b
MATERNAL
FEED
CONSUMPTION
(G/KG/DAY)
DAYS
1
4
MEAN+S.D.
84.6 + 22.2
79.9 + 14.1
74.4 + 17.0
56.9 + 13.8**
1 22]c
( 23)c,d
[ 21]C
DAYS
4
7
MEAN+S.D.
122.2 + 24.7
123.6 + 19.8
120.0 + 28.3
98.6 + 20.0**
DAYS
7
10
MEAN+S.D.
147.9 + 15.6
144.0 + 15.4
( 20]c 145.4 + 18.6
121.7 + 23.5**
[ 22)C
DAYS 10
14e
MEAN+S.D.
174.0 + 14.1
175.9 + 17.7
166.7 + 29.0
148.9 + 25.9**
( 221c
DAYS. 1
14e
MEAN+S.D.
137.8 + 16.2
136.9 + 15.5
133.0 + 23.8
110.4 + 19.6**
( 22)c
[ 24)d
----------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF LACTATION
I 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 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 fee
were not tabulated on days 14 to 21 of lactation.
Significantly different from the vehicle control group value (p<0.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FEATILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C14 (PAGE 1): ESTROUS CYCLING, MATING AND FERTILITY - SUMMARY - Fo GENERATION
FEMALE RATS
-------------------DOSAGE GROUP DOSAGE (MG/KG/DAY) ----------------------------ESTROUS CYCLING
---------------------- --------- - ---------------------------
I 0 (VEHICLE) -----------------------------------
ii
III
0.1
0.4
---------------------------
- ---------------
IV 1.6 -----------------
RATS EVALUATED
ESTROUS 28 DAYS
STAGES/
N MEAN+S.D.
15
6.S +
0.7
is
6.5 +
0.8
15 5.7 + 1.3
15
6.1 +
0.
RATS WITH CONSECUTIVE
6 OR MORE
DAYS OF DIESTRUS
N
3
4
5
2
RATS WITH 6 OR MORE
CONSECUTIVE
DAYS OF ESTRUS
N
1
0
1
0
---------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C14 (PAGE 2): ESTROUS CYCLING, MATING AND FERTILITY - SUMMARY - Po GENERATION
FEMALE RATS
------------------------------------------ ---------------------
--------------------- - --, ----------
DOSAGE GROUP
I
ii
III
IV
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
1.6
----------------------------------------------------------------------------------------------------------------
MATING AND FERTILITY
RATS IN COHABITATION
N
35
35
35
34a
DAYS IN COHABITATION
b
MEAN+S.D.
2.7 +
1.8
[ 341
2.6 +
1.3
2.9 +
3.1
2.1 + 1.2 t 311
RATS THAT MATED
N(%)
35(100.0)
35(100.0)
34( 97.1)
34(100.0)
FERTILITY INDEX c
NIN (t)
33/35 94.3)
32/35 91.4)
28/34 82.4)
29/34 85.3)
RATS WITH CONFIRMED
MATING DATES
N
34
33
34
31
MATED BY FIRST MALE d DAYS 1-7
N(%)
34(100.0)
33(100.0)
33( 97.0)
31(100.0)
MATED BY SECOND MALE d DAYS B-14
N(%)
0( 0.0)
o( o.o)
1( 2.9)
0( 0.0)
RATS PREGNANT/RATS
IN
COHABITATION
NIN
33/35
32/35
28/35
29/34
(t)
( 94.3)
91.4)
80.0)
85.3)
----------------------------------------------------------------------------------------------------------------
[ I = 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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL SIUI)Y NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C15 (PAGE 1): NECROPSY OBSERVATIONS
SUMMARY - Fo GENERATION
FEMALE PATS
------------------ ---------- ---- --------- - -------------- ----------------------------
DOSAGE GROUP
-------------------
DOSAGE (MG/KG/DAY)
I
ii
III
IV
0 (VEHICLE)
0.1
0.4
------------------------------------ ------ - --------------------------------------------------------1-.-6-------
RATS EXAMINED a N 3S 35 35 35
MORIBUND SACRIFICED N 0 0 0 lb
APPEARED NORMAL N 35 3S 34 34b
SPLEEN:
ADHERED TO ABDOMINAL
ADIPOSE TISSUE
N
0
0
KIDNEYS:
RIGHT, PELVIS, MODERATE
DILATION
N
0
0
---------------------------------------------------------------------------------------------------------------
a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at nec b. Rat 8938 was moribund sacrificed on day 36 of study.
PROTOCOL 418-008:
COMBINED ORAL (GAV)@GE@ PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXIC
TABLE C16 (PAGE 1): CAESAREAN-SECTIONING
OBSERVATIONS
- SUMMARY - Fo GENERATION
FEMALE RATS
---------- --- ---------- -- ----------------- -------- ------------------
-- --- -----------------------
DOSAGE GROUP
I
ii
DOSAGE (MG/KG/DAY)
III
IV
---------- -------------- -- ------------0--(-VEHICLE) 0.1
0.4
1.6
- -------- ----------------------- ---- ------------------------
RATS ASSIGNED TO
CAESAREAN-SECTIONING N 10 10 10 10
PREGNANT
N(t)
10(100.0)
7( 70.0)
6( 60.0)
9( 90.0)
RATS PREGNANT AND
CAESAREAN-SECTIONED
ON DAY 10 OF GESTATION N 10 7 6 9
CORPORA LUTEA
MEAN+S.D.
16.6 + 3.6
14.6 +
6.6
14.8 +
4.3
15.7 +
4.6
IMPLANTATIONS
MEAN+S.D.
13.5 + 4.0
11.8 +
5.6
12.2 +
5.6
12.9 +
4.2
VIABLE EMBRYOS
N MEAN+S.D.
133
13.3 +
4.1
83
11.8 +
5.6
73
12.2 +
5.6
115 12.8 + 4.1
NONVIABLE
EMBRYOS
N MEAN+S.D.
2
0.2 +
0.6
0
0.0 +
0.0
0
0.0 +
0.0
1
0.1 +
0.3
DAMS WITH ANY NONVIABLE EMBRYOS
N(%)
1( 10.0)
0( 0.0)
0( 0.0)
1( 11.1)
DAMS WITH ALL NONVIABLE
EMBRYOS
N0 0 0 0
DAMS WITH VIABLE EMBRYOS
N(t)
10(100.0)
7(100.0)
6(100.0)
9(100.0)
NONVIABLE
EMBRYOS/LITTER
MEAN+S.D.
1.7 + 5.3
0.0 + 0.0
0.0 +
0.0
0.6 + 1.8
---------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C17 (PAGE 1): NATURAL DELIVERY OBSERVATIONS
- SUMMARY - Fo GENERATION
FEMALE RATS
--------DOSAGE GROUP DOSAGE (MG/KG/DAY) - ----------------RATS ASSIGNED TO NATURAL DELIVERY
-------------------
-------
- -- ------ ------ --- I --- ------------- -
--
I
ii
III
0 (VEHICLE)
0.1
0.4
---------------- -------------------------------------------------
N
25
25
25
---IV
1.6 ------------
24a
PREGNANT
N(%)
23( 92.0)
25(100.0)
22( 88.0)
20( 83.3)
DELIVERED
LITTERS
N(%)
23(100.0)
25(100.0)
22(100.0)
20(100.0)
DURATION OF GESTATION b MEAN+S.D.
IMPLANTATION PER DELIVERED
SITES LITTER
N MEAN+S.D.
DAMS WITH STILLBORN
PUPS
N(t)
22.7 +
0.4
t 221
342
14.9 +
1.9
5( 21.7)
22.8 + 0.4 241
384 15.4 + 2.2
2( 8.0)
22.5 + 0.7 221
323 14.7 + 3.5
5( 22.7)
22.4 +
0.5
17)
295
14.8 +
1.7
4( 20.0)
DAMS WITH NO LIVEBORN PUPS N(%)
0( 0.0)
0( 0.0)
0( 0-0)
0( 0.0)
GESTATION
INDEX c
ft
NIN
DAMS DAYS
WITH ALL PUPS 1-4 POSTPARTUM
DYING
100.0 23/ 23
0( 0.0)
100.0 25/ 25
0( 0.0)
100.0 22/ 22
0( 0-0)
100.0 20/ 20
2( 10.0)
DAMS WITH ALL PUPS DYING
DAYS 5-21 POSTPARTUM
N
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 ti 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).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTIIITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C18 (PAGE 1): LITTER OBSERVATIONS
(NATURALLY DELIVERED PUPS) - SUMMARY - Fl GENERATION
LITTERS
------ -- - ----------------------
MATERNAL
DOSAGE GROUP
MATERNAL DOSAGE (MG/KG/DAY) ---------------------------- I -----
DELIVERED LITTERS WITH
ONE OR MORE LIVEBORN
PUPS
N
----
---------- --------------------------------- ----- -------
I
ii
III
IV
0 (VEHICLE)
0.1
0.4
1.6
-------- -----------------------------------------------------------
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(i)
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(i)
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 DAYS DAYS DAYS DAYS
1 2- 4 5- 7 8-14 15-21
NIN(T) NIN(T) NIN(T)
HIN(I;) NIN(T)
2/313( 2/311( 0/184( 0/184( 0/184(
0.6) 0.6) 0.0) 0.0) 0.0)
3/346( 3/358( 0/200( 0/200( 0/200(
0-9)a 0.8) 0.0) 0.0) 0.0)
1/297( 4/296( 0/169( 1/169( 2/168(
0.3) 1.4) 0.0) O@6) 1.2)
27/254( 59/227(
6/131( 1/125( 0/124(
10.6) 26.0)*
4.6)-* 0.8) 0.0)
VIABILITY INDEX b
t
NIN
98.7 309/313
98.3 340/346a
98.3 292/297
66.1* 168/254
LACTATION INDEX c
t
100.0
100.0
98.2
94.6**
NIN
184/184
200/200
166/169
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@S0.05).
Significantly different from the vehicle control group value (p@S0.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
RE PRODUCTION TOXICI
TABLE C18 (PAGE 2): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - Fl 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
SURVIVING PUPS/LITTER a
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.
13.6 + 2.3 13.4 + 2.1
8.0 + 0.0 8.0 + 0.0 8.0 + 0.0 8.0 + 0.0
14.4 + 2.4 1 24]c
14.2 + 2.4
8.0 + 0.0
8.0 + 0.0
8.0 + 0.0
8.0 + 0.0
13.5 + 3.3 13.3 + 3.3
7.7 + 1.1 7.7 + 1.1 7.6 + 1.1 7.5 + 1.2
12.7 + 2.6 8.4 + 4.0 6.6 + 2.6* 6.2 + 2.8** 6.2 + 2.8** 6.2 + 2.8**
PERCENT MALE PUPS PER NUMBER OF PUPS SEXED
DAY 1 b DAY 4 PRECULLING
MEAN+S.D. MEAN+S.D.
46.3 + 17.0 46.8 + 16.9
53.9 + 14.4 [ 24)C
53.2 + 15.0
S2.8 + 11.9 53.0 + 11.6
55.1 + 17.8 57.0 + 21.4
DAY 4 POSTCULLING
MEAN+S.D.
48.9 + 11.2
49.0 + 6.2
50.8 + 5.5
f lejd 53.8 + 19.7
DAY 7
MEAN+S.D.
48.9 + 11.2
49.0 + 6.2
t 20]e 51.9 + 6.3
( 18)d 51.7 + 23.2
DAY 14
MEAN+S.D.
48.9 + 11.2
49.0 + 6.2
51.6 + 5.9
[ i8)d 51.8 + 23.0
DAY 21
MEAN+S.D.
48.9 + 11.2
49.0 + 6.2
52.4 + 6.7
[ iB]d 51.8 + 23.0
[ 18)d ---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTPARTUM
( ) - 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 additional pup on day 2 of lactation. d. Excludes values for litters that had no surviving pups.
e. Excludes values for litters 8874 and 8899; a sexing error was found prior to weighing on day I 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 PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE C18 (PAGE 3): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - Fl GENERATION LITTERS
---------------------------------------------------------------------------------------------------------------
MATERNAL DOSAGE GROUP
I
ii
III
IV
14ATERNAL 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. HEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
PUP WEIGHT/LITTER (GRAMS)
13.6 + 2.2 13.4 + 2.1
8.0 + 0.0 8.0 + 0.0 8.0 + 0.0 8.0 + 0.0
14.3 + 2.4 1 24]b
14.2 + 2.4
8.0 + 0.0
8.0 + 0.0
8.0 + 0.0
8.0 + 0.0
13.4 + 3.4 13.3 + 3.3
7.7 1.1 7.7 + 1.1 7.6 1.1 7.5 + 1.2
11.6 + 3.5
9.3 + 3.0** [ lela
7.3 + 1.4 t 18]a
6.9 + 1.9* [ lila
6.9 + 1.9** f 18)a
6.9 + 1.9** 18]a
DAY I DAY 4 PRECULLING
MEAN+S.D. MEAN+S.D.
6.6 + 0.6 9.2 + 1.2
6.6 + 0.5 [ 24]b
8.9 + 0.8
6.4 + 0.7 8.9 + 1.3
5.7 + 0.5** 7.3 + 1.1**
DAY 4 POSTCULLING
MEAN+S.D.
9.4 + 1.2
9.0 + 0.7
9.0 + 1.3
t lija 7.5 + 1.2**
DAY 7
MEAN+S.D.
14.8 + 1.9
14.3 + 1.2
14.0 + 1.4
[ 18)a 11.0 + 1.8**
DAY 14
MEAN+S.D.
31.1 + 3.3
30.5 + 2.3
29.9 + 2.3
( 18]a 24.4 + 3.3**
DAY 21
MEAN+S.D.
49.8 + 5.1
48.6 + 3.6
48.2 + 4.5
t 18]a 40.3 + 4.3**
t lela ---------------------------------------------------------------------------------------------------------------
DAY - DAY POSTPARTUM t I = 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:SO.01).
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C19 (PAGE 1): CLINICAL OBSERVATIONS
FROM BIRTH TO DAY 21 POSTPARTUM
- SUMMARY - Fl GENERATION
PUPS
-------- -- ----------- ----------------------------- -- - -------------------------------------------------
MATERNAL
DOSAGE GROUP
MATERNAL DOSAGE (MG/KG/DAY) --------------------------------------
I
0 (VEHICLE) ----- ----
ii
III
IV
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
NIN
PLACENTAS
NOT REMOVED
NIN
NOT NESTING
NIN
PERSISTENT
CLINICAL OBSERVATIONS:
a
0/ 0 0/ 0 0/ 0
0/ 0 0/ 0 0/ 0 TOTAL FREQUENCY
0/ 0 0/ 0 0/ 0 (DAYS x PUPS)/LITTERS
0/ 0 0/ o 0/ 0 WITH OBSERVATIONS
TAIL: MISSING
NIN
0/ 0
0/ 0
0/ 0
0/ 0
LEFT FORELIMB:
CANNIBALIZED
NIN
0/ 0
0/ 0
0/ 0
0/ 0
HEAD:
DOMED
NIN
0/ 0
0/ 0
17/ 1
7/ 1
PORTION OF TAIL MISSING
NIN
0/ 0
0/ 0
0/ 0
20/ 1
UMBILICAL HERNIA
NIN
0/ 0
15/ 1
0/ 0
0/ 0
LEFT HINDPAW:
DIGITS, MISSING
NIN
21/ 1
0/ 0
0/ 0
0/ 0
TAIL: BENT
NIN
0/ 1
0/ 0
0/ 0
0/ 0
----------------------------------------------------------------------------------------------------------------
STATISTICAL NIN = TOTAL
ANALYSES FREQUENCY
WERE RESTRICTED
TO THE NUMBER OF LITTERS
(DAYS x PUPS)/LITTERS
WITH OBSERVATIONS
WITH OBSERVATIONS.
a. Tabulation restricted to adverse observations; all other pups appeared normal. .* Significantly different from the vehicle control group value (p<0.01).
PROTOCOL 41B-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C20 (PAGE 1); REFLEX AND PHYSICAL DEVELOPMENT
- SUMMARY - Fl GENERATION
LITTERS
--------------------- -- --
MATERNAL
DOSAGE GROUP
MATERNAL DOSAGE (MG/KG/DAY) ------------ -------- --- -
SURFACE RIGHTING a
-------------------
-------------------
---- -------------------- --
I
ii
III
IV
0 (VEHICLE)
0.1
0.4
1.6
----- ------------
----- ------------------- -- -------------------------- --
N
23
25
22
20
DAY
I
DAY
2
MEAN+S.D. MEAN+S.D.
46.0 + 20.0 38.7 + 24.7
51.6 + 24.3 [ 24]C
34.0 + 24.8
37.0 + 22.0 32.7 + 17.9
29.4 + 23,5 20.4 + 16.1
DAY
3
DAY
4
MEAN+S.D. MEAN+S.D.
47.8 + 27.6 71.0 + 31.4
43.4 + 27.4 74.4 + 22.7
39.4 + 28.6 61.5 + 28.1
[ igjb 11.9 + 10.7
( 19]b 32.4 + 21.5
DAY
5
MEAN+S.D.
85.9 + 21.8
91.0 + 20.6
84.1 + 19.0
[ 18)b 41.2 + 32.9
DAY
6
MEAN+S.D.
90.8 + 21.7
95.5 + 12.4
90.9 + 17.3
1 18]b 47.1 + 30.1
DAY
7
DAY
a
MEAN+S.D. MEAN+S.D.
94.6 + 13.0
96.7 +
8.6
93.5 + 16.2 95.5 + 10.8
93.8 + 13.2
98.3 +
5.8
( 18]b 60.2 + 33.6
[ 18)b 77.6 + 29.3
DAY
9
MEAN+S.D.
97.8 +
6.1
98.5 +
5.5
99.4 +
2.7
( 18]b 85.4 + 27.9
DAY
10
MEAN+S.D.
99.4 +
2.6
99.5 +
2.5
100.0 +
0.0
( 18]b 89.6 + 28.5*
DAY
11
MEAN+S.D.
100.0 +
0.0
99.5 +
2.5
100.0 +
0.0
[ 18)b 94.4 + 16.2
DAY
12
MEAN+S.D.
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
t lolb 93.0 + 24.0
DAY
13
MEAN+S.D.
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
f lojb 94.4 + 23.6
DAY
14
MEAN+S.D.
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
[ 18]b 94.4 + 23.6
[ 18]b ---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTPARTUM
[ I = NUMBER OF VALUES AVERAGED
a. The average percentage of pups meeting the criterion for the developmental b. Excludes values for dams that had no surviving pups.
landmark tested on each day pos
C. Excludes values for dam 8842, which delivered one additional pup on day 2 of lactation. Significantly different from the vehicle control group value (plo.05). Significantly different from the vehicle control group value (p<0.01).
PROTOCOL 418-008:
COMBINED ORAL (GAV4GE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI(
TABLE C20 (PAGE 2): REFLEX AND PHYSICAL DEVELOPMENT
- SUMMARY - Fi GENERATION
LITTERS
MATERNAL MATERNAL ------SURFACE
------------- ------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) -- ----------------------
RIGHTING (Cont.)a
N
---
--------------- --- --- -------------------
I
ii
III
0 (VEHICLE)
0.1
0.4
------------------------------------------------
23
25
22
---- --- ----------IV
1.6 ---- ---------------
20
INCLUDED IN ANALYSES
DAY
is
DAY
16
N MEAN+S.D. MEAN+S.D.
23
100.0 +
0.0
100.0 +
0.0
25
100.0 +
0.0
100.0 +
0.0
22
100.0 +
0.0
100.0 +
0.0
18b 97.2 + 11.8 97.2 + 11.8
DAY
17
MEAN+S.D.
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
MEAN%+S.D.c
2.4 +
1.8
2.0 +
1.2
2.7 +
1.6
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 + 33.5
50.8 + 35.4*
43.9 + 38.8*
8.4 + 19.8
DAY
4
MEAN+S.D.
99.2 +
3.7
97.6 +
8.5
98@3 +
6.3
47.7 + 47.6
DAY
5
DAY
6
MEAN+S.D. MEAN+S.D.
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
t 18]b 81.9 + 32.1
f 18]b 93.0 + 20.7
DAY
7
MEAN+S.D. MEAN%+S.D.c
100.0 +
0.0
3.1 +
0.7
100.0 +
0.0
3.4 +
0.6
100.0 +
0.0
3.5 +
0.7
( 18]b
100.0 +
0.0
t 18]b
4.7 +
1.0
[ 18]b --------------------------------------------------------------------------------------------------------------
DAY = DAY POSTPARTUM
( I = NUMBER OF VALUES AVERAGED a. The average percentage of pups meeting the criterion for the developmental landmark tested on each day po 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<0.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
s,rUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C20 (PAGE 3): REFLEX AND PHYSICAL DEVELOPMENT
- SUMMARY - Fl GENERATION
LITTERS
------------------- ------------------------
- --------------------
MATERNAL
DOSAGE GROUP
I
ii
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
--------------------------------------------- ---- ---------------------
EYE OPENING a
N
23
25
-- ------------------------ ----------
III
IV
0.4
1.6
-- -----------------------------------
22
18b
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 + 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 +
S.9
DAY
18
MEAN+S.D.
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
MEANV+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 b. Excludes values for dams that had no surviving pups.
landmark tested on each day pos
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:SO.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER!
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C20 (PAGE 4): REFLEX AND PHYSICAL DEVELOPMENT
- SUMMARY - Fl GENERATION
LITTERS
- -------------------- - ---- --------------- ----------
MATERNAL
DOSAGE GROUP
MATERNAL DOSAGE (MG/KG/DAY)
-----------------------------
I
0 (VEHICLE) ---------------------------
ACOUSTIC STARTLE a
N
23
DAY
13
MEAN+S.D.
75.5 + 31.9
DAY
14
MEAN+S.D.
64.2 + 25.1
DAY
is
MEAN+S.D.
88.6 + 21.9
DAY
16
MEAN+S.D.
95.1 + 14.5
DAY
17
MEAN+S.D.
98.9 +
5.2
DAY
18
MEAN+S.D.
100.0 +
0.0
DAY
19
MEAN+S.D.
100.0 +
0.0
DAY
20
DAY
21
MEAN+S.D. MEAN+S.D.
100.0 + 100.0 +
0.0 0.0
---------------------- --- ----------
ii
III
0.1
0.4
--------------------------- -----------
------------IV
1.6 -------------
25
22
18b
83.0 + 20.4
69.7 + 21.0
39.3 + 27.4*
B7.0 + 18.2
78.6 + 23.7
52.3 + 40.8*
78.5 + 34.1
77.1 + 27.7
68.7 + 29.6
81.5 + 32.9
80.9 + 29.7
67.3 + 36.0*
91.5 + 20.6
89.2 + 22.9
76.6 + 35.1*
95.5 + 14.4
96.0 11.8
81.9 + 36.2*
99.0 +
5.0
98.3 +
8.0
84.5 + 32.1*
100.0 +
0.0
100.0 +
0.0
94.4 + 16.2*
100.0 +
0.0
100.0 +
0.0
97.2 + 11.8
MEANI+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 post 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<0.01).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAIL POSTNATAL
REPRODUCTION
TOXICI
TABLE C20 (PAGE 5): REFLEX AND PHYSICAL DEVELOPMENT
- SUMMARY - Fl GENERATION
LITTERS
--------------- --- ----------------------------- - -------------------------------------- --------------------
MATERNAL
DOSAGE
MATERNAL DOSAGE ----------------
GROUP
1
11
111
(MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
-------------------------------- --------------------------------------
IV -------------1-.6---------
AIR RIGHTING a
N
23
25
22
18b
DAY
14
MEAN+S.D.
23.9 + 27.7
13.5 + 14.4
13.0 + 15.8
3.5 +
8-.4**
DAY
is
MEAN+S.D.
48.4 + 28.8
33.5 + 22.2
35.5 + 23.0
3.5 +
5.8**
DAY
16
MEAN+S.D.
64.7 + 26.8
66.0 + 21.5
46.8 + 26.3*
21.3 + 25.0**
DAY
17
DAY
18
DAY
19
DAY
20
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
79.3 + 25.7
97.8 +
8.1
100.0 +
0.0
100.0 +
0.0
77.0 + 19.0
90.5 + 15.0
99.0 +
3.5
100.0 +
0.0
73.0 + 21.9
93.9 + 13.3
98.3 +
8.0
100.0 +
0.0
40.8 + 31.5** 60.6 + 22.5** 7S.2 + 30.1** 93.8 + 16.2**
DAY
21
MEAN+S.D.
100.0 +
0.0
100.0 +
0.0
100.0 +
0.0
93.8 + 16.2**
MEAN%+S.D.c
15.5 +
1.2
15.9 +
0.8
16.1 +
1.1
17.5 +
0.8**
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
f I = NUMBER OF VALUES AVERAGED
a. The average percentage of pups meeting the criterion for the developmental b. Excludes values for dams that had no surviving pups.
landmark tested on each day post
C. The average day postpartum that at least 50% of the pups had the developmental Significantly different from the vehicle control group value (p@0.05).
Significantly different from the vehicle control group value (p@0.01).
measure present.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE C21 (PAGE 1): NECROPSY OBSERVATIONS - SUMMARY - Fl 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
--------------------------------------------------------------------------------------------------------------
TOTAL PUPS STILLBORN
OR FOUND DEAD a
N
8
6
STILLBORN
N
5
1
FOUND DEAD
N
3
5
8
71
4
6
4
65
NO MILK IN STOMACH b
N(lk)
2( 66.7)
0( 0.0)
3( 75.0)
49( 75.4)
HINDLIMBS AND/OR PORTION TAIL: MISSING c
OF N(t)
0( 0.0)
0( 0.0)
0( 0.0)
0( 0.0)
WHOLE BODY EDEMA
N(Pi)
0( 0.0)
o( o.o)
0( 0.0)
1( 1.4)
--------------------------------------------------------------------------------------------------------------
PUPS SACRIFICED AND NECROPSIED ON DAYS 4 OR 21 POSTPARTUM a
LITTERS EVALUATED PUPS EVALUATED
N
23
25
22
18d
N
259
305
209
161
APPEARED NORMAL LITTER INCIDENCE PUP INCIDENCE
N(t) N(t)
23(100.0) 259(100.0)
25(100.0) 305(100.0)
20( 90.9) 206( 98.6)
18(loo.0) 161(100.0)
BRAIN: LATERAL VENTRICLES, LITTER INCIDENCE
PUP INCIDENCE
MODERATE N(%) N(t)
TO SEVERE DILATION 0( 0-0) 0( 0.0)
0( 0-0) 0( 0.0)
1( 4.5) 2( 1.0)
o( o.0) 0( 0.0)
KIDNEYS: RIGHT, PELVIS, SLIGHT DILATION
LITTER INCIDENCE
N(t)
0( 0.0)
0( 0.0)
1( 4.5)
0( 0.0)
PUP INCIDENCE
N(t)
0( 0.0)
o( o.o)
1( 0.5)
0( 0.0)
---------------------------------------------------------------------------------------------------------------
a. Complete necropaies 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.
PROTOCOL 418-008:
COMBINED ORAI, (GAVAGE) FERTILITY,
DEVELOPMENTAL
PPOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUCT10N
TOXIC
TABLE C22 (PAGE 1): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
--- ---------------------------DOSAGE GROUP 1
------------- --------- --------------------0 (VEHICLE) MG/KG/DAY
-----------------------
-------
---------------- ------------------------------------------------------------------------------------- -------
RAT
DESCRIPTION
-----------------------------------------------------------------------------------------------------------
--
8801 8802
DG( 11- 12)
CHROMODACRYORRHEA NO ADVERSE FINDINGS
8803
NO ADVERSE FINDINGS
8804 8805 8806 8807 8808 8809 8810 8811 8812 8813 8814 8815 8816 8817 8818
DL( 2- 21) DS( 27- 44)
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
HEAD
8819 8820 8821 8822 8823 8824 8825 8826 8827 8828 8829 8830 8831 8832
DG( 0- 1)
DL( 2- 21)
DL(
21
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
LIMBS a LIMBS a
8833
NO ADVERSE FINDINGS
8834
NO ADVERSE FINDINGS
8835
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
DG = DAY OF PRESUMED
a. observation confirmed at necropsy.
GESTATION
DL = DAY OF LACTATION
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C22 (PAGE 2): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
------------------------ --DOSAGE GROUP 11
---------------------------
RAT #
--- -----------------------
0.1 MG/KG/DAY ---------------------------
DESCRIPTION
-1----------------- I -----------------------
-- -------------------- -------------------------------
-------------------------------- --------------------------- ------------------- -----------------------------
8836 8837 8838 8839 8840 8841 8842
8843 8844 8845 8846 8847 8848 8849 8850 8851 8852 8853 8854 8855
8856 8857 8858 8BS9 8860 8861 8862 8863 8864 8865
DS( 5- 6)
DS( ]jG( DL(
2- 43) 0- 21) I- 21)
DG( DL(
3- 21) I- 21)
DL(
21
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
8866
DS( 37- 43)
INCISORS:
MISSING/BROKEN
DG(
0
INCISORS:
GROWN IN
8867
NO ADVERSE FINDINGS
8868
NO ADVERSE FINDINGS
8869
NO ADVERSE
FINDINGS
8870
NO ADVERSE
FINDINGS
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
DG = DAY OF PRESUMED
a. observation confirmed at necropsy.
GESTATION
DL = DAY OF LACTATION
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SP014SOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C22 (PAGE 3): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA
Fo GENERATION
FEMALE RATS
------------------------------ -----------
DOSAGE GROUP 111
0.4 MG/KG/DAY
-------------------------- --I -----------
------------ ----- ----- -------------------------------------------------------------------------------------------
RAT #
DESCRIPTION
------- ----------------------------- -----------
------------------ ---------------------------------------
8871
DS( S8- 64)
CHROMODACRYORRHEA
8872
NO ADVERSE FINDINGS
8873
DS( 21- 42)
LOCALIZED ALOPECIA:
LIMBS
8874
DG( 0- 10)
LOCALIZED ALOPECIA: NO ADVERSE FINDINGS
LIMBS a
8875
NO ADVERSE FINDINGS
8876 8877
NO ADVERSE NO ADVERSE
FINDINGS FINDINGS
8878 8879 8880
NO ADVERSE NO ADVERSE NO ADVERSE
FINDINGS FINDINGS FINDINGS
8881
NO ADVERSE FINDINGS
8882
NO ADVERSE FINDINGS
8883
DG( 9- 10)
INCISORS:
MISSING/BROKEN
a
8884 8885 8886 8887 8888 8889
NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE
FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS
8890
NO ADVERSE FINDINGS
8891
NO ADVERSE FINDINGS
8892 8893
DL( 20- 21)
LOCALIZED NO ADVERSE
ALOPECIA: FINDINGS
LIMBS a
8894
NO ADVERSE FINDINGS
8895
NO ADVERSE FINDINGS
8896
DS( 34- 45)
LOCALIZED ALOPECIA:
LIMBS
DG( 0- 20)
LOCALIZED
ALOPECIA:
LIMBS
8897
DL( 1- 21) DS( 21- 45)
LOCALIZED LOCALIZED
ALOPECIA: ALOPECIA:
LIMBS a LIMBS
DG( 0- 20) DL( I- 21)
LOCALIZED LOCALIZED
ALOPECIA: ALOPECIA:
LIMBS LIMBS a
8898
NO ADVERSE FINDINGS
8899
NO ADVERSE FINDINGS
8900
DS( 13- 45)
LOCALIZED ALOPECIA:
LIMBS
DG( 0- 21) DG( 18- 21) DL( I- 21)
LOCALIZED LOCALIZED LOCALIZED
ALOPECIA: ALOPECIA: ALOPECIA:
LIMBS UNDERSIDE LIMBS a
DL( I- 21)
LOCALIZED ALOPECIA:
UNDERSIDE a
----------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
DG = DAY OF PRESUMED GESTATION
DL = DAY OF LACTATION
a. observation confirmed at necropsy.
PROTOCOI, 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C22 (PAGE 4): CLINICAL OBSERVAIIONS
- INDIVIDUAL DATA
Po GENERATION
FEMALE RATS
-------- - -------------------------
- ------------------
--------------------------- ----------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
-------- - --------------------------
------- ------------ -------------------------------------------------
RAT #
DESCRIPTION
-------- ----------------------------
- ---------------------------------------------------------------------
8901
NO ADVERSE FINDINGS
8902
NO ADVERSE FINDINGS
8903
NO ADVERSE FINDINGS
8904
DS( 16- 26)
INCISORS: MISSING/BROKEN
DS(
27
INCISORS:
GROWN IN
8905
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
DG = DAY OF PRESUMED GESTATION
DL = DAY OF LACTATION
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
SI'UR)Y NIJMBER: 6295-9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE C22 (PAGE 5): CLINICAL OBSERVATIONS
INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
-------------------- I ----------- ----- - - ---
DOSAGE GROUP IV
1.6 MG/KG/DAY
------------ -------- ------------------
---
RAT # --------------------
DESCRIPTION ------------ ----------------
------------- -- - ----- -- --------------- - --------------------------- --------------------------------------------------------------------------------------------------
8906
8907 8908 8909
DS( 10- 23)
DS(
24
DS( 21- 31)
DS(
32
LOCALIZED ALOPECIA:
ALOPECIA
NO LONGER
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
LOCALIZED ALOPECIA:
ALOPECIA NO LONGER
LIMBS APPARENT
UNDERSIDE APPARENT
8910 8911 8912 8913 8914 8915 8916 8917 8918 8919 8920 8921 8922 8923 8924 8925
8926 8927 8928
DL(
21
DG( 9- 10)
DG( 14- 20) DL( I- 21)
DS( 25- 44)
LOCALIZED NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE LOCALIZED NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE LOCALIZED LOCALIZED NO ADVERSE NO ADVERSE LOCALIZED
ALOPECIA: FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS
ALOPECIA: FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS FINDINGS
FINDINGS FINDINGS ALOPECIA: ALOPECIA: FINDINGS FINDINGS ALOPECIA:
UNDERSIDE a
LIMBS a
BACK BACK a LIMBS
DG( 0- 21)
LOCALIZED
ALOPECIA:
LIMBS
DL( I- 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
8934
DL(
21
LOCALIZED ALOPECIA:
LIMBS a
8935
NO ADVERSE FINDINGS
8936
NO ADVERSE FINDINGS
8937
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DS - DAY OF STUDY
DG = DAY OF PRESUMED GESTATION
DL = DAY OF LACTATION
PROTOCOL 418-008:
COMBINED
ORAI, (GAVAGE)
PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATA 1, REPRODUCTION
TOXIC
TABLE C22 (PAGE 6): CLINICAL OBSERVATIONS
INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
-- -- ------ ---------------------- -- -- - -- ---------
------------------------ - -- ------ -------
DOSAGE GROUP IV
1.6 MG/KG/DAY
------ ------------------ I - ------ ------------------
--------------------------- -------------------
RAT #
DESCRIPTION
------------ ----------------------------- ---I ------------- - ---------------------------- -------------------
8938
DS( 35- 36)
CHROMODACRYORRHEA
a
DS( 35- 36)
CLEAR ORAL EXUDATE
DS(
36
PTOSIS a
DS(
36
HUNCHED POSTURE
DS(
36
LABORED BREATHING
8939
DS(
36
DS( 56- 67)
MORIBUND LOCALIZED
SACRIFICED ALOPECIA:
LIMBS
DL( 1- 21)
LOCALIZED ALOPECIA:
LIMBS a
8940
NO ADVERSE FINDINGS
--------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
DG = DAY OF PRESUMED GESTATION
DL = DAY OF LACTATION
a. observation confirmed at necropsy.
PROTOCOL 418-008!
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C22 (PAGE 7): CLINICAL OBSERVATIONS
INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
-- -------- -- --------- --------------- - 11---
DOSAGE GROUP V
3.2 MG/KG/DAY
------------------ ---------------------- -
---
----
-----------
---------
----------------
- ----------
RAT
DESCRIPTION
------- ---------------- -------------------------- ------------
--------------- ------------------------- ----------------------------- ---------------------------------------
8941 8942
DS( DG(
6- 42) 0- 10)
LOCALIZED LOCALIZED NO ADVERSE
ALOPECIA: ALOPECIA:
FINDINGS
LIMBS LIMBS a
8943
NO ADVERSE FINDINGS
8944 8945 8946 8947 8948 8949
8950
DG( 18- 20)
DG( DL(
3- 20) I- 2)
LOCALIZED NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE LOCALIZED LOCALIZED NO ADVERSE
ALOPECIA: FINDINGS FINDINGS FINDINGS FINDINGS
ALOPECIA: ALOPECIA:
FINDINGS
UNDERSIDE
LIMBS LIMBS a
8951 8952 8953 8954
8955 8956
8957
DS( 20- 42) DG( 0- 10)
DG( IS- 20)
DL(
1
DL(
2
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
LOCALIZED
ALOPECIA:
LIMBS
LOCALIZED
ALOPECIA:
LIMBS a
NO ADVERSE FINDINGS
LOCALIZED
ALOPECIA:
BACK
LOCALIZED
ALOPECIA:
BACK
ALOPECIA
NO LONGER APPARENT
NO ADVERSE
FINDINGS
89se 8959 8960 8961 8962
DG( 10- 21)
NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE INCISORS:
FINDINGS FINDINGS FINDINGS FINDINGS MISALIGNED
8963 8964 8965 8966 8967
DL(
1
DG( DG( DL(
15- 20) 15- 20)
I
INCISORS: NO ADVERSE NO ADVERSE NO ADVERSE NO ADVERSE LOCALIZED LOCALIZED LOCALIZED
MISALIGNED FINDINGS FINDINGS FINDINGS FINDINGS ALOPECIA: ALOPECIA: ALOPECIA:
a
UNDERSIDE
BACK
UNDERSIDE
a
8968
DL(
1
LOCALIZED NO ADVERSE
ALOPECIA: FINDINGS
BACK a
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
DG = DAY OF PRESUMED
a. Observation confirmed at necropsy.
GESTATION
DL = DAY OF LACTATION
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C22 (PAGE 8): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
-------------------------DOSAGE GROUP V ---------- -----------------------
------------
3.2 MG/KG/DAY ------------
---------------- ------ ------- --------------------- --------------------------------------- ------------------------------
RAT #
DESCRIPTION
---------------------------------- ----------------------------------------------------------------------------
8969
DS( 38- 43) DG( 0- 21)
LOCALIZED LOCALIZED
ALOPECIA: ALOPECIA:
UNDERSIDE UNDERSIDE
8970
DL(
I)
DS( 37- 44)
LOCALIZED ALOPECIA;
UNDERSIDE a
INCISORS:
MISSING/BROKEN
DS( 38- 40)
CHROMODACRYORRHEA
DG( 0- 20)
INCISORS:
MISSING/BROKEN
DG( 9- 20)
CHROMODACRYORRHEA
DL( 1- 2)
INCISORS:
MISSING/BROKEN
a
8971
NO ADVERSE FINDINGS
8972
NO ADVERSE FINDINGS
8973
DG( 16- 21)
LOCALIZED
ALOPECIA:
BACK
DL( I- 2)
LOCALIZED
ALOPECIA:
BACK a
8974
NO ADVERSE FINDINGS
8975
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DS = DAY OF STUDY
DG = DAY OF PRESUMED
a. Observation confirmed at necropsy.
GESTATION
DL = DAY OF LACTATION
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NOMBER:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXIC
TABLE C23 (PAGE 1): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
---------------------- --- --- ------ ------- ----- ----------------- ------- --- ------------------- ---- --
DAY
1
--------------------------
8
is
22
29
------------------------
36
42a
--------------------------
- - ------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------------- ------------------------------ ---------------------------
8801
219.
217.
218.
224.
226.
226.
239.
8802
257.
252.
265.
268.
272.
289.
296.
8803
240.
243.
250.
258.
269.
272.
287.
8804
237.
241.
251.
255.
261.
256.
266.
8805
215.
220.
230.
226.
229.
234.
240.
8806
260.
262.
285.
270.
285.
296.
318.
8807
236.
243.
246.
253.
259.
264.
274.
8BO8
247.
248.
250.
266.
270.
266.
275.
8809
216.
226.
233.
228.
240.
246.
249.
8810
253.
255.
261.
268.
278.
262.
283.
8811
234.
238.
248.
246.
261.
261.
264.
8812
251.
254.
272.
283.
291.
297.
300.
8813
227.
226.
246.
248.
252.
265.
268.
8814
255.
260.
283.
286.
297.
302.
316.
8815
228.
227.
226.
233.
246.
241.
247.
8816
239.
251.
257.
252.
265.
271.
270.
8817
220.
213.
230.
225.
239.
247.
256.
8818
254.
284.
293.
309.
333.
339.
355.
8819
232.
241.
253.
249.
257.
273.
268.
8820
239.
235.
242.
246.
256.
253.
258.
8821
231.
246.
264.
264.
272.
274.
280.
8822
237.
249.
256.
257.
265.
271.
267.
8823
232.
245.
249.
248.
261.
265.
268.
8824
244.
256.
275.
274.
291.
305.
300.
8825
230.
235.
239.
250.
260.
260.
268.
8826
230.
244.
258.
250.
263.
258.
255.
--------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 41B 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBERT
6295.9)
AND PERINATAL/POSTNATAb
REPRODUCTION
TOXIC
TABLE C23 (PAGE 2): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
------ ------ --------------- ---- ----
-- ------------- - ---- ------------ ---
-------- -------
DAY
1
8
is
22
29
36
42a
------------- ---------------- ------------------- -----------------
----------------
----------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------------------------------------------------------------
-----------
8827 8828
234. 243.
240. 249.
247. 259.
246. 268.
254. 274.
260. 275.
259. 288.
8829
223.
239.
247.
250.
258.
259.
265.
8830
255.
2S?.
274.
278.
271.
276.
278.
8831
231.
240.
243.
250.
255.
257.
262.
8032
247.
263.
269.
200.
280.
28S.
284.
8833
236.
242.
247.
248.
263.
267.
266.
8834
248.
261.
272.
27S.
266.
303.
294.
8835
223.
231.
238.
236.
243.
239.
240.
--------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C23 (PAGE 3): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
----------------------------- -------- --------- ------------------
DAY
1
8
is
22
29
36
42a
---------------------------------------- ---------------------------
------- ----------------------------------------------
-------------------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------------------------------------------
--------------------------- -------------
8836
222.
223.
228.
232.
240.
241.
241.
8837
253.
258.
265.
272.
289.
285.
290.
8838
227.
240.
253.
248.
256.
267.
270.
8839
237.
235.
240.
239.
251.
256.
255@
8840
228.
224.
237.
244.
251.
265.
275.
8841
244.
247.
257.
258.
285.
290.
295.
8842
238.
244.
247.
258.
263.
264.
276.
8843
233.
247.
250.
257.
267.
274.
277.
8844
221.
228.
237.
239.
243.
253.
266.
8845
239.
251.
257.
258.
268.
272.
285.
8846
224.
228.
233.
233.
241.
246.
246.
8847
244.
252.
263.
264.
272.
278.
283.
8848
224.
236.
252.
248.
251.
255.
250.
8849
253.
259.
274.
265.
285.
289.
293.
8850
229.
238.
248.
252.
258.
267.
275.
8851
249.
255.
265.
266.
280.
290.
290.
8852
226.
229.
236.
238.
248.
253.
257.
8853
239.
249.
263.
258.
257.
262.
260.
8854
236.
249.
260.
269.
277.
279.
275.
Bess
245.
272.
268.
266.
274.
267.
278.
8856
225.
230.
239.
234.
238.
252.
246.
8857
249.
249.
254.
254.
268.
271.
274.
8858
231.
242.
243.
243.
255.
255.
258.
8859
246.
241.
251.
268.
265.
279.
289.
8860
234.
242.
256.
266.
280.
288.
290.
8861
242.
255.
264.
262.
270.
275.
274.
--------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Last value recorded before cohabitation.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C23 (PAGE 4): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
- ----------------------------------------
----- ---------------------- ----------------------
- - ------
DAY
1
a
15
22
29
36
42a
-------------------------------------------------- ----------------------------------------------- -----------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
------------------------------------------------------------------------- -------------------------------------
8862
236.
252.
258.
268.
269.
284.
209.
8863
243.
252.
260.
262.
258.
267.
270.
8864
229.
236.
238.
249.
251.
2S2.
256.
8865
243.
250.
263.
264.
269.
279.
278.
8866
235.
233.
246.
247.
253.
262.
265.
8867
236.
246.
2S5.
265.
265.
271.
275.
8868
223.
239.
251.
254.
256.
267.
273.
8869
252.
262.
276.
284.
291.
290.
298.
8870
238.
242.
247.
255.
260.
261.
263.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418-008:
COMBINED ORAL (GAVACE) FERTILITY,
DEVELOPMENTAI,
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295,9)
AND PER INATAL/ POST14ATAL REPRODUCTION
TOXICI
TABLE C23 (PAGE 5): BODY WEIGHTS - PRECOHABITATION
INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
------ --- ------------------------------ I ------------ -- ---- --- ---------------- -- -- --------------------
DAY
1
8
15
22
29
36
42a
---------- ------------------- -- -------------------- -- -------- ------------------- -----------------------
RAT
DOSAGE GROUP 111
0.4 MG/KG/DAY
--------------------------------- ---- --------------- -------------------------------------------------------
8871 8872 8873 8874
212. 254. 239. 237.
224. 256. 248. 248.
225. 269. 250. 245.
220. 274. 254. 254.
233. 276. 263. 270.
231. 275. 250. 272.
238. 204. 267. 278.
8875 8876 8877 8878 8879 8880 8881 8882 8803
221. 255. 232. 237. 223. 251. 223. 238. 230.
230. 269. 232. 247. 232. 251. 231. 248. 232.
239. 275. 236. 255. 242. 254. 248. 260. 246.
237. 271. 238. 252. 244. 268. 254. 262. 248.
241. 290. 239. 253. 252. 267. 256. 277. 261.
253. 294. 247. 261. 261. 273. 258. 292. 265.
254. 297. 248. 260. 275. 275. 265. 294. 262.
8884 8885 8886 8887 8888 8889
230. 231. 242. 229. 258. 229.
231. 254. 246. 238. 271. 238.
241. 264. 255. 246. 277. 245.
234. 269. 258. 253. 284. 248.
234. 294. 267. 262. 291. 256.
233. 300. 274. 266. 295. 263.
240. 299. 272. 265. 297. 262,
8890
241.
263.
273.
275.
291.
298.
302.
8891
222.
232.
241.
238.
246.
249.
254.
8892
245.
252.
260.
258.
275.
272.
273.
8893
236.
245.
250.
258.
262.
264.
261.
8894
253.
269.
276.
281.
295.
297.
300.
8895 8896
223. 248.
228. 249.
229. 261.
234. 260.
237. 267.
233. 276.
237. 271.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C23 (PAGE 6): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
-------------------------------------- ------- ---------------------- -------------------- ----------------------
DAY
1
8
is
22
29
36
42a
---------------------- ------------- ---- --- ---------------------- -------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------------- -----------------------------------------------------------------
6897
232.
247.
258.
263.
275.
279.
281.
8898
257.
273.
282.
285.
284.
289.
294.
8899
240.
241.
252.
262.
284.
278.
283.
8900
240.
247.
259.
260.
270.
266.
265.
8901
232.
238.
243.
239.
254.
261.
262.
8902
255.
266.
217.
265.
282.
294.
297.
8903
232.
242.
251.
249.
262.
260.
261.
8904
247.
252.
266.
274.
282.
262.
288.
8905
225.
229.
226.
231.
239.
238.
246.
----------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C23 (PAGE 7): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA
Po GENERATION
FEMALE RATS
---------------------------- ---------------- ------ ---------------- ----- -----------------------
------
DAY
1
8
15
22
29
36
42a
-------------------------------------------- ------- -------------------------------------------- ---- --------
RAT #
DOSAGE GROUP IV
--------------------------------------------
1.6 MG/KG/DAY -- --------------------------------------------------------------
8906
220.
223.
229.
234.
233.
243.
246.
8907
259.
260.
264.
265.
275.
277.
277.
8908
243.
256.
252.
250.
258.
258.
257.
8909
226.
226.
237.
229.
238.
243.
239.
8910
22S.
234.
243.
244.
252.
254.
261.
8911
252.
253.
258.
259.
269.
263.
270.
8912
238.
242.
245.
248.
253.
256.
258.
8913
242.
245.
253.
251.
256.
262.
261.
8914
216.
215.
227.
222.
221.
218.
228.
8915
261.
272.
290.
309.
302.
308.
312.
8916
226.
227.
241.
235.
242.
245.
252.
8917
248.
250.
257.
260.
268.
270.
274.
8918
223.
239.
249.
242.
252.
257.
254.
8919
250.
258.
269.
262.
292.
291.
299.
8920
239.
251.
260.
259.
270.
267.
272.
8921
241.
249.
256.
259.
266.
265.
268.
8922
230.
226.
234.
226.
234.
234.
231.
8923
248.
244.
254.
239.
254.
247.
256.
8924
243.
242.
250.
243.
257.
261.
261.
8925
242.
246.
253.
254.
266.
265.
270.
8926
222.
225.
235.
240.
245.
241.
243.
8927
245.
249.
254.
256.
267.
266.
265.
8928
234.
232.
243.
242.
243.
246.
254.
8929
245.
254.
254.
253.
256.
255.
256.
8930
229.
241.
251.
255.
257.
260.
259.
8931
254.
257.
273.
272.
276.
274.
288.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418-008:
COMBINED ORAL ((3AVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RA7S (SPONSOR'S STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICI
TABLE C23 (PAGE 8); BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
- ---------------------- I -------------------------
DAY
1
8
15
22
29
36
42a-------------------- --- - --------------------
- ----------------------
-------------------------------------------------
RAT #
DOSAGE GROUP IV --------------1-.-6 --M-G-/K-G-/-DA-Y-
----------------------- ---------------------------- -------------------------------------------------
8932
221.
228.
238.
232.
241.
241.
242.
8933
240.
244.
249.
248.
272.
273.
268.
8934
226.
224.
228.
232.
235.
232.
242.
8935
244.
254.
263.
264.
262.
266.
266.
8936
240.
251.
255.
269.
267.
273.
277.
8937
251.
264.
264.
272.
278.
276.
280.
8938
231.
244.
245.
247.
250.
219.
MORIBUND SACRIFICED
ON DAY 36 OF STUDY
8939
241.
248.
257.
264.
272.
275.
273.
8940
248.
263.
272.
289.
293.
302.
304.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C23 (PAGE 9): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
--------- -
DAY -------------
------------ ----- -- - --- ---------------------
1
a
is
22
29
36
42a
--------------------- -- --------------------------
- - ----------------------
-------------
- - --------------------- -----------------
RAT N
DOSAGE GROUP V
------------- ------------------------
3.2 MG/KG/DAY -----------------------------------------------------------------
8941 8942 8943 8944 8945 8946 8947
225. 252. 232. 227. 220. 255. 239.
224. 249. 227. 230. 222. 267. 237.
225. 256. 230. 226. 219. 264. 239.
228. 253. 217. 220. 222. 259. 234.
218. 256. 224. 227. 222. 261. 239.
220. 257. 219. 218. 219. 255, 236.
227. 263. 214. 224. 218. 256. 239.
8948
248.
244.
245.
245.
255.
247.
247.
8949 8950 8951 8952 8953 8954 8955 8956
215. 250. 238. 238. 225. 249. 220. 236.
218. 254. 248. 236.
224. 247. 220. 238.
213. 247. 246. 241. 226. 250. 230. 236.
216. 247. 247. 238. 218. 249. 221. 241.
213. 246. 248. 232. 226. 252. 226. 229.
213. 252. 244. 235. 226. 254. 222. 232.
211. 261. 244. 238. 228. 264. 233. 230.
8957 8958
226. 253.
231. 253.
233. 250.
222. 249.
229. 252.
222. 254.
237. 261.
8959 8960 8961 8962 8963 8964 8965 8966
235. 242. 219. 245. 237. 234. 231. 239.
247. 255. 226. 253. 242. 238. 232. 245.
252. 264. 219. 255. 240. 232. 231. 243.
250. 266. 226. 248. 243. 240. 234. 248.
248. 272. 218. 254. 240. 241. 241. 244.
245. 264. 219. 250.
237. 238. 241. 243.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C23 (PAGE 10): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
-------------------------
DAY
1
-------------------------
------
6 ------
-----
15 -----
------- ------ -- -------- -------------- --------------------------- -
22
29
36
42a
------ ------- ---------------------------- ------------------- ---------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
------------------------- -------------------------------------------------------------------------------------
8967
230.
235.
234.
224.
237.
242.
241.
8968
238.
235.
246.
241.
238.
230.
237.
8969
227.
231.
231.
233.
234.
226.
232.
8970
249.
268.
269.
279.
278.
246.
260.
8971
238.
250.
256.
258.
265.
266.
264.
8972
238.
235.
223.
220.
221.
216.
219.
8973
238.
239.
238.
235.
240.
242.
243.
8974
236.
241.
234.
237.
230.
228.
229.
8975
236.
240.
244@
242.
241.
243.
252.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C24 (PAGE 1) : MATERNAL BODY WEIGHTS - PRESUMED GESTAI ION - INDIVIDUAL
DATA - Fo GENERATION
FEMALE RAT
-----
-- --- --------------------
PREGNANCY
--- ------------------ ---- ---------------------------------- -------
STATUS ------------
DAY 0
1
------------------------
2
3
4
I --- ------------------
5
6
7
8
9
1
-------------I ----------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
------------------------------------- -----------------------------------------------------------------------
8801 p 8802 P 8803 P 8804 P 8805 p 8806 P 8807 P 8808 p 6809 p 8810 p 8811 P 8812 P
232.
240.
245.
243.
245.
244.
252.
249.
253.
257.
26
290.
298.
304.
312.
312.
320.
321.
324.
330,
335.
33
274.
282.
286.
293.
292.
299.
299.
298.
308.
308.
30
269.
278.
282.
291.
297.
301.
299.
305.
307.
315.
31
249.
254.
261.
256.
263.
266.
268.
268.
273.
279.
28
315.
322.
322.
326.
331.
339.
340.
342.
346,
353.
35
271.
284.
286.
285.
290.
297.
296.
298.
304.
303.
31
269.
283.
282.
285.
282.
287.
285.
289.
295.
287.
29
247.
256.
256.
256.
266.
264.
263.
266.
270.
276.
28
283.
288.
293.
290.
297.
296.
305.
303.
305.
311.
30
266.
273.
275.
284.
282.
285.
288.
292.
295.
297.
30
NO CONFIRMED
MATING DATE
8813 P 8814 P 0815 p 8816 P 8817 NP 8818 NP 8819 p 8820 P 8821 P 8822 P 8823 P 8824 P 8825 P
269.
283.
283.
285.
287.
286.
297.
300.
300.
303.
30
311.
317.
325.
320.
329.
329.
335.
340.
344.
349.
35
238.
246.
259.
259.
269.
275.
277.
278.
281.
286.
30
254.
269.
276.
275.
277.
281.
292.
29S.
292.
299.
31
268.
260.
256.
266.
264.
268.
270.
271.
271.
269.
26
349.
360.
356.
364.
370.
363.
372.
378.
378.
380.
377
268.
274.
282.
280.
290.
292.
293.
300.
299.
304.
309
253.
260.
267.
267.
272.
275.
277.
279.
283.
286.
291
277.
281.
288.
292.
292.
301.
299.
302.
313.
307.
313
265.
269.
277.
276.
282.
282.
285.
288.
290.
295.
299
272.
273.
275.
280.
281.
277.
287.
283.
287.
293.
295
298.
300.
298.
306.
306.
305.
306.
305.
314.
316.
322
262.
271.
279.
280.
204.
281.
284.
285.
289.
294.
299
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBERI
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C24 (PAGE 2): MATERNAL BODY WEIGHTS
PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
-------------------PREGNANCY
------------------
-- - --------------------- ---- -- ------------------
---------------
STATUS
DAY 0
1
2
3
4
5
6
7
8
--------------------------------------- --------------------------------------------------------
9
10
---------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
-----------------------------------------------------------------------------------------------
------------
8826 P
258.
272.
276.
282.
284.
288.
292.
293.
299.
302.
7 308.
8827 P
271.
275.
280.
284.
266.
208.
292.
294.
298.
304.
308.
8828 P 8829 P 8830 P 8831 P
283. 270. 278. 262.
290. 277. 281. 263.
296. 284. 287. 268.
299. 286. 287. 275.
304. 287. 289. 275.
300. 290. 292. 276.
304. 291. 296. 280.
312. 294. 298. 284.
308. 300. 299. 284.
313. 298. 307. 290.
320. 311. 306. 293,
8832 P
288.
285.
293.
297.
302.
303.
310.
309.
317.
315.
323.
8833 P
265.
277.
276.
280.
283.
286.
290,
286.
293.
292.
299.
8834 P
292.
296.
298.
305.
310.
317.
314.
317.
323.
327.
330.
8835 P
247.
250.
259.
262.
266.
270.
274.
280.
280.
286.
289.
----------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY - DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C24 (PAGE 3): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
--------------------- ------------------------- -- ---------------------- -- - ---------------------------- ----
PREGNANCY
STATUS
DAY 13
14
15
16
17
18
19
------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------------------------------------- ---
8801 p
270.
274.
280.
286.
294.
308.
324.
8802 P
20
21
22
23
---------------------------------
---------------------------------
330.
340.
8803 P 8804 P 8805 p 8806 p
320. 328. 293.
332. 330. 299.
339. 341. 306.
347. 354. 310.
354. 365. 330.
375. 387. 339.
387. 393,. 350.
400. 412. 368.
413. 423. 382.
8807 P 8808 p 8809 p
324. 314.
330. 322.
334. 326.
341. 333.
358. 346.
373. 354.
388. 373.
394. 382.
411. 389.
8810 p
8811 p 8812 P
316.
322.
333.
NO CONFIRMED
MATING DATE
342.
354.
365.
378.
387.
400.
8813 P 8814 P 8815 p
320. 369.
326. 374.
336. 378.
338. 387.
351. 404.
369. 428.
368. 430.
377. 450.
396. 465.
8816 p
8817 NP 8818 NP 8819 P 8820 P
274. 381. 329.
276@ 375. 332.
264. 376. 337.
262. 382. 356.
263. 384. 370.
263. 388. 383.
261. 368. 390.
259. 353. 413.
261. 373. 424.
265. 384.
264. 375.
8821 P 8822 P
330.
337.
342.
351.
368@
385.
418.
408.
428.
8823 P 8824 P 8825 P
304. 330.
307. 336.
312. 340.
322. 352.
336. 368.
344. 384.
355. 398.
364. 404.
411.
----------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED
IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGEI PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NLTMBER: 6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICI
TABLE C24 (PAGE 4): MATERNAL BODY WEIGHTS
PRESUMED GESTATION
- INDIVIDUAL
DATA
Fo GENERATION
FEMALE PATS
-- ---- ------------------- -------- ------ ------- --- - --------------------------------------------- -----
PREGNANCY
STATUS
DAY 13
14
15
16
17
18
19
20
21
22
23
------- ------------------- --------- --------------------- ---------------------------------------------------
RAT #
DOSAGE GROUP 1
------- -----------------------------
0 (VEHICLE) MG/KG/DAY ------- ------------------------------------------------------------------
8826 P 8827 P 8828 P 8829 P
315. 317. 335.
323. 322. 333.
330. 328. 343.
336. 337. 360.
347. 348. 376.
355. 363. 388.
362. 378. 406.
377. 390. 413.
384. 404. 432.
8830 P
316.
322.
330.
338.
359.
380.
387.
402.
414.
8831 P
310.
310.
320.
332.
348.
357.
372.
392.
403.
8832 P
343.
349.
3S6.
370.
384.
402.
412.
429.
437.
8833 P
310.
312.
319.
331.
343.
365.
377.
403.
400.
8834 P
346.
350.
363.
376.
398.
410.
430.
450.
458.
8835 P
305.
308.
316.
325.
337.
346.
362.
377.
380.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT DAY = DAY OF
MP = NOT PREGNANT PRESUMED GESTATION
(VALUES EXCLUDED FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTA1,
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C24 (PAGE 5): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
INDIVIDUAL
DATA - Fo GENERATION
FEMALE PATS
PR-E-GN-A-NC-Y------------------------- ------- -------------------
--------------------- ------ ----------------
STATUS
DAY 0
1
2
3
4
----------------------------------------------------------------
5
6
7
8
9
10
------------------------------ ----------------
RAT #
DOSAGE GROUP 11
--------------------------------------------
0.1 MG/KG/DAY -------------------------------------------------------------------
8836 P 8837 P 8836 P 8839 P 8840 P 8641 P 8842 P
237. 282. 268. 256. 272. 306. 262.
244. 297. 270. 266. 276. 307. 267.
246. 303. 276. 270. 286. 306. 279.
248. 310. 280. 267. 284. 311. 278.
252. 317. 284. 270. 290. 316. 284.
257. 318. 287. 277.
293. 320. 283.
260. 325. 293. 280. 296. 323. 282.
258. 325. 295. 284.
299. 324. 280.
260. 327. 295. 282. 306. 328. 290.
263. 332. 305. 284. 310. 330. 290.
267. 348. 306. 290. 314. 343. 303.
8843 P
266.
274.
288.
287.
292.
294.
301.
297.
298.
306.
308.
8844 P 8845 P 8846 P 8847 P 8848 P 6849 P
259. 285. 246. 279. 244. 294.
257. 296. 252. 279. 251. 294.
266. 295. 258. 290. 260. 302.
268. 299. 260. 290. 263. 302.
268. 304. 266. 297. 269. 304.
270. 303. 263. 295. 270. 312.
271. 305. 264. 295. 272. 306.
267. 309. 268. 303. 279. 304.
272. 311. 269. 299. 279. 311.
280. 309. 272. 309. 284. 316.
289. 317. 277. 309. 294. 320.
8850 NP 8851 p
268. 291.
274. 296.
285. 301.
286. 310.
286. 308.
295. 310.
294. 315.
294, 314.
295. 320.
297. 320.
309. 324.
8852 P
261.
264.
270.
270.
269.
273.
279.
270.
280.
278.
284.
8853 P
264.
270.
277.
281.
281.
281.
285.
291.
286.
288.
294.
8854 P
279.
278.
280.
290.
288.
288.
299.
296.
297.
303.
303.
8855 P
272.
281.
282.
288.
291.
291.
295.
292.
298.
304.
312.
0856 NP
a
a
252.
265.
258.
258.
256.
257.
254.
254.
259.
8857 P
268.
273.
279.
282.
280.
280.
279.
283.
286.
290.
294.
8858 p
2S8.
262.
264.
271.
273.
274.
277.
280.
281.
284.
288.
8859 P
207.
285.
286.
298.
302.
302.
310.
301.
309.
310.
314.
8860 P
293.
298.
303.
308.
307.
304.
311.
309.
310.
316.
319.
----------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT
DAY = DAY OF PRESUMED GESTATION
(VALUES EXCLUDED
FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Value was not recorded.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C24 (PAGE 6): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL
DATA - Fo GENERAT10N
FEMALE PATS
------------ -------------------------------PREGNANCY
----------- --------
----------------------------- ------- -------
STATUS
DAY 0
1
2
3
4
5
6
7
8
9
10
------------ ---------------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 11
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.
298. 311. 288. 276. 299. 291. 294. 294. 315. 289.
301. 318. 287. 277. 297.
292. 293. 296. 318. 293.
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.
----------------------------------------------------------------------------------------------------------------
P = PREGNANT
MP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C24 (PAGE 7): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
----------- -------------- ---------------------------- ------------------------PREGNANCY
-------------- -------------
STATUS
DAY 13
14
is
16
17
18
19
20
21
22
23
------------------------------------------------------- -------------------------------------------------------
RAT #
DOSAGE GROUP Il
0.1 MG/KG/DAY
----------------------------------------------------- ---------------------------------------------------------
8836 P
8837 P
8838 P 8839 P
321.
322.
332.
340.
363.
382.
392.
409.
421.
8840 P 8841 P 8842 P 8843 P
327. 356. 298.
335. 360. 309.
345. 366. 319.
354. 377. 338.
377. 376. 344.
393. 393. 367.
401. 405. 384.
420. 421. 395.
426. 433. 405.
8844 P
8845 P 8846 P 8847 P 8848 P
332. 290. 321.
337. 295. 324.
346. 301. 330.
354. 313. 338.
369. 321. 351.
377. 340. 374.
385. 347. 382.
401. 361. 386.
410. 370. 404.
8849 P 8850 NP
332.
343.
358.
370.
382.
396.
411.
422.
8851 P 8852 P 8853 P 8854 P 8855 P 8856 NP
336. 295. 311. 322. 328.
346. 299. 319. 326. 332.
348. 300. 332. 331. 337.
358. 312. 337. 338. 346.
376. 322. 352. 354. 370.
384. 325. 381. 359. 376.
395. 341. 393. 378. 388.
413. 352. 405. 402. 403.
432. 366. 425. 410. 416.
8857 P 8858 P 8859 P
312. 305.
315. 313.
319. 318.
328. 330.
349. 349.
358. 358.
373. 374.
385. 389.
398. 410.
8860 p
335.
341.
349.
356.
377.
386.
404.
411.
427.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
PERTILI STUDY
r),, DEVELOPMENTAL NIJMBER: 6295.9)
AND PER INA'I'AL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE C24 (PAGE 8): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
------------------- ------- -------------------PREGNANCY
------------------------ -------------------- ------ ----
STATUS
DAY 13
14
is
16
-------------------------------------------------
RAT #
DOSAGE GROUP 11
0.1
-------------------------------------------------
17
18
19
-------------------------
20
21
22
23
--------------------------------
MG/KG/DAY - -----------------------------------------------------------
8861 NP
8862 P
348.
3Sl.
359.
373.
382.
400.
402.
423.
432.
8863 P
313.
318.
327.
331.
349.
370.
379.
398.
8864 P 8865 P
299. 317.
301. 320.
307. 333.
319. 339.
329. 356.
338. 359.
349. 370.
364. 381.
366. 398.
8866 P
320.
323.
327.
341.
356.
367.
388.
401.
412.
8867 P
317.
324.
329.
339.
352.
373.
382.
393.
403.
299
8868 P
326.
329.
335.
342.
357.
376.
384.
403.
406.
8869 P
344.
349.
3S7.
368.
385.
399.
407.
424.
446.
8870 P
304.
305.
313.
326.
341.
343.
364.
375.
374.
----------------------------------------------------------------------------------------------------------------
P = PREGNANT DAY = DAY OF
NP = NOT PREGNANT PRESUMED GESTATION
(VALUES EXCLUDED FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C24 (PACE 9): MATERNAL BODY WEIGHTS
PRESUMED GESTATION - INDIVIDUAL
DATA - Fo GENERATION
FEMALE RAT
----------- ------- --------- --- ------PREGNANCY
---- --- - -------------------------------------- --------
STATUS
DAY 0
1
2
3
4
5
6
7
8
9
1
-------------------------------
RAT
DOSAGE GROUP -11-1--------------0-.4- M-G-/K-G-/-D-AY--- -------------------------------------------- -----
--------------------------------------------------------------------------------------------------------------
8871 NP
MATING NOT CONFIRMED
8872 P
282.
285.
291.
298.
302.
307.
301.
306.
303.
310.
31
8873 P
259.
266.
268.
276.
271.
278.
280.
282.
284.
290.
30
8874 P
281.
261.
286.
291.
293.
296.
301.
300.
301.
304.
31
887S P
262.
266.
265.
271.
266.
268.
271.
275.
279.
279.
28
8876 P 8877 P 8878 NP
294.
309.
311.
315.
319.
318.
321.
320.
328.
330.
33
238.
251.
251.
257.
254.
261.
265.
264.
266.
271.
27
262.
264.
262.
266.
264.
268.
275.
271.
273.
277.
28
8879 MP
276.
277.
270.
265.
261.
265.
259.
260.
256.
264.
26
8880 p
274.
284.
293.
296.
301.
301.
302.
308.
307.
309.
31
8881 p
259.
266.
268.
270.
273.
280.
278.
280.
279.
285.
28
8882 P
289.
302.
299.
295.
299.
296.
299.
296.
304.
302.
30
8883 NP
251.
261.
262.
270.
278.
277.
284.
283.
281.
275.
28
8884 P
236.
242.
251.
251.
256.
257.
262.
263.
266.
267.
28
8885 P 8886 NP
309.
316.
319.
332.
329.
333.
336.
336.
346.
349.
35
273.
278.
276.
280.
284.
287.
289.
289.
290.
296.
30
8887 P
266.
269.
276.
274.
274.
272.
288.
285.
288.
291.
29
8888 p
292.
295.
304.
306.
304.
310.
312.
310.
314.
322.
32
8889 p
286.
286.
294.
297.
298.
298.
294.
300.
296.
302.
30
8890 p
292.
302.
308.
310.
309.
315.
320.
322.
325.
327.
32
8891 P
262.
264.
266.
273.
272.
277.
279.
280.
286.
294.
29
8892 P
277.
275.
283.
279.
279.
283.
287.
294.
299.
303.
30
8893 P
26S.
268.
280.
276.
278.
281.
280.
283.
288.
289.
29
8894 P
302.
306.
307.
314.
309.
316.
318.
318.
319.
322.
32
8895 p
234.
238.
244.
246.
244.
254.
256.
255.
261.
266.
27
--------------------------------------------------------------------------------------------------------------
P = PREGNANT DAY = DAY OF
NP = NOT PREGNANT PRESUMED GESTATION
(VALUES EXCLUDED FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C24 (PAGE 10): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
---------- -- --- ----------- I - -------- -- ---------------- - -------- I -----------
-----------
PREGNANCY
STATUS
DAY 0
1
2
3
4
5
6
7
----------- -- -------------------- ------- ----------------------- ----------- ---------
8
9
10
--------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------- -- ----------------------------------------------------
-------------------------------------------
8896 p
264.
268.
276.
280.
284.
289.
289.
289.
297.
304.
307
8897 P
269.
281.
279.
290.
288.
302.
299.
300.
301.
308.
315
8898 P
297.
299.
305.
300.
311.
311.
314.
315.
315.
319.
320
8899 p
289.
288.
292.
294.
299.
304.
308.
308.
312.
314.
321
8900 p
258.
266.
270.
280.
282.
281.
290.
291.
287.
294.
305
8901 p
260.
266.
271.
273.
266.
271.
278.
276.
275.
282.
282
8902 P
288.
298.
302.
303.
307.
312.
315.
317.
327.
328.
332
8903 NP
256.
254.
265.
271.
279.
282.
281.
287.
290.
287.
292
8904 NP
286.
284.
291.
294.
290.
287.
294.
293.
295.
293.
297
890S p
251.
253.
253.
258.
262.
265.
265.
267.
276.
273.
280
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RAIS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PEPINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C24 (PAGE 11): MATERNAL. BODY WEIGHTS
PRESUMED GESTATION
- INDIVIDUAI, DATA - Fo GENERATION
FEMALE RATS
---------------PREGNANCY
----------
---------------
-------------------
-- ------------ ------------
STATUS
DAY 13
14
is
16
17
18
19
20
21
22
23
------------------------------ ---------------- ----- ----------------------- ---------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------------------- -----------------------------------------------------
---------------------------------
8871 NP
MATING NOT CONFIRMED
8872 P 8873 P
325.
331.
340.
352.
372.
389.
410.
425.
430.
8874 P 8875 P 8876 P 8877 P
324. 296. 351.
330. 302. 351.
340. 306. 357.
352. 318. 367.
363. 331. 382.
388. 342. 380.
393. 357. 396.
408. 370. 399.
410. 411.
8878 NP
8879 NP
8880 P
8881 p 8882 P 6883 NP
301. 320.
300. 320.
308. 329.
318. 345.
329. 363.
336. 382.
359. 398,
364. 414.
381. 423.
8884 P
8885 p 8886 NP
370.
373.
383.
396.
407.
416.
435.
454.
471.
8887 P
8888 p
8889 p
312.
318.
319.
333.
347.
361.
373.
386.
8890 p
338.
346.
351.
358.
371.
386.
393.
413.
42S.
8891 p
307.
316.
327.
341.
359.
371.
388.
396.
8892 P
322.
328.
332.
351.
350.
362.
371.
386.
385.
8893 P
303.
314.
321.
332.
351.
360.
378.
393.
373.
8894 P
332.
342.
338.
345.
349.
356.
366.
371.
379.
380.
8895 p
290.
294.
305.
314.
336.
346.
364.
387.
393.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PPOS IN RATS (SPONSOR'S STUIIY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C24 (PAGE 12): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL
DATA - Fo GENERATION
FEMALE RAT
--- ---------------------------PREGNANCY
- ---------- -------------- -------------- ----------- ------------
STATUS
DAY 13
14
15
16
17
18
19
20
21
22
2
----- ------------------ -------------- ----------------------------- ----------------------------
PAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
-----------------------------------------------------------------------------
---------------------------------
8896 p
314.
318.
325.
328.
345.
356.
370.
380.
8897 P
323.
329.
340.
351.
368.
378.
391.
408.
8898 p 8899 p 8900 p 8901 p 8902 P 8903 NP 8904 NP 8905 P
332. 333.
339. 340.
3SO. 345.
353. 35S.
364. 369.
382. 377.
386. 390.
393. 405.
407.
313.
326.
333.
339.
36S.
372.
379.
395.
409.
306.
308.
314.
329.
344.
352.
363.
372.
380.
343.
351.
354.
363.
380.
402.
419.
434.
427.
290.
295.
296.
288.
292.
292.
285.
285.
283.
284.
280
296.
301.
301.
297.
298.
298.
298.
297.
292.
295.
292
298.
301.
312.
326.
341.
359.
380.
391.
397.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT DAY = DAY OF
NP = NOT PREGNANT PRESUMED GESTATION
(VALUES EXCLUDED FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS ISPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
-roxICIT
TABLE C24 (PAGE 13): MATERNAL BODY WEIGHTS - PRESIJMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
------ ------------ ------------ - - - --------
-- ------- -----------------------------------------
PREGNANCY
STATUS
DAY 0
1
-------------------- ------------ ---
RAT N
DOSAGE GROUP IV
-------------------- ----------------
2
3
---------
1.6 ----------
4
5
6
7
8
9
------------------------------------------------------
MG/KG/DAY -------------------------------------------------------
10 ------
------
8906 p
NO CONFIRMED
MATING DATE
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
275.
282.
278.
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. 249.
255. 260.
255. 263.
263.
267.
276.
236.
244.
243.
262.
271.
279.
250.
254.
261.
256.
264.
268.
NO CONFIRMED MATING DATE
270. 268. 258. 270. 283. 264. 277. 234. 32S. 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.
274. 268. 261. 268. 285. 269. 278. 233. 334. 262. 294. 274. 313. 285. 264. 236. 255. 270. 207. 250. 290. 262. 275.
276. 274. 262. 274. 290. 275. 279. 237. 335. 265. 291. 279. 316. 287. 277. 240. 258. 273. 288.
251. 289. 263. 277.
272. 272. 264. 269. 290. 275, 284. 242. 339. 261. 293. 279. 328. 287. 278. 241. 254. 270. 297. 253. 286. 268. 283.
270. 274. 266. 273. 291. 276. 285. 239. 342. 271. 299. 287. 327. 291. 282. 244. 256. 276. 292. 254. 290. 272. 284.
272. 278. 273. 277. 299. 282. 290. 240. 346. 270. 298. 283. 333. 293. 280, 246. 259. 276. 294. 258. 298. 275. 286.
277. 276. 279. 283. 308. 295.
293. 244. 354. 283. 314. 290. 341. 299. 289. 254. 263. 280. 296. 260. 298. 279. 291.
-----------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICIT
TABLE C24 (PAGE 14): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL
DATA - Po GENERATION
FEMALE RATS
-- -------------------------- ---PREGNANCY
------------ ----------
----------- - - ------------ ----------- -------
STATUS
DAY 0
1
-------------------------- ----
2
3
4
5
6
7
8
9
10
------------ ---------- ------------------ ------------------------- -------
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
------------------------------------------------ ---------------------------------------------------------------
8931 P 8932 P 8933 NP 8934 P 8935 P 8936 P 8937 P 8938
288. 237. 271. 234. 261. 279. 281. MORIBUND
291.
282.
247.
250.
274.
27S.
239.
241.
266.
264.
286.
286.
284.
287.
SACRIFICED
ON DAY
288. 251. 281. 245. 263. 290. 288. 36 OF
298. 252. 282. 249. 265. 293. 294. STUDY
289. 256. 286. 246. 272. 294. 299.
303. 257. 289. 254. 271. 295. 300.
296. 260. 297. 257. 277. 299. 297.
298. 265. 296. 259. 283. 298. 306.
308. 267. 298. 262. 277. 303. 301.
304. 266. 301. 274. 285. 308. 297.
8939 P
NO CONFIRMED
MATING DATE
8940 P
298.
304.
308.
302.
307.
315.
318.
322.
.322.
319.
324.
----------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT
(VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVACE@ PFOS IN RATS (SPONSOR'S
FSRTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C24 (PAGE 15): MATERNAL BODY WEIGHTS
PRESUMED GESTATION
- INDIVIDUAL
DATA - Po GENERATION
FEMALE RAT
--------------PREGNANCY
------- ----- - ----------
----- - ------------------
- -- --- -----------------
STATUS
DAY 13
14
15
16
17
18
19
--------------- ---------------- -----------------------------------------------
20
21
22
2
- --------------------------
RAT #
DOSAGE GROUP
IV
GROUP IV
1.6 MG/KG/DAY
-------------------------------- --- I ------- --------------------------------------
--------------------------
8906 p
NO CONFIRMED
MATING DATE
8907 NP
8908 P
8909 p 8910 p
292.
296.
302.
312.
322.
333.
345.
351.
366.
8911 p
8912 P
8913 P 8914 MP 8915 P
299.
308.
318.
330.
343.
351.
365.
381.
245.
239.
240.
240.
240.
236.
241.
238.
234.
238.
23
8916 P
8917 P
8918 NP 8919 p 8920 P 8921 P 8922 P
302.
285.
276.
277.
273.
270.
276.
274.
270.
271.
27
357.
365.
374.
389.
412.
427.
436.
452.
309.
316.
320.
334.
346.
352.
364.
376.
389.
300@
300.
308.
317.
336.
350.
362.
372.
390.
8923 NP 8924 P
266.
264.
264.
260.
263.
262.
252.
246.
242.
248.
24
8925 P 8926 P 8927 P 8928 P 8929 P 8930 P
312.
316.
324.
270.
273.
281.
318.
323.
333.
293.
296.
307.
302.
306.
319.
NO CONFIRMED MATING DATE
328. 294. 341. 316. 326.
338. 306. 363. 327. 338.
354. 323. 380. 340. 355.
371. 329. 400. 350. 360.
386. 343. 424. 357. 369.
395.
373. 391.
--------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE@ PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C24 (PACE 16): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATI
---------------------------PREGNANCY
------ ------
-------------- --- --- ----- ------------------ - ----- I -----------
STATUS
DAY 13
14
is
16
17
is
19
20
21
---------------------------------------------------------------- ----------------------------
22
23
-----------------
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
321.
324.
335.
338.
356.
376.
396.
408.
413.
283.
287.
298.
312.
326.
341.
360.
377.
282.
280.
278.
278.
278.
280.
282.
277.
271.
282.
282
286.
283.
295.
313,
329.
341.
355.
369.
296.
309.
313.
315.
337.
349.
360.
373.
323.
325.
337.
351.
365.
377.
393.
404.
408.
319.
328.
330.
340.
346.
360.
374.
368.
405.
MORIBUND
SACRIFICED
ON DAY 26 OF STUDY
NO CONFIRMED MATING DATE
8940 P
338.
336.
349.
365.
382.
406.
425.
434.
---------------------------------------------------------------------------------------------------------------
P - PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 41B-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C24 (PAGE 17): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
-----------------PREGNANCY
--------------------------
--- ----- ------ --- -
----------------------- ---------
STATUS
DAY 0
1
2
3
-------------------------------------------------
RAT #
DOSAGE GROUP V
3.2
4
5
6
-------------------------
MG/KG/DAY
7
8
9
10
----------------------------------
----------------------------------------------------------------------------------------------------------------
8941 P
217.
226.
219.
224.
221.
220.
225.
228.
230.
231.
241.
8942 P
268.
260.
274.
276.
279.
279.
288.
286.
292.
289.
294.
8943 P
217.
218.
219.
213.
216.
216.
218.
218.
221.
228.
235.
8944 P
219.
222.
226.
224.
227.
226.
231.
232.
230.
232.
236.
8945 NP
221.
228.
235.
229.
233.
228.
230.
234.
231.
238.
238.
8946 P
274.
272.
277.
273.
280.
278.
277.
289.
285.
287.
293.
8947 P
242.
243.
248.
250.
253.
255.
252.
265.
266.
269.
287.
8948 P
237.
241.
234.
229.
228.
233.
246.
250.
253.
263.
268.
8949 P
208.
215.
214.
219.
225.
226.
230.
228.
232.
231.
238.
8950 p
262.
269.
270.
269.
269.
276.
278.
278.
279.
283.
288.
8951 P
232.
246.
242.
238.
247.
246.
249.
255.
256.
257.
259.
8952 NP
232.
237.
237.
238.
237.
244.
242.
234.
242.
245.
246.
8953 P
224.
232.
234.
234.
232.
237.
242.
240.
246.
245,
248.
8954 P
249.
255.
264.
266.
272.
266.
272.
276.
271.
276.
277.
8955 P
218.
230.
233.
233.
231.
238.
237.
235.
239.
241.
250.
8956 P
233.
237.
236.
242.
238.
245.
244.
243.
246.
253.
259.
8957 NP
218.
227.
226.
226.
237.
231.
236.
235.
240.
244.
243.
8958 P
260.
263.
265.
264.
268.
259.
283.
266.
263.
273.
264.
89s9 p
258.
258.
257.
254.
259.
261.
270.
267.
262.
260.
270.
8960 p
264.
262.
267.
268.
270.
274.
274.
274.
286.
283.
291.
8961 P
226.
236,
230.
228.
236.
235.
236.
241.
235.
240.
242.
8962 P
244.
263.
256.
268.
260.
263.
262.
272.
262.
262.
265.
8963 NP
219.
239.
245.
244.
252.
246.
247.
252.
257.
259,
258.
8964 P
239.
240.
245.
241.
238.
241.
245.
250.
246.
251.
265.
896S P
238.
241.
241.
242.
241.
244.
246.
252.
257.
257.
266.
----------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT
DAY = DAY OF PRESUMED GESTATION
(VALUES EXCLUDED
FROM AVERAGES)
ALL WEIGHTS WERE RECORDED
IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORA], (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVEBOPMENTAL
STUDY NUMBER!
6295.9)
AND PERINATAb/POSTNATAL
REPRODUCTION
TOXIC
TABLE C24 (PAGE 18); MATERNAL BODY WEIGHTS
- PRESUMED GESTATION
- INDIVIDUAB
DATA - Fo GENERATION
FEMALE RATI
--- ------------- ------- ------ --------
-- -- ---------- ---------------------------------------- ------
PREGNANCY
STATUS
DAY 0
1
2
3
4
5
6
7
8
9
--- ------------- ------- ------ -------- I ---- -------------- ----------------------------------------
1 ------
PAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
-------------------------------- -------------- ---------------------------------------------------------------
8966 P
245.
248.
249.
254.
254.
259.
260.
260.
265.
268.
280
8967 P
228.
230.
240.
235.
238.
246.
245.
245.
248.
244.
253
8968 P
230.
227.
228.
233.
227.
240.
238.
242.
244.
256.
251
8969 P
225.
235.
232.
234.
238.
242.
244.
242.
252.
257.
260
8970 P
258.
261.
260.
268.
265.
277.
276.
276.
280.
264.
266
8971 P
262.
266.
270.
270.
272.
279.
284.
284.
285.
298.
294
8972 NP
207.
211.
217.
214.
219.
223.
227.
224.
224.
229.
231
8973 P
238.
239.
239.
240.
243.
243.
249.
250.
248.
246.
259
8974 P
231.
236.
232.
231.
230.
236.
233.
232.
228.
235.
237
8975 P
255.
254.
259.
259.
259.
262.
263.
262.
267.
270.
273
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VABUES EXCLUDED FROM "ERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C24 (PAGE 19): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATI
----------- ------------------------- ------- ------ - ------------- --------- -- ----------PREGNANCY
-- -------------
STATUS
DAY 13
14
15
16
17
18
19
20
21
----------- --------------------------------------- I -----------------------------------------
22
23
--- -------------
RAT #
DOSAGE GROUP V
-------------------------------------
8941 P
3.2 MG/KG/DAY -------------------------------------------------------
--- -------------
8942 P 8943 P 8944 P 8945 NP 6946 P 8947 P
307.
320.
327.
333.
347.
368.
380.
389.
396.
243.
243.
250.
264.
277.
294.
307.
314.
242.
249.
256.
268.
278.
293.
304.
314.
230.
231.
230.
227.
232.
234.
225.
221.
219.
223.
222
304.
311.
318.
327.
335.
354.
370.
384.
8948 P
8949 P 8950 P 8951 P
250. 306.
251. 308.
257. 312.
269. 319.
280. 332.
299. 340.
312. 353.
324. 359.
327.
8952 NP 8953 P
246.
243.
240.
239.
242.
276.
242.
236.
241.
240,
244
8954 P
8955 P 8956 p 8957 NP 8958 P
256.
257.
265.
274.
283.
300.
314.
321.
242.
261.
270.
280.
288.
313.
326.
334.
346.
235.
234.
233.
239.
239.
229.
237.
237.
240.
234.
238
8959 p 8960 P 8961 p 8962 P 8963 NP
289. 299. 263. 259.
299. 297. 265. 259.
301. 308. 270. 266.
282. 325. 285. 276.
311. 334. 302. 290.
332. 352. 315. 314.
342. 367. 326. 334.
353. 381. 340. 34S.
404. 351.
8964 P 8965 P
265.
270.
279.
298.
311.
330.
347.
359.
364.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT
(VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL PFOS IN PATS
(GAVAGE) (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C24 (PAGE 20): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
INDIVIDUAL
DATA - Po GENERATION
FEMALE RAT
-------------------PREGNANCY
--------------------------
--------- --- ------------------------ --- -------------
STATUS
DAY 13
14
15
16
---------------------------------------------------
17
is
19
20
21
22
2
----------------------------------------------------------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8966 P
8967 P
275.
277.
279.
297.
308.
329.
344.
350.
8968 p
260.
263.
267.
279.
292.
300.
313.
317.
8969 p
264.
267.
276.
294.
304.
320.
346.
344.
344.
8970 P
261.
273.
285.
294.
312.
330.
344.
357.
8971 P
302.
311.
315.
323.
343.
358.
372.
384.
8972 NP 8973 P
228.
228.
224.
222.
223.
220.
221.
221.
209.
215.
21
272.
274.
278.
297.
310.
322.
341.
342.
355.
8974 P
246.
250.
259.
269.
288.
306.
323.
336.
338.
8975 P
286.
297.
304.
315.
330.
342.
358.
365.
382.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT
(VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL
418 006:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL STUDY NLJMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C25 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
------------- ------ --- ----------------------------- ----------------- ---- ------ -------------------------
DAY 1
4
7
10
14
21
------------------------------------------------------------------------------ - I ------------------------------
PAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817
267.
251.
296.
313.
303.
306.
265.
256.
308.
301.
295.
303.
300.
301.
312.
331.
292.
310.
339.
338.
NOT PREGNANT
262. 322. 320. 274. 306. 296. 326. 341. 304. 337.
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.
8818
NOT PREGNANT
8819
319.
330.
334.
349.
354.
342.
8821
315.
328.
320.
323.
341.
342.
8823
284.
292.
296.
325.
311.
320.
8824
300.
315.
318.
312.
345.
336.
8826
290.
285.
301.
296.
319.
330.
8827
302.
300.
334.
314.
316.
341.
8828
308.
310.
313.
329.
347.
315.
8830
288.
310.
315.
321.
328.
328.
8831
276.
263.
289.
345.
313.
320.
8832
318.
331.
334.
347.
338.
333.
8833
293.
296.
291.
316.
309.
325.
8834
328.
332.
340.
315.
306.
356.
8835
264.
286.
299.
321.
314.
336.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF LACTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERI'ILITY, DEVELOPMENTAL
PFOS IN PATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI
TABLE C25 (PAGE 2): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
------------ ---- I ----------------
DAY 1
4
----------------------------------
RAT #
DOSAGE GROUP 11
------------ ---------------------
---
------ -------------- ---------------------------------------------
7
10
14
21
---------------------------- --- -----------------------------------------
0.1 MG/KG/DAY --------------------------------------------------------------------------
8838
293.
312.
307.
323.
314.
318.
8840
290.
301.
309.
321.
334.
335.
8841
326.
325.
333.
338.
342.
337.
8842
284.a
298.
288.
296.
322.
317.
8845
311.
306.
300.
330.
340.
326.
8846
264.
279.
276.
289.
293.
292.
8847
298.
289.
298.
302.
282.
312.
8849
318.
312.
309.
327.
334.
331.
8851
320.
339.
331.
342.
356.
339.
8852
274.
279.
291.
308.
300.
306.
8853
279.
296.
304.
322.
337.
327.
8854
301.
317.
317.
325.
339.
340.
8855
310.
318.
314.
321.
330.
337.
8857
290.
299.
297.
312.
337.
336.
8858
298.
308.
309.
328.
324.
310.
8860
306.
305.
306.
311.
328.
333.
8862
337.
344.
333.
346.
364.
351.
8863
295.
296.
299.
310.
318.
319.
8864
283.
276.
286.
297.
300.
313.
8865
298.
302.
312.
321.
320.
316.
8866
288.
284.
304.
304.
323.
330.
8867
293.
300.
304.
316.
331.
342,
8868
282.
287.
295.
308.
322.
321.
8869
330.
330.
332.
345.
357.
357.
8870
291.
298.
296.
308.
316.
315.
--------------------------------------------------------------------------------------------------------------
DAY = DAY OF LACTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (C).
a. Dam 8842 delivered one additional pup on day 2 of lactation; values for day 1 of lactation excluded from statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C25 (PAGE 3): MATERNAL BODY WEIGHTS
LACTATION - INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
------------------------- ------------- -------- ---- --- -------------------- --------------- -- ------------
DAY 1
4
7
10
14
21
-- ---------------- ----------------------------------- -------------------------------------------------------
PAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------------------------------------------------------------
8871
NOT PREGNANT
---------------
8872 8874 8875 8876 seal 8882 8885 8889 8890 8891 8892 8893 8894 889S 8896 8897 8898 8899 8900 8901 8902 8903
298.
301.
296.
305.
272.
285.
332.
331.
278.
267.
276.
2S2.
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
316. 312. 290. 344. 277. 298. 358. 308.
303. 283. 293. 299. 323. 282. 295. 316. 300. 313. 306. 297. 310.
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.
342. 328. 303. 350. 321. 337. 355. 332. 350. 305. 326. 331. 333. 302. 316. 346. 325. 330. 347. 324. 3S8.
8904
NOT PREGNANT
8905
270.
298.
299.
306.
316.
338.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF LACTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE@ PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NIIMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C25 (PACE 4): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
------------------------------- -------------------
--------------------------- ----------------------------
DAY 1
4
7
10
14
21
---------------------------------- ---------------------------------------------------------------------------
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
------------------------------------- ------------------------------------------------------------------------
8906 8909 8913 8914
269. 267. 288. NOT
258. 278. 286. PREGNANT
270. 287. 300.
284. 304. 313.
300. 304. 331.
314. 307. 321.
8918
NOT PREGNANT
8919 8920 8921 8923
357. 303. 292. NOT
346. 298. 278. PREGNANT
351. 297. 287.
344. 308. 303.
363, 318. 319.
370. 326. 339.
8925 8926 8927 8928 8929 8930 8931 8932 8933
315. 266. 310. 280. 308. 290. 318. 276. NOT
301.
305.
252.
248.
276.
291.
284.
290.
NO SURVIVING
288.
294.
311.
311.
277.
273.
PREGNANT
PUPS
313.
257. 307. 309. ON DAY 306. 320. 287.
331.
340.
270.
288.
321.
33S.
336.
331.
2 OF LACTATION
328.
336.
330.
327.
308.
318.
8934
290.
278.
270.
286.
299.
314.
893S
298.
293.
293,
304.
318.
325.
8936
296.
280.
NO SURVIVING
PUPS ON DAY 4 OF LACTATION
8937
313.
295.
314.
317.
329.
356.
8938
MORIBUND
SACRIFICED
ON DAY 36 OF STUDY
8939
309.
310.
302.
310.
315.
316.
8940
311.
323.
322.
343.
365.
366.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF LACTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL ((,AVAGE) FERTILITY,
DEVELOPMENTAI,
PFOS IN RATS (SIION,;OR'S STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICIT
TABLE C25 (PAGE 5) : MATERNAL BODY WEIGHTS - LACTATION
INDIVIDI)AL DATA - Fo GENERATION
FEMALE PATS
------ -- --------- ----------- --- - ------------------ ---- --
DAY 1
4
--------- ------------------------
7
10
14
21
-- ---------------------------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
----------------------------------- - ---------------------------
8942 8943 8944 8945
292.
NO
250.
NO
a
NO
NOT PREGNANT
SURVIVING SURVIVING SURVIVING
PUPS PUPS PUPS
ON DAY ON DAY ON DAY
I OF 1 OF 1 OF
LACTATION LACTATION LACTATION
-------- -------- ---- ------------------------------------------- ------------------------------------- ---- --------------------
8946 8949 8950 8952
315.
NO
256.
NO
a
NO
NOT PREGNANT
SURVIVING SURVIVING SURVIVING
PUPS PUPS PUPS
ON DAY ON DAY ON DAY
2 OF 2 OF 1 OF
LACTATION LACTATION LACTATION
8955 8956 8957
246.
NO
272.
NO
NOT PREGNANT
SURVIVING SURVIVING
PUPS PUPS
ON DAY ON DAY
I OF 2 OF
LACTATION LACTATION
8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972
286.
NO SURVIVING
292.
NO SURVIVING
262.
NO SURVIVING
268.
NO SURVIVING
292.
NO SURVIVING
284.
NO SURVIVING
271.
NO SURVIVING
243.
NO SURVIVING
278.
NO SURVIVING
301.
NO SURVIVING
NOT PREGNANT
PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS PUPS
ON DAY ON DAY ON DAY ON DAY ON DAY ON DAY ON DAY ON DAY ON DAY ON DAY
2 OF I OF 2 OF I OF 2 OF 1 OF 2 OF 1 OF 2 OF 2 OF
LACTATION LACTATION LACTATION LACTATION LACTATION LACTATION
LACTATION LACTATION LACTATION LACTATION
8973
261.
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8974
257.
NO SURVIVING PUPS ON DAY I OF LACTATION
8975
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C26 (PAGE 1)! FEED CONSUMPI'ION VALUES - PRECOHABITATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
-----
- --------- -----------
DAYS
1- 8 8- 15
---------------------15- 22 22- 29 29- 36 36
----------------------42a
- - ------------------
RAT--#-----------D-O-S-AG-E----GR-O-UP-- 1- -------------0--(-V-E-HI-C-L-E-)-- MG/KG-/-D-A-Y-------------------- - --------------------
------- ------------------------- - ------------------------- --------------------------- - ---------------------
8801 8802 8603 8804
118. 122. 132. 143.
ill. 138. 134. 142.
107. 115. 140. 143.
106. 136. 137. 133.
104. 141. 127. 142.
98. 124. 119. 109.
8805
138.
148.
87.
140.
119.
109.
8806
162.
171.
174.
161.
154.
149.
8807
127.
145.
136.
127.
120.
117.
8808 8809 asio
139. 134. 133.
146. 127. 144.
151. 125. 149.
135. 129. 181.
132. 126. 123.
Ill. 112. 113-
8811 8812
b 151.
131, 146.
130. 141.
130. 141.
123. 142.
105. 114.
8813
129.
136.
124.
122.
131.
99.
8814
156.
170.
150.
148.
153.
129.
8815
126.
169.
133.
136.
116.
121.
8816 8817 0818
159. 118. 179.
130. 132. 177.
126. 124. 180.
141. 134. 185.
131. 151. 174.
133. 114. 145.
8819
130.
131.
125.
129.
140.
103.
8820
123.
134.
131.
124.
120.
110.
8821
142.
142.
138.
137.
139.
iis.
8822
128.
124.
128.
130.
124.
103.
8823
128.
129.
128.
128.
121.
103.
8824
150.
163.
15S.
166.
154.
117.
8825
148.
128.
145.
134.
131.
118.
8826
120.
127.
120.
129.
125.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAb/POSTNATAb
REPRODUCTION
TOXICI
TABLE C26 (PAGE 2): FEED CONSUMPTION
VALUES - PRECOHABITATION
- INDIVIDUAL
DATA - Po GENERATION
FEMALE RATS
---------------DAYS
----------------------- ----- - -------------------1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
------------------------- ------------
---------------- -----------------------
RAT #
DOSAGE GROUP 1
----- - --------------------0 (VEHICLE) MG/KG/DAY
- --------------------------------------
---------------- ----------------------------------------------------------------------------------------------
8827 8828 8829 8830 8831
112. 120. 124. 152. 127.
114. 131. 137. 146. 135.
110. 130. 132. 162. 133.
120. 138. 129. 168. 144.
116. 135. 133. 153.
b
99. 126. 125. 130. 116.
8832
126.
124.
130.
137.
145.
104.
8833 8834 8835
130. 131. 116.
138. 143. 122.
155. 146. 138.
169. 159. 134.
136. 163. 119.
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
PFOS IN PATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C26 (PAGE 3): FEED CONSUMPTION
VALUES
PRECOHABITATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
------------------------ -------------- -- ---- -
DAYS
I- 8 8- 15 15- 22 22 29
------------------ ------ -- - ----------------- -----------29 36 36- 42a
----------------------- ---------------------------------------------------- -- ---------------- - ------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------------------------------------------------------------------------
------------
8836
122.
125.
125.
124.
110.
106.
8837
128.
130.
139.
144.
132.
642.b
8838
139.
136.
162.
127.
136.
Ill.
8839
127.
135.
122.
105.
113.
99.
8840
136.
173.
152.
136.
138.
119.
8841
131.
147.
142.
155.
149.
116.
8842
143.
145.
147.
120.
130.
112.
8843
155.
160.
163.
168.
115.
151.
8844
133.
136.
134.
130.
138.
124.
8845
139.
144.
143.
149.
94.
129.
8846
127.
595.b
126.
lie.
123.
99.
8847
140.
150.
141.
138.
142.
116.
8848
140.
166.
156.
127.
124.
96.
8849
143.
156.
149.
153.
151.
129.
8850
146.
618.b
142.
128.
132.
122.
8851
246.
145.
142.
149.
143.
124.
8852
130.
127.
127.
131.
124.
112.
8853
136.
144.
127.
132.
127.
98.
0854
153.
163.
159.
159.
149.
113.
8855
157.
159.
150.
148.
139.
122.
8856
126.
133.
127.
126.
159.
105.
8857
119.
123.
128.
143.
138.
115.
8858
134.
124.
125.
128.
122.
109.
8859
122.
136.
143.
163.
150.
138.
8860
138.
618.b
160.
ISS.
149.
128.
8861
138.
129.
119.
134,
135.
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.
PROIOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (f,PONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABI,E C26 (PAGE 4): FEED CONSUMPTION
VALUES - PRECOHABITAI'ION
- INDIVIDUAL
DATA - Po GENERATION
FEMALE PATS
---- ---- ----------------------
-------
DAYS
1- 8 8- 15 15----2-2---2-2-----2-9---2-9----3-6- 3-6---4-2a------------- ----- --------------------------
---------------------------- ------------------------ - --------------- ----- --------------------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------- ------------------------- I ----------------------- --------------------------
8862
131.
132.
136.
136.
140.
124.
8863
122.
129.
129.
125.
135.
ill.
8864
120.
622.b
135.
128.
130.
122.
8865
137.
142.
130.
14S.
159.
123.
8866 8867
118. 129.
116. 123.
120. 124.
130. 130.
128. 134.
110. 107.
8868
126.
123.
128.
133.
139.
110.
8869
146.
141.
141.
148.
c
128.
8870
127.
124.
133.
128.
121.
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 ORAI, (GAVAGE) PFOS IN RATS (SPONSOR'S
FSRTILITY, DEVELOPMENTAL STUDY NLTMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C26 (PAGE 5): FEED CONSUMPTION
VALUES - PRECOHABITATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
------------ --
DAYS ---------------
RAT # ---------------
-- -------------- -------------- ----------- ----------------------------- --------------- --
I- 8 8- 15 15- 22 22- 29 29- 36 36 42a
----------------------------- -- -------- ---------- ------- -------------------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------- -----------------------------------------------------------------
8871 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. IS6. 877.b 144. 136. 121. 124. 132. 139. 123. 157. 131. 138. iss. 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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE@ FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE C26 (PAGE 6): FEED CONSUMPTION
VALUES - PRECOHABITATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
----------------------------------------- 1-@ ---------------- ---------- ------------------ --------------------
DAYS
1- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
---- ------------------------------------ -- --------------- --------------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---- ----------------------------------------------------------------------------------------------------------
8897
197.
523-b
154.
157.
152.
124.
8898
158.
iso.
132.
121.
117.
ill.
8899
134.
140.
138.
158.
141.
130.
8900
130.
131.
149.
145.
143.
114.
8901
115.
110.
116.
130.
130.
107.
8902
143.
72.
153.
isi.
158.
123.
8903
122.
lie.
121.
124.
122.
104.
8904
146.
138.
139.
143.
148.
128.
8905
ill.
110.
119.
119.
114.
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.
PROTOCOL 416-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C26 (PAGE 7): FEED CONSUMPTION
VALUES - PRECOHABITATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
---------- ------------------ ---------- ------------ -- ------------ ---------- --------------- --------------
----------
DAYS
I- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
----------------------------- -------------------------------------------------------
--------------
RAT 4
DOSAGE GROUP IV
---------- -----------------------------
1.6 MG/KG/DAY -------------------------------------------------------
--------------
8906
122.
137.
133.
115.
118.
100.
8907
139.
142.
129.
127.
123.
103.
8906
145.
155.
121.
123.
108.
103.
8909
127.
137.
129.
119.
118.
101.
8910
133.
132.
124.
117.
116.
ill.
8911
138.
146.
142.
129.
120.
114.
8912
124.
130.
124.
114.
114,
99.
8913
130.
136.
132.
129.
117.
108.
8914
130.
128.
107.
100.
98.
92.
8915
172.
182.
3175.b
158.
138.
125.
8916
131.
139.
129.
128.
132.
116.
8917
129.
129.
128.
127.
139.
112.
8918
189.
147.
147.
155.
136.
108.
8919
161.
149.
131.
167.
169.
129.
8920
147.
149.
139.
139.
123.
119.
8921
144.
147.
145.
152.
138.
128.
8922
105.
109.
110.
115.
97.
92.
8923
129.
127.
110.
12S.
107.
94.
8924
123.
113.
ios.
119.
112.
104.
8925
122.
136.
135.
141.
132.
121.
8926
131.
132.
127.
123.
114.
98.
8927
114.
119.
125.
138.
128.
121.
8928
118.
121.
121.
116.
107.
106.
8929
172.
140.
149.
123.
123.
110.
8930
144.
144.
135.
125.
138.
103.
8931
139.
136.
128.
125.
139.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C26 (PAGE 8): FEED CONSUMPTION
VALUES - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
------------ ---- -- ------------- -------
DAYS
1- 8 8- 1S 15- 22
------------ -----------------------------
-- ----------------- I ---------------------------------- ----------
22- 29 29- 36 36- 42a - - ---------------------------------------------------------------
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8932
130.
125.
116.
128.
125.
107.
8933
205.
176.
132.
154.
168.
164.
8934
109.
ill.
115.
121.
110.
101.
8935
145.
135.
134.
124.
136.
110.
8936
130.
123.
128.
123.
131.
112.
8937
141.
132.
131.
137.
157.
149.
8938
126.
ill.
119.
116.
86.
MORIBUND SACRIFICED
ON DAY 36 OF STUDY
8939
124.
123.
125.
124.
121.
109.
8940
157.
b
165.
165.
165.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C26 (PAGE 9): FEED CONSUMPTION VALUES - PRECOHABITATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
------------------------ ----------- ----------------------------------- -------------------------------------
DAYS
1- a 8- 15 15- 22 22- 29 29- 36 36- 42a
- ---------------------------------- -------------------------------------------------------------------------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
------------------------------------ -------------------------------------------------------------------------
8941
120.
119.
105.
93.
84.
84.
8942
114.
128.
107.
117.
102.
102.
8943
113.
114.
92.
93.
82.
80.
8944
128.
114.
106.
106.
86.
87.
8945
126.
125.
113.
ill.
107.
81.
8946
145.
139.
120.
112.
103.
83.
8947
128.
114.
105.
110.
98.
94.
8948
137.
134.
128.
131.
112.
102.
8949
116.
104.
108.
90.
90.
69.
8950
134.
131.
116.
124.
113.
109.
8951
136.
122.
121.
Ill.
102.
92.
8952
115.
108.
102.
98.
98.
86.
8953
123.
139.
119.
122.
109.
99.
8954
120.
139.
119.
121.
112.
117.
8955
117.
128.
109.
108.
100.
101.
89S6
115.
110.
112.
109.
96.
86.
8957
122.
123.
98.
114.
96.
95.
8958
127.
195.
114.
112,
106.
110.
89s9
132.
124.
121.
109.
94.
91.
8960
147.
141.
132.
136.
120.
112.
8961
102.
88.
93.
95.
97.
83.
8962
139.
126.
107.
132.
122.
117.
8963
126.
117.
Ill.
117.
105.
100.
6964
116.
93.
106.
112.
100.
98.
8965
114.
109.
109.
ill.
112.
104.
8966
134.
123.
117.
122.
112.
103.
--------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI(
TABLE C26 (PAGE 10): FEED CONSUMPTION
VALUES - PRECOHABITATION
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATI
----------------------------- - --------------------- - ----------------- --- ----
DAYS
I- 8 8- 15 15- 22 22- 29 29- 36 36- 42a
----------------- ------------------------------------------------------------------
------------------ ------------------------------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
------------------------------------------------------ -------------------- -----------------------------------
8967
lie.
106.
87.
132.
108.
97.
8968
Ill.
116.
107.
Ill.
87.
91.
8969
113,
110.
114.
120.
104.
95.
8970
171.
150.
157.
136.
110.
95.
8971
130.
132.
141.
140.
140.
120.
8972
102.
91.
91.
102.
82.
87.
8973
117.
103.
118.
114.
103.
102.
8974
124.
94.
100.
103.
108.
163.
8975
122.
106.
115.
ill.
ill.
99.
--------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF STUDY
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418 008:
COMBINED OPAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 1): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
------------ ------------------ ----- PREGNANCY
------------ --- ------------------------ --- --------- -------------
STATUS DAYS 0 - 1
1- 2
2- 3
3- 4
4- 5
5- 6
6- 7 7 -
--------------------------------------------------------------------------------------
8 a - 9 9 - 10 10 -----------------------
RAT #
DOSAGE GROUP 1
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
16.
19.
14.
24.
17.
17.
16.
is.
23.
15.
21.
28.
30.
24.
31.
32.
22.
26.
25.
27.
22.
27.
23.
25.
27.
21.
25.
25.
27.
22.
24.
17.
24.
26.
20.
29.
25.
31.
23.
25.
17.
21.
20.
24.
is.
22.
28.
18.
22.
25.
28.
26.
29.
24.
33.
25.
21.
24.
29.
27.
26.
23.
13.
27.
25.
18.
23.
26.
26.
18.
24.
19.
16.
24.
22.
15.
21.
22.
19.
18.
21.
19.
18.
20.
21.
21.
19.
23.
22.
21.
20.
20.
22.
12.
27.
23.
13.
22.
21,
17.
11.
23.
22.
16.
24.
21.
27.
is.
23.
25.
NO CONFIRMED
MATING DATE
8813 P
24.
15.
31.
21.
16.
24.
22.
26.
19.
22.
2
8814 P
15.
20.
21.
23.
23.
26.
29.
27.
25.
30.
3
8815 P
15.
26.
20.
23.
27.
23.
22.
24.
27.
24.
8816 P
20.
23.
20.
21.
24.
27.
25.
22.
26.
24.
8817 NP
7.
12.
19.
25.
22.
22.
29.
20.
24.
24.
1
8818 NP
20.
is.
26.
28.
is.
30.
29.
30.
26.
30.
2
8819 p
15.
20.
21.
22.
20.
24.
24.
32.
21.
26.
2
8820 P
19.
22.
23.
19.
24.
20.
19.
24.
22.
21.
8821 P
20.
24.
17.
27.
22.
16.
25.
20.
28.
18.
2
8822 P
19.
24.
20.
20.
21.
21.
17.
23.
22.
22.
8823 P
14.
19.
22.
17.
18.
19.
22.
20.
23.
20.
2
8824 P
17.
16.
23.
19.
18.
18.
22.
19.
24.
26.
2
8825 P
21.
24.
26.
16.
27.
22.
17.
21.
24.
21.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT DAYS = DAYS
NP = NOT OF PRESUMED
PREGNANT GESTATION
(VALUES EXCLUDED
FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295-9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C27 (PACE 2): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
INDIVIDUAL DATA - Fo GENERATION
------------------- ---------------------------- ------------------- ------
------- --- --------------------
PREGNANCY
STATUS DAYS 0 - 1
1- 2
2- 3
3- 4
4- 5
5- 6
6- 7
7- 8 8 - 9
9 - 10 10 -
------------------- -------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8826 P
is.
25.
25.
21.
26.
26.
30.
21.
26.
27.
2
8827 P
17.
21.
22.
22.
17.
25.
25.
20.
25.
21.
2
8828 P
21.
26.
17.
28.
17.
19.
23.
24.
28.
25.
2
8829 P
25.
25.
25.
22.
23.
21.
21.
22.
22.
20.
8830 P
23.
22.
25.
23.
24.
25.
23.
25.
20.
27.
2
8831 P
11.
22.
22.
15.
23.
23.
25.
19.
26.
26.
2
8832 P
18.
19.
26.
26.
21.
25.
22.
33.
20.
25.
3
8833 P
19.
19.
23.
is.
28.
22.
17.
22.
20.
27.
1
8834 P
17.
19.
25.
22.
23.
24.
30.
24.
27.
26.
2
8835 P
18.
26.
24.
22.
26.
27.
31.
22.
24.
29.
1
---------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILTTY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINAI'AL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C27 (PAGE 3): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
INDIVIDUAL DATA - Fo GENERATION
-------------------PREGNANCY
---------------------------
--------------------------
------------------- ------------
STATUS DAYS 13
14 14 - 15 15 - 16 16
17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 -
-------------------- ---------------------------- --------------------------- -------------------- -----------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8801 p 8802 P
20.
22.
19.
23.
22.
20.
18.
20.
8803 P 8804 P 8805 p 8806 P
25.
25.
26.
31.
30.
29.
22.
24.
13.
25.
23.
28.
29.
27.
27.
27.
20.
22.
16.
19.
24.
19.
20.
20.
19.
8807 P soos p 8809 P
25.
24.
20.
24.
25.
27.
20.
22.
23.
26.
25.
28.
28.
27.
22.
22.
8810 p
8811 p 8812 P 8813 P 8814 P 8815 P
22.
24.
23.
24.
21.
22.
20.
20.
13.
NO CONFIRMED
MATING DATE
26.
24.
23.
23.
23.
16.
19.
18.
28.
24.
28.
27.
29.
22.
26.
24.
16.
8816 p 8817 NP 8818 NP 8819 p 8820 P
19.
16.
17.
16.
16.
15.
15.
20.
is.
13.
1
29.
17.
24.
27.
26.
7.
9.
le.
29.
19.
1
26.
24.
29.
30.
26.
26.
25.
21.
8821 P 8822 P
24.
28.
22.
28.
25.
20.
18.
26.
8823 P
17.
21.
22.
22.
18.
22.
20.
21.
8824 P
22.
23.
22.
2S.
20.
21.
16.
12.
8825 P
---------------------------------------------------------------------------------------------------------------
P = PREGNANT DAYS = DAYS
NP = NOT OF PRESUMED
PREGNANT GESTATION
(VALUES EXCLUDED
FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FEPTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S SI'UDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C27 (PAGE 4@: MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
--------------PREGNANCY
-----------------------
-------------------- ---
------------------------- --------
STATUS DAYS 13 - 14 14 - 15 15 - 16 16 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 23 23 -
------------------ -------------------------- --------------------------
-----------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------- -----------------------------------------------------------------
8826 P 8827 P 8828 P 8829 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.
8830 P
24.
2S.
28.
8831 P
18.
24.
26.
8832 P
28.
26.
30.
8833 P
18.
23.
26.
8834 P
24.
25.
28.
8835 P
23.
27.
26.
---------------------------------------------
29.
28.
22.
21.
21.
25.
24.
25.
23.
20.
29.
27.
22.
26.
23.
23.
25.
25.
23.
20.
26.
26.
25.
22.
20.
23.
17.
22.
23.
12.
-----------------------------------------------------------------
P = PREGNANT DAYS = DAYS
NP = NOT OF PRESUMED
PREGNANT GESTATION
(VALUES EXCLUDED
FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C27 (PAGE 5): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
--------- --- ---------- -
------------------------ --------------------------- ---------------------------
PREGNANCY
STATUS DAYS 0 ------------------------
1- 2 2 - 3 3 - 4 4 - 5 5 - 6 6 - 7 7 -- -------------------------- ---------------------------
8
8 - 9 9 - 10 10 -
---------------------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
------------------------ -- -------------------------- --------------------------------------------------------
8836 P
19.
17.
18.
16.
19.
19.
16.
19.
18.
17.
8837 P
23.
26.
26.
22.
28.
28.
24.
22.
27.
21.
8838 P
15.
16.
23.
20.
17.
20.
23.
24.
22.
23.
2
8839 P
22.
19.
21.
18.
24.
22.
16.
19.
20.
16.
8840 P
21.
17.
26.
25.
22.
23.
25.
28.
21.
26.
2
8841 P
16.
19.
21.
23.
26.
30.
23.
25.
32.
21.
2
8842 P
20.
23.
18.
25.
14.
15.
21.
23.
22.
24.
2
8843 P
25.
27.
31.
23.
32.
28.
22.
27.
27.
26.
8844 P
17.
21.
20.
17.
21.
21.
21.
22.
24.
23.
884S P
23.
17.
23.
25.
20.
22.
21.
26.
22.
24.
2
8846 P
19.
22.
23.
24.
18.
21.
23.
22.
21.
24.
2
8847 P
16.
21.
22.
22.
le.
22.
24.
27.
21.
24.
2
8848 P
15.
24.
22.
19.
20.
22.
21.
20.
20.
21.
8849 P
17.
23.
22.
21.
22.
26.
20.
22.
25.
30.
2
8850 NP
23.
27.
25.
26.
26.
24.
23.
25.
24.
24.
8851 p
17.
25.
26.
21.
22.
26.
31.
21.
24.
32.
2
8852 P
14.
18.
18.
15.
18.
23.
19.
20.
18.
24.
1
8853 P
20.
17.
21.
22.
19.
24.
22.
22.
18.
23.
2
8854 P
11.
25.
25.
16.
26.
27.
31.
19.
25.
28.
2
8855 P
14.
24.
22.
23.
le.
23.
27.
22.
24.
26.
2
8856 NP
a
a
24.
15.
25.
24.
19.
20.
19.
18.
8857 P
16.
18.
22.
19.
21.
18.
22.
19.
22.
25.
2
8858 P
11.
23.
20.
17.
21.
24.
25.
20.
23.
24.
2
8859 P
19.
24.
31.
21.
32.
30.
18.
26.
27.
26.
8860 P
18.
25.
23.
19.
23.
23.
23.
22.
24.
27.
2
---------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 6) : MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
---------- -------------------- - - - -------------------- I ------------------------ - - -- -----------------
PREGNANCY
STATUS DAYS 0 - 1 1 - 2 2 - 3 3 - 4 4 - 5 5 - 6 6 - 7 7 - 8 8 - 9 9 - 10 10 ------ -------------------------- ----- ----------------------------------------------------------------------
RAT N
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------- ----------------------------------------------------------------------------
8861 NP
21.
is.
25.
17.
25.
23.
22.
23.
20.
25.
8662 P
25.
20.
29.
24.
21.
24.
24.
30.
26.
30.
8863 P
21.
22.
22.
21.
18.
20.
21.
24.
20.
25.
8864 P
20.
21.
24.
19.
25.
22.
17.
21.
23.
24.
8865 P 8866 P 8867 P 8868 P 8869 P
16.
26.
20.
20.
27.
26.
29.
26.
24.
27.
21.
23.
18.
25.
23.
20.
25.
24.
28.
21.
21.
16.
24.
21.
17.
23.
20.
24.
19.
23.
23.
21.
26.
26.
16.
19.
22.
27.
22.
25.
11.
23.
25.
20.
25.
23.
34.
22.
27.
31.
8870 P
22.
23.
26.
21.
28.
23.
20.
22.
23.
28.
--------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI(
TABLE C27 (PAGE 7): MATERNAL FEED CONSUMPTION VALUES - PRESUMED GESTATION - INDIVIDUAL DATA - Fo GENERATIOT
---- -------------- -------------- ----
----------------------------------------------------------------
PREGNANCY
STATUS DAYS 13
14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23
---- --------- ---- -------------- ---- --- ------------------------------------------------------------------
RAT #
DOSAGE GROUP 11
---- --------------------------------------
0.1 MG/KG/DAY ----------------------------------------------------------------
8836 P
8837 P
8838 P 8839 P
22.
21.
27.
26.
26.
22.
22.
22.
8840 P 8841 P 8842 P 8843 P
22.
24.
27.
28.
25.
24.
26.
15.
24.
28.
22.
18.
18.
19.
20.
20.
25.
26.
28.
25.
30.
24.
22.
is.
8844 P
8845 P 8846 P 8847 P 8848 P
26.
26.
25.
26.
23.
23.
24.
24.
21.
21.
22.
23.
23.
19.
17.
Is.
20.
21.
23.
21.
22.
24.
22.
19.
8849 P 8850 NP
27.
29.
24.
31.
20.
24,
17.
8851 P 8852 P 8853 P 8854 P 8855 p 8856 NP
22.
19.
27.
23.
23.
23.
24.
23.
19.
16.
21.
20.
18.
22.
18.
is.
23.
23.
23.
26.
25.
24.
23.
21.
23.
23.
27.
24.
18.
24.
30.
27.
21.
25.
25.
26.
22.
28.
23.
20.
8857 P 8858 P 8OS9 p
22.
20.
21.
24.
23.
23.
21.
20.
21.
23.
23.
26.
24.
27.
24.
27.
8860 p
2S.
26.
26.
30.
24.
24.
19.
22.
--------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 8): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
----------------------PREGNANCY
- -- ---------- -----------------------I ---- ---------------------------
-------
STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23
--- ------------------------------------------------------------------------------------------------
-------
RAT #
DOSAGE GROUP Il
0.1 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8861 NP
8862 P
28.
21.
28.
29.
29.
21.
a
18.
8863 P
22.
22.
21.
23.
23.
23.
22.
22.
8864 P
21.
23.
28.
24.
29.
26.
20.
17.
8865 P
22.
24.
30.
26.
19.
19.
22.
21.
8866 P
24.
24.
21.
24.
23.
26.
19.
22.
8867 P
25.
20.
24.
24.
24.
24.
23.
21.
19.
8868 P
26.
21.
23.
26.
25.
16.
19.
15.
8869 P
21.
24.
24.
27.
27.
26.
21.
18.
8870 p
16.
21.
26.
24.
23.
24.
22.
12.
--------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAYS = DAYS ALL WEIGHTS
OF PRESUMED GESTATION WERE RECORDED IN GRAMS
(G).
a. Spilled feed precluded the calculation of this value.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICIT
TABLE C27 (PAGE 9): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
F
------------------------------------------ ------------ ---------- ---------------------------------------------
PREGNANCY
STATUS DAYS 0 - 1
1- 2
2- 3
3- 4 4 - 5
5- 6
6- 7
7- 8
8- 9
9 - 10 10 -
----------------------------------------------------------------------------------------------------------------
RAT N
DOSAGE GROUP 111
0.4 MG/KG/DAY
------------------------------------------------------- --------------------------------------------------------
8871 NP
MATING NOT CONFIRMED
8872 P 8873 P 8874 P 8875 P 8876 P
21.
26.
24.
26.
24.
20.
22.
20.
18.
19.
18
16.
is.
22.
21.
23.
21.
21.
20.
25.
23.
15.
22.
25.
24.
17.
27.
23.
24.
22.
27.
23
13.
20.
17.
14.
15.
24.
21.
16.
22.
23.
le
19.
21.
24.
21.
22.
28.
23.
24.
26.
28.
24
8877 P 8878 NP
le.
le.
22.
15.
22.
18.
18.
is.
21.
19.
17.
19.
19.
12.
22.
21.
18.
24.
21.
21.
8879 NP 8880 P 8881 p 8882 P 8883 NP
19.
18.
17.
9.
18.
15.
13.
10.
15.
15.
18.
23.
23.
20.
26.
20.
18.
24.
22.
19.
is.
17.
20.
21.
22.
21.
20.
19.
21.
21.
20
19.
20.
15.
Is.
17.
20.
21.
20.
22.
20.
12
17.
17.
24.
20.
25.
24.
20.
23.
13.
24.
8884 P
19.
26.
20.
24.
24.
22.
22.
23.
24.
26.
8885 P
21.
30.
27.
25.
25.
30.
33.
24.
28.
36.
22
8886 NP 8887 P 8888 P 8889 P 8890 p 8891 p
19.
21,
21.
19.
22.
21.
18.
21.
26.
22.
21.
20.
22.
15.
20.
22.
17.
25.
21.
19.
18.
24.
26.
22.
26.
21.
23.
24.
24.
22.
15.
21.
24.
20.
16.
20.
20.
14.
13.
18.
is
19.
23.
21.
16.
24.
22.
16.
23.
20.
23.
18
15.
20.
22.
18.
23.
23.
23.
24.
22.
27.
23
8892 P 8893 P
15.
16.
14.
20.
24.
25.
23.
24.
34.
21.
28
19.
23.
20.
19.
22.
21.
17.
19.
20.
23.
22
8894 P 0895 P
22.
24.
25.
21.
23.
23.
20.
25.
22.
19.
25
12.
20.
19.
17.
21.
20.
16.
20.
22.
22.
21
----------------------------------------------------------------------------------------------------------------
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 (CAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 10): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
---------- ---- --------------- --- --- ----- -------------PREGNANCY
----- ----------- ----- --- ------------------
STATUS DAYS 0 - 1
1- 2
2- 3
3- 4
4- 5 5- 6 6- 7
7- 8
8 - 9 9 - 10 10
---------- -------------------- --- --- ------------------- --------------- --------------- ------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------- ------------------------ ------------------- -------------------------------
--- ------------------
8896 p
12.
22.
20.
14.
24.
20.
27.
20.
23.
26.
2
8897 P 8898 p 8899 p 8900 p
14.
27.
26.
19.
26.
23.
27.
24.
26.
24.
2
19.
15.
26.
21.
19.
20.
23.
25.
18.
20.
2
14.
23.
23.
19.
23.
26.
26.
20.
26.
30.
1
18.
24.
29.
24.
25.
26.
28.
25.
29.
31.
2
8901 p
19.
25.
23.
13.
19.
25.
20.
15.
25.
18.
2
8902 P
20.
22.
24.
19.
24.
23.
21.
21.
26.
28.
1
8903 NP
12.
18.
27.
22.
22.
24.
21.
22.
21.
26.
2
8904 NP
18.
23.
27.
17.
21.
24.
18.
23.
17.
27.
1
8905 P
18.
21.
23.
20.
21.
22.
19.
20.
is.
23.
1
---------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERI[LITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C27 (PAGE 11): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
------ ------------- PREGNANCY
--------------- - --- -- - ------ ------------ -------- --------------- --- -------
STATUS DAYS 13 - 14 14 - IS 15 - 16 16
17 17 - 18 18 - 19 19 - 20 20
------------------------ ----------------- ---- ------------------------ ---------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------------------------------------------- I ----------------------------------
8871 NP
MATING NOT CONFIRMED
- 21 21
22 22 -
-------------- ---
-------------------
23 23 -------
-------
8872 P 8873 P
24..
23.
22.
25.
26.
26.
23.
20.
8874 P 8875 P 8876 P 8877 P
24.
26.
26.
24.
24.
23.
21.
14.
21.
is.
23.
19.
21.
24.
21.
19.
23.
26.
24.
28.
20.
26.
23.
24.
19.
8870 NP
8879 NP
8880 p
8881 p 8882 P 8883 NP
16.
22.
22.
21.
le.
22.
18.
18.
20.
22.
22.
25.
28.
28.
23.
15.
6.
8884 P
8885 P 8886 NP
23.
26.
27.
28.
22.
25.
27.
24.
8887 P
8888 P
8889 P
17.
la.
23.
22.
24.
20.
21.
22.
8890 p
20.
23.
24.
21.
22.
22.
20.
19.
8891 P
21.
24.
26.
27.
20.
18.
18.
8892 P
28.
30.
28.
21.
21.
29.
20.
15.
8893 P
24.
23.
27.
26.
24.
29.
21.
16.
8894 P
29.
24.
23.
26.
26.
29.
25.
20.
48.
8895 P
19.
23.
23.
25.
22.
25.
23.
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C27 (PAGE 12): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
F
---- ----------------------- ----- -------- ----- --I --------- --------------------- ------------- - ----------
PREGNANCY
STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19
20 20 - 21 21 - 22 22
------ ------------------------------------------- ---- I ---------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
23 23 ----------
------------------------------------------------------------------------------------------------------------
8896 P
20.
17.
24.
26.
18.
21.
22.
22
8897 P
23.
29.
27.
23.
26.
23.
27.
27
8898 p
22.
20.
23.
22.
24.
18.
16.
16
8899 p
23.
24.
23.
21.
33.
24.
21.
13
8900 p
27.
25.
31.
32.
2S.
22.
25.
20
8901 p
21.
22.
26.
30.
22.
25.
19.
17
8902 P
18.
20.
22.
20.
27.
27.
20.
9
8903 NP 8904 NP 8905 P
19.
23.
15.
19.
18.
16.
11.
12
16.
14.
9
18.
20.
22.
17.
21.
22.
20.
13
16.
21.
15
22.
21.
27.
27.
24.
28.
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 (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C27 (PAGE 13): MATERNAL FEED CONSUMPT10N
VALUES
PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
- ------------------------- - - -- --------- - ------ ---- -- --------------------PREGNANCY
------------------------
STATUS DAYS 0 - 1 1 - 2 2 - 3 3 - 4 4
5
5- 6
6- 7
7- 8
8- 9
9 - 10 10 -
---------------------------------------------------------------- ----------------------------------------------
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
21.
18.
22.
16.
17.
23.
20.
20.
18.
24.
20.
16.
19.
22.
18.
15.
23.
22.
15.
24.
20.
22.
20.
29.
23.
16.
16.
20.
10.
23.
16.
14.
16.
Is.
13.
18.
17.
22.
18.
16.
19.
26.
18.
15.
22.
17.
NO CONFIRMED
MATING DATE 11. 19. 20.
19. 21. 20. 21. 24. 25. 19. 19. 21. 26. 19. 18. 18. 16. 21. 21. 22. 22. 27.
26. 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. 15. 32. 22. 21. 20. 32. 20. 26. 21. 22. 21. 25.
20. 20. 19. 23.
12. 17. 25. 15. 19. 20. 22. 16. 21. 17. 19. 21. 26. 22. 22. 15. 11. 13. 24. 14. 18. 14. 17.
14. 19. 17. 19. 24. 19. 21. 16. 28. 25. 23. 22. 32. 16. 19. le. 21. 23. 24. 22. 24. 25. 31.
------------------------
13.
17,
13.
18.
24.
27.
2
14.
19.
21.
21.
19.
20.
22.
23.
1
19.
19.
1
19.
24.
19.
20.
20.
22.
23.
23.
2
25.
32.
3
22.
21.
2
28.
21.
2
15.
16.
17.
19.
2
9.
20.
20.
21.
2
15.
18.
2
15.
22.
2
20.
18.
2
20.
24.
2
---------------------------------------------------------------------------------------------------------------
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 OPAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 14): MATERNAL FEED CONSUMPTION
VALUES - PRESUMEI) GESTATION
- INDIVIDUAL DATA - Fo GENERATION
----------------- -----------------PREGNANCY
-------- -
---------- ------- ------ ------------ ---------------
STATUS DAYS 0 - 1
1- 2
2- 3
3- 4
4- 5
5
6
6 - 7 7 - 8 8 - 9 9 - 10 10
--------------------------------------------------- ------------- --------------------------------------------
RAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
-----------------------------------------------------------------
--------------------------------------------
0931 P 8932 P 8933 NP 8934 P 8935 P 8936 P 8937 P 8938 8939 P
15.
19.
21.
21.
19.
21.
22.
21.
24.
21.
21.
20.
19.
17.
20.
20.
18.
21.
15.
19.
21.
27.
20.
29.
26.
24.
28.
49.
46.
24.
21.
18.
19.
21.
20.
19.
25.
16.
27.
19.
20.
16.
22.
22.
18.
25.
17.
29.
13.
24.
19.
17.
17.
19.
18.
20.
20.
22.
18.
23.
20.
21.
21.
23.
24.
23.
18.
22.
14.
22.
MORIBUND
SACRIFICED
ON DAY 36 OF STUDY
NO CONFIRMED MATING DATE
8940 P
24.
24.
19.
27.
25.
26.
30.
20.
28.
20.
--------------------------------------------------------------------------------------------------------------
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
PPOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 15): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
---- --------------------- ------- --- ------------------------- -------------------------------------PREGNANCY
------
STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 - 20 20 - 21 21 - 22 22 - 23 23 ---------------------------------- ---------------------------------------------------------------------------
PAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8906 p
NO CONFIRMED
MATING DATE
8907 NP
8908 p
8909 p 8910 p
21.
22.
22.
27.
20.
25.
21.
20.
8911 p
8912 P
8913 P 8914 NP 8915 P
19.
26.
25.
26.
20.
21.
26.
18.
B.
13.
13.
16.
12.
7.
7.
12.
11.
11.
8916 p
8917 P
8918 NP 8919 p 8920 P 8921 P 8922 P
7.
10.
13.
12.
6.
16.
20.
14.
32.
29.
31.
34.
36.
21.
27.
21.
23.
26.
27.
19.
25.
22.
24.
15.
24.
18.
32.
28.
34.
15.
27,
9.
13.
8923 NP 8924 P
is.
15.
13.
16.
15.
2.
2.
7.
9.
10.
8925 P 8926 P 8927 P 8928 P 8929 P 8930 P
23.
22.
24.
24.
28.
28.
28.
20.
20.
17.
22.
23.
27.
16.
19.
23.
26.
30.
29.
31.
30.
30.
18.
26.
20.
25.
25.
30.
16.
23.
23.
28.
23.
30.
27.
32.
16.
22.
24.
NO CONFIRMED
MATING DATE
--------------------------------------------------------------------------------------------------------------
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 ORAI, (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 16): MATERNAL FEED CONSUMPTION
VALUES
PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
--- --------- ------ -----------PREGNANCY
-------
-----------
- ---- ------------- -- ---------- ------------
STATUS DAYS 13 - 14 14 - 15 15 - 16 16 - 17 17
18 18 - 19 19 - 20 20
21 21 - 22
-------------------------------- ---- --- ------------ I-- ----------------------------------------
22 - 23 23 ---------- -
PAT #
DOSAGE GROUP IV
1.6 MG/KG/DAY
-------------------------------- -------- --------------------------------------------------------------------
8931 P 8932 P
22.
21.
26.
29.
24.
24.
23.
22.
23.
22.
25.
24.
25.
24.
24.
16.
8933 NP 8934 P
19.
23.
23.
a
21.
22.
11.
20.
24.
22.
29.
26.
31.
20.
b
40.
17.
8935 P
30.
22.
25.
30.
30.
19.
25.
8936 P
23.
21.
26.
26.
25.
19.
22.
15.
8937 P
22.
26.
23.
25.
27.
28.
28.
23.
8938
MORIBUND
SACRIFICED
ON DAY 36 OF STUDY
8939 P
NO CONFIRMED
MATING DATE
8940 P
19. .
31.
28.
30.
35.
35.
16.
23.
--------------------------------------------------------------------------------------------------------------
P = PREGNANT DAYS = DAYS
NP = NOT PREGNANT OF PRESUMED GESTATION
(VALUES EXCLUDED,FROM
AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Spilled feed precluded the calculation of this value.
b. value was not recorded.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 17): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
--- -- ---------------------PREGNANCY
------------------- - - --- ---------------- --- --- ----------
STATUS DAYS 0 - 1
1- 2
2
3
3 - 4 4 - 5 5 - 6 6 - 7 7 - 8 a - 9 9 - 10 10
------------ --- ---------------------
------------------- ---- -------------------- --- --------------
RAT #
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
14.
12.
IS.
9.
15.
13.
15.
14.
10.
17.
10.
15.
18.
Is.
is.
20.
20.
22.
B.
21.
12.
13.
il.
12.
15.
9.
17.
14.
14.
20.
13.
ls.
15.
15.
27.
15.
15.
12.
14.
19.
Is.
16.
15.
16.
13.
14.
14.
11.
17.
15.
17.
18.
9.
23.
15.
17.
24.
18.
19.
15.
18.
17.
Is.
18.
16.
16.
19.
19.
18.
20.
13.
11.
8.
11.
17.
24.
24.
24.
26.
18.
16.
12.
20.
16.
17.
18.
12.
20.
12.
18.
17.
21.
18.
19.
21.
16.
27.
19.
22.
25.
17.
14.
21.
13.
19.
18.
16.
20.
12.
is.
15.
16.
11.
16,
18.
14.
10.
17.
17.
16.
18.
18.
18.
11.
21.
19.
is.
20.
14.
is.
16.
22.
19.
13.
22.
19.
19.
17.
16.
14.
18.
18.
13.
18.
20.
is.
17.
18.
17.
21.
13.
12.
19.
17.
15.
20.
13.
21.
13.
23.
13.
18.
16.
is.
15.
11.
19.
13.
22.
18.
19.
19.
16.
16.
16.
25.
10.
17.
17.
17.
14.
13.
Is.
is.
is.
22.
16.
11.
12.
18.
16.
19.
18.
20.
17.
21.
19.
22.
21.
23.
12.
18.
17.
14.
20.
10.
22.
10.
20.
22.
28.
17.
18.
21.
19.
14.
21.
12,
20.
16.
19.
17.
19.
15.
23.
19.
19.
19.
15.
17.
8964 P
18.
15.
13.
16.
14.
15.
18.
16.
17.
19.
8965 P
13.
12.
17.
11.
19.
19.
19.
24.
13.
21.
--------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAYS = DAYS OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (C).
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C27 (PAGE 18): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
F
------- --- -- --------------------- - - ---
------------------------------------------------- ---------- ---
PREGNANCY
STATUS DAYS 0 - 1 1 - 2 2 - 3 3
4
4- 5
5- 6
6- 7
7- 8
8 - 9 9 - 10 10 -
------------------------------------ -- -----------------------------------------------------------------------
RAT #
DOSAGE GROUP V
------------------------------------
3.2 MG/KG/DAY ---------------------------------------------------------------------------
8966 P
16.
is.
18.
18.
19.
20.
17.
20.
20.
16.
8967 P
16.
20.
11.
16.
18.
17.
17.
16.
18.
19.
19
6968 P
7.
16.
15.
11.
20.
12.
20.
16.
20.
17.
19
8969 P
14.
18.
13.
20.
19.
16.
19.
17.
25.
14.
18
8970 P
23.
17.
25.
20.
2S.
26.
Ia.
2S.
16.
10.
a
8971 P
21.
21.
22.
19.
22.
23.
25.
22.
24.
29.
21
8972 NP
S.
17.
18.
10.
22.
16.
15.
17.
13.
19.
15
8973 P
16.
is.
17.
16.
19.
18.
19.
13.
19.
15.
23
8974 P
16.
16.
27.
18.
19.
15.
17.
16.
15.
is.
17
8975 P
16.
18.
17.
17.
17.
17.
22.
16.
18.
20.
18
----------------------------------------------------------------------------------------------------------------
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) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
ST(JDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL,
REPRODUCTION
TOXIC
TABLE C27 (PAGE 19): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fo GENERATION
----------------PREGNANCY
------------- -- -- --- -- - ------------- --------- -------------- - ---------- ----
STATUS DAYS 13 ------------- ----
RAT # ------------------
- 14 14 - 15 15 - 16 16 - 17 17 - 18 18 - 19 19 ------------- - --------- --------------- -----------
DOSAGE GROUP V
3.2 MG/KG/DAY
--------------------------- ----------------------------
20 20 - 21 21 - 22 22 - 23 23 --------------- - ---------- -----
----------------- ---------- -----
8941 P 8942 P 8943 P 8944 P 8945 NP 8946 P 8947 P
22.
24.
23.
24.
29.
21.
21.
22.
15.
19.
19.
22.
is.
20.
20.
17.
18.
19.
21.
23.
20.
22.
21.
16.
13.
12.
12.
17.
14.
10.
4.
11.
12.
10.
21.
22.
24.
26.
26.
24.
22.
21.
8948 P
8949 P 8950 P 8951 p
20.
18.
21.
24.
25.
18.
27.
22.
19.
23.
29.
a
21.
23.
17.
8952 NP 8953 P
14.
17.
12.
14.
11.
14.
9.
12.
15.
11.
8954 P
8955 P 8956 P 6957 NP 8958 P
16.
17.
21.
21.
23.
23.
16.
19.
21.
18.
23.
26.
25.
13.
17.
S.
is.
16.
16.
4.
9.
13.
13.
25.
23.
89s9 p 8960 p 8961 P 8962 P 8963 NP
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.
8964 P 8965 P
15.
20.
25.
26.
28.
17.
21.
--------------------------------------------------------------------------- ----------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAYS = DAYS ALL WEIGHTS
OF PRESUMED GESTATION
WERE RECORDED
IN GRAMS
(G).
a. Wet feed precluded the calculation of this value.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C27 (PAGE 20): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fo GENERATION
----------PREGNANCY
--- --- ------------ ------ ------ -------------- ----- -------- I -------------- ----- ------------
STATUS DAYS 13 - 14 14 - 15 15 - 16 16
17 17 - 18 18 - 19 19 - 20 20 - 21 21
22 22 - 23 23
----------- --- --- -------------- ---------------------------------------------------------------------------
RAT #
DOSAGE GROUP V
3.2 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8966 P
8967 P
21.
16.
26.
23.
28.
29.
20.
8968 P
is.
17.
21.
25.
15.
17.
22.
8969 P
16.
20.
20.
2S.
25.
27.
12.
12.
8970 P
24.
24.
26.
28.
28.
22.
23.
8971 P
21.
22.
24.
26.
28.
27.
27.
14.
8972 NP
12.
14.
11.
11.
14.
12.
15.
0.
12.
is.
8973 P
19.
21.
25.
25.
24.
23.
le.
20.
8974 P
14.
16.
20,
19.
28.
19.
24.
21.
8975 P
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) PFOS IN RATS (SPONSOR'S
FE:RTIIITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C28 (PAGE 1): MATERNAL FEED CONSUMPTION
VALUES - LACTATION
INDIVIDUAL
DATA - Fo GENERATION
FEMALE RA
-------------------------------------------- -------- - -------- -- I ----------------------------- ---------- DAYS 1 - 4 4 - 7 7 - 10 10 - 14a
---------------------------------------------------- ----------------------------------------- ----------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8801
52.
106.
125.
212.
8803
88.
123.
142.
268.
8804
141.
163.
167.
270.
8805
52.
78.
137.
b
8807
54.
159.
165.
252.
8808
56.
91.
117.
209.
8811
92.
127.
156.
223.
8812
c
127.
155.
255.
8813
81.
98.
132.
229.
8814
87.
117.
155.
218.
8817
NOT PREGNANT
8818
NOT PREGNANT
8819
76.
121.
146.
234.
8821
89.
106.
130.
206.
8823
75.
110.
135.
220.
8824
81.
98.
116.
238.
8826
59.
115.
b
211.
8827
62.
61.
113.
205.
8828
59.
116.
145.
225.
8830
79.
107.
131.
209.
8831
54.
114.
149.
245.
8832
81.
110.
146.
198.
8833
86.
98.
155.
227.
8834
72.
104.
136.
216.
8835
102.
140.
161.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C28 (PAGE 2): MATERNAL FEED CONSUMPTION
VALUES - LACTATION - INDIVIDUAL DATA - Fo GENERATION
FEMALE RA
--------------------------------------------- -----------------------------
DAYS 1 - 4 4 - 7 7 - 10 10 - 14a --------------------------------------------- I ----------------------------
- ----------------------- -------------------------------------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------------------- -----------------------------------------------------------------
8838 8840 8841 8842 8845
84.
98.
139.
226.
55.
127.
123.
225.
64.
ill.
147.
230.
72.
87.
122.
210.
62.
95.
130.
220.
8846
82.
159.
153.
257.
8847
64.
94.
117.
152.
8849
51.
99.
129.
221.
8851 8852
86.
104.
69.
120.
140. 146.
244. 228.
8853
82.
119.
132.
229.
8854
b
143.
165.
262.
8855
98.
121.
128.
219.
8857
63.
99.
142.
246.
8858
74.
116.
134.
233.
8860
56.
104.
113.
244.
8862 8863 8864 8865
96.
130.
87.
118.
60.
103.
68.
117.
143. 144. 140. 135.
255. 188. 219. 205.
8866
68.
117.
109.
215.
8867
81.
123.
116.
255.
8868
61.
105.
142.
236.
8869
68.
100.
132.
220.
8870
so.
110.
142.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C28 (PAGE 3): MATERNAL FEED CONSUMPTION
VALUES - LACTATION - INDIVIDUAL
DATA - Fo GENERATION
FEMALE RA
----------- ---------------DAYS 1 - 4 4
-----------------------------
---------------------
7
7 - 10 10 - 14a
----------------------
- -------------------- ---- ------------------------------------------------------- ------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------- ---------------------- - --- ---------------------------------------------------
8871
NOT PREGNANT
8872
80.
133.
154.
247.
8874
79.
107.
136.
163.
0875
80.
113.
126.
213.
8876
67.
100.
125.
183.
8881
53.
96.
125.
214.
8882
66.
95.
164.
249.
8885
61.
114.
120.
196.
8889
65.
101.
127.
196.
8890
49.
68.
123.
215.
8891
74.
Ill.
136.
218.
8892
63.
99.
133.
209.
8893
47.
115.
146.
204.
8894
52.
72.
102.
124.
8895 8896
71.
100.
138.
206.
64.
123.
156.
269.
8897
b
166.
161.
266.
8898
46.
84.
120.
148.
8899
91.
169.
135.
249.
8900
62.
126.
145.
235.
8901
63.
c
127.
229.
8902
59.
84.
143.
231.
8903
NOT PREGNANT
8904
NOT PREGNANT
8905
95.
b
151.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS ISPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C28 (PAGE 4): MATERNAL FEED CONSUMPTION
VALUES - LACTATION
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE
----------- ---------------------
DAYS 1 - 4 4 - 7 --------------------------------- -
RAT #
DOSAGE GROUP IV
---------------------------------
8906 8909 8913 8914
44.
85.
71.
98.
57.
104.
NOT PREGNANT
----- ---------- ----------- -------------I --- ----------------------------
7 - 10 10 - 14a ------------------- I -------- ---------------------------------------------
1.6 MG/KG/DAY
--------------------------------------------------------------------------
110.
202.
121.
200.
109.
195.
8916
NOT PREGNANT
8919
54.
122.
114.
204.
8920 8921 8923
42.
74.
so.
109.
NOT PREGNANT
83. 131.
150. 209.
8925 8926 8927 8928 8929 8930
46.
86.
32.
58.
41.
66.
65.
95.
NO SURVIVING
55.
102.
129. 67. 74.
120.
PUPS ON DAY 120.
198. 122. 117. 203. 2 OF LACTAT10N 229.
8931 8932 8933
44.
66.
50.
72.
NOT PREGNANT
83. 119.
148. 184.
8934 8935 8936 8937 8938
36. 55. 39. 39. MORIBUND
68.
Ill.
190.
94.
118.
199.
NO SURVIVING PUPS ON DAY 4 OF
102.
141.
218.
SACRIFICED
ON DAY 36 OF STUDY
LACTATION
8939
43.
53.
82.
147.
8940
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND 1,ERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C28 (PAGE 5): MATERNAL
FEED CONSUMPTION
VALUES - LACTATION
INI)IVIDUAL DATA - Fo GENERATION
FEMALE P-
------------ ---
DAYS ---------- -----
RAT N ----------------
8942
8943 8944 8945 8946 8949 8950 8952 8955 8956 8957
----------------- ----
---- ---------------------
1 - 4 4 - 7 7 - 10 10 - 14a
----------------------
--------------------------- -
DOSAGE GROUP V -----------------------
NO SURVIVING NO SURVIVING NO SURVIVING NOT PREGNANT
PUPS PUPS PUPS
ON DAY ON DAY ON DAY
3.2 MG/KG/DAY ---------------------- ----- 1 OF LACTATION 1 OF LACTATION 1 OF LACTATION
NO SURVIVING NO SURVIVING NO SURVIVING NOT PREGNANT NO SURVIVING NO SURVIVING NOT PREGNANT
PUPS PUPS PUPS
ON DAY ON DAY ON DAY
2 OF 2 OF 2 OF
LACTATION LACTATION LACTATION
PUPS PUPS
ON DAY ON DAY
I OF LACTATION 2 OF LACTATION
------------------- --- - ----------------------------- --- I ------------------------------------------------
89s9
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
8972
NOT PREGNANT
8973
NO SURVIVING
PUPS ON DAY 2 OF LACTATION
8974
NO SURVIVING
PUPS ON DAY 1 OF LACTATION
8975
NO SURVIVING
PUPS ON DAY I 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.
PROTOCOL 418-ooo:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PEPINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C29 (PAGE 1): ESTROUS CYCLING AND DAYS IN COHABITATION
- INDIVIDUAI, DATA - Fo GENERATION FEMALE RATS
---------------------- ---------- ----------
PRECOHABITATION
ESTROUS STAGES/
DAYS IN
RAT
28 DAYS
COHABITATION
---------------------------------------------
--
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------- - --
8801
7
2
----------------------
RAT 4 ---------------------------------------------
8819
-- ---------- ---------- -
PRECOHABITATION ESTROUS STAGES/
28 DAYS ---------------------------
DA
COHA ------
---------------------------
8802
6
1
8820
8803
-
2
8821
8804
3
8822
8805
6a
7
8823
8806 8807 8808
-
1
7
2
-
2
8824
6a
8825
8
8826
-
8809
7
1
8827
-
8810 Boll 8812
7
1
-
4
14b
8828
7
8829
7
8830
-
8813
-
3
8831
8814 8815
7
3
-
1
8832
6a
8833
-
8816 8817
1
5c
7
8834
6
8835
-
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.
PROTOCOL 410-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVEI,OPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAb
REPRODUCTION
TOXICI
TABLE C29 (PAGE 2): ESTROUS CYCLING AND DAYS IN COHABITATION
- INDIVIDUAL DATA
Fo GENERATION
FEMALE RATS
-- ------- -------------------- ------------------ -
PRECOHABITATION
RAT ---------
ESTROUS STAGES/
DAYS IN
28 DAYS --------------------
COHABITATION ---- ------------- -
DOSAGE GROUP 11
0.1 MG/KG/DAY
----------------------------------------------------
8836
1
-- -
------ --
------ ------------- -
RAT --------------------- -----------------------
8854
----------------------- ----
PRECOHABITATION
ESTROUS STAGES/
DAY
28 DAYS
COHAB
----------------------------
----------------------------
8837 8838
1
-
3
88S5
-
8856
7
8839
7
1
8857
-
8840
6a
3
8858
-
8841
5
8859
-
8842
-
2
8860
-
8843
7
1
8861
-
8844 8845 8846 8847
-
1
-
3
7
3
-
3
8862
6
8863
Ga
8864
8
8865
-
8848
5
1
8866
8849
7
4
8867
8850
-
1
8868
Sa
8851
7
4
8869
-
8852
7
4
8870
7
8853
6a
3
---------------------------------------------------------------------------------------------------------------
a. Six or more consecutive days of diestrus observed.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXIC
TABLE C29 (PAGE 3): ESTROUS CYCLING AND DAYS IN COHABITATION
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
-------- --- - -------------------
--------------- -
PRECOHABITATION
ESTROUS STAGES/
RAT
28 DAYS
------------------------------------
DAYS IN
COHABITATION ----------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
------------ ----------------------- ------- ----------- --
8871
14a
---- - -------------------------------------------
PRECOHASITATION
ESTROUS STAGES/
DA
RAT
28 DAYS
COHA
-------------------------------------------------
----------------------------------------------- -
8889
7
887@
1
8890
-
8873 8874 8875
1
8091
6b
3
8892
5
4
8893
-
8876
-
4
8894
8877
6
1
8895
8878 8879
-
1
1
8096
6b
8897
8880
-
1
8898
8881 8882 8883 8884 8885
6
4
-
4
1
3c
1
7
4
8899
5b
8900
5
8901
6b
8902
6
8903
-
8886
3b
1
8904
7
8887
1
8905
7
8888
1
---------------------------------------------------------------------------------------------------------------
a. Mating not confirmed.
b. Six or more consecutive days of diestrus observed. c. Six or more consecutive days of estrus observed.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCT10N
TOXICI
TABLE C29 (PAGE 4): ESTROUS CYCLING AND DAYS IN COHABITATION
- INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
------------------
RAT ------------------
DOSAGE GROUP IV ------------------
8906
------------------- ------ ---------------------
PRECOHABITATION
ESTROUS STAGES/
DAYS IN
28 DAYS
COHABITATION
---------------------------- ---------------------
1.6 MG/KG/DAY -------------------- ----------------------------
6a
14b
----- --- - ------------------------------
PRECOHABITATION
ESTROUS STAGES/
DAY
RAT
28 DAYS
COHAB
------------------------------------------
-- ------------------------ ---------------
8924
-
8907
-
1
8925
6
8908
7
1
8926
-
8909 8910 8911 8912
5
4
-
1
7
1
-
1
8927
6
8926
6
8929
6
0930
-
8913
-
4
8931
8914
6
3
8932
8915 8916
6
1
-
1
8933
4a
8934
6
8917
7
1
8935
8918
-
4
8936
8919
-
3
8937
8920 8921 8922
-
4
-
2
7
1
8938 0939 8940
MORIBUND 7 -
SACRIFIC 1
8923
-
3
---------------------------------------------------------------------------------------------------------------
a. Six or more consecutive days of diestrus observed.
b. No confirmed mating date.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C29 (PAGE 5): ESTROUS CYCLING AND DAYS IN COHABITATION
- INDIVIDUAL DATA
Fo GENERATION
FEMALE RATS
- -----------------------
-- ----------------------- ------------------ I-- ---- - ---------------------------
PRECOHABITATION
ESTROUS STAGES/
DAYS IN
RAT
28 DAYS
COHABITATION
- -----------------------
--------------------------
PAT ---------------------
PRECOHABITATION
ESTROUS STAGES/
DAYS
28 DAYS '
COHABI
-----------------------------------
DOSAGE GROUP V - ------------------------
3.2 MG/KG/DAY ------------------------------------------------------
- ---------------------------
8941
1
8959
13
8942
6
13
8960
-
5
8943
-
4
8961
7
4
8944
7
4
8962
-
2
8945
-
2
8963
6
1
8946
7
12
8964
-
3
8947
8
1
8965
8
1
8948
6
1
8966
-
1
8949
6
3
B967
6
2
8950
-
4
8968
7
4
8951
6
1
8969
-
2
8952
-
2
8970
7
3
8953
7
1
8971
-
1
8954
-
1
8972
1
8955
2
8973
2
8956
3
8974
3
8957 - 4 8975 4
8958
7
1
-----------------------------------------------------------------------------------------------------------------
PROTOCOL
416 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FFRTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C30 (PAGE 1): NECROPSY OBSERVATIONS
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE PATS
--- ----------------------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ----------------------------
RAT
NUMBER --------
I
-
----
DAY OF
NECROPSY -- -- -- -
----------------------
PREGNANCY
DOSAGES
STATUS
ADMINISTERED
------------------ --
---------------------------- ----------
OBSERVATIONS
a
---------------------------------------
0 (VEHICLE)
8801
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
8802
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8803
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8804 8805 8806
DL 21
p
DL 21
p
DG 10
p
85
ALL TISSUES APPEARED
NORMAL.
90
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
8807
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
8808
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
8809
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8810
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8811
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8812
DL 21
p
88
ALL TISSUES APPEARED
NORMAL.
8813
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8814
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8815
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8816
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8817
DG 25
NP
73
ALL TISSUES APPEARED
NORMAL.
8818
DG 25
NP
69
ALL TISSUES APPEARED
NORMAL.
8819
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8820
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8821
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8822
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8823
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8824
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8825
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8026
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8827
DL 21
p
90
ALL TISSUES APPEARED
NORMAL.
8828
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
8829
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8830
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8831
DL 21
p
67
ALL TISSUES APPEARED
NORMAL.
8832
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8833
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
8834
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8835
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
DS
DAY OF STUDY
DG = DAY OF (PRESUMED) GESTATION
P
PREGNANT
NP = NOT PREGNANT
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RAI'S (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICI
TABLE C30 (PAGE 2): NECROPS@' OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
--------- --------------- -
--------------------- --------------------------- --- --- - ---- --------------
DOSAGE GROUP
RAT
DAY OF
PREGNANCY
DOSAGES
DOSAGE (MG/KG/DAY) -----------------------
NUMBER
NECROPSY
STATUS
ADMINISTERED
OBSERVATIONS
a
--------------------- ---------------------------------------------------------
ii
0.1
8836
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8837
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8838
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8839
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8840
DL 21
p
es
ALL TISSUES APPEARED
NORMAL.
8841
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8842
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8843
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8844
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8845
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8846
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8847
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8848
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8849
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8050
DG 10
NP
52
ALL TISSUES APPEARED
NORMAL.
8851
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8852
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8853
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8854
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8855
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8856
DG 10
NP
52
ALL TISSUES APPEARED
NORMAL.
8857
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8858
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8859
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8860
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8861
DG 10
NP
52
ALL TISSUES APPEARED
NORMAL.
8862
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8863
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8864
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
8865
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8866
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8867
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8868
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8869
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8870
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
DS
DAY OF STUDY
DG = DAY OF (PRESUMED) GESTATION
P
PREGNANT
NP = NOT PREGNANT
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C30 (PAGE 3): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
---------- ---------------------
DOSAGE DOSAGE
GROUP (MG/KG/DAY)
RAT NUMBER
--------------------------------III
0.4
8871
8872
8873
8874 8875
8876 8677
8878
8879
8880
8881
8882
8883
8884
8885 8886
8887
8888
8889
8890
8891
8892
8093
8894
8895
8896
8897
8898
------------- I ------------- --------------- ----------
DAY OF
PREGNANCY
DOSAGES
NECROPSY
STATUS
ADMINISTERED
OBSERVATIONS
a
-------------------------------------------------------
-------------------------
DS 81
NP
DL 21
p
DG 10
p
DL 21
p
DL 21
p
DL 21
p
DG 10
p
DG 10
NP
DG 10
NP
DG 10
p
DL 21
p
DL 21
p
DG 10
NP
DG 10
p
DL 21
p
DG 10
NP
DG 10
p
DG 10
p
DL 21
p
DL 21
p
DL 21
p
DL 21
p
DL 21
p
DL 21
p
DL 21
p
DL 21
p
DL 21
p
DL 21
p
80
ALL TISSUES APPEARED
NORMAL.
85
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
86
ALL TISSUES APPEARED
NORMAL.
86
ALL TISSUES APPEARED
NORMAL.
87
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
87
ALL TISSUES APPEARED
NORMAL,
87
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
86
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
95
ALL TISSUES APPEARED
NORMAL.
84
ALL TISSUES APPEARED
NORMAL.
86
ALL TISSUES APPEARED
NORMAL.
87
ALL TISSUES APPEARED
NORMAL.
84
ALL TISSUES APPEARED
NORMAL.
85
ALL TISSUES APPEARED
NORMAL.
84
ALL TISSUES APPEARED
NORMAL.
86
ALL TISSUES APPEARED
NORMAL.
86
ALL TISSUES APPEARED
NORMAL.
85
ALL TISSUES APPEARED
NORMAL.
---- --------
8899
DL 21
p
86
KIDNEYS:
RIGHT, PELVIS, MODERATE DI
ALL OTHER TISSUES APPEARED
NORMAL.
8900
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8901
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8902
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
8903
DG 25
NP
67
ALL TISSUES APPEARED
NORMAL.
8904
DG 25
NP
67
ALL TISSUES APPEARED
NORMAL.
8905
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
----------------------------------------------------------------------------------------------------------------
DS
DAY OF STUDY
DG = DAY OF (PRESUMED) GESTATION
P
PREGNANT
NP = NOT PREGNANT
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at necr
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
PERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODIICTION TOXICIT
TABLE C30 (PAGE 4): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
------------- - - - - --------------- ---- ------ - - ------------- - - - - --------------- ---- ------------
DOSAGE GROUP DOSAGE (MG/KG/DAY) ------------ - ---
RAT
DAY OF
NUMBER
NECROPSY
-------------------- -----
PREGNANCY
DOSAGES
STATUS
ADMINISTERED
OBSERVATIONS
a
--------------------- -----------------------
------------
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
DC 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
ALL OTHER TISSUES APPEARED
NORMAL.
8920
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8921
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8922
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8923
DG 25
NP
69
ALL TISSUES APPEARED
NORMAL.
8924
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8925
DL 21
p
83
ALL TISSUES APPEARED
NORMAL.
8926
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
8927
DL 21
p
82
ALL TISSUES APPEARED
NORMAL.
8928
DL 21
p
85
ALL TISSUES APPEARED
NORMAL.
8929
DL 2
p
67
ALL TISSUES APPEARED
NORMAL.
8930
DL 21
p
86
ALL TISSUES APPEARED
NORMAL.
8931
DL 21
p
87
ALL TISSUES APPEARED
NORMAL.
8932
DL 21
p
82
ALL TISSUES APPEARED
NORMAL.
8933
DG 25
NP
68
ALL TISSUES APPEARED
NORMAL.
8934
DL 21
p
83
ALL TISSUES APPEARED
NORMAL.
8935
DL 21
p
as
ALL TISSUES APPEARED
NORMAL.
8936
DL 4
p
69
ALL TISSUES APPEARED
NORMAL.
8937
DL 21
p
84
ALL TISSUES APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
DS DAY OF STUDY DG = DAY OF (PRESUMED)
P
PREGNANT
NP = NOT PREGNANT
GESTATION
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at necr
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE@ PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATALI POSTNATAL
REPRODUCTION
TOXIC
TABLE C30 (PAGE 5): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
---------- --------------------- ------- - ----------------- ----- -------------------------------------------
DOSAGE GROUP
RAT
DAY OF
PREGNANCY
DOSAGES
DOSAGE (MG/KG/DAY)
NUMBER
NECROPSY
STATUS
ADMINISTERED
OBSERVATIONS
a
---------- ----------------------------- ---------------------------------------------------------------------
IV (Cont.)
1.6
8938
DS 36
p
35
MORIBUND SACRIFICED ON DAY 36 OF $Tt
ALL TISSUES APPEARED NORMAL.
8939
DL 21
p
87
ALL TISSUES APPEARED NORMAL.
8940
DL 21
p
84
ALL TISSUES APPEARED NORMAL.
---------------------------------------------------------------------------------------------------------------
DS
DAY OF STUDY
DG = DAY OF (PRESUMED) GESTATION
P
PREGNANT
NP = NOT PREGNANT
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERlNATAIi/POSTNATAL
REPRODUCTION
TOXICI
TABLE C30 (PAGE 6): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
----------- I ----- - - ------------ - -- --------------------- - ----------------------------
DOSAGE GROUP
RAT
DOSAGE (MG/KG/DAY)
NUMBER
----------------------------------------
v
DAY OF
PREGNANCY
NECROPSY
STATUS
------------ - --
DOSAGES
ADMINISTERED
OBSERVATIONS
a
------- --------------- ----------------------------
3.2
8941
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8942
DL I
p
76
ALL TISSUES APPEARED
NORMAL.
8943
DL I
p
66
ALL TISSUES APPEARED
NORMAL.
8944
DL 1
p
66
ALL TISSUES APPEARED
NORMAL.
8945
DG 25
NP
68
ALL TISSUES APPEARED
NORMAL.
8946
DL 2
p
74
ALL TISSUES APPEARED
NORMAL.
8947
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8948
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8949 8950 8951 8952
DL 2
p
DL 1
p
DG 10
p
DG 25
NP
66
ALL TISSUES APPEARED
NORMAL.
66
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
67
ALL TISSUES APPEARED
NORMAL.
8953
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8954
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8955
DL 1
p
64
ALL TISSUES APPEARED
NORMAL.
8956 8957 8958
DL 1
p
DG 25
NP
DC 10
p
66
ALL TISSUES APPEARED
NORMAL.
70
ALL TISSUES APPEARED
NORMAL.
52
ALL TISSUES APPEARED
NORMAL.
8959
DL 2
p
76
ALL TISSUES APPEARED
NORMAL.
8960
DL 1
p
68
ALL TISSUES APPEARED
NORMAL.
8961
DL 2
p
66
ALL TISSUES APPEARED
NORMAL.
8962
DL 1
p
65
ALL TISSUES APPEARED
NORMAL.
8963
DG 10
NP
52
ALL TISSUES APPEARED
NORMAL.
8964
DL 2
p
66
ALL TISSUES APPEARED
NORMAL.
8965
DG 10
p
52
ALL TISSUES APPEARED NORMAL.
8966
DG 10
p
52
ALL TISSUES APPEARED
NORMAL.
8967
DL 1
p
63
ALL TISSUES APPEARED
NORMAL.
8968
DL 2
p
66
ALL TISSUES APPEARED
NORMAL.
8969
DL 1
p
65
ALL TISSUES APPEARED
NORMAL.
8970
DL 2
p
66
ALL TISSUES APPEARED
NORMAL.
8971
DL 1
p
63
ALL TISSUES APPEARED
NORMAL.
8972
DG 25
NP
67
ALL TISSUES APPEARED
NORMAL.
8973
DL 2
p
66
ALL TISSUES APPEARED
NORMAL.
8974
DL 1
p
66
ALL TISSUES APPEARED
NORMAL.
8975
DL I
p
67
ALL TISSUES APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
DS
DAY OF STUDY
DG = DAY OF (PRESUMED) GESTATION
P
PREGNANT
NP = NOT PREGNANT
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table C22) for external observations confirmed at nec
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI
TABLE C31 (PAGE 1): CAESAREAN-SECTIONING
OBSERVATIONS
- INDIVIDUAL
DATA - Fo GENERATION
FEMALE RATS
------------- ----- I ----------- --------- --------------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---- -
----------------------------
-----------
-------------------------------------------------------------- -------------------------------- --------------
VIABLE EMBRYOS ------------------------
NONVIABLE EMBRYOS ---- -- --- ----
IMPLANTATION
SITES
CORPORA LUTEA
---------------- ----------------
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RAT
HORN
TOTAL
HORN
TOTAL
HORN
TOTAL
OVARY
TOTAL
--------------------------------------------------------------------------------------------------------------
8802 8806 8809 8810 8815 8816 6820 8822 882S 8829
8
9
17
0
0
0
a
9
17
8
10
18
5
11
16
0
0
0
5
11
16
11
11
22
8
5
13
0
0
0
a
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
is
3
1
4
0
0
0
3
1
4
5
6
11
10
3
13
0
0
0
10
3
13
12
a
20
12
7
19
0
0
0
12
7
19
13
7
20
--------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED OPAL IGAVA(3E) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C31 (PAGE 2): CAESAREAN-SECTIONING
OBSERVATIONS
- INDIVIDUAL DATA
Fo GENERATION
FEMALE RATS
---------- -------------------- ----- - ------------------------- ------- ------------ --
DOSAGE GROUP 11
0.1 MG/KG/DAY
---------- ------------------------- - -----------------------------------------------------
VIABLE EMBRYOS
NONVIABLE EMBRYOS
------------------------ - - ---, --------
IMPLANTATION
SITES
CORPORA
LUTEA
---------- ----- ---------------
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RAT
HORN
TOTAL
HORN
TOTAL
HORN
TOTAL
OVARY
TOTAL
----------- ----------------------------------------------------------------------------- --
8836 8837
4
4
8
0
0
0
4
4
8
4
5
9
11
6
17
0
0
0
11
6
17
11
7
is
8839
9
7
16
0
0
0
9
7
16
11
9
20
8843
6
9
15
0
0
0
6
9
is
9
9
18
8844 8848 8850
6
8
14
5
7
12
NOT PREGNANT
0
0
0
6
8
14
11
8
19
0
0
0
5
7
12
6
10
16
8856
NOT PREGNANT
--- --------------------------------
-------------------
8859 8861
1
0
1
0
0
0
1
0
1
2
0
2
NOT PREGNANT
---------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008!
COMBINED ORAL (GAVAGS) FERTIUITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAU/POSTNATAU
REPRODUCTION
TOXICIT
TABLE C31 (PAGE 3): CAESAREAN-SECTIONING
OBSERVATIONS
- INDIVIDUAL DATA - Fo GENERATION
FEMALE RATS
-----------------------------------------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
-- ------------------------ -----------------------------
-------------------------------------------------------------------------------------------------------
VIABLE EMBRYOS
NONVIABLE
EMBRYOS
------------------------
---------------
IMPLANTATION
SITES
CORPORA LUTEA
------------- --------------
RIGHT LEFT
RIGHT LEFT
RAT
HORN
TOTAL
HORN
TOTAL
-----------------------------------------------------
RIGHT LEFT
RIGHT LEFT
HORN
TOTAL
OVARY
TOTAL
----------------------------------------------------------
8873 8877 8878
8
7
15
4
9
13
NOT PREGNANT
0
0
0
8
0
0
0
4
7
is
9
9
13
4
7
16
9
13
8879
NOT PREGNANT
8880 8883
7
6
13
NOT PREGNANT
0
0
0
7
6
13
8
10
18
8884 8886
1
0
1
0
0
0
1
0
1
6
1
7
NOT PREGNANT
8887
9
6
15
0
0
0
9
6
15
10
8
18
8888
12
4
16
0
0
0
12
4
16
12
5
17
----------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVACE@ FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
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 -----------
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RAT
HORN
TOTAL
HORN
TOTAL
HORN
TOTAL
OVARY
TOTAL
-------------------- ----------------------------------------------------------- -------------------------
8907
NOT PREGNANT
------
8908
4
9
13
0
0
0
4
9
13
4
11
is
8910
10
3
13
0
0
0
10
3
13
13
6
19
8911
9
8
17
0
0
0
9
8
17
10
9
19
8912
9
6
15
0
0
0
9
6
is
9
6
15
8915
10
8
18
1
0
1
11
8
19
11
12
23
8916
5
6
11
0
0
0
5
6
11
6
7
13
8917
5
6
11
0
0
0
5
6
11
8
9
17
8922
7
6
13
0
0
0
7
6
13
7
6
13
8924
4
0
4
.0
0
0
4
0
4
5
2
7
----------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE C31 (PACE 5): CAESAREAN-SECTIONING
OBSERVATIONS - INDIVIDUAL DATA - Fo GENERATION FEMALE RATS
-- -----------------------------------------------------------------------------------------------I ----------
DOSAGE GROUP V
3.2 MG/KG/DAY
-------------------------------------------------------------------------------------------------------------
VIABLE EMBRYOS
NONVIABLE EMBRYOS IMPLANTATION SITES
CORPORA LUTEA
----- ------------------ ---------------- ---------------- ----------------
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
RIGHT LEFT
PAT
HORN
TOTAL
HORN
TOTAL
HORN
TOTAL
OVARY
TOTAL
---------------- ---------------------------------------------------------------------------------------------
8941 8947 8948 89si 89S3 8954 8958 8963
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
8
13
0
0
0
5
8
13
5
8
13
2
1
3
0
0
0
2
1
3
6
4
10
6
8
14
0
0
0
6
8
14
8
10
18
NOT PREGNANT
8965
7
8
15
0
0
0
7
8
15
8
8
16
8966
9
6
15
0
0
0
9
6
15
10
9
19
--------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C32 (PAGE 1): LITTER OBSERVATIONS
(CAESAREAN-DELIVERED
EMBRYOS) - INDIVIDUAL DATA - Pl GENERATION LIT
------- ----------
----- ------ --------- ---------------------------------- --- --------------- ----------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
------------------------------------- ----- -------------------------------------- I --------------- ----------
NUMBER OF LIVE
---- CONCEPTUSES
------
EMBRYOS
NONVIABLE
----------------------------------- --------------------------------------
--------------------------
RAT
TOTAL
N
N
-------------------------------------------
8802
17
8806
16
8809
13
-------------------------------------------------------
17
0
0.0
16
0
0.0
13
0
0.0
----------
8810
14
14
0
0.0
8615
10
8816
13
8820
14
8822
4
8825
13
8829
19
12
2
16.7
13
0
0.0
14
0
0.0
4
0
0.0
13
0
0.0
19
0
0.0
--------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAb/POSTNATAL
REPRODUCTION
TOXICI
TABLE C32 (PAGE 2): LITTER OBSERVATIONS
(CAESAREAN-DELIVERED
EMBRYOS) - INDIVIDUAL DATA - Fl GENERATION
LTTI
------- ----------------------------- -------------- -- ------------ ---------------- ---------------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
-------------------------------------------------------
-------------------------------------------------------
NUMBER OF LIVE
EMBRYOS -------------------------------------------------------
RAT #
TOTAL
N
-------------------------------------------------------
CONCEPTUSES
------
NONVIABLE -------------------- -------------------------------- --
N
!k
-------------------------------------------------------
8836
8
8
0
0.0
8837
17
8839
16
17
0
0.0
16
0
0.0
8843
15
8844
14
8848
12
15
0
0.0
14
0
0.0
12
0
0.0
8850
NOT PREGNANT
8856
NOT PREGNANT
8859
1
1
0
0.0
8861
NOT PREGNANT
---------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C32 (PAGE 3): LITTER OBSERVATIONS
(CAESAREAN-DELIVERED
EMBRYOS) - INDIVIDUAL DATA - Fl GENERATION LIT
-------- -------------------- ------DOSAGE GROUP 111
-------------------------------------
----------------------------------- ------------------
0.4 MG/KG/DAY --------------------------------------------------------
-----------------------------
NUMBER OF LIVE EMBRYOS
--------------------------------------------
---- CONCEPTUSES
--- --
NONVIABLE -------------------------------------------------
RAT #
TOTAL
N
N
t
----------------------------- ----------------------------------------------------------------
-----------------------------
8873 8877 8878
15 13 NOT PREGNANT
is
0
0.0
13
0
0.0
8879
NOT PREGNANT
8880 8883
13 NOT PREGNANT
13
0
0.0
8884 8886
1 NOT PREGNANT
1
0
0.0
8887
15
is
0
0.0
8888
16
16
0
0.0
--------------------------------------------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPON!;OR'S STUDY NUMBER:
6295-9)
AND PERINATAL/POSTNATAL
REFIRODUCTION TOXICI
TABLE C32 (PAGE 4): LITTER OBSERVATIONS
(CAESAREAN-DELIVERED
EMBRYOS) - INDIVIDUAL DATA - F) GENERATION LITT
---------------------------- --------
DOSAGE GROUP IV ----------------------- ---- --------
--------
-----
NUMBER OF LIVE EMBRYOS
-----------------------
------------ ------------- ------------------ --------
1.6 MG/KG/DAY
-------------------------------------------------- ---
---- CONCEPTUSES
------
NONVIABLE
-------------------------------------------------------
----------------------------------------------
RAT
TOTAL
N
N
--------------------------------------
-------------------------------------------------------
----------------
8907
NOT PREGNANT
8908
13
8910
13
8911
17
8912
is
8915
18
8916
11
8917
11
8922
13
8924
4
--------------------------------------
13
0
0.0
13
0
0.0
17
0
0.0
is
0
0.0
19
1
5.3
11
0
0.0
11
0
0.0
13
0
0.0
4
0
0.0
------------------------------------------------------------------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PPOS IN RAI'S (SPONSOR'S S7'ODY NUMBER:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXICI
TABLE C32 (PAGE 5): LITTER OBSERVATIONS
(CAESAREAN-DELIVERED
EMBRYOS) - INDIVIDUAL DATA - Fl GENERATION LITT
--------------------- -- -------- ------------ --- ------------- -- ------ ---- ----------------------
DOSAGE GROUP V
3.2 MG/KG/DAY
------------------------ --------------------- --- ------------------------
--- ----------------------- ------
NUMBER OF LIVE
--- CONCEPTUSES
------
EMBRYOS
NONVIABLE
------------------------ -------- ------------ --- ------------------------ ---- ---------------------------
RAT #
TOTAL
---------------------------------
N
N
%
------------ --- ------------------------ ---- ------------------------------
8941
16
8947
16
8948
13
8951
13
16
0
0.0
16
0
0.0
13
0
0.0
13
0
0.0
8953
13
13
0
0.0
8954
3
3
0
0.0
8958 8963
14 NOT PREGNANT
14
0
0.0
8965
15
15
0
0.0
8966
is
15
0
0.0
---------------------------------------------------------------------------------------------------------------
PROTOCOL 41B 008:
COMBINED ORAL PFOS IN RATS
(GAVAGE) (SPONSOR'S
FERRILITY,
DEVELOPMENTAL
S'IIIDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPROI)IJCTION TOXIC
TABLE C33 (PAGE 1): EMBRYONAL VITAL STATUS
- ---------- ------------------------ - ----
DOSAGE GROUP 1
0 (VEHICLE@
---------------------------------------------
EMBRYO #
1
2
3
4
5
6
---------------------------------------------
RAT # CLs
8802 8/10
A
A
A
A
A
A
8806 11/11
A
A
A
A
A
A
INDIVIDUAL DATA - Fl GENERATION
LITTERS
--------------------- ---------------------------
MG/KG/DAY
--------------------- ---------------------------
7
8
9
10
11
12
13
14
15
16
---------------------- ---------------------------
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
--- -------
--- -------
17
18
19
--- -------
A
8809 S/ 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
PROTOCOL 418-008:
COMBINED ORAL (GAVAGEI PFOS IN RATS (SPONSOR'S
FERTIIITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI(
TABLE C33 (PACE 2): EMBRYONAL VITAL STATUS - INDIVIDUAL DATA - Fl GENERATION LITTERS
------------------ ---------- --------
-- ----------------------- ----- ----------
DOSAGE GROUP Il
0.1
---------------------------------------
EMBRYO N
1
2
3
4
---------------------------------------
RAT # CLS
MG/KG/DAY
- -- ----------------------- ----------------
5
6
7
8
9
10
11
12
13
14
I ---------------------------------------------
8836 4/ 5
A
A
A
A/ A
A
A
A
--------- ------------
------------------------
15
16
17
18
19
------------------------
8837 ll/ 7
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
A
8839 ll/ 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 Il/ 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
CLS
CORPORA LUTEA/OVARY
EMBRYO
DENOTES POSITION OF CERVIX
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXIC
TABLE C33 (PACE 3): EMBRYONAL VITAL STATUS - INDIVIDUAL DATA - Fl GENERATION LITTERS
---- --------------------- ------ --------------
DOSAGE GROUP 111 ---- ----------------------------
0.4 MG/KG/DAY ---------------
EMBRYO #
1
2
3
4
5
6
7
--------------------------------------------------
RAT # CLs
8873
9/ 7
A
A
A
A
A
A
A
---------- ------------------ --------------------------
------------------------------------------------------------
8
9
10
11
12
13
14
15
16
17
le
19
------------------------------------------------------------
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
CLS = CORPORA LUTEA/OVARY
EMBRYO
DENOTES POSITION OF CERVIX
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAb
REPRODUCTION
TOXICI
TABLE C33 (PACE 4): EMBRYONAL VITAL STATUS - INDIVIDUAL DATA - Fl GENERATION LITTERS
---------------------- ----------------
DOSAGE GROUP IV
1.6 MG/KG/DAY
--- -------------------------------------------
EMBRYO #
1
2
3
4
5
6
-------------------------------------------
PAT # CLs
8907
NOT PREGNANT
- --- ----------------------- ------------------
----------------------------- ------------------
7
8
9
10
11
12
13
14
15
16
I -----------------------------------------------
---------------
---------------
17
18
19
---------------
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 0/ 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
CLs = CORPORA LUTEA/OVARY
EMBRYO
DENOTES POSITION OF CERVIX
PROTOCOL 418-008;
COMBINED ORAL (GAVACE@ FSRTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STIIDY NUMBER: 6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE C33 (PAGE 5): EMBRYONAL VITAL STATUS
INDIVIDUAL DATA - Fl GENERATION LITTERS
----------------------------- ---------------- ------- -------------------------------- ------------------
DOSAGE GROUP V
3.2 MG/KG/DAY
------------------------------------------------------------------------------------------------------------
EMBRYO #
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19
------------------------------------------------------------------------------------------------------------
RAT # CLs
8941 10/ 9
A
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
A
8948 0/ 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 S/ 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
CLS = CORPORA LUTEA/OVARY
EMBRYO
DENOTES POSITION OF CERVIX
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C34 (PAGE
1): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY
Fo GENERATION
FEMALE RATS/Fl GENERATION
LITTERS
AND SEX - INDIVIDUAL
DATA -
----------------------------------------------------- - ------------------------- ------------------------- -
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
----------------------------------------------------- I ----------------------------
---------------------------
DURATION OF
LITTER DELIVERED
RAT/
GESTATION
LIVE STILL- TOTAL
LITTER NUMBER
(DAYS) N
BORN N
BORN N
BORN N
I m
--------------------------------------------------------
NUMBER OF LIVE PUPS AT
COMPLETION
OF DAY POSTPARTUM
4a
4b
F
m
F
m
F
-------------------------
7
14
21
m
F
m
F
m
F
---------------------------
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817
23 23 23 23 23 23 23
c 22 23 NOT PREGNANT
9
1
10
12
1
13
is
0
is
17(l) 0
17
13
0
13
9
1
10
12
0
12
17
0
17
12
0
12
13
0
13
6
3
7
5
6
9
4 12
a
5
3
6
6
6
4 13
3
9
7
6
6
3
7
5
6
9
4 11
8
5
3
6
6
6
4 13
3
9
7
6
5
3
4
4
4
4
4
4
4
4
3
5
4
4
4
4
3
5
4
4
5
3
4
4
4
4
4
4
4
4
3
5
4
4
4
4
3
5
4
4
5
3
4
4
4
4
4
4
4
4
3
5
4
4
4
4
3
5
4
4
5
3
4
4
4
4
4
4
4
4
3
5
4
4
4
4
3
5
4
4
8818
NOT PREGNANT
8819
23
8821
23
8823
22
8824
22
8826
22
8827
23
8828
23
8830
23
8831
22
8832
23
8833
23
8834
23
8835
23
12
0
14
0
12
0
is
0
13
0
14
0
12
3
16
0
15
0
17
0
15(l) 0
13
1
16
0
12 14 12 15 13 14 15 16 15 17 15 17[31 16
3
9
7
7
7
s
9
6
5
8
s
9
2 10
11
5
10
5
6 11
8
6
6
7
12
4
3
9
7
6
7
5
9
6
5
a
5
9
2 10
11
5
10
5
6 11
8
6
6
7
12
4
3
5
3
5
4
4
4
4
4
4
4
4
2
6
4
4
4
4
4
4
4
4
4
4
7
1
3
5
3
5
4
4
4
4
4
4
4
4
2
6
4
4
4
4
4
4
4
4
4
4
7
1
3
5
3
5
4
4
4
4
4
4
4
4
2
6
4
4
4
4
4
4
4
4
4
4
7
1
3
5
3
5
4
4
4
4
4
4
4
4
2
6
4
4
4
4
"4 4
4
4
4
4
71
--------------------------------------------------------------------------------------------------------------
M
MALE
F = FEMALE
NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM.
NUMBER OF PUPS IN WHICH CANNIBALIZATION a. Number of live pups preculling. b. Number of live pups postculling.
AND/OR AUTOLYSIS PRECLUDED THE DETERMINATION
OF VIABILITY.
c. No confirmed mating date.
PROTOCOL
418-008.,
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS TN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C34 (PAGE 2): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY
Fo GENERATION
FEMALE RATS/Fl GENERATION
LITTERS
AND SEX - INDIVIDUAL DATA -
-------- ----------------------------- ------ ------------------------------------------------------- --------
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
-------- ------------------------------------ ---- -------------------------------------------------- --------
DURATION OF
LITTER DELIVERED
NUMBER OF LIVE PUPS AT
RAT/
GESTATION
LIVE STILL- TOTAL
COMPLETION
OF DAY POSTPARTUM
LITTER
(DAYS)
BORN
BORN
BORN
1
4a
4b
7
14
21
NUMBER
N
N
N
N
m
F
m
F
m
F
m
F
m
F
m
F
---------------------------------------------------------------------------------------------------------------
8838
22
17
0
17
10
7
10
7
4
4
4
4
4
4
4
4
8840
23
19(1)
0
19
12
6
12
6
4
4
4
4
4
4
4
4
8841
23
14
0
14
9
5
9
5
4
4
4
4
4
4
4
4
8842c
23
15
0
is
5 10
5 10
4
4
4
4
4
4
4
4
8845
23
13(l) 0
13
3
9
3
8
3
5
3
5
3
5
3
5
8846
23
is
0
is
8
7
8
7
4
4
4
4
4
4
4
4
8847
23
14
0
14
9
5
9
5
4
4
4
4
4
4
4
4
8849
22
17
0
17
10
7
10
6
4
4
4
4
4
4
4
4
8851
23
15(l) 0
15
5
9
5
9
4
4
4
4
4
4
4
4
8852
23
10
0
12(21
7
3
73
5
3
5
3
5
3
5
3
8853
23
19
0
19
13
6
13
6
4
4
4
4
4
4
4
4
8854
23
14
0
14
8
6
8
6
4
4
4
4
4
4
4
4
8855
23
15
0
15
5 10
5 10
4
4
4
4
4
4
4
4
8857
23
15
0
15
96
9
6
4
4
4
4
4
4
4
4
8858
23
10
1
11
2
8
2
8
2
6
2
6
2
6
2
6
8860
23
15
0
15
7
8
7
8
4
4
4
4
4
4
4
4
8862
23
14
0
14
7
7
7
7
4
4
4
4
4
4
4
4
8863
22
16
0
16
12
4
12
4
4
4
4
4
4
4
4
4
8864
23
10
0
10
5
5
s5
4
4
4
4
4
4
4
4
8865
22
14
0
14
10
4
10
4
4
4
4
4
4
4
4
4
8866
23
16
0
16
9
7
9
7
4
4
4
4
4
4
4
4
8867
23
13
0
13
5
8
5
8
4
4
4
4
4
4
4
4
8868
22
14
0
14
8
6
7
6
4
4
4
4
4
4
4
4
8869
23
16
1
17
11
5
11
5
4
4
4
4
4
4
4
4
8870
23
11
0
11
s
6
5
6
4
4
4
4
4
4
4
4
---------------------------------------------------------------------------------------------------------------
M
MALE
F = FEMALE
NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY 1 POSTPARTUM.
NUMBER OF PUPS IN WHICH CANNIBALIZATION a. Number of live pups preculling.
b. Number of live pups postculling.
AND/OR AUTOLYSIS
PRECLUDED THE DETERMINATION
OF VIABILITY.
C. Dam 8842 delivered one additional pup on day 2 of lactation; values for day I postpartum excluded from gro statistical analyses.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAb
REPRODUCTION
TOXICIT
TABLE C34 (PAGE 3): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY AND.SEX - INDIVIDUAL DATA -
Po GENERATION
FEMALE RATS/Fl GENERATION
LITTERS
-------------- ---- - ---------------- ---- ---------------------------- ------------------ ------ ------------
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
------------------------------------------- ---------------------- ----------------------------
-- ------------
DURATION OF
LITTER DELIVERED
NUMBER OF LIVE PUPS AT
RAT/
GESTATION
LIVE STILL- TOTAL
COMPLETION
OF DAY POSTPARTUM
LITTER
(DAYS)
BORN
BORN
BORN
I
4a
4b
7
14
21
NUMBER
N
N
N
N
m
F
m
F
m
F
m
F
m
F
m
F
----------------------------------------------------------------------------------------------------------------
8871
NOT PREGNANT
8872 8874c 8875 8876 seal 8882 8885 8889 8890 8891 8892 8893 8894 8895 0896d 8897d 8898 8899C 8900 8901 8902 8903 8904
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
13
1
14
15
0
15
13
0
13
7(l) 0
7
14
0
14
17
0
17
14
2
16
14
0
14
12
0
12
15
0
15
12
0
12
13
0
13
3
0
3
17
0
17
14
0
14
14
0
14
12
1
13
16
0
16
15
1
16
13
0
13
is
1
16
8
5
11
4
9
4
3
3
5
9
8
9
9
5
9
5
5
7
6
9
6
6
8
5
2
1
9
8
8
6
5
9
8
4
8
8
6
9
5
8
7
8
8
5
11
4
9
4
3
3
5
9
8
9
9
5
9
5
5
7
6
9
6
6
8
5
2
1
9
7
8
6
5
9
8
4
8
8
6
8
5
8
7
7
4
4
4
4
4
4
3
3
4
4
4
4
5
3
4
4
4
4
4
4
4
4
4
4
2
1
4
4
4
4
4
4
4
4
4
4
4
4
3
5
4
4
4
4
5
3
4
4
3
3
4
4
4
4
5
3
4
4
4
4
4
4
4
4
4
4
2
1
4
4
4
4
4
4
4
4
5
3
4
4
3
5
4
4
4
4
5
3
4
4
3
3
4
4
4
4
5
3
4
4
4
4
4
4
4
4
4
4
2
1
4
4
4
4
4
4
4
4
4
3
4
4
3
5
4
4
4
4
s
3
4
4
3
3
4
4
4
4
5
3
4
4
4
4
4
4
4
4
4
2
2
1
4
4
4
4
4
4
4
4
4
3
4
4
3
5
4
4
8905
22
19
0
19
8 11
8 10
4
4
4
4
4
4
4
4
-----------------------------------------------------------------------------------------------------------------
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;
excluded from group averages and statistical analyses.
values for day 4 postpartum
postculling
were
d. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The pup
arbitrarily distributed between the two dams and values will be included in group averages and statistical a
PROTOCOB 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAb/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C34 (PAGE 4):
NATURAL DELIVERY,
IMPLANTAT10N
SITES, AND PUP VIABILITY
Fo GENERATION
FEMALE RATS/Fl GENERATION
LITTERS
AND SEX - INDIVIDUAL
DATA -
---------------------------------------- ----------------------- ----- I ------------------- -- ------------------
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
----------------------------------- ---- ---------------------------------------------------------------------
DURATION OF
LITTER DELIVERED
NUMBER OF LIVE PUPS AT
RAT/
GESTATION
LIVE STILL- TOTAL
COMPLETION
OF DAY POSTPARTUM
LITTER
(DAYS)
BORN
BORN
BORN
1
4a
4b
7
14
21
NUMBER
N
N
N
N
m
F
m
F
m
F
m
F
m
F
m
F
----------------------------------------------------------------------------------------------------------------
8906 8909 8913 8914
c 22 22 NOT PREGNANT
14(l) 0
14
11
0
11
12
0
12
8
5
4
7
5
7
6
4
4
7
4
7
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
8918
NOT PREGNANT
8919 8920 8921 8923
22 23 23 NOT PREGNANT
16
0
16
9(1) 0
9
11
2
13
10
6
6
2
9
2
10
5
5
1
8
2
4
4
5
1
6
2
4
4
5
1
6
2
4
4
5
1
6
2
4
4
5
1
6
2
8925 8926 8927 8928 8929 8930 8931 8932 8933
22 22 22 23 23
c 22 22 NOT PREGNANT
12
0
12
12
0
12
17
0
17
12
0
12
8
0
a
15(5)
0
15
11(7)
0
11
17
0
17
2 10
3
9
6 11
7
5
6
2
7
3
4
-
11
6
1
8
1
3
3
5
7
s
--
7
3
4
-
7
4
1
7
1
3
3
5
4
4
--
5
3
4
-
4
4
1
7
1
3
-2
4
4
-
-
5
3
4
-
4
4
1
6
1
3
-
2
4
4
-
-
5
3
4
-
4
4
1
6
1
3
-2
4
4
-
-
5
3
4
-
4
4
8934 893S 8936 8937 8938
22 22 23 23 MORIBUND
13
0
12
0
15(4)
1
9
2
SACRIFICED
ON DAY
13 12 16 11 36 OF STUDY
76
7
5
7
4
5
4
6
4
6
5
-
-
5
3
4
4
4
4
-
-
5
3
4
4
4
4
-
-
5
3
4
4
4
4
-
-
5
3
4
4
4
4
-
-
5
3
8939
c
13(8)
0
13
3
2
3
2
3
2
3
2
3
2
3
2
8940
22
15(l) 1
16
9
5
8
5
4
4
4
4
4
4
4
4
-----------------------------------------------------------------------------------------------------------------
M
MALE
F = FEMALE
( = NUMBER OF PUPS DYING BEFORE WEIGHING a. Number of live pups preculling.
ON DAY 1 POSTPARTUM.
b. Number of live pups postculling.
c. No confirmed mating date.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (!,PONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C34 (PAGE 5): NATURAL DELIVERY,
IMPLANTAT10N
SITES, AND PUP VIABILITY AND SEX - INDIVIDUAL
Fo GENERATION
FEMALE RATS/Fl GENERATION
LITTERS
DATA -
- ------------------------- ----- ------------ -------- ------ ----------- --------------------------- -------
MATERNAL
DOSAGE GROUP V
3.2 MG/KG/DAY
--------------------------- ------ ---------------------------- -----------------------------------------------
DURATION OF
LITTER DELIVERED
NUMBER OF LIVE PUPS AT
RAT/
GESTATION
LIVE STILL- TOTAL
COMPLETION
OF DAY POSTPARTUM
LITTER
(DAYS)
BORN
BORN
BORN
1
4a
4b
7
14
21
NUMBER
N
N
N
N
m
F
m
F
m
F
m
F
m
F
m
---------------------------------- ----------------------------------------------------------------------------
8942
23
6(6) 0
6
8943
22
2(2) 4
6
8944
22
3(3) 2
5
6945
NOT PREGNANT
8946
22
8949
22
8950
22
9
3
12
12
0
12
4 (4) 2
6
4
5
6
6
-
-
8952
NOT PREGNANT
8955
22
7(7) 2
9
-
-
8956 8957
22 NOT PREGNANT
13(2)
0
13
6
5
8959
22
8960
23
8961
22
8962
22
8964
22
8967
22
8968
22
8969
22
10(2)
3
4(4) 9
11(1)
3
i(l) 3
13(3)
1
0
8
4(2)
6
S(S)
0
13 13 14
4 14
9(1) 10
5
4
4
-
-
6
4
-
-
8
2
-
-
2 -
8970
22
9
2
11
8971
22
13
0
13
8972
NOT PREGNANT
5
4
7
6
8973
23
8974
23
10(9)
1
11
o(B)
3
11
1
-
-
8975
22
12(12) 0
12
-
---------------------------------------------------------------------------------------------------------------
M
MALE
F = FEMALE
NUMBER OF PUPS DYING BEFORE WEIGHING ON DAY I POSTPARTUM.
NUMBER OF PUPS IN WHICH CANNIBALIZATION a. Number of live pups preculling.
AND/OR AUTOLYSIS
PRECLUDED THE DETERMINATION
OF VIABILITY.
b. Number of live pups postculling.
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C35 (PAGE 1): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl G
- ------------------- -
MATERNAL DOSAGE GROUP 1 ------------------------ ----
PAT/
---------- - ---0 (VEHICLE)
-------------------
--------------------- ----MG/KG/DAY
-----------------------------
- -- ------------ - ----------------------------------
LI7"rER
DAY 1
DAY 4a
DAY 4b
DAY 7
DAY 14
NUMBER
m
F
T
m
F
T
m
F
T
m
F
T
m
F
T
---------------------- --------------------------------------------------------------------------- ------------
8801 8003 8804 8805 8807 8808 8811 8812 8813 8814 8817
7.2
6.7
7.0
10.1
9.8 10.0
10.1
9.8 10.0
15.3 14.9 15.1
31.3 30.1 30.9
46
6.9
6.8
6.8
10.2 10.5 10.3
10.0 10.7 10.3
15.3 16.2 15.8
29.8 33.4 31.6
49
7.5
6.6
6.9
9.7
9.0
9.3
10.0
9.7
9.8
14.8 14.7 14.7
34.8 32.8 33.8
56
5.7
5.3
5.4
7.2
6.6
6.7
7.2
6.8
7.0
10.1
9.3
9.7
27.6 23.9 25.7
46
7.3
6.9
7.2
9.9
9.2
9.6
10.0
9.1
9.5
15.5 14.2 14.9
34.0 31.9 33.0
54
7.1
7.0
7.1
9.9
9.6
9.7
9.9
9.8
9.8
14.5 14.5 14.5
29.1 28.8 28.9
49
7.9
7.5
7.7
11.4 11.0 11.2
11.6 11.4 11.5
17.6 17.1 17.3
35.5 34.0 34.7
58
7.2
6.7
6.8
10.3
9.2
9.4
10.3 10.1 10.2
16.2 15.8 16.0
35.4 34.2 34.8
58
7.3
6.6
6.8
10.2
9.5
9.6
10.2
9.6
9.8
15.7 14.8 15.2
30.2 29.7 29.9
51
8.1
8.0
8.1
12.5 12.0 12.3
12.6 12.0 12.2
20.2 18.8 19.5
39.8 37.7 38.8
64
NOT PREGNANT
Bale
NOT PREGNANT
8819
7.5
6.8
7.0
11.0
9.9 10.2
11.0
8821
7.1
6.7
6.9
9.6
9.4
9.6
9.8
882i
6.6
6.3
6.5
9.5
9.1
9.3
9.6
8824
6.0
5.6
5.9
8.2
7.5
7.9
8.4
8826
6.4
6.1
6.2
8.7
8.4
8.S
8.6
8827
6.3
5.5
5.8
8.6
7.7
8.0
8.9
8828
6.8
6.5
6.6
9.2
8.8
8.8
9.2
8830
6.6
6.1
6.4
8.5
8.4
8.5
8.8
8831
6.4
6.0
6.3
8.4
7.7
8.2
8.4
8832
6.2
5.9
6.0
8.3
7.9
8.0
8.6
8833
6.3
6.0
6.2
9.0
8.4
8.8
9.3
8834
6.7
6.2
6.4
9.8
9.2
9.4
9.9
8835
5.8
5.6
5.8
7.9
8.2
8.0
8.6
---------------------------------------------------------
10.6 10.7
17.1 16.5 16.7
35.3 33.9 34.5
54
9.5
9.6
1S.9 15.6 15.7
31.3 30.0 30.5
so
9.2
9.4
14.8 14.4 14.6
30.6 29.7 30.1
50
7.9
8.1
13.6 12.6 13.1
28.3 27.5 27.9
45
8.4
8.5
13.9 13.4 13.6
28.9 27.4 20.2
44
8.0
8.5
11.7 11.1 11.4
23.6 22.5 23.0
41
9.0
9.0
14.6 14.4 14.4
33.2 32.2 32.4
52
8.6
8.7
14.6 13.8 14.2
29.9 29.2 29.S
49
8.0
8.2
13.8 13.1 13.4
32.0 31.8 31.9
49
8.4
8.5
14.4 14.5 14.5
30.6 30.7 30.6
so
8.4
8.9
16.6 14.7 1S.6
34.0 30.9 32.5
53
9.2
9.6
15.5 14.6 15.1
31.3 29.8 30.6
46
7.7
8.5
14.4 15.0 14.5
32.8 29.7 32.4
50
-----------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL IGAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C35 (PAGE 2): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GE
--------------- ---MATERNAL DOSAGE GROUP 11
------------- --- ------- ------ -------------0.1 MG/KG/DAY
---- -------- --------------------
---------------------------------------------------- ------ ----------------------------- --------------------
RAT/
LITTER NUMBER
DAY 1
m
F
T
DAY 4a
m
F
T
DAY 4b
m
F
T
DAY 7
m
F
T
DAY 14 m
-------------------------- -------------------------------- ----------------------------- -------------------- -
8838
5.9
5.6
5.8
8.3
7.8
8.1
8.4
8.0
8.2
13.9 13.0 13.4
32.0 31.5 31.8
51.
8840
6.4
6.2
6.3
7.9
7.5
7.7
8.3
8.0
8.1
12.8 12.8 12.8
29.6 29.9 29.8
48.
8841
6.5
6.6
6.5
8.8
9.0
8.9
9.0
9.0
9.0
14.8 14.6 14.7
32.5 31.8 32.1
48.
8842c
6.8
6.6
6.7
9.3
8.7
8.9
9.3
8.7
9.0
14.5 13.9 14.2
28.7 28.4 28.5
45.
8845
7.0
6.6
6.7
10.0 10.0 10.0
10.0 10.2 10.1
13.9 14.0 14.0
29.9 29.9 29.9
51.
8846
6.4
5.8
6.1
9.1
8.4
8.8
9.2
8.8
9.0
14.3 13.4 13.8
31.5 29.8 30.7
49.
8847
6.6
6.6
6.6
9.4
9.2
9.3
9.7
9.3
9.5
14.8 14.4 14.6
26.4 25.6 26@O
46.
8849
5.7
5.2
5.5
7.9
7.3
7.7
8.1
7.4
7.7
13.0 12.2 12.6
29.3 28.1 28.7
46.
8851
6.3
5.8
6.0
8.5
8.3
8.4
8.7
8.0
8.4
13.8 12.4 13.2
29.8 28.4 29.1
50.
8852
6.5
6.0
6.4
9.9
9.5
9.8
9.9
9.5
9.8
15.1 14.7 15.0
31.3 31.1 31.2
49.
8853
5.9
6.0
5.9
7.0
7.6
7.2
7.9
7.8
7.9
13.0 12.0 13.0
28.7 28.8 28.8
46.
8854
7.1
6.7
6.9
9.5
9.2
9.4
9.1
9.1
9.1
15.4 14.7 15.0
33.2 31.2 32.2
49.
8855
6.6
6.1
6.3
8.9
8.3
8.5
8.9
8.6
8.8
14.6 13.9 14.2
30.9 28.6 29.8
44.
8857
6.4
6.2
6.4
8.9
8.2
8.6
9.0
8.5
8.8
14.3 13.8 14.0
31.3 31.2 31.3
51.
8858
7.6
7.1
7.2
11.0 10.3 10.5
11.0 10.1 10.4
17.6 15.8 16.2
34.2 31.5 32.2
55.
8860
6.6
6.2
6.4
9.5
8.8
9.2
9.8
8.9
9.3
15.8 14.2 15.0
31.4 29.0 30.2
50.
6862
6.8
6.5
6.6
9.7
9.4
9.6
9.7
9.7
9.7
15.8 15.6 15.7
35.5 34.3 34.9
sa.
8863
6.0
6.3
6.1
8.8
8.9
8.8
9.6
8.9
9.3
15.4 14.1 14.8
31.3 29.4 30.3
46.
8864
7.2
6.9
7.1
9.0
8.8
8.9
9.2
8.8
910
14.1 14.4 14.3
31.4 31.6 31.5
48.
8865
6.2
5.6
6.1
8.7
8.3
8.6
8.7
8.3
8.5
14.4 13.4 14.0
31.3 29.7 30.5
51.
8866
6.2
6.0
6.2
7.5
7.4
7.5
7.7
7.8
7.7
11.0 10.9 11.0
24.0 24.3 24.2
39.
8867
7.7
6.6
7.0
10.7
9.2
9.8
11.0
8.6
9.8
17.5 14.1 15.8
32.6 29.9 31.2
54.
8868
6.4
5.9
6.2
9.8
8.8
9.3
10.3
9.0
9.7
16.1 14.8 15.4
35.6 32.8 34.2
54.
8869
6.6
6.2
6.5
8.8
8.1
8.5
8.7
8.2
8.5
13.8 13.2 13.5
31.3 28.9 30.1
50.
8870
6.8
6.3
6.5
10.0
9.1
9.5
10.2
9.3
9.7
17.3 15.4 16.4
34.7 32.2 33.4
53.
----------------------------------------------------------------------------------------------------------------
M = MALE
P = FEMALE
ALL WEIGHTS WERE RECORDED
a. Preculling.
T = TOTAL (SUM OF PUP WEIGHTS/NUMBER
IN GRAMS (G).
MEAN LITTER WEIGHTS
OF LIVE INCLUDE
PUPS) ONLY
DAY WEIGHTS
= DAY POSTPARTUM OF LIVE PUPS.
b. Postculling.
C. Dam 8842 delivered one additional pup on day 2 of lactation; values for day 1 postpartum excluded from grou statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C3S (PAGE 3): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl
------------------------
----------
MATERNAL
DOSAGE GROUP 111
0.4
-----------------------------------------
RAT/
---------- ---- ---------- - ----- - --- --- ----------- -----------
MG/KG/DAY ----------------------------------------------------
---------------
LITTER NUMBER
DAY 1
m
F
T
DAY 4a
m
F
T
DAY 4b
m
F
T
DAY 7
m
F
T
DAY 14
m
F
T
----------------------------------------- --------------------------------------------------------------------
8871
NOT PREGNANT
8872 8074c 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894 8895 8896d 8897d 8898 8899C 8900 8901 8902 8903
6.2
6.0
6.2
8.3
8.3
8.3
8.6
8.5
8.6
13.6 13.0 13.3
30.5 29.1 29.8
5
6.0
5.6
S.9
8.9
8.0
8.6
9.4
8.3
9.0
15.1 13.3 14.4
29.3 27.5 28.6
4
6.7
6.6
6.7
9.4
9.6
9.5
9.6
9.6
9.6
15.1 14.8 14.9
29.8 29.6 29.7
4
8.7
8.3
8.5
13.1 12.7 12.9
13.1 12.7 12.9
17.8 17.7 17.7
33.6 33.7 33.6
5
6.3
5.9
6.0
8.3
7.7
7.9
8.6
7.4
8.0
14.1 12.0 13.1
30.7 27.8 29.2
so
6.9
6.2
6.5
8.9
8.2
8.5
8.9
8.8
8.8
13.2 13.4 13.3
30.2 30.4 30.3
53
6.8
6.5
6.7
9.3
8.8
9.1
9.5
9.1
9.3
15.3 14.9 15.1
31.5 29.9 30.9
51
5.7
5.8
5.7
7.1
7.1
7.1
7.2
7.2
7.2
12.2 11.8 12.0
26.6 25.8 26.2
38
6.7
6.5
6.6
10.0
9.8
9.9
10.2 10.1 10.2
14.6 14.2 14.4
30.6 30.2 30.4
51
6.2
6.2
6.2
8.9
9.0
9.0
9.5
9.2
9.4
14.6 14.2 14.4
31.0 30.7 30.8
48
6.6
6.4
6.6
9.2
9.0
9.1
9.3
8.8
9.0
14.2 13.5 13.9
28.4 27.8 28.1
38
6.5
6.0
6.3
8.2
7.7
8.0
8.S
7.6
8.1
14.1 12.6 13.4
30.4 22.5 26.4
48
8.2
7.6
8.0
11.6 11.3 11.5
11.6 11.3 11.5
17.0 16.6 16.9
30.8 31.7 31.1
46
5.4
5.9
5.6
7.4
7.8
7.6
7.8
8.1
7.9
12.6 12.9 12.8
29.1 28.1 28.6
47
6.3
5.6
6.0
9.0
8.2
8.6
9.4
8.6
9.0
14.2 13.4 13.8
33.4 31.8 32.6
52
6.7
6.5
6.5
6.7
6.2
6.5
6.2
5.8
6,0
8.9
8.8
8.8
9.2
8.8
9.1
9.1
8.6
8.8
9.2
8.8
9.0
14.8 13.9 14.4
32.8 31.5 32.2
46
9.4
8.8
9.1
14.0 13.4 13.7
26.6 25.6 26.1
43
8.8
8.8
8.8
14.2 14.2 14.2
32.3 31.8 32.1
54
6.5 6.7 6.4 NOT
5.6 6.2 6.0 PREGNANT
6.1 6.4 6.2
9.2
8.2
8.6
9.2
8.5
8.8
7.9
7.7
7.8
9.1
8.8
9.0
15.0 14.6 14.8
32.0 31.7 31.8
52
9.1
8.8
8.9
10.3 11.5 11.0
24.5 26.2 25.6
42
8.0
7.6
7.8
13.6 12.4 13.0
31.8 29.7 30.8
50
8904
NOT PREGNANT
890S
5.8
5.7
5.8
8.0
7.4
7.7
8.3
7.0
7.6
13.8 12.5 13.2
33.6 31.2 32.4
53
---------------------------------------------------------------------------------------------------------------
M = MALE
F = FEMALE
ALL WEIGHTS WERE RECORDED
a. Preculling.
T = TOTAL (SUM OF PUP WEIGHTS/NUMBER
IN GRAMS (G).
MEAN LITTER WEIGHTS
OF LIVE INCLUDE
PUPS) ONLY
DAY WEIGHTS
= DAY POSTPARTUM OF LIVE PUPS.
b. Postculling.
C. A sexing error was found prior to weighing on day 7 postpartum; values for day 4 postpartum postculling we 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 p
arbitrarily distributed between the two dams and values will be included in group averages and statistical
PROTOCOL 410-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C35 (PAGE 4): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA
Fl GE
------------------- - - -- -----------------------
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
------- ----------------------------------------------------
--- ----------------------
---------------------------------------------------------------
RAT/ LITTER
NUMBER
DAY 1
DAY 4a
DAY 4b
DAY 7
DAY 14
m
F
T
m
F
T
m
F
T
m
F
T
m
F
T
m
------89-0-6--------4-.-9 ----5-.-0----4-.-9-----7-.-5----7-.-4-----7.-5------7-.6-----7-.4-----7-.-6----1-1-.-9---1-1-.-4----11-.-6-----26-.-8----2-6.-2----2-6-.-5 ----42.
8909
6.4
6.0
6.1
8.5
8.0
8.2
8.5
8.4
8.4
12.9 12.9 12.9
27.3 27.1 27.2
42.
8913
5.7
S.6
5.7
8.0
7.8
7.9
8.0
8.1
8.1
11.6 11.8 11.7
24.6 25.0 24.8
40.
8914
NOT PREGNANT
8918
NOT PREGNANT
6919 0920 8921 8923
5.8
5.4
5.7
5.9
5.7
5.8
6.5
6.2
6.4
NOT PREGNANT
7.1
6.5
6.9
8.4
9.5
8.6
8.8
8.6
8.7
7.4
6.7
7.1
11.8 10.3 11.0
27.1 23.8 25.4
46.
8.4
9.S
6.6
11.3 13.4 11.6
22.7 24.4 23.0
40.
9.4
8.6
9.2
13.2 12.2 13.0
26.2 25.2 26.0
44.
8925 8926 8927 8928 8929 8930 8931 8932 8933
5.4 5.9 5.6 7.1 6.0 5.1 S.1 5.6 NOT
5.6 5.6 6.1 6.5 6.0 5.7 ---
5.3 PREGNANT
5.6 5.6 5.9
6.8 6.0 5.3 5.1 5.S
7.8
6.9
6.1
6.1
5.0
4.7
8.6
8.3
NO SURVIVING
8.1
7.0
7.5
---
5.9
5.4
7.0 6.1 4.8 8.5
PUPS 7.8 7.5 5.7
7.8 6.1 5.0 9.1 ON DAY 8.5 7.5 6.0
7.3
7.@4
6.1
6.1
4.7
4.8
8.4
8.8
2 POSTPARTUM
7.0
7.9
--- 7.5
5.4
5.7
11.5 8.5 ---
13.2
10.6 8.3 6.3
12.4
10.7 8.4 6.3
12.8
13.0 10.9
9.2
10.3 --8.7
12.0 10.9
9.0
26.3 22.7
---
26.6
24.7 19.9 14.6 25.4
24.9 20.6 14.6 26.0
28.8 25.3 20.8
25.0 ---
20.6
27.4 25.3 20.7
37. 35.
-43.
49. 43. 36.
8934 8935 8936
5.6
5.0
5.3
5.8
5.4
5.6
5.4
5.2
5.3
6.4
5.7
6.1
6.6
5.7
6.2
10.2
8.5
9.3
24.4 21.5 23.0
38.
6.5
6.5
6.5
6.6
6.7
6.6
10.2 10.5 10.4
24.1 24.2 24.2
40.
NO SURVIVING
PUPS ON DAY 4 POSTPARTUM
8937 8938
7.0
6.6
6.8
8.8
9.0
8.9
8.8
9.0
8.9
12.8 11.8 12.4
28.2 26.8 27.7
45.
MORIBUND
SACRIFICED
ON DAY 36 OF STUDY
8939
5.3
4.9
5.1
8.2
7.8
8.0
8.2
7.8
8.0
11.4 10.7 11.1
23.5 22.4 23.1
39.
8940
5.8
5.4
5.7
7.6
6.8
7.3
8.6
7.1
7.9
13.8 11.2 12.5
30.7 25.4 28.0
49.
----------------------------------------------------------------------------------------------------------------
M = MALE ALL WEIGHTS
F = FEMALE WERE RECORDED
T = TOTAL (SUM IN GRAMS (G).
OF PUP WEIGHTS/NUMBER MEAN LITTER WEIGHTS
OF LIVE INCLUDE
PUPS) ONLY
DAY = DAY POSTPARTUM WEIGHTS OF LIVE PUPS.
a. Preculling.
b. Postculling.
PROTOCOL 418-OOR:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C35 (PAGE 5): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl G
----------- ---- ----------------------- ---- --- ----------- ----------
MATERNAL
DOSAGE GROUP V
3.2 MG/KG/DAY
---------------------------- --------
---------------- ----------------------- -------------------------------- ---------------------------- --------
RAT/
LITTER NUMBER -----------
DAY 1
DAY 4a
DAY 4b
DAY 7
DAY 14
m
F
T
m
F
T
m
F
T
m
F
T
m
F
------------------------------------------------------------------------------------------
T
p
---------
8942 8943 8944 8945
NO SURVIVING NO SURVIVING NO SURVIVING NOT PREGNANT
PUPS PUPS PUPS
ON DAY ON DAY ON DAY
1 OF 1 OF I OF
LACTATION LACTATION LACTATION
8946 8949 8950 8952
5.6
5.2
5.2
4.8
NO SURVIVING
NOT PREGNANT
5.3 5.0
PUPS
NO SURVIVING PUPS ON DAY 2 OF LACTATION NO SURVIVING PUPS ON DAY 2 OF LACTATION ON DAY 1 OF LACTATION
8955 8956 8957
NO SURVIVING
5.3
5.0
NOT PREGNANT
PUPS 5.2
ON DAY 1 OF NO SURVIVING
LACTATION PUPS ON DAY
2 OF
LACTATION
8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972 8973 8974 8975
5.0
4.8
NO SURVIVING
5.0
5.0
NO SURVIVING
6.0
6.0
NO SURVIVING
---
S.1
NO SURVIVING
5.8
5.7
5.8
5.4
NOT PREGNANT
S.3
---
NO SURVIVING
NO SURVIVING
4.9 PUPS
5.0 PUPS
6.0 PUPS
5.1 PUPS
5.8 5.6
5.3 PUPS PUPS
NO SURVIVING ON DAY 1 OF NO SURVIVING ON DAY I OF NO SURVIVING ON DAY 1 OF NO SURVIVING ON DAY 1 OF NO SURVIVING NO SURVIVING
PUPS ON LACTATION
PUPS ON LACTATION
PUPS ON LACTATION
PUPS ON LACTATION
PUPS ON PUPS ON
DAY DAY DAY DAY DAY DAY
2 OF 2 OF 2 OF 2 OF 2 OF 2 OF
NO SURVIVING ON DAY 1 OF ON DAY 1 OF
PUPS ON DAY LACTATION LACTATION
2 OF
LACTATION LACTATION LACTATION LACTATION LACTATION LACTATION LACTATION
----------------------------------------------------------------------------------------------------------------
M= ALL a.
MALE
F=
WEIGHTS WERE
Preculling.
FEMALE RECORDED
T = TOTAL (SUM OF PUP WEIGHTS/NUMBER
IN GRAMS (G).
MEAN LITTER WEIGHTS
OF LIVE INCLUDE
PUPS) ONLY
DAY WEIGHTS
= DAY POSTPARTUM OF LIVE PUPS.
b. Postculling.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C36 (PAGE 1): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
-------PUP
-------RAT/
---------- -------------------------- - -----------------
#
1
2
3
4
5
6
7
8
9
------------------------------- I -------------------------
-- ------------------------- -------------
10
11
12
13
14
15
16
----- ---------------------- I --------------
LITTER
MATERNAL DOSAGE GROUP 1
--------------------- --------------------------
8801 8803 8804 8805 8807 8808 Bell 8812 8813 8814 B817
6.9
7.4
7.2
5.9
8.1
7.7
5.4
5.7
7.1
6.8
7.7
7.1
7.9
8.3
7.2
7.3
7.1
7.8
8.4
8.6
NOT PREGNANT
7.2 7.7 6.9 5.8 7.0 6.5 8.4 7.9 7.1 8.2
7.5 6.7 7.0 6.0 8.0 6.3 8.2 6.2
6.6 7.8
7.1 7.6 7.6
5.3 7.1 7.1 7.4 6.6 5.9 7.6
7.0 6.4 7.5 5.4 7.6 6.7 7.1 7.0 6.3 8.3
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
DAY 1
--------------------------------------------------------------
ms
6.5
6.7
6.8
6.8
ms
7.2
6.4
6.6
6.7
7.0
6.8
6.9
6.8
5.1
6.9
6.2
6.9
6.9
6.8
5.3
4.9
5.7
5.4
5.3
5.3
5.0
5.3
5.3
5.2 F
7.5
7.4
6.8
7.0
6.8
6.4
7.5
7.7
7.2
7.3
FS
7.4
7.3
7.7
7.8
7.6
7.3
6.5
5.7
7.5
6.7
6.9
6.8
6.4
6.7
6.6
6.3
6.6
7.2
6.8
6.4
6.8
6.5
7.9
8.7
7.9
7.8
8.0
7.9
7.7
8818
NOT PREGNANT
8819
7.6
7.5
7.4
3.8
6.9
7.5
7.0
7.2
6.8
7.4
7.3
7.8
8823
6.7
6.7
7.1
6.5
6.7
6.4
6.0
6.7
6.1
5.9
6.6
6.3
8824 8826
6.2
5.3
S.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
8827
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
8828
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
8830
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
8831
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
8832
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
8833
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
8834
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
8835
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PERTII,ITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE C36 (PAGE 2): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA - Fl GENERATION
PUPS
-------------------- ------- --------------------
PUP #
1
2
3
4
5
6
---------------------------- -------------------
RAT/
---- ------------------------ --- --------------------- ----
7
8
9
10
11
12
13
14
15
16
1
--------------------------- -------------------------------
LITTER
MATERNAL DOSAGE GROUP Il
0.1 MG/KG/DAY
POSTPARTUM
DAY 1
---------------------------------------------------------------------------------------------------------------
8838 8840 8841
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
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
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
8842a
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
8845
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
8846 8847
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
8849 8851
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
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 PD 1
8852
6.5
6.9
7.1
6.2
6.4
6.5
6.2
5.0
5.9
6.3
uu
uu
8853
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
8854
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
8855
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
8857 8858
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
8860
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
8862
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
8863
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
8864
7.1
7.3
7.0
7.1
7.7
6.8
6.9
6.6
7.2
7.1
8865
6.3
5.8
5.8
6.4
6.1
6.9
6.0
6.2
6.2
6.7
610
5.5
5.1
5.9
8866
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
8867
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
8868
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
8869
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
F
8870
6.9
6.5
6.8
6.9
6.7
6.5
S-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 NUMBER
LETTER FOLLOWING
A-ALIVE, "SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, C-CULLED, M-MISSING
POSTPARTUM
THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
a. Dam 8842 delivered one additional statistical analyses.
pup on day 2 of lactation; values for day 1 postpartum
excluded
from gro
PROTOCOL 418-008:
COMBINED ORAI, (GAVA(;E@ PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 3): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERATION PUPS
------- ------ I ----------------- -----
---------- ----------------- ------ -------- ------
PUP #
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
1
-------------------------------- -------------------------- ---------------------------------------------------
RAT/
LITTER
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM DAY I
-------------------------------- --------------------------------------------------------------------------
8871
NOT PREGNANT
8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894
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
6.0
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
6
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
8895 8896 8897 8898
8899 8900 8901 8902 8903
5.8
5.8
6.0
5.8
5.6
3.0
5.8
5.5
5.0
5.9
5.8
6.1
5.6
6.0
5.9
5.5
6
6.5
6.6
6.2
6.1
5.7
6.1
7.0
6.5
S.8
6.0
4.6
5.4
6.0
S.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
S.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
8904
NOT PREGNANT
8905
5.9
6.2
5.2
5.6
6.1
5.7
S.9
6.0
6.0
5.8
5.5
5.9
6.0
5.4
5.9
5.5
5
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C36 (PAGE 4): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERATION PUPS
-------------- -------------- I -------------- ------------- -- --------------------- - -----------------------
PUP #
1
2
3
4
------------------------------------
5
6
7
8
9
10
11
12
13
14
is
16
------------------------------------------------------------------------
RAT/
LITTER
MATERNAL DOSAGE GROUP IV
------------------------------------------------------------
8906 8909 8913 8914 8918 8919 8920 8921
8923 8925 8926 8927 8928 8929 8930 8931 8932 8933
5.2
5.1
6.0
6.2
5.4
5.5
NOT PREGNANT
NOT PREGNANT
5.8
6.0
6.1
5.9
7.2
7.3
NOT PREGNANT
5.5
5.4
6.1
5.9
6.3
4.8
7.1
7.7
6.6
5.9
6.0
5.0
5.4
4.8
5.7
5.5
NOT PREGNANT
5.6 6.8 5.8
6.2 S.9 6.6
5.4 5.6 6.0 7.1 5.9 4.5 5.2 4.6
5.1
4.7
4.4
5.7
3.6
6.6
5.0
6.4
5.9
6.7
6.3
5.7
5.6
6.0
5.3
5.7
5.9
6.2
5.8
5.8
6.2
5.6
5.7
6.1
5.3
6.4
6.8
5.3
6.5
5.6
4.7
5.2
5.6
S.8
5.8
6.0
5.0
5.7
5.1
5.2
5.3
4.9
6.0
5.7
6.3
7.2
7.4
7.4
6.0
6.7
6.3
6.0
S.5
6.0
6.0
4.4
4.8
5.7
5.3 MD 1
5.0 MD I MD 1 MD I MD 1
6.1
5.6
5.7
5.5
6.6
1.6 MG/KG/DAY
POSTPARTUM
DAY 1
--------------------------------------------------
5.3
5.3
4.1
5.0
5.2 FD 1
6.1
5.3
6.3
5,7
6.0
5.6
5.3
5.7
5.4
5.5
5.4
5.4
5.3
5.4
5.5
FD 1
6.7
ms
ms
6.1
6.2
6.0
6.0
5.6
5.7
4.8
5.7
6.4
6.3
6.3
5.9
6.1
6.1
5.6
6.0
6.2
6.5
6
6.5
7.0
5.9
6.2
MD 1 MD 1 5.7
5.8
5.5
5.0 FD 1
MD I FD 1 FD 1
5.6
5.6
5.6
6.0
4.9
5.0
5.3
4.8
5
8934
5.8
5.9
5.0
5.6
5.4
5.7
5.7
5.0
5.2
5.4
4.9
4.9
4.8
8935
6.2
6.2
5.3
5.6
6.1
5.7
5.7
5.3
4.7
5.7
5.2
5.9
8936 8937
5.5
5.1
5.5
5.6
5.8
5.1
5.2
5.4
ms
MD 1
5.3
5.2
5.3
5.1
5.0
5.1
7.8
6.7
6.7
7.2
6.5
ms
6.9
6.4
6.5
6.4
PS
8938
MORIBUND
SACRIFICED
ON DAY 36 OF STUDY
8939
5.4
4.9
5.6 MD I MD 1 4.9
4.9 FD I FD 1 FD 1 FD I FD 1 FD 1
8940
5.6
6.5
S.6
6.0
6.7
s.3
6.2
5.6
5.0 MD 1
5.1
5.3
5.8
5.2
5.7
FS
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVACE) PFOS IN RATS (SPONSOR'S
FERTII@ITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI(
TABLE C36 (PAGE 5): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERATION PUPS
-----------------
PUP #
1
----------------
---------------------- --
-- ------------------------ -------------------- --- - --------
2
3
4
5
6
7
6
9
10
11
12
13
14
15
16
--------------------- ---- - ---------------------------------------------------- ----------
RAT/
LITTER
MATERNAL DOSAGE GROUP V
----------------- ----------------------
3.2 MG/KG/DAY
POSTPARTUM
DAY 1
---------------------------------------------------------------
8942
MD 1 MD 1 MD 1 MD 1 FD I FD 1
8943
MD I ms
ms
ms
ms
FD 1
8944
MD 1 ms
FS
FD I FD 1
8945
NOT PREGNANT
8946 8949 8950
5.4
5.6
5.9
5.3
ms
ms
5.0
5.3
5.2
5.0
5.3
FS
5.1
S.0
5.1
5.7
5.0
5.2
4.9
4.7
4.7
4.6
4.9
4.8
ms
FD 1 FD 1 FD I FD 1
FS
8952
NOT PREGNANT
8955 8956 8957
ms
MD 1 MD I MD 1 MD I
FS
FD I FD 1 FD 1
5.5
5.1
5.3
5.7
5.0
5.3
5.6
5.0
4.8
5.3
4.9
5.1 FD 1
NOT PREGNANT
8959 8960
8961 8962
5.1
5.1
5.2
4.8 MD 1 ms
ms
4.8
4.9
5.0
4.5 FD I FS
MD 1 MD 1 MD 1 ms
ms
ms
ms
FD 1
FS
PS
FS
FS
FS
4.9
4.8
4.9
5.1
5.2
5.1
ms
4.7
5.2
5.1
4.8 FD 1 FS
FS
ms
ms
ms
FD 1
8964 8967 8968 8969
5.3
6.0
6.3
6.2
6.8
5.6
5.5
611
6.3
ms
ms
ms
ms
FS
FS
FS
FS
FS
uu
ms
ms
4.8
5.4 FD I FD 1 FS
FS
FS
FS
5.2 MD I MD 1 4.3
4.3
5.7
6.2
6.0
6.4
8970 8971 8972
5.9
5.9
5.7
6.0
5.5
ms
5.4
5.9
5.8
5.8
FS
6.0
5.8
6.1
5.5
6.3
5.6
5.6
5.0
4.9
5.5
5.2
5.1
6.4
NOT PREGNANT
8973
5.3
5.2
5.7
6.3
5.1
5.5
ms
5.5
5.6
4.7 FD 1
8974
MD I MD 1 MD 1 MD 1 ms
ms
FD 1 FD 1 FD 1 FD 1 FS
8975
MD 1 MD I MD 1 MD 1 MD 1 MD 1 FD 1 FI) I FD I FD 1 FD 1 FD 1
--------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) F'ERTILITY, DEVELOPMEN-1@AL
PFOS IN RATS (SPON@3OR'S STUDY NUMBER:
6295.1))
AND PERINATAL/POSTNATAt,
REPRODUCTION
TOXIC
TABLE C36 (PAGE 6): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSI'PARTUM - INDIVIDUAL DATA
Fl GENERATION
PUPS
-------------PUP #
-------------RAT/
--------------------
1
2
3
4
--------------------
-- ----
5 -- ----
-------------------
6
7
a
9
-------------------
------- ---------------
10
11
12
13
------------------------
-- ----------------
14
is
16
1
---- ---------------
LITTER
MATERNAL
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
DAY 4 P
-------------- ----------------------- ---- --------------------- ----------------------------------------------
8801 8803 8804 8805 8807 8808 8811 8812 6813 8814 8817
10.2 10.8 10.0
9.8
9.6 10.1
ms
10.1
9.3
9.9
8.3 10.1 10.8 10.0 10.1 11.4 10.7
ms
9.5 10.2 11.3 10.4 10.9
9.0
9.3
9.4 10.3 10.4
9.9
9.6
5.9
9.7 10.2
9.1
9.6
7.9
9.5
9.5
7.5
6,S
7.7
7.0
7.2
6.6
5.7
6.4
6.4
6.9
6.8
6.3
6.7
6.9
6.5 FM 4 FE
10.2 10.0
9.8
9.2
9.5 10.6 10.1
9.9
9.2
9.0
9.5
9.2
8.9
10.0 10.5
9.1 10.0
9.2 10.3
8.3
9.6 10.0
FS
11.3 ll.S 11.1 11.9 10.7 12.1 11.5 11.5 11.0
9.7 11.1 11.4
10.2 10.7 10.9
9.3
8.3
9.4
7.4
8.4
9.7
9.0
9.9
8.5
9.0
9.7
9.3
9.9 10
10.4 10.1 10.0
9.4
9.5
9.8
9.3
8.9
9.5
9.3 10.1
9.4
12.6 12.6 12.1 12.5 12.9 12.6 12.2 12.0 12.2 11.4 12.5 12.2 11.9
NOT PREGNANT
Belo
NOT PREGNANT
8819
11.4 10.5 11.1 10.8
5.4 10.4 10.8 10.6 10.4 10.2
9.9 10.7
8821
7.3
6.8
7.7
6.9
7.6
6.6
6.6
6.9
6.4
6.9
6.7
7.1
6.6
6.9
8823
9.7
9.2
9.7
9.0
9.4
9.8
9.6
9.1
8.7
9.4
9.2
9.0
8824
7.4
8.9
8.8
8.7
8.7
7.0
7.1
8.6
8.7
6.7
5.9
7.8
8.6
8.4
7.8
8826
8.6
8.7
8.3
9.o
8.8
8.2
8.8
7.8
8.6
8.6
8.5
8.4
8.7
8827
8.7
7.4
8.8
9.0
9.1
8.1
6.1
7.6
7.9
8.2
8.3
7.4
8.2
7.6
8828
9.0
9.3
ms
8.6
9.3
8.9
8.4
9.4
7.7
8.8
8.9
9.1
8.6
PS
FS
8830
6.2
8.4
7.9
9.2
8.5
8.2
9.1
8.8
9.1
9.0
8.8
8.0
8.7
8.0
8.5
9.0
8831
8.6
8.4
8.6
9.2
8.5
7.8
8.8
8.0
8.2
8.2
7.5
7.8
8.1
6.7
8.4
8832
9.6
8.0
7.6
8.4
8.5
7.7
8.4
6.8
7.7
7.7
7.6
8.1
7.1
8.2
8.1
8.9
8
8833
9.8
8.6
9.4
9.0
9.0
9.5
8.3
8.8
8.7
8.8
7.7
8.5
8.3
8.7 FD 1
8834
9.8
9.4
9.9
9.6 10.0
9.8
ms
9.8
8.5
9.3
9.6
9.1
9.4
8.6
FU
FU
8835
9.3
8.5
8.5
8.6
7.7
9.0
8.4
7.8
7.4
7.8
8.1
8.2
4.6
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.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICIT
TABLE C36 (PAGE 7): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
- ----------PUP #
-------------
----------------------- -----
1
2
3
4
5
---------------------- ------
-- ---- --------------
6
7
8
9
------- --------------
------ --------------------------------------
10
11
12
13
14
15
16
17
-- --- -------------------- -----------------
RAT/
LITTER
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
POSTPARTUM
DAY 4 PRECU
------------- ---------------------- ------ --------------------------------------------------------------------
8838
7.1
8.6
7.4
8.4
8.2
8.3
8.6
8.3
8.9
9.0
7.7
8.3
8.3
7.9
7.4
7.6 - 7.
8840 8841
8.8
8.0
8.8
6.7
8.7
7.9
8.3
6.9
6.9
7.7
7.3
8.4
8.4
4.9
7.6
8.0
7.
9.1
7.7
8.7
9.4
8.7
8.2
8.6
9.6
9.4
9.7
8.8
8.2
8.9
9.3
8842 8845
9.3
9.4
9.4
9.2
9.3
9.2
9.2
8.3
9.5
8.6
8.7
7.9
7.8
9.1
8.8
10.0 10.4
9.7
9.4 MD 1
9.8 10.8
9.7 10.2 10.0 10.5
9.4 FD 2
8846 8847 8649 8851
9.0
9.1
9.3
9.0
8.5
9.8
9.0
8.8
9.0
7.8
8.0
7.9
9.1
8.9
8.1
9.4
9.8
9.1
9.6
8.6
9.1
8.8 10.1 10.1
9.2
9.6
9.0
8.6
9.4
8.4
8.2
8.0
7.8
7.4
8.3
7.2
8.4
7.8
7.5
7.5
7.0
7.2
7.5
7.2
7.2 FM 4
8.7
8.1
8.7
9.4
7.8
8.6
7.6
9.0
7.4
9.1
8.2
7.9
8.6
8.6 FD 1
8852 8853
8854 8855 8857 8858
10.1
9.7 10.1 10.2 10.0
9.6
9.6
9.5
9.0
9.9
uu
uu
6.9
6.6
8.5
7.6
7.2
7.8
6.2
7.6
6.0
5.3
7.8
5.8
8.0
7.9
7.4
6.5
8.4
8.4
9.8
8.8
9.4
9.6
9.7 10.4 10.0
9.6
8.9 10.0
8.1
9.5
9.2
8.9
8.8
9.0
9.1
8.7
8.1
9.1
8.9
8.3
6.9
9.0
7.8
8.4
8.1
8.0
9.5
8.5
9.4
8.6
8.6
9.4
8.8
8.9
8.3
8.8
7.3
8.5
8.0
8.8
8.0
10.6 11.5
ms
10.9 10.9
9.7
9.8 10.0 10.8 10.6
9.9
8860 8862
8.3
9.7 10.0
9.4 10.4
9.5
9.4
8.3
8.6
8.6
9.7
8.9
9.4
8.3
8.8
9.4
9.5
9.8 10.0
9.6 10.1
9.6
8.8
8.9
9.2 10.1
9.8
9.3 10.1
8863 8864
8.1
9.2
8.8
8.3
8.3
8.9
6.9 10.1
9.4 10.4
8.8
8.8
9.0
9.2
9.4
8.1
9.8
8.5
8.5
9.8
8.4
9.0
8.6
8.7
8.9
8.8
8865 8866 8067
9.0
8.5
8.6
8.8
8.S
8.8
8.2
9.3
8.3
9.3
8.0
8.6
8.0
8.6
7.7
7.2
7.3
7.3
6.8
7.1
0.1
7.6
8.1
6.8
7.6
7.7
8.3
7.0
7.4
7.4
11.1 11.2
9.8 10.4 11.1
9.3
8.7
8.9
7.8
8.5
9.7 10.5 10.S
8868 8869 8870
10.4 10.1
8.6 10.5
8.4 10.0 10.3 MD 2
9.0
8.2
9.5
8.4
8.8
8.8
8.4
8.8
9.2
8.8
9.1
8.9
8.8
7.9
9.1
8.4
9.0
8.2
7.3
9.4
7.6
7.8
FS
9.9 10.3 10.2 10.3
9.4
9.0
8.0
9.4
9.8
8.9
9.4
-----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST SECOND NUMBER
LETTER LETTER FOLLOWING
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
A-ALIVE, "SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008!
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAB PPOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE C36 (PAGE 8): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERATION PUPS
--------------- --------------I ------------
PUP #
1
2
3
4
5
6
------------ -------------------------------
RAT/
------ ------ -------------------------------------------- -
7
8
9
10
11
12
13
14
is
16
1
----------------------------------------------------------------
LIrrrER #
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM DAY 4 PREC
------------ --------------------------------------------------------------------------------------------------
8871
NOT PREGNANT
8872 8874 8875 8876
8.3 7.2 7.9 9.3 9.0 8.5 7.7 8.6 ms
8.9 9.4 7.7 7.7 7.9
9.0 8.0 10.0 9.1 7.4 7.9 9.6 9.2 9.4 9.5 8.7 8.5 7.0 8.2 8.2
9.2 10.1
9.4 9.5 9.0 9.3 9.2 9.7 9.7 9.6 8.9 10.2
9.7
13.6 12.6 13.0 MD 1 12.7 14@l 11.4
8881 8882 8885 8889 8890 8891 8892 8893 8894
9.9 8.3 7.9 7.0 8.5 7.6 8.0 7.6 7.7 7.8 6.7 8.0 8.5 7.4
8.6 9.8 8.8 8.7 8.1 9.4 8.6 9.3 7.6 8.4 8.4 9.3 6.0 8.6 7.9 8.9 8
8.0 10.3 10.0 9.0 9.1 9.6 9.4 9.5 ms
9.1 8.4 8.8 8.2 9.4 8.9 FS
6.4 7.6 6.9 6.8 7.0 7.3 7.6 7.0 7.2 7.7 7.2 7.0 6.7 6.6
10.9 9.1 9.8 1011 10.1 9.8 9.0 10.3 10.0 10.0 9.3 10.0
10.0 8.4 7.1 9.3 9.7 8.9 8.4 9.1 8.6 9.3 9.8 9.1 8.9 9.0 8.8
9.2 9.0 8.7 9.2 8.9 10.0 9.3 9.2 8.8 8.9 8.3 9.3
7.7 8.3 7.9 8.3 8.6 8.6 8.1 8.5 7.9 7.7 7.1 7.9 8.1
11.8 11.3 11.3
8895 8896 8897 8898
8899 8900 8901 8902 8903
7.8 7.9 6.4 7.3 7.6 7.2 7.2 8.2 6.9 7.5 8.1 7.3 8.4 7.2 8.4 7.5 FM 8.7 9.9 9.4 8.4 9.0 0.2 9.1 9.3 8.8 8.0 6.9 8.6 8.9 8.0 9.4 8.7 7.8 9.8 8.9 8.3 8.5 9.3 8.6 8.1 9.2 9.0 9.1 9.2 9.5 9.3 9.3 9.3 9.6 8.9 9.2 8.9 8.7 9.3 8.5 8.7 FS 8.0 10.7 9.0 9.8 8.9 9.4 9.1 8.1 9.0 5.4 8.3 9.4 9.6 9.2 8.8 9.0 8.9 9.8 9.0 8.8 9.2 9.4 7.4 9.1 8.2 9.1 8.6 7.7 8.3 7.6 FM 2 FS 9.1 9.4 8.9 8.9 8.8 9.6 7.8 9.2 8.6 8.7 8.5 7.6 9.0
8.6 7.6 7.6 7.6 7.9 8.1 7.8 6.9 7.4 7.9 7.7 7.4 8.0 8.4 FM 3 FS NOT PREGNANT
8904
NOT PREGNANT
8905
8.0 7.1 8.6 8.4 8.2 7.4 8.2 8.2 8.4 7.3 8.3 8.2 7.3 7.4 6.9 6.3 7.
----------------------------------------------------------------------------------------------------------------
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-CUBLED, M-MISSING
NUMBER FOLLOWING "SECOND LETTER" INDICATES THE DAY POSTPARTUM THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C36 (PAGE 9): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
- - ---------- -------------- -
PUP #
1
2
3
- - --------------------------
RAT/
LITTER
MATERNAL
DOSAGE
-------------------------------
8906
7.8
6.6
8.2
8909
8.6
8.4
9.2
8913
8.7
8.1
7.2
8914
NOT PREGNANT
8918
NOT PREGNANT
-- -----
-------------
4
5
6
7
8
-- ------ ----------------
----------- ----- --------- ----------- ----- ---
9
10
11
12
13
14
is
16
------------ ----- --------------------- ----------
GROUP IV
1.6 MG/KG/DAY
POSTPARTUM
DAY 4 PRE
------------------------------------------------------------------------------
7.7
7.1
7.6 MD 2 MD 2
7.5
7.9
6.5
7.9 FM 3 FD 1
7.7
8.4
7.3
8.3
6.7
8.5
8.5
8.5
8.2 MD 3 6.6
8.0
8.7
7.6
7.3
8.1
8.7
8919 8920 8921 8923
6.8
7.0
7.6
8.1
6.7
7.4
7.1
6.8
6.2
7.3
7.2
7.1
6.2
6.2
5.9 FM 2
8.8
8.7
8.4
8.3
8.0 MD 2 9.5 FM 2 FD 1
9.0 10.4
9.5
7.1
6.4
9.5
9.5
8.6 MD 2 ms
ms
8.6
8.6
NOT PREGNANT
8925 8926 8927 8928 8929
7.8 MM 2 4.1
7.7
7.0
8.5
7.0
5.6
7.1
8.1 FM 2 FD 2
6.1 MD 3 MD 2
5.0
6.7
6.6 FM 3 FM 3 FD 2 FD 2 FD 2 FD 2
4.7
5.0
5.2 MD 3 MD 2 MD 2
5.0
4.6
4.7
4.8
4.3 FM 4 FD 3 FD 3 FD 2 FD 2 F
6.1
9.4
9.2
8.6
8.5
9.2
9.3
8.7
8.9
7.7
7.7
8.4
MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 FM 2
8930 8931 8932 8933
7.1
8.3
7.1
8.4
8.6
8.5
8.6 MD I MD 1 MD 1 7.4
6.9
6.6 FD I FD 1
7.0
7.9
8.2
7.0 MD 1 MD 1 MD 1 MD 1 MD 1 FD 1 FD 1
6.3
5.8
5.7
5.9
6.6
4.8
6.4 MM 3 MM 3 MD 3 MD 2
4.9
4.8
5.9
5.9 FM 3 F
NOT PREGNANT
8934 893@S 8936 8937 8938
5.8
6.2
6.9
7.3
6.2
6.5
MD 4 MD 4 MD 4
9.9
8.2
8.4
MORIBUND SACRIFICED
6.2 6.1 MD 4 8.8
ON
6.5 6.0 MD 2 8.5 DAY 36
7.0 MD 2
6.9 MD 4
MM 2 MD 2
ms
9.5
OF STUDY
6.3 7.1 MD 1 9.3
5.5 5.7 ms 8.3
5.5 6.0 MD 1 FM 2
5.5 6.7 FD 4 FS
FM 3 7.1
FD 4
FD 2 FD 3 FD 3 FD 1 FD 1
8939
8.9
7.3
8.4 MD I MD 1 7.6
8.0 FD 1 FD 1 FD I FD I FD 1 FD 1
8940
6.2
7.3
8.5
6.2
8.7
6.4
8.9
8.5 MD 2 MD 1 5.6
6.8
8.3
7.0
6.2
FS
--------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAI,
STUDY NUMBER:
6295 9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 10): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA
Fl GENERATION
PUPS
PUP # --------- ---
-------------------- ---- -------------------- -- - --- -------------
1
2
3
4
5
6
7
8
9
10
11
12
----------------------------------------------------- -----------------
--------------------- ----
13
14
is
16
1
--------------------------
PAT/
LITTER ------------
8942 8943 8944 8945 8946 8949 8950 8952
MATERNAL
DOSAGE GROUP V
3.2 MG/KG/DAY
POSTPARTUM
DAY 4 PREC
--------------------------------------------------------------------------------------------------
MD 1 MD 1 MD 1 MD 1 FD 1 FD I
MD 1 ms
ms
ms
ms
FD 1
MD 1
ms
PS
NOT PREGNANT
FD 1 FD 1
MD 2 MM 2
ms
MD 2 MD 2 FD 1
MD 2 MD 2 FD 1
MM 2 MD 2 FD 1
ms MD 2 FD I
ms MD 2
FS
FD 2 FM 2
FD 2 FM 2
FD 2 FD 2
FD 2 FD 2
FM 2 FD 2
FS FD 2
NOT PREGNANT
89ss 8956 8957
ms
MD 1 MD 1
MD 2 MD 2 MD 2
NOT PREGNANT
MD I MD 2
MD I MD 2
FS MD 2
FD I MD 1
FD 1 FD 2
FD 1 FD 2
FD 2
FD 2
FD 2
FD 1
8959 8960 8961 8962
MD 2 MD 2 MD 2 MD 2 MD I ms
ms
FD 2 FD 2 FD 2 FD 2 FD 1
FS
MD 1 MD 1 MD I ms
ms
ms
ms
FD 1
FS
FS
PS
FS
PS
MD 2 MD 2 MD 2 MD 2 MD 2 MM 2
ms
FD 2 FD 2 FD 2 FM 2 FD I
FS
FS
ms
ms
ms
FD 1
8964 8967 8968 8969
MM 2 MM 2 MM 2 MM 2 MD 2 MD 2 MD 2 MD 2 MM I ms
ms
ms
ms
FS
FS
FS
FS
FS
uu
ms
ms
FD 2 FM 2 FD 1 FD I
FS
FS
FS
FS
MD I MD I MD 1 FD 1 FM 1
FM 2 FD 2 FM 1 FD 1
8970 8971 8972
MD 2 MD 2 MD 2 MM 2 MM 2 MM 2
NOT PREGNANT
MD 2 MM 2
MD 2 MD 2
ms MD 2
FD 2 MD 2
FD 2 FM 2
FD 2 FM 2
FD 2 FM 2
PS FD 2
FD 2
FD 2
8973
MM 2 MD I MD 1 MD 1 MD 1 MD I ms
FD I FD I FD 1 FD 1
8974
MD 1 MD 1 MD 1 MD 1 ms
ms
FD 1 FD I FD 1 FD 1
FS
8975
MD 1 MD 1 MD I MD 1 MD 1 MD 1 FD I FD 1 FD 1 FD I FD 1 FD I
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER!
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 11): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
------ -- -----------------------
PUP #
1
2
3
4
------ - ------------------------
RAT/
------5
---- --
6 -----
----------- - - ----- -----------------
7
8
9
10
11
12
13
------------- -------------------------
---------------------
14
15
16
1
---------------------
LITTER
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
POSTPARTUM DAY 4 PO
--------------------------------------------------------------- -----------------------------------------------
aeoi 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817
MC 4 10.8
8.3 10.1
MC 4
9.3
7.5
6.5
MC 4 MC 4
10.0 10.5
11.3 MC 4
10.2 10.7
10.4 10.1
MC 4 12.6
NOT PREGNANT
10.0 MC 4
MC 4 7.7
MC 4 9.1
11.1 10.9
10.0 12.1
9.8 10.0 10.3
7.0 9.2 10.0 11.9 9.3 FC 4 MC 4
9.6 MC 4 10.4
7.2 MC 4
9.2
MC 4 FC 4
9.5 12.9
10.1 11.4
9.9 FC 4 10.6 10.3 12.1 FC 4
9.8 12.6
ms MC 4
9.6 FC 4 10.1 FC 4 11.5 PC 4
9.3 MC 4
10.1 ms
FC 4 FC 4
9.9 9.6 11-S FC 4 FC 4 12.0
9.3
FC 4 FC 4 FC 4
9.2 10.0 11.0 FC 4 FC 4 FC 4
9.9 10.2 10.2 FC 4
9.0 FS FC 4 FC 4 9.3 11.4
11.3 FC 4 FC 4 PC 4
PC 4 9.9
10.1 12.5
10.4 9.6 6.3 9.2
11.4 FC 4 FC 4 FC 4
10.9 FC 4
6.7 8.9
PC 4
11.9
FC 4 6.9
9.7
9.5 FC 4 FM 4 FD
PC 4
9.9 10.
8818
NOT PREGNANT
8819
11.4 10.5 11.1 10.8 FC 4 10.4 10.8 FC 4 FC 4 10.2 FC 4 10.7
8821 8823
MC 4
9.7 10.1 MC 4
9.5
9.9 MC 4 MC 4
9.5
9.7 FC 4
8.9
9.4 FM 2
9.7
9.2
9.7 MC 4 MC 4 MC 4
9.6
9.1 FC 4
9.4
9.2
9.0
8824 8826 8827 8828 8830 8831 8832 8833 8834 8835
MC 4 8.6
8.9 MC 4 MC 4
8.7
8.3 MC 4
8.7 MC 4
7.1 MC 4
8.7
8.8 FC 4 FC 4
7.8
8.6
6.7 FC 4
7.8
8.6
8.6
8.5 FC 4 FC 4
8.4 PC 4
8.7 MC 4 8.8
9.0
9.1
8.1 FC 4 FC 4 FC 4
8.2
8.3 FC 4 FC 4
7.6
9.0
9.3
ms
8.6
9.3
8.9 FC 4
9.4 FC 4 FC 4
8.9 FC 4
8.6
PS
FS
MC 4
8.4 MC 4 MC 4 MC 4 MC 4
9.1
8.8
9.1 MC 4 MC 4 FC 4
8.7
8.0
8.5
9.0
MC 4 MC 4 MC 4 MC 4 8.5 MC 4 8.8
8.0 MC 4
8.2
7.5
7.8
8.1 FC 4
8.4
9.6 MC 4 MC 4
8.4
8.5
7.7
8.4 FC 4
7.7 FC 4 FC 4 FC 4 FC 4 FC 4 FC 4
8.9
8.
9.8 MC 4
9.4
9.0
9.0 MC 4 MC 4 MC 4 FC 4
8.8
7.7
8.5 FC 4
8.7 FD 1
9.8 MC 4
9.9 MC 4 10.0
9.8
ms
FC 4 FC 4
9.3
9.6 FC 4
9.4
8.6
FU
FU
uu
9.3
8.5
8.5
8.6
7.7 FC 4 FC 4 FC 4 MC 4 MC 4 MC 4
8.2 MC 4
8.4 MC 4
8.8
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL
418 008:
COMBINED ORAL IGAVAGE) FERTILITY,
DEVELOPMENTAL
PPOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C36 (PAGE 12): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
------------PUP #
------------RAT/
-------------------- -- -- ---- I ---------------------------------- -----------------------------
1
2
3
4
5
6
7
8
----------------------------------------------
9
10
11
12
13
14
15
16
-------------------------------------------------
LITTER
MATERNAL
DOSAGE GROUP 11
------------------------------------------------------------
0.1 MG/KG/DAY
POSTPARTUM DAY 4 POS
-------------------------------------------------
8838 8840
8841 8842 8845 8846 8847 8849 8851 8852
MC 4
8.6 MC 4
8.4
8.2 MC 4
8.6 MC 4 MC 4 MC 4 FC 4
8.3
8.3
7.9 PC 4 FC 4
MC 4 MC 4 MC 4 MC 4
8.7 MC 4
8.3 MC 4 MC 4
7.7 MC 4
8.4
8.4 FC 4 7.6 FC 4
9.1 MC 4
8.7 MC 4
0.7 MC 4 MC 4 MC 4
9.4
9.7
8.8
8.2 FC 4
9.3
9.3 MC 4
9.4
9.2
9.3 FC 4 FC 4 FC 4
9.5
8.6
8.7
7.9 PC 4 FC 4 FC 4
10.0 10.4
9.7 FC 4 MD 1 FC 4 10.8 FC 4 10.2 10.0 10.5
9.4 FD 2
MC 4 MC 4
9.3 MC 4 MC 4
9.8
9.0
8.8
9.0 FC 4 FC 4 FC 4
9.1
8.9
8.1
9.4
9.8 MC 4
9.6 MC 4 MC 4 MC 4 MC 4 10.1
9.2
9.6
9.0 FC 4
9.4
8.4
8.2 MC 4 MC 4 MC 4 MC 4 MC 4 8.4 MC 4
7.5
7.5 FC 4 PC 4
7.5
7.2
7.2 F
8.7
8.1
8.7
9.4 MC 4 FC 4 FC 4 FC 4
7.4 FC 4
8.2
7.9
8.6 FC 4 FD 1
10.1 MC 4 10.1 10.2 MC 4
9.6
9.6
9.5
9.0
9.9
uu
uu
8853 8854 8855 8857 8858
MC 4 8.4 8.9 9.5
10.6
MC 4 MC 4 MC 4 MC 4 11.5
8.5 8.8
9.0 MC 4
ms
MC 4 MC 4
9.1 MC 4 FC 4
MC 4 9.6 8.7
MC 4 FC 4
7.8 MC 4 7.6 MC 4 MC 4 7.8 MC 4 MC 4
7.9
7.4 FC 4
9.7 MC 4 MC 4 FC 4
8.9 10.0
8.1
9.5 FC 4
8.1 FC 4
8.9 FC 4 FC 4
9.0 FC 4
8.4 FC 4 FC 4
9.4
8.8 MC 4
8.3
8.8 FC 4
8.5
8.0
8.8 FC 4
9.7
9.8 10.0 10.8 10.6
9.9
8860 8862 8863 8864
MC 4
9.7 MC 4 MC 4 10.4
9.5
9.4 FC 4
8.6
8.6
9.7 FC 4 FC 4 FC 4
8.8
9.4 MC 4
9.8 MC 4 MC 4 10.1
9.6
8.8 FC 4 FC 4 10.1
9.8 FC 4 10.1
MC 4
9.2 MC 4 MC 4 MC 4 MC 4 MC 4 10.1 MC 4 10.4 MC 4
8.8
9.0
9.2
9.4
8.1
9.8
8.5
8.5
9.8 MC 4
9.0
8.6
8.7 FC 4
8.8
8865 8866 8867 8868 8869 8870
MC 4
8.5
8.6 MC 4 MC 4 MC 4 MC 4
9.3
8.3 MC 4
8.0
8.6
8.0
8.6
MC 4
7.2 MC 4
7.3 MC 4 MC 4
8.1 MC 4
8.1 FC 4
7.6
7.7
8.3 FC 4 PC 4 7.4
11.1 11.2 MC 4 10.4 11.1
9.3 FC 4
8.9
7.8
8.5 FC 4 FC 4 FC 4
10.4 10.1 MC 4 10.5 MC 4 MC 4 10.3 MD 2
9.0 FC 4
9.5 PC 4
8.8
8.8
8.4
8.8 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4
9.1
8.4 MC 4
8.2 FC 4
9.4
7.6
7.8
1
9.9 10.3 10.2 10.3 MC 4
9.0 FC 4 FC 4
9.8
8.9
9.4
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
SECOND NUMBER
LETTER FOLLOWING
A-ALIVE, "SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, C-CULLED, M-MISSING
POSTPARTUM
THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 13):
PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
------- --------------------------
.
------- -- ---------------------------------------------- I ---------
PUP N
1
2
3
------- ---- ------------------
4
5
6
7
8
9
10
11
12
13
14
15
16
1
----- -- ---------------------------------------------------------------------
PAT/
LITTER
MATERNAL
DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM DAY 4 POST
-------------------------------------- ------------------------------------------------------------------------
8871
NOT PREGNANT
8872 8874a 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894
8.3 MC 4 MC 4 13.6
9.9 MC 4 MC 4 MC 4 10.9 10.0
9.2 MC 4 11.8
MC 4 MC 4 10.1 12.6
8.3 MC 4 MC 4 MC 4 MC 4 MC 4
9.0 8.3 11.3
7.9 10.0
9.4 13.0
7.9 MC 4
10.0 MC 4
9.8 MC 4 MC 4 MC 4 11.3
9.3 9.1 MC 4 MD 1 MC 4 8.7 MC 4 MC 4 10.1 9.3 MC 4 MC 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
MC 4 MC 4
9.3 14.1
7.6 9.4 9.6 7.3 PC 4
8.9 10.0
8.6
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 MC 4
9.7
ms MC 4 MC 4
FC 4 9.3 9.5 7.0
10.3 FC 4 PC 4
8.5
FC 4 FC 4
ms MC 4 10.0 FC 4
8.8 7.9
8.9 9.5 9.8
7.8 8.4 9.1 7.7 10.0 9.3 8.9 7.7
9.4 8.7 8.9
6.7 FC 4 FC 4
7.2 PC 4
9.8 8.3 7.1
7.7 8.5 10.2
FC 4 9.3 8.8 7.0
10.0 9.1 9.3 7.9
FC 4
7.9
FC 4
8.2
9.7
FC 4 FC 4 PC 4
6.7
7.4 8.6 9.4 PC 4
FC 4 FC 4
FC 4
8.2
FC 4 8.9 8.8
8.9 FC FS
8695 8896 8897 8898 8899a 8900 8901 8902 8903
MC 4
7.9 MC 4
7.3
7.6 MC 4 MC 4
8.2 MC 4 7.5
8.1 FC 4
8.4 FC 4
8.4 FC 4 FM
MC 4
9.9
9.4 MC 4
9.0 MC 4
9.1 MC 4
8.8 FC 4 FC 4
8.6
8.9
8.0
9.4
8.7 MC 4
9.8
8.9 FC 4 FC 4
9.3
8.6
8.1 FC 4 FC 4
9.1 FC 4
9.5 MC 4
9.3
9.3
9.6 MC 4 MC 4 MC 4
8.7
9.3
8.5
8.7
FS
8.0 MC 4 MC 4
9.8
8.9 MC 4
9.1
8.1
9.0 FC 4
8.3 FC 4 PC 4 FC 4 FC 4 9.0
8.9
9.8
9.0
8.8 MC 4 MC 4 FC 4
9.1 FC 4
9.1
8.6 FC 4
8.3 FC 4 FM 2
FS
9.1
9.4
8.9
8.9 MC 4 MC 4 PC 4
9.2
8.6
8.7
8.5 PC 4 PC 4
8.6 MC 4
7.6
7.6 MC 4
8.1 MC 4 FC 4
7.4
7.9
7.7
7.4 PC 4 FC 4 FM 3 FS
NOT PREGNANT
8904
NOT PREGNANT
8905
8.0 MC 4
8.6
8.4 MC 4 MC 4
8.2 MC 4 FC 4
7.3 PC 4 FC 4 FC 4 FC 4
6.9
6.3
7
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED
IN GRAMS (G).
FIRST SECOND NUMBER
LETTER LETTER FOLLOWING
M-KALE, F-FEMALE, U-SEX UNDETERMINABLE
A-ALIVE, "SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
a. A sexing error was found prior to weighing on day 7 postpartum for litter 8874; values for day 4 postpartu excluded from group averages and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 14): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
----------- ------------------ -
PUP
2
3
--------------------------------
4 ---- 5------6----- 7 -----8 ------9-----1-0 --- * 1-1---- -12- - -1-3-----1-4- -- i-s-----1-6-----1-7-- -- ------------- --------------- ----------------------------------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP IV
1.6 MG/KG/DAY
POSTPARTUM
DAY 4 POST(
----------------------------------------------------------------------------------------------------------------
8906 8909 8913 8914
MC 4 MC 4
8.2
8.6
8.4
9.2
0.7
0.1
7.2
NOT PREGNANT
7.7
7.1
7.6 MD 2 MD 2
7.7
8.4 FC 4
8.3 FC 4
8.2 MD 3 FC 4
8.0
8.7
7.5
7.9
8.5 PC 4
7.6 FC 4
6.5
7.9 FM 3 FD 1
8-S
8.1 FC 4
8918
NOT PREGNANT
8919 8920 8921 8923
MC 4 MC 4
7.6
8.1
6.7
7.4 MC 4 MC 4 MC 4 MC 4
7.2
7.1
6.2
6.2 PC 4 FM 2
8.8
8.7
8.4
8.3
8.0 MD 2
9.5 FM 2 FD 1
9.0 10.4
9.5 MC 4 MC 4
9.5
9.5
8.6 MD 2
ms
ms
8.6
8.6
NOT PREGNANT
8925 8926 8927 8928 8929
7.8 MM 2 FC 4
7.7
7.0
8.5
7.0
5.6
7.1
8.1 FM 2 FD 2
6.1 ND 3 MD 2
5.0
6.7
6.6 FM 3 FM 3 FD 2 FD 2 FD 2 FD 2
4.7
5.0
5.2 MD 3 MD 2 MD 2 5.0
4.6
4.7
4.8
4.3 FM 4 FD 3 FD 3 FD 2 FD 2 FD
MC 4
9.4
9.2
8.6 MC 4
9.2 MC 4
8.7
8.9 FC 4
7.7
8.4
MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 FM 2
8930 8931 8932 8933
MC 4
8.3 MC 4
8.4
8.6
8.5
8.6 MD 1 MD 1 MD 1 7.4
6.9
7.0
7.9
8.2
7.0 MD 1 MD 1 MD I MD 1 MD 1 FD I FD 1
6.3 MC 4 MC 4 MC 4
6.6
4.8
6.4 MM 3 MM 3 MD 3 MD 2 4.9
NOT PREGNANT
6.6 FD 1 FD 1
4.8
5.9
5.9 FM 3 FD
834 8935 8936 8937
MC 4 7.3
MD 4 9.9
6.2 MC 4 MD 4
8.2
6.9 MC 4 MD 4
8.4
MC 4 6.1
MD 4 8.8
6.5 6.0 MD 2 8.5
7.0 6.9 MM 2 ms
MD 2 MD 4 MD 2
9.5
6.3 7.1 MD 1 9.3
5.5 FC 4
ms 8.3
5.5 6.0 MD I FM 2
5.5 6.7 FD 4 PS
FM 3 7.1
FD 4
FD 2 FD 3 FD 3 FD 1 FD 1
8938
MORIBUND SACRIFICED
ON DAY 36 OF STUDY
8939
8.9
7.3
8.4 MD I MD 1 7.6
8.0 FD 1 FD 1 FD 1 FD 1 FD 1 FD 1
8940
MC 4 MC 4
8.5 MC 4
0.7 MC 4
8.9
8.5 MD 2 MD 1 FC 4
6.8
8.3
7.0
6.2
FS
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST SECOND NUMBER
LETTER LETTER FOLLOWING
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
A-ALIVE, "SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PPOS IN RATS (SPONSOR''; STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 15): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
INDIVIDUAL DATA - Fl GENERATION
PUPS
--- ---------- --------------------
PUP #
1
2
3
4
------------------------------------
RAT/ LITTER
MATERNAL
DOSAGE GROUP
-- -5
-
V
--------------- - -- ------ -------------- - - --------
6
7
8
9
10
11
12
13
14
15
--------------------------------------------------------
--1-6-----1---------
3.2 MG/KG/DAY
POSTPARTUM
DAY 4 POST
--8-9-4-2 --------M-D--1----MD---I---M-D--1---M-D--1---F-D--I-
8943
MD I ms
ms
ms
ms
8944
MD 1 ms
FS
FD I FD 1
8945
NOT PREGNANT
- -----------------------------------------------------------------FD I FD 1
8946 8949 8950 8952 8955 8956 8957
MD 2 MD 2 MD 2
MM 2 MD 2 MD 2
ms
FD 1 FD I
NOT PREGNANT
ms
ND 1 MD 1
MD 2 MD 2 MD 2
NOT PREGNANT
MM 2 MD 2 FD I
MD I MD 2
ms MD 2 FD 1
MD 1 MD 2
ms MD 2
FS
FS MD 2
FD 2 FM 2
FD 1 MD 1
FD 2 FM 2
FD 1 FD 2
FD 2 FD 2
FD 1 FD 2
FD 2 FD 2
FD 2
FM 2 FD 2
FD 2
FS FD 2
FD 2
FD 1
8959 8960 8961 8962 8964
8967 8968 6969 8970 8971 8972
MD 2 MD I MD 2
ms MM 2
ms ms MD I MD 2 MM 2 NOT
MD 2 MD 1 MD 2
ms MM 2
ms ms MD I MD 2 MM 2 PREGNANT
MD 2 MD 1 MD 2
ms MM 2
ms FD 2 MD 1 MD 2 MM 2
MD 2 ms
MD 2 FD 1 MM 2
FS FM 2 FD 1 MD 2 MM 2
MD I ms
ms
ms
ms
ms
MD 2 MM 2 ms
MD 2 FS
FD I FM 1 MD 2 MD 2
MD 2 FS
FD I
ms MD 2
MD 2 FS FS
FD 2 MD 2
FD 2 FD 1 FD 2
MD 2 FS FS
FD 2 FM 2
FD 2 FS
FD 2
MM 1 uu FS
FD 2 FM 2
FD 2 FS
FD 2
ms
FS
FD 2 FM 2
FD 2 FS
FM 2 FM 2
FS FD 2
FD I
FS
FS
FS
FD I
FS
FD 2 FM 1
FD 2 FD 2
FS FD 1
8973
MM 2 MD I MD 1 MD I MD 1 MD I ms
FD 1 FD I FD 1 FD 1
8974
MD I MD 1 MD I MD I ms
ms
FD I FD 1 FD 1 FD 1 FS
8975
MD 1 MD I MD I MD 1 MD I MD I FD 1 FD 1 FD 1 FD 1 FD 1 FD 1
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST SECOND
LETTER LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXI
TABLE C36 (PAGE 16): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDLVIDUAL
DATA - Fl GENERATION
PUP
--------------------
PUP N
1
--------------------
----------------
------ --------------------------- ------- --------
2
3
4
5
6
7
8
9
10
11
12
13
14
------------------ - -----------------------------------------------------
-----------
15
16
-------------
RAT/
LITTER ------------
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
DAY 7
I -------- ------------------------------------------------------------------------- --------------
MC 4 16.1 15.1 15.3 14.6 15.2
ms
14.9 15.6 14.3
17.3 15.2 MC 4 12.7 MC 4 15.9 MC 4 ms
FC 4 15.4 15.4 17.5 16.7
MC 4 14.8 MC 4 13.2 15.5 15.5 15.5 FC 4 FC 4 13.6 FC 4 14.5 FC 4 FC 4 15.2
10.5 MC 4
10.1 MC 4
10.5 MC 4
9.3 16.4
9.7 MC 4
FC 4 15.3
FC 4 14.5
FC 4 15.9
FC 4 14.6
PC 4 14.7
FC 4 PC 4
10.3 14.0
8.7 13.6
8.6 FC 4 FM 4 F
15.6 13.5 14.S 13.7 15.0 14.8 FC 4 14.2 14.7
FS
17.8 MC 4 17.8 16.9 MC 4 17.9 16.3 17.5 17.0 FC 4 FC 4 17.5
16.1 16.0
17.0 15.4
15.0 15.6
16-S FC 4
FC 4 14.6
FC 4 15.4
FC 4 14.2
FC 4 FC 4
FC 4 FC 4
FC 4 15.6
17.0 14.4
FC 4 FC 4 16.1 FC 4 14.9 1 FC 4
MC 4 20.0 20.3 MC 4 20.0 20.3 MC 4 18.0 FC 4 18.8 19.3 FC 4 19.2
NOT PREGNANT
Bole
NOT PREGNANT
8819
16.9 17.5 16.9 15.9 FC 4 16.6 16.2 FC 4 FC 4 16.6 PC 4 17.0
8821
MC 4 15.2 16.3 MC 4 16.3 16.7 MC 4 MC 4 15.4 14.8 FC 4 15.8 15.1 FM 2
8823
14.8 15.2 15.4 MC 4 MC 4 MC 4 14.0 14.9 FC 4 13.5 14.7 14.6
8824
MC 4 14.9 MC 4 MC 4 10.8 MC 4 14.0 MC 4 14.7 13.6 FC 4 12.8 10.7 13.4 FC 4
8826
14.4 13.8 13.3 MC 4 14.1 FC 4 FC 4 12.3 13.7 14.2 13.3 FC 4 FC 4
8827
10.9 MC 4 11.5 13.0 11.4 11.0 FC 4 FC 4 FC 4 11.4 10.5 FC 4 PC 4 11.6
8828
15.1 14.0
ms
14.9 14.6 14.3 FC 4 14.6 PC 4 PC 4 13.9 FC 4 13.7
FS
FS
8830
MC 4 15.0 MC 4 MC 4 MC 4 MC 4 14.1 14.7 14.4 MC 4 MC 4 FC 4 14.3 13.6 14.7 12.8
8831
MC 4 MC 4 MC 4 MC 4 13.4 MC 4 14.1 13.9 MC 4 13.6 13.6 13.0 12.6 FC 4 13.3
8832
14.6 MC 4 MC 4 13.6 13.7 15.7 14.4 FC 4 13.8 FC 4 FC 4 FC 4 FC 4 FC 4 FC 4 14.9 1
8833
16.5 MC 4 16.6 16.0 17.2 MC 4 MC 4 MC 4 FC 4 14.1 14.2 15.0 FC 4 15.6 FD 1
8834
16.0 MC 4 15.1 MC 4 15.5 15.5
ms
FC 4 FC 4 14.9 14.8 FC 4 15.0 13.7
FU
FU
8835
16.0 14.9 14.4 14.2 15.0 FC 4 FC 4 FC 4 MC 4 MC 4 MC 4 13.9 MC 4 13.3 MC 4 14.0
--------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST SECOND
LETTER LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 17): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA
Fl GENERATION
PUPS
------------PUP #
------------ PAT/
-------------------
1
2
3
4
5
------------------------ -
- - -----------------------
6
7
8
9
10
--- ------------------------
------------ ----------------- I ---------
11
12
13
14
15
16
1
------------------------------ ---------
LITTER
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
POSTPARTUM
DAY 7
-------------- ------------------------ - ---------------------------- -------------------------------------
8838 8840
8841 8842 8845 8846 8847 8849 8851 8852
MC 4 MC 4 15.7 14.6 13.7 MC 4 14.4 13.0 13.2 14.4
13.4 MC 4 MC 4 MC 4 14.6 MC 4 15.5 12.9 13.2 MC 4
MC 4 MC 4 14.3 14.3 13.3 13.7 MC 4 MC 4 15.2 15.2
13.9 MC 4 MC 4 14.6 FC 4 MC 4 14.8 MC 4 13.8 15.5
13.8 11.4 15.0 14.5 MD 1 MC 4 MC 4 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
14.5 13.6 MC 4 FC 4 13.8 14.7 MC 4 MC 4 FC 4 14.8
MC 4 MC 4 MC 4 FC 4 FC 4 15.1 MC 4 13.6 FC 4 14.4
MC 4 MC 4 14.4 13.6 13.0 12.4 14.5 MC 4 13.4 14.3
MC 4 12.9 15.6 13.8 14.4 FC 4 14.3 12.4 FC 4 15.S
PC 4 MC 4 1S.1 14.4 14.5 FC 4 14.6 12.6 12.6
uu
13.5 13.5 13.5 13.8 14.4 PC 4 14.3 FC 4 12.3
uu
12.5 12.6 FC 4 FC 4 FD 2 13.4 FC 4 PC 4 11.5
12.4 FC 4 14.3 FC 4
14.1 14.4 11.9 FC 4
FC 4 12.6
FC 4
13.5
12.3 FD 1
FC 4 13 FC 4 12
12.2 FM
8853 8854 8855 8857 8858
MC 4 MC 4 12.3 MC 4 MC 4 13.2 MC 4 13.9 MC 4 MC 4 12.8 MC 4 MC 4 12.8 12.6 FC 4 13
16.2 MC 4 16.1 MC 4 14.8 14.4 MC 4 MC 4 FC 4 13.0 15.1 16.1 14.5 FC 4
15.0 MC 4 14.2 15.2 13.9 14.1 FC 4 13.4 FC 4 FC 4 14.6 FC 4 13.5 FC 4 FC 4
13.7 MC 4 MC 4 MC 4 MC 4 14.7 15.1 MC 4 13.8 12.9 FC 4 14.3 14.1 13.8 FC 4
17.4 17.7
ms
FC 4 FC 4 15.0 15.2 16.3 16.6 16.6 15.1
8860 8862 8863 8864
MC 4 16.0 MC 4 15.8
16.0 MC 4 14.1 12.S
MC 4 15.5 MC 4 13.7
MC 4 MC 4 MC 4 14.4
16.2 MC 4 MC 4 MC 4
15.4 15.4 MC 4 14.8
15.7 16.4 MC 4 14.2
FC 4 15.7 16.3 14.4
15.3 FC 4 MC 4 FC 4
13.8 FC 4
16.3 14.4
13.6 14.4 MC 4
FC 4 16.3 15.1
FC 4 PC 4 12.6
FC 4 16.1 14.9
13.9 15.4
13.4
8865
MC 4 14.2 15.9 MC 4 MC 4 MC 4 MC 4 13.5 14.2 MC 4 14.0 12.6 13.5 13.7
8866 8867
MC 4 17.8
10.8 16.9
MC 4 MC 4
11.8 17.6
MC 4 17.6
MC 4 12.3
10.6 FC 4
MC 4 14.1
10.9 15.2
FC 4 14.7
11.7 FC 4
9.7 FC 4
11.4 PC 4
FC 4
FC 4
10.8
8868 8869 8870
16.3 IS.8 MC 4 16.6 MC 4 MC 4 15.8 MD 2 15.2 FC 4 14.5 FC 4 14.3 15.0
13.0 14.3 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 14.2 13.5 MC 4 14.7 FC 4 12.9 12.9 12.2
F
17.8 16.9 17.2 17.4 MC 4 15.7 FC 4 FC 4 1S.7 15.3 14.8
---------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL IGAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C36 (PAGE 18): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
INDIVIDUAL
DATA - PI GENERATION
PUPS
------
PUP ------
RAT/
---- --
#
1
--------
------------------
2
3
4
------------------
----------------------- 1. 1------ ---------------------------------------
5
6
7
8
9
10
11
12
13
14
15
16
1
- ----------------------- - ----------------------------------------------
LITTER -------
8871 8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892
8893 8894 8895 8896 8897 8898 8899 8900 8901 8902 8903
---
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM
DAY 7
--- ------------------- - ------------------------------------------------------------------------
NOT PREGNANT
14.1 MC 4 MC 4 19.1
MC 4 MC 4 16.0 17.9
12.7 15.3 14.8 16.3
14.6 14.5 MC 4 MD 1
12.9 MC 4 MC 4 17.5
MC 4 MC 4 14.8 19.8
MC 4 16.1 MC 4 15.8
MC 4 MC 4 14.9
ms MC 4 MC 4
14.0 14.2 14.8
12.5 15.5 15.5
11.9 13.1 14.0
FC 4 FC 4 14.7
13.7 13.7
13.1
15.7 13.6 13.4 MC 4 13.7 10.9 FC 4 FC 4 FC 4 12.5 12.8 FC 4 FC 4 11.9
MC 4 MC 4 MC 4 14.0 13.1 13.5 MC 4 12.4 FC 4 14.5 FC 4 13.5 FC 4 12.7 FC 4 12.8 FC
MC 4 MC 4 15.3 MC 4 MC 4 15.7 15.5 14.8
ms
14.5 FC 4 15.7 FC 4 14.6 15.0
FS
MC 4 MC 4 MC 4 MC 4 12.4 12.7 11.9 11.9 MC 4 10.7 11.8 12.8 12.1 FC 4
15.2 MC 4 14.9 14.3 14.1 FC 4 FC 4 14.5 14.3 14.3 FC 4 13.9
14.1 14.0
MC 4 15.2
MC 4 MC 4
13.5 MC 4
15.2 13.8
15.6 14.0
FC 4 FC 4
FC 4 FC 4
FC 4 13.9
13.7 13.9
14.3 12.5
15.1 13.6
FC 4 FC 4 13.S
MC 4 16.1
14.0 17.9
MC 4 16.6
MC 4
13.8
14.2
MC 4 14.3
11.2
12.8
13.5
13.0
FC 4
MC 4 12.9
MC 4 14.1
14-S 15.0
13.8 MC 4
12.5 MC 4
14.6 14.7
13.2
8.5
12.9 MC 4
NOT PREGNANT
MC 4 13.9 MC 4 13.9 MC 4 15.8
9.2 13.1
12.7 MC 4 15.6 14.2 14.4
15.0 12.5 14.7
13.0 14.5 14.2 14.2 15.5 MC 4 MC 4 MC 4
MC 4 MC 4 FC 4
MC 4 MC 4 MC 4 MC 4 13.6
MC 4 14.4 FC 4 MC 4 13.9
FC 4 FC 4 MC 4
11.9 MC 4 14.9 MC 4 14.8 14.9 12.4 FC 4
MC 4 12.7 13.7 13.0 14.7 FC 4 12.6 12.3
12.1 FC 4 14.0 13.1 FC 4 14.5
10.0 12.3
13.2 FC 4 FC 4 14.1 14.9 14.0 10.0 12.3
FC 4 13.8 FC 4 13.5 FC 4 FC 4 FC 4 12.9
12.8 13.2 12.9
FS FC 4 15.0 PC 4 FC 4
FC 4 13.9 FC 4
FC 4 FC 4
FC 4
13.4 FC 4 FM
FC 4 FM 2
12.9 FS
FM 3 FS
8904
NOT PREGNANT
8905
13.5 MC 4 14.8 14.2 MC 4 MC 4 12.8 MC 4 FC 4 12.6 FC 4 FC 4 FC 4 FC 4 13.3 12.8 11
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST SECOND NUMBER
LETTER LETTER FOLLOWING
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
A-ALIVE, S-STILLBORN,
U-UNCERTAIN,
D-DIED,
'SECOND LETTER' INDICATES THE DAY POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 19): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERAT10N
PUPS
-------- ----------------
PUP #
1
2
-------------------------
RAT/
------------ ------- - ---- ------------------- --
3
4
5
6
7
8
9
10
11
------------------- - ---- -------------------- --
----------------------- - -- -----
12
13
14
is
16
17
------------------------ --------
LITTER
MATERNAL
-------------------------
8906
MC 4 MC 4
8909
12.0 12.7
8913
12.3 11.6
8914
NOT PREGNANT
DOSAGE GROUP IV
1.6 MG/KG/DAY
---------------------------------------------------
11.9 13.6 12.1
12.8 13.3 10.3
11.7 13.2 MD 3
11.2 FC 4 FC 4
MD 2 12.8 11.2
MD 2 FC 4 12.2
12.4 12.6 11.7
11.5 FC 4 FC 4
11.6 13.1 12.3
POSTPARTUM
DAY 7
----------------------------------
10@l FM 3 FD I
FC 4
8918
NOT PREGNANT
8919 8920 8921 8923
MC 4 MC 4 11.4 11.3 12.7 14.0 NOT PREGNANT
11.5 11.2 12.8
12.0 10.9 MC 4
12.3 11.6 MC 4
11.2 MD 2 13.2
MC 4 13.4 13.0
MC 4 FM 2 13.7
MC 4 FD 1 MD 2
MC 4 ms
11.4 ms
11.1 11.9
9.3 12.4
9.5 PC 4 FM 2
8925 8926 8927 8928 8929 8930 8931 8932 8933
11.5 MM 2 FC 4 11.9 10.5
8.2 10.6 12.2 11.2
9.8 FM 2 FD 2
8.5 MD 3 MD 2
9.3
6.9
8.8 FM 3 FM 3 FD 2 FD 2 FD 2 FD 2
MD 5 MC 4
MD 5 13.7
MD 5 13.0
MD 3 13.1
MD 2 MC 4
MD 2 13.0
6.5 MC 4
6.1 12.8
FD 5 12.1
FM 5 FC 4
FM 5 11.4
FM 4 13.2
FD 3 FD 3 FD 2 FD 2 FD
MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 FM 2
MC 4 12.6 MC 4 13.1 12.8 13.2 13.3 MD I MD 1 MD 1
9.8
9.7 11.3 FD 1 FD 1
10.2 11.9 11.9
9.7 MD 1 MD 1 MD 1 MD I MD 1 FD 1 FD 1
10.5 MC 4 MC 4 MC 4
7.8
8.3 10.1 MM 3 MM 3 MD 3 MD 2
9.5
9.2
8.1
8.1 FM 3 FD
NOT PREGNANT
8934
MC 4
9.3 10.7 MC 4
9.9 10.7 MD 2
8.1
8.4
8.1
9.5 FM 3 FD 2
8935
@11.3 MC 4 MC 4
9.6
9.6 10.5 MD 4
9.2 FC 4 10.6 10.7 11.5
8936 8937 8938
MD 4 MD 4 MD 4 13.1 12.8 13.0 MORIBUND SACRIFICED
MD 4 12.2
ON
MD 2 13.1 DAY 36
MM 2 MD 2
ms
11.9
OF STUDY
MD 1 12.2
ms 11.3
MD 1 FM 2
FD 4 FS
FD 4 FD 3 FD 3 FD I
8939
11.7 10.2 12.4 MD 1 MD 1 10.9 10.5 FD 1 FD 1 FD 1 FD 1 FD 1 FD 1
8940
MC 4 MC 4 14.2 MC 4 13.2 MC 4 13.8 13.8 MD 2 MD I FC 4
9.8 13.8 10.4 10.8
----------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RAI!@ (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICII
TABLE C36 (PAGE 20); PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDI)AL DATA - Fl GENERATION
PUPS
---------------------------
PUP #
1
2
3
----- ------------------------
RAT/
--------------------
4
5
6
7
----------------------
--- I --
8 --- --
-------------------
9
10
11
12
-------------------
--------------------- -
13
14
is
16
17
--- ----------------------
LITTER
MATERNAL DOSAGE
------------------------------
8942 8943 8944 8945
MD 1 MD 1 MD 1
NOT
MD 1 ms ms
PREGNANT
MD 1 ms FS
GROUP V
--------------------------
MD I FD 1 FD 1
ms
ms
FD 1
FD 1 FD 1
3.2 MG/KG/DAY ----------------------
POSTPARTUM
DAY 7
------------------------------
8946 8949
8950 8952
MD 2 MD 2 MD 2
MM 2 MD 2 MD 2
ms
FD 1 FD I
NOT PREGNANT
MM 2 MD 2 FD 1
ms MD 2 FD I
ms MD 2
FS
FD 2 FM 2
FD 2 FM 2
FD 2 FD 2
FD 2 FD 2
FM 2 FD 2
FS FD 2
8955 8956 8957
ms
MD 1 MD 1 MD I MD I
MD 2 MD 2 MD 2 MD 2 MD 2
NOT PREGNANT
FS MD 2
FD I MD 1
FD I FD 2
FD 1 FD 2
FD 2
FD 2
FD 2 FD 1
8959 8960 8961 8962
MD 2 ND 2 MD 2 MD 2 MD 1 ms
ms
FD 2 FD 2 FD 2 FD 2 FD 1 FS
MD 1 MD 1 MD 1 ms
ms
ms
ms
FD 1
FS
FS
FS
FS
FS
MD 2 MD 2 MD 2 MD 2 MD 2 MM 2 ms
FD 2 FD 2 FD 2 FM 2 FD 1 FS
FS
ms
ms
ms
FD 1
8964 8967 8968 8969 8970 8971 8972
MM 2 ms ms
MD 1 MD 2 MM 2
NOT
MM 2 ms ms
MD 1 MD 2 MM 2 PREGNANT
MM 2 ms
FD 2 MD I MD 2 MM 2
MM 2 FS
FM 2 FD I MD 2 MM 2
MD 2 FS
FD I FM 1 MD 2 MD 2
MD 2 FS
FD 1
ms MD 2
MD 2 FS FS
FD 2 MD 2
MD 2 FS FS
FD 2 FM 2
MM I uu FS
FD 2 FM 2
ms
FS
FD 2 FM 2
FM 2
FS FD 2
FD 2 FD 2
FM I FD 1 FD 2
8973
MM 2 MD 1 MD 1 MD 1 MD 1 MD 1
ms
FD 1 FD I FD 1 FD 1
8974
MD 1 MD 1 MD 1 MD 1
ms
ms
FD 1 FD I FD 1 FD 1 FS
8975
MD 1 MD I MD I MD 1 MD I MD 1 FD 1 FD I FD 1 FD 1 FD I FD 1
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOIIMENTAL
PPOS IN RATS (SPONSOR'S STUDY NUMBER;
6195.9)
AND PERINATAL/POSTNATAL,
REPRODUCTION
TOXIC
TABLE C36 (PAGE 21): PUP BODY WETGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA
Fl GENERATION
PUPS
----
------- ------------------
PUP #
1
2
3
------------ --------------
RAT/
-- -- ------ ---------- - -
4
5
6
7
a
------------- ---------- I ---
---------------------- -
9
10
11
12
------------------------
--- ---------------- --
13
14
15
16
------------------------
LITTER
MATERNAL
DOSAGE
--- ---------------------------
GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------- ------------------------
POSTPARTUM
DAY 14
------------------------
8801
MC 4 30.5 30.8 31.7 32.1 31.5
ms
30.6 29.5 30.3
8803
30.2 26.7 MC 4 31.1 MC 4 31.1 MC 4 ms
FC 4 28.6 35.5 34.1 35.2
8804 8805 8807 8808
MC 4 27.5 MC 4 31.6
35.2 28.6 MC 4 28.1
MC 4 27.4 MC 4 27.6
34.6 26.8 34.7 29.2
36.3 24.1 MC 4 29.4
32.9 FC 4 34.2 29.5
32.7 FC 4 32.7 FC 4
FC 4 FC 4 34.5 27.6
FC 4 FC 4 31.8 28.2
33.5 FC 4 31.3
FS
FC 4 PC 4 FC 4
33.0 24.0 31.9
FC 4 FC 4 31.9 23.9 23.5 FC 4 FM 4 F 32.5
8811
35.5 MC 4 36.1 35.4 MC 4 34.9 34.2 33.8 33.2 FC 4 FC 4 34.6
8812 8813
35.7 30.8
35.8 30.2
34.0 29.7
36.3 FC 4
FC 4 27.4
FC 4 28.3
FC 4 29.9
FC 4 FC 4
FC 4 FC 4
FC 4 32.2
32.4 30.5
FC 4 FC 4 35.8 FC 4 35.7 3 FC 4
8814 8817
MC 4 39.0 NOT PREGNANT
40.4
MC 4 40.9
39.0
MC 4 38.8
FC 4 38.0
38.1
FC 4 35.8
8818
NOT PREGNANT
8819 8821 8823
35-2 MC 4 31.1
36.5 30.8 30.0
34.3 30.9 30.9
34.3 MC 4 MC 4
PC 4 32.1 MC 4
34.4 31.0 MC 4
33.4 MC 4 30.3
FC 4 MC 4 30.2
FC 4 30.4 FC 4
34.2 30.9 30.4
FC 4 FC 4 29.8
33.4 29.0 28.4
28.8 FM 2
8824
MC 4 30.4 MC 4 MC 4 29.9 MC 4 21.8 MC 4 31.2 21.7 PC 4 30.7 28.3 29.4 FC 4
8826
29.5 27.4 28.9 MC 4 29.7 FC 4 FC 4 28.1 28.4 27.3 26.0 FC 4 PC 4
8827
22.6 MC 4 24.2 25.2 22.3 24.1 FC 4 FC 4 FC 4 23.8 22.6 FC 4 FC 4 19.5
8828
33.1 33.2
ms
31.8 32.0 31.7 FC 4 32.0 FC 4 FC 4 33.1 FC 4 32.6
FS
PS
8830
MC 4 29.5 MC 4 MC 4 MC 4 MC 4 30.2 28.7 31.1 MC 4 MC 4 FC 4 27.4 29.3 29.1 31.0
8831
MC 4 MC 4 MC 4 MC 4 33.0 MC 4 31.2 32.9 MC 4 30.8 32.2 31.5 31.6 FC 4 31.8
8832
32.4 MC 4 MC 4 28.6 30.4 30.8 29.6 FC 4 29.1 FC 4 PC 4 FC 4 PC 4 FC 4 FC 4 31.4 3
8833
34.2 MC 4 34.4 33.0 34.6 MC 4 MC 4 MC 4 FC 4 29.4 31.3 31.1 FC 4 31.7 FD 1
8834
31.4 MC 4 30.8 MC 4 31.2 31.9
ms
FC 4 FC 4 29.1 30.5 FC 4 29.0 30.7
FU
FU
8835
34.6 33.3 33.4 31.9 29.7 FC 4 FC 4 FC 4 MC 4 MC 4 MC 4 33.0 MC 4 31.9 MC 4 31.4
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 22): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
-- - ------------------
PUP #
1
2
------------------------
RAT/
------- ----------- -- ---- ----- -------------- --- ---------
3
4
5
6
7
8
9
10
11
12
13
-------------------- -------- --------------------- -------------
---14
-------- - -----
15
16
1
---------- -----
LITTER
MATERNAL
DOSAGE GROUP 11
---------------------------------------------
0.1 MG/KG/DAY
POSTPARTUM
DAY 14
-------- -------------------- -----------------------------------
8838 8840 8841 8842 8845 8846
8847 8849 8851 8852 8853 8854 8855 8857 8858
MC 4 MC 4 33.2 28.0 30.4 MC 4
32.0 MC 4 MC 4 MC 4 29.7 MC 4
MC 4 MC 4 31.5 28.5 29.5 33.0
30.7 MC 4 MC 4 29.9 FC 4 MC 4
32.8 29.3 32.7 28.3 MD I MC 4
MC 4 MC 4 MC 4 FC 4 FC 4 31.6
32.7 31.5 MC 4 FC 4 29.6 30.8
MC 4 MC 4 MC 4 FC 4 FC 4 30.7
MC 4 MC 4 32.5 29.1 30.4 28.2
MC 4 31.9 30.9 27.6 28.5 FC 4
FC 4 MC 4 30.2 28.9 30.4 FC 4
31.1 25.9 33.3 27.9 30.5 FC 4
32.2 28.9 FC 4 FC 4 FD 2 30.4
29.9 FC 4 32.7 FC 4
30.9
FC 4 30.2 FC 4
29.7
FC 4 32 FC 4 30
26.9 27.4 MC 4 26.7 MC 4 MC 4 MC 4 MC 4 24.7 24.7 25.8 25.7 FC 4 26.4
28.3 30.9 MC 4 MC 4 MC 4 MC 4 MC 4 29.4 MC 4 28.7 26.8 FC 4 FC 4 29.3 28.1 28.1 FM
29.6 27.5 32.2 29.9 MC 4 FC 4 FC 4 FC 4 28.2 FC 4 26.5 30.2 28.7 FC 4 FD 1
31.0 MC 4 31.8 31.5 MC 4 31,0 31.0 30.3 31.3 31.7
tiu
uu
MC 4 33.0 31.5 31.0 33.9
MC 4 MC 4 MC 4 MC 4 34.5
29.2 34.7 29.0 MC 4
ms
MC 4 MC 4 30.5
MC 4 FC 4
MC 4 33.0 32.5 MC 4 FC 4
29.7 32.1 29.8 31.4 32.4
MC 4 MC 4 FC 4 32.6 30.5
29.1 MC 4 26.8 MC 4 30.2
MC 4 FC 4 FC 4 30.3 30.0
MC 4 33.6 FC 4 31.7 31.8
26.9 32.1 30.0 FC 4 34.0
MC 4 28.5 FC 4 29.8
MC 4 30.8 28.0 30.2
28.9 FC 4 FC 4 33.1
20.7
FC 4 FC 4
FC 4 28
8860 8862 8863 8864
MC 4 34.6 MC 4 31.9
28.2 MC 4 31.1 33.5
MC 4 36.3 MC 4 32.0
MC 4 MC 4 MC 4 28.1
28.3 MC 4 MC 4 MC 4
33.3 35.2 MC 4 32.2
35.7 36.0 MC 4 30.7
FC 4 34.3 28.8 32.5
31.7 FC 4 MC 4 FC 4
29.5 FC 4 32.5 30.9
28.5 34.7 MC 4
FC 4 33.5 32.9
FC 4 FC 4 30.4
FC 4 34.7 31.0
26.2 28.1
27.9
8865 8866 8867 8868 8869 8870
MC 4 33.1 31.0 MC 4 MC 4 MC 4 MC 4 30.3 30.7 MC 4 28.9 30.8 28.6 30.4
MC 4 35.0
25.2 32.9
MC 4 MC 4
22.8 28.0
MC 4 34.3
MC 4 24.1
21.6 FC 4
MC 4 32.4
26.6 32.0
FC 4 31.2
20.5 FC 4
23.3 FC 4
26.9 FC 4
FC 4
FC 4 26.5
34.5 36.0 MC 4 35.1 MC 4 MC 4 37.0 MD 2 33.3 FC 4 31.7 FC 4 32.6 33.5
30.6 29.8 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 31.8 33.0 MC 4 28.4 FC 4 30.8 27.7 28.6
F
35.1 34.2 34.0 35.6 MC 4 31.7 FC 4 FC 4 32.0 31.4 33.5
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED
IN GRAMS (G).
FIRST LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
SECOND NUMBER
LETTER FOLLOWING
A-ALIVE, "SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, C-CULLED, M-MISSING
POSTPARTUM
THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAV4GE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER!
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C36 (PAGE 23); PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA - Fl GENERATION
PUPS
----------------------------
PUP #
1
2
3
----------------------------
RAT/
-- ------ ---- - ------------
4
5
6
7
8
-----------------------------
-------------------- ----------- -
9
10
11
12
13
14
------------------------------------
-----------------
15
16
17
----------------
LITTER
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------- ------------------------------------------------
8871
NOT PREGNANT
POSTPARTUM
DAY 14
----------------------------------
8872 8874 8875 8876 8881 8882 8885 8889 8890 8891 8892 8893 8894
29.6 MC 4 MC 4 34.0 29.6 MC 4 MC 4 MC 4 30.0 31.5 26.5 MC 4 28.3
MC 4
MC 4 31.5 33.2 30.6 MC 4 MC 4 MC 4 MC 4
MC 4 28.9 31.6 33.2
31.2 30.4 29.1 33.5 32.9 MC 4 31.6 MC 4 29.9 MC 4 MC 4
MC 4 31.7
31.8 29.4 MC 4 MD 1 MC 4 30.8 MC 4 MC 4 31.0 31.4 MC 4 MC 4
29.4 MC 4 MC 4 37.6 29.7 29.2 MC 4 27.6 31.5 30.8 28.3 26.0
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 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
ms MC 4 MC 4
FC 4 FC 4
ms MC 4 30.4 FC 4 27.2 16.7
29.5 29.8 30.9
28.5 31.3 28.7 26.2 29.8 30.7 27.6 25.8
27.9 28.4 28.0
28.1 28.7 29.6
FC 4 FC 4 29.7
31.0 26.7
27.0
27.5 FC 4 FC 4 28.7
FC 4 31.1 FC 4 29.9 FC 4 29.5 FC
FC 4 29.7 FC 4 31.2 32.7
FS
27.7 26.3 23.2 PC 4
FC 4 29.8
28.9 28.7
31.2 27.5
FC 4 FC 4 31.9
27.7 19.8 PC 4
8895 8896 8897
8898 8899 8900 8901 8902 8903
MC 4 MC 4 32.6
29.5 34.1 32.4
MC 4 32.6 MC 4
28.8 MC 4 33.6
29.2 34.2 32.6
MC 4 MC 4 FC 4
MC 4 32.6 FC 4
28.8 MC 4 32.6
MC 4 31.1 31.2
29.4 FC 4 31.4
28.3 FC 4 FC 4
FC 4 33.5 FC 4
28.6 31.8 30.9
PC 4 30.9 FC 4
26.2
FC 4 FM
27.0 MC 4 26.3 27.0 25.9 MC 4 MC 4 MC 4 24.8 26.6 26.8 24.4
FS
33.8 33.2 22.4
MC 4 31.7 24.2
MC 4 31,8 26.9
33.8 31.2 24.3
29.8 MC 4 MC 4
MC 4 MC 4 MC 4
31.8 FC 4 FC 4
MD13 31.1 23.9
32.0 FC 4 28.8
FC 4 32.8 30.1
32.9 30.8 24.1
FC 4 FC 4 FC 4
FC 4 32.0 FC 4
FC 4 FC 4
FC 4 FM 2
30.6 FS
33.2 MC 4 31.3 30.6 MC 4 32.3 MC 4 FC 4 30.9 29.2 30.3 28.4 FC 4 FC 4 FM 3 FS NOT PREGNANT
8904
NOT PREGNANT
8905
35.1 MC 4 34.4 33.2 MC 4 MC 4 31.9 MC 4 FC 4 31.8 FC 4 FC 4 FC 4 FC 4 31.6 29.6 31.
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED
IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABI,E C36 (PAGE 24): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
---- -------------------------- --------------------- ------------------------- ------------------------ ------
PUP #
1
2
3
---- --------------------------
PAT/
4
5
6
7
8
9
10
11
12
13
14
is
16
-------------------- ---------------------------------------------------------
LITTER
MATERNAL
DOSAGE GROUP IV
1.6 MG/KG/DAY
---- -----------------------------------------------------------------------
8906 8909 8913 8914
MC 4 MC 4 27.0 24.6 26.1 22.4 NOT PREGNA.NT
26.0 29.3 24.3
28.3 28.2 25.5
27.6 26.8 MD 3
25.5 FC 4 FC 4
MD 2 25.7 24.6
MD 2 FC 4 24.3
26.4 27.5 25.2
28.1 FC 4 FC 4
24.4 28.5 26.1
POSTPARTUM
DAY 14
---------------------------------
25.7 FM 3 FD 1
FC 4
8918
NOT PREGNANT
8919 8920 8921 8923
MC 4 MC 4 21.9 22.6 25.8 27.3 NOT PREGNANT
26.4 24.4 26.5
26.9 22.1 MC 4
28.3 22.3 MC 4
26.7 MD 2 25.6
MC 4 24.4 26.9
MC 4 FM 2 25.4
MC 4 FD 1 MD 2
MC 4 ms
25.9 ms
23.1 24.1
24.2 26.4
21.9 FC 4 FM 2
8925 8926 8927 8928 8929 8930 8931 8932 8933
26.3 MM 2 FC 4 26.4 21.5 24.2 27.3 22.2 26.7 FD10 FM 2 FD 2
22.7 MD 3 MD 2 21.6 21.2 16.8 FM 3 FM 3 FD 2 FD 2 FD 2 FD 2
MD S MC 4
ND 5 26.9
MD 5 25.5
MD 3 28.4
MD 2 MC 4
MD 2 25.6
15.5 MC 4
13.8 25.7
FD 5 24.9
FM 5 FC 4
FM 5 26.7
FM 4 24.4
FI) 3 FD 3 FD 2 FD 2 F
MM 2 MM 2 MM 2 MM 2 MM 2 MM 2 FM 2 FM 2
MC 4 27.1
28.9 24.0
MC 4 23.4
28.5 26.8
30.0 MD I
28.3 MD 1
28.4 MD I
MD 1 MD I
MD 1 MD 1
MD 1 FD I
24.0 FD 1
27.7
23.4 FD 1 FD 1
19.4 MC 4 NOT PREGNANT
MC 4
MC 4
23.1
23.5
17.3 MM 3 MM 3 MD 3 MD 2 22.3
21.1
19.8 19.2 FM 3 F
8934
MC 4 22.9 23.5 MC 4 25.5 25.8 MD 2 23.3 20.8 21.0 20.9 FM 3 FD 2
8935
21.7 MC 4 MC 4 23.1 25.7 26.0 MD 4 23.5 FC 4 22.7 26.2 24.3
8936 8937
MD 4 28.3
MD 4 27.2
MD 4 29.5
MD 4 27.6
MD 2 28.6
MM 2 ms
MD 2 28.9
MD 1 25.7
ms 25.7
MD 1 FM 2
FD 4 FS
FD 4
FD 3
FD 3
8938
MORIBUND SACRIFICED
ON DAY 36 OF STUDY
8939
26.1 22.9 21.6 MD 1 MD 1 23.4 21.5 FD 1 FD 1 FD I FD 1 FD I FD 1
8940
MC 4 MC 4 29.6 MC 4 33.2 MC 4 29.2 30.8 MD 2 MD I FC 4 24.0 24.3 23.9
--------------------------------------------------------------------------------------------------------------
FD I 29.4
FD 1 FS
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST SECOND
LETTER LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RARS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C36 (PAGE 2S):
PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA
Fl GENERATION
PUPS
--------------- --------------
PUP #
1
2
3
------------------------------
RAT/
-------
4 -------
--------------------
5
6
7
8
--------------------
-------------------------- -
9
10
11
12
13
-----------------------------
---------------------
14
15
16
1
--------------------
LITTER
MATERNAL
DOSAGE
------------------------------
GROUP V ----------------------------
3.2 MG/KG/DAY
POSTPARTUM
DAY 14
----------------------------- ---------------------
8942 8943 8944 8945
MD 1 MD 1 MD I
NOT
MD 1 ms ms
PREGNANT
MD I ms FS
MD 1 ms
FD I
FD I ms
FD 1
FD I FD 1
8946 8949 8950 8952
MD 2 MD 2 MD 2
MM 2 MD 2 MD 2
ms
FD 1 FD 1
NOT PREGNANT
MM 2 MD 2 FD 1
ms MD 2 FD I
ms MD 2
FS
FD 2 FM 2
FD 2 FM 2
FD 2 FD 2
FD 2 FD 2
FM 2 FD 2
FS FD 2
8955 8956 8957
ms
MD 1 MD 1 MD 1 MD 1
FS
MD 2 MD 2 MD 2 MD 2 MD 2 MD 2
NOT PREGNANT
FD 1 MD 1
FD 1 FD 2
FD 1 FD 2
FD 2
FD 2
FD 2 FD 1
8959 8960 8961 8962 8964 8967 8968 8969 8970 8971 8972
MD 2 MD 1 MD 2
ms MM 2
ms ms MD 1 MD 2 MM 2 NOT
MD 2 MD 1 MD 2
ms MM 2
ms ms MD I
MD 2 MM 2
PREGNANT
MD 2 MD 1 MD 2
ms MM 2
ms FD 2 MD I MD 2 MM 2
MD 2 ms
MD 2 FD 1 MM 2
FS FM 2 FD 1 MD 2 MM 2
MD 1 ms
MD 2
MD 2 FS
FD 1 FM 1 MD 2 MD 2
ms ms MM 2
MD 2 FS
FD 1
ms MD 2
ms ms ms
MD 2 FS FS
FD 2 MD 2
FD 2 FD I FD 2
FD 2 FS
FD 2
MD 2 FS FS
MM I uu PS
FD 2 FM 2
FD 2 FM 2
FD 2 FS
FD 2
ms
FS
FD 2 FM 2
FD 2 FS
FM 2 FM 2
FS FD 2
FD I FS
FS
FS
FD 1 FS
FD 2 FM 1
FD 2 FD 2
FS FD 1
8973
MM 2 MD I MD 1 MD 1 MD 1 MD 1 ms
FD 1 FD I FD 1 FD 1
8974
MD I MD 1 MD 1 MD 1
ms
ms
FD 1 FD 1 FD 1 FD 1
FS
8975
MD 1 MD 1 MD 1 MD 1 MD 1 MD 1 FD I FD 1 FD I FD 1 FD 1 FD I
---------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUI)Y NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C36 (PAGE 26): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
----------
PUP # ----------
PAT/
-------- ---- - -- ---------- I ------
1
2
3
4
5
6
-------------- --- ------------------
------ --
7
8
---------
----------------- - -------------------------------
9
10
11
12
13
14
15
16
---------------------------------------------------
LITTER
MATERNAL DOSAGE GROUP 1
-----------------------------------------------
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817 8818
MC 4 47.1 49.5 43.0 MC 4 53.7 47.6 47.6 MC 4 MC 4 46.3 53.2 59.0 MC 4 58.4 56.3 52.4 50.3 MC 4 64.0 NOT PREGNANT NOT PREGNANT
47.4 MC 4 MC 4 45.9 MC 4 47.6 60.0 59.5 SO.2 68.0
47.0 56.5 55.8 45.4 53.0 48.6 58.0 57.7 PC 4 MC 4
45.8 MC 4 55.2 39.6 MC 4 48.1 MC 4 FC 4 52.3 64.0
46.0 50.0 59.7 FC 4 56.3 47.1 58.0 FC 4 52.0 63.0
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
DAY 21
--------------------------------------------------------------
ms
46.0 47.0 44.3
MC 4 ms
FC 4 50.9 43.9 46.8 55.0
51.1 FC 4 FC 4 52.3 FC 4 53.3 FC 4 PC 4 56.3
FC 4 FC 4 FC 4 FC 4 FC 4 41.0 37,7 39.1 FC 4 FM 4 F
55.4 52.5 50.1 50.9 PC 4 49.7 50.3
FC 4 50.0 48.6
FS
56.0 55.0 54.0 FC 4 FC 4 56.0
FC 4 FC 4 FC 4 FC 4 51.2 FC 4 FC 4 56.1 PC 4 52.6 5
50.7 FC 4 FC 4 47.8 46.5 FC 4
MC 4 63.0 FC 4 56.0 62.0 FC 4 63.0
8819
51.0 56.6 54.7 52.3 FC 4 52.5 50.2 FC 4 FC 4 52.6 FC 4 54.0
8821
MC 4 51.9 50.3 MC 4 50.4 52.6 MC 4 MC 4 49.8 52.0 FC 4 49.7 49.0 FM 2
8823
48.0 51.0 51.0 MC 4 MC 4 MC 4 50.0 48.0 FC 4 49.0 51.0 49.0
8824
MC 4 47.0 MC 4 MC 4 48.0 MC 4 36.0 MC 4 49.0 46.0 FC 4 46.0 44.0 33.0 FC 4
8826
43.0 43.0 45.0 MC 4 45.0 FC 4 FC 4 40.0 44.0 42.0 42.0 FC 4 FC 4
8827
42.4 MC 4 42.8 39.5 40.8 42.9 FC 4 FC 4 FC 4 36.1 40.7 FC 4 FC 4 36.2
8828 8830 8831
53.0 MC 4 MC 4
52.1 54.3 MC 4
ms MC 4 MC 4
50.9 MC 4 MC 4
52.2 MC 4 49.0
52.1 MC 4 MC 4
FC 4 50.1 50.0
49.6 45.4 51.0
PC 4 49.8 MC 4
FC 4 MC 4 49.0
50.6 MC 4 49.0
FC 4 FC 4 49.0
49.7 50.3 48.0
FS 46.1 FC 4
PS 47.3 49.0
43.8
8832 8833
48.7 53.4
MC 4 MC 4
MC 4 56.7
49.9 52.3
50.6 52.8
52.4 Sl.O FC 4 50.4 FC 4 FC 4 FC 4 FC 4 FC 4 PC 4 50.2 47 MC 4 MC 4 MC 4 FC 4 49.6 45.1 47.8 FC 4 48.4 FD 1
8834 8835
47.0 50.0
MC 4 54.0
47.0 51.0
MC 4 53.0
46.0 47.0
47.0 FC 4
ms FC 4
FC 4 FC 4
FC 4 MC 4
44.0 MC 4
43.0 MC 4
FC 4 50.0
43.0 MC 4
45.0 49.0
FU MC 4
FU 47.0
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS FIRST LETTER SECOND LETTER
WERE
RECORDED M-14ALE,
A-ALIVE,
IN GRAMS (G).
F-FEMALE,
U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
D-DIED,
C-CULLED,
M-MISSING
(PRESUMED CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTII,ITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C36 (PAGE 27): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
INDIVIDUAL
DATA - Fl GENERATION
PUPS
--------------
-- ------ -------------- -- --------
-------------------- ---------------------
---------
PUP #
1
2
3
4
5
--------------- I ----------------------------
6
7
8
9
10
11
12
13
14
15
16
17
- ---------------------------------------------------------------
PAT/
LITTER
MATERNAL DOSAGE GROUP Il
--------------------------------------------
0.1 MG/KG/DAY
POSTPARTUM
DAY 21
-------------------------------------------------------------------
8838 8840 8841 8842 8845 8846 8847 8849 8851 8852 8853 8854 8855 8857 8858
MC 4 49.3 MC 4 50.6 53.2 MC 4 52.1 MC 4 MC 4 MC 4 FC 4 47.9 50.3 51.5 FC 4 FC 4 47.
MC 4 MC 4 MC 4 MC 4 41.6 MC 4 51.9 MC 4 MC 4 51.3 MC 4 48.0 47.7 PC 4 45.6 FC 4 47.
48.0 MC 4 49.0 MC 4 48.0 MC 4 MC 4 MC 4 49.0 47.0 49.0 47.0 FC 4 53.0
43.6 MC 4 46@2 45.1 4S.7 PC 4 FC 4 FC 4 45.5 45.1 47.5 48.4 FC 4 PC 4 FC 4
51.0 51.5 52.8 FC 4 MD 1 FC 4 47.4 FC 4 51.6 49.9 50.4 51.4 FD 2
MC 4 47.0
MC 4 44.1
48.8 MC 4
MC 4 44.3
MC 4 MC 4
47.6 MC 4
48.9 MC 4
53.6 MC 4
48.6 48.6
PC 4 46.7
FC 4 44.1
FC 4 44.0
48.5 PC 4
46.9 43.7
44.9
44.6 47.3 MC 4 MC 4 MC 4 MC 4 MC 4 47.1 MC 4 45.7 43.3 PC 4 PC 4 44.4 44.4 44.5 FM
50.0 50.0 46.0 55.0 MC 4 FC 4 FC 4 FC 4 41.0 PC 4 46.0 48.0 50.0 FC 4 FD 1
50.0 MC 4 49.0 50.0 MC 4 48.0 51.0 48.0 48.0 49.0
uu
uu
MC 4 48.0
MC 4 MC 4
43.6 48.0
MC 4 MC 4
MC 4 53.0
47.7 49.0
MC 4 MC 4
46.0 MC 4
MC 4 FC 4
MC 4 44.0
47.5 51.0
MC 4 50.0
MC 4 47.0
46.1 PC 4
48.6
FC 4 46.
45.0 MC 4 44.0 45.0 4S.0 42.0 FC 4 40.0 FC 4 PC 4 41.0 FC 4 44.0 PC 4 PC 4
54.0 54.0
MC 4 56.0
MC 4 ms
MC 4 FC 4
MC 4 PC 4
51.0 52.0
50.0 48.0
MC 4 53.0
52.0 50.0
53.0 54.0
FC 4 50.0
50.0
50.0
54.0
PC 4
8860 8862 8863 8864
MC 4 55.5 MC 4 48.9
47.0 MC 4 45.2 52.0
MC 4 58.9 MC 4 48.9
MC 4 MC 4 MC 4 45.6
52.0 MC 4 MC 4 MC 4
54.0 59.7 MC 4 50.9
47.0 59.5 MC 4 48.0
FC 4 54.8 45.6 48.0
43.0 FC 4 MC 4 PC 4
45.0 FC 4 49.6 48.0
48.0 58.2 MC 4
FC 4 55.2 44.4
FC 4 PC 4
50.3
FC 4 55.7 45.9
49.0 42.5
42.8
8865 8866 8867 8868 8869 8870
MC 4 52.0 54.0 MC 4 MC 4 MC 4 MC 4 51.0 50.0 MC 4 50.0 47.0 51.0 48.0
MC 4 40.1 MC 4 37.6 MC 4 MC 4 41.5 MC 4 37.6 FC 4 35.1 42.1 41.5 PC 4 FC 4 38.4
49.0 56.0 MC 4 57.0 56.0 42.0 FC 4 50.0 52.0 52.0 PC 4 FC 4 FC 4
51.1 57.3 MC 4 57.0 MC 4 MC 4 52.8 MD 2 53.3 FC 4 52.1 FC 4 50.1 51.5
48.0 48.0 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 53.0 51.0 MC 4 47.0 FC 4 44.0 51.0 45.0
FS
54.7 53.8 53.1 53.2 MC 4 50.4 FC 4 FC 4 47.3 48.0 48.6
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
SECOND NUMBER
LETTER -- A-ALIVE,
FOLLOWING
"SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, C-CULLED, M-MISSING
POSTPARTUM
THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPON!;OR'S STUDY NLJMBER: 6295.9)
AND PERINATAL/POSTNATAL
REFIRODUCTION TOXIC
TABLE C36 (PAGF 28): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
INDIVIDUAL
DATA - Fl GENERATION
PUPS
--------------- ---- ----------------
PUP #
1
2
3
4
--------------- ----------------------
- --
5 -----
---- ---------------------
6
7
8
9
10
--------------------------
--------------------- ---------------
11
12
13
14
is
16
------------------ --- ---------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM
DAY 21
--------------- ---------------------- --------------------------------- --------------------- ---------------
8871
NOT PREGNANT
8872 8874 8875 8876
49.9 MC 4 MC 4 57@O
MC 4 MC 4 51.0 S8.0
50.8 48.0 50.0 57.0
55.0 50.8 MC 4 MD 1
49.4 MC 4 MC 4 S5.0
MC 4 MC 4 49.0 59.0
MC 4 50.8 MC 4 52.0
MC 4 MC 4 49.0
ms MC 4 MC 4
46.5 46.8 48.0
49.7 49.1 51.0
47.7 48.3 48.0
FC 4 FC 4 48.0
52.7 46.6
45.6
Seel 8882 8885 8889 8890 8891 8892 8893 8894
SO.0 50.0 52.0 MC 4 48.0 45.0 FC 4 FC 4 FC 4 48.0 45.0 FC 4 FC 4 42.0
MC 4 MC 4 MC 4 55.0 52.0 53.0 MC 4 52.0 FC 4 51.0 FC 4 52.0 FC 4 55.0 PC 4 56.0 F
MC 4 MC 4 52.0 MC 4 MC 4 49.0 54.0 51.0
ms
48.0 FC 4 Sl.O FC 4 53.0 50.0
FS
MC 4 MC 4 MC 4 MC 4 38.4 39.0 37.0 39.2 MC 4 35.8 36.1 40.9 34.5 FC 4
50.9 MC 4 50.9 51.1 51.4 FC 4 FC 4 51.1 52.6 49.6 FC 4 52.7
50.8 MC 4 MC 4 47.7 48.3 47.4 FC 4 FC 4 FC 4 44.8 48.9 48.1 FC 4 FC 4 49.6
40.0 40.0 MC 4 MC 4 39.0 36.0 FC 4 FC 4 38.0 40.0 37.0 39.0
MC 4 56.1 MC 4 MC 4 49.8 35.9 MC 4 51.8 42.0 47.1 FD17 FD16 FC 4
48.6
43.7
44.3
8895 8896a 8897a
MC 4 MC 4 45.0
50.3 56.0 46.0
MC 4 52.0 MC 4
48.0 MC 4 48.0
46.9 51.0 45.0
MC 4 MC 4 FC 4
MC 4 -51.0 FC 4
42.7 MC 4 48.0
MC 4 48.0 46.0
47.2 FC 4 47.0
47.0 FC 4 FC 4
FC 4 48.0 FC 4
45.3 48.0 43.0
FC 4 48.0 FC 4
43.8
FC 4 F?
8898 8899 8900 8901 8902 8903
43.0 MC 4 51.0 MC 4 50.0 50.0 40.0 41.0 49.9 MC 4 NOT PREGNANT
42.8 MC 4 54.0 47.0 54.2
46.1 S3.0 55.0 51.0 50.1
41.6 56.0 MC 4 MC 4 MC 4
MC 4 MC 4 MC 4 MC 4 48.6
MC 4 56.0 FC 4 FC 4 MC 4
MC 4 MD13 51.0 49.0 FC 4
40.8 52.0 PC 4
49.0 45.8
46.5 FC 4 50.0 45.0 46.8
41.0 56.0 52.0 41.0 48.4
41.5 FC 4 FC 4 FC 4 48.7
FS FC 4 52.0 FC 4 FC 4
FC 4 FC 4
FC 4
FC 4 FM 2
53.0 FS
FM 3 FS
8904
NOT PREGNANT
8905
52.4 MC 4 55.0 54.6 MC 4 MC 4 50.5 MC 4 FC 4 47.3 FC 4 FC 4 FC 4 FC 4 50.5 49.2 51
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
a. On day 15 postpartum, the pups from litter 8897 were discovered in the litter box with litter 8896. The p arbitrarily distributed between the two dams and values will be included in group averages and statistical
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INA,rAl,/ POSTNATAL
REPRODUCTION
TOXIC
TABLE C36 (PAGE 29):
PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - Fl GENERATION
PUPS
----------------------
PUP #
1
2
---------------------RAT/
----- -- ------------------------ -- ---------------- - --------- ---------------- --
3
4
5
6
7
8
9
10
11
12
13
14
15
16
---------------------------------- ---- ------------------ - - -------------------------
LITTER
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
POSTPARTUM
DAY 21
-------------------------------- ---------------------------- ------------------
8906 8909 B913
MC 4 37.0 41.0
MC 4 46.0 39.0
39.0 42.0 44.0
41.9 43.0 36.0
42.5 43.0 MD 3
45.7 FC 4 FC 4
MD 2 44.0 41.0
MD 2 FC 4 41.0
41.1 43.0 42.0
38.7 FC 4 FC 4
46.8 41.0 39.0
42.5----FM---3---F-D--1--------------FC 4
8914
NOT PREGNANT
8918
NOT PREGNANT
8919 8920 8921 8923
MC 4 MC 4 42.0 42.0 42.9 46.1 NOT PREGNANT
48.9 38.0 45.5
45.0 42.0 MC 4
45.3 39.0 MC 4
46.0 MD 2 45.7
MC 4 38.0 45.3
MC 4 FM 2 43.6
MC 4 FD 1 MD 2
MC 4 ms
42.7 ms
41.5 43.4
41.0 38.2 39.7
FC 4 FM 2
8925 8926 8927 8928 8929
37.5 35.8 MD 5 MC 4 MM 2
MM 2 MD 3
MD 5 47.7 MM 2
FC 4 MD 2 MD 5 40.8 MM 2
36.7 34.6 MD 3 41.0 MM 2
34.3 29.4 MD 2
MC 4 MM 2
34.2 34.7 MD 2 43.9 MM 2
37.8 FM 3 27.4 MC 4 FM 2
38.1 FM 3 34.9 42.7 FM 2
29.2 FD 2 FD 5 41.1
FD10 FD 2 FM 5 FC 4
FM 2 FD 2 FM 5 39.7
FD 2 FD 2 FM 4 42.9
FD 3 FD 3 FD 2 FD 2 P
8930 8931 8932 8933
MC 4 48.3 41.0 45.0 34.3 MC 4 NOT PREGNANT
MC 4 45.0 MC 4
47.9 42.0 MC 4
52.4 MD I 38.8
47.0 MD 1 38.9
50.4 MD 1 32.3
MD 1 MD 1 MM 3
MD I MD 1 MM 3
MD 1 FD I MD 3
46.7 FD 1 MD 2
37.6 35.7
39.0 FD 1 FD 1 37.8 33.3 33.8 FM 3 F
8934 8935 8936 8937 8938
MC 4 39.2 38.7 42.0 MC 4 MC 4 MD 4 MD 4 MD 4 45.1 48.2 41.4 MORIBUND SACRIFICED
MC 4 42.9 MD 4 46.2
ON
38.3 37.1 MD 2 44.2 DAY 36
37.3 MD 2
38.7 MD 4
MM 2 MD 2
ms
46.2
OF STUDY
33.5 42.5
MD I 40.6
33.7 FC 4
MS 41.7
36.5 38.6 MO I FM 2
35.4 37.1 FD 4
FS
FM 3 40.4 FD 4
FD 2 FD 3
FD 3
FD I FD 1
8939 8940
39.0 37.0 41.0 MD 1 MD 1 37.0 38.0 FD 1 FD 1 FD I FD 1 FD I FD 1
MC 4 MC 4 50.1 MC 4 50.9 MC 4 46.8 49.6 MD 2 MD 1 FC 4 46.5 40.9 38.9 38.7
FS
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVACE@ PFOS IN RATS (SPONSOR'S
FERTIIITY, DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATALIPOSTNATAI,
REPRODUCTION
TOXICI
TABLE C36 (PAGE 30):
PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA
PI GENERATION
PUPS
------------ -- ------------------------- --------------------
PUP #
1
2
3
4
------------------------------------
5
6
7
8
------------------------
RAT/
------------ ---------------
9
10
11
12
13
----------------------------
------------------
14
15
16
1
------------------
LITTER
MATERNAL
DOSAGE GROUP V
--------------------------------------------------------------
3.2 MG/KG/DAY
POSTPARTUM
DAY 21
---------------------------- -------------------
8942 8943 8944
MD 1 MD 1 MD 1
MD 1 ms ms
MD 1 ms PS
MD 1 ms
FD 1
FD 1 ms
FD 1
FD 1 FD 1
8945
NOT PREGNANT
8946 8949 8950
MD 2 MM 2
ms
MD 2 MD 2 FD 1
MD 2 MD 2 FD 1
MM 2 MD 2 FD 1
ms MD 2 FD 1
ms MD 2
FS
FD 2 FM 2
FD 2 FM 2
FD 2 FD 2
FD 2 FD 2
FM 2 FD 2
FS FD 2
8952
NOT PREGNANT
8955 8956 8957
ms
MD 1 MD 1
MD 2 MD 2 MD 2
NOT PREGNANT
MD 1 MD 2
MD I MD 2
FS MD 2
FD 1 MD 1
FD 1 FD 2
FD 1 FD 2
FD 2
FD 2
FD 2 FD 1
8959 8960 8961 8962
MD 2 MD 2 MD 2 MD 2 MD 1 ms
ms
FD 2 FD 2 FD 2 FD 2 FD 1 FS
MD I MD 1 MD 1
ms
ms
ms
ms
FD I
FS
FS
FS
FS
FS
MD 2 MD 2 MD 2 MD 2 MD 2 MM 2 ms
FD 2 FD 2 FD 2 FM 2 FD 1 FS
FS
ms
ms
ms
FD 1
8964 8967
8968 8969 8970 8971 8972
MM 2 ms ms
MD 1 MD 2 MM 2
NOT
MM 2 ms ms
MD 1
MD 2 MM 2 PREGNANT
MM 2 ms
FD 2 MD 1 MD 2 MM 2
MM 2 FS
FM 2 FD 1 MD 2 MM 2
MD 2 FS
FD I FM 1 MD 2 MD 2
MD 2 FS
FD I
ms MD 2
MD 2 FS FS
FD 2 MD 2
MD 2 MM 1 ms
FS
uu
FS
FS
FS
FD 2 FM 2
FD 2 FM 2
FD 2 FM 2
FM 2
FS FD 2
FD 2 FM 1 FD 1 FD 2 FD 2
8973 8974
MM 2 MD 1 MD I MD 1 MD 1 MD 1 MD 1 MD 1
MD 1 ms
MD 1 ms
ms FD 1
FD 1 FD 1
FD 1 FD 1
FD 1 FD 1
FD 1 FS
8975
MD 1 MD 1 MD I MD I MD I MD 1 FD 1 FD 1 FD 1 FD 1 FD 1 FD 1
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE FIRST LETTER SECOND LETTER
NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEKALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVACE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C37 (PAGE 1): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERATI
---------------------
-------------- -------
PUP #
1
2
3
4
5
6
7
8
-------------------------------- ----- -------- -----
RAT/
---------------------- --------- ------------------------
9
10
11
12
13
14
15
16
17
18
19
20
-------------- --------------------------------------------
LITTER
MATERNAL
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8801 8803 8804 8805 8807 8808 8811 8812 8813 8814 8817
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 P A F A F A MC 4 M A MC 4 M A M A M A F A FC 4 PC 4 F A PC 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 P 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 N 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 P 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
8818 NOT PREGNANT
8819
M A M A M A F A PC 4 F A F A FC 4 FC 4 F A FC 4 F A
8821 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
8823
M A M A M A MC 4 MC 4 MC 4 M A F A FC 4 F A F A F A
8824 MC 4 M A MC 4 MC 4 M A MC 4 M A MC 4 M A F A FC 4 F A P A P A FC 4
8826
M A N A M A MC 4 M A FC 4 FC 4 F A F A F A F A FC 4 FC 4
8827
M A MC 4 M A M A M A F A FC 4 FC 4 FC 4 P A F A FC 4 FC 4 P A
8826
M A M A M S F A P A F A FC 4 F A FC 4 FC 4 F A FC 4 F A F S F S
8830
MC 4 N 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
8831 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
8832
M A MC 4 MC 4 M A M A M A F A FC 4 F A FC 4 FC 4 PC 4 FC 4 FC 4 FC 4 F A F A
8833
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
8834
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
8835
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C37 (PAGE 2): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA - Fl GENERATI
--------------- -------------------------
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 11
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8838
8840 8841
8842a 8845 8846 8847 8849 8851 8852 8853
8854 8855 8857 88S8
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
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 F A FD 1
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
M A MC 4 M A NA
N A M A M A FC 4 FC 4 FC 4 M A FC 4 MD 1 FC 4 F A FC 4
PA FA
FA FA
FA FA
F A FC 4 FC 4 FC 4 P A FD 2
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
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
M A M A MC 4 MC 4 MC 4 MC 4 MC 4 M A MC 4 M A F A PC 4 FC 4 F A F A F A FM 4
M A M A M A M A MC 4 FC 4 FC 4 FC 4 F A FC 4 P A P A F A FC 4 FD 1
N A MC 4 M A M A MC 4 M A M A F A F A F A U U U U
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 PC 4 F A FC 4 F A
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
M A MC M A MC
4 M A M A MA 4 MC 4 MC 4 MC 4
F A PC 4 F A FC 4 FC 4 F A FC 4 M A M A MC 4 M A F A FC 4 F A
F A FC 4 FC 4 F A F A FC 4
M A M A M S FC 4 FC 4 F A F A F A F A F A F A
8860 8862 8863 8864
MC 4 M A MC 4 MC 4 M A M A M A FC 4 F A F A P A FC 4 FC 4 FC 4 M A MC 4 M A MC 4 MC 4 M A M A P A FC 4 FC 4 F A F A FC 4 F A
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 M A M A M A M A MC 4 P A F A F A FC 4 F A
FA FA
FA
8865 8866 8867
MC 4 MC 4
MA
M A M A MC 4 MC 4 MC 4 MC 4 M A M A MC 4 M A MC 4 MC 4 M A MC 4 M A MC 4 M A M A P A FC 4 F A
M A MC 4 F A F A F A F A M A FC 4 F A F A F A FC 4 FC 4 F A P A FC 4 FC 4 FC 4
FA
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 8870
MA MA
M A MC 4 MC 4 MC M A M A M A MC
4 MC 4 MC 4 MC 4 4 F A FC 4 FC 4
MA FA
M A MC 4 F A FA
F A FC 4
FA
FA
FA
PS
---------------------------------------------------------------------------------------------------------------
FIRST SECOND NUMBER
LETTER LETTER FOLLOWING
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
A-ALIVE, "SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES
THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
a. Dam 8842 delivered one additional statistical analyses.
pup on day 2 of lactation;
values for day I postpartum
excluded
from gro
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE C37 (PAGE 3): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERATI
----------- -------------------- ------------------ --------- ---- -------------
11 - ------------------- -
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 111
0.4 MG/KG/DAY
------------ --------------------------------------- -------------------------------------------------------- -
8871 NOT PREGNANT
8872 8874a 8875 8876
M A MC 4 MC 4 MC 4 MC 4 M A
M A MA
M A M A M A MC 4 MC 4 MC 4 M S M A M A MC 4 MC 4 M A MC 4 MC 4 M A MC 4 MC 4 M A MC 4 M A MC 4 M A MD 1 F A F A F A
PA MA PA
FA MA FA
F A FC 4 F A FC 4 FA FA
FA FA
FA
8881 8882 8885 8889 8890 8891 8892 8893 8894
M A M A M A MC 4 M A F A FC 4 FC 4 FC 4 MC 4 MC 4 MC 4 M A M A M A MC 4 M A FC 4 MC 4 MC 4 M A MC 4 MC 4 M A M A M A M S
MC 4 MC 4 MC 4 MC 4 M A M A M A M A MC 4
M A MC 4 M A M A M A PC 4 FC 4 P A F A
M A MC 4 MC 4 M A M A M A FC 4 FC 4 FC 4 M A M A MC 4 MC 4 M A M A FC 4 FC 4 F A MC 4 M A MC 4 MC 4 N A M A MC 4 M A F A M A M A PA
F A F A FC 4 FC 4 P A PC 4 F A FC 4
FA F A FC 4
F A FC 4 F A FC 4 F A M A
F A F A P A F A FC 4
F A FC 4 F A
F A F A F A FC 4 FC 4 F A
F A FA F A
F A FD17 FD16 FC 4
F A FC 4 FS
8895 8896b 8897b 8898
8899a 8900 8901 8902 8903
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 2
MC 4 M A M A MC 4 M A MC 4 M A MC 4 F A FC 4 PC 4 F A F A P A
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
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
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
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 PC 4 FM 2 F S
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
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
NOT PREGNANT
8904 NOT PREGNANT
6905
M A MC 4 M A M A MC 4 MC 4 M A MC 4 FC 4 F A FC 4 FC 4 FC 4 FC 4 F A F A F A FC 4 FM 3
---------------------------------------------------------------------------------------------------------------
FIRST LETTER
M-MALE, F-FEMAUE, 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; from group averages and statistical analyses.
values for day 4 postpartum
postct
b. On day 15 postpartum, the pups from litter 0897 were discovered in the litter box with litter 8896. The pu
arbitrarily distributed between the two daMB and values will be included in group averages and statistical
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C37 (PAGE 4): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERATI
-- -P-UP--#-----1------2 ---------------------
RAT/
-3-----4------5-----6-----7---- a ---------------------------
-------------------------------------------- --------- -----
9
10
11
12
13
14
15
16
17
18
19
20
------------------------------------------ ------------------
LITTER
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8906 8909 8913
8914 8918
MC 4 MC 4 M A MA MA MA M A MA M A
NOT PREGNANT NOT PREGNANT
M A M A M A MD 2 MD 2 M A P A FC 4 F A FC 4 M A MD 3 FC 4 F A F A
FA FA P A FC 4 F A FC 4
F A F A FM 3 FD 1 FA F A FC 4
8919 8920 8921 8923
MC 4 MC 4 M A M A M A M A MC 4 MC 4 MC 4 MC 4 M A M A M A M A M A MD 2 F A FM 2 FD 1 M A N A M A MC 4 MC 4 M A M A M A MD 2 M S
NOT PREGNANT
FA MS
FA FA
FA FA
P A FC 4 FM 2
8925 8926 8927 8928 8929 8930 8931 8932 8933
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 2 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 I 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 3
NOT PREGNANT
8934 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
8935
M A MC 4 MC 4 M A M A M A MD 4 F A FC 4 F A F A F A
8936 8937
MD 4 ND 4 MD 4 MD 4 MD 2 MM 2 MD 2 MD 1 M A MA M A MA M A M S FA FA
M S MD 1 FD 4 FD 4 FD 3 FD 3 FD 1 FD 1 F A FM 2 F S
8938 MORIBUND SACRIFICED
ON DAY 36 OF STUDY
8939
M A M A M A MD 1 MD 1 F A F A FD I FD I FD I FD I FD 1 FD 1
8940 MC 4 MC 4 M A MC 4 M A MC 4 M A M A MD 2 MD 1 PC 4 F A F A F A F A F S ---------------------------------------------------------------------------------------------------------------
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C37 (PAGE 5): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERAT
-------- ----------------------
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
---------------------------------- ---------------------------------------------------
8942 8943 8944
MD 1 MD 1 MD I MD I FD 1 FD 1 MD 1 M S M S M S M S FD 1 MD 1 M S P S FD 1 FD 1
----------------------
8945 NOT PREGNANT
8946 8949 8950
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
8952 NOT PREGNANT
8955 8956 8957
M S MD 1 MD 1 MD MD 2 MD 2 MD 2 MD NOT PREGNANT
1 MD 2 MD
1 P S rD 2 MD 2 MD
I FD I FD 1 1 FD 2 FD 2 FD 2 FD 2 FD 2 FD 1
8959 8960 8961 8962 8964 8967 8968 8969
MD 2 MD 2 MD 2 MD 2 MD I M S M S FD 2 FD 2 FD 2 FD 2 FD 1 F S MD I MD 1 MD 1 M S M S M S M S FD 1 F S F S F S F S F S
MD 2 MD 2 MD 2 MD 2 MD 2 MM 2 M S M S M S FD 1
M S FD 2 FD 2 FD 2 FM 2 FD 1
FS
FS
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 FD 1
M S M S M S FS F S F S F S F S U U
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 I FD 1 FM 1
8970 8971 8972
MD 2 MD 2 MD MM 2 MM 2 MM NOT PREGNANT
2 MD 2 MM
2 MD 2 MD
2 M S FD 2 FD 2 FD 2 FD 2 F S 2 MD 2 MD 2 FM 2 FM 2 FM 2 FD 2 FD 2 FD 2
8973 MM 2 MD 1 MD 1 MD I MD 1 MD 1 M S FD 1 FD I FD I FD 1 8974 MD 1 MD 1 MD 1 MD 1 M S M S FD 1 FD 1 FD 1 FD 1 F S
8975 MD 1 MD 1 MD 1 MD 1 MD I 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-MLSSING
(PRESUMED CANNIBALIZED)
NUMBER FOLLOWING
"SECOND LETTER" INDICATES
THE DAY POSTPARTUM
THE EVENT OCCURRED.
PROTOCOL 418-008!
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C38 (PAGE 1): CLINICAL OBSERVATIONS
FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - Fl GENERATION P
--- --------------------- ------------------------ -- ---------------------------- ------------------------- -
MATERNAL
DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS
a
----------------------------- -------------------- -
------------------------------------------------------ -
I
0 (VEHICLE)
8819
14 5 21
1/12 PUPS: 1/ 8 PUPS:
LEFT LEFT
HINDPAW, HINDPAW,
THIRD AND FOURTH THIRD AND FOURTH
8826
14-21
1/ 8 PUPS: TAIL, BENT (2.0 CM FROM BASE).B
0.1
8867
7-21
1/8 PUPS: UMBILICAL HERNIA.B
III 0.4
IV 1.6
8893 8925
14-15 16
17-21
2- 4 5-10 11-21
2/8 PUPS: 3/7 PUPS: 2/6 PUPS:
HEAD, HEAD, HEAD,
DOMED. DOMED. DOMED.B
1/ 9 PUPS: 1/ 8 PUPS: 1/ 7 PUPS:
PORTION PORTION PORTION
OF TAIL OF TAIL OF TAIL
MISSING. MISSING. 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 REMOV
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 REMOV
----------------------------------------------------------------------------------------------------------------
a. Tabulation restricted to adverse observations; b. Observation confirmed at necropsy.
all other pups appeared normal.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C39 IPAGE 1): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
-----------------
POSTPARTUM
DAY
------------ - -------- --- ---------------- ----- -------- --------
1
2
3
4
5
6
7
8
------------ -----------
9
10
-M-A-TE-R-N-A-L/-L-I-T-TE-R------#-------M-AT-E-RN-A-L----D-O-SA-G-E---G-R-OU-P----1 -------------- 0
-------------- --------------------------------(VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8801 8803 8804 8805 8807 8808 8.811
S/ 9 55.6%
5/12 41.7% 11/15 73.3% 12/16 75.0%
5/13 38.S%
S/ 9 55.6%
4/12
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
5/ 9 55.6%
4/12 33.3%
3/15 20.0%
2/16 12.5%
7/13 53.8%
6/ 9 66.7%
9/ 9 100.0%
12/12 100.0%
6/15 40.0%
7/15 46.7% 13/13 100.0%
7/ 9 77.8%
5/ 8 62.5%
6/ 8 75.0%
a/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
6/ 8 75.0%
6/ 8 7S.0%
6/ 8 75.0%
7/ 8
8
87.5%
100
33.3t;
100.0%
8812 8813
11/17 64.7%
6/12
13/17 76.5%
5/12
12/17 70.6%
8/12
11/17 64.7% 12/12
7/ 8 87.5%
8/ 8 100.0%
50.0%
41.7%
66.7%
100.0%
8814
8/13
11/13
13/13
61.5%
84.6%
100.0%
8819
10/12
3/12
4/12
10/12
8/ 8
8821
83.3% 6/14
25.0% 9/13
33.3% 11/13
83.3% 10/13
100.0% 8/ 8
42.8%
69.2%
84.6%
76.9%
100.0%
8823
2/12
1/12
9/12
12/12
16.7%
8.3!k
75.0%
100.0%
8824 8826 8827
4/15 26.7%
2/13 15.4%
5/14
3/15 20.0%
4/13 30.8%
3/14
6/15 40.0%
3/13 23.1%
1/14
8/15 53.3%
1/13 7.7% 3/14
4/ 8 SO.0%
3/ 8 37.5%
4/ 8
S/ 8 62.5%
1/ a 12.5%
4/ 8
4/ 8 50.0%
6/ 8 75.0%
8/ 8
6/ 8 75.Ot
6/ 8 75.0%
7/ 8 87.5%
7/ 8 87.5%
8/ a 100.0%
8/ 8 100.0%
8828
35.7% 6/12
21.4% 8/12
7.1% 7/12
21.4% 12/12
50.0%
50.0%
100.0%
50.0%
66.7%
58.3%
100.0%
----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICIT
TABLE C39 (PAGE 2): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
------------------------------------- ------------ --- --------------------- --------------- ----------------
POSTPARTUM DAY
1
2
3
4
5
6
7
a
9
10
1
----------------------------------------------------------------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
----------- ---------------------------------------------------------------------------------------------------
8830
8/16
3/16
10/16
16/16
50.0%
18.8%
62.5%
100.0%
8831
9/15
4/15
6/15
15/15
8832
60.0% 5/17
26.7% 3/17
40.0% 7/17
100.0% 7/17
B/ 8
8833
29.4% 1/14
17.6% 6/14
41.2% 2/14
41.2% 9/14
100.0% a/ 8
7.1%
42.8%
14.3%
64.3%
100.0%
8834
8/13
5/13
2/13
4/13
5/ 8
7/ 8
6/ 8
8/ a
8835
61.5!k 5/16
38.5% 4/16
15.4% 4/16
30.8% 4/16
62.5% 4/ 8
87.5% a/ 8
75.0%
100.0%
31.2%
25.0%
25.0%
25.0%
so.ot
100.0%
----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTALNUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND IIERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C39 (PAGE 3): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
---------------
POSTPARTUM
DAY
------------- ------------------------
1
2
3
4
---5
--------6
--------------- - ---- -------------
7
8
9
10
-M-A-TE-R-N-A-L/-L-I-T-TE-R---- #-------M-A-TE-R-N-AL----D-O-S-AG-E---G-R-O-UP----1-1 --------------0-.-1--M-G-/K-G-/-D-AY --------------------------------------------------- --------------------------- --------------------------- ----------------------------- -------
8838 8840
9/17 52.9% 10/18
3/17 17.6%
8/18
1/17 5.9% 9/18
9/17 52.9% 18/18
B/ 8 100.0%
8841
55.6% 14/14
44.4%
50.0%
ioo.ot
100.0%
8842a 8845 8846 8847 8849 8851 8852
6/14 42.Bti
8/12 66.7%
9/15 60.0% 11/14 78.6%
8/17 47.0%
8/14 57.1%
3/10
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
9/15 60.0%
7/11 63.6%
3/15 20.Oti
5/14 35.7%
9/17 52.9t
0/14 0.0% 4/10
10/15 66.71; 11/11 100.0% 13/15 86.7%
9/14 64.3%
5/16 31.2%
8/14 57.1% 10/10
B/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0%
8/ 8 100.0!k
4/ 8 50.0%
4/ 8 50.0%
3/ 8 37.5%
5/ 8 62.5%
6/ 8 75.Ot
8/ 8 100.0%
8853
30.0% 15/19
40.0% 7/19
40.0% 11/19
100.0% 11/19
a/ 8
8854 8855
78.9% 7/14
50.0% 7/15
36.8% 2/14
14.3% 4/15
57.9t 1/14 7.1% 8/15
57.9t
100.0%
5/14 35.7% 12/15
5/ 8
7/ 8
5/ 8
6/ 8
7/ 8
7/ 8
7
62.5t
87.5%
62.5%
75.0%
87.5%
87.5%
87
8/ 8
8857 8858 8860 8862 8863
46.7% 8/15
S3.3%
4/10 40.0%
9/15 60.Ot 11/14 78.6%
2/16 12.5%
26.7% 8/15
53.3% 1/10
10.0% 6/lS
40.0% 5/14
35.7% 4/16
25.0'4
53.3% 2/15
13.3% 7/10
70.0% 5/15
33.3% 3/14
21.4t 6/16
37.5%
80.0% 15/15 100.0%
9/10 90.0%
6/IS 40.0%
8/14 57.1% 13/16 81.2%
100.0%
B/ 8 100.0%
7/ 8 87.5%
7/ 8 87.5%
8/ 8 100.0%
S/ 8 62.5t
B/ a 100.0%
6/ 8 7S.0%
6/ 8 75.0%
8/ 8 100.0%
---------------------------------------------------------------------------------------------------------------
NIN a.
= NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER
Dam 8842 delivered one additional statistical analyses.
pup on day 2 of lactation; values for
OF PUPS IN THE LITTER day 1 postpartum excluded
from gro
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPROI)UCTION TOXIC
TABLE C39 (PAGE 4): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
-------------------------- - --------------------------- ---- ----- ----------- ---------- ----
POSTPARTUM
DAY
1
2
3
4
5
6
7
8
9
-------------------------------- ----------------------------------------------------------------
------------
10 ------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP 11
0.1 MG/KG/DAY
-------------------------------------------------------------------------------------------------
8864 8865 8866 8867 8868
3/10 30.0%
5/14 35.7%
8/16 50.0%
2/13 15.4%
3/14
2/10 20.0%
2/14 14.3%
4/16 25.0%
2/13 15.4%
4/13
1/10 10.0%
7/14
50.0% 5/16
31.2% 4/13
30.8% 10/13
6/10 60.0% 14/14 100.0% 12/16 75.0%
9/13 69.2% 13/13
7/ 8 87.S%
8/ 8 100.0%
1/ 8 12.5%
7/ 8 87.5%
B/ 8 100.0!k
7/ 8 87.5%
5/ 8 62.5%
G/ 8 75.0%
8/ a 100.0%
8869
21.4t 16/16
30.8%
76.9%
100.0%
------------
100.0%
8870
2/11
1/11
7/11
6/11
a/ 8
18.2%
9.1%
63.6%
54.5%
100.0%
--------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVEI,O['MENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABI,E C39 (PAGE 5): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
--- - ------------------------------------- ---------------
POSTPARTUM
DAY
1
2
3
4
5
---- -------------------------------------------------------
- --- -------------------------
6
7
8
-------------------------------
------------------
9
10
------------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP
--- ---------------------------------------
8872
4/13
1/13
4/13
8874
30.8% 2/15
7.7% 6/14
30.8% 8/15
111 - -------------
10/13 76.9% 15/15
S/ 8 100.0%
0.4 MG/KG/DAY --------------------------------------------------
8875 8876
13.3% 5/13
38.5% 2/ 6
42.8% 9/13
69.2% 4/ 6
53.3% 5/13
38.5% 4/ 6
100.0% 6/13
46.2% 6/ 6
7/ 8 87.5%
B/ 8 100.0%
8881 8882 8885 8889 8890
33.3% 6/14
42.8% 8/17
47.0% 11/14 78.6%
1/14 7.1% 3/12
66.7% 4/14
28.6% 8/17
47.0% 4/14
28.6% 6/14
42.81 4/12
66.7% 1/14 7.1%
13/17 76.5!k
8/14 57.1%
0/14 0.0% 3/12
100.0% 8/14
57.1% 12/17 70.6%
7/14
50.0% 3/14
21.4% 12/12
6/ 8 75.0%
6/ 8
75.0% 5/ 8
62.5% 4/ 8
50.0%
B/ a 100.0%
7/ 8 87.5%
4/ 850.0%
4/ 8 50.0%
8/ 8 100.0%
7/ 8 87.5%
5/ 8 62.5%
8/ 8 100.0%
8/ 8 100.0%
8891
25.0% 6/15
33.3% 5/15
25.0% 15/15
100.0%
40.0%
33.3%
100.0%
8892 8893
6/12 50.0%
1/13
5/12 41.7%
6/13
5/12 41.7%
5/13
6/12 50.0%
4/13
3/ 8 37.5%
B/ 8
S/ 8 62.5%
S/ 8 62.5%
6/ 8 75.0%
7/ 8 87.5%
S/ 8 100.0%
8894
7.7% 0/ 3
46.2% 0/ 3
38.5% 3/ 3
30.8%
100.0%
0.0%
0.0%
100.0%
8895
4/17
1/16
4/16
9/16
4/ 8
8/ a
8896 8897
23.S% 7/14
50.0% 8/14
6.2% 1/14 7.1% 4/14
25.0% 2/14
14.3% 1/14
S6.2% 9/14
64.3% 14/14
50.0% 7/ 8
87.5%
100.0% 7/ 8
87.5%
7/ 8 87.5%
B/ 8 100.0%
57.1*
28.6%
7.1%
100.0%
8898 8899
8/12 66.7%
9/16 56.2*
5/12 41.7%
5/16 31.21t
8/12 66.7%
6/16 37.5%
5/12 41.7%
8/16 50.0!k
8/ 8 100.0%
7/ 8 87.5%
S/ 8 100.0%
----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAb/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C39 (PAGE 6): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION
LITTERS
------------- -- ------
POSTPARTUM
DAY
1
------------- ---------
------------------ --------------------------- ------- ------------------ -- ----------
2
3
4
5
6
7
-------------------------------------------------------
8
9
10
1
--------------------- ----------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
------------- --------------------------------------------------------------------------------------------------
8900 8901
8/15 53.3%
8/13
5/14 35.71;
5/13
1/14 7.1% 3/13
8/14 S7.1%
4/13
7/ 8 87.5%
6/ 8
5/ 8 62.5%
B/ 8
5/ 8 62.5%
7/ 8 87.5%
B/ 8 100.0!k
8902 8905
61.5% 0/15 0.0% 6/19
31.6%
38.5% 4/15
26.7% 3/19
15.8%
23.1% 4/14
28.6!k 4/18
22.2%
30.8% 3/14
21.4% 5/18
27.8%
7S.0% 7/ 8
87.5t 7/ 8
87.5%
100.0% a/ a
100.0% 8/ 8
100.0%
-----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C39 (PAGE 7): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
----------------------------------------------
POSTPARTUM
DAY
1
2
3
----------------------------- -----------------
-------------------------- ---------------------- -------------
4
5
6
7
8
9
10
---------------------------- ---------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
----------------------------------------- ---------------------------------------------------------------------
8906 8909 8913 8919 8920 8921
5/13 38.5%
4/11 36.4%
7/12 58.3%
8/16 50.0%
0/ 8 0.0% 3/11
2/11 18.2%
1/11 9.1% 2/12 16.7% 5/15 33.3ti 1/ 6 16.7% 1/10
2/10 20.0%
1/11 9.lt 1/11 9.1% 3/15 20.0%
0/ 6 0.0% 3/10
3/10 30.0%
7/11 63.6%
8/11 72.7t
3/15 20.0%
3/ 6 so.ot
6/10
5/ 8 62.5%
3/ 8 37.5%
0/ a O.Ot 8/ 8 100.0% 2/ 6 33.3% 8/ 8
3/ 8 37.5%
5/ 8 62.5%
2/ 8 25.0%
5/ 8 62.5%
7/ 8 87.5%
S/ 8 62.5%
7/ a 87.St
a/ 8 100.0%
6/ a 75.0%
8/ 8 100.0%
5/ 8 62.5%
7/ 8 87.5&
B/ 100.
o/ 6 0.0%
4/ 6 66.7%
6/ 6 ioo.oi;
8925 8926 8927 8928 8929
27.3% 0/12 0.0% 5/12
41.7t 15/17 88.2%
2/12 16.7%
0/ 8
10.0%
30.0%
60.Ot
0/ 9 0.0%
2/ 9 22.2%
0/ 9 0.0%
0/ 7 0.0%
0/ 4 0.0%
1/ 4 25.0%
2/12
1/ 8
2/ 8
16.7%
12.5%
25.0%
3/12
1/12
4/12
25.0%
8.3%
33.3%
NO SURVIVING
PUPS ON DAY
100.0%
3/ 8
2/ 8
37.5%
25.0%
0/ 4
0/ 4
0.0%
0.0%
0/ 2
1/ 2
0.0%
50.0%
3/ 8
3/ 8
37.5%
37.5]k
2 POSTPARTUM
B/ 8 100.0%
0/ 4 0.0% 0/ 2 0.0% 4/ 8 50.0%
1/ 4 25.Ot
0/ 2 0.0% 7/ 8 87.5%
2/ 4 50.0%
0/ 2 0.0% a/ 8 100.0%
1/ 4 25.0%
0/ 2 0.0%
2/ 50.
1/ so.
0.0%
8930 8931 8932 8934 8935 8936
1/10 10.0%
0/ 4 0.0% 11/17 64.7% 3/13 23.1% 3/12 25.0% 4/11 36.4%
5/10 50.0%
0/ 4 0.0% 1/16 6.2% 0/11 0.0% 4/12 33.3!k 3/ 8 37.5%
2/10 20.0%
0/ 4 0.0% 1/11 9.1% 1/10 10.0% 3/12 25.0!k 0/ 6 O.Ot
3/10
S/ 8
30.0%
62.5%
0/ 4
0/ 4
0.0%
0.0%
2/11
3/ 8
18.2%
37.5%
1/10
1/ 8
io.ot
12.5%
1/11
4/ 8
9.1%
50.0%
NO SURVIVING
PUPS
5/ 8 62.5%
1/ 4 25.0%
3/ 8 37.5%
3/ 8 37.5%
2/ 8 25.0%
ON DAY
6/ 8
7/ 8
75.0%
87.5%
1/ 4
2/ 4
25.Ot
50.0%
6/ 8
8/ 8
75.0%
100.0%
2/ 0
4/ 8
25.0%
50.0%
2/ 8
7/ 8
25.0%
87.5%
4 POSTPARTUM
8/ 8 100.0%
2/ 4 50.0%
B/ 8 100.0%
6/ 8 75.0%
4/ 4 100.0%
B/ 8 100.0%
----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C39 IPAGE 8): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
--------- ---------------------------- - --------------- ------------- -------------------------- -- ------
POSTPARTUM
DAY
1
2
3
-------------------------------------------
4
5
6
7
8
9
10
-----------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP IV
1.6 MG/KG/DAY
------
--------------------------------------------------------------------------------------------------------------
8937
2/ 9
3/ 8
0/ 8
4/ 8
6/ 8
7/ 8
a/
22.2%
37.5%
0.0%
50.0%
75.0%
87.5%
100.0%
8939
1/ 5
2/ 5
0/ 5
2/ 5
1/ 5
3/ 5
4/ 5
3/
20.0%
40.0%
0.0%
40.0%
20.Ot
60.0%
80.0%
60.Ot
ioo.ot
8940
4/14
5/13
4/13
6/13
6/ 8
6/ 8
4/ 8
7/ 8
8/ 8
28.6%
38.5%
30.Bt
46.2t
75.0%
75.0%
50.0%
87.5%
100.0%
--------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C39 (PAGE 9): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
------------------ ---------- -------- I ------ -------- -------- -- ------ ---------- ---- -------------------
POSTPARTUM
DAY
14
is
16
17
18
----------------------------------------------------------------
19
20
21
--------- ---------- ---- -------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
-----------------------------------------------------------------------------------------------
---------------
8927
0/ 2
1/ 2
1/ 2
2/ 2
0.0%
50.0%
50.0%
100.0%
------------------------------------------------------------
---------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C39 (PAGE 10): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION
LITTERS
------------------------
---------------------- --------------------- -- -- --- -----------------------
POSTPARTUM
DAY
1
------------------------
2
3
4
s
6
7
8
9
10
---- ------------------------------------------------ I--------------------------------
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 8949 89SO
0/ 9
NO SURVIVING PUPS ON DAY 2 OF
0.0%
0/12
NO SURVIVING
PUPS ON DAY 2 OF
0.0%
NO SURVIVING PUPS ON DAY 2 OF LACTATION
LACTATION LACTATION
8955
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8956 8959 8960
2/11
NO SURVIVING
PUPS ON DAY 2 OF
18.2%
0/ 8
NO SURVIVING
PUPS ON DAY 2 OF
0.0%
NO SURVIVING PUPS ON DAY I OF LACTATION
LACTATION LACTATION
8961 8962
2/10 20.OP6
NO SURVIVING
NO SURVIVING PUPS ON DAY 2 OF PUPS ON DAY 1 OF LACTATION
LACTATION
8964 8967
0/10
NO SURVIVING PUPS ON DAY 2 OF
0.0%
NO SURVIVING PUPS ON DAY 1 OF LACTATION
LACTATION
8968 8969
0/ 2
NO SURVIVING PUPS ON DAY 2 OF
0.0%
NO SURVIVING PUPS ON DAY 1 OF LACTATION
LACTATION
8970 8971 8973
0/ 9 0.0% 0/13 0.0% 0/ 1
NO SURVIVING NO SURVIVING NO SURVIVING
PUPS ON DAY 2 OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY 2 OF LACTATION
0.0% --------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICIT
TABLE C39 (PAGE 11): SURFACE RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
----------------------------------------------------------------------------------------------------------------
POSTPARTUM DAY
1
2
3
4
5
6
7
0
9
10
1
----------------------------------------------------------------------------------------------------------------
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 I OF LACTATION
8975
NO SURVIVING PUPS ON DAY 1 OF LACTATION
----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTALNUMBER OF PUPS IN THE LITTER
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C40 (PAGE 1): PINNA UNFOLDING - INDIVIDUAL DATA - Fl GENERATION
LITTERS
------ -------------------- -- ------------------ I
POSTPARTUM
DAY
2
3
4
5
----------- --------------------------------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP 1
---------------------------------------------------
8801
0/ 9
9/ 9
0.0%
100.0%
8803
12/12
---- -------------- - ------------------------------------
6
7
--------------------- I -------------------------------------
0 (VEHICLE) MG/KG/DAY --- ----------------------------------------- -------------
8804 880S 8807 8808
100.0% 0/15 0.0% 0/16 0.0% 0/13 0.0% 0/ 9
9/15 60.0%
3/16 18.8% 10/13 76.9%
9/ 9
15/15 100.0%
15/15 100.01
13/13 100.0%
8811 8812
0.0% 9/12 75.0% 17/17
100.0% 12/12
100.0%
8813 8814
100.0% 0/12 O.Ot
13/13
12/12 100.0%
8819 8821
100.0% 0/12 0.0% 0/13
11/12 91.7% 13/13
12/12 100.0%
8823
0.0% 0/12
100.0% 12/12
8824 8826 8627 8828
0.0% 0/15 0.096 0/13 0.0% 0/14 0.0% 0/12 0.0%
100.01; 5/15
33.3% 1/13 7.7% 5/14
35.7%
12/12 100.0%
15/15 100.0%
13/13 100.0%
14/14 100.0%
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENI'AL, AND PERINATAL/POSTNATAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295-9)
RFPRODUCTION
TOXICIT
TABI.E C40 (PAGE 2): PINNA UNFOLDING - INDIVIDUAL DATA - Fl GENERATION LITTERS
-- -- ------ ---- I -------- -
POSTPARTUM
DAY
2
3
------------ -----------------------
-- -------------- -----
4
5
6
-------------------------
----
7 -----
------------------ - ----------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------
-- -------------------------------------------------
8830 8831
0/16 0.0% 0/15
16/16 100.0%
15/15
0.0%
100.0%
8832
0/17
10/17
14/17
8/ 8
0.096
58.8%
82.4%
100.0%
8833
0/14
6/14
14/14
0.0%
42.8%
100.0%
8834
0/13
4/13
13/13
O.Ot
30.8%
100.0%
8835
0/16
4/16
16/16
0.0!k
25.0%
100.0%
----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUI)Y NUMBER:
6295.9)
AND PEPINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C40 (PAGE 3): PINNA UNFOLDING - INDIVIDUAL DATA - Fl GENERATION i,i*rl,ERS
------ ----------
----
-------- ------
- -- ---------- -- ---
POSTPARTUM
DAY
2
------ -------------------
3
4
5
6
7
- ------ -------- -
- --------------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP 11
0.1 MG/KG/DAY
----------------------------------------------- - ------------------------
-- --- ---------------
------
- ------------------- - - --------
---------------------- --- --------
8838
0/17
14/17
11/17
B/ 8
0.0%
82.4%
64.7%
100.0%
8840
0/18
15/18
18/18
8841
0.0% 0/12
83.3% 14/14
100.0%
0.0%
100.0%
8842
0/15
15/15
0.0%
100.0%
8845
0/11
10/11
11/11
0.0%
90.9%
100.0%
8846
0/15
10/15
15/15
8847
0.0% 0/14
66.7% 3/14
100.0% 14/14
0.0%
21.4%
100.0%
8849
3/17
0/17
12/16
8/ 8
17.6%
0.0%
75.0%
100.0%
8851
0/14
1/14
14/14
0.0%
7.1%
100.0%
8852
0/10
6/10
10/10
0.0%
60.01;
100.0%
8853
0/19
10/19
19/19
0.0%
52.6%
100.0%
8854
0/14
2/14
14/14
0.0%
14.3%
100.0%
8855
0/15
5/15
15/15
0.0%
33.3%
100.0%
8857
0/15
4/15
15/15
0.0%
26.7%
100.0%
oese
0/10
8/10
10/10
0.0%
80.0%
100.0%
8860
0/15
3/15
15/15
0.0%
20.0%
100.0%
8862
0/14
10/14
14/14
0.0%
71.4%
100.0%
8863
0/16
13/16
16/16
0.0%
81.2%
100.0%
----------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL, 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PPOS IN RATS (SPONSOR'S STUDY NUMB8R:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C40 (PAGE 4): PINNA UNFOLDING - INDIVIDUAL DATA
Fl GENERATION LITTERS
-------
---------------- -
-- ----- -
POSTPARTUM
DAY
2
I ----------------
3
4
5
--- ------------------ --
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP Il
------- ------------------- ------- I ------------------
8864
0/10
1/10
10/10
8865
0.0% 0/14
10.0% 2/14
100.0% 14/14
8866
0.0% 0/16
14.3% 1/16
100.0% 16/16
8867
0.0% 8/13
6.2% 13/13
100.0%
61.5%
100.0!k
8868
0/13
6/13
13/13
0.0%
46.2%
100.0%
8869
0/16
2/16
16/16
8870
0.0% 0/11
12.5% 10/11
100.0% 11/11
0.0%
90.9%
100.0%
------------------------------------------------------
- - -- ------------------- -------- -- -- -----
6
7
- ------ ------------------- ----------------- --------
0.1 MG/KG/DAY ----------------------------------------
-------------
------------------------------------------- -----------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (G7kVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMEIJTAL
STUDY NUMBER:
6295@9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C40 (PAGE 5): PINNA UNFOLDING
INDIVIDUAL DATA - Fl GENERATION
LITTERS
----------------------
-------- --------- -
POSTPARTUM
DAY
2
3
4
5
6
I -------------------------- - ------- ------------ -
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP 111
0.4
--------- -- ------------------- - - -- -----------------------
8872
0/13
1/13
13/13
-------------
---------- -
7
------------- ------------------ --------------
MG/KG/DAY
-----------------------------------------------
8874 8875 8876
0.0% 0/15 0.0% 0/13 O.Oft 2/ 6
7.7% S/15 33.3% 11/13 84.6% 6/ 6
100.0% 15/15
100.0% 13/13
100.0%
8881 8882 8885 8889 8890
33.3% 0/14 0.0% 0/17 O.Ot 0/14 0.0% 0/14 0.0% 0/12
100.0% 0/14 0.0%
17/17 100.0%
1/14 7.1% 0/14 0.0% 12/12
14/14 100.0%
14/14 100.0%
10/14 71.4%
8/ 8 ioo.ot
8891
0.0% 0/15
100.0% 8/15
15/15
8892
0.0% 0/12
53.3% 12/12
100.0%
8893
0.0% 0/13
100.0% 6/13
13/13
8894
0.0% 3/ 3
46.2%
100.0%
100.0%
8895
0/16
4/16
16/16
8896
0.0% 0/14
25.0% 3/14
100.0% 14/14
8897
0.0% 0/14
21.4% 3/14
100.0% 14/14
8898 8899
0.0% 0/12 0.0% 0/16
21.4% 7/12
58.3% 2/16
100.0% 11/12
91.7t 16/16
B/ 8 100.0%
0.0%
12.5t
100.0%
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
s,rUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C40 (PAGE 6): PINNA UNFOLDING - INDIVIDUAL DATA - Fl GENERATION LITTERS
-----------------
POSTPARTUM
DAY
-----------------
-- ----------------------
2
3
4
--------------------------
-- --------------------
5
6
7
-- ------------------------
--------------------- --- - -------------------------- ----- - -------
MATERNAL/LITTER
MATERNAL
DOSAGE GROUP
--------------------------------------------
111
0.4 MG/KG/DAY
----------------------------
---------------------------
- -------
8900
0/14
0/14
14/14
0.0%
0. oi; 100.0%
8901
0/13
2/13
13/13
0.0%
15.4%
100.0%
8902
0/15
1/14
14/14
0.0%
7.1%
100.0%
8905
0/19
13/18
18/18
0.0%
72.2%
100.0%
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C40 (PAGE 7)! PINNA UNFOLDING - INDIVIDUAL DATA
Fl GENERATION
LITTERS
POSTPA-RT-U-M-----DA-Y---------2 ----- 3- -------4------- -5-------- 6 - -----------------------------------------------------------
------------------
7 -----------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
--------------------------------------------------------------------------
8906
0/11
1/10
10/10
0.0%
10.0%
100.01;
8909
0/11
0/11
11/11
8913
0.0% 0/12
0.0% 1/11
100.0% 11/11
8919
0.0% 0/15
9.1% 1/15
100.0% 2/15
8/ 8
8920
0.0% 0/ 6
6.7% 0/ 6
13.3% 6/ 6
100.0%
0.0%
0.0%
100.0%
8921
0/10
5/10
10/10
6925
0.0% 0/ 9
50.01; 0/ 9
100.0% 0/ 9
8/ 8
8926
0.0% 0/ 7
0.0% 0/ 4
0.0% 0/ 4
100.0% 2/ 4
4/ 4
8927
0.0% 0/13
0.0% 0/ 8
0.0*4 0/ 8
50.0% 0/ 2
100.0% 1/ 2
2/ 2
8928
0.0% 0/12
o.oi; 9/12
0.0% 12/12
0.0%
SO.0%
100.01;
8929
0.0%
75.0%
ioo.ot
NO SURVIVING PUPS ON DAY
2 POSTPARTUM
---------------------- ----- ------------------------------------------------------------ --
8930
0/10
0/10
2/10
a/ 8
0.0%
0.0%
20.0%
100.0%
8931
0/ 4
0/ 4
0/ 4
4/ 4
0.0%
0.0%
0.0%
100.0%
8932
0/17
0/11
0/11
3/ 8
8/ 8
0.0%
0.0%
0.0%
37.5%
100.0%
8934
0/11
0/10
0/10
2/ 8
2/ 8
8/ 8
0.0%
0.0%
0.0%
25.0%
25.0%
100.0%
8935
0/12
1/12
0/11
5/ 8
8/ 8
0.0%
8.3%
O.Ot
62.5%
100.0%
8936
0/ 8
0/ 6
NO SURVIVING
PUPS ON DAY 4 POSTPARTUM
O.Ot
0.0%
-------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSINATAL
REPRODUCTION
TOXICI
TABLE C40 (PAGE 8): PINNA UNFOLDING
INDIVIDUAL
DATA
Fl GENERATION
LITTERS
--------------- ----------------------
POSTPARTUM
DAY
2
3
---------------------------------------
-------------- I
4
5
--
------------------------
6
7
--
---------I ---------------
MATERNAL/LITTER
MATERNAL DOSAGE GROUP --I-V---------------1.-6--M-G-/-K-G/-D-A-Y--------- --
--------------------------------- --------------------- ----------------------------
8937
0/ 8
0/ a
8/ B
------------------------------------------------
0.0%
o.ot
100.01
8939
4/13
0/ 5
2/ 5
5/ 5
30.8t
0.0%
40.0%
100.0%
8940
0/13
0/13
11/13
8/ 8
0.0%
0.0%
84.6%
ioo.oi;
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REIIRODUCTION
TOXICI
TABLE C40 (PAGE 9): PINNA UNFOLDING - INDIVIDUAL DATA - Fl GENERATION LITTERS
-------- ------------------------------ -- -- ---- ----------- ---- -------- I ---------------
POSTPARTUM
DAY
2
3
4
5
6
7
---------------------------------------- ----------------------- - ---------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
-------- ------------------------------------ -------------------- ---------------------------
8942
NO SURVIVING
PUPS ON DAY I OF LACTATION
- --------- ---- I---------- --------------
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
---------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C40 (PAGE 10): PINNA UNFOLDING - INDIVIDUAL DATA - Fl GENERATION LITTERS
------
POSTPARTUM
DAY
-------
MATERNAL/LITTER ----------------
--- ------------- -
--- ------------------------- ----- -------
2
3
4
5
6
7
--------- I ------------------------------------------------------
#
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
---------------- ---------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNAI'AL REPRODUCTION
TOXICI
TABLE C41 (PACE 1)! EYE OPENING - INDIVIDUAL
DATA - Fl GENERATION
LITTERS
- ---- --------------------- - --------------------------- ----------------------------------------------------
POSTPARTUM
DAY
12
13
14
15
16
17
is
---------------------------------------------------------------------------------------
----------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
------------------------------------------------------------------------------------------------------------
8801
0/ a
0/ 8
1/ a
6/ 6
a/ 8
0.0%
0.0%
12.5yd
75.0%
100.0%
8803
0/ 8
4/ 8
8/ 8
0.0%
50.0%
100.0%
8804
0/ 8
2/ 8
4/ 8
S/ 8
8805
0.0% 0/ 8
25.0% 0/ 8
50.0% S/ 8
100.0% B/ a
0.0%
0.0%
62.5%
100.0%
0807
0/ 8
0/ 8
2/ 8
6/ 8
8/ a
0.0%
0.0%
25.0%
75.0%
100.0%
8808
0/ 8
0/ 8
2/ 8
8/ 8
0.0%
0.0%
25.0%
100.0!k
8811
0/ 8
2/ 8
6/ 8
8/ a
0.01
25.0%
75.01;
100.0%
8812
0/ 8
1/ a
8/ a
0.0%
12.5%
ioo.oi;
8813
0/ 8
0/ 8
3/ 8
8/ 8
o.o%
0.0%
37.Slk
100.0%
8814
0/ a
3/ 8
a/ 8
o.ot
37.5%
100.0%
8819
0/ 8
0/ 8
8/ 8
0.0%
0.0%
100.0%
8821
0/ 8
0/ 8
4/ 8
7/ 8
8/ 8
0.0%
0.0%
50.0!k
87.5%
100.0%
8823
0/ 8
1/ 8
5/ 8
7/ 8
B/ 8
0.0%
12.5%
62.5%
87.5%
100.0%
8824
0/ a
0/ 8
6/ 8
8/ 8
0.0%
0.0%
75.0%
100.0%
8826
0/ 8
0/ 8
1/ 8
6/ 8
8/ 8
8827
0.0% 0/ 8
0.0% 0/ 8
12.5% 4/ 8
75.0% 7/ 8
100.0% 8/ 8
0.0%
0.0%
50.0%
87.5*
100.0%
8828
0/ 8
0/ 8
6/ 8
B/ a
0.0%
0.0%
75.0%
ioo.oi;
---------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AN[) PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C41 (PAGE 2): EYE OPENING - INDIVIDUAL DATA
Fl GENERATION
LITTERS
-------------- ------------ --------- --- -- - ----- ------------ --- --- -------------------
----------
POSTPARTUM
DAY
12
13
14
15
------------ --------------------------------------
16
17
18
---------------- ---- -------------------
----------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
----------------------------------------------------- --------------------------------------------- -----------
8830
0/ 8
0/ 8
B/ 8
0.0t,
0.0%
100.0%
8831
0/ a
0/ 8
1/ 8
7/ 8
8/ 8
O.Ot
0.0%
12.5%
87.5%
100.0%
8832
0/ 8
0/ a
4/ 8
8/ 8
0.0%
0.0%
50.0%
100.0%
8833
0/ 8
0/ 8
0/ 8
6/ 8
8/ 8
0.0%
0.0%
0.0%
75.0%
100.094
8834
0/ a
0/ 8
2/ 8
8/ 8
0.0%
0.0%
25.0%
100.0%
8835
0/ 8
0/ 8
6/ 8
8/ 8
0.0%
0.01
75.0%
100.0%
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILTTY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C41 (PAGE 31: EYE OPENING
INDIVIDUAL
DATA - Fl GENERATION
LITTERS
-------------------
POSTPARTUM
DAY
-------------------
------------ ---------------- ------ ------------------ --
12
13
14
15
16
17
18
----------------------------- ----------------------------
------ ---------------------------------------
-----
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------
-----
8838 8840 8841 8842
0/ 8 0.0% 0/ 8 0.0% 0/ a 0.0% 0/ 8
0/ 8 0.0% 0/ 8 0.0% 0/ 8 o.oi; 0/ 8
3/ 8 37.5%
S/ a 62.5%
1/ 8 12.5%
1/ 8
B/ a ioo.oi;
B/ 8 100.0%
7/ 8 87.5%
7/ 8
B/ 8 100.0%
8/ 8
884S 8846
0.0% 0/ 8 0.0% 0/ 8
0.0% 0/ 8 0.0% 0/ 8
12.5% 3/ 8
37.5t 2/ 8
87.5td 8/ 8
100.0% 8/ a
100.0%
8847
0.0% 0/ 8
0.096 0/ 8
25.0% 0/ 8
ioo.ot 2/ 8
8/ 8
8849
0.0% 0/ 8
0.0% 0/ 8
0.0% 0/ 8
25.0% 2/ 8
100.0% B/ 8
8851
0.0% 0/ 8
0.0% 0/ 8
0.0% 3/ 8
25.0% B/ 8
100.0%
0.0%
0.0%
37.5%
ioo.ot
8852
0/ a 0.0%
0/ 8 0.0%
6/ 8 75.0%
B/ 8 100.0%
8853
0/ 8 o.ol;
0/ 8 0.0%
4/ 8 50.0%
8/ 8 100.0%
88S4
0/ 8
0/ 8
4/ 8
B/ 8
0.01
0.0%
50.0%
100.0%
8855 8857
0/ 8 0.0% 0/ 8
0/ 8 0.0!k 0/ 8
0/ 8 0.0% 2/ 8
2/ 8 25.0%
8/ 8
8/ a 100.0%
8858
0.0% 0/ 8
0.0% 0/ 8
25.0% 1/ 8
100.0!k B/ 8
8860
0.014 0/ 8
0.0% 0/ 8
12.5% 8/ 8
100.0%
0.0%
0.0%
100.0%
8862
0/ 8
0/ 8
0/ 8
6/ 8
B/ 8
8863
0.0% 0/ 8 0.014
0.0% 0/ 8 0.0%
0.0% 4/ 8 50.0%
75.0% S/ 8
100.0%
100.0%
8864
1/ 8
4/ 8
7/ 8
8/ 8
12.5%
50.Ot
87.5%
100.01;
8865
0/ 8
0/ 8
0/ 8
S/ 8
0.0%
0.0%
0.0%
100.0%
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PPOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C41 (PAGE 4): EYE OPENING - INDIVII)UAL DATA - Fl GENERATION LITTERS
-----------
------------------- -
POSTPARTUM
DAY
12
13
14
------------- - ------------------------
----------------------
15
16
17
-----------------------
----- ----------------------
18 ------------------------------
---------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------------------- - -------------------------------------------------------------------
8866
0/ 8
1/ a
1/ 8
4/ 8
B/ 8
8867
0.0% 0/ a
12.5% 2/ 8
12.5% 8/ 8
50.0%
100.0%
0.0%
25.0%
100.0%
8868
0/ 8
0/ 8
2/ 8
7/ 8
8/ 8
0.0%
0.0%
25.0%
87.5t
100.0%
8869
0/ 8
0/ 8
2/ 8
7/ 8
a/ 8
0.0%
0.0%
25.0%
87.5%
100.0%
8870
0/ 8
0/ 8
1/ 8
8/ a
0.0%
0.096
12.5%
100.0%
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COM13INED ORAL (G4VAGE) PPOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE C4] (PAGE 5): EYE OPENING - INDIVIDUAL DATA
Fl GENERATION
LITTERS
----- --POSTPARTUM
---------
-------------
DAY
12
-------------
------------- ------------
13
14
15
----------------------------
------------ -- -------- 1-@ -
16
17
18
------------ --------------
---------------------------------------------------------
f4ATERNAL/LITTER
#
MATERNAL
DOSAGE
--------------------------------------
GROUP 111
0.4 MG/KG/DAY
-----------------------------------------------------------------------
8872
1/ 8
2/ 8
6/ 8
8/ 8
8874 8875 8876
12.5% 0/ 6 O.ot 0/ 8 0.0% 0/ 6
25.0% 0/ 8 0.0%
0/ 8 0.0% 0/ 6
75.0% 0/ 8 0.0% 0/ 8 0.0% 6/ 6
100.0% 5/ 8
62.5% 8/ a
100.0%
B/ 8 100.0%
8881 8882
0.0% 0/ 8 0.0% 0/ 8
0.0% 0/ a 0.0% 0/ 8
100.0% 0/ 8 0.0% 2/ 8
2/ 8 25.0%
6/ 8
8/ 8 100.0%
8/ 8
8885 8889 8890 8891
0.0% 0/ 8 0.0% 0/ 8 0.0% 0/ a 0.0% 0/ 8
0.0% 0/ a 0.0% 0/ a 0.0% o/ 8 0.0% o/ 8
25.Ot 6/ 8
75.0% 0/ 8 0.0%
1/ 8 12.5%
3/ 8
7@.0% B/ 8
100.0!k
5/ 0 62.5%
6/ 8 75.0%
8/ a
100.0%
8/ 8 100.0%
8/ 8 100.0%
8892
0.0% 0/ 8
0.0!k 0/ 8
37.5% 3/ 8
100.0!k 7/ 8
8/ 8
8893 -8894
0.0% 0/ 8 0.0% 0/ 3
0.0% 0/ 8 0.0% 1/ 3
37.5* 2/ 8
2S.0% 3/ 3
87.5% 5/ 8
62.5%
100.0% 6/ 7
85.7%
6/ 6 100.0%
0.01
33.3%
100.0%
8895
0/ a
0/ 8
0/ 8
2/ 8
B/ 8
8896a
0.0% 0/ 8
0.0% 0/ 8
0.0% 2/ 8
25.0% 8/ 8
100.0%
8897a
0.0% 0/ 8
0.0% 0/ 8
25.0% 2/ 8
100.01* 8/ 8
8898
0.0% 0/ 8
0.0% 0/ 8
25.0% 1/ 6
100.014 S/ 8
8/ 8
8899
0.0% 0/ 8
0.0% 1/ 7
12.5% 3/ 7
62.5t 7/ 7
100.0%
0.0%
14.3%
42.8%
100.0%
----------------------------------------------------------------------------------------------------------------
NIN = 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 pu
arbitrarily distributed between the two dams and values will be included in group averages and statistical
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERT11,ITY, DEVELOPMENTAL
PPOS IN RAIS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICII
TABLE C41 (PAGE 6): EYE OPENING @ INDIVIDUAL DATA - Fl GENERATION LITTERS
-------------------- ---------------------------- --------------------------
------------ --------- - -
POSTPARTUM
DAY
12
13
14
15
16
17
16
------------------------------ ---- I ------------- --------------------------
-------------------------- ------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
------------------------------------------------- -------------------------- - ---------------------------------
8900
0/ 8
1/ 8
1/ 8
a/ 8
8901
0.0% 0/ 8 0.0%
12.5% 0/ 8 0.0%
12.51; 3/ 8
37.5%
100.0% B/ 8
100.0%
8902
0/ 8
0/ 8
3/ 8
8/ 8
8905
0.0% 0/ 8
0.0% 0/ 8
37.5% 2/ 8
100.0% 8/ 8
0.0%
0.0%
25.0*
100.0%
------------------------------------------------- --------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POf;TNATAL
REPRODUCTION
TOXIC
TABLE C41 (PAGE 7): EYE OPENING - INDIVIDUAL DATA - Fl GENERATION LITTERS
--------- - ----------------
POSTPARTUM
DAY
12
----------------------------
----------- -- -- -------------
13
14
15
16
-------------------------------
---I - -----------------
17
18
-----------------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP IV
1.6 MG/KG/DAY
------------------------------------------------------------------------------------
8906 8909 8913
0/ 8 0.01 0/ 8 0.0% 0/ 8
0/ 8 0.0%
0/ 8 0.0% 0/ a
0/ a 0.0% o/ 8 0.0% 2/ 8
4/ 8 50.0%
7/ 8 67.5t
B/ 8
B/ 8 100.0%
8/ 8 100.0%
8919
0.0% 0/ a
0.0% 0/ 8
25.0% 0/ 8
100.0% 3/ 8
8/ 8
8920 8921 8925 8926 8927 8928 8929
0.0%
o.oi;
0/ 6
0/ 6
O.Ot
0.0%
0/ 8
0/ 8
0.0%
0.09,
0/ 7
0/ 7
0.0%
0.0%
0/ 4
0/ 4
O.Ot
0.0%
1/ 2
1/ 2
50.0%
50.0%
0/ 8
0/ a
0.0%
0.0!k
NO SURVIVING
PUPS
0.0% 0/ 6 0.096 0/ 8 0.0% 0/ 7 0.0%
0/ 4 0.0% 1/ 2 50.0% 2/ 8 25.0% ON DAY
37.5%
100.0%
0/ 6 0.0%
1/ 6 16.7%
0/ 8 0.0% 0/ 7
B/ 8 100.0%
3/ 7
O.Otd
42.8%
0/ 4
1/ 4
0.0%
25.0%
2/ 2 100.0%
3/ 8
8/ 6
37.5!k
100.0%
2 POSTPARTUM
6/ 6 100.0ir
7/ 7 100.0%
3/ 4 75.0!k
4/ 4 100.0t,
- --------- ------------------------------------
-------------------------
8930
0/ 8
0/ 8
1/ 8
1/ 8
5/ 8
8/ 8
8931
0.0% 0/ 4
0.0% 0/ 4
12.S% 3/ 4
12.5% 4/ 4
62.5%
100.0%
0.0%
0.0%
75.0%
100.0%
8932
0/ 8
0/ 8
0/ 8
0/ 8
2/ 8
8/ 8
0.0%
o.oi;
0.0%
0.0%
25.0%
100.0%
8934
0/ 8
0/ a
0/ 8
0/ 0
2/ 8
8/ 8
0.0%
0.0%
0.0%
0.0%
25.0%
ioo.ot
8935
0/ 8
0/ 8
1/ 8
2/ 8
4/ 8
8/ 8
8936
0.0%
0.0%
12.5%
NO SURVIVING
PUPS ON DAY
25.0%
50.0%
4 POSTPARTUM
100.0%
--------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE@ PFOS IN RATS (SPONSOR'S
FERTIUITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C41 (PAGE 8@: EYE OPENING - INDIVIDUAL DATA - Fl GENERATION LITTERS
------------------ --------------------------- ----------------------- --- ----------------------------------
POSTPARTUM
DAY
-----------------
12
13
14
15
16
17
18
------------------------------------------------------- ----------------------------------
MATERNAL/LITTER ------------------
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
-------------------------------------------------------
----------------------------------
8937
1/ 8
2/ 8
1/ 8
4/ 8
8/ 8
12.5%
25.0%
12.5%
50.0%
100.0%
8939
0/ 5
0/ 5
0/ 5
1/ 5
S/ 5
0.0%
0.0%
0.0%
20.0%
100.0%
8940
0/ a
0/ 8
3/ 8
5/ 8
8/ 8
0.0%
0.0%
37.5%
62.5t
100.0%
--------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED
ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER!
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C41 (PAGE 9): EYE OPENING - INDIVIDUAL DATA - Fl GENERATION LITTERS
------------------
POSTPARTUM
DAY
------------------
---------------------- --- -- ------------I --- ------- --------------------------------
12
13
14
15
16
17
18
- --------------------------- -------------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP V
3.2 MG/KG/DAY
----------------------------------------------- ---------------------------------------------------------------
8942
NO SURVIVING PUPS ON DAY 1 OF LACTATION
8943 8944 8946 8949 8950 895S 8956 8959 8960 8961 8962
NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING
PUPS ON DAY 1 OF LACTATION PUPS ON DAY I OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY I OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY 1 OF LACTATION PUPS ON DAY 2 OF LACTATION 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 8970 6971
NO SURVIVING NO SURVIVING NO SURVIVING
PUPS ON DAY 1 OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY 2 OF LACTATION
8973
NO SURVIVING
PUPS ON DAY 2 OF LACTATION
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
PERTII,TTY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE C41 (PAGE 10): EYE OPENING - INDIVIDUAL DATA - Fl GENERATION LITTERS
------------
---- ------------- -- ------ - -- ------------------- ------- -------------------- -----------
POSTPARTUM
DAY
12
13
14
is
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
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418 008:
COMBINED ORAB (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C42 (PAGE 1): ACOUSTIC STARTLE
INDIVIDUAL
DATA - Fl GENERATION
LITTERS
------------------
POSTPARTUM
DAY
13
14
-----------------------------------
--- --- ----------
15
16
--- ---------------
-------- ------- -I ----------------------- -------------
17
18
19
20
21
-------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------- -----------------------------------------------------------------------
8801
7/ 8
8/ 8
8803 8804 8805 8807 8808
87.51k 6/ 8
75.0* S/ a
100.0% 2/ 8
25.Oli 7/ 8
87.5!k 6/ 8
100.0% 5/ 8
62.5t
6/ 8 75.0%
8/ 8 100.0%
B/ 8
3/ 8 37.5%
6/ 8 75.0%
3/ 8 37.5%
B/ a 100.0%
6/ 8 75.0%
8/ 8 100.0%
Bell 8812 8813
75.0% 0/ 8 0.0% 1/ a
12.5% 8/ 8
ioo.oir 5/ 8
62.5% 3/ 8
37.5%
7/ 8 87.5%
4/ 8 50.0%
6/ 8 75.01;
8/ a 100.0%
6/ a 75.0%
B/ 8 100.0%
8814 8819
100.0% 5/ 8
62.Slk S/ 8
2/ 8 25.0%
4/ 8 50.0%
8/ 8 100.0%
8821
100.0% 7/ 8
8/ 8
8823 8824
87.St 6/ 8
75.0% 8/ 8
100.0% 4/ 8
50.01;
3/ 8 37.5%
8/ a 100.0%
8826
100.0% 8/ 8
8827
100.0% 1/ 8
3/ 8
B/ 8
12.5%
37.5%
100.09,
8828
6/ 8
7/ 8
8/ 8
75.0%
87.5%
100.0%
-----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE C42 (PAGE 2): ACOUSTIC STARTLE - INDIVIDUAL DATA - Fl GENERATION LITTERS
------- ------------------------- --- ------------------------------------------
POSTPARTUM
DAY
13
14
15
16
17
18
19
------- ------------------------------ I -----------------------------------------
----- - ---------------------
20
21
-----------------------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------- -----------------------------------------------------------------------
8830
8/ 8
100.0%
8831
S/ 8 100.0%
8832 8833
7/ 8 87.5%
6/ a
8/ 8 100.0%
a/ a
8834
75.0% 8/ 8
100.0%
8835
100.0% 8/ 8
100 .oyt
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-OOB:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C42 (PAGE 3): ACOUSTIC STARTLE
INDIVIDUAL DATA - Fl GENERATION
LITTERS
---------------------------------------- ------- ------------ - ---------------------------------------------
POSTPARTUM
DAY
13
14
is
16
17
le
19
20
21
------------------------------------------------- ------------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
8838 8840
7/ 8 87.5%
6/ 8
5/ B 62.5%
7/ 8
3/ 8 37.5%
5/ 8
0/ 8 0.0% 1/ 8
7/ 8 87.5%
7/ 8
7/ 8 87.5%
8/ 8
6/ 8 75.0%
0/ 8 100.0%
75.0%
87.5%
62.5%
12.5%
87.5%
100.0%
8841
3/ 8
4/ 8
1/ 8
2/ 8
7/ 8
8/ a
37.5%
50.0%
12.5%
25.0%
87.5%
100.0%
8842
7/ 8
6/ 8
7/ 8
1/ 8
5/ 8
B/ a
87.596
75.0%
87.S%
12.5%
62.5%
100.0%
8845
8/ 8
8846 8847
100.0% 6/ 8
75.0% S/ 8
8/ 8 100.0%
8849
100.0% 3/ 8
a/ 8
8851
37.5% 6/ 8
100.0% a/ 8
8852
75.0% S/ 8
ioo.oi;
8853 8854
100.0% 7/ 8
87.5% 8/ 8
7/ 8 87.5%
6/ 8 75.01;
6/ 8 75.0%
0/ 8 100.0%
8855
100.0% 8/ 8
8857
100.0% 8/ 8
100.0*
8858
8/ 8
100.0%
8860 8862
7/ 8 87.5%
7/ 8
5/ 8 62.5%
8/ 8
0/ 8 0.0%
7/ 8 87.5%
B/ 8 100.0%
87.5%
100.0%
8863
8/ 8
100.0% ---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE C42 (PAGE 4): ACOUSTIC STARTLE - INDIVIDUAL DATA - Fl GENERATION LITTERS
-------------------- ----------------------------- ---------------- ---------------------------- -------------
POSTPARTUM
DAY
13
14
15
-------------------------------------------
16
17
18
19
20
21
----- -------------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8864
5/ 8
8/ 8
62.5%
100.0%
8865
S/ 8
8866
100.0% 3/ 8
6/ 8
B/ 8
8867
37.5t 8/ 8
100.0%
7S.0%
100.0%
8868
6/ 8
4/ 8
1/ 8
S/ 8
75.0%
50.0%
12.5%
100.0%
8869
7/ 8
5/ 8
2/ 8
5/ 8
4/ 8
5/ 8
B/ 8
87.5%
62.Svi
25.0%
62.5%
50.0%
62.5%
100.0%
8870
6/ 8
5/ a
4/ 8
5/ 8
1/ 8
3/ 8
8/ a
75.0%
62.5?t
50.Ot
62.5%
12.5%
37.5%
100.0!k
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C42 (PAGE 5); ACOUSTIC STARTLE - INDIVIDUAL DATA - Fl GENERATION LITTERS
------------------------
POSTPARTUM
DAY
13
--------------------------
------- --------------
14
is
16
-----------------
17
is
-----19
------- -------- --- ----
20
21
MATERNAL/LITTER
#
MATERNAL - -D-O-SA-G-E---G-R-O-UP----11-1----- - -----0-.-4--M-G-/-KG-/-D-A-Y- ------ - ---------------------- ----
------------------------------------------------------- -------------------------------------------------------
8872
4/ 8
7/ 8
6/ 8
1/ 8
1/ 8
6/ 8
B/ 8
8874
50.0% 4/ 8
87.5% a/ 8
75.0%
12.5%
12.5%
75.0%
100.0%
8875 8876 Beal
50.0% 4/ 8
50.0% 2/ 6
33.3% 6/ 8
100.0% 4/ 8
50.0% 4/ 6
66.7% 8/ 8
6/ 8 75.0%
5/ 6 83.3%
a/ 8 100.Ot
4/ 6 66.7%
6/ 6 100.0%
8882 8885
75.0% 4/ 8
50.0% a/ 8
100.0% 3/ 8
37.5%
4/ 8 50.091
4/ 8 50.0%
4/ 8 50.0%
B/ 8 100.0*
8889
100.0% B/ 8
8890 8891
100.0% 6/ 8
75.0% a/ 8
7/ 8 87.5%
5/ 8 62.5%
8/ 8 ioo.ot
8892 8893
100.0% 4/ 8
50.0% 6/ 8
4/ 8 50.0%
5/ 8
3/ 8 37.5%
8/ 8
6/ 8 75.0%
8/ 8 ioo.ot
8894
75.0% 3/ 3
62.5%
100.0%
100.0%
8895 8896a 8897a 8898 8899
S/ a 62.5%
7/ 8 87.5%
4/ 8 50.0%
5/ 8 62.5%
7/ 7
a/ 8 100.0%
7/ 8 87.5%
3/ 8 37.5%
6/ 8 75.0%
5/ 8 62.5%
5/ 8 62.5%
3/ 8 37.5%
6/ 8 75.0%
7/ 8 87.5%
0/ 8 0.0%
8/ 8 100.0%
6/ 8 75.0%
8/ 8 100.0%
8/ 8 100.0%
100.0% ---------------------------------------------------------------------------------------------------------------
NIN = 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 p
arbitrarily distributed between the two dams and values will be included in group averages and statistical
PROTOCOL 418-008:
COMBINED ORAL IGAVAGE) PFOS IN PATS (RPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295 9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C42 (PAGE 6): ACOUSTIC STARTLE - INDIVIDUAL DATA - Fl GENERATION LITTERS
--------------------------------
--------------- -----------
---------------- ---------- -----------------
POSTPARTUM
DAY
13
---------------------------------
14
15
16
17
18
19
20
21
---------------------------- ----------------------------- -----------------
MATERNAL/LITTER
#
MATERNAL
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------- ---------------------------- -----------------------------------------------
8900
5/ 8
5/ 8
1/ 8
5/ 8
5/ 8
4/ 8
a/ a
8901
62.5% 6/ a
62.5% 3/ 8
12.5% 3/ 8
62.5% 4/ 8
62.5% 5/ 8
so.ot 7/ 8
100.0i; 5/ 8
a/ 8
8902
75.0% 4/ 8
37.5% B/ 8
37.5%
50.0%
62.5%
87.5%
62.5%
100.0%
50.0%
100.0%
8905
6/ 8
7/ 8
a/ 8
75.0%
87.5%
100.0%
--------------------------------------------------------------- -----------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-000:
COMBINED
ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PPOS IN RATS (SPONSOR'.'; STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C42 (PAGE 7): ACOUSTIC STARTLE - INDIVIDUAL DATA - Fl GENERATION LITTERS
-- -- ------- ---------------------------
---- -------------------- - ----------------- -------- ----------
POSTPARTUM
DAY
13
14
15
------------------------------------------
16
17
18
19
20
21
--------------------------- --------------------------- I ----------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
------------------------------------------ ---------------------------- --------------------------------------
8906
4/ 8
a/ 8
50.0%
100.0%
8909
4/ 8
5/ 8
3/ 8
6/ 8
8/ a
8913 8919
50.0% 4/ 8
50.0% 4/ 8
62.5% 4/ 8
50.0% 1/ 8
37.5% S/ 8
62.5% 5/ 8
75.0% 4/ 8
50.0% 8/ 8
100.0% 6/ 8
75.0%
8/ 8 100.0!k
8920 8921
50.0% 3/ 6
so.ol; 4/ 8
12.5% 3/ 6
50.0% S/ 8
62.S% 3/ 6
50.0%
100.0% 2/ 6
33.3%
4/ 6 66.7%
3/ 6 50.0%
4/ 6 66.7!k
G/ 6 100.0%
SO.0%
100.0%
8925 8926 8927 8928
0/ 7 0.0% 1/ 4 25.0!k 0/ 2 0.0% 4/ 8
2/ 7 28.6%
0/ 4 0.0% 0/ 2 0.0% 8/ 8
4/ 7 57.1%
1/ 4 25.0%
0/ 2 0.0%
S/ 7 71.4%
0/ 4 0.0% 0/ 2 o.oys
1/ 7 14.3%
4/ 4 100.0%
1/ 2 50.0%
0/ 7 o.o%
2/ 7 28.6%
7/ 7 100.0%
0/ 2 0.0%
0/ 2 0.0%
1/ 2 50.0%
1/ 2 50.0%
so.ot
100.0%
8929
NO SURVIVING
PUPS ON DAY 2 POSTPARTUM
8930
4/ 8
8/ 8
50.0%
100.0%
8931
1/ 4
0/ 4
2/ 4
2/ 4
4/ 4
25.0%
0.0%
50.0%
50.0%
100.0%
8932
0/ 8
2/ 8
S/ 8
B/ 8
0.0%
25.0%
62.5%
100.0%
8934 8935
2/ 8 25.0%
7/ 8
3/ 8 37.5%
6/ 8
5/ 8 62.5%
7/ 8
5/ 8 62.5'k
4/ 8
1/ 8 12.5%
0/ 8
2/ 8 25.0%
8/ 8
2/ 8 25.0%
4/ 8 50.0%
8/ 8 ioo.oi;
87.5%
75.0%
87.5%
50.0%
0.0%
ioo.oi;
8936
NO SURVIVING
PUPS ON DAY 4 POSTPARTUM
---------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE C42 (PAGE 8): ACOUSTIC STARTLE - INDIVIDUAL DATA - Fl GENERATION LITTERS
- --------------------------------------------- -- ------------------------------------------------------
POSTPARTUM DAY
13
14
15
16
17
18
19
20
21
--------------------------------------------------- --------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
----------------------------------------------------------------------------------------------------------
8937 6939 8940
2/ 8 25.0%
1/ 5 20.0%
8/ 8
8/ 0 100.0%
0/ 5 o.oi;
4/ S 80.0%
1/ 5 20.0%
3/ 5 60.0%
S/ 5 100.0%
100.0% ---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTALMEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008!
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C42 (PAGE 9): ACOUSTIC STARTLE - INDIVIDUAL DATA - Fl GENERATION LITTERS
--------- - ---------------- ------
POSTPARTUM
DAY
13
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 I 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 8955 8956
NO SURVIVING NO SURVIVING NO SURVIVING
PUPS ON DAY 2 OF LACTATION PUPS ON DAY 1 OF LACTATION PUPS ON DAY 2 OF LACTATION
8959
NO SURVIVING
PUPS ON DAY 2 OF LACTATION
8960 8961 8962 8964 8967 8968
NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING NO SURVIVING
PUPS ON DAY 1 OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY 1 OF LACTATION PUPS ON DAY 2 OF LACTATION PUPS ON DAY I OF LACTATION 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
--------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED
ORAL (GAVAGE@ FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUI)Y NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C42 (PAGE 10): ACOUSTIC STARTLE - INDIVIDUAL DATA - Pl GENERATION LITTERS
-----------------
POSTPARTUM
DAY
-----------------
---- ------------------------
13
14
15
-------------- ----------- - - ------------
16
17
18
19
20
-------------------21
MATERNAL/LITTER
0 -----M-A-T-ER-N-A-L ----D-OS-A-G-E ---G-R-OU-P- V- -------------3.-2--M-G-/-K-G/-D-A-Y----------------------------- ----------
---------------------- --------------------------------------------------- ------------------------------------
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
8974
NO SURVIVING PUPS ON DAY I OF LACTATION
8975
NO SURVIVING
PUPS ON DAY 1 OF LACTATION
----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL,POSTNATAL
REPRODUCTION
TOXICIT
TABLE C43 (PAGE 1): AIR RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
-----------------
POSTPARTUM
DAY
14
---- -----------------
- --------------- ----------
is
16
17
---------------------------
---------------- ----------
la
19
20
---------------------------
----------------------------
21 ------------------------------
MATERNAL/LlrrTER
#
MATERNAL DOSAGE GROUP 1
------------------------- --------------------------
8801
2/ 8
2/ 8
S/ 8
8/ 8
0 (VEHICLE) MG/KG/DAY I ---------------------------
------------------------------
8803
25.0% 4/ 8
25.0% S/ 8
62.5% a/ 8
100.0%
SO.0%
62.5%
100.0%
8804 8005 8807
1/ 8 12.5%
0/ 8 0.0% 3/ 8
6/ 8 7S.0%
2/ 8 25.0%
6/ 8
6/ 8 75.0%
3/ 8 37.5%
4/ 8
7/ 8 87.St
8/ 8 100.0%
B/ 8
B/ 8 100.0%
8808
37.5% S/ 8
7S.0% 3/ 8
50.0% 5/ 8
100.0% 5/ a
B/ 8
8811
62.5% 1/ 8
37.St S/ 8
62.5% 8/ 8
62.5%
100.0%
12.5%
62.5%
100.0%
8812
6/ 8
6/ 8
8/ 8
8813
75.0% 1/ 8
75.0% 6/ 8
100.0% 7/ 8
8/ 8
8814
12.5% B/ 8
75.0%
87.5%
100.0%
100.0%
8819
1/ 8
B/ a
12.5%
100.0%
8821
5/ 8
3/ 8
6/ 8
B/ 8
62.5%
37.5%
75.0%
100.0%
8823
1/ 8
2/ 8
4/ 8
7/ 8
8/ 8
8824
12.5% 0/ 8
25.0% 3/ 8
50.0% 3/ 8
87.5% 4/ 8
100.0% 5/ 8
8/ 8
8826
0.0% 0/ 8
37.5% 0/ 8
37.5% 2/ 8
50.0% 3/ 8
62.Sik 8/ 8
100.0%
8827
0.0% 0/ a
0.0% 1/ 8
25.0% 1/ 8
37.5% 8/ 8
100.0%
0.0%
12.5%
12.5%
100.0%
8828
0/ 8
5/ 8
5/ 8
6/ 8
8/ 8
0.0%
62.S%
62.5%
75.0%
100.0%
----------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/ POSTNATAL
REPRODUCTION
TOXIC
TABLE C43 (PAGE 2): AIR RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
---------------- ---------------------------- ------------- ---------- -------- -------------------------- - -
POSTPARTUM
DAY
14
15
16
17
18
19
20
21
-------------- -----------------------------------------------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8830 8831 8832
2/ 8 2S.0%
0/ 8 0.0% 1/ a
4/ 8 50.01
3/ 8 37.5%
0/ 8
4/ 8 50.01
4/ 8 50.01
3/ 8
3/ 8 37.5%
3/ 8 37.S%
3/ 8
8/ 8 100.0%
S/ 8 100.0%
8/ 8
8833
12.5% 1/ 8
0.0% 6/ 8
37.5% a/ 8
37.5%
100.0%
12.S%
75.0%
100.0%
8834 8835
1/ 8 12.5%
1/ 8 12.5%
3/ 8 37.5%
2/ 8 25.0%
4/ 8 50.0%
5/ 8 62.5%
5/ 8 62.5%
4/ 8 50.0!k
7/ 8 87.5%
8/ 8 100.0%
B/ 8 ioo.ot
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C43 (PAGE 3): AIR RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
---------------------------------------------------
POSTPARTUM
DAY
14
15
16
17
18---- ---1-9---------20---------2-1 -------
---------------
---------------------------------------------------------------------------------------------------------------
14ATERNAL/LITTER
N
MATERNAL DOSAGE GROUP Il
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8830
1/ 8
6/ 8
S/ 8
7/ 8
B/ 8
8840
12.5% 0/ 8
75.0% 1/ 8
62.5% 6/ 8
87.596 7/ 8
100.0% 8/ 8
8841
0.0% 2/ 8
12.5% 3/ 8
75.0% 2/ 8
87.5% 8/ 8
10010%
8842
25.0% 0/ 8
37.5% 2/ 8
25.0% S/ a
100.0%
0.0%
25.0%
100.0!k
8845
2/ 8
0/ 8
7/ 8
7/ 8
8/ 8
8846
25.0% 1/ 8
0.0% 3/ 8
87.5% B/ a
87.5t
100.0%
12.5%
37.5%
100.0%
8847
0/ a 0.0%
3/ 8 37.5*
7/ 8 87.5%
6/ 8 75.0%
8/ 8 100.0%
8849
0/ a
S/ 8
0/ 8
0.0%
62.5%
100.0%
8851
1/ 8
3/ 8
5/ 8
6/ 8
B/ a
8852
12.5% 0/ 8
37.5% 1/ 8
62.5% 4/ 8
75.0% 5/ 8
100.0% 6/ 8
a/ 8
8853
0.0% 1/ 8 12.5%
12.5% 4/ 8
50.0%
50.0% 5/ 8
62.5%
62.5% 7/ 8
87.5%
75.0% a/ 8
100.0%
100.096
8854
0/ 8
1/ 8
4/ 8
6/ 8
5/ 8
8/ 8
8855
0.0% 0/ 8
12.5% 1/ 8
50.0% 3/ 8
75.0% 3/ 8
62.5% 8/ 8
100.0%
0.0%
12.5%
37.5%
37.5%
100.0%
8857 Bess 8860
3/ 8 37.S%
2/ 8 25.0%
3/ 8
1/ 8 12.5%
3/ 8 37.5%
5/ 8
3/ 8 37.5%
6/ 8 75.0%
5/ 8
5/ 8 62.5%
S/ 8 62.5%
6/ 8
7/ 6 87.5t
6/ 8 75.0%
6/ 8
B/ 8 100.0%
B/ 8 100.0%
B/ 8
8862
37.5% 0/ 8
62.5% 0/ 8
62.5% 5/ 8
75.0% 3/ 8
75.0% S/ 8
100.0% 8/ a
8863
0.0% 2/ 8 25.0%
0.0% 5/ 8 62.5%
62.5% 5/ 8
62.5%
37.5% 5/ 8
62.5%
62.5% a/ 8
100.0%
100.0%
---------------------------------------------------------------------------------------------------------------
NIN m NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C43 (PAGE 4): AIR RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
--- -----------------------------------------
POSTPARTUM
DAY
14
15
16
--- -----------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP
---------------- ------------ ------------------------ I ----------
17
18
19
20
21
----------------------------- ---------------------- ----- ------
11
0.1 MG/KG/DAY
--------------------------------------------------------------------------- -----------------------------------
8864
0/ 8
5/ 8
6/ 8
B/ 8
0.01
62.5%
75.0%
100.0%
8865
1/ 8
3/ 8
2/ 8
5/ 8
4/ 8
7/ 8
8/ 8
8866
12.5% 3/ 8
37.5% 1/ 8
25.0% 6/ a
62.5% 4/ 8
so.ot 7/ 8
87.5% 8/ 8
100.0%
37.5%
12.5%
75.0'k
50.0%
87.5%
100.0%
8867 8868
3/ 8 37.5%
0/ 8
5/ 8 62.5%
3/ 8
6/ 8 75.0*
7/ 8
7/ 8 67.5%
6/ 8
7/ 8 87.5%
8/ 8
7/ 8 87.5%
B/ a 100.014
0.0%
37.5%
87.5%
75.0%
100.0%
8869
2/ 8
2/ 8
4/ 8
6/ 8
a/ 8
25.0%
25.0%
50.096
75.0%
10010%
8870
0/ 8
1/ 8
5/ 8
a/ 8
0.0%
12.5%
62.5%
100.0%
--------------------------------------------- -----------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
TABLE C43 (PAGE 5): AIR RIGHTING
INDIVIDUAL DATA - Fl GENERATION LITTERS
REPRODUCTION
TOXIC
POSTPAR-T-U-M- --D-A-Y--------14- -- ---15-- -- -1-6---------17 --- -1-8--------1-9---------20 -- ----21--------------------------------------- I -- ------------------ -------------------------------------
-------------- ----------------
MATERNhL/LITTER
#
MATERNAL
DOSAGE GROUP 111
------------------------------------ ------------------
8872
2/ 8
2/ 8
3/ 8
B/ 8
0.4 MG/KG/DAY ------------------------------------------------------
8874 8875 8876
25.0% 0/ 8 0.0% 1/ a
12.5% 2/ 6
25.0% 2/ 8
25.0% 0/ 8 0.0% 4/ 6
37.5% 6/ 8
7S.0% 3/ 8
37.5% 6/ 6
100.0% 5/ 8
62.5% 7/ 8
87.5%
8/ 8 100.0%
8/ 8 100.0%
8881 8882
33.3% 1/ 8
12.5% 2/ 8
66.7% 2/ 8
25.Ot 5/ 8
100.0% 2/ 8
25.0% 5/ 8
5/ 8 62.5%
5/ 8
S/ 8 100.0%
B/ 8
8885 8889 8890 8891
25.0% 2/ 8
25.0% 4/ 8
50.0% 1/ 8
12.5t 3/ 8
62.5% 3/ 8
37.5% 0/ 8 0.0% 5/ 8
62.5% 4/ 8
62.5% 3/ 8
37@5'4 0/ 8 0.0% 4/ 8
50.0% 6/ 8
62.5% B/ 8
100.0?6 8/ 8
ioo.ot 6/ 8
75.0% 6/ 8
100.0%
B/ 8 ioo.ot
8/ 8
8892
37.5% D/ 8
50.0% 6/ 8
75.0% 2/ 8
75.0% 3/ 8
100.0% 8/ 8
8893
0.0% 0/ 8
75.0% 1/ a
25.0% 2/ 7
37.5% 2/ 6
100.0% 4/ 6
6/ 6
8894
O.Ot 0/ 3
12.5% 1/ 3
28.6% 2/ 3
33.3% 3/ 3
66.7%
100.0%
8895
0.0% 0/ 8
33.3% 1/ 8
66.7% 8/ 8
ioo.ot
0.0%
12.5%
100.0%
8896a
0/ 8
3/ 8
3/ 6
6/ 8
8/ 8
8897a 8898 8899
0.0% 3/ 8 37.5% 0/ 8 0.0% 1/ 7
37.5% 5/ 8
62.5% 5/ 8
62.5% 3/ 7
37.5t 4/ 8
50.0% 2/ 8
25.0% S/ 7
75.0% 6/ 8
75.0% 5/ 8
62.5% 6/ 7
100.0% 8/ 8
100.0% 5/ 8
62.5% 7/ 7
5/ 8 62.5%
8/ 8 100.0%
14.3%
42.8%
71.4%
85.7%
100.0%
---------------------------------------------------------------------------------------------------------------
NIN = 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 p
arbitrarily distributed between the two dams and values will be included in group averages and statistical
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C43 (PAGE 6): AIR RIGHTING
INDIVIDUAL
DATA - Fl GENERATION
LITTERS
------ --------------------- --
POSTPARTUM
DAY
14
-------------------------------
15 -----
--1-6---------17 ------ -18---- ----19---------20-------- 21 ----------------------------------------------------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
----------------------------------------------------------------------------------------------------------------
8900
0/ 8
2/ 8
1/ 8
4/ 8
8/ 8
0.0%
25.0%
12.5%
50.0%
100.0%
8901
0/ 8
0/ 8
3/ 8
5/ 8
5/ 8
8/ 8
8902
0.0% 0/ 8
0.0% 2/ 8
37.5% 4/ 8
62.5% 5/ 8
62.5% 6/ 8
100.0% 8/ a
8905
0.0% 0/ 8 0.0%
25.0% 3/ 8
37.5%
50.0% 2/ 8
25.0%
62.5% 3/ 8
37.5%
75.0% B/ 8
100.0%
100.0%
----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGS) FI@RTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S R;TUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAI,
REPRODUCTION
TOXIC
TABLE C43 (PA(;E 7): AIR RIGHTING
INDIVII)UAL DATA - Fl GENERATION LITTERS
------ -------
POSTPARTUM
DAY
--------------
MATERNAL/LITTER --------------
8906
8909
8913
8919
8920
8921
8925
8926
8927
8928
8929
-------------------
-- --
14
15
16
-------------------
#
MATERNAL DOSAGE GROUP
------------------- ------
0/ a 0.0% 1/ a 12.5% 0/ 8 0.0%
1/ 8 12.St
0/ a 0.0% 1/ 8 12.5%
1/ 8 12.5%
3/ 8 37.5%
1/ 8 12.5%
0/ 8
0/ 8
2/ 8
0.0% 0/ 6 0.0% 0/ a 0.0% 0/ 7
O.Ot 0/ 6 0.0% 0/ 8 O.Ot 0/ 7
25.0% 1/ 6
16.7% 1/ 8
12.5% 2/ 7
0.0% 0/ 4
0.0% 0/ 4
28.6% 0/ 4
0.0%
0.0%
0.0%
0/ 2 0.0%
0/ 2 0.0%
0/ 2 0.0%
0/ a
1/ 8
0.0%
12.5%
NO SURVIVING
PUPS
3/ 8 37.5%
ON DAY
--------------- --- --------- ---------------
17
18
19
20
21
------------------- ----------------------------
IV
1.6 MG/KG/DAY
---------------------------------------------
4/ 6 50.0%
6/ 8 75.0%
6/ 8 75.0%
8/ 8 100.01;
4/ 8
8/ 8
50.0%
100.0%
G/ 8
4/ 8
8/ 8
75.0%
50.014
100.0%
4/ 8
6/ 8
B/ 8
50.01;
75.0%
100.0%
1/ 6
3/ 6
6/ 6
16.7%
50.0%
100.0%
3/ 8
5/ 8
7/ a
8/ 8
37.5%
62.St
87.5%
100.0!k
3/ 7
3/ 7
4/ 7
7/ 7
42.8%
42.8%
57.1%
100.0%
0/ 4
2/ 4
0/ 4
2/ 4
2/ 4
0.0% 0/ 2 0.0% 6/ 8
50.0% 0/ 2 O.Ot' 4/ 8
0.0!k 1/ 2 50.0% 8/ 8
50.0% 1/ 2
50.0%
50.0% 1/ 2
50.0%
75.0%
50.Ok
100.0%
2 POSTPARTUM
- ------ ---------------------- ---------------
8930 8931 8932 8934
a/ 8 0.0% 1/ 4 25.0% 0/ a 0.0% 0/ 8
0/ 8 0.0% 0/ 4 0.0% 0/ 8 0.0% 0/ 8
0/ 8 0.0% 0/ 4 0.0%
2/ 8 25.0%
8/ 8
7/ 8 87.5%
0/ 4 0.0% 3/ 8 37.5%
6/ 8 75.Ot
2/ 4 50.0%
5/ 8 62.5%
2/ 8 25.0%
2/ 4 50.0%
5/ 8 62.5%
B/ 8 ioo.ot
4/ 4 100.0%
7/ 8 87.5%
7/ 8 87.5%
0.0%
0.0%
100.0%
8935
0/ 8
1/ a
0/ 8
3/ 8
4/ 8
7/ 8
8/ 8
0.0%
12.5%
0.0%
37.5%
50.0%
87.5%
100.0%
8936
NO SURVIVING PUPS ON DAY 4 POSTPARTUM
--------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NTJMBER: 6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICI
TABLE C43 (PAGE 8): AIR RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
----------------------- -- ------------------
--------------------- ---------------------- -- ----- --
POSTPARTUM
DAY
14
is
16
17
-------------------------- ----------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP IV
18
19
20
21
--------------------------------------------
1.6 MG/KG/DAY
--------- --
---------------------------------------------------- ---------------------------I ------------------ ------------
8937
0/ 8
1/ 8
4/ 8
1/ 8
6/ 8
8/ 8
0.0%
12.5%
50.0%
12.5%
75.0%
100.0%
8939
0/ 5
0/ 5
0/ 5
0/ 5
3/ 5
3/ 5
5/ 5
8940
0.0% 2/ 8
o.oi; 0/ 8
0.0% 2/ 8
0.0% 5/ 8
60.0% 5/ 8
60.0% 8/ 8
100.0%
25.0*
0.0%
25.0%
62.5%
62.5%
100.0%
-----------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C43 (PAGE 9): AIR RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
-------
----------------------------- ------------------------ -------- ---- ------------------- -----------
-P-O-S-TP-A-R-TUMI 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 IJACTATION
8961
NO SURVIVING
PUPS ON DAY 2 OF LACTATION
8962
NO SURVIVING
PUPS ON DAY I 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 I 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
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008!
COMBINED ORAL (GAVAGE) FERTIBITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE C43 (PAGE 10): AIR RIGHTING - INDIVIDUAL DATA - Fl GENERATION LITTERS
------------------------ --- --------------- -- ---- --- -------------
------- ------------- --------
POSTPARTUM DAY
14
15
16
17
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 I OF LACTATION
---------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTALMEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C44 (PAGE 1): PUPIL CONSTRICTION
- INDIVIDUAL DATA - Fl GENERATION LITTERS
------ -------------------- -- ----------------------
POSTPARTUM
DAY
21
-------------------------------
---------------- -- --
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 1
-------------------------------------------------------
8801
S/ 8
----------------------- ----- --- ---- -------------
- ----------------------- ----------------------------0 (VEHICLE) MG/KG/DAY
-----------------------------------------------------
8803
100.0% 8/ 8
100.0%
8804
S/ 8
100.0%
8805
B/ a
8807
100.Oft 8/ 8
8808
100.0% 8/ 8
8811
100.0% a/ 8
100.0%
8012
8/ 8
8813
100 .op, 8/ 8
8814
100.0% a/ a
8819
100.0% 8/ 8
8821
100.0% 8/ 8
8823
100.01; 8/ 8
8824
ioo.oi; 8/ 8
8826
100.0% 8/ 8
8827
100.0!k 8/ 8
100.0%
8828
8/ 8
100.01---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE C44 (PAGE 2): PUPIL CONSTRICTION - INDIVIDUAL DATA - Fl GENERATION LITTERS
------- ------ --------------------- ----------- --- --------- --------------------------------------------
POSTPARTUM DAY
21
---------------------------------------------------- -----------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
------------------------------------------------------------------------------------------------------------
8830
8/ 8
8831
100.0% 8/ 8
8832
100.0% B/ 8
100.0%
8833
B/ 8
8834
100.0% 8/ 8
8835
100.0% 8/ 8
100.0%
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTALMEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C44 (PAGE 3): PUPIL CONSTRICTION
- INDIVIDUAL DATA - F] GENERATION LITTERS
------- - --- ------ ----------- ------------- - -------------
---------------------------- -----------------
POSTPARTUM
DAY
21
------------------------------------------------------------------------------------------ --------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------------------------------------------- ----------------------------------------------
8838
B/ 8
100.0%
8840
8/ 8
100.0!k
8841
8/ a
100.0%
8842
B/ 8
100.0%
8845
B/ 8
100.0%
8846
8/ 8
100.0%
8847
8/ 8
100.0%
8849
8/ 8
100.0%
8851
8/ 8
100.0%
8852
8/ 8
100.0%
8853
a/ 8
100.0%
8854
B/ a
100.0%
8855
B/ a
100.0!k
8857
8/ 8
100.0%
8858
8/ 8
100.0!k
8860
8/ 8
100.0%
8862
B/ 8
100.0%
8863
8/ a
100.0%
------------------------------------------------------------------------------------------------------
--------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C44 (PAGE 4): PUPIL CONSTRICTION
- INDIVIDUAL DATA - Fl GENERATION LITTERS
---------------------------- ----------------------------------------------------- I ------------ -- ----------
POSTPARTUM
DAY
21
---------------------------- I ----------------------------------------------------------------------------------
MATEPNAL/LITTER
#
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8864
8/ 8
8865
100.0% 8/ 8
100.0%
8866 8867
a/ 8 100.0%
8/ 8
8868
100.0% 8/ 8
8869
100.0% a/ 8
100.0%
8870
8/ 8 100.0%
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C44 (PAGE 5): PUPIL CONSTRICTION
- INDIVIDUAL DATA - PI GENERATION
LITTERS
-------------------- ---- -------------- ------ I - ---------------------------------------------------
POSTPARTUM
DAY
21
----- --------------------------------------------------- I -----------------------------------------------------
MATERNAb/LITTER
#
MATERNAL
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8872
8/ a
100.0*
8874
B/ 8
100.0%
8875
8/ 8
100.0%
8876
6/ 6
100.0%
8881
8/ 8
100.0%
8882
8/ 8
ioo.ot
8885
8/ 8
ioo.oi;
8889
8/ 8
100.0%
8890
a/ 8
100.0%
8891
8/ 8
100.0%
6892
8/ 8
100.0%
8893
6/ 6
100.0%
8894
3/ 3
100.0%
8895
8/ 8
100.0%
8896a
8/ 8
100.0%
8897a
8/ 8
100.0%
8898
8/ 8
100.0!k
8899
7/ 7
100.0%
----------------------------------------------------------------------------------------------------------------
KIN = 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 pu
arbitrarily distributed between the two dams and values will be included in group averages and statistical
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C44 (PAGE 6): PUPIL CONSTRICTION
- INDIVIDUAL DATA - Fl GENERATION LITTERS
--------------------------------- ----------------- ----------- - ---------------------- -------------------
POSTPARTUM
DAY
21
---------------------------------- ----------------------------- ------------------------- -------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
--------------------------------- ----------------------------- ----------------------------------------------
8900
8/ 8
100.0%
8901
8/ a
100.0%
8902
B/ a
100.0%
8905
B/ 8
100.0%
---------------------------------------------------------------------------------------------------------------
NIN - NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER!
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C44 (PAGE 7): PUPIL CONSTRICTION
INDIVIDUAL DATA - Fl GENERATION
LITTERS
------------ ----- ---------------------
POSTPARTUM
DAY
21
----------------
-------- ----------------
--------------------------------------- -------- ------------------- --------- ----------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP IV
1.6 MG/KG/DAY
--------------------------------------- --------------------------- --------------------------
8906
8/ 8
100.0%
8909
8/ a
100.0%
8913
a/ 8
100.0%
8919
S/ 8
100.0%
8920
6/ 6
100.0%
8921
8/ 8
100.0%
8925
7/ 7
100.0%
8926
4/ 4
100.0%
8927
2/ 2
100.0%
8928
B/ 8
ioo.ot
8929
NO SURVIVING
PUPS ON DAY 2 POSTPARTUM
---------------------------------------
8930
8/ 8
8931
100.0% 4/ 4
8932
100.0* 8/ a
8934
100.0% B/ a
8935
100.0% 8/ 8
ioo.ot
8936
NO SURVIVING
PUPS ON DAY 4 POSTPARTUM
---------------------------------------------------------------------------------------------------------------
NIN - NUM13EROF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C44 (PAGE 8): PUPIL CONSTRICTION
- INDIVIDUAL DATA - Fl GENERATION
LITTERS
-------------- ---------------
POSTPARTUM
DAY
21
-- ------------------------------------------
----------------------------------
-M-A-TE-R-N-A-L/-L-I-T-TE-R------# -----MA-T-E-RN-A-L--
------------------------------
8937
8/ 8
D-O-SAG-E---G-R-O-UP----I-V -- ----------1-.-6--M-G-/-KG-/-D-A-Y --------------------------------------------------------------------------------------------------------------------------
8939
100.0% 5/ 5
100.0%
8940
a/ a
100.0%
-----------------------------------------------------------------------------------------------------------------
NIN m NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C44 (PAGE 9@: PUPIL CONSTRICTION
- INDIVIDUAL DATA - Fl GENERATION LITTERS
------------------ ------ - --------------------------------------------- ----------------------------
POSTPARTUM
DAY
21
---------------------------------------------- ----------------------------------------------------------------
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
8942
NO SURVIVING PUPS ON DAY I 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
---------------------------------------------------------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUC71ON
TOXICIT
TABLE C44 (PAGE 10): PUPIL CONSTRICTION
- INDIVIDUAL DATA - PI GENERATION LITTERS
------------------ -- ----- --------------- - -- - - ------------ ---- ---------------------- -
POSTPARTUM
DAY
21
---------------------------- ---------------- - --------- ------------ --------------- ----------- -
MATERNAL/LITTER
#
MATERNAL DOSAGE GROUP V
3.2 MG/KG/DAY
---------------------------- ---------------- -I -----------------------------------------------------
8973
NO SURVIVING PUPS ON DAY 2 OF LACTATION
- --------------------------
8974
NO SURVIVING
PUPS ON DAY I OF LACTATION
8975
NO SURVIVING
PUPS ON DAY I OF LACTATION
----------------------------------------------- ----------------------------------------------------------------
NIN = NUMBER OF PUPS IN EACH LITTER WITH DEVELOPMENTAL MEASURE/TOTAL NUMBER OF PUPS IN THE LITTER
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C45 (PAGE 1): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
PUPS
------- ----------- ----- ---------- --- ------- ---- ----------- I --- -- - -----I ----------- ---------------
MATERNAL
DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS
a
------------------------------------ ---------------------------- ---------------------------------------------
I
0 (VEHICLE)
8801
1
1 PUP: STILLBORN.
ALL TISSUES
4,21
ALL PUPS APPEARED
NORMAL.
8803
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
ALL OTHER TISSUES APPEAR
ALL PUPS APPEARED
NORMAL.
8807
4,21
ALL PUPS APPEARED
NORMAL.
8808
1 4,21
1 PUP: STILLBORN. ALL PUPS APPEARED
ALL TISSUES NORMAL.
Ball 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 ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS
APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED
NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL.
8828
1 4,21
3 PUPS: ALL PUPS
STILLBORN.
ALL
APPEARED
NORMAL.
TISSUES
8830
4,21
ALL PUPS APPEARED
NORMAL.
8831
4,21
ALL PUPS APPEARED
NORMAL.
8832
4,21
ALL PUPS APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation.
individual pup clinical observations table (Table C38) for external clinical observations confirmed at nec
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE C45 (PAGE 2): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
PUPS
--- --------- ------------------ ----
MATERNAL
DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
-------------------------------------
I (Cont.)
0 (VEHICLE)
8833
- -----------
-- ----- ----------- --- -------- ---------------
DAY(S) POSTPARTUM
OBSERVATIONS
a
------------------------------------------------------------------------
1 4,21
1 PUP: FOUND DEAD. ALL TISSUES ALL PUPS APPEARED NORMAL.
8834
1 4,21
1 PUP: FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEAR
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. individual pup clinical observations table (Table C38) for external clinical observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXLCI
TABLE C45 (PAGE 3): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
PUPS
-- ------- -------------------- -----
MATERNAL
DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
-------------------------------------
ii
0.1
8838
--------------- -------------------------------------- -----------------
DAY(S) POSTPARTUM
OBSERVATIONS
a
-------------------------------------------------------------------------
4,21
ALL PUPS APPEARED NORMAL.
8040
1 4,21
1 PUP: FOUND DEAD. ALL TISSUES ALL PUPS APPEARED NORMAL.
8841 6842 8844
4,21 4,21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL. NORMAL.
884S
1 2 4,21
1 PUP: 1 PUP! ALL PUPS
FOUND DEAD. ALL FOUND DEAD. ALL
APPEARED NORMAL.
TISSUES TISSUES
8846 8847 8849
4,21 4,21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL. NORMAL.
8851
1 4,21
1 PUP: FOUND DEAI). ALL TISSUES
ALL PUPS APPEARED
NORMAL.
8852 8BS3 8854 8855 8857
4,21 4,21 4,21
4,21 4,21
ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS
APPEARED APPEARED APPEARED APPEARED APPEARED
NORMAL. NORMAL. NORMAL. NORMAL. NORMAL.
8858
1 4,21
1 PUP: STILLBORN. ALL PUPS APPEARED
NORMAL.
8860
4,21
ALL PUPS APPEARED
NORMAL.
8862
4,21
ALL PUPS APPEARED
NORMAL.
8863
4,21
ALL PUPS APPEARED
NORMAL.
8864
4,21
ALL PUPS APPEARED
NORMAL.
8865
4,21
ALL PUPS APPEARED
NORMAL.
8866
4,21
ALL PUPS APPEARED
NORMAL.
8867
4,21
ALL PUPS APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. individual pup clinical observations table (Table C38) for external clinical observations confirmed at nec
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICIT
TABLE C45 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fl GENERATION PUPS
----------------- --------- -------------------------------------------------------------------------------
MATERNAL DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
----------------------------------------------------------------------------------------------------------------
il (Cont.)
0.1
8868
2
1 PUP: FOUND DEAD. ALL TISSUES
4,21
ALL PUPS APPEARED NORMAL. -
8869
1 4,21
1 PUP: STILLBORN. ALL TISSUES A 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.
individual pup clinical observations table (Table C38) for external clinical observations confirmed at necr
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERI'ILITY, DEVELOPMENTAL
SI'TJDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C45 (PAGE 5): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
PUPS
--------------
MATERNAL
DOSAGE
MATERNAL DOSAGE
---------------III
0.4
----------------------------
GROUP (MG/KG/DAY)
LITTER NUMBER
-----------------------------
8872
--------------------- ----- ------ ---------------------- ----
DAY(S) POSTPARTUM
OBSERVATIONS
a
----------------------------- ----------------------------- ----
1 4,21
1 PUP: STILLBORN. ALL PUPS APPEARED
NORMAL.
8874 8875
4,21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL.
9876
1
21
1 PUP: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES ALL PUPS APPEARED NORMAL.
APPEAR
8881 8882
4,21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL.
8885
1
21
1 PUP: STILLBORN. ALL PUPS APPEARED
ALL TISSUES NORMAL.
8889 8890 8891
4,21 4,21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL. NORMAL.
8892
4
21
ALL PUPS APPEARED NORMAL. 1 PUP: KIDNEYS, RIGHT, PELVIS,
ALL OTHER TISSUES APPEAR ALL OTHER PUPS APPEARED NORMAL.
8893
4
16
17
21
ALL PUPS APPEARED
NORMAL.
1 PUP: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEAR
1 PUP: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEAR
1 PUP: BRAIN, LATERAL VENTRICLE
ALL OTHER TISSUES APPEAR
1 PUP: BRAIN, LATERAL VENTRICLE
ALL OTHER TISSUES APPEAR
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. individual pup clinical observations table (Table C38) for external clinical observations confirmed at nec
PROTOCOL 418-006:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN PATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C45 (PAGE 6): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION PUPS
------- --- ----- ---------------- - ---------- I ----------------------------- ------------------------- -------
MATERNAL
DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS
a
---------------------------------------------------------------------------------------------------------------
III (Cont.)
0.4
8896
4,21
ALL PUPS APPEARED
NORMAL.
8897
4,21
ALL PUPS APPEARED
NORMAL.
8898
1 4,21
1 PUP: STILLBORN.
ALL TISSUES
ALL PUPS APPEARED NORMAL.
8899
13 4,21
1 PUP: FOUND DEAD. ALL TISSUES ALL PUPS APPEARED NORMAL.
8900
1 4,21
1 PUP: STILLBORN. ALL PUPS APPEARED
ALL TISSUES NORMAL.
8901
4,21
ALL PUPS APPEARED NORMAL.
8902
1 4,21
1 PUP: STILLBORN. ALL PUPS APPEARED
ALL TISSUES NORMAL.
8905
4,21
ALL PUPS APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation.
individual pup clinical observations table (Table C38) for external clinical observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE C45 (PAGE 7): NECROPSY OBSERVATIONS
INDIVIDUAL DATA - Fl GENERATION
PUPS
---------------------------------------------
MATERNAL
DOSAGE GROUP
LITTER
- ----- ------------------- ----------------------
------
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
-------------------------------------------------
DAY(S) POSTPARTUM
OBSERVATIONS
a
---------------------------------------------------
----------
IV
1.6
8906
1
1 PUP:
FOUND DEAD.
NO MILK IN S
4,21
ALL OTHER ALL PUPS APPEARED
TISSUES NORMAL.
APPEARE
8909
4,21
ALL PUPS APPEARED
NORMAL.
0913
3 4,21
1 PUP: FOUND DEAD. ALL TISSUES
ALL PUPS APPEARED
NORMAL.
8919
4,21
ALL PUPS APPEARED
NORMAL.
8920
1
2
21
1 PUP:
FOUND DEAD.
NO MILK IN S
ALL OTHER TISSUES
APPEARE
1 PUP:
FOUND DEAD.
NO MILK IN S
ALL OTHER TISSUES
APPEARE
ALL PUPS APPEARED NORMAL.
8921
1 4,21
1 PUP: STILLBORN. ALL OTHER
1 PUP! STILLBORN. ALL PUPS APPEARED
WHOLE BODY ED TISSUES APPEARE
ALL TISSUES A NORMAL.
892S
2
10 4,21
1 PUP:
FOUND DEAD.
NO MILK IN S
ALL OTHER TISSUES
APPEARE
1 PUP: FOUND DEAD. ALL TISSUES
ALL PUPS APPEARED
NORMAL.
8926
2
5 PUPS: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEAR
3
1 PUP:
FOUND DEAD.
NO MILK IN S
ALL OTHER TISSUES
APPEARE
21
ALL PUPS APPEARED
NORMAL.
----------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation.
individual pup clinical observations table (Table C38) for external clinical observations confirmed at necr(
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL REPRODUCTION
TOXICI
TABLE C45 (PAGE 8): NECROPSY OBSERVATIONS
-------------- - --- -------- ----------- -
MATERNAL
DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
-----------------------------------------
IV (Cont.)
1.6
8927
INDIVIDUAL DATA - Fl GENERATION
PUPS
------------------------- ------------- -- ------ --- ---------
DAY(S) POSTPARTUM
OBSERVATIONS
a
----------------------------------------------------------------
2
4 PUPS: FOUND DEAD. NO MILK IN
1 PUP: FOUND DEAD. ALL TISSUES
3
3 PUPS:
FOUND DEAD.
ALL TISSUE
5
4 PUPS:
FOUND DEAD.
NO MILK IN
ALL OTHER TISSUES APPE
21
ALL PUPS APPEARED
NORMAL.
8928
4,21
ALL PUPS APPEARED
NORMAL.
8930
1 4,21
4 PUPS:
I PUP: ALL PUPS
FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEA
FOUND DEAD. ALL TISSUES
APPEARED
NORMAL.
8931
1
21
1 PUPS: 6 PUPS: ALL PUPS
FOUND DEAD. ALL TISSUE
FOUND DEAD. NO MILK IN
APPEARED
NORMAL.
8932
2
1 PUP: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEAR
3
2 PUPS: FOUND DEAD. ALL TISSUE
4,21
ALL PUPS APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation.
individual pup clinical observations table (Table C38) for external clinical observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PPOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C45 (PAGE 9): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA
Fl GENERATION
PUPS
-- -------------------- -- --------------------------
MATERNAL
DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
DAY(S) POSTPARTUM
----- --- ----------------------- - ---------------------------
IV (Cont.)
1.6
8934
1
4,21
-------------------------- -------------
OBSERVATIONS
a
--------------------------------------------
2 PUPS: ALL PUPS
FOUND DEAD. ALL TISSUE
APPEARED
NORMAL.
8935
4 4,21
1 PUPS: FOUND DEAD. ALL TISSUE
ALL PUPS APPEARED
NORMAL.
8936
1
1 PUP: STILLBORN.
ALL TISSUES
4 PUPS:
FOUND DEAD. NO MILK PR
ALL OTHER TISSUES APPEA
2
2 PUPS:
FOUND DEAD. NO MILK PR
3
2 PUPS:
FOUND DEAD. NO MILK PR
ALL OTHER TISSUES APPEA
4
6 PUPS:
FOUND DEAD.
NO MILK PR
ALL OTHER TISSUES APPEA
8937
1
21
8939
1
21
2 PUPS: ALL PUPS
STILLBORN.
ALL
APPEARED NORMAL.
TISSUES
2 PUPS: 6 PUPS:
ALL PUPS
FOUND FOUND
DEAD. DEAD.
ALL TISSUE NO MILK IN
ALL OTHER TISSUES
APPEARED
NORMAL.
APPEA
8940
1
1 PUP: FOUND DEAD. ALL TISSUES
I PUP: STILLBORN.
ALL TISSUES
4,21
ALL PUPS APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. individual pup clinical observations table (Table C38) for external clinical observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RAT@; (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE C4S (PAGE 10): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
PUPS
- ---------------------------
MATERNAL
DOSAGE GROUP
MATERNAL DOSAGE (MG/KG/DAY) --------------------------- -
v
3.2
L@-IT-T-ER----- -----------
--- * --------------------------------------------------
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS
a
-------------------------- ---------------------------------------------------
8942
1
6 PUPS:
FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEI
8943
1
4 PUPS: 2 PUPS:
STILLBORN. FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEA
8944
1
2 PUPS: 3 PUPS:
STILLBORN. FOUND DEAD.
NO MILK IN
8946
1
2
3 PUPS: 7 PUPS:
FOUND DEAD. ALL TISSUE FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEP
8949
2
9 PUPS:
FOUND DEAD.
ALL TISSUE
8950
1
2 PUPS: 4 PUPS:
STILLBORN. FOUND DEAD.
8955
1
2 PUPS: 7 PUPS:
STILLBORN.
ALL TISSUES
FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEA
8956
1
1 PUP: FOUND DEAD. NO MILK IN
BOTH HINDLIMBS,
MISSING;
MISSING.B
ALL OTHER TISSUES APPEAR
I PUP: FOUND DEAL). ALL TISSUES
2
11 PUPS: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEA ----------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation.
individual pup clinical observations b. Presumed cannibalized by dam.
table (Table C38) for external clinical observations
confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE C45 (PAGE 11): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - Fl GENERATION PUPS
------------------------------------ ---------------------------------- --------------------- ------------
MATERNAL DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
--------------------------------------------- --------------------------------------------------------------
V (Cont.)
15
8959
1
3 PUPS: STILLBORN. ALL TISSUES
2 PUPS: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEA
2
8 PUPS: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEA
8960
1
9 PUPS: 4 PUPS:
STILLBORN. ALL TISSUES FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEA
8961
1
2
3 PUPS: STILLBORN. ALL TISSUES I PUP: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEAR 8 PUPS: FOUND DEAD. NO MILK IN
PORTION OF TAIL, MISSIN ALL OTHER TISSUES APPEA
8962
1
3 PUPS: I PUP:
STILLBORN. ALL TISSUES FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEAR
8964
1
2
1 PUP: I PUP:
5 PUPS:
STILLBORN. ALL TISSUES I FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEAR
FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEAE
8967
1
8 PUPS: STILLBORN. ALL TISSUES
8968
1
2
6 PUPS: 2 PUPS:
1 PUP:
STILLBORN. ALL TISSUES FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEAR FOUND DEAD. NO MILK IN S
ALL OTHER TISSUES APPEARE ----------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation.
individual pup clinical observations table (Table C38) for external clinical observations confirmed at necr b. Presumed cannibalized by dam.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE C45 (PAGE 12): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
PUPS
--------
----------------------------
MATERNAL
MATERNAL ---------
DOSAGE GROUP
LITTER
DOSAGE (MG/KG/DAY)
NUMBER
----------------------------
V (Cont.)
3.2
8969
----------------------- --- ----------------------------- ----------
DAY(S) POSTPARTUM
OBSERVATIONS
a
------------------------ --- ------------------------------ ----------
1
4 PUPS: FOUND DEAD. NO MILK--It
ALL OTHER TISSUES APPE
8970
1
2
2 PUPS: 9 PUPS:
STILLBORN.
ALL TISSUES
FOUND DEAD. NO MILK It
ALL OTHER TISSUES APPEI
8971
2
6 PUPS:
FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPE;
8973
1
1 PUP: 9 PUPS:
STILLBORN.
ALL TISSUES
FOUND DEAD. No MILK IN
ALL OTHER TISSUES APPE;
8974
1
3 PUPS: 8 PUPS:
STILLBORN. FOUND DEAD.
ALL TISSUES ALL TISSU
8975
1
12 PUPS: FOUND DEAD. NO MILK IN
ALL OTHER TISSUES APPEAR ---------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation.
individual pup clinical observations table (Table C38) for external clinical observations confirmed at nec
APPENDIX D REPORT TABLES -Fl GENERATION
MALE RATS
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE Dl (PAGE 1): CLINICAL OBSERVATIONS
- SUMMARY - Fl GENERATION MALE RATS
--------- - - - - ----------- -- - -- -- ---- ---- -----
---- ----------- - -- -- -----------------
DOSAGE GROUP
I
ii
III
DOSAGE (MG/KG/DAY) ------------
----------- ---
0 (VEHICLE) 0.1
0.4
-- ------- --------------------------------------- - -----------------------
MAXIMUM POSSIBLE INCIDENCE
2207/ 25 2196/ 25 221S/ 25
FOUND DEAD
2a,b
lc
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
SO/ 4
38/ 1
BASE OF TAIL: LACERATION
0/ 0
0/ 0
11/ 1
SNOUT:
SWOLLEN
0/ 0
8/ 2
3/ 1
RED PERIORAL SUBSTANCE
o/ o
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 o/ o
66/ 4 16/ 3** 29/ 1 24/ 1
0/ 0 0/ 0 0/ o 0/ 0
BACK: SCAB
14/ 1
B/ 2
0/ 0
URINE-STAINED
ABDOMINAL
FUR
0/ 0
4/ 1
0/ o
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
NIN = TOTAL NUMBER OF OBSERVATIONS/NUMBER
OF RATS WITH OBSERVATION.
a. Rat 13105 was found dead on day 67 postweaning.
PER GROUP.
b. Rat 13116 was found dead on day 06 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<0.01).
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) FERTILITY,
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AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE DI (PAGE 2): CLINICAL OB@';ERVATIONS - SUMMARY - Fl GENERATION MALE RATS
DOSAGE DOSAGE
-------------GROUP (MG/KG/DAY)
MAXIMU-M---P-O-S-S-IB-LE ---I-N-C-ID-E-N-C-E ------
---- -- ---------------- --- ----------------- - - -- -------------------
1
11
111
0 (VEHICLE) 0.1
0.4
----------------------------------------------- ---------------------------
2207/ 25 2196/ 25 2215/ 25
FOUND DEAD
2a,b
lc
0
EARS:
SWOLLEN AND PURPLE
9/ 1
0/ 0
0/ 0
PALES
2/ 1
0/ o
0/ 0
GASPING
1/ 1
0/ 0
0/ 0
EXCESS SALIVATION
1/ 1
0/ 0
0/ 0
EYES: DILATED PUPIL
1/ 1
0/ o
0/ 0
--------------------------------------------------------------------------------------------------------------
STATISTICAL
ANALYSES OF CLINICAL OBSERVATION
DATA
MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER
WERE RESTRICTED OF RATS EXAMINED
TO THE NUMBER PER GROUP.
OF RATS WITH OBSERVATIONS.
NIN = TOTAL NUMBER OF OBSERVATIONS/NUMBER
OF RATS WITH
a. Rat 13105 was found dead on day 87 postweaning.
OBSERVATION.
b. Rat 13116 was found dead on day 86 postweaning.
c. Rat 13138 was found dead on day 66 postweaning.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D2 (PAGE 1): BODY WEIGHTS - SUMMARY
Fl GENERATION
MALE RATS
---------- - --- ------ ------- ------ ------
-------------
DOSAGE GROUP
11
DOSAGE (MG/KG/DAY) ----------
0 (VEHICLE)
0.1
----- ---------------------------- ----------------------------
RATS TESTED N 25 25
BODY WEIGHT (C)
------------------- - ------- ---111 0.4
------------------------------------
25
DAY
1
DAY
a
MEAN+S.D. MEAN+S.D.
54.0 +
5.8
101.6 + 10.3
52.1 + 98.2 +
5.3 8.1
50.8 + 4.9
1 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 DAY 36
MEAN+S.D. MEAN+S.D.
285.0 + 21.1 338.2 + 25.6
279.4 + 17.2 334.7 + 20.9
277.2 21.0 332.4 + 22.8
DAY 43
MFAN+S.D.
381.1 + 30.3
377.9 + 21.6
373.3 + 26.2
DAY 50 DAY 57
MEAN+S.D. MEAN+S.D.
420.5 + 33.4 448.4 + 34.2
414.0 + 25.3 437.0 + 29.5
410.6 32.9 436.8 + 37.4
DAY 64
MEAN+S.D.
472.2 + 36.9
465.1 + 34.3
462.6 44.0
PRECOHABITATION
b
MEAN+S.D.
TERMINAL
BODY
508.6 + 42.8
499.2 + 39.0 24]C
494.8 + si.1
WEIGHT d
MEAN+S.D.
542.0 + 50.9 [ 23)C
533.0 + 43.6 ( 24]c
522.3 + 54.6
---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEAMING
II a. b-
= NUMBER Excludes
OF VALUES AVERAGED values that were not recorded.
Precohabitation body weights were recorded rats were 85 to 97 days of age.
on the day that cohabitation
began for the Fl generation rats; a
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.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D3 (PAGE 1): BODY WEIGHT CHANGES
SUMMARY - Fl GENERATION
MALE RATS
------------------ ------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) --------------- ---- -----------------
RATS TESTED
N
0 ------
--------------------
I (VEHICLE) --------------------
25
ii 0.1
25
-------------------- --- ---------
III
0.4 ---------------------
-------------
25
BODY WEIGHT CHANGE (G)
DAYS
1
8
DAYS 8
15
MEAN4S.D. MEAN+S.D.
+47.7 + 5.5 +60.2 + 6.8
446.1 + 3.9 *58.0 + 5.3
+46.5 [
+58.1
+ 4.8 231a
+ 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
459.7 + 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 + 0.5
+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 4 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
MEAN+S.D.
DAY 1 -
+454.6 + 40.7
+447.1 + 36.5
( 24]c
+443.5 + 51.4
I 23]a
TERMINATION d
MEAN+S.D.
+488.0 + 48.6
+480.9 + 41.2
+471.2 + 55.3
f 23)C
[ 24]C
I 23]a
----------------------------------------------------------------------------------------------------------------
DAY(S) = DAY(S) POSTWEANING
( I = 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 Fl generation rats; a 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.
PROTOCOL 418-008:
COMBINED ORAL IGAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/ POSTNATAL
REPRODUCTION
TOXI
TABLE D4 (PAGE 1): ABSOLUTE FEED CONSUMPTION
VALUES (G/DAY) - SUMMARY - Fl GENERATION MALE RATS
--------- - -----------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ----------
- -----------RATS TESTED
---------------------- - -
I
0 (VEHICLE@
-------------------------- --
N
25
------------ ------------- ---------------
ii
III
0.1
0.4
------------------------------------------
25
25
-------------------
FEED CONSUMPTION
IG/DAY)
DAYS 1 - 8
MEAN+S.D.
14.7 + 1.5
13.8 + 1.3*
13.4 + 2.9**
DAYS 8 - 15
MEAN+S.D.
21.7 + 1.5
22.1 + 2.3
20.8 + 3.2
DAYS 15 - 22 DAYS 22 - 29
MEAN+S.D. MEAN+S.D.
26.0 + 2.2 ( 24]a
28.8 + 2.0
25.8 + 1.4 29.2 + 1.6
25.4 + 1.7 28.5 + 2.3
DAYS 29 - 36
MEAN+S.D.
30.3 + 3.5
30.0 + 3.1
29.9 + 2.3
DAYS 36 - 43
MEAN+S.D.
32.2 + 2.8
32.6 + 2.9
31.7 + 2.6
DAYS 43 - 50
DAYS 50 - 57
MEAN+S.D.
MEM+S.D.
32.4 + 3.4
( 24]a 32.3 + 2.8
33.0 + 3.3
[ 24]a 31.7 + 2.2
31.7 + 3.1
31.5 + 3.1
DAYS 57 - 64b DAYS 1 - 64b
MEAN+S.D. MEAN+S.D.
30.5 + 2.7 1 22)a
27.3 + 1.7 1 22]a
30.2 + 4.1 27.6 + 1.5
30.9 + 3.2 27.1 1.9
--------------------------------------------------------------------------------------------------------------
DAYS = DAYS POSTWEANING
I I = 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).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
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AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D5 (PAGE 1): RELATIVE FEED CONSUMPTION
VALUES (G/KG/DAY) - SUMMARY - Fl GENERATION
MALE RATS
-------------- ----------- - ----------- 11 -------------
DOSAGE GROUP
I
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
-------------------------------------------------------
RATS TESTED
N
25
-------------- --------------------------
ii
0.1
0.4
-----------------------------------------
25
25
--------- ---------
FEED CONSUMPTION
(G/KG/DAY)
DAYS
1
8
DAYS
8
15
MEAN+S.D. MEAN+S.D.
189.9 + 17.6 165.5 + 11.0
184.9 + 17.8 174.5 + 16.3
183.6 + 38.1 [ 23)a
166.4 + 23.9
DAYS 15
22
DAYS 22
29
MEAN+S.D. MFAN+S.D.
135.6 + 7.2 ( 24)b
113.5 + 5.4
137.6 + 7.1 117.1 + 4.6*
137.3
7.6
115.3 + 4.8
DAYS 29
36
MEAN+S.D.
97.3 + 8.9
97.7 + 8.1
98.1 + 4.2
DAYS 36
43
MEAN+S.D.
89.6 + 6.2
91.4 + 6.9
90.0 + 6.6
DAYS 43
50
DAYS 50 - S7
MEAN+S.D. MEAN+S.D.
80.7 + 5.5 24]b
74.5 + 4.6
83.4 + 7.6 24]b
74.7 + 4.1
80.9
6.0
74.2 + 3.8
DAYS 57 - 64C
MEAN+S.D.
67.2 + 4,7 [ 22]b
67.1 + 8.4
68.6 + 3.8
DAYS
I - 64C
MEAN+S.D.
96.2 + 4.1
97.4 + 3,8
96.6 + 3.6
[ 22]b
[ 23]b
----------------------------------------------------------------------------------------------------------------
DAYS = DAYS POSTWEANING
I I = 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@0.05).
PROTOCOL 418-008:
COMBINED
ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295 9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D6 (PAGE 1): SEXUAL MATURATION
- SUMMARY - Fl GENERATION MALE RATS
--------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ----------- ----------------------
14ALE RATS
N
- ----------------- -
-- -- ---------------------- --------------
I
ii
III
0 (VEHICLE)
0.1
0.4
- - ------------------- - ----------------------------------------------
25
25
25
PREPUTIAL
SEPARATION
a MEAN+S.D.
45.0 + 2.1
--------------------------------------------------------------a. Average day postpartum that the prepuce was observed to be
45.7 + 2.3
45.1 + 1.8
---------------------------------------------separated.
PROTOCOL 418-008:
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ORAL (GAVAGEI FERTILITY,
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PFOS IN RA'rs (SPONSOR'S STUDY NUMBER:
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AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D7 (PAGE 1): PASSIVE AVOIDANCE PERFORMANCE
SUMMARY - Fl GENERATION
MALE RATS
------------------- --------DOSAGE GROUP DOSAGE (MG/KG/DAY)
----------------------------MALE RATS
----
---------------- - ----
I 0 (VEHICLE) ----------------- -----
------------------ ------- - ---------- I
ii
III
0.1
0.4
---------------------------------------
---- --------------
SESSION la N 23 25 22
TRIALS LATENCY LATENCY FAILED
TO CRITERION TRIAL lb TRIAL 2b
TO LEARN c
MEAN+S.D. MEANS.D. MEAN+S.D.
N(t)
4.8 8.9 21.4
0(
+ 1.0 + 5.0 15.8 0.0)
6.1 7.8 20.1
1(
+ 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
MEAN+S.D.
3.3 + 2.6
3.6 + 2.2
3.5
LATENCY TRIAL lb
MEAN+S.D.
32.8 + 22.2
28.2 23.5
33.1
------------------------------------------------------------------------------------------------
a. Sessions I (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week b. The latency was recorded in seconds.
+ 2.7
-+ 22.4 7 -------------
interval.
C. Number of rats that did not meet the criterion in session 1 (Learning Phase).
PROTOCOL 418-008:
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PPOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D8 (PAGE 1): WATERMAZE
PERFORMANCE
- SUMMARY - Fl GENERATION.MALE
RATS
--------------------------DOSAGE GROUP DOSAGE (MG/KG/DAY) ---------------------------
MALE RATS
-------------
---------- - I --------
------------ ------------- ----
1
11
0 (VEHICLE)
0.1
--------------------------------------------------------
------- --------111 0.4
------------------
SESSION la
N
23
25
21
TRIALS ERRORS LATENCY FAILED
TO CRITERION PER TRIAL
TRIAL 2b TO LEARN c
MEAN+S.D. MEAN+S.D. MEAN+S.D.
N(t)
9.1 0.37
11.7 0(
+ 3.1 + 0.17 + 7.4 0.0)
9.4 0.40 13.7
2(
+ 3.0 0.24 + 13.9 8.0)
9.0 0.43 10.6
0(
+ 3.0 0.22 + 6.0 @.0)
SESSION 2a N 23 23 21
TRIALS ERRORS LATENCY
TO CRITERION PER TRIAL
TRIAL lb
MEAN+S.D. MEAN;S.D. MEAN+S.D.
6.4 + 0.12 + 10.3 +
2.6 0.20 8.3
6.3 + 0.08 + 9.1
1.9 0.11 6.5
5.5 + 0.09 10.7 +
0.9 0.15 6.7
---------------------------------------------------------------------------------------------------------------
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. Number of rats that did not meet the criterion in Session 1 (Learning Phase); Session 2 (Retention Phase) rats were excluded from group averages and statistical analyses.
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) FERTILRTY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D9 (PAGE 1): MATING AND FERTILITY - SUMMARY - Fl GENERATION MALE PATS
---------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY)
---------------- ---------------------
RATS IN COHABITATION
N
------
0 -------
---------------- ---------- --------
I
ii
(VEHICLE)
0.1
---------------------- ---------------
--------------- --------III 0.4
-------------------------
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(l)
20( 87.0)
22( 91.7)
25(100.0)
FERTILITY INDEX e,f
NIN (t)
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(t)
20(100.0)
22( 92.0)
25(100.0)
RATS PREGNANT/RATS
IN
COHABITATION
g
NIN
19/23
20/24
24/25
(t)
82.6)
83.3)
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY.
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERrNATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D10 (PAGE 1): NECROPSY OBSERVATIONS
- SUMMARY - Fl GENERATION MALE RATS
---------------------------------------DOSAGE GROUP DOSAGE (MG/KG/DAY)
I ------------ - ---I
0 (VEHICLE)
-----------ii
0.1
-------
----------------
III 0.4
---
------
-------------------------------------- --------------- --------------------------------------------------------
RATS EXAMINED a N 25 25 25
FOUND DEAD N 2b,c Id 0
APPEARED
NORMAL
N
23
21d
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 1 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 necr 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).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATALIPOSTNATAL
REPRODUCTION
TOXIC
TABLE D10 (PACE 2): NECROPSY OBSERVATIONS
SUMMARY - Fl GENERATION
MALE RATS
---------------------
DOSAGE GROUP DOSAGE (MG/KG/DAY) -----------------------------
RATS EXAMINED a
------------- ------ ------- ----------------
I
ii
---
0 (VEHICLE)
0.1
----------- --- ------------------------
N
25
25
----------------------- --------
0.4 --------------------------------
25
FOUND DEAD N 2b,c id 0
URINARY BLADDER:
WALLS, THICKENED
AND
NUMEROUS
CALCULI
N
0
1
0
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 Ic 0 0
--------------------------------------------------------------------------------------------------------------a. Refer to the individual clinical observations table (Table D13) for external observations confirmed at nec 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.
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TABLE Dll (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS - SUMMARY - Fl GENERATION MALE PATS
---------------------------------------------- --
DOSAGE GROUP DOSAGE (MG/KG/DAY)a
I 0 (VEHICLE)
------------------------------------------------- --
RATS TESTED
N
25
---------- ------------------ -----------------------
ii
0.1
0.4
-------------------------------------------------------
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 WITHOUT
VESICLES 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 1 2i]b
1.80 + 0.16 i 23]b
1.72 + 0.24 [ 22]b
1.05 + 0.19
0.63 + 0.04 1.79 + 0.12
1.62 + 0.20 I 24]b
0.96 + 0.15
EPIDIDYNIS RIGHT TESTIS RIGHT PROSTATE ALL WEIGHTS WERE
RECORDED
MEAN+S.D.
0.67 + 0.06
0.66 + 0.05
0.64 + 0.04
[ 21]b
MEAN+S.D.
1.78 + 0.18
1.79 + 0.15
1.82 + 0.12
MEAN+S.D.
0.93 + 0.19
1 21]b 0.91 + 0.22
0.89 + 0.19
---------------------------------------------------------------------------------IN GRAMS (G).
t I = 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).
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TABLE D12 (PAGE 1): RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY WEIGHT
SUMMARY - Fl GENERATION
MALE RATS
---------- ----------- ---DOSAGE GROUP DOSAGE (MG/KG/DAY)a ---------------------------
- ---- ---- ---------
---- -----------
I
0 (VEHICLE) ----------------
- -------------------
ii 0.1
------ ---------------------- 0.4
RATS TESTED
- --------------- ---------------------------------- N 25 25 25
INCLUDED IN ANALYSES
N
23a
24a
25
TERMINAL BODY WEIGHT
EPIDIDYMIS
LEFT
TESTIS LEFT
SEMINAL VESICLES WITH FLUID
SEMINAL WITHOUT
VESICLES FLUID
MEAN+S.D. MEAN+S.D. MEAN+S.D.
MEAN+S.D.
MEAN+S.D.
542.0 + 50.9 0.124 + 0.017 0.329 + 0.041
0.325 + 0.068
0.193 + 0.037
533.0 + 43,6
0.122 + 0.014 [ 23]b
0.332 + 0.043 ( 23]b
0.325 + 0.055 ( 22]b
0.198 + 0.037
522.3 + 54.6 0.121 + 0.014 0.346 + 0.037
0.316 + 0.055 ( 24]b
0.184 + 0.032
EPIDIDYMIS
RIGHT
MEAN+S.D.
TESTIS RIGHT
MEAN+S.D.
PROSTATE
MEAN+S.D.
------------------------------
0.124 + 0.016 0.331 + 0.043 0.172 + 0.035
0.125 + 0.012 [ 21]b
0.339 + 0.042 [ 21]b
O@171 + 0.043
0.122 + 0.015 0.351 + 0.037 0.170 + 0.035
ALL WEIGHTS [ I = NUMBER
WERE RECORDED IN G-R-AM-S----(G-)-.-------------------------------------------------------------------------
OF VALUES AVERAGED
PATIOS (t) = (ORGAN WEIGHT/TERMINAL
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).
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TOXICI
TABLE D13 (PACE 1): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION MALE RATS
------------- ------ --------------
DOSAGE GROUP 1
0
----- ------ ---------- ---- --- -- -----------(VEHICLE) MG/KG/DAY
--- -
------------------
------------------ ---------------- -----------------------------
RAT #
DESCRIPTION
---------------------------------------------
-------------------- ------------------------------------------------------------------------------------------
13101
NO ADVERSE FINDINGS
13102
NO ADVERSE FINDINGS
13103
NO ADVERSE FINDINGS
13104
NO ADVERSE FINDINGS
13105
DP(
87
FOUND DEAD
13106
DP( 52- 65)
BACK: SCAB (1-0 CM IN DIAMETER)
DP(
66
SCAB HEALED
13107
NO ADVERSE FINDINGS
13108 13109
DP( 81- 89)
EARS: SWOLLEN AND PURPLE a NO ADVERSE FINDINGS
13110
DP( 32- 33)
INCISORS:
MISALIGNED
DP(
34 )
INCISORS:
REALIGNED
DP( 32- 89)
CHROMODACRYORRHEA
a
DP( 38- 89)
INCISORS:
MISALIGNED
a
13111
NO ADVERSE FINDINGS
13112
NO ADVERSE FINDINGS
13113
NO ADVERSE FINDINGS
13114
NO ADVERSE FINDINGS
13115
NO ADVERSE
FINDINGS
13116
DP( 67- 72)
CHROMORHINORRHEA
DP(
79
CHROMORHINORRHEA
DP(
86
FOUND DEAD
13117
NO ADVERSE FINDINGS
13118
DP( 68- 76)
INCISORS:
MISSING/BROKEN
DP(
77
INCISORS:
GROWN IN
13119
NO ADVERSE FINDINGS
13120
NO ADVERSE FINDINGS
13121
NO ADVERSE FINDINGS
13122
DP( 55- 87)
INCISORS:
MISALIGNED
a
DP( 80- 85)
LOCALIZED ALOPECIA:
LIMBS
DP(
86 )
ALOPECIA NO LONGER APPARENT
DP( 84- 87)
INCISORS:
MISSING/BROKEN
a
13123
NO ADVERSE FINDINGS
13124
DP(
81
EYES: DILATED PUPIL
DP(
81
EXCESS SALIVATION
DP(
81
GASPING
DP( 81- 82)
RALES
13125
NO ADVERSE FINDINGS
----------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
a. Observation confirmed at necropsy.
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TABLE D13 (PAGE 2): CLINICAL OBSERVATIONS
INDIVIDUAL DATA - Fl GENERATION
MALE RATS
------------- --------------- DOSAGE GROUP 11
--------------------------------RAT #
----------
----------------------- ----------------------- --- -----------0.1 MG/KG/DAY ----------- ------------------------- --
-------------------------------------
DESCRIPTION
---------------------------------------------------------------------
13126 13127 13128 13129
13130 13131
DP( 43- 46)
DP(
47
DP( 40- 49)
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
INCISORS: INCISORS:
MISSING/BROKEN GROWN IN
NO ADVERSE
FINDINGS
BACK: ABRASION (1.5 CM X 0.5 CM)
DP( SO- 51)
BACK: SCAB (0.5 CM IN DIAMETER)
DP(
52 )
SCAB HEALED
DP( 52- 53)
LOCALIZED ALOPECIA:
BACK
DP(
54 )
ALOPECIA NO LONGER APPARENT
DP( 73- 74)
CHROMORHINORRHEA
DP( 73- 75)
CHROMODACRYORRHEA
DP( 73- 87)
INCISORS:
MISSING/BROKEN
DP(
88
INCISORS:
GROWN IN
DP(
80
CHROMORHINORRHEA
13132
DP( 82- 89)
INCISORS:
MISALIGNED a
NO ADVERSE FINDINGS
13133
DP( 52- 70)
LOCALIZED ALOPECIA:
LIMBS
DP(
71 )
ALOPECIA NO LONGER APPARENT
DP( 71- 82)
LOCALIZED ALOPECIA:
BACK
DP(
83 )
ALOPECIA NO LONGER APPARENT
13134
DP( 80- 89)
LOCALIZED NO ADVERSE
ALOPECIA: FINDINGS
LIMBS a
13135
NO ADVERSE FINDINGS
13136
NO ADVERSE
FINDINGS
13137 13138
DP(
66
NO ADVERSE FOUND DEAD
FINDINGS
13139 13140
NO ADVERSE NO ADVERSE
FINDINGS FINDINGS
-----------------------------------------
---------------------------------------------------------------------------------------------------------------DP = DAY POSTWEANING
a. Observation confirmed at necropsy.
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TOXIC
TABLE D13 (PAGE 3): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION MALE RATS
--- ------------------- ---- ----- -----------
DOSAGE GROUP 11
0.1 MG/KG/DAY
----------------------------------- ---------------
RAT #
DESCRIPTION
------ --------- --
---------------------- --- -
- ---------------------- -------------------------------
----------------------------------- ---------------- ---------------------------------------------------------
13141
DP( 32- 34)
CHROMORHINORRHEA
DP( 32- 36)
SNOUT:
SWOLLEN
DP(
37 )
SWELLING RESOLVED
DP( 32- 46)
CHROMODACRYORRHEA
DP( 37- 41)
INCISORS:
MISSING/BROKEN
DP(
42 )
INCISORS:
GROWN IN
DP( 51- 64)
INCISORS:
MISALIGNED
DP(
65
INCISORS:
REALIGNED
DP(
62
CHROMODACRYORRHEA
DP( 64- 67)
CHROMODACRYORRHEA
DP( 75- 88)
INCISORS:
MISALIGNED a
DP( 85- 88)
INCISORS:
MISSING/BROKEN
a
13142
DP(
51
CHROMODACRYORRHEA
DP(
51
CHROMORHINORRHEA
DP(
51
PERIORAL SUBSTANCE
DP( 51- 53)
SNOUT:
SWOLLEN
DP(
54 )
SWELLING RESOLVED
DP( 51- 78)
INCISORS:
MISALIGNED
DP(
79 )
INCISORS:
REALIGNED
DP( 81- 88)
INCISORS:
MISALIGNED a
13143
DP( 19- 22)
URINE-STALNED
ABDOMINAL
FUR
13144
DP( 39- 50)
BACK: ABRASION (1.5 CM X 0.5 CM)
DP(
51
ABRASION NO LONGER APPARENT
DP(
43
CHROMORHINORRHEA
DP( 51- 52)
LOCALIZED ALOPECIA:
BACK
DP(
S3
ALOPECIA NO LONGER APPARENT
DP(
65
CHROMORHINORRHEA
DP( 65- 79)
INCISORS:
MISSING/BROKEN
DP(
so )
INCISORS:
GROWN IN
13145
DP( 40- 44)
INCISORS:
MISSING/BROKEN
DP(
45
INCISORS:
GROWN IN
13146
DP(
21
SOFT OR LIQUID FECES
---------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
a. Observation confirmed at necropsy.
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TABLE D13 (PAGE 4): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
MALE RATS
-----
--------------------- -- - ----------- ------
DOSAGE GROUP 11
0 1 MG/KG/DAY
- -- ----------------------- - ------------------------
RAT #
DESCRIPTION
---------------------------------
-------------------------
--------------- ------------------
--------------------------- - ------------------------------------------------------- ------------------
13147 13148
DP( DP( DP( DP( DP( DP( DP( DP( DP( DP( DP( DP(
53 ) 53- 74)
7S ) S3- 88) 60- 73) 63- 71)
72 ) 63- 86)
87 ) 78- 88) 29- 58)
59 )
CHROMODACRYORRHEA
INCISORS:
MISSING/BROKEN
INCISORS:
GROWN IN
INCISORS:
MISALIGNED a
CHROMODACRYORRHEA
CORNER OF LEFT EYE:
ABRASION
HEALED
ABRASION
LOCALIZED ALOPECIA:
HEAD
ALOPECIA
NO LONGER APPARENT
CHROMODACRYORRHEA
a
LEFT SIDE OF BACK; ABRASION HEALED
ABRASION
(1-0 CM IN DIAMETER)
13149
DP( DP( DP( DP( DP( DP( DP( DP(
29- SS) 51- 58) 59- 64)
65 ) 59- 64)
65 ) 4- 9)
10
RIGHT SIDE OF BACK: ABRASION (l.S CM X 1.0 CM)
LEFT SIDE OF BACK: ABRASION (0-5 CM IN DIAMETER)
BACK: SCAB SCAB HEALED
(0.5 CM IN DIAMETER)
RIGHT SIDE OF BACK: SCAB HEALED
SCAB (0-5 CM IN DIAMETER)
INCISORS: INCISORS:
MISSING/BROKEN GROWN IN
13150
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANIN(3
a. ObBervation confirmed at necropsy.
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TABLE D13 (PAR.E S): CLINICAL OBSERVATIONS
- INDIVIDUAL DA-I'A - Fl GENERATION MALE RATS
---- --- ----------------------
DOSAGE GROUP 111 -------------------------------
- - ----------------- --
0.4 MG/KG/DAY ------ ---------------- ---
----- ----------------- -- ------------------------------------------ --- --------------------
RAT #
DESCRIPTION
------------------------------- ---------------------------- -------------------------------------------------
l3lSl
NO ADVERSE FINDINGS
13152
DP( 10- 20)
TAIL:
LACERATION
(5.0 CM FROM BASE)
13153
DP( 62- 91)
INCISORS:
MISALIGNED a
13154
DP( 52- 67)
RIGHT SIDE OF HEAD: ABRASION (1.5 CM IN DIAMETER)
DP(
68
ABRASION HEALED
DP(
82
CHROMORHINORRHEA
1315S
DP(
54
CHROMORHINORRHEA
DP(
54
RED PERIORAL SUBSTANCE
DP( 54- 56)
SNOUT:
SWOLLEN
DP(
57 )
SWELLING RESOLVED
DP( 54- 91)
CHROMODACRYORRHEA
a
DP( 54- 91)
INCISORS:
MISALIGNED
a
DP( 78- 91)
INCISORS:
MISSING/BROKEN
a
13156
NO ADVERSE FINDINGS
13157
NO ADVERSE FINDINGS
13158
NO ADVERSE FINDINGS
13159
DP( 35- 50)
LEFT FORELIMB:
ABRASION
DP(
51 )
ABRASION NO LONGER APPARENT
13160
DP( 64- 89)
INCISORS:
MISALIGNED
a
13161
NO ADVERSE FINDINGS
13162
NO ADVERSE FINDINGS
13163
NO ADVERSE FINDINGS
13164
NO ADVERSE FINDINGS
13165
NO ADVERSE FINDINGS
13166
NO ADVERSE FINDINGS
13167
NO ADVERSE FINDINGS
13168
NO ADVERSE FINDINGS
13169
NO ADVERSE FINDINGS
13170
NO ADVERSE FINDINGS
13171
DP( 81- 82)
RED SUBSTANCE:
PENIS
13171
DP( 81- 82)
RED SUBSTANCE:
PENIS
DP(
84 )
CHROMORHINORRHEA
13172
DP( 69- 70)
CHROMORHINORRHEA
DP(
78
CHROMORHINORRHEA
13173
NO ADVERSE FINDINGS
13174
DP( 68- 70)
INCISORS:
MISSING/BROKEN
DP(
71
INCISORS:
GROWN IN
13175
NO ADVERSE FINDINGS
----------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
a. Observation confirmed at necropsy.
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TOXICI
TABLE D14 (PAGE 1): BODY WEIGHTS - INDIVIDUAL I)ATA - Fl GENERATION MALE RATS
------ -------- ------ ------- ------ -- -------- --- ------- ---------------
-- -------------------- --
DAY 1
8
15
22
-------------------------------------------------
29
36
43
----------- ---------------
50
S7
64
71
-------------------------------
PAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
-------------------------------------------------------------------------------
------------------------------
13101
59.
105.
158.
216.
270.
323.
360.
396.
435.
458.
478
13102
42.
84.
143.
209.
274.
316.
365.
395.
430.
449.
473
13103
55.
100.
153.
216.
276.
325.
367.
398.
433.
455.
489
13104
54.
102.
168.
232.
303.
349.
393.
437.
459.
486.
509
13105
54.
110.
173.
240.
310.
367.
416.
453.
474.
504.
S24
13106
53.
106.
166.
236.
308.
350.
400.
441.
457.
486.
506
13107
56.
108.
167.
233.
289.
356.
405.
444.
475.
500.
532
13108
60.
110.
170.
232.
295.
346.
401.
434.
470.
472.
512
13109
62.
110.
170.
234.
285.
345.
390.
426.
459.
490.
523
13110
55.
103.
156.
224.
292.
306.
356.
387.
422.
460.
478
13111
59.
109.
174.
244.
311.
374.
417.
455.
495.
519.
541
13112
55.
106.
169.
234.
296.
355.
388.
430.
454.
473.
505
13113
54.
101.
154.
210.
272.
318.
364.
410.
430.
469.
511
13114
64.
121.
185.
250.
310.
366.
409.
444.
464.
490.
510
13115
51.
97.
154.
218.
272.
330.
358.
390.
401.
419.
428
13116
52.
89.
143.
203.
254.
307.
336.
370.
399.
422.
434
13117
46.
91.
164.
213.
272.
330.
373.
421.
443.
472.
487
13118
50.
94.
147.
201.
258.
308.
336.
376.
398.
420.
430
13119
48.
93.
168.
217.
281.
339.
380.
432.
473.
505.
537
13120
48.
92.
159.
214.
279.
338.
396.
440.
481.
500.
539
13121
53.
95.
145.
207.
259.
311.
345.
388.
415.
433.
449
13122
62.
120.
182.
247.
315.
374.
414.
461.
474.
484.
518
13123
62.
118.
190.
261.
329.
401.
459.
512.
541.
579.
607
13124
51.
90.
145.
201.
2S5.
309.
347.
382.
410.
428.
448
13125
44.
87.
143.
200.
261.
312.
353.
391.
417.
433.
4S3
---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Precohabitation body weights were recorded on the day cohabitation rats were 85 to 97 days of age.
was begun in the Fl generation
rats; at
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TOXICI
TABLE D14 (PAGE 2): BODY WEIGHTS - INDIVIDUAL DATA
Fl GENERATION
MALE RATS
---------------------------------
DAY 78
85
-------------
----- -------------
------- --- ------------- -
-----------
-----------------------------------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
-----------------------------------------------------------------------------
------------------- --------------------------------------------
13101
496.
513.
13102
477.
503.
13103
513.
535.
13104
525.
544.
13105 13106 13107
541. 539. 552.
569. 555. 567.
13108
541.
548.
13109
533.
538.
13110
509.
512.
13111 13112
S63. 523.
579. 532.
13113 13114
506. 538.
516. 562.
13115 13116
436. 445.
444. 454.
13117
515.
528.
13118
445.
456.
13119
556.
577.
13120
S58.
587.
13121
468.
485.
13122
530.
554.
13123
617.
640.
13124
469.
434.
13125
477.
500.
---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
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TOXICIT
TABLE D14 (PAGE 3): BODY WEIGHTS - INDIVIDUAL DATA - Fl GENERATION MALE PATS
-------------- ----- ------------------ -- ----- -------------- ---- -- ---- I----------- --- --
DAY 1
8
15
--------------- ----- ----------------------
22
29
36
----- -------------------
43
50
S7
-------- ------------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------- ------------------------------------------------- --------------------------------
- ----------
64
71
- -----------
- -----------
13126
44.
89.
143.
202.
264.
308.
344.
375.
401.
423.
443.
13127
54.
105.
165.
229.
296.
342.
387.
419.
446.
471.
494.
13128 13129 13130 13131 13132 13133
48.
93.
149.
212.
264.
36.
75.
124.
187.
237.
54.
97.
152.
221.
283.
55.
100.
162.
227.
289.
56.
103.
155.
216.
270.
54.
99.
156.
220.
277.
317. 295. 347. 347. 323. 336.
362. 338. 405. 400. 361. 382.
382. 356. 441. 445. 401. 418.
399. 365. 473. 431. 448. 471.
410. 385. 512. 508. 460. 472.
435. 412. 542. 546. 501. 502.
13134
52.
100.
160.
229.
297.
356.
403.
444.
457.
509.
536.
13135
50.
96.
155.
223.
286.
338.
384.
424.
441.
489.
517.
13136
50.
92.
150.
218.
274.
328.
369.
410.
422.
463.
490.
13137
61.
104.
156.
210.
270.
327.
370.
398.
478.
445.
467.
13138
52.
100.
161.
224.
281.
334.
390.
450.
469.
498.
b
13139 13140
56,
109.
170.
240.
300.
354.
401.
440.
398.
496.
510.
46.
84.
139.
197.
256.
314.
348.
374.
396.
417.
439.
13141
49.
89.
144.
206.
260.
283.
335.
385.
410.
417.
440.
13142
51.
100.
163.
228.
296.
366.
409.
416.
456.
494.
523.
13143
47.
94.
146.
202.
260.
328.
373.
415.
446.
478.
508.
13144
52.
100.
169.
244.
304.
354.
378.
417.
411.
436.
430.
13145
58.
106.
160.
221.
276.
330.
373.
404.
437.
460.
477.
13146
54.
99.
152.
214.
273.
329.
374.
417.
448.
475.
504.
13147
56.
102.
157.
216.
276.
335.
370.
407.
443.
461.
474.
13148
59.
113.
176.
236.
301.
352.
390.
429.
453.
494.
522.
13149
56.
106.
174.
241.
305.
370.
409.
442.
471.
487.
499.
13150
52.
100.
166.
228.
289.
354.
392.
441.
454.
468.
493.
----------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Precohabitation body weights were recorded
rats were 85 to 97 days of age.
on the day cohabitation
was begun in the Fl generation
rats; at
b. Rat 13138 was found dead on day 66 postweaning.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D14 (PAGE 4): BODY WEIGHTS - INDIVIDUAL DATA - Fl GENERATION MALE RATS
------------- -------- -------------- -
DAY 78
8s
------------------------------------------
RAT #
DOSAGE GROUP 11
-------------------------------------------
- ----------------- ----------------------- --- ----- ------------
------------------------------------------------------ -----------0.1 MG/KG/DAY
-------------------------------------------------------------------
13126
442.
463.
13127 13128 13129 13130 13131 13132 13133 13134 13135 13136 13137 13138 13139 13140 13141 13142 13143
504. 439. 428. 568. 536. 511. 516.
549. 527. 501. 473. FOUND 539. 448. 461. 552. 520.
523. 459. 451. 592. 571. 535. 532. 575. 559. 524. 493. DEAD ON DAY 66 POSTWEANING 556. 460. 487. 573. S42.
13144 1314S
435. 494.
466. 505.
13146
520.
542.
13147
489.
503.
13148
533.
557.
13149
510.
542.
13150
512.
529.
---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL IGAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE D14 (PAGE 5): BODY WEIGHTS - INDIVIDUAL DATA - Fl GENERATION MALE RATS
------------------ ------ ------------- ---- ------------------- -- -- ----------- - ----------------------- ---
DAY 1
8
15
-------- --------------------------------
22
29
36
43
so
57
64
71
-------- ------------------------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
-------- ------------------------------------------------------ ------------------------------------------------
13151
53.
99.
155.
211.
279.
330.
382.
418.
448.
465.
498.
13152
51.
104.
160.
223.
283.
337.
373.
405.
439.
464.
495.
13153 13154
51.
101.
50.
103.
168. 167.
238. 228.
305. 291.
356. 338.
408. 380.
446. 411.
477. 440.
488. 461.
514. 485.
13155 13156 13157
55.
99.
151.
210.
263.
316.
358.
402.
412.
436.
449.
52.
94.
148.
206.
260.
308.
342.
373.
398.
412.
437.
57.
106.
164.
235.
316.
374.
430.
478.
517.
554.
582.
13158
48.b
91.
145.
210.
269.
323.
375.
410.
435.
461.
483.
13159 13160 13161 13162 13163 13164
43.b
81.
134.
190.
253.
306.
358.
391.
425.
455.
482.
51.
97.
158.
217.
280.
334.
382.
429.
462.
492.
520.
S4.
96.
IS2.
206.
253.
306.
334.
359.
37S.
395.
403.
47.
95.
159.
233.
305.
372.
410.
453.
479.
511.
516.
50.
99.
162.
226.
286.
344.
389.
412.
447.
471.
489.
47.
86.
133.
189.
244.
302.
332.
362.
380.
395.
417.
13165
51.
103.
159.
220.
276.
325.
365.
420.
453.
477.
501.
13166
49.
92.
152.
209.
262.
320.
368.
406.
434.
460.
493.
13167
48.
91.
145.
211.
274.
333.
380.
411.
437.
460.
485.
13168
46.
95.
152.
219.
275.
335.
377.
418.
438.
462.
489.
13169
55.
98.
154.
212.
267.
326.
357.
403.
424,
446.
471.
13170
49.
94.
152.
211.
281.
344.
386.
436.
459.
505.
S24.
13171
47.
90.
148.
205.
266.
316.
348.
380.
404.
421.
445.
13172 13173
62.
112.
172.
232.
298.
349.
384.
424.
443.
524.
486.
59.
115.
184.
257.
326.
386.
412.
470.
503.
525.
568.
13174 13175
44.
92.
154.
221.
275.
335.
380.
411.
440.
463.
484.
40.
77.
134.
197.
244.
295.
322.
336.
352.
362.
370.
----------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Precohabitation body weights were recorded on the day cohabitation was begun in the Fl generation rats; at
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
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE D14 (PAGE 6): BODY WEIGHTS - INDIVIDUAL DATA - Fl GENERATION MALE RATS
---- ----- - ------------------------------- ----------------------------------------------------- -------
DAY 78
as
-------------------------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------------------------------------------------------------------------------------------------------------
13151
500.
524.
13152 13153
504. 524.
533. 546.
13154 13155 13156 13157 13158 13159
497. 464. 446. 603. 496. 503.
501. 477. 464. 627. 506. 520.
13160
538.
544.
13161 13162 13163 13164 13165 13166 13167
415. 534. 498. 421. 501. 504. 495.
424. 549. 533. 438. 519. 520. 520.
13168 13169
491. 485.
515. 502.
13170
549.
582.
13171
453.
465.
13172 13173
485. 571.
509. 596.
13174
510.
510.
13175
388.
----------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DFVELOPMENTAL
STUDY NUMBEP:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXICIT
TABLE D15 (PAGE 1): FEED CONSUMPTION
VALUES - INDIVIL)UAL DATA - Fl GENERATION MALE PATS
--- -------- - ----------- ---------------- ------ - ------------ ---,
DAYS 1 - 8
8 - 15 15 - 22 22 - 29 29
36 36 - 43 43 - 50 50
---- ----------------------------------------------- - ------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLS) MG/KG/DAY
--------------
- 57 57 - 64a ---------------
- ------------------
----------------------------------------------------- - -------------------------- -------------------------- --
13101 13102 13103 13104 13105 13106 13107 13108 13109 13110 13111 13112 13113 13114 13115 13116 13117 13118 13119 13120
103. 75.
113. 102. 121. 106. 118. 110. 105.
96. 100.
80. 105. 114. 102.
91. 103. 101. 100.
100.
145. 134. 147. 157. 180. 164. 164.
155. 147. 144. 163. 157. 148. 160. 145. 132. 151. 145. 148. 145.
166. 170. 181. 192. 215. 212. 187. 185.
b 179. 194. 197. 170. 185. 171. 160. 169. 161. 181. 178.
176. 197. 194. 205. 227. 217.
201. 197. 198. 215. 218. 218. 192. 209. 194. 180. 192. 179. 203. 195.
192. 205. 205. 226. 246. 228. 232. 207. 211. 157. 215. 233. 198. 213. 199. loo. 194. 177. 215. 207.
189. 201. 202. 218. 233. 221. 231. 217. 219. 204. 226. 253.
209. 241. 218. 216. 250. 209. 248. 252.
200. 194.
b 227. 248. 228. 224. 228. 219. 192. 230. 239. 232. 236. 203. 214.
252. 200. 250. 247.
210. 213. 233. 236. 255. 231. 230. 232. 228. 214. 224. 235. 216. 223. 191. 206. 227. 182. 239. 236.
200. 197. 217. 216. 241. 220.
b 168. 225. 226. 234. 220. 234. 219. 183. 199. 225. 185. 225. 238.
13121 13122
101. 116.
142. 159.
168. 202.
isa. 227.
188. 252.
217. 250.
222. 264.
222. 225.
208. b
13123
113.
163.
203.
221.
262.
269.
281.
281.
b
13124
102.
IS2.
179.
203.
251.
223.
184.
231.
206.
13125
100.
159.
176.
202.
209.
221.
232.
244.
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.
PROTOCOL 418-008:
COMBINED ORAI, (GAVAGE@ PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL STUDY NIJMBER: 6295.9)
AND PERINA,rAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D15 (PAGE 2): FEED CONSUMPTION
VALUES - INDIVIDUAL DATA - Fl GENERATION
MALE PATS
-- ----- ------------------- --
DAYS 1 - 8
8
15
-- ----- -----------------------
--- -----------
- ------ - ------- -- -- - ---------- - ------- - ------
15 - 22 22 - 29 29
36 36
43 43 - 50 50
57 57 - 64a
--- -------------- - ------------------------ -------------- ------- -- ------
PAT #
DOSAGE GROUP Il
0.1 MG/KG/DAY
-------------------------------- ------------------ ----------------------------------------- -----------------
13126 13127 13128 13129 13130
89.
134.
98.
157.
92.
141.
81.
141.
94.
153.
163. 190. 175. 172. 186.
190. 209.
191. 185. 205.
194. 219. 213. 207. 219.
195. 215. 208. 203. 226.
199. 223. 196. 195. 227.
194. 219. 203. 192. 231.
192. 210. 192. 184. 233.
13131
94.
151.
184.
205.
208.
220.
223.
214.
218.
13132
112.
145.
170.
186.
189.
205.
209.
204.
202.
13133 13134 13135 13136 13137 13138
99. 106.
93. 95. 76. 101.
151. 149.
146. 139. 204. 169.
182. 180. 180. 175. 167. 186.
214. 215. 212. 204. 193. 214.
222. 219. 216. 201. 207. 215.
232. 227. 219. 201. 210. 246.
225. 237. 235. 211. 221. 260.
226. 229. 237. 211. 211. 253.
219. 235. 236. 205. 202. 250.
13139
91.
163.
197.
218.
234.
239.
242.
236.
235.
13140
93.
146.
177.
200.
205.
249.
226.
227.
200.
13141
92.
140.
158.
189.
149.
218.
252.
203.
203.
13142 13143 13144 13145
98. 99. 105. 104.
190. 146. 165. 153.
191. 175. 202. 185.
217. 197. 224. 203.
279. 206. 209. 196.
284. 248. 250. 220.
302. 260.
b 223.
222. 247. 225. 229.
101. 236. 210. 212.
13146
104.
163.
185.
199.
194.
221.
247.
234.
234.
13147
100.
165.
182.
207.
216.
237.
238.
232.
221.
13140
104.
158.
178.
196.
194.
250.
228.
230.
235.
13149
120.
165.
195.
219.
222.
240.
229.
224.
215.
131SO
84.
144.
181.
214.
219.
237.
235.
224.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PPOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE D15 (PAGE 3): FEED CONSUMPTION VALUES
INDIVIDUAL DATA - Fl GENERATION MALE RATS
- -------------------------- ------------------ -1 ---------------
-- ----- ----------- --- ------
DAYS 1 - 8 8 - 15 15 - 22 22 - 29 29 - 36 36 - 43 43 50 50 - 57 57 - 64a
------------------------------ ------------------ ---------------------------------- ------------I ---------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------------I ------ - --------------------------------------------------------
13151
Be.
138.
165.
187.
195.
212.
275.
223.
215.
13152
95.
142.
178.
196.
206.
207.
191.
209.
212.
13153
102.
158.
198.
217.
221.
224.
218.
219.
201.
13154
108.
155.
189.
204.
214.
209.
223.
215.
216.
13155
103.
141.
168.
177.
197.
197.
213.
189.
200.
13156
99.
142.
170.
186.
207.
191.
191.
197.
187.
13157
99.
145.
183.
219.
233.
244.
250.
256.
252.
13158
90.
130.
169.
183.
208.
214.
220.
226.
208.
13159
81.
127.
165.
178.
202.
209.
207.
224.
216.
13160
81.
144.
172.
200.
222.
23S.
235.
238.
244.
13161
90.
141.
160.
177.
185.
189.
180.
175.
179.
13162
85.
150.
200.
230.
248.
241.
236.
233.
236.
13163
100.
174.
189.
215.
215.
252.
204.
239.
227.
13164
94.
136.
167.
164.
178.
208.
197.
188.
180.
13165
19.
157.
169.
198.
193.
231.
235.
239.
234.
13166
95.
146.
163.
187.
199.
223.
229.
217.
214.
13167
98.
144.
172.
191.
200.
209.
212.
220.
210.
13168
92.
183.
184.
203.
209.
224,
227.
220.
207.
13169
94.
160.
172.
194.
199.
236.
234.
226.
218.
13170
106.
158.
185.
212.
219.
242.
239.
237.
255.
13171
88.
59.
189.
209.
209.
247.
226.
223.
210.
13172
107.
169.
186.
212.
218.
219.
228.
217.
206.
13173
iso.
164.
202.
235.
243.
228.
239.
263.
262.
13174
103.
151.
179.
205.
212.
247.
242.
238.
229.
13175
89.
138.
177.
185.
203.
210.
197.
180.
185.
---------------------------------------------------------------------------------------------------------------
DAYS = DAYS POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Last value recorded before cohabitation.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE D16 (PAGE 1): SEXUAL MATURATION
- INDIVIDUAL DATA - Fl GENERATION
MALE RATS
-------------- ----------------------------
DOSAGE GROUP
I
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
-------------- ----------------------------
-- -----------------------
ii 0.1 ----------------------------
-------------------- ----------------------------------
---------
III 0.4 ---------
--------------
PREPUTIAL
PREPUTIAL
PREPUTIAL
RAT # SEPARATION
(DAY)
RAT N SEPARATION
(DAY)
RAT # SEPARATION (D
---------------------------- -------------------------------------------------------------------
13101
47
13126
44
13151
47
13102
42
13127
44
13152
43
13103
43
13128
46
13153
46
13104
45
13129
52
13154
43
13105
so
13130
46
13155
47
13106
46
13131
44
13156
46
13107
44
13132
42
13157
48
13108
45
13133
45
13158
45
13109
47
13134
46
13159
46
13110
45
13135
46
13160
46
13111
44
13136
45
13161
47
13112
44
13137
46
13162
45
13113
46
13138
45
13163
41
13114
40
13139
45
13164
44
13115
43
13140
46
13165
44
13116
44
13141
46
13166
46
13117
46
13142
44
13167
44
13118
46
13143
52
13168
42
13119
44
13144
45
13169
43
13120
46
13145
46
13170
48
13121
44
13146
48
13171
46
13122
45
13147
45
13172
44
13123
43
13148
42
13173
44
13124
47
13149
46
13174
45
13125
48
13150
46
1317S
47
----------------------------------------------------------------------------------------------------------------
DAY = DAY POSTPARTUM
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER;
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D17 (PAGE 1): PASSIVE AVOIDANCE PERFORMANCE
- INDIVIDUAL DATA - Fl GENERATION MALE RATS
------------------------------- ------I--- ---- -------------- ----------------------------------- -- ----------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
----------------------------------------- --- --------------- ---------- I---------------------------
-----------
SESSION la --------------------------
SESSION 2a -------------------
RAT
TRIALS TO
LATENCY b
TRIALS TO
LATENCY b
NUMBER
CRITERION
TRIAL 1
TRIAL 2
CRITERION
TRIAL I
---------------------------------------------------------------------------------------------------------------
13101
6
8
10
is
25
13102
5
15
18
3
is
13103
4
12
26
3
46
13104
5
7
16
3
34
13106
4
12
13
3
12
13107
5
16
6
3
45
13108
5
4
8
3
6
13109
6
9
38
3
18
13110
3
22
60
2
60
13111
4
8
28
4
60
13112
4
2
20
3
19
13113
5
10
4
3
27
13114
6
1
6
2
60
13115
4
7
21
3
8
13116
4
5
28
2
60
13117
6
8
11
2
60
13118
4
7
32
2
60
13120
5
5
23
2
60
13121
5
5
7
3
7
13122
6
6
14
3
48
13123
4
11
36
3
2
13124
3
17
60
3
12
13125
7
7
7
3
10
----------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D17 (PAGE 2): PASSIVE AVOIDANCE
PERFORMANCE
- INDIVIDUAL DATA - Fl GENERATION
MALE RATS
---------DOSAGE
-----------
------------------------
- --------------
GROUP 11
0.1 MG/KG/DAY
--------------------------
-----------------------
- -- ------------------- - - - --------------------------------------- --------------
SESSION la --------------------
SESSION 2a -------------------
RAT
TRIALS TO
LATENCY b
TRIALS TO
LATENCY b
NUMBER
CRITERION
TRIAL I
TRIAL 2
CRITERION
TRIAL 1
---------------------------------------------------------------------------------------------------------------
13126
4
3
15
4
6
13127
4
6
17
5
11
13128
4
9
17
3c
60
13129
7
14
3
4
13
13130
6
6
16
2
60
13131
9
15
3
4
60
13132
8
2
9
3
11
13133d
15
12
6
8
25
13134
3
16
60
3
27
13135
5
14
11
13
13
13136
5
7
21
4
60
13137
10
1
1
3
13
13138
4
2
4
3
7
13139
5
2
5
2
60
13140
4
13
56
3
4
13141
5
4
42
3
is
13142
12
5
2
3
24
13143
4
6
19
3
12
13144
7
5
4
2
60
13145
7
4
14
2
60
13146
3
13
60
6
19
13147
5
14
60
3
7
13148
5
4
8
3
8
13149
8
9
22
2
60
13150
4
9
28
3
7
---------------------------------------------------------------------------------------------------------------
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 tria
towards the criterion.
d. Rat did not meet the criterion in Session I (Learning Phase); values for Session 2 (Retention Phase) were
averages and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PPOS IN PATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D17 (PAGE 3): PASSIVE AVOIDANCE PERFORMANCE
INDIVIDUAL DATA - Fl GENERATION MALE RATS
------------------- ----------- - ---------- ----- - I ------------------- -
------------------------ ------
DOSAGE GROUP 111 ---------------------
0.4 MG/KG/DAY ------------- ---------- -
----------------------
--------------------------------
SESSION la ---- ---------------------
SESSION 2a
RAT
TRIALS TO
LATENCY b
NUMBER
CRITERION
TRIAL 1
TRIAL 2
--------------------- -----------------------------
--------- - -------
TRIALS To
LATENCY b
CRITERION
TRIAL 1
---------------------------------------------------------
13151
4
18
56
3
19
13152
5
6
10
15
12
13153
5
is
5
3
17
13154
4
8
10
3
42
13156
5
14
60
3
43
13157
4
6
30
3
19
13158
4
21
16
3
24
13160
5
9
3
2
60
13161
4
7
26
2
60
13162
7
5
3
2
60
13163
7
1
5
3
13
13164
6
8
24
2
60
13165
6
2
13
2
60
13166
6
15
13
3
a
13168
4
14
12
4
60
13169
6
5
52
3
25
13170
4
8
13
5
9
13171
4
10
55
3
4
13172
4
9
10
3
14
13173
3
25
60
3
54
13174
4
13
45
4
60
13175
4
13
4
3
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE DIB IPAGE 1): WATERMAZE PERFORMANCE
- INDIVIDUAL DATA - Fl GENERATION
MALE RATS
-------------- --------------------- ----- - ----- ---
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
------------------------------------ -----------------
---------- ----- ------ ---- --------- ------------------------------------------------
---------- --------
SESSION la
SESSION 2a
------------------ -----------
------------------------------
RAT
TRIALS TO
ERRORS/
LATENCY b
TRIALS TO
ERRORS/
LATENCY b
NUMBER
CRITERION
TRIAL
TRIAL 2
CRITERION
TRIAL
TRIAL 1
----------------------------------------------------------------------------------------------------------------
13101
7
0.28
13
5
0.00
11
13102
6
0.17
9
12
0.33
6
13103
7
0.43
19
5
0.00
6
13104
is
0.27
11
5
0.00
6
13106
7
0.28
14
5
0.00
9
13107
8
0.25
5
5
0.00
5
13108
11
0.18
13
5
0.00
s
13109
14
0.50
is
is
0.33
13
13110
10
0.20
6
7
0.14
12
13111
7
0.43
11
5
0.00
5
13112
10
0.20
7
5
0.00
6
13113
7
0.71
38
6
0.17
16
13114
12
0.42
10
5
0.00
11
1311S
8
0.62
8
9
0.33
13
13116
7
0.57
18
5
0.00
8
13117
6
0.17
5
5
0.00
5
13118
12
0.50
22
6
0.83
42
13120
6
0.50
6
5
0.00
6
13121
9
0.44
11
9
0.22
7
13122
13
0.46
s
5
0.00
7
13123
6
0.17
6
7
0.14
9
13124
6
0.17
8
5
0.00
5
13125
15
0.53
9
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICI
TABLE D18 (PAGE 2): WATERMAZE PERFORMANCE
- INDIVIDUAL DATA - Fl GENERATION
MALE RATS
- ------------------------------ I ----------- ------------ -- ------------------- -------------------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
- ---- ------------------------------------------------- - -- -------------------------------------------------
SESSION la ------------------------------
SESSION 2a
RAT
TRIALS TO
ERRORS/
LATENCY b
NUMBER
CRITERION
TRIAL
TRIAL 2
----------------------------------------------------------
T-RIAL-S---T-O-----ER-R-O-RS-/-------L-AT-E-N-CY-- b
CRITERION
TRIAL
TRIAL 1
-- -------------------------------------------------
13126 13127
6
0.17
8
10
0.50
48
5
0.00
10
5
0.00
7
13128
9
0.22
7
9
0.11
4
13129c
15
0.60
7
13130
10
0.80
9
13131
7
0.28
12
13132
a
0.25
7
13133
6
0.17
6
6
0.17
26
5
0.00
4
5
0.00
5
10
0.10
7
5
0.00
6
13134
9
0.22
5
9
0.22
7
13135
15
0.80
10
5
0.00
5
13136
13
0.85
60
5
0.00
9
13137
6
0.17
9
5
0.00
6
13138c
15
0.93
13
9
0.22
19
13139 13140
8
0.25
6
12
0.50
16
10
0.30
32
5
0.00
10
13141
8
0.25
a
5
0.00
15
13142
12
0.25
7
8
0.25
7
13143
10
0.30
7
6
0.17
21
13144
7
0.28
13
7
0.14
10
13145
6
0.17
7
5
0.00
5
13146
10
0.70
39
6
0.17
11
13147
9
0.33
13
5
0.00
4
13148
6
0.17
8
5
0.00
5
13149
12
0.50
7
10
0.30
6
13150
7
0.28
10
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) exclu averages and statistical analyses.
PROTOCOL 418-008!
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D18 (PAGE 3): WATERMAZE PERFORMANCE
- INDIVIDUAL DATA - Fl GENERATION
MALE RATS
-------- ------------DOSAGE GROUP 111
-------------- I --------------------------------------0.4 MG/KG/DAY
-------- --- -
-------------
------------------------------------- ------------------------------------------------------ --- -------------
SESSION la ------------------------------
SESSION 2a ------------------------------
RAT
TRIALS TO
ERRORS/
LATENCY b
TRIALS TO
ERRORS/
LATENCY b
NUMBER
CRITERION
TRIAL
TRIAL 2
CRITERION
TRIAL
TRIAL I
--------------------------------------------------------------------------------------------------------------
13151
10
0.50
17
6
0.17
12
13152
6
0.17
5
7
0.28
8
13153
7
0.71
31
5
0.00
10
13154
6
0.33
14
7
0.28
is
13156
13
0.31
6
5
0.00
7
13157
9
0.56
7
5
0.00
5
13158
7
0.28
11
6
0.50
32
13160
6
0.17
4
5
0.00
9
13161
14
0.64
10
8
0.38
10
13162
11
0.45
11
5
0.00
11
13163
6
0.67
6
5
0.00
8
13164
9
0.56
9
5
0.00
10
13165
8
1.12
11
6
0.17
23
13166
is
0.40
10
5
0.00
10
13168
14
0.28
5
5
0.00
6
13169
7
0.28
15
5
0.00
5
13170
6
0.33
8
6
0.17
19
13171
8
0.2S
4
5
0.00
6
13172
12
0.42
12
5
0.00
5
13173
7
0.28
is
5
0.00
8
13174
9
0.33
12
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
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODIJCTION TOXICII
TABLE D19 (PAGE 1): MATING AND FERTILITY - INDIVIDUAL DATA - Fl GENERATION MALE PATS
-- - ------ - --------------- --------
------------ I - ---------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
------------- ---------------- -------------------------------------
----------------------------------------------------
------------------------
RAT -------------
DAYS IN
FEMALE PREGNANCY
COHABITATION
MATING STATUS
MATING DATE
STATUS
--------------------------------------------------------------------------------------------------
13101 13102 13103 13104 13105 13106 13107 13108a 13108b 13109 13110a 13110b 13111c
3
m
c
P(13202)
4
m
c
P(13225)
3
m
c
P(13201)
3
m
c
P(13213)
7
DID NOT MATE
-(13217)
1
m
c
P(13208)
4
m
c
NP(13209)
2
m
c
P(13218)
2
m
c
P(13220)
4
m
c
P(13210)
2
m
c
P(13216)
7
m
c
P(13223)
13112a 13112b 13113 13114
13115 13116 13117 13118 13119 13120 13121c
2
m
c
I
m
c
7
m
c
1
m
c
4
m
c
1
m
c
7
DID NOT MATE
1
m
c
7
DID NOT MATE
1
m
c
P(13211) P(13217) P(13224) P(13207) P(13214) P(13204) -(13223) P(13212) -(13220) P(13206)
13122
1
m
c
P(13219)
13123
4
m
c
P(13203)
13124
2
m
c
P(13215)
13125
2
m
c
P(13222)
----------------------------------------------------------------------------------------------------------------
M = MATED C = CONFIRMED
( ) = FEMALE
RAT NUMBER
P= a. b. c.
PREGNANT
NP = NOT PREGNANT
Result of first cohabitation period.
male rat mated early in the first cohabitation period and was cohabited with a second Rat was not assigned to cohabitation because there were no available female rats.
female
rat.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D19 (PAGE 2): MATING AND FERTILITY - INDIVIDUAL DATA - Fl GENERATION MALE RATS
------------------ -----------------------
- ------------- ---------- - ----- --------------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
------- ---------- ------------------------ ------------------------------ - ----- --------------------
DAYS IN
FEMALE PREGNANCY
RAT
COHABITATION
MATING STATUS
MATING DATE
STATUS
-------------------------------------------------------------------------- ----------------------------
- -----------------
13126a 13126b 13126c 13127a 13127b 13128 13129 13130 13131 13132 13133a 13133b 13134 13135 13136 13137 13138d
1
m
c
P(13239)
6
DID NOT MATE
-(13228)
7
DID NOT MATE
-(13245)
5
m
c
P(13229)
1
m
c
P(13234)
2
m
c
P(13242)
1
m
c
P(13241)
3
m
c
P(13249)
7
DID NOT MATE
-(13234)
7
m
c
P(13237)
2
m
c
P(13226)
1
m
c
NP(13228)
3
m
c
P(13238)
2
m
c
P(13250)
7
DID NOT MATE
-(13245)
5
m
c
P(13227)
13139
6
m
c
13140
P(13230)
3
m
c
NP(13243)
13141
2
m
c
P(13233)
13142
2
m
c
RP(13244)
13143
3
m
c
P(13246)
13144
5
m
c
P(13232)
13145
3
m
c
P(13247)
13146
3
m
c
P(13240)
13147
4
m
c
P(13231)
13148
1
m
c
P(13235)
13149
3
m
c
P(13248)
13150
3
m
c
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.
PROTOCOL 418-008t
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D19 (PAGE 3): MATING AND FERTILITY - INDIVIDUAL DATA - Fl GENERATION MALE PATS
------------ -- --- ---------------- - - --- --- ------------- -------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
--- ----
-------------- --
---------------------------------------- --- ------------------------------------------------------------------
DAYS IN
RAT
COHABITATION
FEMALE PREGNANCY
MATING STATUS
MATING DATE
STATUS
---------------------------------------------------------------------------------------------------------------
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
3
m
c
P(13257)
1
m
c
P(13251)
1
m
c
P(13256)
4
m
c
P(13270)
2
m
c
P(13273)
1
m
c
P(13262)
3
m
c
P(13266)
4
m
c
P(13264)
2
m
c
P(13263)
1
m
c
P(13265)
2
m
c
P(13268)
1
m
c
P(13261)
2
m
c
P(13259)
2
m
c
P(13275)
7
m
c
P(13253)
4
m
c
P(13252)
1
m
c
NP(13274)
5
m
c
P(13254)
3
m
c
P(13260)
2
m
c
P(13271)
4
m
c
P(13269)
2
m
c
P(13255)
4
m
c
P(13267)
3
m
c
P(13272)
1
m
c
P(13258)
----------------------------------------------------------------------------------------------------------------
M = MATED
( ) = FEMALE RAT NUMBER
C = CONFIRMED
P - PREGNANT
NP = NOT PREGNANT
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS TN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL STUDY NIJMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D20 (PACE 1): NECROPSY OBSERVATIONS
INDIVIDUAL DATA - Fl GENERATION
MALE RATS
-- ------------- -- -DOSAGE GROUP DOSAGE (MG/KG/DAY) ----------------------
I 0 (VEHICLE)
---- ---------------
--- ----- -------------------- ---------------------- - ------
RAT
DAY OF
DOSAGES
NUMBER
NECROPSY
ADMINISTERED
OBSERVATIONS
a
---------------------- ----- ----------------------------------------------------------
13101 13102 13103 13104
DP 91
90
ALL TISSUES APPEARED NORMAL.
DP 90
89
ALL TISSUES APPEARED NORMAL.
DP 90
89
ALL TISSUES APPEARED NORMAL.
DP 90
89
ALL TISSUES APPEARED NORMAL.
13105
DP 87
87
FOUND DEAD ON DAY 87 POSTWEANING
(ONE HOUR AN
DOSAGE).
LUNGS: ALL LOBES, DARK RED.
ALL OTHER TISSUES APPEARED NORMAL.
13106 13107 13108 13109 13110 13111 13112 13113 13114 13115
13116
DP 90
89
ALL TISSUES APPEARED
NORMAL.
DP 90
89
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
DP 88
87
ALL TISSUES APPEARED NORMAL.
DP 88
87
ALL TISSUES APPEARED NORMAL.
DP 86
85
FOUND DEAD ON DAY 86 POSTWEANING
(DEATH OCCUR
THORACIC CAVITY:
DARK RED CLOTTED MATERIAL.
EXTERNAL OBSERVATIONS:
RED PERINASAL
ALL OTHER TISSUES APPEARED NORMAL.
SUBSTAN
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 nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILIT'F, DEVELOPMENTAL STUDY NT)MBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE D20 (PAGE 2): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION MALE RATS
---------------------DOSAGE GROUP DOSAGE (MG/KG/DAY) ----------------------
ii 0.1
-- - --- --------- ------- ---------------------------- ---------------- ----------- -
RAT
DAY OF
DOSAGES
NUMBER
NECROPSY
ADMINISTERED
OBSERVATIONS
a
--------------------------- -----------------------------------------------------------
13126 13127 13128 13129 13130 13131
13132 13133
DP 91
90
ALL TISSUES APPEARED
NORMAL.
DP 91
90
ALL TISSUES APPEARED
NORMAL.
DP 90
89
ALL TISSUES APPEARED
NORMAL.
DP 90
89
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
DP 89
OB
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
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 13136 13137
DP 89
88
ALL TISSUES APPEARED NORMAL.
DP 89
88
ALL TISSUES APPEARED NORMAL.
DP 89
Be
ALL TISSUES APPEARED NORMAL.
13138
DP 66
65
FOUND DEAD ON DAY 66 POSTWEANING
(DEATH OCCURR
ALL TISSUES APPEARED NORMAL.
13139 13140 13141 13142
DP 89
Be
ALL TISSUES APPEARED NORMAL.
DP 88
87
ALL TISSUES APPEARED NORMAL.
DP 88
87
ALL TISSUES APPEARED NORMAL.
DP 88
87
ALL TISSUES APPEARED NORMAL.
13143
DP 88
87
KIDNEYS:
LEFT, PELVIS, SLIGHT DILATION AND SI
(PINPOINT TO 0.2 CM IN DIAMETER).
URETERS:
LEFT, DILATED.
URINARY BLADDER:
WALLS, THICKENED
AND NUMEROU
(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 nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE@ PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAb
TABLE D20 (PAGE 3): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA
Fl GENERATION
MALE RATS
REPRODUCTION
TOXIC
DOSAGE DOSAGE -------
GROUP- ----------------- RA-T- ----- -DA-Y--O-F-------DO-S-AG-E-S ----- ----- ----- ---------- -----------
(MG/KG/DAY)
NUMBER
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 13147
DP 88
87
ALL TISSUES APPEARED NORMAL.
DP 88
87
ALL TISSUES APPEARED NORMAL.
13140
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 nec
PROTOCOL 418 008:
COMBINED OPAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PEPINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D20 (PAGE 4): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION MALE RATS
------------- - DOSAGE GROUP DOSAGE (MG/KG/DAY) ------------- ----
III 0.4
------------------------- ----------------------------- ------------------------- ---------
RAT
DAY OF
DOSAGES
NUMBER
NECROPSY
ADMINISTERED
OBSERVATIONS
a
------------------------- ------------------------------------------------------------------
13151 13152 13153 13154 13155 13156 13157 13158 13159 13160 13161
DP 91
90
ALL TISSUES APPEARED
NORMAL.
DP 91
90
ALL TISSUES APPEARED
NORMAL.
DP 91
90
ALL TISSUES APPEARED
NORMAL.
DP 91
90
ALL TISSUES APPEARED
NORMAL.
DP 91
90
ALL TISSUES APPEARED
NORMAL.
DP 91
90
ALL TISSUES APPEARED
NORMAL.
DP 90
89
ALL TISSUES APPEARED
NORMAL.
DP 90
89
ALL TISSUES APPEARED
NORMAL.
DP 90
89
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
DP 89
88
ALL TISSUES APPEARED
NORMAL.
13162
DP 89
88
ABDOMINAL ADIPOSE TISSUE:
RED WITH FIRM AREAS
ALL OTHER TISSUES APPEARED
NORMAL.
13163 13164 13165 13166 13167
13168 13169 13170 13171 13172
DP 88
87
ALL TISSUES APPEARED
NORMAL.
DP 88
87
ALL TISSUES APPEARED
NORMAL.
DP 88
87
ALL TISSUES APPEARED
NORMAL.
DP 80
87
ALL TISSUES APPEARED NORMAL.
DP 88
87
ALL TISSUES APPEARED
NORMAL.
DP 88
87
ALL TISSUES APPEARED
NORMAL.
DP 88
87
ALL TISSUES APPEARED
NORMAL.
DP 88
87
ALL TISSUES APPEARED
NORMAL.
DP 88
87
ALL TISSUES APPEARED
NORMAL.
DP 87
86
ALL TISSUES APPEARED
NORMAL.
13173
DP 87
86
KIDNEYS:
BILATERAL, LARGE (LEFT
4.94 G; RIGH
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 necr
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINAI'AL/POSTNATAL
REPRODUCTION TOXICI
TABLE D21 (PAGE 1): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY INDIVIDUAL DATA - Fl GENERATION MALE RATS
-------------------------------------------------------------------------------------------------------------
EPIDIDYMIS
TESTIS
SEMINAL VESICLES SEMINAL VESICLES
EPIDIDYMIS
LEFT
LEFT
WITH FLUID
WITHOUT FLUID
RIGHT
PAT TERMINAL BODY
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
It TBW
WT.
TBW
WT.
TBW
WT.
TSW
WT.
t TBW
--------------------------------------------------------------------------------------------------------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
13101
553.
0.68
0.12
2.03
0.37
1.76
0.32
1.11
0.20
0.77
0.14
13102
517.
0.74
0.14
1.79
0.35
2.09
0.40
1.41
0.27
0.74
0.14
13103
552.
0.61
0.11
1.76
0.32
1.44
0.26
1.17
0.21
0.60
0.11
13104
562.
0.70
0.12
1.82
0.32
1.79
0.32
1.13
0.20
0.70
0.12
13105a
574.
0.67
----
1.64
----
1.85
----
0.59
----
0.70
----
13106
568.
0.62
0.11
1.77
0.31
1.48
0.26
0.93
0.16
0.67
0.12
13107
596.
0.59
0.10
1.72
0.29
2.21
0.37
1.29
0.22
0.59
0.10
13108
561.
0.54
0.10
1.54
0.27
1.53
0.27
0.93
0.16
0.59
0.10
13109
548.
0.72
0.13
1.75
0.32
2.19
0.40
1.34
0.24
0.60
0.11
13110
527.
0.68
0.13
1.63
0.31
1.03
0.20
0.89
0.17
0.59
0.11
13111
584.
0.77
0.13
2.23
0.38
1.81
0.31
1.03
0.18
0.76
0.13
13112
534.
0.52
0.10
1.63
0.30
1.23
0.23
0.81
0.15
0.69
0.13
13113
523.
0.84b
0.16
2.10
0.40
1.96
0.37
0.89
0.17
0.71
0.14
13114
570.
0.68
0.12
1.79
0.31
2.35
0.41
1.15
0.20
0.71
0.12
13115
448.
0.70
0.16
1.81
0.40
1.72
0.38
0.89
0.20
0.62
0.14
13116c
456.
0.67
----
1.62
----
1.90
----
0.56
----
0.67
----
13117
532.
0.66
0.12
1.75
0.33
1.73
0.32
0.99
0.19
0.60
0.11
13118
468.
0.66
0.14
1.70
0.36
1.97
0.42
0.96
0.20
0.64
0.14
13119
592.
0.63
0.11
1.73
0.29
1.72
0.29
1.11
0.19
0.71
0.12
13120
598.
0.71
0.12
1.67
0.28
1.38
0.23
0.85
0.14
0.70
0.12
13121
488.
0.60
0.12
1.71
0.35
1.92
0.39
1.07
0.22
0.67
0.14
13122
560.
0.62
0.11
1.55
0.28
1.40
0.25
0.91
0.16
0.62
0.11
13123
651.
0.74
0.11
1.77
0.27
1.88
0.29
0.91
0.14
0.73
0.11
13124
434.
0.61
0.14
1.64
0.38
1.75
0.40
1.22
0.28
0.67
0.15
13125
500.
0.70
0.14
1.85
0.37
1.97
0.39
0.89
0.18
0.73
0.15
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL B
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL,
REPRODUCTION
TOXICIT
TABLE D21 (PAGE
2): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS
INDIVIDUAL DATA
Fl GENERATION
MALE RATS
(%) OF ORGAN WEIGHT TO TERMINAL
BODY W
--------------------------------------- ------------- ------------------------------------- ----- -------------
PROSTATE
RAT
TERMINAL BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
t TBW
---------------------------------------------------------------------------------------------------------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
----------------------------------------------------------------------------------
13101
553.
1.11
0.20
13102
517.
0.71
0.14
13103
552.
0.55
0.10
13104
562.
1.04
0.18
13105a
574.
1.42
----
13106
568.
0.90
0.16
13107
596.
0.96
0.16
13108
561.
1.02
0.18
13109
548.
0.55
0.10
13110
527.
0.75
0.14
13111
584.
1.15
0.20
13112
534.
0.78
0.15
13113
523.
0.94
0.18
13114
570.
1.09
0.19
13115
448.
0.72
0.16
13116b
456.
0.99
----
----------------------------
13117
532.
0.73
0.14
13118
468.
1.05
0.22
13119
592.
0.93
0.16
13120
598.
1.11
0.18
13121
488.
0.90
0.18
13122
560.
0.93
0.17
13123
651.
1.29
0.20
13124
434.
1.01
0.23
13125
500.
1.13
0.23
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. t TBW = (ORGAN WEIGHT/TERMINAL
B
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBBR:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D21 (PAGE 3): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL BODY INDIVIDUAL DATA - Fl GENERATION MALE RATS
------------------------------------------------------------------------------ ----------------------------
EPIDIDYMIS
TESTIS
SEMINAL VESICLES
SEMINAL VESICLES
EPIDIDYMIS
LEFT
LEFT
WITH FLUID
WITHOUT FLUID
RIGHT
RAT
TERMINAL BODY
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
!k TBW
WT.
TBW
WT.
TBW
WT.
t TBW
WT.
TBW
-------------------------------------------------------------------------------------------------------------
DOSAGE GROUP 11
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. 60S. 589. 548. 547. 588. 570. 527. 501. 502. 571. 465. 490. 584. 560. 480. 512. 550. 517. 569. 544. 540.
0.59 o.s7 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 0.3S 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
0.3S 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 0.5S 0.68 0.70 0.59 0.75 0.58
0.65 0.70 0.70 0.64 0.39d 0.72 0.72 0.49f 0.64 0.74
0.14 0.11 0.13 0.14 0.10 0.11 0,12 0.12 0.081 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
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (C).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
B
a. Rat 13134 had a small and flaccid left epididymis, a flaccid right epididymis and purple and flaccid testes
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 a
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 an
analyses.
See the individual necropsy observations table (Table D20).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295-9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D21 (PAGE 4): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (t) OF ORGAN WEIGHT TO TERMINAL BODY INDIVIDUAL DATA - Fl GENERATION MALE RATS
-------------------- -------------------------------------------------------- ---------------------------------
PROSTATE
RAT
TERMINAL
BODY
ABS.
REL.
NUMBER
WEIGHT
WT.
t TBW
---------------------------------------------------------------------------------------------------------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
13126 13127 13128 13129 13130 13131
13132 13133 13134 13135 13136 13137 13138a 13139 13140 13141 13142
470. 531. 474. 459. 605. 589. 548. 547. 588. 570. 527. 501. 502. 571. 46S. 490. 5B4.
0.67 0.81 0.86 0.55 I.oo 0.93 0.58 0.60 1.38 0.89 1.06 0.89 0.83 0.89 0.82 1.04 0.80
0.14 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
13143 13144 13145 13146 13147 13148
560. 480. 512. 550. 517. 569.
0.75 1.14 1.35 0.63 1.18 1.06
0.13 0.24 0.26 0.11 0.23 0.19
13149
544.
0.91
0.17
13150
540.
1.01
0.19
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS.
a- Rat 13138 was found dead day 66 postweaning;
WT. = ORGAN WEIGHT.
REL. t TBW
values excluded from group averages
= (ORGAN WEIGHT/TERMINAL
B
and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILTTY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE D21 (PAGE 5): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS 1%) OF ORGAN WEIGHT TO TERMINAL BODY W INDIVIDUAL DATA - PI GENERATION MALE RATS
------------------------------------------------- ---------------------------------------------- --------------
EPIDIDYMIS
TESTIS
SEMINAL VESICLES
SEMINAL VESICLES
LEFT
LEFT
WITH FLUID
WITHOUT FLUID
RAT
TERMINAL BODY
ABS.
REL.
ABS.
REL.
ABS.
REL.
ABS.
REL.
NUMBER
WEIGHT
WT.
t TBW
WT.
t TBW
WT.
t TBW
WT.
TBW
-------------------------------------------------------------------------------------------------
EPIDIDYMIS
RIGHT
ABS.
REL.
WT.
TSW
--------------
DOSAGE GROUP 111
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
532. 549. 571. 526. 477. 469. 644. 522. 529. 560. 435. 557. 527. 439. 532. 539. 524. 523. 512. 589. 469. 513. 606.
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
0.12 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
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
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
1.44 1.88 1.48 1.87 1.61 1.75 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
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
0.66 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
0.12 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
0.64 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
0.12 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
13174
519.
0.64
0.12
1.86
0.36
1.76
0.34
0.91
0.18
0.64
0.12
13175
394.
0.59
0.15
1.73
0.44
1.36
0.34
0.60
0.15
0.58
0.15
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW = (ORGAN WEIGHT/TERMINAL
B
a. Damaged during processing (weight affected); values excluded from group averages and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE D21 (PAGE
6): TERMINAL BODY WEIGHTS AND ORGAN WEIGHTS AND RATIOS (%) OF ORGAN WEIGHT TO TERMINAL
INDIVIDUAL
DATA - Fl GENERATION
MALE RATS
BODY
---------------------------- ---------------------------- ----------------------------- -----------------------
RAT NUMBER
TERMINAL WEIGHT
BODY
PROSTATE
ABS.
REL.
WT.
TBW
---------------------------------------------------------------------------------------------------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
13151
532.
1.01
0.19
13152
549.
1.41
0.26
13153
571.
0.91
0.16
13154
526.
0.85
0.16
13155
477.
0.80
0.17
13156
469.
0.61
0.13
13157
644.
1.05
0.16
13158
522.
0.83
0.16
13159
S29.
0.85
0.16
13160
560.
1.06
0.19
13161
435.
0.83
0.19
13162
557.
0.62
0.11
13163
527.
0.80
0.15
13164
439.
0.93
0.21
13165
532.
1.03
0.19
13166
539.
0.79
0.15
13167
524.
0.97
0.18
13168
523.
1.09
0.21
13169
512.
0.91
0.18
13170
589.
0.76
0.13
13171
469.
1.07
0.23
13172
513.
0.64
0.12
13173
606.
0.96
0.16
13174
519.
0.95
0.18
13175
394.
0.52
0.13
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
ABS. WT. = ORGAN WEIGHT.
REL. % TBW - (ORGAN WEIGHT/TERMINAL
E
APPENDIX E REPORT TABLES - Fl GENERATION
FEMALE RATS
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE El (PAGE 1): CLINICAL OBSERVATIONS
- SUMMARY - Fl GENERATION FEMALE RATS
---------------------- -------------------- -------- ---------------- --------------------------- --- ---------
DOSAGE DOSAGE
GROUP (MG/KG/DAY)
I 0 (VEHICLE)
ii 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
0
lb
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
S/ 1
9/ 1
19/ 3
EARS:
SWOLLEN AND PURPLE
B/ 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
I/ 1
0/ 0
0/ 0
---------------------------------------------------------------------------------------------------------------
STATISTICAL
ANALYSES OF CLINICAL OBSERVATION
DATA
MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER
WERE RESTRICTED OF RATS EXAMINED
TO THE NUMBER PER GROUP.
OF PATS WITH OBSERVATIONS.
NIN = TOTAL NUMBER OF OBSERVATIONS/NUMBER
OF RATS WITH OBSERVATION.
a. Rat 13205 was excluded from study on day 7 postweaning; b. Rat 13221 was found dead on day 28 postweaning.
the sex was incorrectly
identified.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS ISPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295-9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE El (PAGE 2): CLINICAL OBSERVATIONS
SUMMARY - Fl GENERATION
FEMALE RATS
------------- -- -------------------- ---
- ---------------------- -- ------------------------
DOSAGE GROUP DOSAGE (MG/KG/DAY) -----------------------------------------
I
ii
III
0 (VEHICLE) 0.1
0.4
- - -----------------------------------------------------
PRESUMED GESTATION:
a
-------------------
MAXIMUM POSSIBLE INCIDENCE
509/ 23
539/ 24
540/ 25
MORTALITY
0
0
0
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
75/ 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
0/ 0
0/ 0
1/ 1
CHROMORHINORRHEA
14/ 2
1/ 1
0/ 0
SOFT OR LIQUID FECES
0/ 0
1/ 1
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
MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER
OF RATS EXAMINED
NIN = TOTAL NUMBER OF OBSERVATIONS/NUMBER
OF RATS WITH OBSERVATION.
a. Restricted to rats with a confirmed mating date.
TO THE MMBER PER GROUP.
OF RATS WITH OBSERVATIONS.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PPOS IN RATS (SPON@;OR'S STUDY NUMBER:
6295.9)
AND PERINATAb/POSTNATAL
REPRODUCTION
TOXICI
TABLE El (PAGE 3): CLINICAL OBSERVAIIONS
- SUMMARY - Fl GENERATION FEMALE PATS
----------------------------------- -DOSAGE GROUP DOSAGE (MG/KG/DAY)
--------------------------------------
LACTATION:
------------ ---------- -- -------------------------------------------
--------------------------
I
ii
III
0 (VEHICLE) 0.1
0.4
-------------------------------------------
MAXIMUM POSSIBLE INCIDENCE
462/ 22
441/ 21
493/ 24
FOUND DEAD
0
0
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
0/ 0
0/ 0
s/ 5**
EARS: SWOLLEN AND PURPLE
45/ 3
84/ 4
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:
A13RASION
0/ 0
9/ 1
0/ 0
TIP OF TAIL MISSING
21/ 1
0/ 0
0/ 0
LEFT HINDPAW:
THIRD AND FOURTH DIGITS MISSING
21/ 1
0/ 0
o/ o
URINE-STAINED
ABDOMINAL
FUR
I/ 1
0/ 0
0/ 0
---------------------------------------------------------------------------------------------------------------
STATISTICAL
ANALYSES OF CLINICAL OBSERVATION
DATA WERE RESTRICTED
MAXIMUM POSSIBLE INCIDENCE = (DAYS x RATS)/NUMBER
OF RATS EXAMINED
NIN = TOTAL NUMBER OF OBSERVATIONS/NUMBER
OF RATS WITH OBSERVATION.
a. Dam 13257 was found dead on day 10 of lactation.
TO THE NUMBER PER GROUP.
OF RATS WITH
OBSERVATIONS.
Significantly different from the vehicle control group value (p:SO.01).
PROTOCOL 418-008:
COMBINED ORAL ((;AVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (S['ONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE E2 (PAGE 1): BODY WEIGHTS
PRECOHABITATION
- SUMMARY - Fl GENERATION FEMALE RATS
--------- -------------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) --------- -------------------------
RATS TESTED
N
------------- -------------------------------------------------------
I
ii
III
0 (VEHICLE)
0.1
0.4
----------------------------------------------------------------------
25
25
25
INCLUDED IN ANALYSES
N
24a
25
25
BODY WEIGHT (G)
DAY
1
MEAN+S.D.
51.1 + 6.1
SO.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
MEAN+S.D.
194.0 + 21.7
200.5 + 13.1
193.9 + 16.6
t 23)b
DAY 36
MEAN+S.D.
217.4 + 24.9
226.8 + 15.2
217.8 + 17.4
1 23]b
DAY 43
MEAN+S.D.
234.9 + 25.2
245.1 + 14.6
237.9 + 20.0
[ 23]b
DAY 50
MEAN+S.D.
251.1 + 27.4
261.4 + 20.0
251.2 + 20.9
t 23)b
DAY 57
MEAN+S.D.
259.6 + 29.0
272.7 + 20.7
262.7 + 24.4
( 23]b
DAY 64
MEAN+S.D.
273.2 + 31.4
282.7 + 19.6
272.3 + 25.0
[ 23]b
PRECOHABITATION
c
MEAN+S.D.
282.8 + 33.6
294.0 + 16.3
280.3 + 26.9
[ 23)b
---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING ( I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly 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 Fl generation rats; rats were 85 to 97 days of age.
PROTOCOL 418-008:
COMBINED ORAL PFOS IN RATS
(GAVAGE) (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E3 (PAGE 1): BODY WEIGHT CHANGES
----------- -------------------- ------
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ----------------------------------------
PATS TESTED
N
INCLUDED IN ANALYSES
N
BODY WEIGHT CHANGE (G)
- PRECOHABITATION
- SUMMARY - Fl GENERATION
FEMALE PATS
--- - ------------------------------------------------- ----- ------
I
ii
III
0 (VEHICLE)
0.1
0.4
----- --------------------------------------------------------------
25
25
25
24a
25
25
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 15 - 22
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 I
HEAN+S.D. MEAN+S.D. MFAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
+25.8 + 12.8 t 231&,b
+23.4 + 10.4 ( 23]a,b
+17.5 + 9.2 1 23]a,b
+16.2 + 6.6 ( 23]a,b
+8.5 + 6.8
( 23]a,b +13.6 + 7.6
( 23]a,b +222.3 + 28.9
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
+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
PRECOHABITATION
c
MEAN+S.D.
+231.9 + 30.7
+243.6 + 17.3
+231.6 + 25.1
[ 23]a,b
---------------------------------------------------------------------------------------------------------------
DAY(S) = DAY(S) POSTWEANING
[ I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; b. Excludes values for rat 13221, which was found dead day 28 postweaning.
the sex was incorrectly
C. Precohabitation body weights were recorded on the day that cohabitation rats were 85 to 97 days of age.
began for the Fl generation
rats;
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE E4 (PAGE 1): MATERNAL BODY WEIGHTS - GESTATION - SUMMARY - Fl 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 + 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 + 2S.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 + 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 + 28.2
----------------------------------------------------------------------------------------------------------------
DAY = DAY OF GESTATION
a. Excludes values for rat 1320S, which was excluded from study on day 7 postweaning; the sex was incorrectly
b. Excludes values for rat 13221, which was found dead on day 28 postweaning.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E4 (PAGE 2): 14ATERNAL BODY WEIGHTS - GESTATION - SUMMARY - Fl GENERATION
FEMALE RATS
-------------------------------
DOSAGE GROUP
DOSAGE (MG/KG/DAY)
-------------------------------
RATS TESTED
N
-------------------- - ------------------- -- -- -----------------------------
I
ii
0 (VEHICLE)
0.1
-------------------------------------------------
III
0.4 ----------------------
------
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
MEAN+S.D.
408.3 + 35.6
414.7 + 27.7
402.8 + 32.0
DAY 20
MEAN+S.D.
420.8 + 34.4
428.0 + 30.3
417.7
34.4
----------------------------------------------------------------------------------------------------------------
DAY = DAY OF GESTATION
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; b. Excludes values for rat 13221, which was found dead on day 28 postweaning.
the sex was incorrectly
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN PATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E5 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - GESTATION
- SUMMARY - Fl GENERATION
FEMALE RATS
---------------- ------------- ---------------------------------------------------------------------------- --
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ---------------- ----
--------
1 0 (VEHICLE) ------------------------------
11
0.1
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 + g.g
+20.0 + 6.2
DAYS 14
17
MEAN+S.D.
+27.5 + 13.7
+31.2 + 9.4
430.0 + 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; b. Excludes values for rat 13221, which was found dead on day 28 postweaning.
the sex was incorrectl
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE E6 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - SUMMARY - Fl GENERATION FEMALE RATS
------ ---------------------------------------------------------------------------------------------------------
DOSAGE GROUP
I
ii
III
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
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
I
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
MEAN+S.D.
331.5 + 31.2
340.2 + 19.1
324.2 + 23.2
DAY 14
MEAN+S.D.
358.9 + 29.2
368.3 + 21.8
352.4 + 23.6
DAY 21
MEAN+S.D.
338.0 + 31.0
356.0 + 18.4
f 23)c 341.3 + 17.8
[ 23)c ---------------------------------------------------------------------------------------------------------------
DAY = DAY OF LACTATION
( I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly 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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E7 (PAGE 1): MATERNAL BODY WEIGHT CHANGES - LACTATION - SUMMARY - Fl GENERATION
FEMALE RATS
---------- ------------------------------------- ---- --------------------------------------------------------
DOSAGE GROUP
I
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
----------------------------------------------------------------------
RATS TESTED
N
25
ii
III
0.1
0.4
-----------------------------
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
I- 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
MEAN+S.D.
+27.3 + 12.8
+28.0 + 15.6
+30.1 + 10.4
DAYS 14 - 21
MEAN+S.D.
-20.9 + 17.1
-12.3 + 12.6
( 23)C -11.0 + 17.0
DAYS
1 - 21
MEAN+S.D.
+12.3 + 19.1
+21.3 + 15.3
( 23]c +21.2 + 18.7
( 23]c --------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF LACTATION
I I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectl)
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<0.05).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE EB (PAGE 1): ABSOLUTE FEED CONSUMPTION VALUES (G/DAY) - PRECOHABITATION - SUMMARY
Fl GENERATION FEM
-------- ----------------------- --------------------------------------------------------------------------
DOSAGE GROUP
I
ii
III
DOSAGE (MG/KG/DAY) --------I
0 (VEHICLE)
0.1
0.4
----------------------------------------------------------------------------------------------------
PATS TESTED
N
25
25
25
INCLUDED IN ANALYSES
N
24a
25
25
FEED CONSUMPTION (G/DAY)
DAYS I - 8
MEAN+S.D.
13.6 + 1.3
13.7 + 1.2
12.6 + 1.7*
DAYS 8 - 15
MEAN+S.D.
18.9 + 1.4 [ 23)b
19.1 + 1.5
18.9 + 2.4
DAYS 15 - 22 DAYS 22 - 29
MEAN+S.D. MEAN+S.D.
20.4 + 2.3 [ 23)b
20.5 + 2.8 C 23)c
21.2 + 1.6 21.4 + 2.1
20.8 + 1.9 ( 24]b
20.8 + 2.0
DAYS 29 - 36 DAYS 36 - 43
MEAN+S.D. MEAN+S.D.
20.5 + 2.7 ( 23)C
22.4 + 3.8
21.4 + 2.4 24.4 + 4.0
20.7 + 2.1 ( 24]b
23.6 + 3.9
[ 22]b,c
DAYS 43 - 50
MEAN+S.D.
22.9 + 3.2
23.8 + 3.5
23.6 + 3.9
DAYS 50 - 57
MEAN+S.D.
[ 22]b,c 23.2 + 3.7
[ 23]C
I 24]b 23.5 + 3.0
[ 24]b 22.3 + 2.9
DAYS 57 - 64d DAYS I - 64d
MEAN+S.D. MEAN+S.D.
21.5 + 2.3 [ 23]c
20.4 + 1.8
21.9 + 2.0 I 2i]b
21.2 + 1.7
21.5 + 3.0 f 24]b
20.6 + 1.9
[ 23)c
f 2i]b
[ 24]b
--------------------------------------------------------------------------------------------------------------
DAYS - DAYS POSTWEANING
[ I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; 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@S0.05).
the sex was incorrectl
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE E9 (PAGE 1): RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - PRECOHABITATION - SUMMARY - Fl GENERATION
--------------------------------------------------------------------------------------- ------------------
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 - IS DAYS 15 - 22 DAYS 22 - 29 DAYS 29 - 36 DAYS 36 - 43 DAYS 43 - 50 DAYS SO - 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 1 23]b
113.2 + 12.9 [ 23]c
99.9 + 9.6 1 23)c
100.2 + 18.4 [ 2i]b,c
95.3 + 13.6 [ 22]b,c
91.5 + 14.7 I 23]c
80.9 + 6.4 [ 23]c
109.6 + 8.8
166.7 + 11.4
136.4 + 7.6
114.2 + 6.8
100.3 + 7.8
103.4 + 16.7
93.9 + 11.6 I 2i]b
88.4 + 11.3
79.0 + 6.7 [ 24]b
109.2 + 6.6
167.7 + 18.5
137.8 + 11.9 [ 24]b
114.6 + 6.8
100.9 + 7.8 ( 24]b
104.1 + 18.9
96.8 + 17.6 [ 24)b
86.9 + 8.1
80.3 + 9.2 ( 24]b
109.5 + 9.1
( 23]c
( 2i)b
[ 24]b
---------------------------------------------------------------------------------------------------------------
DAYS = DAYS POSTWEANING
f I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 1320S, which was excluded from study on day 7 postweaning; the sex was incorrectly 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.
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTIBITY,
I)EVETOPMENTAL
S@l'UDY NTJMBER: 6295.9)
AND PER INAI'AL/P(-)STNATAL REPRODUCTION
TOXIC
TABLE EIO (PAGE 1): MATERNAL ABSOLUTE FEED CONSUMPTION
VALUES (G/DAY) - GESTATION
------ ---------------- - -- ---- ------ - --
DOSAGE GROUP
1
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
---- ----------- -------- -- --------------- --- ----
PATS TESTED
N
2S
- ----------------
11 0.1 ------------------
25
-----
-----
INCLUDED IN ANALYSES
N
23a,b
25
PREGNANT
N
22
21
MATERNAL
FEED
CONSUMPTION
(G/DAY)
- SUMMARY - Fl GENERATION
------------- --
111 0.4 ------------- - I
25
---------------
2S
24
DAYS
0
7
DAYS
7
10
MEAN+S.D. MEAN+S.D.
25.2 + 2.2 27.2 + 3.0
25.0 + 2.6 f 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 27.8 + 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 f I = NUMBER OF VALUES
AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; b. Excludes values for rat 13221, which was found dead on day 28 postweaning. C. Excludes values that were associated with spillage.
the sex was incorrectly
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINAIAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE Ell (PAGE 1): MATERNAL RELATIVE FEED CONSUMPTION VALUES (G/KG/DAY) - GESTATION - SUMMARY - Fl GENERATI
----------------------DOSAGE GROUP DOSAGE (MG/KG/DAY) ----------------------RATS TESTED
-------------------------- -- -----------------------
I
ii
0 (VEHICLE)
0.1
--------------------------- --------------------------
N
25
25
------------------------------III 0.4
-------------------------------
25
INCLUDED IN ANALYSES
N
23a,b
25
2S
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 f 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 + 7.8 76.7 + 10.2
74.0 + 7.6 70.3 + 10.0
75.8 + 7.1 [ 23]c
75.7 + 6.8
DAYS 17
20
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
73.8 + 5.0
75.9 + 5.2
---------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF GESTATION
I I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; b. Excludes values for rat 13221, which was found dead on day 28 postweaning. c. Excludes values that were associated with spillage.
the sex was incorrectly
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY.
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E12 (PAGE 1): MATERNAL ABSOLUTE FEED CONSUMPTION
VALUES (G/DAY) - LACTATION
SUMMARY - Fl GENERATION
- --- -------------------- ---------------------- -- - ----------------------
DOSAGE GROUP DOSAGE (MG/KG/DAY) ------------------------
I
ii
0 (VEHICLE)
0.1
---- ---- ----------------- ---- -----------------------
RATS TESTED
N
25
25
--------------------------III 0.4
--- ----------------------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
MEAN+S.D.
54.0 + 6.1
57.4 + 7.1
52.0 + 7.3
DAYS
1
14d
MEA.N+S.D.
44.4 + 4.6
47.1 + 6.2
[ 23]e 42.2 + 5.5
[ 23]e --------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF LACTATION
( I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectl
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 f
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).
PROTOC*OL 418-008:
COMBINED ORAL PFOS IN RATS
(GAVAGE) (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TA13LE E13 (PAGE 1): MATERNAL RELATIVE
------ ---------------------
DOSAGE GROUP
DOSAGE ------
(MG/KG/DAY) ------------------- ----------
RATS TESTED
N
FEED CONSUMPTION VALUES (G/KG/DAY) - LACTATION - SUMMARY
Fl GENERATI
-------- ------
I 0 (VEHICLE) ---------------
25
-------------
---- ---- ----------------ii
0.1 ---- ----------------------
25
----- ------------
III
0.4 -----
------------
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 DAYS
I- 4 4- 7
MEAN+S.D. MEAN+S.D.
90.6 + 24.7 113.2 + 20.8
89.0 + 15.0 1 19)c
117.1 + 22.9
78.9 + 16.0 111.9 + 20.2
DAYS
7 - 14d
MEAN+S.D.
157.6 + 21.9
162.3 + 20.2
154.1 + 17.7
DAYS
1 - 14d
MEAN+S.D.
133.4 + 19.9
136.6 + 17.6
[ 23]e 128.8 + 15.1
( 23]e ---------------------------------------------------------------------------------------------------------------
DAYS = DAYS OF LACTATION
t I = NUMBER OF VALUES AVERAGED
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly
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 fe
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E14 (PAGE 1): SEXUAL MATURATION - SUMMARY - Fl GENERATION FEMALE RATS
-------
--- ---------------- ---
DOSAGE GROUP
DOSAGE (MG/KG/DAY) ------- - ---- --------------------
FEMALE RATS
N
- ---- ---------------- --
I 0 (VEHICLE) ----------------------------
25
------ ---- I -ii
0.1 ------ -------
25
------------------------- ---
III 0.4 -----------------------------
25
INCLUDED IN ANALYSES
N
24a
25
25
VAGINA PATENT b
MEAN+S.D.
31.1 + 1.8
31.1
--------- ---------------------------------------------------------------
a. Excludes values for female rat 13205, which was excluded from study b. Average day postpartum that the vagina was patent.
+ 2.0
30.5 + 1.4
-------------------------------------
on day 7 postweaning; the sex was inco
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'!; STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE EIS (PAGE 1): PASSIVE AVOIDANCE PERFORMANCE
- SUMMARY - Fl GENERATION
FEMALE RATS
------------- ------ -------------------DOSAGE GROUP DOSAGE (MG/KG/DAY)
-------------- ------ ------------------FEMALE RATS
---- ----------- -- ------
1 0 (VEHICLE) --------------------------
------ -------------------
11
111
0.1
0.4
------ --------------------
------------
SESSION la
N
22b
25
22
TRIALS LATENCY LATENCY FAILED
TO CRITERION TRIAL lc TRIAL 2c
TO LEARN d
MEAN+S.D. MEAN+S.D. MEAN+S.D.
N(t)
6.4 8.0 23.2
1(
+ 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
MEAN+S.D.
LATENCY TRIAL lc
MEAN+S.D.
------------------------------------------
4.0 + 2.9
3.3 + 2.7
2.8 + 1.2*
26.0 + 21.3
38.4 + 23.7
40.3 24.6
------------------------------------------------------- ------------
a. Sessions I (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 c. The latency was recorded in seconds.
d. Number of rats that did not meet the criterion in Session I (Learning Phase).
Significantly different from the vehicle control group value (p<0.05).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) 1,FOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
S'I'UDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E16 (PAGE 1): WATERMAZE PERFORMANCE
SUMMARY - Fl GENERATION
FEMALE RATS
- - ------------ - DOSAGE GROUP DOSAGE (MG/KG/DAY)
---------------- --FEMALE RATS
---------- -- ---------- --- I ----------------- -
I
0 (VEHICLE) ------------------------ --- ------ -----------
-- - ------------------------------ -----
IT 0.1 -- ---
III
0.4 ----------------------------------
SESSION la
N
21
25
21
TRIALS ERRORS LATENCY FAILED
TO CRITERION PER TRIAL
TRIAL 2b TO LEARN c
MEAN+S.D. MEAN+S.D. MEAN+S.D.
N(t)
11.2 + 2.7 0.51 + 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 0.51
14.5 2(
+ 2.5 + 0.27 8.2 9.5)
SESSION 2a
N
18
22
18d
TRIALS TO CRITERION
MEAN+S.D.
7.3 + 3.2
7.5 + 3.0
6.3 + 1.8
ERRORS PER TRIAL
MEAN+S.D.
0.16 + 0.18
0.15 + 0.14
0.17 + 0.20
LATENCY TRIAL lb
MEAN+S.D.
14.4 + 12.1
10.4 + 5.6
10.7 3.5
---------------------------------------------------------------------------------------------------------------
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. Number of rats that did not meet the criterion in Session 1 (Learning Phase); Session 2 (Retention Phase)
rats were excluded from group averageb and statistical analyses. d. Excludes values for rat 13264, which was not tested during Session 2 (Retention Phase).
PROTOCOL 418-006:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICITY
TABLE E17 (PAGE 1): MATING AND FERTILITY
SUMMARY - Fl GENERATION
FEMALE RATS
------- ------- -----DOSAGE GROUP DOSAGE (MG/KG/DAY)
----------------------
RATS IN COHABITATION
---------------------- - - - -------- --- ------------ - --------
I
ii
0 (VEHICLE)
0.1
-------------------------- ---- -------------------------------------
N
23a,b
25
III 0.4 ----
25
-----------------
----
DAYS IN COHABITATION
C
MEAN+S.D
3.6 + 3.2
3.9 + 2.8
2.6 + 1.5
RATS THAT MATED
N(t)
23(100.0)
24( 96.0)
25(100.0)
FERTILITY INDEX d
NIN (t)
22/23 95.6)
21/24 87.5)
24/25 96.0)
RATS WITH CONFIRMED
14ATING DATES
N
23
24
25
RATS 14ATING e DAYS 1- 7 DAYS 8-14
N(t) N(%)
20( 87.0) 3( 13.0)f
22( 91.7) 2( 8.3)
25(100.0) 0( 0.0)
RATS PREGNANT/RATS
IN
COHABITATION
MIN
22/23
21/25
24/25
(ti)
( 95.6)
84.0)
96.0)
------------------------------------------------------------------------------------------------------------------
a. Excludes values for rat 13205, which was excluded from study on day 7 postweaning; the sex was incorrectly id
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
rats on day I of cohabitation.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PEPINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E18 (PAGE 1): NECROPSY OBSERVATIONS
- SUMMARY - Fl GENERATION
FEMALE PATS
--- -- ---------- --------
- - -- -------------------------------------
DOSAGE GROUP
I
ii
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
--------------------------------------------------------------------------
RATS EXAMINED a
N
25
25
-------------------------
III 0.4 ----------------------------
25
-----------
FOUND DEAD
N
lb
0
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
Ic
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) for external observations confirmed
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 was incorrectly identified.
------at nec
PROTOCOL 416-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINAIAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E19 (PAGE 1): NATURAL DELIVERY OBSERVATIONS
SUMMARY - Fl GENERATION
FEMALE RATS
---------------------DOSAGE GROUP DOSAGE (MG/KG/DAY) ---------------------RATS ASSIGNED TO NATURAL DELIVERY
------------------------ - ---------------------------
I
0 (VEHICLE) -------------------------- --- -
ii 0.1 ----------------------
N
23a,b
25
------------------ ----- ------III 0.4
--------------------------------
25
PREGNANT
N(%)
22( 95.6)
21( 84.0)
24( 96,0)
DELIVERED
LITTERS
N(t)
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
PER DELIVERED LITTER
N MEAN+S.D.
338
15.4 +
2.9
352 16.8 + 2.2
369 15.4 + 2.2
DAMS WITH STILLBORN
PUPS
N(%)
4( 18.2)
3( 14.3)
9( 37.5)
DAMS WITH NO LIVEBORN PUPS
N
GESTATION
INDEX d
t
NIN
DAMS WITH ALL PUPS DYING
DAYS 1-4 POSTPARTUM
N
0 100.0 22/ 22
0
0 100.0 21/ 21
0
0 100.0 24/ 24
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
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 t
the first pup was delivered.
d. Number of rats with live offspring/number of pregnant rats.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN PATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E20 (PAGE 1): LITTER OBSERVATIONS
(NATURALLY DELIVERED PUPS) - SUMMARY
F2 GENERATION
LITTERS
----------------- - --- ------------ ----------- -- -------------------
----------------------
MATERNAL
DOSAGE GROUP
1
11
111
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
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.S
357 14.9 + 2.6
LIVEBORN
MEAN+S.D. N(i)
14.1 4
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)
O.S + 0.9 13( 3.6)
PUPS FOUND DEAD OR PRESUMED CANNIBALIZED
DAY DAYS DAYS DAYS DAYS
1 2- 4 5- 7
8-14 15-21
NIN(%) NIN(%) NIN(T) NIN(T) NIN(%)
2/310( 7/308( 0/171( 0/171( 0/171(
0.6) 2.3) 0.0) 0.0) 0.0)
2/318( 2/316( 2/167( 1/165( 0/164(
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
t
NIN
97.1 301/310
98.7 314/318
96.2 331/344
LACTATION INDEX c
%
100.0
98.2
96.7
NIN
171/171
164/167
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 sacrific
b. Number of live pups on day 4 (preculling) postpartum/number of liveborn pups on day I postpartum.
c. Number of live pups on day 21 (weaning) postpartum/number of live pups on day 4 (poatculling) postpartum.
PROTOCOL 418-008:
COMBINED ORI@L (GAVAGE) FERTILITY, DEVEI,OPMENTAL PFOS IN RAT!@ (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE E20 (PAGE 2): LITTER OBSERVATIONS (NATURALLY DELIVERED PUPS) - SUMMARY - F2 GENERATION LITTERS
-- -------------------------- ------------------------- ---------------------- --------------------------
MATERNAL DOSAGE GROUP
I
ii
III
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
-- --------------------------- ------------------------------------------------------------------------------
DELIVERED LITTERS WITH
ONE OR MORE LIVEBORN PUPS
N
22
21
24
SURVIVING PUPS/LITTER a
DAY 1 b DAY 4 PRECULLING DAY@.4 POSTCULLING DAY 7 DAY 14 DAY 21 PERCENT MALE PUPS PER NUMBER OF PUPS SEXED
MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D. MEAN+S.D.
14.1 + 3.5 13.7 + 3.3
7.8 + 0.8 7.8 + 0.8 7.8 + 0.8 7.8 + 0.8
15.1 + 2.4 15.0 + 2.8
8.0 + 0.2 7.8 + 0.5 7.8 + 0.7 7.8 + 0.7
14.3 + 2.5
13.8 + 2.4
8.0 + 0.2
7.8 + 0.7
7.7 + 0.8 f 2i]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
MEAN+S.D.
47.0 + 10.0
49.2 + 2.6
48.3 + 6.2
DAY 21
MEAN+S.D.
47.0 + 10.0
49.2 + 2.6
( 24]c 48.3 + 6.2
1 24]c ---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTPARTUM
( 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 13257; the dam was found dead on day 10 of lactation; eight pups were sacrifice
PROTOCOL 418-008:
COMBINED ORAI, (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E20 (PAGE 3): LITTER OBSERVATIONS
(NATURALLY DELIVERED PUPS) - SUMMARY - P2 GENERATION LITTERS
------- ------------------------
MATERNAL
DOSAGE GROUP
MATERNAL DOSAGE (MG/KG/DAY) ------------------------ --------
DELIVERED LITTERS WITH
ONE OR MORE LIVEBORN
PUPS
N
---------------- ------------------------------------ -------------- --- --
I
ii
III
0 (VEHICLE)
0.1
0.4
--------------------------------------- --------------------------------------
22
21
24
LIVE LITTER SIZE AT WEIGHING
DAY I
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.
PUP WEIGHT/LITTER
(GRAMS)
14.0 + 3.5 13.7 + 3.3
7.8 + 0.8 7.8 + 0.8 7.8 + 0.8 7.8 + 0.8
15.0 + 2.6 15.0 + 2.8
8.0 + 0.2 7.8 + 0.5 7.8 + 0.7 7.8 + 0.7
14.2 + 2.5
13.8 + 2.4
7.9 + 0.3
7.8 + 0.7
7.7 + 0.8 ( 23]a
7.7 + 0.8 23]a
DAY I
MEAN+S.D.
6.3 + 0.8
6.1 + 0.5
6.2 + 0.5
DAY 4 PRECULLING
MEAN+S.D.
8.7 + 1.6
8.2 + 1.0
8.0 + 1.3
DAY 4 POSTCULLING
MEAN+S.D.
8.8 + 1.6
8.3 + 1.0
8.0 + 1.3
DAY 7
MEAN+S.D.
14.7 + 2.4
13.9 + 2.2
12.8 + 2.6*
DAY 14
MEAN+S.D.
32.0 + 3.5
31.8 + 3.1
28.9 + 4.7**
DAY 21
MEAN+S.D.
50.1 + 5.1
49.2 + 5.0
[ 23]a 46.5 + 6.3
[ 23]a ---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTPARTUM
t I = NUMBER OF VALUES AVERAGED
a. Excludes values for litter 13257; the dam was found dead on day 10 of lactation; eight pups were sacrifice
Significantly different from the vehicle control group value (p!0.05).
Significantly different from the vehicle control group value (p:SO.01).
PROTOCOL 418 008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVEI,OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E21 (PAGE 1): CLINICAL OBSERVATIONS
FROM BIRTH TO DAY 21 POSTPARTUM
- SUMMARY - P2 GENERATION
PUPS
---------------------------- --- ------------------------ --------------------------- -- ---------------------
MATERNAL
DOSAGE GROUP
I
ii
III
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
--------------------------------------------------------------------------------------------------
------------
LITTERS EXAMINED (N)
22
21
24
---------------------------------------------------------------------------------------------------------------
TRANSIENT CLINICAL OBSERVATIONS:
a
TOTAL FREQUENCY
(DAYS x PUPS)/LITTERS
WITH OBSERVATIONS
NOT NURSING OR NESTING
NIN
1/ 1
o/ o
0/ 0
DECREASED
MOTOR ACTIVITY
NIN
1/ 1
o/ o
0/ 0
COLD TO TOUCH
NIN
1/ 1
0/ 0
0/ 0
PERSISTENT
CLINICAL OBSERVATIONS:
a
TIP OF TAIL MISSING
NIN
TOTAL FREQUENCY 21/ 1
(DAYS x PUPS)/LITTERS 0/ 0
WITH OBSERVATIONS 1/ 1
UMBILICAL HERNIA
NIN
0/ 0
0/ 0
IS/ 1
---------------------------------------------------------------------------------------------------------------
STATISTICAL
ANALYSES WERE RESTRICTED
TO THE NUMBER OF LITTERS WITH OBSERVATIONS.
NIN = TOTAL FREQUENCY
(DAYS x PUPS)/LITTERS
WITH OBSERVATIONS
a. Tabulation restricted to adverse observations; all other pups appeared normal.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.@9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E22 (PAGE 1): NECROPSY OBSERVATIONS
SUMMARY - F2 GENERATION
PUPS
-------------------------------------- -- - --------------------------------------------------- -------------
MATERNAL
DOSAGE GROUP
I
ii
III
MATERNAL DOSAGE (MG/KG/DAY)
0 (VEHICLE)
0.1
0.4
---------------------------------------------------------------------------------------------------------------
LITTERS EXAMINED (N)
22
21
24
---------------------------------------------------------------------------------------------------------------
TOTAL PUPS STILLBORN
OR FOUND DEAD a
N
9
12
19
STILLBORN
N
4
7
12
FOUND DEAD
N
5
5
7
NO MILK IN STOMACH b
N(t)
2( 40.0)
4( 80.0)
4( 57.1)
---------------------------------------------------------------------------------------------------------------
PUPS SACRIFICED
AND NECROPSIED
ON DAYS 4, 10 OR 21 POSTPARTUM
a
LITTERS EVALUATED PUPS EVALUATED
APPEARED NORMAL LITTER INCIDENCE PUP INCIDENCE
N N
N(t) N(%)
22 301
21( 95.4) 300( 99.7)
21 311
20( 95.2) 310( 99.7)
24 325
24(100.0) 325(100.0)
LIVER: MEDIAN AND LITTER INCIDENCE PUP INCIDENCE
LEFT
LATERAL LOBES, N(%) N(%)
TAN RAISED AREA 0( 0.0) o( o.o)
1( 4.8) 1( 0.3)
o( o.o) 0( 0.0)
BRAIN:
HYDROCEPHALY,
EXTREME DILATION OF ALL VENTRICLES
LITTER INCIDENCE PUP INCIDENCE
N(%) N(%)
1( 4.5) 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 b. Analysis restricted to pups found dead and necropsied.
precluded evaluation.
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE E23 (PACE 1): CLINICAL OBSERVATIONS
- INDLVIDUAL DATA - Fl GENERATION FEMALE RATS
- -- ------------------------ ------------------- -- ---------------------------- --------------- ------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
RAT #
DESCRIPTION
---------------------------------------------------------------------------------------------------------------
13201 13202 13203 13204
DP(
77
DP( 23- 24) DP( 72- 75) DG( 0- 21) DG( 5- 21)
CHROMORHINORRHEA
NO ADVERSE FINDINGS
URINE-STAINED
ABDOMINAL
FUR
EARS: SWOLLEN AND PURPLE
EARS: SWOLLEN AND PURPLE
LOCALIZED ALOPECIA:
LIMBS
13205b 13206
DL( I- 21) DL( I- 21)
DP(
7)
DP( 69- 75)
DP( 69- 75)
EARS:
SWOLLEN AND
LOCALIZED ALOPECIA:
PURPLE a LIMBS a
SACRIFICED; INCISORS:
THE SEX WAS INCORRECTLY MISSING/BROKEN
INCISORS: MISALIGNED
IDENTIFIED
13207
DG( DG( DG( DG( DG( DL( DP(
0- 12) 13 )
0- 12) 13 )
18- 21) 1- 21)
71- 74)
INCISORS:
MISSING/BROKEN
INCISORS:
GROWN IN
INCISORS:
MISALIGNED
INCISORS:
REALIGNED
INCISORS:
MISSING/BROKEN
INCISORS:
MISSING/BROKEN
a
EARS:
SWOLLEN AND PURPLE
DG( 0- 21)
EARS:
SWOLLEN AND PURPLE
13208
DL( 1- 21) DP( 9- 16)
EARS:
SWOLLEN
URINE-STAINED
AND PURPLE a
ABDOMINAL
FUR
DP( 11- 16)
DP(
17
PERIVAGINAL
SWELLING
SWELLING RESOLVED
DP(
71
DP(
72
LEFT FOREPAW:
SWOLLEN
SWELLING RESOLVED
DP( 71- 74) DG( 0- 21) DG( 7- 21) DG( 16- 18)
LOCALIZED ALOPECIA: LOCALIZED ALOPECIA: LOCALIZED ALOPECIA: CHROMORHINORRHEA
LIMBS LIMBS UNDERSIDE
DG( 16- 21)
CHROMODACRYORRHEA
DG( 16- 21)
INCISORS:
MISALIGNED
DL( 1- 21) DL( I- 21)
DL( I- 21)
CHROMODACRYORRHEA
a
INCISORS:
MISALIGNED
LOCALIZED ALOPECIA:
a LIMBS a
DL( 1- 21)
LOCALIZED ALOPECIA:
UNDERSIDE
DL(
20
URINE-STAINED
ABDOMINAL
FUR
13209
NO ADVERSE FINDINGS
---------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
DG = DAY OF GESTATION
a. observation confirmed at necropsy.
DL = DAY OF LACTATION
b. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE@ PFOS IN RATS (SPONSOR'S
FERTIUITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICII
TABLE E23 (PACE 2): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA
Fl GENERATION
FEMALE RATS
------------------------------------------ -------------------- ------------------------------------------------
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
----------------------------------------------------------------------------------------------------------------
RAT #
DESCRIPTION
----------------------------------------------------------------------------------------------------------------
13210
DP( 62- 77)
INCISORS:
MISALIGNED
13211
13212 13213 13214 13215
DP( DG( DG( DG( DG( DL( DL( DP( DG( DL(
76-.77) 0- 2) 0- 20) 4)
17- 20) I- 21) I- 21) 1- 75) 0- 22) I- 21)
CHROMODACRYORRHEA
CHROMODACRYORRHEA
INCISORS:
MISALIGNED
CHROMODACRYORRHEA
INCISORS:
MISSING/BROKEN
INCISORS: INCISORS:
MISSING/BROKEN MISALIGNED a
LEFT HINDPAW:
THIRD AND
LEFT HINDPAW:
THIRD AND
LEFT HINDPAW:
THIRD AND
NO ADVERSE FINDINGS
NO ADVERSE FINDINGS
NO ADVERSE NO ADVERSE
FINDINGS FINDINGS
a
FOURTH FOURTH FOURTH
DIGITS DIGITS DIGITS
MISSING MISSING MISSING
13216 13217
DP( 65- 74) DG( 0- 21) DL( I- 21) DP( 65- 71)
LOCALIZED LOCALIZED LOCALIZED INCISORS:
ALOPECIA:
LIMBS
ALOPECIA:
LIMBS
ALOPECIA:
LIMBS a
MISSING/BROKEN
DP(
72 )
INCISORS:
GROWN IN
DP( 65- 80)
INCISORS:
MISALIGNED
DP( 69- 73)
CHROMODACRYORRHEA
DP(
79 )
CHROMORHINORRHEA
DG( DL( DL(
0- 21) I- 2)
3
INCISORS: INCISORS: INCISORS:
MISALIGNED MISALIGNED REALIGNED
13218 13219
NO ADVERSE NO ADVERSE
FINDINGS FINDINGS
13220
DG( 0- 11)
TAIL:
SHEATH MISSING
DG( 0- 11)
TIP OF TAIL BLACK
DG( 12- 21)
TIP OF TAIL MISSING
13221
DL( I- 21)
DP(
28
TIP OF TAIL MISSING a FOUND DEAD
13222
NO ADVERSE FINDINGS
13223
NO ADVERSE FINDINGS
13224
DL( 19- 21)
EARS: SWOLLEN AND PURPLE a
13225
DG(
5)
CHROMORHINORRHEA
DG( 12- 21)
CHROMORHINORRHEA
DL( I- 6)
CHROMORHINORRHEA
-----------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
DG = DAY OF GESTATION
DL = DAY OF LACTATION
a. Observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E23 (PAGE 3): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION FEMALE RATS
---------------------------------------------------- -------------------------- ----------------------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------------------------------- -- ---------------------------------------------------- --
RAT N
DESCRIPTION
---------------------------------------------------------------------------------------------------------------
13226 13227 13228
13229 13230
13231 13232
DG( DG( DG( DG(
10- 24) 25 )
11- 24) 25
DG( 2- 20) DL( I- 21)
DP( 72- 78)
DG(
0)
D(I( 0- 3)
DG(
4
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 a
NO ADVERSE FINDINGS
INCISORS: MISSING/BROKEN
INCISORS: GROWN IN
INCISORS:
MISSING/BROKEN
INCISORS:
GROWN IN
DG(
9
CHROMORHINORRHEA
DG( 9- 21)
INCISORS:
MISSING/BROKEN
13233 13234
DG( 9- 21) DL( 1- 21) DL( I- 21) DL( IS- 16)
DP( 73- 81)
DG( 0- 21)
DG(
19 )
INCISORS:
MISALIGNED
INCISORS:
MISSING/BROKEN
a
INCISORS:
MISALIGNED
a
CHROMORHINORRHEA
NO ADVERSE FINDINGS
EARS:
SWOLLEN AND PURPLE
EARS:
SWOLLEN AND PURPLE
SOFT OR LIQUID FECES
13235
DL( 1- 21)
DL( 5- 11)
DG(
22
EARS: SWOLLEN AND PURPLE a
CHROMODACRYORRHEA
RED PERIVAGINAL
SUBSTANCE
13236
NO ADVERSE FINDINGS
13237 13238
DL( 13- 21) DP( 75- 76)
CHEST: ABRASION (0.5 CM X 0.3 CM)a
INCISORS:
MISALIGNED
DG( 0- 21) DL( I- 21)
INCISORS: INCISORS:
MISALIGNED MISALIGNED a
DL( 10- 21)
INCISORS:
MISSING/BROKEN
a
13239
NO ADVERSE FINDINGS
13240
NO ADVERSE FINDINGS
13241
NO ADVERSE FINDINGS
13242
NO ADVERSE
FINDINGS
---------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
DG = DAY OF GESTATION
a. Observation confirmed at necropsy.
DL = DAY OF LACTATION
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E23 (PAGE 4): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION FEMALE RATS
--------------------------DOSAGE GROUP Il
------ --- -----------------------0.1 MG/KG/DAY
-------------------
--- - ---------------------
---------------------------------------------------------------------------------------
RAT #
DESCRIPTION
I ----------- -----------
---------------------------------- ----------------------------------------------------------------------------
13243
DP( 65- 75)
CHROMODACRYORRHEA
DP( 65- 75)
INCISORS:
MISALIGNED
DG( 0- 25)
CHROMODACRYORRHEA
a
DG( 0- 25)
INCISORS:
MISALIGNED a
13244
DP( 38- 47)
BACK: ABRASION (0.3 CM IN DIAMETER)
DP( 38- 48)
LOCALIZED ALOPECIA:
BACK
DP(
49
ALOPECIA NO LONGER APPARENT
DP(
48
BACK: SCAB (0.3 CM IN DIAMETER)
DP(
49
SCAB NO LONGER APPARENT
DP( 72- 74)
LOCALIZED ALOPECIA:
HEAD
DG( 0- 4)
LOCALIZED ALOPECIA!
HEAD
DG(
5)
ALOPECIA NO LONGER APPARENT
13245
DP( 51- 59)
INCISORS:
MISSING/BROKEN
13246
DP(
60 )
DP( 38- 48)
INCISORS: GROWN IN LOCALIZED ALOPECIA:
BACK
DP(
49 )
ALOPECIA
NO LONGER APPARENT
DP( 72- 75)
EARS: SWOLLEN AND PURPLE
DG( 0- 21)
EARS: SWOLLEN AND PURPLE
DG( 10- 21)
LOCALIZED ALOPECIA:
LIMBS
DL( 1- 21)
EARS: SWOLLEN AND PURPLE a
DL( I- 21)
LOCALIZED ALOPECIA:
LIMBS
13247
NO ADVERSE FINDINGS
13248
DG(
2
INCISORS:
MISALIGNED
DG(
3
INCISORS:
REALIGNED
DG( 2- 11)
INCISORS:
MISSING/BROKEN
DG(
12 )
INCISORS:
GROWN IN
DG( 7- 21)
LOCALIZED ALOPECIA:
LIMBS
DG( 10- 21) DL( I- 21)
EARS: EARS:
SWOLLEN SWOLLEN
AND PURPLE AND PURPLE a
DL( 1- 21)
LOCALIZED ALOPECIA:
LIMBS a
DL(
21
INCISORS:
MISSING/BROKEN
a
13249
NO ADVERSE FINDINGS
13250
DP( SO- 60)
INCISORS!
MISSING/BROKEN
DP(
61 )
INCISORS: GROWN IN
----------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
DG = DAY OF GESTATION
DL = DAY OF LACTATION
a. Observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E23 (PAGE 5): CLINICAL OBSERVATIONS
INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
--- ---- --------------- ----------------- --------- ------ -----------
--- ----------------- -----------
DOSAGE GROUP 111
0.4 MG/KG/DAY
------------------------------------------------------------------------ --------------------------------------
RAT #
DESCRIPTION
---------------------------------------------------------------------------------------------------------------
13251 13252
13253
DG( DL( DL( DG(
4- 20) I- 20)
21 ) I- 15)
NO ADVERSE INCISORS: INCISORS: INCISORS: INCISORS:
FINDINGS MISALIGNED MISALIGNED REALIGNED MISSING/BROKEN
13254
DG(
16 )
DP( 49- 53)
INCISORS: INCISORS:
GROWN IN MISSING/BROKEN
13255 13256
DP( 54- 55)
DP( 48- 67)
DP(
68
DL(
1
INCISORS:
GROWN IN
INCISORS:
MISSING/BROKEN
INCISORS:
GROWN IN
RED PERIVAGINAL
SUBSTANCE
13257
DL(
10
FOUND DEAD
13258 13259
13260
DG( 11- 21) DL( I- 21) DG( 6- 9)
NO ADVERSE FINDINGS
EARS:
SWOLLEN AND PURPLE
EARS:
SWOLLEN AND PURPLE a
INCISORS:
MISSING/BROKEN
DG(
10 )
INCISORS:
GROWN IN
13261
DG( 10- 21) DL( I- 21)
DG( 3- 5) DG( 3- 21)
EARS:
SWOLLEN AND PURPLE
EARS:
SWOLLEN AND PURPLE a
INCISORS:
MISSING/BROKEN
INCISORS:
MISALIGNED
DL( 1- 12)
INCISORS:
MISALIGNED
DL(
13
INCISORS:
REALIGNED
13262
NO ADVERSE FINDINGS
13263
NO ADVERSE FINDINGS
13264
DL(
1
RED PERIVAGINAL
SUBSTANCE
13265
DP( 55- 73)
INCISORS:
MISALIGNED
DG( 0- 21)
INCISORS:
MISALIGNED
DG( 7- 21)
LOCALIZED ALOPECIA:
LIMBS
DG( 8- 21)
CHROMODACRYORRHEA
DG( DL( DL(
21 ) I- 5) I- 21)
RED PERIVAGINAL
SUBSTANCE
CHROMODACRYORRHEA
INCISORS:
MISALIGNED a
DL( I- 21)
LOCALIZED ALOPECIA:
LIMBS a
DL( 9- 21)
LOCALIZED ALOPECIA:
UNDERSIDE a
DL( 10- 20)
CHROMODACRYORRHEA
DL( 19- 21)
INCISORS:
MISSING/BROKEN
a
---------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
DG = DAY OF GESTATION
DL = DAY OF LACTATION
a. observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERrNATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E23 (PAGE 6): CLINICAL OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
--------------------------- --@-I ------ ----------------- ------------------------- -------------- -----------
DOSAGE GROUP 111 --------------------------- --
0.4 MG/KG/DAY ---------------------------------------------------
--------------------------
RAT #
DESCRIPTION
----------------------------------------------------------------------------------- --------------------------
13266
NO ADVERSE FINDINGS
13267
NO ADVERSE FINDINGS
13268
DP( 71- 74)
INCISORS:
MISALIGNED
DP( 72- 74) DG( 0- 2)
CHROMODACRYORRHEA CHROMODACRYORRHEA
DG( 0- 20) DG( 3- 8)
INCISORS: LOCALIZED
MISALIGNED ALOPECIA:
HEAD
DG(
9
DG(
4
ALOPECIA NO LONGER CHROMODACRYORRHEA
APPARENT
DL( I- 21)
INCISORS:
MISALIGNED a
DL( 20- 21)
INCISORS:
MISSING/BROKEN
a
13269
DL(
1)
RED PERIVAGINAL
SUBSTANCE
13270
DP( 62- 76)
INCISORS:
MISALIGNED
DP( 65- 72)
CHROMODACRYORRHEA
DG( 0- 21)
INCISORS:
MISALIGNED
DL(
1)
RED PERIVAGINAL
SUBSTANCE
DL( 1- 21)
INCISORS:
MISALIGNED a
DL( 9- 21)
INCISORS:
MISSING/BROKEN
a
13271
DP( 56- 74)
INCISORS:
MISALIGNED
DP( 58- 61)
CHROMODACRYORRHEA
DP( 69- 74)
CHROMODACRYORRHEA
DG( 0- 21)
CHROMODACRYORRHEA
DG( 0- 21)
INCISORS:
MISALIGNED
DL( I- 21) DL( I- 21)
CHROMODACRYORRHEA
a
INCISORS:
MISALIGNED a
13272
DP(
74
URINE-STAINED
ABDOMINAL
FUR
DG(
0
URINE-STAINED
ABDOMINAL
FUR
13273
DG(
21
RED PERIVAGINAL
SUBSTANCE
13274
NO ADVERSE FINDINGS
13275
DL(
I
RED PERIVAGINAL
SUBSTANCE
--------------------------------------------------------------------------------------------------------------
DP = DAY POSTWEANING
DG = DAY OF GESTATION
DL = DAY OF LACTATION
a. observation confirmed at necropsy.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN I?ATS (SPONSOR'S
FERTILITY,
DEVEI@OPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E24 (PAGE 1): BODY WEIGHTS - PRECOHABITATION
INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
-------------- -
DAY 1
8
---------------------------
RAT #
DOSAGE GROUP
---------------------------- -
13201 13202 13203 13204 13205b
53.
95.
46.
86.
45.
77.
53.
97.
------ - --- --- ---
---------- ------- ---------
15
22
29
36
43
50
-------------------- -- -------------------------------
1
0 (VEHICLE) MG/KG/DAY
-------------------- -- --I -------------------------------
138.
170.
188.
217.
233.
245.
122. 114. 137.
143. 142. 168.
166. 165. 194.
186. 171. 204.
211. 203. 228.
220. 217. 234.
---------- 1-1 ----------
57
64
71
-----------------------
-----------------------
261.
271.
279
233.
253.
261
222.
236.
238
236.
243.
257
13206
55.
101.
145.
188.
226.
249.
262.
272.
270.
298.
307
13207
61.
107.
154.
184.
229.
257.
276.
289.
307.
320.
340
13208
57.
96.
139.
165.
229.
228.
257.
287.
293.
297.
324
13209 13210
54.
94.
125.
151.
167.
188.
200.
215.
227.
239.
249
50.
90.
138.
170.
200.
224.
254.
262.
280.
298.
301
13211
54.
92.
140.
182.
180.
211.
244.
257.
284.
298.
310
13212
56.
95.
146.
177.
208.
217.
234.
250.
251.
278.
278
13213
50.
94.
141.
189.
222.
247.
257.
278.
282.
303.
317
13214
64.
109.
152.
187.
202.
238.
260.
274.
284.
290.
309
13215
49.
83.
121.
148.
169.
190.
202.
221.
228.
242.
238.
13216
45.
78.
117.
154.
184.
207.
223.
247.
256.
272.
272.
13217
44.
80.
136.
174.
199.
237.
251.
266.
272.
289.
291.
13218
51.
93.
139.
173.
181.
214.
217.
235.
249.
261.
262.
13219
46.
85.
130.
164.
182.
204.
220.
238.
243.
248.
261.
13220
49.
82.
120.
154.
182.
214.
212.
237.
239.
243.
246.
13221
57.
100.
142.
170.
FOUND DEAD ON DAY 28 POSTWEANING
13222
59.
105.
158.
198.
228.
268.
277.
307.
317.
327.
338.
13223
42.
81.
112.
141.
166.
186.
200.
212.
215.
224.
c
13224
43.
81.
128.
177.
203.
235.
264.
285.
291.
320.
c
13225
44.
87.
134.
169.
192.
208.
218.
227.
230.
233.
c
----------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Precohabitation body weights were recorded on the day cohabitation was begun in the Fl generation
rats were 85 to 97 days of age. b. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
rats; at
C. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 64 p
was the last day on which the youngest rats (in this group) had a body weight value recorded.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629@,.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E24 (PAGE 2): BODY WEIGHTS - PRECOHABITATION
- INDIVIDUAL DATA - Fl GENERATION FEMALE RATS
----- ------
---- -----RAT #
------------
-- - --------------- ---- ----- --- --- ------
DAY 1
8
15
22
29
-------------------- ---- -----------------------
DOSAGE GROUP Il
0.1 MG/KG/DAY
-------------------- - -------------- -----------
-
---------- --------------
36
43
50
57
- ----------------- ----------
------ - ---
64
7
-------- ---
----- -- ---------- ---------------------------
13226
52.
87.
129.
161.
188.
210.
229.
236.
253.
261.
26
13227
52.
91.
135.
162.
184.
208.
226.
238.
254.
266.
j7
13228
44.
88.
130.
155.
180.
200.
224.
226.
244.
254.
25
13229
41.
78.
116.
154.
172.
200.
217.
22S.
246.
24S.
26
13230
55.
96.
141.
177.
202.
226.
245.
256.
266.
272.
28
13231
50.
94.
141.
180,
214.
244.
264.
284.
286.
305.
31
13232
53.
95.
136.
170.
195.
214.
229.
244.
246.
266.
28
13233
51.
92.
146.
178.
207.
238.
271.
288.
317.
302.
31
13234
48.
88.
139.
180.
215.
252.
266.
283.
299.
309.
33
13235
42.
82.
128.
164.
191.
222.
245.
266.
282.
301.
31
13236
51.
96.
142.
177.
198.
224.
238.
262.
276.
275.
29
13237
57.
99.
150.
180.
206.
227.
246.
262.
258.
272.
27
13238
53.
94.
142.
170.
193.
214.
232.
245.
256.
264.
28
13239
54.
100.
147.
191.
222.
236.
250.
288.
284.
289.
30
13240
50.
90.
139.
181.
208.
236.
251.
269.
267.
280.
284
13241
50.
86.
128.
166.
195.
222.
237.
248.
260.
280.
28
13242
50.
90.
133.
170.
198.
227.
248.
258.
278.
282.
301
13243
43.
so.
141.
178.
220.
254.
265.
285.
287.
308.
307
13244
57.
97.
139.
177.
192.
216.
241.
259.
259.
278.
293
13245
53.
98.
142.
189.
215.
244.
259.
275.
300.
294.
312
13246
50.
90.
134.
164.
184.
211.
231.
242.
252.
271.
267
13247
52.
93.
136.
171.
202.
240.
258.
282.
284.
302.
303
13248
52.
95.
145.
ISO.
206.
226.
251.
261.
279.
278.
293
13249
52.
94.
146.
183.
216.
238.
246.
260.
271.
286.
282
13250
50.
95.
144.
178.
209.
240.
258.
293.
314.
328.
326
---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Precohabitation body weights were recorded on the day cohabitation rats were 85 to 97 days of age.
was begun in the Fl generation rats; at
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E24 (PAGE 3): BODY WEIGHTS
PRECOHABITATION
- INDLVIDIJAL DATA - Fl GENERATION
FEMALE RATS
------
--------- ------
----------- ----
------ ------
-
-------------
DAY 1
8
----- - -------------------- ------
15
22
29
- - ------------------ I --
36
43
50
57
64
7
---------------------- --- - - ---------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
------- ------------------------------------------------------------------------------------ I ----------------
13251
46.
102.
153.
187.
220.
246.
266.
279.
301.
312.
32
13252
43.
83.
120.
175.
183.
209.
227,
244.
255.
257.
27
13253
42.
91.
137.
162.
193.
203.
230.
228.
241.
252.
26
13254
47.
92.
138.
168.
172.
194.
211.
223.
233.
233.
25
13255
46.
90.
133.
172.
197.
214.
246.
258.
280.
286.
29
13256
46.
88.
124.
153.
189.
207.
228.
247.
251.
275.
28
13257
so.
92.
139.
187.
224.
254.
288.
301.
316.
340.
34
13258
52.
95.
133.
173.
200.
220.
249.
2S7.
265.
275.
28
13259
50.
93.
133.
163.
190.
212.
234.
247.
252.
266.
27
13260
49.
86.
130.
162.
199.
231.
252.
266.
267.
284.
29
13261
53.
87.
131.
162.
192.
212.
233.
249.
259.
264.
26
13262
51.
92.
136.
177.
197.
224.
250.
264.
284.
284.
30
13263
48.
90.
142.
179.
204.
228.
245.
250.
263.
268.
26
13264
45.
83.
122.
150.
173.
203.
208.
230.
230.
236.
24
13265
52.
97.
143.
179.
201.
229.
260.
283.
300.
307.
29
13266
47.
82.
123.
163.
188.
212.
236.
249.
269.
284.
28
13267
48.
86.
126.
153.
172.
201.
214.
231.
240.
253.
25
13268
46.
89.
130.
162.
185.
207.
216.
230.
236.
243.
25
13269
58.
97.
136.
159.
173.
19S.
212.
230.
240.
265.
28
13270
so.
93.
139.
165.
199.
235.
243.
258.
273.
277.
27
13271
47.
90.
124.
lS2.
169.
194.
218.
229.
235.
244.
24
13272
62.
115.
165.
203.
236.
255.
270.
293.
308.
310.
31
13273
57.
102.
143.
173.
204.
231.
244.
253.
267.
285.
294
13274
42.
86.
129.
165.
185.
210.
231.
234.
257.
252.
276
13275
40.
78.
125.
168.
203.
218.
236.
246.
246.
255.
---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTWEANING
ALL WEIGHTS WERE RECORDED IN GRAMS (G). a. Precohabitation body weights were recorded on the day cohabitation
rats were 85 to 97 days of age.
was begun in the Fl generation
rats; a
b. Because body weight values were recorded at weekly intervals, based on each rat's day postweaning, day 64
was the last day on which the youngest rats (in this group) had a body weight value recorded.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXIC
TABLE E25 (PAGE 1): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA - Fl GENERATION FEMALE RAT
---------- --------------------------- ------------------------------- ----------------------- -----------
PREGNANCY
STATUS
DAY 0
1
2
3
4
5
6
7
8
9
1
---------- -----------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------- ---------------------------- -------------------------------------------------------------------
13201 P 13202 P 13203 P 13204 P 13205a
284.
298.
298.
304.
308.
311.
308.
308.
316.
319.
32
265.
274.
281.
284.
285.
292.
297.
301.
303.
312.
32
250.
256.
267.
275.
273.
277.
279.
283.
286.
291.
30
257.
246.
270.
275.
280.
285.
287.
294.
300.
299.
30
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
307.
304.
312.
321.
321.
326.
334.
341.
345.
345.
35
324.
330.
340.
344.
358.
357.
365.
371.
377.
381.
38
308.
314.
316.
331.
329.
332.
341.
343.
346.
344.
36
259.
264.
263.
268.
269.
274.
272.
273.
281.
280.
27
294.
306.
305.
312.
31S.
311.
323.
326.
329.
337.
33
304.
315.
323.
322.
330.
335.
347.
349.
353.
362.
36
288.
296.
301.
309.
308.
309.
316.
314.
327.
333.
33
317.
325.
332.
339.
345.
349.
351.
357.
365.
368.
37
301.
309.
318.
323.
322.
332.
330.
336.
346.
347.
35
243.
248.
250.
257.
260.
261.
260.
265.
276.
279.
28
283.
290.
297.
299.
302.
306.
305.
312.
312.
324.
32
309.
316.
318.
324.
326.
327.
334.
340.
340.
342.
34
273.
275.
282.
283.
286.
291.
298.
300.
306.
313.
32
252.
258.
266.
270.
270.
275.
277.
277.
284.
288.
29
246.
261.
268.
273.
279.
282.
285.
290.
288.
292.
29
FOUND DEAD ON DAY 28 POSTWEANING
13222 P
336.
338.
351.
352.
348.
352.
359.
365.
364.
373.
37
13223 P
253.
266.
265.
265.
267.
271.
273.
279.
280.
282.
28
13224 P
329,
341.
345.
350.
349.
358.
3S6.
363.
360.
367.
37
13225 P
234.
244.
253.
256.
260.
263.
266.
270.
273.
278.
28
--------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
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.
PROTOCOL 418-008:
COMBINED ORAL (GA"GE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E25 (PAGE 2): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL
DATA - Fl GENERATION
FEMALE RATS
---------------------------PREGNANCY
- - -------------- --------
--------------------- -------------------------------
STATUS
DAY 13
14
15
16
17
18
19
20
21
22
23
---------------------------- ---------------------------- @-I ---------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
13201 P 13202 P
13203 P 13204 P 13205a
339. 340. 300. 324.
342. 340. 306. 338.
346. 350. 320. 345.
353. 363. 328. 354.
372. 375. 348. 366.
389. 394. 353. 381.
398. 408. 358. 397.
418. 424. 369. 406.
431.
355. 422.
13206 P 13207 P 13208 P
370392. 366.
375. 406. 377.
387. 416. 379.
390. 416. 373.
399. 443. 362.
412. 447. 390.
427. 476. 404.
432. 496. 423.
428. 498. 403.
13209 NP 13210 P
276.
280.
284.
280.
276.
273.
277.
274.
275.
279.
282
360.
367.
372.
393.
410.
416.
432.
453.
13211 P
385.
388.
391.
394.
406.
420.
424.
424.
431.
439.
13212 P 13213 P 13214 P 13215 P 13216 P
354. 386. 362. 300. 342.
361. 393. 370. 303. 347.
370. 403. 382. 312. 350.
372. 415. 390. 327. 354.
390. 433. 407.
343. 366.
404. 445. 422. 362. 389.
414. 464. 430. 379. 407.
433. 472. 446. 389. 417.
442. 477. 462. 398. 433.
13217 P
362.
362.
376.
384.
392.
407.
422.
439.
458.
13218 P
340.
346.
352.
356.
369.
386.
405.
411.
431.
13219 P
313.
317.
322.
325.
342.
363.
375.
393.
402,
13220 P
302.
312.
314.
322.
337.
351.
358.
378.
396.
13221
FOUND DEAD ON DAY 28 POSTWEANING
13222 P
392.
398.
408.
418.
434.
443.
455.
453.
465.
13223 P
298.
303.
311.
316.
334.
352.
362.
379.
396.
13224 P
386.
397@
392.
408.
396.
424.
444.
446.
477.
13225 P
290.
294.
298.
306.
323.
332.
343.
356.
361.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PPOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E25 (PAGE 3): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL
DATA - Fl GENERATION
FEMALE RATS
------ ------------------------------------------------------- ------------------------------------------------
PREGNANCY
STATUS
DAY 0
1
2
3
4
5
6
7
8
9
10
------ --------------------------------------------------------------------------------------------------------
PAT #
DOSAGE GROUP Il
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
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
270. 288. 284. 259. 286. 311. 290. 316. 334. 314. 295. 292. 282. 299. 292. 290. 301. 305. 297. MATING
273.
280.
293.
300.
291.
297.
278.
281.
294.
299.
326.
327.
298.
297.
328.
334.
345.
356.
311.
318.
308.
314.
299.
304.
284.
290.
301.
312.
300.
306.
288.
298.
312.
321.
314.
317.
286.
280.
NOT CONFIRMED
282. 304. 300. 289. 304. 329. 301. 334. 366. 324. 323. 303. 296. 312. 310. 299. 326. 321. 289.
286. 309. 303. 289. 307. 340. 302. 338. 360. 328. 323. 308. 296. 314. 312. 304. 333. 321. 290.
289. 309. 308. 298. 309. 337. 302. 340. 374. 331. 318. 309. 306, 318. 321. 306. 330. 326. 288.
294. 314. 312. 296. 316. 338. 310.
332. 377. 335. 330. 318. 307. 325. 315. 309. 332. 321. 288.
294. 318. 319. 298. 321. 345. 309. 319. 383. 342. 327. 315. 308. 328. 322. 312. 332. 327. 295.
298. 325. 321. 300. 324.
345. 316. 332. 386. 346. 330. 318. 315. 329. 328. 318. 342. 332. 300.
305. 328. 320. 304. 334. 345. 314. 345. 386.
351. 338. 317. 321. 332. 335. 318. 343. 332. 298.
i06 330 320 311 338 355 317 350 388 359 345 310 324 340 338 325 350 336 291
13246 P
280.
283.
286.
295.
297.
304.
303.
303.
305.
312.
318
13247 P
307.
314.
313.
324.
326.
331.
329.
332.
336.
346.
352
13248 P
302.
312.
311.
316.
318.
322.
328.
319.
331.
326.
338
13249 P
279.
283.
289.
297.
296.
301.
304.
306.
310.
311.
320
13250 P
315.
330.
334.
334.
335.
337.
341.
345.
353.
351.
353
---------------------------------------------------------------------------------------------------------------
P = PREGNANT DAY - DAY OF
NP = NOT PREGNANT PRESUMED GESTATION
(VALUES EXCLUDED
FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629',.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E25 (PAGE 4): MATERNAL BODY WEIGHTS - PRESUMED GESTATION - INDIVIDUAL DATA
Fl GENERATION
FEMALE RATS
--------------------------------- ---- --------------- ------ --------------------- ----------------- --------
PREGNANCY
STATUS
DAY 13
14
---------------------------------
is
16
17
18
19
20
21
22
23
---------------------------- ------------------------------------------------
RAT
DOSAGE GROUP Il
0.1 MG/KG/DAY
--------------------------------------------------------------
------------------------------------------------
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
327. 341. 321. 325. 346. 364. 324. 369. 410. 338. 361. 325. 347. 352. 368. 336. 367. 352.
288. MATING
333.
336.
345.
359.
308.
300.
331.
340.
353.
367.
371.
377.
330.
338.
370.
383.
418.
432.
341.
349.
360.
371.
335.
346.
342.
350.
364.
370.
359.
370.
347.
355.
373.
388.
342.
347.
291.
298.
NOT CONFIRMED
350. 374. 297. 347. 366. 395. 350. 397. 435. 351. 386. 356. 365. 367. 380. 366. 399. 340. 302.
362. 374. 304. 355. 379. 410. 3S5. 410. 4S4. 356. 403. 370. 377. 369. 396. 379. 418. 334. 309.
381. 391. 304. 368. 390. 426. 363. 422. 468. 360, 424. 390. 391. 384. 414. 397. 442. 339. 316.
394. 401. 298. 383. 403. 439. 378.
436. 483. 371. 438. 407. 411. 405. 424. 413. 461. 332. 317.
403. 413. 301.
379. 416. 455. 393. 443. 507. 385. 466. 422. 430. 419. 448. 420. 463. 332. 317.
416. 428. 305. 407.
480. 408. 459. 524. 397. 488. 442. 448. 425. 457. 425. 478. 324. 320.
303.
406.
320. 326.
294
32S. 321.
13246 P
335.
330.
340.
345.
360.
371.
382.
397.
13247 P
361.
363.
371.
383.
397.
420.
420.
432.
13248 P
358.
368.
369.
377.
391.
410.
422.
436.
13249 P
334.
341.
350.
360.
380.
401.
403.
417.
13250 P
368.
374.
383.
395.
408.
421.
435.
445.
----------------------------------------------------------------------------------------------------------------
414. 448. 4SB. 440, 464.
P = PREGNANT
NP = NOT PREGNANT (VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
PERTILII'Y, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E25 (PAGE 5): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fl GENERATION
FEMALE RATS
-------------- -------------------- ------------PREGNANCY
- -------------------------
--------------------- --
STATUS
DAY 0
1
2
3
-------------------------------------------------
4
5
6
7
8
9
10
------------------------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
------------------------------------------------- ---------------------------- -------------------------------
13251 P
321.
326.
329.
334.
339.
343.
342.
343.
351.
357.
365
13252 P
276.
290.
290.
297.
297.
302.
306.
309.
310.
314.
316
13253 P
266.
273.
276.
279.
284.
288.
293.
299.
304.
311.
313
13254 P
261.
268.
278.
282.
283.
285.
293.
293.
300.
304.
311
13255 P
294.
305.
305.
303.
309.
311.
311.
311.
317.
322.
329
13256 P
277.
289.
298.
302.
305.
309.
310.
312.
314.
317.
324
13257 P
350.
355.
360.
363.
364.
370.
370.
375.
384.
383.
389
13258 P
282.
294.
300.
304.
308.
311.
314.
318.
322.
325.
330
13259 P
269.
282.
282.
287.
290.
294.
292.
295.
304.
306.
308
13260 P
293.
311.
310.
318.
323.
335.
331.
339.
345.
348.
354
13261 P
261.
250.
280.
277.
275.
289.
287.
290.
290.
298.
300
13262 P
292.
299.
308.
312.
313.
318.
314.
318.
319.
329.
331
13263 P
272.
279.
285.
286.
294.
293.
300.
298.
302.
311.
316
13264 P
243.
252.
256.
260.
261.
265.
270.
273.
271.
280.
279
13265 P
299.
304.
315.
324.
323.
330.
326.
33S.
328.
337.
339
13266 P
282.
300.
302.
308.
311.
314.
315.
321.
326.
329.
337
13267 P
255.
266.
272.
272.
271.
275.
277.
280.
286.
283.
285
13268 P
250.
254.
261.
259.
265.
260.
268.
269.
271.
277.
280
13269 P
277.
283.
296.
294.
288.
294.
298.
294.
298.
300.
304
13270 P
290.
296.
306.
310.
316.
314.
322.
319.
326.
328.
338
13271 P
254.
265.
257.
261.
272.
273,
275.
277.
278.
285.
285
13272 P
314.
321.
332.
336.
330.
338.
347.
348.
356.
355.
363
13273 P
286.
290.
299.
299.
309.
312,
315.
313.
322.
324.
338
13274 NP
272.
274.
286.
287.
286.
206.
290.
293.
296.
299.
301
13275 P
253.
262.
272.
274.
276.
282.
289.
288.
293.
301.
301
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT
(VALUES EXCLUDED FROM AVERAGES)
DAY = DAY OF PRESUMED GESTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E25 (PAGE 6): MATERNAL BODY WEIGHTS - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fl GENERATION
FEMALE RATS
-------------------------------------------PREGNANCY
---------------------------- -------------------------
--------
STATUS
DAY 13
14
15
16
17
18
19
20
21
22
23
----------------------------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
----------------------------------------------------------------------------------------------------------------
13251 P
373.
383.
398.
401.
413.
426.
447.
462.
475.
13252 P
327.
329.
338.
349.
359.
365.
372.
391.
13253 P
332.
342.
343.
355.
373.
386.
406.
424.
427.
13254 P
318.
325.
334.
349.
356.
371.
384.
407.
13255 P
339.
342.
354.
366.
383.
402.
419.
432.
447'.
13256 P
336.
339.
340.
350.
357.
374.
391.
409.
418.
431.
13257 P
411.
408.
419,
431.
444.
468.
473.
497.
515.
13258 P 13259 P
348. 320.
356. 325.
360. 331.
369. 335.
380. 349.
402. 362.
417. 386.
435. 399.
447. 404.
13260 P
374.
372.
377.
384.
405.
423.
432.
457.
468.
13261 P
316.
324.
330.
340.
356.
371.
391.
409.
422.
13262 P
346.
354.
365.
370.
374.
393.
405.
417.
427.
13263 P
330.
340.
340.
349.
362.
380.
388.
364.
404.
13264 P
293.
296.
304.
318.
330.
344.
358.
374,
390.
13265 P
360.
366.
370.
382.
392.
401.
415.
422.
420,
13266 P
342.
34S.
353.
360.
380.
402.
412.
426.
447.
13267 P
298.
304.
314.
323.
345.
354.
363.
383.
13268 P
291.
304.
306.
317.
326.
342.
351.
366.
13269 P
320.
321.
326.
346.
362.
372.
390.
401.
412.
13270 P
348.
357.
359.
378.
399.
399.
425.
437.
445.
13271 P
311.
318.
308.
313.
328.
352.
363.
369.
385.
13272 P
380.
384.
394.
412.
428.
455.
467.
488.
512.
13273 P
342.
351.
356.
365.
379.
399.
420.
434.
454.
13274 NP 13275 P
312. 320.
314. 331.
320. 330.
315. 345.
311. 3S5.
303. 372.
305. 391.
308. 401.
293. 419.
288.
297.
----------------------------------------------------------------------------------------------------------------
P = PREGNANT DAY = DAY OF
NP = NOT PREGNANT PRESUMED GESTATION
(VALUES EXCLUDED FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
.PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E26 (PAGE 1): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fl GENERATION FEMALE RATS
-------------------- ----------------------- -----------------------------------------------------------------
DAY 1
4
7
14
21
--------------------------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
13201 13202 13203 13204 13205a
310. 325. 275. 303.
303. 314. 282. 299.
330. 328. 284. 299.
380. 364. 318. 317.
346. 329. 283. 298.
13206
361.
366.
368.
374.
366.
13207 13208
352. 300.
365. 345.
375. 321.
402. 372.
374. 345.
13209
NOT PREGNANT
13210 13211 13212
365. 373. 336.
354. 367. 327.
364. 361. 348.
388. 374. 365.
368. 351. 351.
13213
374.
380.
378.
409.
370.
13214
331.
340.
340.
371.
348.
13215
294.
299.
292.
332.
276.
13216
307.
321.
317.
361.
332.
13217
334.
338.
351.
363.
361.
13218
334.
338.
327.
371.
338.
13219
292.
282.
292.
317.
326.
13220
276.
288.
308.
329.
322.
13221
FOUND DEAD ON DAY 28 POSTWEANING
13222
382.
369.
372.
386.
380.
13223
285.
301.
304.
330.
289.
13224
377.
361.
351.
366.
372.
13225
279.
276.
284.
306.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION TOXICI
TABLE E26 (PAGE 2): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fl GENERATION FEMALE RATS
-----------
--------------------------------------------------------------------------------------------
DAY 1
4
7
14
21
----------- --------------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
----------- ---------------------------------------------------------------------------------------------------
13226
316."
314.
325.
339.
347.
13227
335.
324.
323.
342.
327.
13228
NOT PREGNANT
13229
312.
301.
312.
335.
332.
13230
349.
344.
340.
361.
355.
13231 13232
362. 313.
363. 313.
365. 325.
375. 355.
370. 350.
13233 13234
353. 371.
357. 382.
362. 394.
415. 409.
401. 388.
13235
327.
314.
330.
355.
345.
13236
335.
356.
364.
379.
363.
13237
337.
360.
357,
366.
370.
13238
333.
347,
334.
384.
349.
13239
314.
317.
328.
373.
343.
13240 13241
352. 324.
336. 323.
340. 334.
351. 358.
3SO. 350.
13242
347.
3S6.
328.
388.
363.
13243
NOT PREGNANT
13244
NOT PREGNANT
13245
NOT PREGNANT
13246
315.
328.
327.
344.
336.
13247
337.
340.
343.
372.
338.
13248
324.
331.
347.
396.
371.
13249
326.
324.
325.
366.
358.
13250
347.
350.
342.
371.
362.
---------------------------------------------------------------------------------------------------------------
DAY = DAY OF LACTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
PROTOCOL 418-008:
COMBINED ORAI, (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E26 (PAGE 3): MATERNAL BODY WEIGHTS - LACTATION - INDIVIDUAL DATA - Fl GENERATION FEMALE RATS
-- ----------------------------- ------------------- -------- --------------- --------------------------------
DAY 1
4
7
14
----------------------------------------------------
21 ----------------------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262
378. 322. 319. 304. 304. 322. 399.
333. 327. 332. 306. 344.
362. 314. 315. 312. 303. 327. 381. 328. 309. 338. 316. 325.
370. 323. 314. 316. 308. 339. 368. 336. 330. 348. 311. 327.
393. 338. 356. 344. 339. 366.
a 349. 356. 398. 322. 361.
376. 331. 342. 326. 356. 349.
334. 354. 363. 325. 342.
13263 13264 13265 13266 13267 13268 13269 13270 13271
305. 282. 355. 310. 284. 284. 312. 339. 296.
300. 277. 345. 308. 277. 277. 311. 336. 295.
312. 288. 332. 316. 278. 286. 315. 340. 316.
340. 321. 360. 350. 321. 315. 334. 362. 354.
327. 317. 328. 342. 316. 332. 341. 364. 340.
13272
348.
354.
358.
398.
379.
13273
326.
326.
332.
380.
319.
13274
NOT PREGNANT
13275
331.
315.
317.
348.
348.
------------------------------------------------------- -------------------------------------------------------
DAY = DAY OF LACTATION
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Dam 13257 was found dead on day 10 of lactation.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILI'I'Y. DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND I'ERINATAL/POSTNATAL
REPRODII('IRON TOXIC
TABLE E27 (PAGE 1): FEED CONSUMPTION
VALUES
PRECOHABITATION
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
- ------------- -------- -- -- -------
DAYS I - 8 8 - 15 15 - 22 22 -- ------------------ ------------------
29 29--- -3-6- -3-6 ----4-3---43 ------------------
RAT # -- -------------
DOSAGE GROUP 1 -------------------------
0 (VEHICLE) MG/KG/DAY - ---- --------------------
13201 13202 13203 13204 13205b
102. 88. 68.
105.
133. 107. 119. 134.
141. 100. 123. 140.
134. 117. 135. 136.
139. 122. 117. 135.
140. 127. 127. 160.
-- - ----------------50 50 - 57 57 - 64a -----------------------
- -144. 131. 145. 144.
--------------------
142. 142. 145. 234.
143. 140. 142. 154.
-----------------
13206
102.
135.
144.
160.
170.
147.
146.
150.
166.
13207 13208
96.
131.
94.
134.
c 143.
161. 172.
157. 138.
161. 133.
164. 172.
170. 173.
157. 139.
13209
95.
121.
121.
122.
107.
119.
133.
133.
123.
13210
91.
139.
154.
162.
170.
d
206.
230.
177.
13211
89.
129.
ISO.
84.
169.
172.
166.
173.
164.
13212
90.
128.
153.
148.
149.
142.
136.
147.
174.
13213 13214
102. 107.
144. 139.
172. 144.
169. 139.
152. 138.
158. 166.
170. d
169. 166.
161. 152.
13215 13216 13217
93.
d
87.
125.
79.
121.
123. 142. 142.
120. 146. 145.
112. 132. 144.
142. 165. 160.
148. 169. 157.
129. 147. 153.
134. 152. 148.
13218
104.
146.
152.
139.
152.
211.
191.
143.
141.
13219
93.
133.
142.
143.
126.
168.
173.
155.
142.
13220
97.
134.
140.
148.
148.
236.
209.
167.
147.
13221
99.
131.
141.
FOUND DEAD ON DAY 28 POSTWEANING
13222
105.
146.
171.
165.
173.
169.
166.
177.
166.
13223
97.
129.
136.
142.
142.
139.
133.
154.
124.
13224
93.
139.
159.
158.
166.
174.
180.
184.
182.
13225
107.
153.
161.
153.
146.
143.
150.
164.
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.
PROTOCOL 418-008:
('OMBINED ORAL (GAVAGE) FERTILIPY,
DEVELOPMENTAL
PFOS IN RAI'S (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINA-IAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E27 (PAGE 2): FEED CONSUMPTION
VALUES - IRECOHABITATION
- INDIVIDUAL I)ATA - Fl GENERATION FEMALE RATS
----- ------- --- --. --- ----------- --- I -- ----- -------
-- ------- --- -------
DAYS 1 - 8
8
15 15 - 22 22 - 2', 29
36 36 43 43
50 50 - 57 57 - 64a
------------ -------
------------ --- --- -- I --------------
-- --------- ----------- -----
RAT #
DOSAGE GROUP Il
- ------------------ ---- ---
0.1 MG/KG/DAY ------------ ---- --- ------------------ -------------- -----------
-----
13226
81.
ill.
131.
133
131.
128.
126.
138.
127.
13227
94.
133.
135.
134
139.
135.
142.
154.
147.
13228
87.
132.
130.
132
136.
149.
139.
155.
154.
13229
86.
123.
140.
127,
142.
196.
133.
149.
137.
13230
98.
134.
153.
149
146.
149.
152.
174.
149.
13231
87.
124.
141.
14B.
154.
154.
160.
155.
138.
13232
93.
119.
139.
138.
128.
13S.
133.
146.
138.
13233
96.
144.
157.
168.
167.
193.
179.
191.
157.
13234
94.
136.
157.
167.
175.
179.
175.
202.
182.
13235
88.
126.
141.
150.
151.
165.
172.
2,70.
167.
13236
92.
129.
140.
136.
135.
142.
159.
155.
136.
13237
101.
136.
142.
141,
137.
137.
150.
218.
134.
13238
105.
145.
147.
147.
147.
155.
177.
193.
156.
13239
Ill.
154.
168.
175,
175.
166.
205.
167.
147.
13240
104.
141.
160.
160.
159.
184.
175.
156.
160.
13241
84.
115.
139.
144.
134.
191.
175.
146.
153.
13242
96.
143.
154.
153@
147.
185.
166.
161.
154.
13243
101.
142.
164.
174.
169.
200.
181.
168.
158.
13244
99.
127.
141.
132.
129.
156.
151.
157.
228.
13245
105.
145.
167.
162.
150.
223.
192.
174.
153.
13246
89.
132.
146.
136.
135.
226.
211.
160.
171.
13247
103.
147.
ls9.
167.
179.
191.
217.
178.
181.
13248
98.
133.
163.
148.
159.
213.
b
181.
16S.
13249
113.
145.
156.
164.
147.
153.
155.
152.
157.
13250
96.
138.
149.
160.
182.
162.
175.
123.
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.
PROTOCOI, 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAI,
STUDY NLTMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE F27 (PACE 3): FEED CONSUMPTION VALUES
PRECOHABITATION
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
---------- -- -
---------
------ ---
-------
DAYS 1
a
8 - 15 15
----------------------
22 22
29 29 - 36 36 - 43 43
50 50 - 57 57 64a
--------------- ----------
--------- --- --- --- ---
-----
RAT -------
DOSAGE GROUP 111
0.4 MG/KG/DAY
-------- ------------------ ----------------------------
---------------- ----------- ------ ------
13251
87.
139.
158.
159.
157.
151.
161.
169.
164.
13252 13253
79.
121.
95.
140.
124. 145.
130. 145.
136. 129.
140. 136.
141. 129.
138. 128.
141. 134.
13254
95.
154.
149.
128.
124.
128.
132.
142.
127.
13255
94.
136.
151.
152.
140.
170.
170.
175.
148.
13256
87.
113.
125.
136.
131.
130.
139.
128.
138.
13257
69,
124.
161.
164.
172.
175.
184.
191.
181.
132SB
80.
103.
137.
143.
147.
155.
150.
144.
151.
13259 13260
85.
125.
137.
133.
132.
146.
133.
138.
143.
94.
124.
146.
161.
169.
170.
170.
164.
162.
13261
89.
116.
130.
138.
132.
146.
145.
141.
134.
13262
100.
136.
149.
146.
146.
155.
169.
173.
143.
13263
97.
136.
156.
153.
143.
189.
b
149,
140.
13264
87.
113.
128.
126.
130.
142.
148.
137.
127.
1326S
78.
132.
146.
155.
153.
194.
193.
186.
161.
13266
85.
121.
139.
137.
131.
182.
188.
171.
158.
13267
88.
113.
126.
132.
131.
143.
172.
148.
137.
13268
82.
135.
146.
145.
139.
154.
163.
150.
142.
13269
107.
136.
145.
134.
162.
245.
240.
177.
196.
13270
102.
144.
151.
155.
ls9.
210.
166.
179.
197.
13271
90.
161.
175.
120.
139.
194.
138.
144.
112.
13272
114.
148.
167.
164.
167.
180.
170.
188.
168.
13273
65.
177.
b
156.
b
164.
178.
164.
164.
13274
97.
134.
148.
152.
156.
182.
221.
166.
150.
13275
64.
130.
lS6.
173.
157.
155.
162.
122.
c
--------------------------------------------------------------------------------------------------------------
DAYS = DAYS POSTWEA.NING
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E28 (PAGE 1): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fl GENERATION
----------------------------PREGNANCY
--------------------- ------------------------- --------------- ------------- --
STATUS DAYS 0 - 7
7 -.10 10 - 14 14 - 17 17 - 20 20 - 25
------------------------------ --------------------- ----------------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
13201 P 13202 P
161. 161.
72.
88.
71.
66.
80.
106.
90.
73.
13203 P
172.
74.
92.
78.
54.
13204 P
169.
82.
113.
86.
72.
13205a
13206 P
178.
87.
114.
97.
94.
13207 P
201.
93.
108.
90.
87.
13208 P
170.
77.
103.
71.
67.
13209 NP
133.
58.
74.
S7.
42.
76.
13210 P
188.
88.
133.
101.
86.
13211 P
199.
94.
131.
93.
81.
13212 P
175.
86.
ill.
98.,
92.
ii2l3 P
208.
98.
116.
94.
al.
13214 P
167.
83.
100.
80.
58.
13215 P
147.
72.
104.
96.
84.
13216 P
176.
80.
98.
72.
76.
13217 P
175.
84.
98.
74.
71.
13218 P
169.
80.
110.
80.
79.
13219 P
166.
75.
98.
80.
82.
13220 P
184.
80.
107.
71.
67.
13221
FOUND DEAD ON DAY 28 POSTWEANING
13222 P
194.
86.
121.
102.
89.
13223 P
163.
55.
86.
70.
74.
13224 P
199.
89.
127.
63.
67.
13225 P
166.
80.
99.
78.
66.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT
NP = NOT PREGNANT
(VALUES EXCLUDED FROM AVERAGES)
DAYS = DAYS 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.
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295-9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E28 (PAGE 2): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL DATA - Fl GENERATION
----------------------------------------------------------------------------------PREGNANCY
---------- - --------------
STATUS DAYS 0 - 7
7 - 10 10 - 14 14 - 17 17 - 20 20 - 25
---------------------------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 11
0.1 MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
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
156. 172. 181. 158. 171. 166. 156. 167. 219. 179. 184. 158. 163. 181. 194. 157. 193. 166. 147. MATING
74.
107.
73.
101.
83.
83.
65.
105.
82.
104.
75.
97.
63.
92.
74.
107.
105.
128.
91.
72.
80.
92.
46.
88.
81.
103.
86.
104.
92.
120.
72.
93.
85.
114.
74.
105.
66.
62.
NOT CONFIRMED
82. 64. 36. 72. 66. 81. 60. 92. 86. 45. 84. 77. 92. 65. 87. 81. 95. 65. 67.
79. 62. 46. 71. 69. 71. 61. 83. 89. 43. 76. 91. 87. 75. 83. 78. 85. 42. 64.
70.
62. 101.
13246 P
180.
74.
94.
75.
72.
13247 P
193.
89.
113.
91.
75.
13248 P
a
85.
115.
80.
76.
13249 P
153.
68.
95.
84.
74.
13250 P
199.
93.
108.
80.
77.
---------------------------------------------------------------------------------------------------------------
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 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E28 (PAGE 3): MATERNAL FEED CONSUMPTION
VALUES - PRESUMED GESTATION
- INDIVIDUAL
DATA - Fl GENERATION
---------- ---- ---------------PREGNANCY
------ ---
------------ ----------- -------------- --------------
----------
STATUS DAYS 0 - 7
7 - 10 10 - 14 14 - 17 17 - 20 20 - 25
---------- ---- ----------------------- -----------------------------------------------------------------------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
---------------------------------------- -----------------------------------------------------------------------
13251 P
161.
82.
102.
89.
87.
13252 P
163.
71.
90.
68.
54.
13253 P
179.
86.
126.
73.
91.
13254 P
181.
75.
104.
72.
81.
13255 P 13256 P
146.
70.
89.
78.
74.
164.
68.
86.
70.
79.
13257 P
180.
86.
114.
91.
87.
13258 P 13259 P
172. 145.
81.
109.
68.
89.
82.
90.
75.
73.
13260 P
200.
98.
a
96.
82.
13261 P
141.
67.
91.
76.
81.
13262 P
163.
75.
99.
83.
81.
13263 P
170.
78.
103.
76.
53.
13264 P
156.
68.
88.
76.
61.
13265 P
172.
76.
114.
104.
102.
13266 P
177.
77.
94.
80.
70.
13267 P
146.
58.
91.
75.
58.
13268 P
141.
71.
96.
72.
70.
13269 P
178.
72.
97.
94.
81.
13270 P
197.
80.
114.
95.
68.
13271 P
154.
60.
96.
67.
75.
13272 P
191.
86.
108.
88.
77.
13273 P
182.
93.
100.
81.
85.
13274 NP
181.
77.
106.
85.
68.
72.
13275 P
176.
81.
104.
77.
77.
---------------------------------------------------------------------------------------------------------------
P = PREGNANT DAYS = DAYS
NP = NOT OF PRESUMED
PREGNANT GESTATION
(VALUES EXCLUDED
FROM AVERAGES)
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
a. Spilled feed precluded the calculation of this value.
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E29 (PAGE 1): MATERNAL FEED CONSUMPTION
VALUES - LACTATION
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RA
------------------- ----------------------------------- ----------------------- -- - ---------- -------------DAYS I - 4 4 - 7 7 - 10 10 - 14a
---------------------------------------------------------------------------------------------------------------
RAT #
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
---------------------------------------------------------------------------------------------------------------
13201
73.
119.
161.
260.
13202
68.
108.
163.
263.
13203
100.
114.
135.
225.
13204
83.
92.
145.
217.
13205b
13206
65.
100.
134.
189.
13207
87.
120.
166.
235.
13208
102.
87.
134.
238.
13209
NOT PREGNANT
13210
142.
113.
158.
249.
13211
60.
79.
113.
172.
13212
74.
112.
158.
22S.
13213
as.
112.
159.
229.
13214
85.
123.
157.
259.
13215
98.
122.
163.
242.
13216
106.
125.
183.
268.
13217
89.
124.
164.
231.
13218
105.
103.
143.
228.
13219
55.
105.
iss.
228.
13220
85.
133.
162.
263.
13221
FOUND DEAD ON DAY 28 POSTWEANING
13222
67.
110.
139.
230.
13223
ill.
128.
163.
121.
13224
73.
87.
133.
205.
13225
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E29 (PAGE 2): MATERNAL FEED CONSUMPTION
VALUES - LACTATION - INDIVIDUAL DATA - Fl GENERATION
FEMALE RJ
---------------------- - --------------------------- --------------------------- -----------------------------
DAYS 1 - 4 4 - 7 7 - 10 10 - 14a
---------------------- - ------------------------------------------------------- -----------------------------
RAT #
DOSAGE GROUP Il
0.1 MG/KG/DAY
------------------------ -------------------------------------------------------------------------------------
13226
72.
110.
152.
245.
13227
67.
102.
138.
231.
13228
NOT PREGNANT
13229
86.
113.
151.
255.
13230
63.
98.
145.
221.
13231
109.
145.
165.
262.
13232
76.
135.
144.
252.
13233
104.
123.
159.
266.
13234
90.
127.
159.
247.
13235
69.
105.
134.
222.
13236
108.
127.
161.
250.
13237
116.
120.
154.
245.
13238
114.
134.
179.
274.
13239
82.
134.
49.
308.
13240
87.
88.
308.
228.
13241
b
103.
138.
221.
13242
112.
112.
180.
279.
13243
NOT PREGNANT
13244
NOT PREGNANT
13245
NOT PREGNANT
13246
100.
123.
174.
242.
13247
76.
93.
121.
178.
13248
b
197.
184.
260.
13249
84.
105.
144.
208.
13250
98.
104.
147.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER;
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E29 (PACE 3): MATERNAL FEED CONSUMPTION
VALUES - LACTATION - INDIVIDUAL
DATA - PI GENERATION
FEMALE
--- -------------------- ---- -- ------------ ---- ------------------------------ ------------------- ------
DAYS 1 - 4 4 - 7 '7 - 10 10 - 14a
--------------------------------- ----------------------------------------------- --------------------- ------
RAT #
DOSAGE GROUP 111
0.4 MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
13251
7S.
110.
159.
240.
13252
67.
92.
122.
201.
132S3 13254
73.
101.
157.
248.
S6.
160.
114.
188.
13255 13256
65. 93.
103. 128.
118. 169.
198. 259.
13257
65.
100.
b
b
13258
Be.
120.
152.
2SS.
13259
89.
113.
156.
216.
13260
95.
115.
180.
267,
13261
82.
82.
108.
143.
13262
36.
77.
103.
208.
13263
89.
117.
123.
226.
13264
82.
113.
138.
224.
13265
65.
72.
119.
188.
13266
67.
96.
147.
198.
13267
68.
88.
132.
210.
13268
62.
99.
147.
220.
13269
98.
Ill.
107.
259.
13270
77.
128.
161.
246.
13271
79.
110.
135.
235.
13272
80.
134.
177.
283.
13273
86.
112.
163.
252.
13274
NOT PREGNANT
13275
74.
101.
132.
203.
---------------------------------------------------------------------------------------------------------------
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. Dam 13257 was found dead on day 10 of lactation.
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E30 (PAGE 1): SEXUAL MATURATION
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
DOSAGE DOSAGE
-- ------GROUP (MG/KG/DAY)
------- ----- -------
-- -------
I 0 (VEHICLE) -----------
------------- ------------------------
------
----------
-
ii 0.1 ---------------------- -
--- --- ------
III 0.4 ---------------
-------
--------
VAGINAL
VAGINAL
RAT # PATENCY (DAY)
RAT # PATENCY (DAY)
--------------------------- ------------------------------------------------
VAGIN
RAT # PATENCY ---- ----------
13201
30
13226
36
13251
30
13202
30
13227
34
13252
30
13203
31
13228
31
13253
30
13204
32
13229
32
13254
30
13205
a
13230
31
13255
30
13206
31
13231
33
13256
32
13207
30
13232
32
13257
29
13208
30
13233
31
13258
29
13209
30
13234
30
13259
32
13210
30
13235
34
13260
31
13211
32
13236
28
13261
31
13212
30
13237
29
13262
29
13213
32
13238
29
13263
30
13214
28
13239
32
13264
33
13215
29
13240
30
13265
31
13216
31
13241
34
13266
30
13217
31
13242
31
13267
28
13218
34
13243
28
13268
33
13219
30
13244
31
13269
30
13220
33
1324S
30
13270
30
13221
30
13246
30
13271
31
13222
29
13247
29
13272
32
13223
34
13248
30
13273
29
13224
35
13249
30
13274
29
13225
34
13250
33
13275
33
---------------------------------------------------------------------------------------------------------------
DAY = DAY POSTPARTUM
a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
PROTOCOL 418 008:
COMBINED ORAL (GAVACE@ FERTIIITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E31 (PAGE 1): PASSIVE AVOIDANCE
PERFORMANCE
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
----------- - - ----------DOSAGE GROUP 1
------------- ---- --------
------
-
--- - --------- ------ --
0 (VEHICLE) MG/KG/DAY
----------
------------------------ ---
------------------------
----
--
---- -----------------------
PAT NUMBER
------------13201 13202 13203 13204 13205c
SESSION la ------------------------ -
SESSION 2a ------- ------------
TRIALS TO
LATENCY b
TRIALS TO
LATENCY b
CRITERION
TRIAL 1
TRIAL 2
CRITERION
TRIAL 1
------------------------------------------------------------------------------------------------
4
4
18
4
10
57
4
9
45
9
5
9
3
8
3
59
3
51
6
9
13206
6
14
19
2
60
13207
5
6
8
3
23
13208 13210 13211
11
2
15
5
20
60
6
2
27
15
12
3
31
4
60
13212 13213
4
7
32
4
18
49
2
60
3
33
13214d
15
10
13
12
60
13215
5
12
13
3
15
13216
5
8
9
3
40
13217
8
4
8
5
5
13218
10
5
8
3
4
13219 13220 13221 13222 13223
5
3
10
10
3
4
4
9
31
4
8
20
4
12
51
9
5
3
3
3
31
3
5
3
9
13224
10
4
4
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 I (Learning Phase); values for Session 2 (Retention Phase) were
averages and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN PATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAI,/POSTNATAL
REPRODUCTION
TOXICI
TABLE E31 (PAGE 2): PASSIVE AVOIDANCE PERFORMANCE
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
- ---- - -------- I --- -------
DOSAGE GROUP 11
0.1
-------- -------------------- I ------
---- 11 -- - ---------- - -----
MG/KG/DAY --------------------- -------
------------
---
------------- -----
---- ----------------------
SESSION la --------------------------
SESSION 2a --------------- ---
RAT NUMBER
TRIALS TO CRITERION
LATENCY b
TRIAL 1
TRIAL 2
TRIALS TO CRITERION
LATENCY b TRIAL 1
--------- --------------------------------- ------------------------------- ---- -----------------------------
13226
5
10
60
2
60
13227
6
5
21
3
22
13228
11
7
35
8
60
13229
6
7
3
3
12
13230
5
8
33
is
1
13231
4
7
17
2
60
13232
4
13
30
3
8
13233
4
6
21
3
11
13234
4
10
9
3
8
13235
4
3
9
3
36
13236
11
5
8
2
60
13237
5
7
5
3
16
13238
4
5
18
2
60
13239
7
3
11
3
59
13240
4
11
60C
3
19
13241
4
4
31
2
60
13242
5
14
9
2
60
13243
3
6
60
3
13
13244
4
5
39
3
11
13245
4
14
8
3
23
13246
4
6
25
2
60
13247
5
3
12
2
60
13248
7
2
3
2
60
13249
5
5
60
2
60
13250
4
12
52
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. towards the criterion.
Shock was delivered and the tria
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUC-TION TOXICI
TABLE E31 (PAGE 3): PASSIVE AVOIDANCE
PEI@FORMANCE - INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
--------------- ----------------------
-- ----------------- - - ---------------------
DOSAGE GROUP 111
0.4 MG/KG/DAY
--------------------------------------- - - - -- ----------------- ------------------------
-- - -------- ------
SESSION la --------------------- ---
RAT
TRIALS TO
LATENCY
NUMBER
CRITERION
TRIAL I
--------------------------------------- ---
SESSION 2a -------------------
b
TRIALS TO
LATENCY b
TRIAL 2
CRITERION
TRIAL 1
---------------------------------------------------
--- -----------
13251
5
4
60
2
60
13252
5
13
60
3
9
13254
4
16
14
3
10
13255
4
4
52
3
9
13256
5
24
60
2
60
13258
4
10
20
2
60
13259
4
17
35
3
38
13260
4
12
26
2
60
13261
6
5
21
2
60
13262
6
10
6
2
60
13263
6
4
45
2
60
13264
4
6
26
3
57
13265
5
10
11
3
58
13266
5
21
16
4
13
13268
7
2
3
4
12
13269
5
2
11
2
60
13270
5
6
9
2
60
13271
6
3
17
7
4
13272
4
a
8
2
60
13273
5
9
9
2
60
13274
7
60
11
3
4
13275
5
3
10
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOP'S
PERTILRTY, DEVELOPMENTAL
STUDY NUMBER!
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E32 (PAGE 1): WATERMAZE PERFORMANCE
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
-------- --- - - --- ----- ---------- -- -
DOSAGE GROUP 1
0 (VEHICLE)
-------------- - -------------------- -----
------- ------------- MG/KG/DAY ---------------------- -
---- -- ------------------ ---- ---------------------------
------------------
SESSION la ------------------- -- -- ----
SESSION 2a
RAT
TRIALS TO
ERRORS/
NUMBER
CRITERION
TRIAL
-------------------------------------
LATENCY b
------ ----- -----------------
TRIALS TO
ERRORS/
LATENCY b
TRIAL 2
CRITERION
TRIAL
TRIAL 1
--------------------------------------------------------------
----------
13201
14
0.57
16
6
0.17
15
13202
13
0.92
14
10
0.20
18
13203c
is
0.53
11
8
0.25
11
13204 13206 13207 13208
13
1.23
22
11
0.27
18
14
0.43
14
9
0.33
5
5
0.00
9
5
0.00
6
10
0.50
45
5
0.00
14
13210
9
0.33
5
7
0.43
4
13211
9
0.33
11
14
0.21
19
13212
11
0.82
14
6
0.17
11
13213
9
0.89
34
s
0.00
7
13214
6
0.17
7
5
0.00
9
13215
11
0.45
5
5
0.00
4
13216
9
0.33
6
5
0.00
7
13217c
is
0.33
5
7
0.43
13
13218
8
0.25
9
7
0.14
9
13219
8
0.25
7
11
0.18
7
13220
11
0.36
7
5
0.00
5
13222
13
0.85
23
15
0.53
39
13223
13
0.54
11
6
0.33
31
13224c
15
0.53
13
5
0.00
5
----------------------------------------------------------------------------------------------------------------
SESSION = TEST SESSION
a. Sessions 1 (Learning Phase) and 2 (Retention Phase) of testing were separated by a one-week b. The latency was recorded in seconds.
interval.
c. Rat did not meet the criterion in Session I (Learning Phase); values for Session 2 (Retention Phase) exclud averages and statistical analyses.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PEI@INAIAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E32 (PAGE 2): WATERMAZE PERFORMANCE
- INF)IVIDUAL DATA - Fl GENERA'I'ION FEMALE RATS
------------- ---- -- ------ -------- ---------- ------------------ ----- - -----------------
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------- --------------------------
------------------------ -- -----------------------
SESSION la
SESSION 2a
------------------------------
RAT
TRIALS TO
ERRORS/
LATENCY b
-------------- --- -----------
TRIALS TO
ERRORS/
LATENCY b
NMBER
CRITERION
TRIAL
TRIAL 2
CRITERION
TRIAL
TRIAL I
--------------------- --------------------------- ------------------------ ---------------------------
--- ------- -----
13226
12
0.50
20
13227
8
0.25
6
13228
10
0.30
6
13229
7
0.57
16
13230c
15
0.67
13
13
0.46
10
13
0,23
19
6
0.17
11
10
0.20
7
15
0.67
21
13231
11
0.45
10
7
0.14
6
13232
8
0.25
7
6
0.33
23
13233
6
0.17
12
5
0.00
7
13234 13235 13236 13237 13236
8
0.62
20
6
0.17
7
10
0.20
10
a
0.50
18
8
0.38
11
10
0.30
8
5
0.00
6
5
0.00
7
7
0.14
8
15
0.47
23
13239 13240
11
0.54
15
11
0.27
8
9
0.11
5
5
0.00
6
13241
12
0.58
18
6
0.17
11
13242c
is
0.27
6
6
0.50
31
13243
6
0.17
11
10
0.20
14
13244c
is
0.67
is
8
0.38
14
13245
12
0.50
41
5
0.00
8
13246
10
0.30
6
6
0.17
18
13247
7
0.28
14
7
0.14
9
13248
6
0.17
5
5
0.00
4
13249
10
0.60
11
6
0.17
12
13250
12
0.67
18
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 I (Learning Phase); values for Session 2 (Retention Phase) exclud averages and statistical analyses.
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN PAIS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E32 (PAGE 3): WATERMA;.E PERFORMANCE
- INDIVIDUAL
DATA - Fl GENERATION
FEMALE RATS
------------------ DOSAGE GROUP 111 - - -------------------- --
----------------------- 0.4 MG/KG/DAY ------------------------ -
- - ------------- --- - ----------- -------- ----------------------- ------------------------
---------
SF.SSION la - ----------------
SESSION 2a
RAT
TRIALS TO
ERRORS/
LATENCY b
NUMBER
CRITERION
TRIAL
TRIAL 2
------------------------- ----------------------------
TRIA-L-S---T-O-----ER-R-OR-S-/- ----L-A-TEN-C-Y-- b
CRITERION
TRIAL
TRIAL 1
--------------------------------------------------
13251
8
0.38
20
13252
15
0.60
7
13254c
15
0.93
17
13255
12
0.25
13
13256
14
0.57
8
13258
10
0.20
10
13259
12
0.42
a
13260c
15
1.27
37
13261
12
0.42
18
13262
10
0.50
8
13263
11
0.54
17
13264
11
0.73
25
13265
9
0.22
13
13266
9
0.56
10
13268
14
0.50
30
13269
12
0.50
9
13270
14
0.36
16
13271
6
0.17
5
13272
11
0.18
5
13273
13
0.77
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
s
0.00
10
5
0.00
7
6
0.17
17
d
d
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
13274
15
0.60
14
8
0.38
16
----------------------------------------------------------------------------------- ---------------------------
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. Rat did not meet the criterion in session 1 (Learning Phase); values for Session 2 (Retention Phase) exclu
averages and statistical analyses. d. Values were not recorded.
PROTOCOL 418 008:
COMBINED ORAL (GAk'AGE) FERTILITY, DEVELOPMENTAI,
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E33 (PAGE 1): DAYS IN COHABII-ATION
INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
- ------------ ------
---
DOSAGE GROUP
1
DOSAGE (MG/KG/DAY)
0 (VEHICLE)
------------------------------------
-----
--- ---------------------------------
----------------------- - ----------------
11 0.1 --- --------------------- -
111
0.4 ----------------
---------------
DAYS IN PAT # COHABITATION ---------------------
RAT # -------------------
DAYS IN
DAYS IN
COHABITATION
RAT # COHABITAT
-------------------------------------------
13201
3
13226
2
13251
1
13202
3
13227
5
13252
4
13203
4
13228
7a
13253
7
13204
1
13229
5
13254
5
13205
b
13230
6
1325S
2
13206
1
13231
4
13256
1
13207
1
13232
5
13257
3
13208
1
13233
2
13258
1
13209
4
13234
a
13259
2
13210
4
13235
1
13260
3
13211
2
.13236
3
13261
1
13212
1
13237
7
13262
1
13213
3
13238
3
13263
2
13214
4
13239
1
13264
4
13215
2
13240
3
13265
1
13216
2
13241
1
13266
3
13217
8
13242
2
13267
4
13218
2
13243
3
13268
2
13219
1
13244
2
13269
4
13220
9
13245
14c
13270
4
13221
d
13246
3
13271
2
13222
2
13247
3
13272
3
13223
14
13248
3
13273
2
13224
7
13249
3
13274
1
13225
4
13250
2
13275
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; c. Mating not confirmed.
the sex was incorrectly
identified.
d. Rat 13221 was found dead on day 28 postweaning.
PROTOCOL 418-008:
COMBINED
ORAL IGAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295-9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E34 (PAGE 1): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION
FEMALE RATS
---------- -------DOSAGE GROUP DOSAGE (MG/KG/DAY) -------------------
I 0 (VEHICLE)
--------------RAT
NUMBER ---------------
13201 13202
-- --- I ---
DAY OF NECROPSY ------------
- --- ------------ ------- --- -------I --------
PREGNANCY
DOSAGES
STATUS
ADMINISTERED
OBSERVATIONS
a
---------------------------------------------- I
--- -----------------------
DL 21
p
DL 21
p
119
ALL TISSUES APPEARED NORMAL.
117
ALL TISSUES APPEARED NORMAL.
13203
DL 21
p
120
KIDNEYS:
LEFT, CORTEX, ROUGH AND PI
ONE CALCULUS (1.0 CM X 0.5 CM X 0.5
URINARY BLADDER: 0.30 CM).
ONE CALCULUS (0.75
ALL OTHER TISSUES APPEARED NORMAL.
13204
DL 21
p
lie
ALL TISSUES APPEARED
NORMAL.
13205b
DP
7
7
SACRIFICED
ON DAY 7 POSTWEANING.
ALL TISSUES APPEARED
NORMAL.
13206 13207
DL 21
p
DL 21
p
118
ALL TISSUES APPEARED
NORMAL.
117
ALL TISSUES APPEARED
NORMAL.
13208
DL 21
p
117
KIDNEYS:
BILATERAL, CORTEX, PITTED;
TAN, GRANULAR MATERIAL.
URINARY BLADDER:
WALLS THICKENED,
0
(1.0 CM IN DIAMETER).
ALL OTHER TISSUES APPEARED
NORMAL.
13209
DG 25
NP
102
ALL TISSUES APPEARED
NORMAL.
13210
DL 21
p
118
ALL TISSUES APPEARED
NORMAL.
13211
DL 21
p
118
ALL TISSUES APPEARED
NORMAL.
13212
DL 21
p
116
ALL TISSUES APPEARED
NORMAL.
13213
DL 21
p
117
ALL TISSUES APPEARED
NORMAL.
13214
DL 21
p
118
ALL TISSUES APPEARED
NORMAL.
13215
DL 21
p
115
ALL TISSUES APPEARED
NORMAL.
13216
DL 21
p
115
ALL TISSUES APPEARED
NORMAL.
13217
DL 21
p
121
ALL TISSUES APPEARED
NORMAL.
13218
DL 21
p
115
ALL TISSUES APPEARED
NORMAL.
13219
DL 21
p
114
ALL TISSUES APPEARED
NORMAL.
13220
DL 21
p
122
ALL TISSUES APPEARED
NORMAL.
---------------------------------------------------------------------------------------------------------------
DP
DAY POSTWEANING
DG = DAY OF (PRESUMED) GESTATION
P
PREGNANT
NP = NOT PREGNANT
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table E23) for external observations confirmed at nec b. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
PROTOCOL 418-008:
COMBINED
ORAL (GAVAGE@ FERTILITY,
DEVELOPMENI'AL
PFOS IN RATS (SPONSOR''3 STUDY NUMBER:
6295.9)
AND PERlNATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E34 (PAGE 2): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - Fl GENERATION FEMALE RATS
--------- ----------------- ------- ----- ---------------------- ---- ---------------------------------------
DOSAGE GROUP
RAT
DAY OF
PREGNANCY
DOSAGES
DOSAGE (MG/KG/DAY)
NUMBER
NECROPSY
STATUS
ADMINISTERED
OBSERVATIONS
a
----------------------------------------- -------------------------------------------------------------------
I (Cont.)
0 (VEHICLE)
13221
DP 28
27
FOUND DEAD ON DAY 28 POSTWEANING.-
ALL TISSUES APPEARED NORMAL.
13222
DL 21
p
113
ALL TISSUES APPEARED NORMAL.
13223
DL 21
p
125
ALL TISSUES APPEARED NORMAL.
13224
DL 21
p
lis
ALL TISSUES APPEARED NORMAL.
13225
DL 21
p
115
ALL TISSUES APPEARED NORMAL.
--------------------------------------------------------------------------------------------------------------
DP
DAY POSTWEANING
DG = DAY OF (PRESUMED) GESTATION
P
PREGNANT
NP = NOT PREGNANT
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table E23) for external observations confirmed at ne
PROTOCOL 418-008:
COMBINED ORAI, (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SIIONSOR'S STUDY NUMBER:
6295 9)
AND PER INATAL/ POSTNATAI,
REPRODUCTION
TABLE E34 (PAGE 3): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA
Fl GENERATION
FEMALE RATS
TOXICIT
DOSAGE DOSAGE
G-R-OU-P--------------------RAT --
(MG/KG/DAY)
NUMBER
------------------------ --
-----D-A-Y--O-F----PREG-N-A-NC-Y--- -D-OSA-G-ES----------- ------------- --------------
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 2S
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
P
PREGNANT
NP = NOT PREGNANT
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table E23) for external observations confirmed at necrc
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE@ FERTILITY,
DEVELOIIMENTAL
AND PERINATAL/POSTNATAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
(,.'95.9)
REPRODUCTION
TOXICI
TABLE E34 (PAGE 4): NECROPSY OBSERVATIONS
- INDIVIDUAL DA'L@A - Fl GENERATION
FEMALE RATS
--- -------- - ---------------- -------- - --------------- ----------- -------------- -------------
DOSAGE GROUP
RAT
DAY OF
PREGNANCY
DOSAGES
DOSAGE (MG/KG/DAY)
NUMBER
NECROPSY
STATUS
ADMINISTERED
OBSERVATIONS
a
-------------- - ------------- - --------------------------- ----------------------------------------
III
0.4
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.
---------------
132S7
DL 10
p
106
FOUND DEAD ON DAY 10 OF LACTATION (D
OVERNIGHT).
THORACIC TRACHEA:
CAVITY:
CONTAINED
WHITE FOAM.
2 ML OF
LUNGS:
DARK RED
ALL OTHER TISSUES
IN COLOR. APPEARED
NORMAL.
13258
DL 21
p
117
ALL TISSUES APPEARED
NORMAL.
13259
DL 21
p
118
ALL TISSUES APPEARED
NORMAL.
13260
DL 21
p
lie
ALL TISSUES APPEARED
NORMAL.
13261
DL 21
p
116
ALL TISSUES APPEARED
NORMAL.
13262
DL 21
p
115
ALL TISSUES APPEARED
NORMAL.
13263
DL 21
p
116
ALL TISSUES APPEARED
NORMAL.
13264
DL 21
p
lie
ALL TISSUES APPEARED
NORMAL.
13265
DL 21
p
iis
ALL TISSUES APPEARED
NORMAL.
13266
DL 21
p
116
ALL TISSUES APPEARED
NORMAL.
13267
DL 21
p
116
ALL TISSUES APPEARED
NORMAL.
13268
DL 21
p
114
ALL TISSUES APPEARED
NORMAL.
13269
DL 21
p
118
ALL TISSUES APPEARED
NORMAL.
13270
DL 21
p
118
ALL TISSUES APPEARED
NORMAL.
13271
DL 21
p
115
ALL TISSUES APPEARED
NORMAL.
13272
DL 21
p
115
ALL TISSUES APPEARED
NORMAL.
13273
DL 21
p
114
ALL TISSUES APPEARED
NORMAL.
13274
DG 25
NP
96
ALL TISSUES APPEARED
NORMAL.
13275
DL 21
p
106
ALL TISSUES APPEARED
NORMAL.
--------------------------------------------------------------------------------------------------------------
DP
DAY POSTWEANING
DG = DAY OF (PRESUMED)
P
PREGNANT
NP = NOT PREGNANT
GESTATION
DL = DAY OF LACTATION
a. Refer to the individual clinical observations table (Table E23) for external observations confirmed at necr
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
629S.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E35 (PAGE
1): NATURAL DELIVERY, IMPLANTATION
SITES, AND PUP VIABILITY
F) GENERATION
FEMALE RATS/F2 GENERATION
LITTERS
AND SEX - INDIVIDIIAL DATA -
----------- ------------ -------------------------------------------
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
----------------------- --------------------------------------------
-----------------------------------------------------
DURATION OF
LITTER DELIVERED
NUMBER OF LIVE PUPS AT
RAT/
GESTATION
LIVE STILL- TOTAL
COMPLETION
OF DAY POSTPARTUM
LITTER
(DAYS)
BORN
BORN
BORN
1
4a
4b
7
14
NUMBER
N
N
N
N
m
F
m
F
m
F
m
F
m
-------------------------------------------------------------------- ---------------------------
13201
23
13202
22
13203
23
13204
23
13205c
14(l) 2
16
15
1
16
16
0
16
18
0
18
7
6
7
6
4
4
4
4
4
6
9
6
9
4
4
4
4
4
a
8
8
6
4
4
4
4
4
10
8
8
8
4
4
4
4
4
13206
23
6
0
6
13207
22
19
0
19
13208
23
13
0
13
13209
NOT PREGNANT
3
3
3
3
3
3
3
3
3
13
6
13
6
4
4
4
4
4
7
6
6
6
4
4
4
4
4
13210 13211 13212 13213 13214 13215 13216 13217 13218 13219 13220 13221
22
17
0
17
24
5
0
5
23
14
0
14
23
is
0
15
22
16(l) 2
18
23
14
0
14
23
is
0
is
23
17
0
17
23
14
0
14
23
15
0
15
23
17
0
17
FOUND DEAD DAY 28 POSTWEANING
10
7
9
7
4
4
4
4
4
3
2
3
2
3
2
3
2
3
6
8
6
8
4
4
4
4
4
1 14
1 14
1
7
1
7
1
9
6
96
4
4
4
4
4
3 11
3 11
3
5
3
5
3
8
7
8
7
4
4
4
4
4
9
8
9
6
4
4
4
4
4
9
5
9
s
4
4
4
4
4
8
7
8
6
4
4
4
4
4
7 10
7 10
4
4
4
4
4
13222
23
9
1
10
2
7
2
7
2
6
2
6
2
13223
23
14
0
14
5
9
5
9
4
4
4
4
4
13224
23
is
0
15
8
7
8
7
4
4
4
4
4
13225
23
12
0
12
7
5
7
s
4
4
4
4
4
-------------------------------------------------------------------------------------------------
M
MALE
F = FEMALE
( = NUMBER OF PUPS DYING BEFORE WEIGHING
a. Number of live pups preculling.
ON DAY I POSTPARTUM.
b. Number of live pups postculling.
c. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
-----------------------------
21
F
M
F
---------------
4
4
4
4
4
4
4
4
4
4
4
4
3
3
3
4
4
4
4
4
4
4
4
4
2
3
2
4
4
4
7
1
7
4
4
4
5
3
5
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
6
2
6
4
4
4
4
4
4
4
4
4
--------------
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E35 (PAGE
2): NATURAL DELIVERY, IMPLANTATION
SITES, AND PUP VIABILITY
PI GENERATION
FEMALE RATS/F2 GENERATION
LITTERS
AND SEX - INDIVIDUAL DATA
MATERNAL----D-O-S-AG-E---G-R-O-UP----1-1------ -- -- 0-.-1--M-G-/-K-G/-D-A-Y-------------------------- ------------- ---------------------
--- -------------------------- ------------------------------------------- ------------- ---------------------
DURATION OF
LITTER DELIVERED
NUMBER OF LIVE PUPS AT
RAT/
GESTATION
LIVE STILL- TOTAL
COMPLETION
OF DAY POSTPARTUM
LITTER
(DAYS)
BORN
BORN
BORN
1
4a
4b
7
14
21
NUMBER
N
N
N
N
m
F
m
F
m
F
m
F
m
F
m
F
---------------------------------------------------------------------------------------------------------------
13226
23
11
1
12
13227
23
13
0
13
13228
NOT PREGNANT
6
5
8
5
6
5
8
5
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243
23 22 23 23 22 23 24 23 23 23 23 23 22 23 NOT PREGNANT
15
0
is
13
0
13
17
0
17
13
0
13
16
0
16
14
5
19
10(2)
0
10
21
0
21
14
0
14
16
0
16
is
0
15
16
0
16
16
0
16
17
0
17
9
6
9
4
6 11
7
6
8
8
a
6
4
4
10 11
7
7
7
9
10
5
8
8
9
7
9
8
9
6
94
6 11
7
6
8
8
8
5
3
4
10 11
7
7
7
9
10
5
8
8
9
7
9
8
4
4
4
4
4
4
4
4
4
4
4
4
3
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
13244
NOT PREGNANT
13245
NOT PREGNANT
13246
23
15
0
15
5 10
5 10
4
4
4
4
4
4
4
4
13247
23
16
0
16
5 11
5 11
4
4
2
4
2
3
2
3
13248
23
17
1
18
8
9
8
9
4
4
4
4
4
4
4
4
13249
23
16
0
16
7
9
7
9
4
4
4
4
4
4
4
4
13250
23
17
0
17
12
5
12
5
4
4
4
4
4
4
4
4
---------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER!
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E35 (PAGE
3): NATURAL DELIVERY, IMPLANTATION SITES, AND PUP VIABILITY
Fl GENERATION
FEMALE RATS/F2 GENERATION
LITTERS
AND SEX - INDIVIDUAL
DATA -
----------------------------------------------------------------------------------------------------------------
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
----------------------------------------------------------------------------------------------------------------
DURATION
OF
LITTER DELIVERED
NUMBER OF LIVE PUPS AT
RAT/
GESTATION
LIVE STILL- TOTAL
COMPLETION
OF DAY POSTPARTUM
LITTER NUMBER
(DAYS) N
BORN N
BORN N
BORN N
I
4a
4b
7
14
21
m
F
m
F
m
F
m
F
m
F
m
----------------------------------------------------------------------------------------------------------------
13251 132S2 13253 13254 13255 13256 13257c 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274
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
13
0
13
is
0
15
15
0
15
17
0
17
14
4
18
14
1
15
is
0
15
15
0
15
13(l) 0
13
18(1)
0
18
14
0
14
11
1
12
15
0
15
16
0
16
7
0
7
18
0
18
17
0
17
13
1
14
14
0
14
15
1
16
10
1
11
16
2
18
16
1
17
7
6
8
7
7
8
6 11
8
6
5
9
6
9
6
9
9
3
8
9
4 10
6
5
9
6
7
9
2
5
7 11
5 12
7
6
10
4
7
8
4
6
11
5
6 10
7
6
8
7
7
7
3
7
8
6
5
a
6
9
6
9
93
7
9
4 10
6
5
9
6
7
9
2
5
6 11
5 12
7
6
10
4
7
a
4
6
11
5
6 10
4
4
4
4
4
4
3
5
4
4
4
4
4
4
4
4
5
3
4
4
4
4
4
4
4
4
4
4
2
5
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
5
3
4
4
4
4
4
4
4
5
3
4
4
2
3
4
3
4
4
4
4
2
5
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
5
3
4
4
4
4
4
5
3
4
4
2
3
3
3
4
4
4
4
2
5
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
5
3
4
4
4
4
4
5
3
4
4
2
3
3
3
4
4
4
4
2
5
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
13275
22
13
1
14
5
8
5
8
4
4
4
4
4
4
4
4
----------------------------------------------------------------------------------------------------------------
M
MALE
F = FEMALE
( = NUMBER OF PUPS DYING BEFORE WEIGHING a. Number of live pups preculling.
ON DAY 1 POSTPARTUM.
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITI, DEVELOPMENTAL STUDY NLJMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E36 (PAGE 1): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA - F2
- --------- ------------------------------------------------------- -- ---- --------------------- --- ---------
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------------------------------------------------------------------------------------------------
RAT/
LITTER
DAY I
DAY 4a
DAY 4b
DAY 7
DAY 14
NUMBER
m
F
T
m
F
T
m
F
T
m
F
T
m
F
T
------------------------------------------------------------------------------------------------------------
13201 13202 13203 13204 13205c
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
8.8
8.9
8.6
14.8 14.9 14.8
34.3 33.3 33.8
5
8.3
7.7
8.0
15.0 14.2 14.6
35.1 34.4 34.8
52
6.2
6.0
6.1
9.7
9.4
9.5
24.5 23.S 24.0
3
7.2
6.6
6.9
11.6 11.0 11.3
27.6 26.3 26.9
43
13206 13207 13208 13209
6.5
6.5
6.5
10.2 10.0 10.1
10.2 10.0 10.1
17.1 16.7 16.9
37.5 36.4 37.0
61
5.9
5.8
5.9
8.0
8.0
8.0
8.2
8.1
8.1
14.6 14.2 14.4
33.1 31.0 32.0
4
6.1
6.0
6.1
9.1
8.8
8.9
9.4
8.9
9.1
14.5 13.9 14.2
30.6 29.9 30.2
4
NOT PREGNANT
13210 13211 13212 13213 13214 13215
5.5
5.6
5.6
6.9
6.8
6.9
7.0
6.8
6.9
10.8 10.5 10.6
27.2 25.4 26.3
43
9.0
8.8
8.9
14.4 14.5 14.5
14.4 14.5 14.5
22.1 21.4 21.8
40.0 38.2 39.3
59
6.2
6.1
6.1
8.6
8.7
8.6
9.0
8.6
8.8
15.8 15.2 15.4
32.9 31.6 32.2
53
6.8
6.8
6.8
8.7
7.8
7.8
8.7
7.6
7.7
14.9 13.4 13.6
33.3 30.4 30.8
49
6.3
6.0
6.2
8.9
8.4
8.7
9.2
8.2
8.8
16.2 14.4 15.3
36.1 33.1 34.6
54
7.2
6.6
6.8
9.5
9.1
9.2
9.S
9.1
9.2
16.6 15.8 16.1
34.9 33.0 33.7
53
13216 13217
6.7
6-5
6.6
6.9
6.3
6.6
8.9
8.7
8.8
8.7
7.8
8.3
9.1
8.9
9.0
15.8 15.4 15.6
33.6 33.0 33.3
54
9.4
8.2
8.8
15.9 14.7 15.3
34.7 33.1 33.9
51
13218
6.5
6.2
6.4
9.4
8.9
9.2
9.8
9.1
9.4
16.4 15.6 16.0
33.7 32.0 32.9
55
13219
6.4
6.1
6.3
8.4
8.1
8.2
8.4
8.1
8.3
13.5 12.8 13.1
30.2 29.0 29.6
51
13220 13221
6.0 FOUND
S.7 DEAD
5.9 ON DAY
7.6
7.6
7.6
28 POSTWEANING
7.8
7.7
7.8
13.8 13.4 13.6
31.9 30.3 31.1
so
13222
7.2
7.0
7.0
10.6 10.2 10.3
10.6 10.4 10.4
16.8 16.4 16.4
34.8 33.7 34.0
48
13223
6.8
6-2
6.4
9.0
9.0
9.3
9.7
9.0
9.4
16.2 15.7 16.0
34.0 33.2 33.6
53
13224
6.8
6.4
6.6
8.8
8.4
8.6
8.8
8.5
8.6
14.1 13.6 13.9
30.3 28.8 29.6
50
13225
6.4
5.9
6.2
9.2
8.1
8.7
9.2
8.3
8.8
15.0 13.6 14.3
31.6 30.2 30.9
so
---------------------------------------------------------------------------------------------------------------
M= ALL a. b.
MALE
F=
WEIGHTS WERE
Preculling.
Postculling.
FEMALE RECORDED
T = TOTAL (SUM OF PUP WEIGHTS/NUMBER
OF LIVE PUPS)
IN GRAMS (G).
MEAN LITTER WEIGHTS INCLUDE ONLY
DAY WEIGHTS
= DAY POSTPARTUM OF LIVE PUPS.
c. Rat 1320S was excluded from study on day 7 postweaning; the sex was incorrectly identified.
PROTOCOL
418 006:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
SL@UDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E36 (PAGE 2): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 G
-------- ----- - -- ----------- -- ---- - - -------------------I ------ ----------------
--- - --- --------
MATERNAL
DOSAGE GROUP Il
0.1 MG/KG/DAY
----------------------------------------- - -------------------- ----- ---------------------- - -------------
RAT/
LITTER
DAY 1
NUMBER
m
F
T
---------------------------------
DAY 4a
DAY 4b
DAY 7
m
F
T
m
F
T
m
F
T
------- -- --------------------------- -----------------
DAY 14
m
F
----------
T ---------
13226 13227 13228
7.1
6.7
6.9
6.2
6.0
6.1
NOT PREGNANT
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
8.6
8.9
8.8
15.0 15.2 15.1
31.9 32.4 32.2
51
13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239
13240 13241
13242 13243
6.2 6.0 6.5 6@7
6.1 6.1 5.4 6.6 7.3 6.7 5.4 6.5 5.6 6.9 NOT
5.7 5.6 6.2 6.7 5.5 6.3
4.8 S.9 6.8 6.4 5.3 6.3 5.3 6.2 PREGNANT
6.0 5.9 6.3 6.7 5.8 6.2 5.1 6.2 7.0 6.5 5.4 6.4 5.5 6.5
7.3
6.6
7.0
7.0
6.6
6.9
7.5
6.6
7.1
11.3
9.8 10.6
30.5 26.8 28.6
47
7.1
6.6
6.9
11.7 11.0 11.4
26.7 25.7 26.2
39
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
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
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
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
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
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
8.9
8.3
6.6
9.0
8.6
8.8
12.5 13.0 12.7
32.5 32.4 32.5
52
9.6
9.3
9.4
9.6
9.3
9.S
17.2 16.8 17.0
37.3 36.8 37.0
57
8.S
8.3
8.4
8.5
8.3
8.4
15.8 15.4 15.6
36.7 35.8 36.2
55
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
6.6
6.2
6.4
7.0
5.9
6.4
11.3
9.3 10.3
28.1 25.2 26.6
42
9.4
8.8
9.1
9.7
9.5
9.6
16.6 1S.7 16.2
36.6 35.1 35.9
56
13244
NOT PREGNANT
13245
NOT PREGNANT
13246
6.4
6.0
6.1
8.1
7.6
7.7
8.1
7.6
7.8
14.1 13.3 13.7
31.8 30.S 31.2
so
13247
6.3
5.9
6.0
6.6
6.3
6.4
6.8
6.3
6.5
10.0 10.3 10.2
28.0 28.1 28.0
45
13248
6.3
6.2
6.2
6.9
6.9
6.9
7.2
7.0
7.1
12.7 11.3 12.0
31.0 29.5 30.2
45
13249
6.6
6.1
6.3
9.1
8.6
8.9
9.1
8.8
9.0
15.3 1S.5 15.4
31.1 31.0 31.1
43
13250
5.9
5.6
5.8
7.9
7.3
7.8
8.1
7.4
7.8
14.2 13.3 13.7
30.6 28.8 29.8
46
---------------------------------------------------------------------------------------------------------------
M = MALE
F = FEMALE
ALL WEIGHTS WERE RECORDED
a. Preculling.
T = TOTAL (SUM OF PUP WEIGHTS/NUMBER
IN GRAMS (G).
MEAN LITTER WEIGHTS
OF LIVE INCLUDE
PUPS) ONLY
DAY WEIGHTS
= DAY POSTPARTUM OF LIVE PUPS.
b. Postculling.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAI,
STUDY NUMBER:
6295.9)
AND PERINATAL/POSI'NATAL
REPRODUCTION
TOXICIT
TABLE E36 (PAGE 3): PUP BODY WEIGHT LITTER AVERAGES FROM BIRTH TO DAY 21 POSTPARTUM
INDIVIDUAL DATA - F2 GE
- ------- --------------------------- -------------------------- - ---------------- - - ----------------------
MATERNAL ---------
DOSAGE GROUP 111
0.4 MG/KG/DAY
--------------------------- ----------------------------- -------------------------------------------
RAT/
LITTER NUMBER ---------
DAY 1
DAY 4a
DAY 4b
DAY 7
DAY 14
m
F
T
m
F
T
m
F
T
m
F
T
m
F
T
---------------------------- --------------------------------------------------------------------------
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274
6.6 5.2 6.1 5.8 6.4 6.8 7.6 7.0
6.5 6.2 7.1 6.0 6.0 6.1 6.6 6.3 S.9 5.8 6.9 6.4 7.3
6.9 6.5 NOT
6.5 4.9 5.6 5.2 6.3 6.4 6.8 6.7 6.5 6.0 6.7 S.4 5.6 5.8 6.2 6.1 5.6 5.5 6.6 6.1 6.6 6.6
6.2 PREGNANT
6.6 5.1 5.9 5.4 6.4
6.5 7.1 6.8 6.5 6.1 6.8 5.7 5.9 6.0 6.3 6.2 5.7 5.6 6.8 .6.2 6.9 6.8 6.3
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 0.6 9.6 8.6 8.6
9.4 6.2 7.9 4.8 7.1 8.8 9.0 9.3 8.7
8.1 6.4 6.4 8.0 7.4 9.9 6.6 5.8 7.1
8.8 8.2 8.7 8.5 8.0
9.6 6.4 8.2 4.9 7.2 9.0 9.5 9.4 8.6 8.5 6.6
6.9 8.5 7.6 10.1 6.8 6.0 6.5 8.9 8.4 9.1 8.6
8.2
10.1 6.6 6.4 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
9.6 6.3 7.6 4.9 7.4 0.8 9.0 9.1 8.7 8.0 6.7 6.4 8.0 7.6 9.9 7.0 6.0 7.1 8.8 8.0 8.8 8.4 8.1
9.8 6.4 8.0 S.0 7.4 9.3 9.8 9.5 8.6 8.3 6.8 6.8 8.5 7.8 10.1 7.2 6.1 7.1 9.0 8.3 9.2 8.5 8.3
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
S.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
25.1 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
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
60. 39.
50. 35. 42. 56.
c 56. 51. 51. 42. 50. 47. 44. 46. 43. 39.
43. 46. 50. 53. 59. 49.
13275
5.6
5.5
5.5
7.8
7.5
7.6
7.9
7.4
7.6
13.2 12.2 12.7
27.6 26.1 26.9
43.
----------------------------------------------------------------------------------------------------------------
M= ALL a.
MALE
F=
WEIGHTS WERE
Preculling.
FEMALE RECORDED
T = TOTAL (SUM IN GRAMS (G).
OF PUP WEIGHTS/NUMBER MEAN LITTER WEIGHTS
OF LIVE INCLUDE
PUPS) ONLY
DAY = DAY POSTPARTUM WEIGHTS OF LIVE PUPS.
b. Postculling.
C. Dam 13257 was found dead on day 10 of lactation; eight pups were sacrificed on day 10 postpartum.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERlNATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E37 (PAGE 1); 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
1
---------- ---------------- ------------- ------------------------------ --------------------------------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
DAY 1
---------- ------------------------------ ---------------------------------------------------------------------
13201 13202 13203 13204 13205a
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
S.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
13206
6.6
6.7
6.1
6.6
6.7
6.3
13207 13208 13209
5.7
6.3
5.5
6.2
5.6
6.2
5.9
5.8
5.8
S.6
5.6
5.8
6.6
5.7
6.1
5.7
5
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
13210 13211
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
9.3
8.5
9.2
9.0
8.6
13212 13213 13214 13215 13216 13217 13218 13219 13220 13221
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
6.6
5.3
6.1
5
7.5
7.1
7.1
6.5
7.2
6.4
6.6
6.S
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
S.7
6.3
6.4
6.3
6.5
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.S
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
5.5
6.0
6
FOUND DEAD ON DAY 28 POSTWEANING
13222 13223 13224 13225
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 FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PPOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL'REPRODUCTION
TOXIC
TABLE E37 (PAGE 2) : PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - F2 GENERATION
PUPS
---------------------------- ---------------
PUP
2
3
4
5
6
7
--8------9---- 1-0---- -11- - -12- - -1-3-----1-4-- --1-5 ----16-----
21
22
23
--------------------------- ----------------------------------------------------- -----------------------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP Il
---------------------------------------------------
0.1 MG/KG/DAY
POSTPARTUM
DAY 1
---------------------------------------------------- -----
13226 13227 13228
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
13229 13230 13231 13232 13233 13234 13235 13236
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
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
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
5.5
13237 13238 13239 13240 13241 13242 13243
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
S.9
5.2
4.9
6.3
S.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
NOT PREGNANT
13244
NOT PREGNANT
13245
NOT PREGNANT
13246 13247 13248 13249 13250
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
6.6
6.7
6.3
6.3
6.7
6.5
6.6
6.0
6.5
6.3
6.0
6.4
6.0
6.3
5.0
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
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER -- M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
SECOND NUMBER
LETTER -- A-ALIVE,
FOLLOWING
"SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, C-CULLED, M-MISSING
POSTPARTUM
THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E37 (PAGE 3): 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
---------------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM
DAY 1
----------------------------------------------------------------------------------------------------------------
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262
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
S.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
S.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.
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
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.
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
13263 13264 13265
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
13266 13267 13268 13269 13270 13271
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.
5.8
6.2
5.7
5.6
6.0
5.5
5.4
6.2
5.6
5.2
5.9
5.5
S.8
5.7
5.7
5.9
S.
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
13272 13273 13274
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.
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.
NOT PREGNANT
13275
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 FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-KALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMSNTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E37 (PAGE 4): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - F2 GENERATION
PUPS
----------------------------------------- ---------------- --------------------- I -
PUP #
1
2
3
4
5
6
7
8
9
10
11
12
------------------------------------------------------------------------------
RAT/
------------------------
13
14
15
16
----------------------
LITTER
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
DAY 4 PRECULLING
--------------------------------------------------------------------------------------------------------------
13201 13202 13203 13204 13205a
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
FS
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
PS
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
13206
10.7 10.1
9.9
9.6 10.4 10.1
13207 13208 13209
7.4
8.6
7.5
7.8
8.3
7.8
8.3
9.3
8.9
8.2
6.5
7.4
8.2
8.2
8.0
8.0
9.0
9.6
9.7
9.2
9.3
8.0 MD 2 8.3
8.9
8.9
7.2
9.8
9.4
NOT PREGNANT
13210 13211
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
13.8 14.9 14.6 14.6 14.4
13212 13213 13214 13215 13216 13217 13218 13219 13220 13221
9.5
9.2
8.0
8.5
7.5
8.7
8.8
8.9
8.9
8.8
9.2
8.4
8.0
8.5
8.7
9.6
7.3
8.0
7.4
7.1
8.1
7.5
8.4
8.3
7.6
7.7
7.7
7.4
6.5
9.8
9.4
7.9
8.5
9.6
9.6
8.1
8.8
8.4 MD 1 ms
ms
7.1
8.3
8.4
9.3
9.3
9.4
9.7
9.6
8.8
9.0
9.1
8.9
9.1
9.S
9.0
9.4
9.0
9.2
9.5
8.2
8.0
8.3
9.7
8.4
9.2
9.6
9.1
8.9
8.2
9.0
9.2
8.0
8.3
7.9
9.5
8.2
9.5
8.7
8.2
9.1
9.3
8.2
8.5
8.3
7.3
8.6
8.0
8.6
6.1
9.9
9.8 10.1
9.0
9.9 10.0
9.1
9.8
7.1
7.9
8.8
9.4
8.8
9.4
8.4
8.4
8.5
8.8
8.3
8.4
8.2
7.9
7.8
8.0
8.3
8.3
8.1
8.0 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
7.9
7.4
7.6
FOUND DEAD ON DAY 28 POSTWEANING
13222
10.7 10.6
ms
10.9 10.0 11.2 11.3
9.0
9.6
9.3
13223
10.1 10.3
9.2
9.6
9.7
9.3
8.7
8.6
8.4
9.0
9.5 10.2
8.6
8.8
13224
9.6
8.3
7.7
9.3
9.3
9.1
8.6
8.2
7.9
8.9
8.3
7.7
8.0
8.7
9.1
13225
9.7
9.0
9.3
9.3
8.7
9.4
9.0
8.2
8.4
7.9
8.7
7.3
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-14ALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPON.'30R'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E37 (PAGE 5): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA - F2 GENERATION
PUPS
------------------- ------------------
PUP #
1
2
3
4
21
22
23
------------------- I ------------------
------- --------------- -- ------------------------------------
5
6
7
8
9
10
11
12
13
14
is
-------
16
1
------------------------------------------------------------------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP 11
0.1 MG/KG/DAY
POSTPARTUM
DAY 4 PRECU
-------------------------------------- -------------------------------------------------------------------------
13226 13227 13228
8.0
8.0
8.4
9.1
9.1
8.7
ms
7.8
9.0
7.2
0.1
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
13229 13230 13231 13232 13233 13234 13235 13236
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
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
7.2
8.8
8
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
7.5
8.7 10.3 MD 2 MD I MD 1
6.9
8.1
7.6
8.8
8.5
8.8
9.3 10.3
9.5 FM
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
7.2
13237 13238 13239 13240 13241 13242 13243
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
8.4
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
8.8
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
NOT PREGNANT
13244
NOT PREGNANT
13245
NOT PREGNANT
13246
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
13247 13248
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
13249 13250
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
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVACE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICT
TABLE E37 (PAGE 6): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA - F2 GENERATION
PUPS
----------------------------- ---- -- --------------- -------------------------- I ------------------------- -
PUP #
1
2
3
4
5
6
7
8
9
10
11
12
--------------------------------------- -------------- ----------------------------
13
14
is
16
1
---------------------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM
DAY 4 PREC
---------------------------------------------------------------------------------------------------------------
13251 13252 13253 13254 132SS 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265
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
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
F
9.4
8.5 10.4 10.0
9.0
ms
8.6
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
7.5
6.9
6.5
6.7
6.4
S.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
B.S
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
13266 13267 13268 13269 13270 13271
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
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
6.7
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
?.S
8.2
6.6
us
9.4
9.3
9.7 10.2
ms
9.4
8.8
8.5
8.4
8.7
8.3
13272 13273 13274
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
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
NOT PREGNANT
13275
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 FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES
THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
PROTOCOL
418 008:
COMBINED OPAL IGAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E37 (PAGE 7): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA
P2 GENERATION
PUPS
---- - ----- -------------------
PUP #
1
2
3
4
---- ----------------------------
RAT/
----- ------------------- ---------------------- - --- -------------------
5
6
7
8
9
10
11
12
13
14
is
16
---------------------------------------------------------------------------
LITTER -------------
MATERNAL
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
------------------- -------------------------------------------------------
13201 13202 13203 13204 13205a
8.9 MC 4 MC 4
7.2
8.3 8.5 MC 4 MC 4
MC 4 8.0
MC 4 MC 4
MC 4 7.9 6.7
MC 4
MC 4 8.9
MC 4 MC 4
8.8 MC 4
6.1 6.7
9.0 8.6 6.2 7.0
8.9 FC 4
5.9 7.7
PC 4 7.1 5.3
MD 4
9.0 7.6 6.1 MM 2
8.5 7.5 FC 4 FC 4
9.3 FC 4 FC 4 FC 4
FC 4 FC 4
5.9 6.7
DAY 4 POSTCULLING -------------------
FD I FC 4
6.6 FC 4
FS FC 4 FM 3
6.1
PS FS FM 2 PC 4
13206
10.7 10.1
9.9
9.6 10.4 10.1
13207 13208 13209
MC 4
8.6
7.S
7.8 MC 4 MC 4 MC 4 MC 4
8.9 MC 4 MC 4 MC 4 MC 4 FC 4
8.0
8.0
9.0
9.6
9.7 MC 4
9.3 MC 4 MD 2
8.3
8.9
8.9 FC 4 FC 4
9.4
NOT PREGNANT
13210 13211
MC 4 MC 4 MC 4 MC 4
7.0
6.5
7.3
7.0 MC 4 MD 2 6.4
6.9
7.2
6.8 FC 4 FC 4 F
13.8 14.9 14.6 14.6 14.4
13212 13213 13214 13215 13216 13217 13218 13219 13220 13221
9.5
9.2 MC 4
8.5 MC 4
8.7
8.8 FC 4 FC 4 FC 4
9.2
8.4
8.0 FC 4
8.7 FC 4
7.3
8.0
7.4 FC 4
8.1 FC 4 FC 4
8.3
7.6 FC 4 FC 4 FC 4
6.5
MC 4
9.4 MC 4 MC 4
9.6
9.6 MC 4 MC 4
8.4 MD 1 ms
ms
7.1
8.3 FC 4
9.3 F(
9.3
9.4
9.7 FC 4
8.8 FC 4
9.1
8.9 FC 4
9.5 FC 4 FC 4
9.0 FC 4
9.5 MC 4
8.0 MC 4
9.7 MC 4
9.2 MC 4
9.1 FC 4 FC 4
9.0
9.2 FC 4
8.3
MC 4
9.5 MC 4
9.5 MC 4 MC 4
9.1
9.3 MC 4
8.5 FC 4 FC 4
8.6 FC 4
8.6 FC 4
7
MC 4 MC 4 10.1 MC 4 MC 4 10.0
9.1
9.8 MC 4 FC 4
8.8
9.4
8.8
9.4
8.4 MC 4 MC 4
8.8
8.3 MC 4 8.2 MC 4
7.8 FC 4
8.3
8.3
8.1 FC 4 FM 2
MC 4 MC 4 MC 4
7.7
7.6
7.8
8.1 FC 4
7.8
7.7 FC 4 FC 4 PC 4
7.9
7.4 FC 4 FC
FOUND DEAD ON DAY 28 POSTWEANING
13222
10.7 10.6
ms
10.9 10.0 11.2 11.3 FC 4
9.6
9.3
13223
MC 4 10.3
9.2
9.6
9.7 FC 4 FC 4
8.6 FC 4 FC 4 FC 4 10.2
8.6
8.8
13224
9.6 MC 4
7@7 MC 4 MC 4
9.1
8.6 MC 4 FC 4 FC 4
8.3 FC 4
8.0
8.7
9.1
13225
MC 4 MC 4
9.3
9.3 MC 4
9.4
9.0
8.2
8.4
7.9
8.7 FC 4
---------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST SECOND NUMBER
LETTER LETTER FOLLOWING
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
A-ALIVE, "SECOND
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS ISPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICII
TABLE E37 (PAGE 8): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - F2 GENERATION
PUPS
----- ----------------------------------- ----------- -
PUP
1
2
3
4
5
6
7
21
22
23
----------------------------------
--------------------
PAT/
------ --------------
8
9
10
11
---------------------
-- -------------- ---------------
12
13
14
15
16
17
-- ------------------------------
LITTER
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
POSTPARTUM
DAY 4 POSTCU
----------------------------------------------------------------------------------------------------------------
13226 13227 13228
MC 4 MC 4
8.4
9.1
9.1
8.7
ms
7.8
9.0 FC 4
8.1
8.9
MC 4 MC 4 10.0 MC 4 MC 4
7.6
8.9
7.9 FC 4
9.4
8.5
9.2
8.6
NOT PREGNANT
13229 13230 13231 13232 13233 13234 13235 13236
MC 4 MC 4 MC 4
9.1 MC 4 MC 4
7.5 MC 4
7.2
MC 4 7.1
10.1 9.4
MC 4 10.8
8.7 8.3
MC 4 7.5
MC 4 9.6 8.3
MC 4 10.3 MC 4
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 I 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
8.0 MC 4 FC 4
9.0 9.8 9.5 8.1 7.2
7.0 7.1 9.6 FC 4 FC 4 MS 7.6 8.7
6.8 6.1 FC 4
PC 4 8.2 ms 8.8
MC 4
FC 4 7.0 9.5 9.3 9.2 ms
8.3
5.6 6.5 FC 4 9.0 8.7 B.S
FC 4
7.0 7.0 PC 4 9.3 FC 4 PC 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. FM FC
13237 13238 13239 13240 13241 13242 13243
8.6
8.2 MC 4
9.6
9.5 MC 4 MC 4
8.4 FC 4
9.6 FC 4 PC 4
0.0
8.6
10.1 MC 4 MC 4
9.7
9.5 MC 4
9.2 FC 4
8.5
9.9
9.2 FC 4 FC 4
9.6 FC 4 FC 4
9.3
8.4 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4
8.6
7.8
9.6 FC 4
7.7
8.0
8.0
8.4 MC 4 MC 4
8.9
8.2 MC 4
8.4 MC 4
7.3
7.6 FC 4
7.4 FC 4 PC 4
7.9 FC 4
7.0
6.7 MC 4 MC 4
7.1
7.1 MC 4 MC 4 MC 4 FC 4 FC 4
4.9
6.0
6.4 FC 4
6.3
9.1
9.1
9.4 MC 4 MC 4 MC 4 MC 4 MC 4 11.2
9.7 PC 4 FC 4 PC 4 FC 4 10.1
9.4
8.
NOT PREGNANT
13244
NOT PREGNANT
13245
NOT PREGNANT
13246 13247 13248 13249 13250
8.1 6.2 7.1 MC 4 7.7
8.3 6.9 MC 4 MC 4 MC 4
7.4 MC 4
6.8 9.3 MC 4
8.6 6.5 MC 4 8.8 MC 4
MC 4 7.4
8.2 9.1 MC 4
FC 4 6.6
MC 4 9.1
MC 4
7.4 FC 4
6.7 MC 4 MC 4
FC 4 FC 4 MC 4
8.2 8.1
8.1 FC 4
6.9 FC 4 MC 4
FC 4 FC 4 FC 4 FC 4
8.5
FC 4 FC 4
7.0 FC 4 MC 4
7.8 FC 4 FC 4 FC 4
8.1
FC 4 6.6
FC 4 9.5 7.4
FC 4 FC 4 FC 4
9.2 7.9
7.0
5.6
6.3
6.5
7.4 FC
8.4 FC 4
7.1
7.2 FC
----------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E37 (PAGE 9): 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
1
--------------- -----------------------------------------------------------------------------------------------
RAT/
LITTER
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM
DAY 4 POSI
--------------- ---------- ------------------------------------------------------------------------------------
13251 13252 13253 13254 13255 13256 13257
13258 13259 13260 13261 13262 13263 13264 13265
13266 13267 13268 13269 13270 13271 13272 13273 13274
MC 4 MC 4
9.2 4.8 MC 4 9.4 10.5 9.8 MC 4 9.0 7.5
MC 4 8.6 8.6
11.2 7.1 6.2 6.7
MC 4 9.0 9.4
MC 4 8.9 NOT
9.5 MC 4 MC 4
5.2 MC 4 MC 4 MC 4 MC 4
8.9 MC 4
6.9 MC 4 MC 4
8.4 10.2
7.9 6.3 6.8 8.7 MC 4 9.3 8.9 7.8 PREGNANT
9.9 6.5 8.3 5.9 MC 4 10.4 MC 4 9.6
8.6 MC 4
6.5 7.8 MC 4 MC 4 10.9 7.5 6.1 MC 4 MC 4 MC 4 9.7 MC 4 8.6
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
MC 4 6.2 8.8
MM 3 MC 4
9.0 9.8 10.4 8.5 MC 4 PC 4 7.0
9.1 MC 4
9.7 7.2 MC 4 MC 4 MC 4 8.6 ms MC 4 8.6
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 8.3ms
9.7 7.3 8.2 FC 4 ms PC 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
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
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
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
9.3 6.7 PC 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
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
PS 9.6 8.2
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 FD
FS
F
FC 4 FC
7.3
FC 4 FC
FC 4
5
us
7.8
8
FC 4 FC
13275
7.4
8.2 MC 4
8.7
7.2
ms
FC 4
7.5
7.0
7.6 FC 4 FC 4
7.6 FC 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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICI
TABLE E37 (PACE 10): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - F2 GENERATION
PUPS
------------------------------------------------ - ------------------- ----------------------------------------
PUP #
1
2
3
4
5
6
7
a
9
10
11
12
13
14
15
16
1
--------------------------------------------- --- --------------------------------------------------------------
RAT/
LITTER
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
DAY 7
---------------------------------------------------------------------------------------------------------------
13201 13202 13203 13204 13205a
14.8 14.5 MC 4 MC 4 MC 4 14.9 14.8 15.1 FC 4 14.4 15.3 14.9 PC 4 FD 1 FS
FS
MC 4 15.0 15.5 IS-5 14.2 MC 4 13.7 FC 4 15.6 14.0 13.7 FC 4 FC 4 FC 4 FC 4
FS
MC 4 MC 4 MC 4
9.5 MC 4 10.7
9.4
9.3 10.5
9.4 FC 4 FC 4
8.2
9.3 FM 3 FM 2
10.4 MC 4 MC 4 MC 4 MC 4 11.9 11.6 12.6 MD 4 MM 2 FC 4 FC 4 11.0 FC 4 11.4 FC 4 11
13206 13207 13208 13209
17.6 17.1 16.5 15.9 16.8 17.3
MC 4 13.1 16.1 15.2 MC 4 MC 4 MC 4 MC 4 13.8 MC 4 MC 4 MC 4 MC 4 FC 4 14.2 13.8 13 14.7 14.6 14.0 MC 4 14.8 MC 4 MD 2 13.2 13.7 14.1 FC 4 FC 4 14.7
NOT PREGNANT
13210 13211
MC 4 21.5
MC 4 22.5
MC 4 22.3
MC 4 22.1
11.2 20.6
9.6 10.9 11.3 MC 4 MD 2 10.2 11.4 10.8
9.7 FC 4 FC 4 FC
13212 13213 13214 13215 13216 13217 13218 13219 13220 13221
16.0 14.9 MC 4 16.5 16.6 MC 4 MC 4 14.1 MC 4
FOUND
16.2 FC 4 15.0 17.2 MC 4 16.2 MC 4 MC 4 MC 4
DEAD
MC 4 15.3 MC 4 1S.5
14.8 14.4 14.2 FC 4
MC 4 MC 4 16@6
16.8
16.1 FC 4 15.7 FC 4
14.1 MC 4 16.1 MC 4
MC 4 16.0 MC 4 MC 4
16.7 MC 4 MC 4 1S.4
MC 4 13.2 13.4 MC 4
MC 4 13.6 13.2 14.7
ON DAY 26 POSTWEANING
15.1 11.8 MC 4 16.3 16.4 1S.5 16.9 13.2 13.7
FC 4 FC 4 MC 4 15.7 MC 4 16.0 16.5 MC 4 FC 4
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
FC 4 FC 4 12.7 FC 4 FC 4 FC 4 16.2 FC 4 13.4
13.7 FC 4
15.4 14.8
FM 2 13.7
16.4 FC FC 4 13. FC 4 FC
13222
16.7 16.8
ms
16.4 16.0 17.5 17.3 FC 4 14.6 16.3
13223
MC 4 17.3 17.4 16.0 14.2 FC 4 FC 4 15.7 FC 4 PC 4 FC 4 15.3 16.9 15.0
13224
16.2 MC 4 15.0 MC 4 MC 4 11.7 13.5 MC 4 FC 4 FC 4 13.9 FC 4 13.4 13.3 14.0
13225
MC 4 MC 4 14.9 15.0 MC 4 14.8 15.1 13.7 13.3 13.1 14.2 FC 4
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE FIRST LETTER SECOND LETTER NUMBER FOLLOWING
RECORDED M-MALE,
A-ALIVE, "SECOND
IN GRAMS (G).
F-FEMALE, U-SEX UNDETERMINABLE
S-STILLBORN,
U-UNCERTAIN,
LETTER" INDICATES THE DAY
D-DIED, POSTPARTUM
C-CULLED, M-MISSING THE EVENT OCCURRED.
(PRESUMED
CANNIBALIZED)
a. Rat 13205 was excluded from study on day 7 postweaning; the sex was incorrectly identified.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E37 (PAGE 11); PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
INDIVIDUAL
DATA - F2 GENERATION
PUPS
-------------------
PUP
1
21
--- ------------------
2
3
4
5
22
23
- -- -----
6
7
------------ ---- ------------------------- - - ------
8
9
10
11
12
13
14
15
16
--- ------------------------------------------RAT/
--------------------------------------------------
----------
LITTER
MATERNAL DOSAGE GROUP Il
0.1 MG/KG/DAY
POSTPARTUM
DAY 7
--------------------------------------------------------------------------------------------------------------
13226 13227 13228
MC 4 MC 4
NOT
MC 4 MC 4 PREGNANT
15.5 17.3
16.0 MC 4
14.5 MC 4
15.7 14.0
ms 15.2
14.6 13.6
15.2 FC 4
FC 4 14.9
13.0 16.0
15.8 15.3
14.6
13229 13230 13231 13232 13233 13234 13235 13236
MC 4 MC 4 MC 4 16.1
MC 4 10.7 17.2 15.9
MC 4 11.9 MC 4 16.2
11.1 12.1 17.3 MC 4
MC 4 MC 4 17.4 MC 4
MC 4 MC 4 17.8 MC 4
11.9 MC 4 FC 4 16.8
10.6 MC 4 FC 4 16.3
11.6 12.2 17.8 FC 4
10.8 11.9 FC 4 PC 4
FC 4 ll.S
16.5 15.9
10.9 10.9
FC 4 16.1
7.4 9.6 FC 4 15.3
10.2 17.0
FC 4 FC 4 FC 4 1
MC 4 MC 4 15.5 14.0 MC 4 MC 4 13.6 14.7 FC 4 13.7 14.6 15.0 FC 4 FC 4 FC 4 14.5
MC 4 17.7 MC 4 MC 4 MC 4 15.2 17.4 15.9
ms
ms
ms
16.1 12.2 14.0 MD 2 MD I MD 1 13.2 13.4 11.2 12.2
15.4 FC 4 16.6 15.S 17.8 Ft
MC 4 13.0
13.9
MC 4 MC 4 MC 4 MC 4 12.7
14.5
11.8
MC 4 13.9
FC 4 12.5
FC 4 FC 4 FC 4 F(
13237 13238 13239 13240 13241 13242 13243
14.0 16.3 14.7 14.6 12.3 16.5
NOT
10.9 MC 4 16.6 MC 4 11.1 15.8 PREGNANT
MC 4 MC 4 MC 4 MC 4 MC 4 15.6
13.1 17.2 MC 4 14.3 MC 4 MC 4
12.0 17.9 MC 4 13.1 10.9 MC 4
MC 4 MC 4 MC 4 MC 4 10.9 MC 4
MC 4 17.4
MC 4 13.9 MC 4 MC 4
12.8 FC 4 MC 4 MC 4 MC 4 MC 4
FC 4 17.5 16.2 13.3 MC 4 18.7
12.9 16.4 15.6 11.5 FC 4 15.9
FC 4 16.6 17.4 FC 4 FC 4 FC 4
FC 4 FC 4 PC 4 12.6
8.9 FC 4
14.3 FC 4 14.8 FC 4 10.3 FC 4
11.8 16.6 15.1 FC 4
7.8 FC 4
FC 4 14.5 13.1 PC 4
14.S
FC 4
FC 4 10.2 16.0 16
13244
NOT PREGNANT
13245
NOT PREGNANT
13246
14.0 15.0 13.5 13.9 MC 4 FC 4 13.3 FC 4 13.9 FC 4 FC 4 14.2 FC 4 FC 4 11.8
13247
10.5
9.4 MC 4 MD 7 MD 6
9.9 FC 4 PC 4 PC 4 FC 4 PC 4 FC 4 11.5 FC 4 10.4
9.3
13248
13.3 MC 4 11.1 MC 4 14.3 MC 4 12.1 MC 4 11.1 FC 4 11.4 FC 4 FC 4 FC 4 11.1 11.6 FC
13249
MC 4 MC 4 15.5 14.5 15.9 15.2 MC 4 16.5 FC 4 FC 4 FC 4 FC 4 14.8 15.3 15.4 FC 4
13250
14.0 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 15.4 MC 4 14.0 MC 4 13.3 13.6 12.7 13.8 13.0 FC
---------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTII,ITY, DEVELOPMENTAL
STUD@' NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E37 (PAGE 12): 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
-------------------------------------------------------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP 111
-------------------------------------------
0.4 MG/KG/DAY
POSTPARTUM
DAY 7
---------------------------- -------------------------------------
132Sl 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264
13265 13266 13267 13268 13269 13270 13271 13272 13273 13274
MC 4 17.4 18.3 17.1 MC 4 16.2 MC 4 16.5 15.2 FC 4 PC 4 14.3 16.3
MC 4 15.6
5.6 MC 4 18.0 16.9
MC 4 MC 4
8.1 MC 4 MC 4 MC 4
11.9 14.6
5.8 MC 4 16.7 MC 4
MC 4 MC 4 MD 4 11.4 16.7 16.5
10.5 12.8 MM 3 MC 4 15.9 15.8
10.4 MC 4 MM 3 10.1
ms 17.6
MC 4 13.1
5.6 10.6 FC 4 FC 4
10.0 15.4 PC 4
MS FC 4 PC 4
FC 4 FC 4 FC 4 MD 5 13.9 16.0
FC 4 10.9
4.8 10.5 FC 4 FC 4
FC 4 PC 4
4.4 FC 4 PC 4
FC 4
10.7 10.2
6.1 10.0 15.9 15.4
10.3 FC 4
7.2 9.2 15.0 14.0
9.9 11.3
13.5 FM 2
FD 4 FM 4 FD 3 F
FC 4 11.6
PS
16.0 14.7
FM 3 PC 4
16.3 MC 4
MC 4 14.6
15.3 14.2
MC 4 MC 4
14.9 13.3
15.3 MC 4
FC 4 14.2
15.1 MC 4
FC 4 13.6
FC 4 MD 1
14.9 13.3
PC 4 13.6
15.1 15.0
FC 4 14.0
13.8 10.7 MC 4
MC 4 9.1
MC 4
MC 4 MD 7
9.5
12.8 ND 6 12.0
MC 4 PC 4 13.2
13.8 FC 4 13.8
13.2 FC 4 12.7
MM 2 FC 4 FC 4
MD 1 10.2
9.9
13.4 8.3
10.6
FC 4 9.1
FD 5
12.4 FD 6
FS
12,3 FC 4
FC 4 FC 4
12.5
FC 4 F
15.3 14.S 15.5
MC 4 11.2 16.5
MC 4 MC 4
8.5
14.8 12.8 17.1
14.7 MC 4 15.1
15.2 MC 4 16.7
MC 4 14.1 14.2
MC 4 11.9
MC 4 12.9
FC 4 PC 4
12.7 12.0
12.9 FC 4
PC 4 FC 4
12.3 FC 4
14.1 FC 4
13.0
12.1 11.7 11.2 MC 4 12.0 MC 4 MM 3 FC 4 PC 4 10.4 FC 4 FC 4 11.5 FC 4 12.5 FC 4 F
8.6
7.5
8.2
8.5 MC 4 FC 4 PC 4
7.9
8.3 FC 4
6.9 FC 4 PC 4 FC 4 FC 4 FC 4
10.6 10.3 MC 4 11.1 MC 4 MC 4 10.9 11.3 10.9 10.7 11.0 FC 4 FC 4
FS
MC 4 14.3 MC 4 14.5 MC 4 MC 4 12.9 MC 4 MC 4 12.9 13.0 12.5 13.6 15.6
13.6 MC 4 MC 4 13.7 14.8 MC 4 15.1 12.6 FC 4 FC 4 FC 4 12.8 13.3 13.8 FC 4 us
16.1 14.3 15.3 15.2
ms
14.2 14.0 FC 4 14.1 14.3 FC 4
MC 4 12.7
NOT
14.8 13.6 PREGNANT
MC 4 13.7
MC 4 MC 4
MC 4 14.7
MC 4 MC 4
15.0 ms
MC 4 12.5
16.0 PC 4
16.9 13.4
MC 4 FC 4
ms FC 4
ms 13.5
FC 4 FC 4
17.3 13.4
13.9 1 FC 4 F
13275
12.3 12.9 MC 4 13.4 14.1
ms
FC 4 12.7 11.3 12.2 FC 4 FC 4 12.5 FC 4
--------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
SECOND L M ER
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.
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINA'I'AL/POSTNATAL
REPRODUCTION
TOXIC
TABLE E37 (PAGE 13): PUP BODY WEIGHTS FROM BIRTI] TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA - F2 GENERATION
PUPS
-------------------
PUP #
1
--------------------
RAT/
- --------------------------
2
3
4
5
6
--- -----------------------
------------------ ---- ---
--------------------
7
8
9
10
11
12
13
14
15
---------------------------- ------------------------
16 -- ---
LITTER
MATERNAL
DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
--------------------- ---------------------------- --------------------------
13201 13202 13203 13204 13205a
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
PC 4 34.5 23.4 MD 4
32.8 33.4 21.8 MM 2
33.5 33.8 FC 4 FC 4
POSTPARTUM
DAY 14
--------------------------------
32.6 PC 4 FD 1 FS
FS
FC 4 FC 4 FC 4 FC 4
FS
FC 4 26.0 22.8 FM 3 FM 2
FC 4 27.1 FC 4 24.4 FC 4 2
13206 13207 13208 13209
38.8 MC 4 31.1
NOT
36.8 35.6 30.3 PREGNANT
36.9 34.1 30.4
37.7 30.9 MC 4
35.4 MC 4 30.5
36.1 MC 4 MC 4
MC 4 MD 2
MC 4 29.5
31.7 32.1
MC 4 29.7
MC 4 FC 4
MC 4 FC 4
MC 4 28.2
FC 4
32.1
29.6 3
13210 13211
MC 4 39.9
MC 4 40.5
MC 4 39.6
MC 4 40.5
27.4 35.9
26.4
26.7
28.3 MC 4 MD 2 26.6
25.8
23.8
25.3
PC 4 FC 4 F
13212 13213 13214 13215 13216 13217 13218 13219 13220 13221
33.6 33.3
31.8 FC 4
MC 4 28.7
34.1 30.3
MC 4 33.3
32.1 FC 4
32.5 31.2
FC 4 FC 4
FC 4 PC 4
FC 4 28.3
31.5 32.7
32.7 FC 4
29.7 FC 4
PC 4 FC 4
28.3
MC 4 34.4 33.4 MC 4 MC 4
36.7 34.3 MC 4 34.9 MC 4
MC 4 36.0 32.2 MC 4 33.5
MC 4 FC 4 MC 4 34.2 MC 4
36.2 34.2
34.8 MC 4 MC 4
34.7 FC 4 MC 4 MC 4 33.9
MC 4 33.1 34.0 34.4 34.1
MC 4 33.1 MC 4 35.4 33.3
36.9 FC 4 32.5 MC 4 MC 4
MD 1 32.8 FC 4 35.0 FC 4
ms FC 4 FC 4 FC 4 34.0
ms FC 4 35.1 FC 4 32.8
29.7 31.6 32.7 33.3 30.9
33.9 PC 4 FC 4 FC 4 30.5
FC 4
31.5 30.3
36.1 F FC 4 3
29.3 MC 4
FOUND
MC 4 MC 4
DEAD
MC 4 30.0 31.4 MC 4 MC 4 33.3 31.7 30.9 ON DAY 28 POSTWEANING
29.9 31.8
MC 4 FC 4
28.1 30.3
FC 4 31.6
28.8 FC 4
28.6 FC 4
30.3 FC 4
FC 4 28.3
FM 2 31.0
FC 4 F
13222 13223 13224 13225
34.5 MC 4 27.2 MC 4
35.2 35.3 MC 4 MC 4
ms 35.1 32.0 32.5
31.6 31.5 MC 4 31.1
35.2 34.0 MC 4 MC 4
33.3 FC 4 30.1 31.6
33.9 FC 4 32.0 31.0
FC 4 34.1 MC 4 30.1
33.6 FC 4 FC 4 29.7
34.8 FC 4 FC 4 30.2
FC 4 29.5 30.9
32.7 FC 4 FC 4
33.3 27.9
32.5 29.4
28.5
--------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED OPAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, I)EVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E37 (PAGE 14): PUP BODY WEIGHTS FROM BIRTH TO I)AY 21 POSTPARTUM
- INDIVIDUAL
DATA - F2 GENERATION
PUPS
--- --------- ------------------- -------------------- ----------------------------- -------------
PUP
1
2
3
4
5
6
7
21
22
23
--- ----------------------------- ------I -------------
8
9
10
11
12
-----------------------------
13
14
15
16
17
---------------------------
RAT/
LITTER
MATERNAL
DOSAGE GROUP 11
------------------------------------------------------
0.1 MG/KG/DAY
POSTPARTUM
DAY 14
---------------------------------------------------------
13226 13227 13228
MC 4 MC 4
NOT
MC 4 MC 4 PREGNANT
33.9 29.5
33.6 MC 4
32.0 MC 4
31.5 31.6
ms 35.1
32.5 31.5
33.4 FC 4
PC 4 33.5
33.6 30.9
31.9 34.2
31.0
13229 13230 13231 13232 13233
13234 13235 13236
MC 4 MC 4 MC 4 30.1 MC 4 MC 4 31.7 28.8 31.3 21.2 FC 4 28.6 28.3 29.2 FC 4
MC 4 27.8 25.8 27.5 MC 4 MC 4 MC 4 MC 4 25.6 25.8 26.2 24.1 26.8
MC 4 33.3
37.8 34.2
MC 4 34.4
36.9 MC 4
36.6 MC 4
37.4 MC 4
FC 4 33.5
FC 4 32.8
35.8 FC 4
PC 4 FC 4
3S.6 34.1
FC 4 33.6
FC 4 35.0
37.7
FC 4 FC 4 36.
MC 4 MC 4 34.8 33.2 MC 4 MC 4 32.7 32.9 FC 4 32.8 31.8 33.1 FC 4 FC 4 FC 4 32.0
MC 4 35.8 MC 4 MC 4 MC 4 33.3 33.4 32.0
ms
ms
ms
32.1 FC 4 35.3 35.4 31.1 FM
29.0 31.6 34.4 MD 2 MD 1 MD 1 31.1 31.6 27.8 29.2
MC 4 32.9
32.1
MC 4 MC 4 MC 4 MC 4 34.2
32.1
29.7
MC 4 31.0
FC 4 30.8
FC 4 FC 4 FC 4 FC
13237 13238 13239 13240 13241 13242 13243 13244
31.9 35.3 MC 4 29.8 33.1 MC 4 MC 4 32.7 FC 4 31.0 FC 4 FC 4 32.0 34.1
37.8 37.7
MC 4 36.4
MC 4 MC 4
38.0 MC 4
37.4 MC 4
MC 4 MC 4
36.1 MC 4
FC 4 MC 4
37.2 37.4
37.8 35.3
36.6 38.1
FC 4 FC 4
FC 4 34.6
35.4 35.2
FC 4 35.1
FC 4
30.3 MC 4 MC 4 31.2 31.2 MC 4 28.0 MC 4 29.6 28.5 FC 4 30.1 FC 4 FC 4 27.5 FC 4
28.2 27.6 MC 4 MC 4 26.7 29.8 MC 4 MC 4 MC 4 FC 4 FC 4 26.2 27.7 23.0 FC 4 23.9
35.7 35.9 36.0 MC 4 MC 4 MC 4 MC 4 MC 4 38.9 36.0 FC 4 FC 4 FC 4 FC 4 35.4 33.1 36.
NOT PREGNANT
NOT PREGNANT
13245
NOT PREGNANT
13246 13247 13248 13249 13250
30.8 28.6 31.8 MC 4 30.2
32.7 27.4 MC 4 MC 4 MC 4
32.3 MC 4 29.2 31.2 MC 4
31.3 MD 7 MC 4 30.6 MC 4
MC 4 MD 6 33.7 31.3 MC 4
FC 4 27.1 MC 4 31.4 MC 4
30.0 FC 4 29.1 MC 4 MC 4
FC 4 FC 4 MC 4 30.9 30.8
31.7 FC 4 29.7 FC 4 MC 4
FC 4 FC 4 PC 4
FC 4 30.4
FC 4 FC 4 29.3 FC 4 MC 4
28.5 FC 4 FC 4 FC 4 31.2
FC 4 25.6 PC 4 32.4 29.8
FC 4 FC 4 FC 4 30.2 28.5
31.9 31.5 29.8 30.7 29.8
FD10 29.2 FC FC 4 27.3 FC
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL PFOS IN RATS (SPONSC)R'S STUDY NUM13ER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E37 (PAGE 15): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL
DATA - F2 GENERATION
PUPS
PUP A ----------
--------------- -- ---- - -- ------- I ----------- ------------------------------------- ---- - --------
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
---------------------------- ------------------------------------------------------------------------
PAT/
LITTER
MATERNAL
DOSAGE GROUP 111
0.4 MG/KG/DAY
POSTPARTUM
DAY 14
-
---------- ----------------------- -----------------------------------------------------------------------------
13251 13252
13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265
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 PC 4 FC 4 PC 4 24.6 23.0 24.7 25.8
29.1 MC 4 30.6 MC 4 35.5 MC 4 34.3 25.4 PC 4 33.3 FC 4 25.S FC 4 32.1 FM 2
21.2 MC 4 37.9
17.0 MC 4 MC 4
14.9 MC 4 34.6
MD 4 24.3 35.5
MM 3 MC 4 35.2
MM 3 24.9
ms
16.9 26.1 FC 4
FC 4 ms
PC 4
FC 4 MD 5 33.9
19.0 24.5 FC 4
11.2 FC 4 FC 4
16.3 21.1 33.8
11.3 24.4 34.3
FD 4 PH 4 FD 3 FD
FC 4 23.3
FS
FS
32.3 FM 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 PC 4 32.4 FC 4 32.4
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 24.5
MC 4 25.6
MC 4 MD 7
34.0 MD 6
MC 4 FC 4
33.4 PC 4
32.8 FC 4
MM 2 FC 4
ND 1 24.5
32.7 21.8
FC 4 24.5
30.4 FD 6
31.4 FC 4
FC 4 FC 4
31.6
FC 4 FC
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 PC 4 26.0 27.2
26.7 30.4 MC 4 29.8 MC 4 MC 4 25.4 28.9 26.4 FC 4 26.9 PC 4 FC 4 FC 4 FC 4 24.7
32.6 31.9 30.9 32.2 33.3 20.6 31.7
13266 13267 13268 13269 13270 13271 13272 13273 13274
26.1 20.1 26.6 MC 4 32.6 32.7 MC 4 30.9 NOT
25.8 23.0 26.2 27.5 MC 4 31.6 35.5 32.2 PREGNANT
28.1 23.5 MC 4 MC 4 MC 4 31.1 MC 4 32.6
MC 4 24.1 25.4 27.1 30.4 36.5 MC 4 MC 4
26.3 MC 4 MC 4 MC 4 31.2
ms MC 4 32.8
MC 4 PC 4 MC 4 MC 4 MC 4 31.4 MC 4 MC 4
MM 3 FC 4 27.5 28.4 33.2 32.1 40.8
ms
FC 4 24.0 27.2
MC 4 29.1 PC 4 MC 4 32.4
FC 4 18.9 27.3 MC 4 FC 4 32.0 39.7 FC 4
27.5 FC 4 26.7 29.3 FC 4 29.7 34.8 31.1
FC 4 22.8 27.2 31.3 @FC 4 FC 4 MC 4 FC 4
FC 4 FC 4 FC 4 28.8 29.2
ms FC 4
25.2 FC 4 FC 4 26.8 30.9
ms 32.2
FC 4 FC 4
FS 29.3 31.2
FC 4 FC 4
25.1 FC 4
FC 4 34.5 30.2
FC 4 FC 4
us 40.8 FC 4
FC 23.
36. FC
13275
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
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
7
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICITY
TABLE E37 (PAGE 16): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA - F2 GENERATION
PUPS
------- ----------- ------ ----------------------------------- 11 ---------- ------- ------ --------------------
PUP #
1
2
3
4
5
6
7
8
9
10
11
12
13
14
is
16
17
-------------------- ---------------------------------------------------------------------- --------------------
RAT/
LITTER
MATERNAL DOSAGE GROUP 1
0 (VEHICLE) MG/KG/DAY
POSTPARTUM
DAY 21
----------------------------------------------------------------------------------------------------------------
13201 13202 13203 13204 13205a
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
PS PS FM 2 FC 4
43.0
13206 13207 13208 13209
60.2 MC 4 50.4
NOT
62.7 47.8 48.4 PREGNANT
61.5 52.5 47.6
59.0 50.6 MC 4
61'.2 MC 4 51.4
57.4 MC 4 MC 4
MC 4 MD 2
MC 4 53.0
47.4 50.0
MC 4 46.4
MC 4 PC 4
MC 4 FC 4
MC 4 46.5
FC 4
44.2
48.5 47.3
13210 13211
MC 4 58.0
MC 4 62.0
MC 4 58.9
MC 4 58.7
44.7 53.2
43.5
42.3
42.5
MC 4 MD 2 41.6
38.2 42.4
42.9
FC 4 FC 4 FC 4
13212 13213 13214 13215 13216 13217 13218 13219 13220 13221
53.2 49.0 MC 4 53.0 58.4 MC 4 MC 4 50.5 MC 4
FOUND
51.0 FC 4 55.4 54.9 MC 4 51.2 MC 4 MC 4 MC 4
DEAD
MC 4 52.2 MC 4 55.6 47.1 42.0 48.0 FC 4 MC 4 MC 4 55.0 53.9 52.9 FC 4 49.2 FC 4 50.2 MC 4 54.3 MC 4 MC 4 52.7 MC 4 MC 4 55.0 MC 4 MC 4 53.6 MC 4 51.7 54.0 MC 4
MC 4 52.8 48.9 48.9 ON DAY 28 POSTWEANING
48.4 41.6 MC 4 54.0 55.8 50.1 56.1 50.6 49.2
FC 4 FC 4 MC 4
50.3 MC 4 53.1 58.5 MC 4 FC 4
FC 4 FC 4 52.9 FC 4 52.6
MC 4 MC 4 50.5 51.5
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
52.2 FC 4
ms FC 4 55.3
FC 4 Sl.l 52.9 FC 4
51.1 FC 4 44.2 48.0 52.9 44.9 53.7 49.9 FC 4
FC 4 FC 4 47.2 FC 4 FC 4 FC 4 49.5 FC 4 44.6
46.4 FC 4
58.8 51.1
FM 2 48.1
54.9 FC 4 FC 4
FC 4 54.3 FC 4
13222
47.7 50.1
ms
48.1 47.2 51.3 48.7 FC 4 51.0 43.7
13223 13224 13225
MC 4 51.7 MC 4
52.2 MC 4 MC 4
55.0 52.3 49.4
49.6 MC 4 48.9
55.1 MC 4 MC 4
FC 4 49.2 53.0
FC 4 48.7 49.1
51.1 MC 4 48.0
FC 4 FC 4 47.9
FC 4 FC 4 45.9
FC 4 48.9 47.1
50.8 FC 4 FC 4
51.2 47.1
48.1 47.1
46.4
------------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
A-ALIVE, S-STILLBORN,
U-UNCERTAIN,
D-DIED,
C-CULI,ED,
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTILITY,
DEVELOPMENTAL
PFOS IN RATS (SPONSOR'S STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICITY
TABLE E37 (PAGE 17): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA - F2 GENERATION
PUPS
---------- -----
PUP
1
21
- -----------
2
3
22
23
---4
--- ------------ ----------- -------- --------- -- -- ----
5
6
7
8
9
10
11
12
13
14
------ --------
15
16
17
------------------------------ ----- ---------------------------- ----------------------------------------------
RAT/
LITTER
MATERNAL DOSAGE GROUP 11
0.1 MG/KG/DAY
POSTPARTUM
DAY 21
------------------------------------ ----------------------------------------------------------------------------
13226 13227 13228
MC 4 MC 4
NOT
MC 4 MC 4 PREGNANT
52.6 49.2
52.5 MC 4
S2.5 MC 4
50.1 51.0
ms 54.6
55.7 51.3
54.0 FC 4
FC 4 54.6
52.6 50.3
51.0 54.4
51.6
13229 13230 13231 13232 13233 13234 13235 13236
MC 4 MC 4 MC 4 53.3 MC 4 MC 4 51.3 MC 4 44.4
MC 4 39.8
58.6 55.9 MC 4 54.2 53.2 SO.6
MC 4 37.3 MC 4 54.3 51.3 MC 4 45.8 MC 4
47.8 38.7 58.1 MC 4 50.2 MC 4 MD 2 MC 4
MC 4 MC 4 58.0 MC 4 MC 4 MC 4 MD 1 MC 4
MC 4 MC 4 53.S MC 4 MC 4 53.4 MD 1 MC 4
46.7 MC 4 FC 4 54.0 49.7 51.0 48.9 46.7
45.7 MC 4 FC 4 55.4 49.9 57.5 46.7 46.2
48.2 40.9 51.7 PC 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
44.4 40.4 FC 4 52.8 47.3 49.7
FC 4
45.7 39.3 FC 4 52.7 FC 4 FC 4
47.2
45.0 54.2 FC 4 56.4 FC 4
FC 4 FC 4 FC 4 50.6 FC 4
FC 4
46.9 52.8 FC 4
57.1
FM 4 FC 4
13237 13238 13239 13240 13241 13242 13243
49.9 59.4 54.4 41.9 45.4 54.3
NOT
53.6 MC 4
57.4 MC 4 43.8 53.4 PREGNANT
MC 4 MC 4 MC 4 MC 4 MC 4 59.2
57.6 58.0 MC 4 47.0 MC 4 MC 4
49.1 55.6 MC 4 49.5 40.5 MC 4
MC 4 MC 4 MC 4 MC 4 41.6 MC 4
MC 4 56.1 MC 4 46.3 MC 4 MC 4
54.2 FC 4 MC 4 MC 4 MC 4 MC 4
FC 4 55.4 56.6 41.9 MC 4 57.3
52.2 58.0 54.8 44.3 FC 4 S2.3
FC 4 57.3 59.3 FC 4 FC 4 FC 4
FC 4 FC 4 FC 4 49.5 42.7 FC 4
49.5 FC 4 52.9 FC 4 49.5 FC 4
51.4 54.9 54.4 FC 4 47.0 FC 4
FC 4 51.8 46.8 FC 4 S@4.8
FC 4
FC 4 44.8 53.4
57.4
13244
NOT PREGNANT
13245
NOT PREGNANT
13246
51.1 50.0 51.3 49.0 MC 4 FC 4 46.3 FC 4 48.4 FC 4 FC 4 50.4 PC 4 FC 4 47.7
13247
46.0 44.5 MC 4 MD 7 MD 6 49.5 PC 4 FC 4 FC 4 FC 4 FC 4 FC 4 43.3 FC 4 43.6 FD10
13248 13249
42.8 MC 4
MC 4 MC 4
46.9 44.4
MC 4 44.8
44.3 43.4
MC 4 42.7
46.2 MC 4
MC 4 45.8
43.9 FC 4
FC 4 FC 4
43.1 FC 4
FC 4 FC 4
FC 4 43.1
PC 4 43.0
43.8 42.2
42.2 FC 4
FC 4
13250
46.2 MC 4 MC 4 MC 4 MC 4 MC 4 MC 4 47.0 MC 4 45.2 MC 4 47.4 42.7 42.8 43.2 43.4 FC 4
-----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
SECOND LETTER
A-ALIVE, S-STILLEORN,
U-UNCERTAIN,
D-DIED, C-CULLED, M-MISSING
(PRESUMED CANNIBALIZED)
NUMBER FOLLOWING
"SECOND LETTER" INDICATES THE DAY POSTPARTUM
THE EVENT OCCURRED.
PROTOCOL
418 008:
COMBINED OPAL (GAVA(;E) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAI,
REPRODUCTION
TOXICIT
TABLE E37 (PAGE 18): PUP BODY WEIGHTS FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL
DATA
F2 GENERATION
PUPS
----------
PUP # ----------
RAT/
------------- ---
-------- -------------
---------------------
1
2
3
4
b
6
7
8
9
10
11
12
13
---------------------------- --------------------------------------------------
----- --------------
14
15
16
17
------I ---------------
LITTER ----------
13251 13252 13253 13254 13255 13256 13257 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272 13273 13274
MATERNAL DOSAGE GROUP Ill
0.4 MG/KG/DAY
POSTPARTUM
DAY 21
-
---------------------------- -------------------------------------------------- ---------------------
MC 4 63.7 59.6 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 39.4
53.2 39.3
MC 4 32.0
53.8 34.0
MC 4 MD 4
48.7 MM 3
MC 4 MM 3
46.0 32.2
53.2 PC 4
FC 4 FC 4
41.2 32.9
FC 4 27.5
51.1 35.8
FC 4 39.5 FM 2 25.9 FD 4 FM 4 FD 3 FD
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 38.7
FS
FS
53.9 MC 4 54.9 S6.3 59.3
ms
FC 4 FC 4 51.7 FC 4 FC 4 54.8 Sl.8 54.2 FM 3
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 53.3
MC 4 51.7 52.7 MC 4 49.4 MC 4 53.1 MC 4 50.7 MD 1 SO.1 50.1 50.6
51.4 41.6
MC 4 43.0
MC 4 MD 7
52.0 MD 6
MC 4 FC 4
49.3 FC 4
51.5 FC 4
MM 2 FC 4
MD 1 40.6
47.9 40.2
PC 4 37.9
48.0 FD 6
46.6 FC 4
FC 4 PC 4
49.8
FC 4 FC
MC 4 47.0
44.2 48.1
MC 4 MC 4 39.S 44.8
49.7 MC 4 MC 4 47.0
S3.3 48.0 46.6 45.2
49.3 46.2 MC 4 46.3
MM 9 47.1 MC 4 44.0
46.7 MC 4 46.1 31.0
FC 4 MC 4 41.7
48.1 MC 4 44.5
51.0 FC 4 FC 4
FD 5 43.2 42.8
FS 43.0 FC 4
FC 4 FC 4
40.7 FC 4
43.6 PC 4
44.6
44.9 35.4 44.0
41.0 40.3 45.4
43.7 MC 4 44.2 MC 4 MM 3 FC 4 FC 4 40.2 FC 4 FC 4 40.4 FC 4 42.6 PC 4 FC
40.6 39.7 MC 4 FC 4 FC 4 39.9 38.9 FC 4 41.7 FC 4 FC 4 FC 4 FC 4 FC 4 35.
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 PC 4 FC 4 52.2 48.7 47.9 FC 4 us
SS.0 49.0 49.2 61.1
ms
51.0 48.6 FC 4 49.5 49.4 FC 4
MC 4 49.8
NOT
63.1 47.5 PREGNANT
MC 4 50.5
MC 4 MC 4
MC 4 49.7
MC 4 MC 4
62.5 ms
MC 4 50.8
55.0 FC 4
55.3 46.0
MC 4 FC 4
ms FC 4
ms 44.8
FC 4 FC 4
51.7 49.9
62.3 PC 4
52. FC
1327S
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 PC 4
----------------------------------------------------------------------------------------------------------------
ALL WEIGHTS WERE RECORDED IN GRAMS (G).
FIRST LETTER SECOND LETTER
M-MALE, F-FEMALE, U-SEX UNDETERMINABLE
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FER'RILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E38 (PAGE 1): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATIO
--- ------------- - - ----- -- ------------
PUP #
1
2
3
4
5
6
7
---------------------------------------------
RAT/
---------
--8---- 9----1-0 ---1-1-----12-----13---- 14----i-s----1-6-----17-----1-8 - 19
20
-------------------------------------------------- -- -----------
LITTER
MATERNAL
DOSAGE GROUP 1
--------------------------------------------
13201 13202 13203 13204 13205a
M A M A MC 4 MC 4 MC 4 M A MC 4 M A M A N A M A MC 4
MC 4 MC 4 MC 4 M A MC 4 M A M A MC 4 MC 4 MC 4 MC 4 M A
MA FA MA MA
0 (VEHICLE) MG/KG/DAY ------------------------------
P A FC 4 F A F A F A FC 4 FD FC 4 F A F A F A FC 4 FC 4 FC
M A F A F A FC 4 FC 4 F A F M A MD 4 MM 2 FC 4 FC 4 F A FC
---------------------------------1 FS FS 4 FC 4 F S A FM 3 FM 2 4 F A FC 4 F A F A
13206 13207 13208 13209
M A MA MA FA FA PA
MC 4 N 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 P A FC 4 F A 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 NOT PREGNANT
13210 13211
MC 4 MC 4 MC 4 MC 4 N A M A M A FA
MA FA
MA
MA
M A MC 4 MD 2
FA
FA
FA
F A FC 4 FC 4 FC 4
13212 13213 13214 1321S 13216 13217 13218 13219 13220 13221
M A N 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 M A FC 4 F A F A F A FC 4 P A FC 4 FC 4 F A F A FC 4 FC 4 FC 4 F A 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 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 M A MC 4 M A MC 4 M A MC 4 M A MC 4 F A PC 4 FC 4 F A F A FC 4 F A 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 MC 4 MC 4 M A MC 4 MC 4 M A N A M A MC 4 FC 4 F A F A F A F A
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 PC 4 FM 2
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
FOUND DEAD ON DAY 28 POSTWEANING
FA
13222
M A M A M S F A F A F A P A FC 4 F A F A
13223 13224 13225
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
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 MC 4 MC 4 M A M A MC 4 M A M A F A F A F A 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)
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E38 (PAGE 2): PUP VITAL STATUS AND SEX FROM BIRTH TO DAY 21 POSTPARTUM
- INDIVIDUAL DATA
F2 GENERATIO
---- ----------------------------------- --- ---------------------- ---- ------------------------ - - --------
PUP #
1
2
3
4
5
6
7
8
9
-------------------------------------------------------
10
11
12
13
14
15
16
17
18
19
20
I------------------------------------------ -------------
PAT/
LITTER
MATERNAL
DOSAGE GROUP 11
0.1 MG/KG/DAY
--------------------------------------------- ------------------------------------------------------------------
13226 13227 13228
MC 4 MC 4 M A M A M A MC 4 MC 4 M A MC 4 MC 4
NOT PREGNANT
MA MA
MS MA
F A F A FC 4 M A FC 4 F A
FA FA
FA FA
FA
13229 13230 13231 13232 13233 13234 13235 13236 13237 13238 13239 13240 13241 13242 13243
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 PC 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
M A M A M A MD 2 MD I MD 1 F A F A F A F A
FS
FS
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 F A F M A M A MC 4 M A M A MC 4 MC 4 F A FC 4 F A PC 4 PC 4 F A F A
M A MC 4 MC 4 M A M A MC 4 M A FC M A M A MC 4 MC 4 MC 4 MC 4 MC 4 MC M A MC 4 MC 4 M A M A MC 4 M A MC M A N A MC 4 MC 4 M A M A MC 4 MC M A M A M A MC 4 MC 4 MC 4 MC 4 MC NOT PREGNANT
4 F A F A F A FC 4 FC 4 F A FC 4 PC 4 4 M A M A F A FC 4 F A F A F A 4 F A F A FC 4 F A FC 4 FC 4 F A FC 4 4 MC 4 FC 4 PC 4 F A F A F A FC 4 P A 4 M A F A FC 4 FC 4 FC 4 FC 4 F A F A
FA
13244
NOT PREGNANT
13245
NOT PREGNANT
1#246
M A M A M A M A MC 4 FC 4 F A FC 4 F A FC 4 FC 4 F A PC 4 FC 4 F A
13247 13248 13249
M A M A MC 4 MD 7 MD 6 F A FC 4 FC 4 FC 4 FC
M A MC 4 M A MC 4 M A MC 4 M A MC 4 F A FC MC 4 MC 4 M A M A M A M A MC 4 F A FC 4 FC
4 FC 4 PC 4 F A FC 4 FC 4 FC
4 P A FC 4 4 FC 4 FC 4 4 FA FA
F A FD10 F A F A FC 4 F A PC 4
FS
132SO
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
-----------------------------------------------------------------------------------------------------------------
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.
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY,
DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PER INATAL/ POSTNATAL
REPRODUCTION
TOXICIT
TABLE E38 (PAGE 3); PUP VITAL STAI'US AND SEX FROM BIRTH TO DAY 21 POSTPARTUM
INDIVIDUAL DATA
F2 GENERATTO
----------- ------------------------ - --------------------------- ------------ --- - -------------------- -- --
PUP #
1
2
3
4
5
------------------------------------
6
7
8
9
10
11
12
13
14
15
16
17
is
19
20
---------------------------------------------------------------------------
RAT/
LITTER
MATERNAL DOSAGE GROUP 111
0.4 MG/KG/DAY
-------------------------------------------------------- -----------------------------------------------
-------
13251 13252 13253 13254 13255 13256 13257a 13258 13259 13260 13261 13262 13263 13264 13265 13266 13267 13268 13269 13270 13271 13272
13273 13274
MC 4 M A M A M A MC 4 M A MC 4 F A F A FC 4 FC 4 F A F A
MC 4 MC 4 M A MC 4 M A M A MC 4 M A FC 4 FC 4 FC 4 F A F A F A F A M A MC 4 M A MC 4 M A MC 4 M A F A FC 4 F A FC 4 F A FC 4 F A FM 2 M A M A M A MD 4 MM 3 MM 3 F A FC 4 FC 4 F A F A F A P A FD 4 FM 4 FD 3 FD 3
MC 4 MC 4 MC 4 M A MC 4 M A M A M S MD 5 F A PC 4 F A F A FC 4 F A F S F S M A MC 4 M A M A M A M S FC 4 FC 4 F A FC 4 FC 4 F A F A F A FM 3
MXIO MC 4 MC 4 MXIO MX10 MX10 FC 4 FC 4 FX10 FC 4 FC 4 FXIO FX10 FX10 FC 4 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
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
FS
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 PC 4 FC 4 FC 4 M A M A MD 7 MD 6 FC 4 FC 4 FC 4 FC 4 P A F A F A FD 6 PC 4 FC 4 MC 4 MC 4 M A M A M A MM 9 F A FC 4 F A F A FD 5 F S 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 M A M A MC 4 M A MC 4 MC 4 M A F A F A PC 4 F A FC 4 FC 4 FC 4 FC 4 F A M A M A FA F A FA FA FA
MA MA MA
M A M A MC 4 M A MC 4 MM 3 FC 4 FC 4 F A FC 4 FC 4 P A FC 4 F A FC 4 FC 4 M A M A M A MC 4 FC 4 FC 4 F A F A FC 4 F A FC 4 PC 4 FC 4 FC 4 FC 4 F 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
FA
MC 4 M A MC 4 M A MC 4 MC 4 M A MA MA
M A MC 4 MC 4 M A M A MC 4 M A MS FA
M A MC 4 MC 4 M A F A M A F A FC 4 FC 4 FC 4 F A FC 4 F A F A FC 4
FA FA
FA FA
FA F A FC 4
US
MC 4 M A MC 4 MC 4 MC 4 MC 4 M A M A M A MC 4 M A MC 4 NOT PREGNANT
M A MC 4 M A M S F A FC 4
M A MC 4 M S F A FC 4 FC 4
M S FC 4 F A FC 4
F A F A PA F A FC 4 FC 4
FA
13275
M A M A MC 4 M A M A M S FC 4 P 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-SACR
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.
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT)
TABLE E39 (PAGE 1): CLINICAL OBSERVATIONS
FROM BIRTH TO DAY 21 POSTPARTUM - INDIVIDUAL DATA - F2 GENERATION Pt
----------------- - ------------------------
MATERNAL
DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
------------------- --------------------- --
I
0 (VEHICLE)
13208
--- --------------------
------------------------ ------------
DAY(S) POSTPARTUM
OBSERVATIONS
a
--- ----------------------------------------------------------------
1
1/13 PUPS: COLD TO TOUCH, DECREASED MOTOR A
NESTING OR NURSING.
13211
1-21
1/ 5 PUPS: TIP OF TAIL MISSING.B
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; b. Observation confirmed at necropsy.
all other pups appeared normal.
PROTOCOL
418 008:
COMBINED ORAI, (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL STUDY NIJMBER: 6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICITY
TA13LE E40 (PAGE 1): NECROPSY OBSERVATIONS
- INDIVIDLIAI, DATA - F2 GENERATION
PUPS
- - ------- -------- --
MATERNAL
DOSAGE GROUP
MATERNAL DOSAGE (MG/KG/DAY) --- -----------------------
I
0 (VEHICLE)
----------------
-- -------I - -----
LITTER
NUMBER
DAY(S) POSTPARTUM
-- - ------------------ ----- - -----------------
13201
1
4,21
- ------
---------------- ------
OBSERVATIONS
a
-----------------------------------
2 PUPS: STILLBORN.
ALL TISSUES A
1 PUP: FOUND DEAD. NO MILK IN ST
ALL OTHER TISSUES APPEARED
ALL PUPS APPEARED
NORMAL.
13202
1
4
21
1 PUP: STILLBORN.
ALL TISSUES AP
ALL PUPS APPEARED NORMAL.
1 PUP: BRAIN, HYDROCEPHALY,
EXTRE
VENTRICLES.
ALL OTHER TISSUES APP
ALL OTHER PUPS APPEARED
NORMAL.
13203
4,21
ALL PUPS APPEARED NORMAL.
13204
4
21
1 PUP: FOUND DEAD. ALL TISSUES A
ALL OTHER PUPS APPEARED NORMAL.
ALL PUPS APPEARED
NORMAL.
13206 13207
21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL.
13208
2 4,21
1 PUP: FOUND DEAI). ALL TISSUES A
ALL PUPS APPEARED
NORMAL.
13210
2 4,21
1 PUP: FOUND DEAD. ALL TISSUES A
ALL PUPS APPEARED
NORMAL.
13211 13212 13213
21 4,21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL. NORMAL.
13214
1 4,21
1 PUP: FOUND DEAD. NO MILK IN ST
ALL OTHER TISSUES 2 PUPS: STILLBORN.
APPEARED
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.
R
individual pup clinical observations table (Table E39) for external clinical observations confirmed at necrol
PROTOCOL 418-008;
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E40 (PACE 2): NECROPSY OBSERVATIONS
INDIVIDUAL DATA - F2 GENERATION
PUPS
----- - ----------- ------
MATERNAL MATERNAL -------
DOSAGE GROUP DOSAGE (MG/KG/DAY) ---------------------
I (Cont.) 0 (VEHICLE)
-------- ------
LITTER
NUMBER
DAY(S)
-------------------------
------ ---------- - ------- ------------ ------------
POSTPARTUM
OBSERVATIONS
a
-------------------------------------- I ----------------
13216 13217 13218 13219 13220
4,21 4,21 4,21 4,21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED ALL PUPS APPEARED ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL. NORMAL. NORMAL. NORMAL.
13222
1 4,21
1 PUP: STILLBORN.
ALL TISSUES A
ALL PUPS APPEARED NORMAL.
13223
4,21
ALL PUPS APPEARED NORMAL.
13224
4,21
ALL PUPS APPEARED NORMAL.
13225
4,21
ALL PUPS APPEARED NORMAL.
----------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. individual pup clinical observations table (Table E39) for external clinical observations confirmed at necr
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSINATAL
REPRODUCTION
TOXICITY
TABLE E40 (PAGE 3): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA
F2 GENERATION
PUPS
--------------
MATERNAL
DOSAGE GROUP
MATERNAL DOSAGE (MG/KG/DAY) ----------------------------
ii 0.1
- ---------- ---------- - -- -- --------------- -- - --------------------- ----
LITTER
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS
a
------------------------------------------------------- --------------------------
13226
1 4,21
1 PUP: STILLBORN. ALL PUPS APPEARED
ALL NORMAL.
TISSUES
AP
13227 13229 13230 13231 13232 13233
4,21 4,21 4,21 4,21 4,21 4,21
ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS
APPEARED APPEARED APPEARED APPEARED APPEARED APPEARED
NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL.
13234
1 4,21
5 PUPS: STILLBORN.
ALL TISSUES A
ALL PUPS APPEARED NORMAL.
13235
1
2 21
2 PUPS:
FOUND DEAD.
NO MILK IN S
ALL OTHER TISSUES APPEARED
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 ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS
APPEARED APPEARED APPEARED APPEARED APPEARED
APPEARED APPEARED APPEARED
NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL. NORMAL.
13247
4
ALL PUPS APPEARED
NORMAL.
6
1 PUP: FOUND DEAD. ALL TISSUES A
7
1 PUP: FOUND DEAD. NO MILK IN ST
ALL OTHER TISSUES APPEARED
10
1 PUP: FOUND DEAD. NO MILK IN ST
ALL OTHER TISSUES APPEARED
21
1 PUP; LIVER, MEDIAN AND LEFT LAT
RAISED AREAS (0.1 CM X 0.1
x 0.5 CM).
ALL OTHER TISSUES APPEARED
ALL OTHER PUPS APPEARED NORMAL. -----------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. individual pup clinical observations table (Table E39) for external clinical observations confirmed at necro
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) FERTII@ITY, DEVELOPMENTAL PFOS IN RATS (SPONSOR'S STUDY NUMBER: 6295.9)
AND PERINATAI/POSTNATAL
REPRODUCTION TOXICI
TABLE E40 (PAGE 4): NECROPSY OBSERVATIONS - INDIVIDUAL DATA - F2 GENERATION PTIPS
--- ----- -- ----------
------- --- ---- -
---------------------- -
MATERNAL DOSAGE GROUP
LITTER
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS a
------- -- - ---------- ------------------------- - ---------------------- ----------------------------
11 (Cont.)
0.1
13248
1
1 PUP; STILLBORN. ALL TISSUES
4,21
ALL PUPS APPEARED NORMAL.
13249
4,21
ALL PUPS APPEARED NORMAL.
13250
4,21
ALL PUPS APPEARED NORMAL.
---------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. individual pup clinical observations table (Table E39) for external clinical observations confirmed at nec
PROTOCOL 418-008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E40 (PAGE 5): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - F2 GENERATION PUPS
---------- -------
MATERNAL
DOSAGE GROUP - ---------L-I-T-T-ER--------- - -
14ATERNAL DOSAGE (MG/KG/DAY)
NUMBER
------------------------------------- --------- -
III
0.4
13251
13252
13253
-------- -------------- ------------------ --- - -- -----
DAY(S) POSTPARTUM
OBSERVATIONS
a
--------------------------------------------
--------------
4,21 4,21 4,21
ALL PUPS APPEARED ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL. NORMAL.
13254
3
4
21
2 PUPS:
2 PUPS: ALL OTHER ALL PUPS
FOUND DEAD. NO MILK IN ALL OTHER TISSUES APPEAR FOUND DEAD.
PUPS APPEARED NORMAL. APPEARED NORMAL.
13255
1
4
5
21
4 PUPS: ALL PUPS 1 PUP: ALL PUPS
STILLBORN.
ALL
APPEARED NORMAL.
FOUND DEAD. ALL
APPEARED NORMAL.
TISSUES TISSUES
13256
1 4,21
1 PUP: STILLBORN.
ALL TISSUES A
ALL PUPS APPEARED
NORMAL.
13257b 13258
4,10 4,21
ALL PUPS APPEARED ALL PUPS APPEARED
NORMAL. NORMAL.
13259
1 4,21
1 PUP:
FOUND DEAD.
NO MILK IN S
ALL OTHER TISSUES
APPEARE
ALL PUPS APPEARED NORMAL.
13260
1 4,21
1 PUP: FOUND DEAD. ALL PUPS APPEARED NORMAL.
13261
4
ALL PUPS APPEARED NORMAL.
6
2 PUPS:
FOUND DEAD.
ALL TISSUES
7
1 PUP:
FOUND DEAD.
NO MILK IN S
ALL OTHER TISSUES
APPEARE
21
ALL PUPS APPEARED
NORMAL.
----------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation. individual pup clinical observations table (Table E39) for external clinical observations confirmed at necr
b. Dam 13257 was found dead on day 10 of lactation; eight pups were sacrificed on day 10 postpartum.
PROTOCOL
418 008:
COMBINED ORAL (GAVAGE) PFOS IN RATS (SPONSOR'S
FERTILITY, DEVELOPMENTAL
STUDY NUMBER:
6295.9)
AND PERINATAL/POSTNATAL
REPRODUCTION
TOXICIT
TABLE E40 (PAGE 6): NECROPSY OBSERVATIONS
- INDIVIDUAL DATA - F2 GENERATION PUPS
-------------
MATERNAL
DOSAGE
- ------------ --------- --------------------------- ----------------
GROUP
LITTER
--------------------
MATERNAL DOSAGE (MG/KG/DAY)
NUMBER
DAY(S) POSTPARTUM
OBSERVATIONS
a
------------- -- ----------------------------------------------------------------------------------------------
III (Cont.)
0.4
13262
1
1 PUP: STILLBORN.
ALL TISSUES A
4
ALL PUPS APPEARED NORMAL.
5
1 PUP:
FOUND DEAD.
NO MILK IN S
21
ALL PUPS APPEARED
NORMAL.
13263 13264 13265 13266 13267
4,21 4,21
21 4,21 4,21
ALL PUPS ALL PUPS ALL PUPS ALL PUPS ALL PUPS
APPEARED APPEARED APPEARED APPEARED APPEARED
NORMAL. NORMAL. NORMAL. NORMAL. NORMAL.
13268
1 4,21
1 PUP: STILLBORN.
ALL TISSUES A
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 A
ALL PUPS APPEARED NORMAL.
13272
1 4,21
2 PUPS: ALL PUPS
STILLBORN.
ALL TISSUES
APPEARED NORMAL.
13273
1 4,21
1 PUP: STILLBORN.
ALL TISSUES A
ALL PUPS APPEARED NORMAL.
13275
1
1 PUP: STILLBORN.
ALL TISSUES A
4,21
ALL PUPS APPEARED
NORMAL.
----------------------------------------------------------------------------------------------------------------
a. Complete necropsies were not performed on pups in which autolysis or cannibalization precluded evaluation.
individual pup clinical observations table (Table E39) for external clinical observations confirmed at necr
II
APPENDIX F PROTOCOL AND AMENDMENTS
418-008:PAGE F-'
.-Argmis
Argus Research LaboratoriesI,nc. 906 Sheehy Drive,BuildingA
Homham, Pennsylvania 190"
T:(215)4434710 F:(215)443-8587
STUDY TITLE: PURPOSE:
TESTING FACILITY: STUDY DIRECTOR: SPONSOR:
PROTOCOL 418-008
SPONSOR'S STUDY NUMBER: 6295.9
Combined Oral (Gavage) FertilitDye,velopmental and PerinataVPostnatalReproduction ToxicityStudy of PFOS in Rats.
The purpose of thisstudy isto testfortoxiceffects/ disturbances resultingfrom PFOS treatment of Crl:CD(DBR VAF/PlusOD male and female ratsbefore cohabitation through mating,gestationand lactation.This study evaluates ICH Harmonised TripartitGeuideline stages A through F of the reproductiveprocess and should detect effectson the estrous cycle,tubaltransport,implantation, gestation,parturitionl,actationand matemal behavior in female rats,on the development of the oftpring of the treatedmale and female rats,and permitdetectionof functionaleffects(e.g.,effectson libidoor epididymal sperm maturation)that may not be detected by histological examinations of male ratreproductiveorgans. Because manifestationsof effectsinduced during thisperiod may be delayed inthe offspring,observationswillbe continued through production of F2 generation litters.
Argus Research Laboratories,Inc. 905 Sheehy Drive,BuildingA Horsham, Pennsylvania 19044-1297 Telephone: (215)443-8710 Telefax: (215)443-8587
Raymond G. York, Ph.D., DABT Associate Directorof Research
3M Toxicology Services 3M Center, Building220-2E-02 St.Paul,Minnesota 55144-1000
418-008:PAGE F-2
ProtDcol 418-008
Page 2
STUDY MONITOR:
ALTERNATE STUDY MONITOR:
MarvinT.Case, D.V.M.,Ph.D. Telephone: (612)733-5180 Telefax: (612)733-1773
Andrew M. Seacat, Ph.D. Telephone: (612)575-3161 Telef-ax: (612)733-1773
REGULATORY CITATION :
Study Design as Modificationof: U.S. Food and Drug Administration(1994). InternationaClonference on Harmonisation; Guidelineon detectionof toxicittyo reproductionformedicinal products. Federal Register,September 22, 1994, Vol. 59, No. 183.
U.S. Food and Drug Administration.Good Laboratory PracticeRegulations;FinalRule. 21 CFR Part 58.
Japanese Ministryof Health and Welfare (1997). Good Laboratory Practice Standard forSafety Studies on Drugs, MHW Ordinance Number 2 1, March 26, 1997.
European Economic Community (1989). Council decision on 28 July 1989 on the acceptance by the European Economic Community of an OECD decisionlrecommendation on compliance withprinciplesof good laboratorypractice.OfficiaJlournal of the European Communities: Legislation.32 (No. L 315; 28 October): 1-17.
REGULATORY
COMPLIANCE:
This study willbe conducted in compliance with the Good Laboratory Practice(GLP) regulationscitedabove.
Allchanges or revisionsof thisprotocolshallbe documented, signed by the Study Directorand the Sponsor, dated and maintained with the protocol.
The QualityAssurance Unit (QAU) willauditthe protocol,the raw data and the report, and willinspectcriticaplhases of the study inaccordance withthe Standard Operating Procedures of Argus Research Laboratories,Inc.
The finalreportwillincludea statement signed by the Study Directorthatthe report accuratelyreflectsthe raw data obtained during the performance of the study and that allapplicableGLP regulationswere followed inthe conduct of the study. Should significandteviationsfrom GLP regulationsoccur,each willbe described in detail, togetherwith how the deviationmight affectthe qualityor integritoyf the study.
418-008:PAGE F-3
PMtoeol 418-008 Page 3
STUDY SCHEDULE: See ATTACHMENT 1 tothe protocol.
TEST ARTICLE AND VEHICLE:
Identification:
Test Article:
Name: Physical Description: Lot/Batch Number: SpecificGravity: Purity: ExpirationDate:
PFOS. Light-coloredpowder. 217. -0.6. 98.9%. May, 2000.
Informationon the identityc,omposition,strengthand purityof the testarticleison file with the Sponsor.
Vehicle:
0.5% Tween 80 inReversed Osmosis Membrane Processed Deionized Water (R.O. Deionized Water). Supplierand lotidentificatiofnTween 80 to be documented inthe raw data.
Neitherthe Sponsor nor the Study Directorisaware of any potentialcontaminants likely to be present in the vehiclethatwould interferewith the resultsof thisstudy. Therefore, no analyses otherthan those mentioned in thisprotocolwillbe conducted.
Safely Precautions:
Gloves, mask, appropriateeye protectionand a uniform/labcoat are to be wom during formulationpreparationand dosage administration.The MaterialSafety Data Sheet (MSDS) isattached to the protocol(ATTACHMENT 2).
Storaae:
Bulk Test Article: Vehicle Components: Prepared Vehicle: Prepared Formulations:
Room temperature. Room temperature. Room temperature. Frozen (-200C).
Alltestarticleshipments to the Testing Facilitsyhould be addressed to the attentionof JulianGulbinski,Manager of Formulations,at the previouslycitedaddress and telephone number.
418-008:PAGE F-4
Pmtocol41 M08 Page 4
Shipments shouldincludeinformatiocnoncerningstorageconditionsand shipping cartonsshouldbe labeledappropriatelyT.he recipiensthoildbe notifieidnadvance of shipment. FORMULATION: Freauency of Preparation:
Formulations(suspensions)willbe prepareddailyatthe TestingFacility.
Detailedpreparationproceduresare attachedtothisprotocol(ATTACHMENT 3). Adjustment forPur:iW:
The testarticlweillbe considered100% pure forthe purpose ofdosage calculations. TestinaFacililRyeserve Samt)les:
The Sponsor willreservea sample (1g)ofeach lotofthe bulktestarticluesed dudng thecourseofthisstudy.The TestingFacilitwyillreservea sample (5mL) ofeach lotof the vehiclecomponents used duringthecourse ofthisstudy.Samples willbe stored underthe previouslycitedconditions. ANALYSE :
Samples additionatlothose describedbelow may be taken ifdeemed necessaryduring the courseofthe study.
Bulk Test ArticleSampling:
No analysesofthe bulktestarticlweillbe conducted duringthe courseofthisstudy. Informationon the stabiliotfythe bulktestarticlieson filewiththe Sponsor. Analyses of Prepared Formulations: Stabili:
Stabilitdyataforpreparedformulationbsracketingthe range ofconcentrationasnd conditionosfthisstudyare on filweiththe Sponsor and willnot be determinedduring the conductofthisstudy.Suspensions willbe prepareddailyattheTestingFacility.
418-008:PAGP- F-5
Protowl 41 "08 Page 5
Homogeneity Analyses:
Homogeneity ofthe testarticlienpreparedsuspensionswillbe verifieduringthe courseofthisstudy.A syringewillbe used towithdrawsamples (5mL each)fromthe top,middleand bottom ofthe highestconcentratioonn the firsdtay ofpreparation. Each sample (5mL) willbe dividedintotwo aliquotso,ne of2 mL and one of3 mL. One aliquot(2mL) willbe shippedforanalysist;heotheraliquot(3mL) willbe retained attheTestingFacilitays a backup sample. Backup samples willbe storedunder the previouslcyitedconditionasnd discardedatthe TestingFacilituypon the requestofthe Sponsor.
ConcentrationAnalyses:
Concentrationofthe prepared testarticlseuspensionswillbe verifiedduringthe course ofthisstudy.A syringewillbe used towithdrawsamples (5mL each)fromeach concentratiodnuringthe firsatnd sixthweek ofdosage administrationE.ach sample (5mL each)willbe dividedintotwo aliquotso,ne of2 mL and one of3 mL. One aliquot (2mL) willbe shippedforanalysist;heotheraliquot(3mL) willbe retainedatthe TestingFacilitays a backup sample. Backup samples willbe storedunder the previouslycitedconditionsand discardedatthe TestingFacilituypon the requestofthe Sponsor.
ShiRpinciInstructions:
Samples tobe analyzedwillbe shipped (frozenon dry ice)to:
KrisJ.Hansen, Ph.D. 3M EnvironmentalTechnology and SafetyServices 935 Bush Avenue Building2-3E-09 St.Paul,Minnesota 55133-3331 Telephone: (612)778-6018 Telefax: (612)778-6176
Both the recipienatnd the Study Monitorwillbe notifieidnadvance of sample shipment.
DISPOSITION:
Prepared formulationwsillbe discardedatthe TestingFacilityA.llremainingbulktest articlweillbe returnedtothe Study Monitoratthe previouslycitedaddress.
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Protoool418-008 Page 6
TEST SYSTEM:
SROcies/Strainand Reason forSelection:
The Crl:CDG)BR VAF/PlusID(Sprague-Dawley)ratwas selectedas the Test System
because: 1) thisstrainof rathas been demonstrated to be sensitiveto reproductive and developmental toxinsand has been widely used throughout industryfor reproductiveand developmental toxiciteyvaluations;2) historicadlata and experience existat the Testing Facility(Ia-n3d);3) the testarticleispharmacologicallyactiveinthe species and strain.
Number.
Initiaplopulationacclimated: 195 virginmale and 205 virginfemale rats. Populationselectedforstudy: 175 male rats(35 per dosage group) and 175 female
rats(35 per dosage group).
Ten mated female ratswillbe assigned to Caesarean-sectioning on day 10 of presumed gestation;the remaining female ratswillbe permittedto deliverlifters.
250 Fl generationpups (25 per sex per dosage group) willbe selectedatweaning on day 21 postpartum forcontinued postnatalobservation.
Body Weight and Age:
Male ratswillbe ordered to weigh from 300 g to 325 g each at receipt,at which time they willbe expected to be at least60 days of age. Female ratswillbe ordered to weigh from 200 g to 225 g each at receipt,at which time they willbe expected to be at least60 days of age. Actual body weights willbe recorded the day afterreceiptand will be documented inthe raw data. The weight ranges willbe includedinthe finalreport.
Sex:
Both Fo and Fl generation male and female ratswillbe evaluated. Only Fo generation male and female ratswillbe given the testarticle.
Source:
Charles River Laboratories,Inc.,Raleigh,North Carolina.
The ratswillbe shipped infifterecdartons by airfreightand/or truckfrom Charles River Laboratories,Inc.,to the Testing Facility.
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Pmtocol 41 M08 Page 7
ldentificabon:
Fo Generation:
Rats are permanently identifieudsing MoneND seff-piercinegar tags (Gey Band and Tag Co., Inc.,No. MSPT 20101). Male and female ratsare assigned temporary numbers at receiptand given unique permanent identificatinounmbers when assigned to the study before administrationofthe firsdtosage of the testarticle.
Fl/F2 Generations:
Pups willnot be individualliydentifiedduring lactationa;llparameters willbe evaluated interms of the lifterA.t weaning, each ratselectedforcontinued observationwillbe identifiewdith a MoneiC self-piercinegar tag.
ANIMAL HUSBANDRY:
Allcage sizes and housing conditionsare incompliance with the Guide forthe Care and Use of Laboratofy Animals(4).
Housing:
Fo Generation Rats/Fl Generation Litters:
Fo generation ratswillbe individuallhyoused instainlesssteelwire-boftomed cages except during the cohabitationand postpartum periods. During cohabitation,each pair of ratswillbe housed inthe male rat'scage. Beginning no laterthan day 20 of presumed gestation,Fo generationfemale ratsassigned to naturaldeliverywillbe individuallhyoused in nestingboxes. Each dam and deliveredliftewrillbe housed in a common nesting box during the postpartum period.
Fl Generation Rats/F2 Generation Ldters:
Afterweaning, the Fl generation ratswillbe individuallhyoused before cohabitation, housed inpairs(one male ratper female rat)during cohabitation,and individually housed aftercohabitation.The same type of caging willbe used as described forthe Fo generation rats.Beginning no laterthan day 20 of presumed gestation, Fl generation female ratswillbe individuallhyoused in nestingboxes. Each dam and deliveredlittewrillbe housed in a common nestingbox duringthe postpartum period.
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Pmtocol41"08 Page 8
Nesting Material:
Bedding material(bed-o'cobsID')wilble suppliedtofemale ratsassigned to natural
delivery.
Bedding willbe changed as oftenas necessary to keep the animals dry and clean. Analyses forpossiblecontamination are conducted annuallyand documented inthe raw data.
Room Air,Temt)eratureand Humidity:
The animal room isindependently supplied with at leastten changes per hour of 100% freshairthat has been passed through 99.97% HEPA filter(sAiroCleanO room). Room temperature willbe maintained at 64OF (180C) to79"F (26*C) and monitored constantly.Room humiditywillalso be monitored constantlyand maintained at 30% to 70%.
jighl:
An automaticallycontrolled12-hour light:12-houdrark fluorescentlightcycle willbe maintained. Each dark period willbegin at 1900 hours EST.
Diet:
Rats willbe given CertifiedRodent Diet6)#5002 (PMI NutritionInternationala)vailable ad libitumfrom individuafleeders.
Wate :
Water willbe availablead libitumfrom individualboffiesattached to the cages or from an automatic watering access system. Allwater willbe from a localsource and passed through a reverse osmosis membrane before use. Chlorinewillbe added to the processed water as a bacteriostatp;rocessed water isexpected to contain no more than 1.2 ppm chlorineat the time of analysis.Water isanalyzed monthly forpossible bacterialcontamination and twiceannually forpossiblechemical contamination.
Contaminants:
Neitherthe Sponsor nor the Study Directorisaware of any potentialcontaminants likely to be present inthe certifieddiet,the drinkingwater or the nestingmaterialat levelsthat would interferweith the resultsof thisstudy. Therefore,no analyses otherthan those routinelyperformed by the feed supplieror those mentioned inthisprotocolwillbe conducted.
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PMtoool 418-008 Page 9
RANDOMIZATION Fo Goneraflon:
AND COHABITATION:
Upon arrival,rats willbe assigned to individual housing on the basis of computergenerated random units.Afteracclimation,male and female ratswillbe selected for study on the basis of physicalappearance and body weights recorded during acclimation.The ratswillbe assigned to dosage groups based on computer-generated (weight-ordered)randomization procedures.
Within each dosage group, consecutiveorder willbe used to assign ratsto cohabitation,one male ratper female rat.The cohabitationperiodwillconsistof a maximum of 14 days. Female ratswith spermatozoa observed ina smear of the vaginalcontents and/or a copulatoryplug observed in situwillbe considered to be at day 0 of presumed gestationand assigned to individuahlousing. Female ratsnot mated withinthe firs7t days of cohabitationwillbe assigned alternatemale ratsthat have mated (same dosage group) and willremain in cohabitationfora maximum of seven additionaldays.
The firsten female ratsper dosage group with a confirmed date of mating willbe assigned to Caesarean-sectioning on day 10 of presumed gestation.The remaining female ratswillbe permittedto naturallydeliverlifters.
A tableof random unitswillbe used to assign fiveratsper group to a pharmacokinetic sample collectionat scheduled sacrificeaftercompletion of the cohabitationperiod (male ratssidng lifterwsith dams allowed to naturallydelivera lifteorr) on day 21 postpartum (female ratsallowed to naturallydeliverlifters).
FI/F2 Generation Pups:
Day 1 of lactation(postpartum)isdefined as the day of birthand isalso the firsdtay on which allpups ina liftearre individuallwyeighed (pup body weights willbe recorded afterallpups in a liftearre deliveredand groomed by the dam).
On day 4 postpartum, a tableof random unitswillbe used to selectpups to be culled, and lifterwsillbe reduced to eightpups each. Whenever possible,the same number of male and female pups per littewrillbe continued on study.
At weaning of the Fl generation pups on day 21 postpartum, a tableof random units willbe used to select25 male and 25 female pups per group, resultingin a totalof 250 Fl generationrats(125 per sex) chosen forconfinued evaluation.At leastone male pup and one female pup per liftewrh,en possible,willbe selected.
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Pmtocol41"08 Page 10
ADMINISTRATION:
Route and Reason for Choice:
The oral (gavage) route was selected for use because: 1) in comparison with the dietaryroute,the exact dosage can be accuratelyadministered;and 2) itisone of the possibleroutesof human exposure.
Method and Freguency:
Dosages willbe adjustedforthe most recentlyrecorded body weight and given at approximatelythe same time each day.
Fo Generation Male Rats:
Male ratswillbe given the testarticloence dailybeginning 28 days before cohabitation (maximum 14 days) and continuingthrough the day before sacrifice.Male ratswillbe sacrificedaftercompletion of the cohabitationperiod.
Fo Generation Female Rats:
Female ratswillbe given the testarticloence dailybeginning 28 days before cohabitation(maximum of 14 days) and continuingthrough day 9 of presumed gestation(ratsassigned to Caesarea n-sectioning)d,ay 24 of presumed gestation(rats assigned to naturaldeliverythatdo not delivera lifteorr) day 20 postpartum (ratsthat delivera lifter).
Fl Generation:
Fl generation pups willnot be directlgyiven the testarticleb,ut may be possibly exposed to the testarticldeuring matemal gestation(inuteroexposure) or via matemal milk duringthe lactationperiod.
Rationale for Dosage Selection:
Dosages willbe selected by the Sponsor on the basis of previous studiesconducted with the testarticle.
418-008:PAGE F-II
Dosage Levels, Concentmgons and Volumes:
Pmt=l 418-008 Page 11
Do"ge Group
1 if 111 IV v
Nun*er ofRaft Do"ge Per Sax !:%!=m
) concentrati(omgntml)
Dosne volume
A!vus Batch Number
35
0 (Vehicle)
35
0.1
35
0.4
0 0.02 0.08
5
B-418-008.A(Day.Month.Year)
5 1 B-418-008-B(Day.Month.Year)
5
B-418-008-C(Day.Month.Year)
35
1.6
0.32
5
B-41B-008-D(Day.Month.Year)
35
3.2
0.64
5
B-416-008-E(Day.Month.Year)
The lostarticlweillbe considered100% pureforft purpose of dosage calculations.
TESTS, ANALYSES AND MEASUREMENTS
- Fo GENERATION:
Viabilitv - Male and Female Rats:
All Periods:
At leasttwice daily.
ClinicalObservations and/or General ARpearance - Male and Female Rats:
AcclimationPeriod:
At leastonce.
Dosage Period: Maternal Behavior:
Twice daily.Priorto dosage administrationand once approximately one hour postdosage.
Days 1, 4, 7, 14 and 21 postpartum. Any observed abnormal behavior willbe recorded daily.
Clinicalobservations may be recorded more frequentlythan citedabove, ifdeemed appropriateby the Study Directorand/or Study Monitor.
Body Weights - Male Rats:
Acclimation Period: Dosage Period: Sacrifice:
At leastonce. Weekly. Terminal weight.
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PMtoool 418-008 Page 12
Body Weights - Female Rats:
AcclimationPeriod:
Dosage Period:
Sacrifice:
At leastonce.
Weekly to cohabitation.Dailyduring presumed gestationand on Days 1,4, 7 and 14 postpartum
(ratsassignedto naturaldelivery).
Terminal weight.
Feed ConsumRtion Values - Male Rats (recordedand tabulated):
Dosage Period:
Weekly.
Food Consumt)tion Values - Female Rats (recordedand tabulated):
Dosage Period:
Weekly to cohabitation.Dailyduring presumed gestation.Days 1,4, 7 and 14 postpartum (rats assigned to naturaldelivery).
Feed consumption not tabulatedafterday 14 postpartum, when itisexpected thatpups willbegin to consume matemal feed.
Feed Consumption Values - Male and Female Rats:
Feed consumption values may be recorded more frequentlythan citedabove ifitis necessary to replenishthe feed. During cohabitation,when two ratsoccupy the same
cage with one feed jar,replenishment of the feed jarswillbe documented. Individual values willnot be recorded or tabulated.
Estrous Cyclinc3and Mating:
A tableof random unitswillbe used to select15 female ratsper group forevaluationof estrous cyclingby examination of vaginalcytologyfor14 days before the startof the cohabitationperiod.
During cohabitation,allfemale ratswillbe evaluated dailyuntilspermatozoa are observed ina smear of the vaginalcontents and/or a copulatoryplug isobserved insitu.
Duration--f Gestation:
The durationof gestationiscalculatedfrom day 0 of presumed gestationto the day the firstpup isobserved.
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PMtocol 418-008 Page 13
FordlittParameters: FertiliItnydex (percentageof matingsthatresultinpregnancies).
Gestation Index (percentage of pregnancies thatresuftin birthof livelitters). Number ofoffspringper litte(rliveand dead pups).
Number of implantationsftes. General conditionof dam and liftedruringthe postpartum period. ViabilitIyndices(percentage of pups bom thatsurvive4 and 7 days).
LactationIndex (percentage of pups born thatsurvive21 days). Caesarean-Sectoning Observations:
Rats willbe Caesarean-sectioned on day 10 of presumed gestation.Placentae that appear abnormal (size,coloror shape) willbe noted inthe raw data. The ratswillbe examined fornumber and distributioonf:
Corpora Lutea. ImplantationSdes.
Viable and Nonviable Embryos. (A viableembryo isoval or crescent shaped, pink,firm and enclosed in an amniotic sac fillewdith clearfluid.A nonviable embryo isamorphous, small,pale pink to tan or deep red to black,softand enclosed inan amnioticsac fillewdith clear,cloudy,or opaque fluid.) Natural Delivery: Female ratswillbe evaluated for: ClinicalObservations During Parturition. Duration of Gestation(day 0 of presumed gestationto the time the firstpup is observed).
Length of Parturitio(ntimeof deliveryof lastpup minus the time of deliveryof the firsptup dividedby N-1 pups ineach lifter). LifterSize (definedas allpups delivered).
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Pmtocol 418-008 Page 14
Pup Viabilitayt Birth.
METHOD OF SACRIFICE -Fo GENERATIO
Rats willbe sacrificed by carbon dioxide asphyxiation. Embryos willbe discarded after examination.
NECROPSY - Fo GENERATION:
Gross lesionswillbe retainedin neutralbuffered 10% formalinforpossiblefuture evaluation(a tableof random unitswillbe used to selectone controlgroup ratof each sex from which alltissuesexamined at necropsy willbe retained,inorder to provide controltissuesforany possiblehistopathologicaelvaluationsof gross lesions).Unless specificallcyitedbelow, allother tissueswillbe discarded.
Male and Female Rats Assigned to Pharmacokinetic SamRIG Collection:
At scheduled sacrificaeftercompletion of the cohabitationperiod (male ratssiringlitters with dams allowed to naturallydelivera littearn)d on day 21 postpartum (female rats allowed to naturallydelivera litterf)i,veratsper group willbe assigned to a pharmacokinetic sample collection.In additionto the appropriateevaluationsdescribed below, blood samples (approximately4 mL per rat)willbe collectedfrom the inferior vena cava intoserum separatortubes and centrifuged.The resultingserum (approximately2 mL) willbe immediatelyfrozen on dry iceand maintained frozen (-700C) untilshipment tothe Sponsor foranalysis.The liverwillbe excised,weighed, and a sample section(laterallobe)willbe frozen and retainedat -700C untilshipment to the Sponsor foranalysis.
Aftercompletion of sample collections,erum and liversection(laterallobe)samples will be shipped (frozenon dry ice)to KrisJ. Hansen, Ph.D.,at the previouslycitedaddress foranalysis.Both the recipientand the Study Monitor willbe notifiedin advance of sample shipment.
Scheduled Sacrificeof Male Rats:
Aftercompletion of the cohabitationperiod,male ratswillbe sacrificedand a gross necropsy of the thoracic,abdominal and pelvicviscerawillbe performed. The following organs willbe excised and weighed and retainedforpossiblehistologiecvaluation: testes,epididymides,prostateand seminal vesicles(weighed with and withoutfluid). The testeswillbe fixedinBouin'ssolutionfor48 to 96 hours and then retainedin neutralbuffered10% formalinforpossiblehistopathologicaelvaluation.The remaining organs willbe retainedin neutralbuffered 10% formalin.
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Pmtocol 41MOB Page 15
Scheduled Sacrifice- Female Rats Assigned to Caesarean-Sectionin-q:
On day 10 of presumed gestation, femaie rats willbe sacrificed,Caesarean-sectioned, and a gross necropsy of the thoracic,abdominal and pelvicviscerawillbe performed. Uteriof apparentlynonpregnant ratswillbe stained with 10% ammonium sulfideto confirm the absence of implantationsites@1)U.teriof nonpregnant ratsand allovaries willbe retainedinneutralbuffered 10% formalinforpossiblefutureevaluation.
Scheduled Sacrifice- Female Rats Assigned to Natural Delive :
Rats thatdo not delivera liftewrillbe sacrificedon day 25 of presumed gestationand examined forgross lesions.Uteriwillbe stainedwith 10% ammonium sulfideto confirm the absence of implantationsites(s).
Aftercompletion of the 21 -day postpartum period,female ratswillbe sacrificeda,nd a gross necropsy of the thoracic,abdominal and pelvicviscerawillbe performed. The number and distributioonf implantationsiteswillbe recorded.
Dams with No Surviving Pui)s:
Dams with no survivingpups willbe sacrificedafterthe lastpup isfound dead, missing or presumed cannibalized.A gross necropsy of the thoracic,abdominal and pelvic viscerawillbe performed. Postpartum data forthese dams willbe excluded from summary tables.
Rats Found Dead or Moribund:
Rats thatdie or are sacrificedbecause of moribund conditionor abortionwillbe examined forthe cause of death or moribund conditionon the day the observationis made. The ratswillbe examined forgross lesions.Testes, epididymides,prostateand seminal vesiclesof male ratswillbe excised and individualorgan weights willbe recorded (seminalvesiclesweighed withand withoutfluid).The testeswillbe fixedin Bouin's solutionfor48 to 96 hours and then retainedinneutralbuffered 10% formalin. The remaining organs willbe retainedin neutralbuffered 10% formalin.Pregnancy statusand uterinecontents of female ratswillbe recorded. Aborted fetusesand/or deliveredpups willbe examined to the extentpossible. Ovaries willbe retainedin neutralbuffered 10% formalin.Uteriof apparentlynonpregnant ratswillbe stainedwith 10% ammonium sulfideto confirmthe absence of implantationsites(').
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Pmtocol 418-008 Page 16
TESTS, ANALYSES AND MEASUREMENTS -Fl GENERATION:
Viabili:
Preweaning Period:
Litterswillbe observed fordead pups at leasttwice daily.The pups ineach littewrillbe counted once daily.
Postweaning Period:
Twice daily.
ClinicalObservations and/or General ADR2aranc
Preweaning Period:
Once daily.
Postweaning Period:
Once weekly.
Matemal Behavior:
Days 1,4, 7, 14 and 21 postpartum. Any observed abnormal behavior willbe recorded daily.
Clinicalobservations may be recorded more frequentlythan citedabove, ifdeemed appropriateby the Study Directorand/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 ratsonly).
LactationPeriod: Sacrifice:
Days 1,4, 7, 10 and 14 (female ratsonly). Terminal weight.
Feed ConsumRtion Values (recordedand tabulated):
Preweaning Period:
Not recorded.
Postweaning Period:
Weekly except during cohabitation.
Presumed Gestation Period: Days 0, 7, 10, 14, 17 and 20 (female ratsonly).
LactationPeriod:
Days 1,4, 7, 10 and 14 (female ratsonly).
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Pmtowl 418-008 Page 17
Feed consumption valuesmay be recordedmore frequentlyifitisnecessaryto replenishthe feed. Duringcohabitationw,hen two ratsoccupy the same cage withone feedjar,valueswillbe documented when feedjarsare filledT.hese intervalwsillnot be
tabulated.
Proweaning Developmental Observations:
The number of pups meeting the criterioinsrecorded on each day of testing.Testing continues untilthe day the criterioinsattainedby allpups inthe lifter.
Surface RightingReflex(abilittyo rightin5 seconds): From day 1 postpartum.
Pinna Unfolding: From day 2 postpartum.
Eye Opening: From day 12 postpartum.
Acoustic StartleResponse: From day 13 postpartum.
AirRightingReflex: From day 14 postpartum.
Pupilconstrictioinsevaluated once, on day 21 postpartum.
Postweaning DevelORmental Observations:
Sexual Maturation:
Female ratswillbe evaluated forthe age of vaginalpatency, beginning on day 28 postpartum. Male ratswillbe evaluated forthe age of preputialseparation,beginning on day 39 postpartum.
Passive Avoidance Testina:
Beginning at 24 1 day postpartum, one male ratand one female ratfrom each lifter, where possible,willbe evaluated ina passive avoidance testforlearning,short-term retentionand long-term retention.
The passive avoidance apparatus consistsof a two-compartment chamber with hinged Plexigias4Dlids.One compartment isfittewdith a brightlightand Plexiglase)floor.The other compartment isfittedwith a gridfloorto 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 testtrialt,he ratisplaced intothe "brightc"ompartment, the slidingdoor isopened and the lightisturned on. The ratisallowed to explore the apparatus untilit enters the "dark"compartment. The slidingdoor isthen immediately closed,the lightis turned offand the briefpulse of currentisdeliveredto the gridfloor.The ratisthen removed from the apparatus and placed intoa holdingcage for30 seconds before the startof the next trialT.rialsare repeated untilthe ratremains inthe "bright'
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PMtoWl 41"08 Page 18
compartment for60 seconds on two consecutivetrial(sthecriteriofnorleaming)or until 15 trialhsave been completed. The latencyto enterthe dark compartment or the maximum 60-second intervailsrecordedforeach trial.
Each ratistestedtwice. The testsessions are separated by a one-week intervala,nd the criterioinsthe same forboth days of testing.
Dosage groups are compared forthe followingdependent measures:
The number of trialtso the criterioinnthe firsstession-thismeasure willbe used to compare groups foroverallleaming performance.
The latency(inseconds) to enterthe "dark"compartment from the "bright" compartment on trial1 inthe firstestsession-thismeasure willbe used to compare groups foractivitlyevelsand exploratorytendencies in a novel environment.
The latency(inseconds) to enter the "dark"compartment from the "bright" compartment on tria2l inthe firsttestsession-thismeasure willbe used to compare groups forshort-termretention.
The number of trialtso the criterioinnthe second testsession-thismeasure will be used to compare groups forlong-term retention.
The latency(inseconds) to enterthe "dark"compartment from the "bright" compartment on trial1 inthe second session-thisvalue isanother indicationof long4erm retention.
Watermaze Testing
Beginning at approximately 70 days postpartum, one male ratand one female ratfrom each littewrillbe evaluated ina water-filleMd-maze forovertcoordination,swimming abilityl,earningand memory.
Each ratistested ina watertight16-gauge stainlesssteelmodified M-maze. The maze isfillewdith water to a depth of approximately nine inches,and the water ismonitored fortemperature (range of 21 OC 1 OC).
On each testtrialt,he ratwillbe placed intothe startingposition(base of the M-maze stem farthestfrom the two arms) and requiredto swim to one of the two goals of the M-maze, inorder to be removed from the water. On the firstrialt,he ratisrequiredto enter both arms of the maze before being removed from the water. The initialrm chosen on trial1 isdesignated the incorrectgoal during the remaining trials.Rats that failto make a correctgoal choice within60 seconds inany given triaalre guided to the correctgoal and are then removed from the water. A 15-second intertriianltervawlill separate each trial.Each ratis requiredto reach a criterioonf fiveconsecutive erroriesstrialtso terminatethe testsession. The maximum number of trialisnany test
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Pmtocol 418-008 Page 19
session is1S. Latency (measured inseconds) to choose the correctgoal or the maximum Msecond intervalisrecorded foreach triala,s isthe number of errors (incorrecttums inthe maze) during each trial.
Each ratistestedtwice. The testsessions are separated by a one-week intervala,nd the correctgoal and the criterioanre the same forboth testsessions.
Dosage groups are compared forthe followingdependent measures:
The number of trialtso criterioonn the firsdtay of testing-thismeasure willbe used to compare groups foroverallleaming performance.
The average number of errors(incorrectturns inthe maze) foreach triaoln the firstday of testing-thismeasure willalso be used to compare groups foroverall leaming performance.
The latency(inseconds) to reach the correctgoal on tria2l ofthe firsdtay of testing-thismeasure willbe used to compare groups forshort-termretention.
The number of trialtso criterioonn the second day of testing-thismeasure will be used to compare groups forlong-term retention.
The average number of errorsforeach trialon the second day of testing-this measure willalso be used to compare groups forlong-term retention.
The latency(inseconds) to reach the correctgoal on tria1l of day 2 of testing-thisisanother indicatorof long-term retention.
RORroductive CaRacitv:
At approximately 90 days of age, the Fl generation ratswithineach dosage group will be assigned to cohabitation,one male ratper female rat,based on computer-generated random unitsor random unittables,with the exclusionof siblingmatings. The cohabitationperiodwillconsistof a maximum of 14 days. Female ratswith spermatozoa observed ina smear of the vaginal contents and/or a copulatory plug observed in situwillbe considered to be at day 0 of presumed gestationand assigned to individuahlousing. Female ratsthatdo not mate withinthe firs7t days of cohabitationwillbe assigned aftemate male ratsfrom the same dosage group that have mated. Female ratswillbe allowed to naturallydeliverand maintain liftertshrough a 21-day postpartum period.
Mating Performance:
As citedabove forFo generation rats.
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Durafion of Gestation:
As citedabove forFo generationrats.
FortililPyarameters:
As citedabove forFo generation rats.
F2 Generation LifterData:
Viabilityc,linicaolbservations and body weights forF2 generation pups willbe recorded as citedabove forFl generation lftters.
METHOD OF SACRIFICE - Fl GENERATION RATS/F2 GENERATION PUPS:
As previouslycitedforFo generation rats.
NECROPSY - Fl GENERATION RATS:
Gross lesionswillbe retainedin neutralbuffered10% formalinforpossiblefuture evaluation(a tableof random unitswillbe used to selectone controlgroup ratof each sex from which alltissuesexamined at necropsy willbe retained,in order to provide controltissuesforany possiblehistopathologicaelvaluationsof gross lesions).Unless specificallcyitedbelow, allothertissueswillbe discarded.
Scheduled Sacrifice- Fl Generation Male Rats:
Rats willbe sacrificedaftercompletion of the 14-day cohabitationperiod. A gross necropsy ofthe thoracic,abdominal and pelvicvisceralwillbe performed. Testes and epididymides of male ratswillbe excised and individualorgan weights willbe recorded. The epididymides willbe retainedinneutralbuffered10% formalin.The testeswillbe fixedinBouin'ssolutionfor48 to 96 hours and then retainedin neutralbuffered 10% formalin.
Scheduled Sacrifice- Fl Goneraflon Female Rats:
Female ratswillbe sacrificedaftercompletion of the 21 -day postpartum period. The number and distributioonf implantationsiteswillbe recorded. Rats that do not delivera littewrillbe sacrificedon day 25 of presumed gestationand uteriwillbe stainedwith 10% ammonium sulfideto confirmthe absence of implantationsites(,)A. gross necropsy of the thoracic,abdominal and pelvicviscerawillbe performed. Female rats withouta confirmed mating date thatdo not delivera liftewrillbe sacrificedon an estimated day 25 of presumed gestation.
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Fl Gonerabon Rats Found Dead or Moribund:
Rats thatdieor are sacrificedbecause ofmoribund conditionor abortionwillbe
examined forthe cause of death or moribund conditionon the day the observationis made. The ratswillbe examined forgross lesions.Testes, epididymides,prostateand seminal vesiclesof male ratswillbe excised and individualorgan weights willbe recorded (seminalvesiclesweighed withand withoutfluid)T.he testeswillbe fixedin Bouin's solutionfor48 to 96 hours and then retainedin neutralbuffered 10% formalin. The remaining organs willbe retainedinneutralbuffered 10% formaiin.Pregnancy statusand uterinecontents of female ratswillbe recorded. Aborted fetuses and/or deliveredpups willbe examined to the extent possible.Ovaries willbe retainedin neutralbuffered 10% formalin.Uteriof apparently nonpregnant ratswillbe stainedwith 10% ammonium sulfideto confirmthe absence of implantationsites(').
Fl Generation Dams with No Surviving PuRs:
Dams with no survivingpups willbe sacrificedafterthe lastpup isfound dead, missing or presumed cannibalized.A gross necropsy of the thoracic,abdominal and pelvic viscerawillbe performed. Postpartum data forthese dams willbe excluded from summary tables.
FlIF2 Generation PuRs Found Dead on Day I PostDartum:
Pups thatdie before examination of the liftefrorpup viabilitwyillbe evaluated forvital statusat birth.The lungs willbe removed and immersed inwater. Pups with lungs that sinkwillbe identifieads stillbom;pups with lungs thatfloatwillbe identifieads livebom, and to have died shortlyafterbirth.Pups with gross lesionswillbe preserved in Bouin's solutionforpossiblefutureevaluation.Should postmortem autolysispreclude these evaluations,itwillbe noted inthe necropsy data.
FI/F2 Generation Pups Found Dead or Moribund on Days 2 to 21 Postpartum.-
Pups found dead or sacrificedue to moribund conditionwillbe examined forgross lesionsand forthe cause of the moribund conditionor death. Pups with gross lesions found on days 2 to 4 postpartum willbe preserved in Bouin'ssolutionforpossiblefuture evaluation;gross lesionsof pups found on days 5 to 21 postpartum willbe preserved in neutralbuffered10% formalin.Should postmortem autolysispreclude these evaluationsitwillbe noted inthe necropsy data.
418-008:PAGE F-22
Protocol418-008 Page 22
FlIF2 Gonerabon Pups Not Selected forConfinued Observation:
Fl and F2 generation pups culled on day 4 postpartum willbe sacrificed and examined forgross lesions;pups with gross lesionswillbe preserved in Bouin's solution. Necropsy willincludea singlecross-sectionof the head at the levelof the frontal-parietsaulture and examination ofthe cross-sectionedbrainforapparent hydrocephaly.
AllFl generation pups culledon day 21 postpartum willbe sacrificedand examined for gross lesions;gross lesionswillbe preserved in neutralbuffered10% formalin. Necropsy willincludea singlecross-sectionof the head at the levelof the frontal-parietsaulture and examination of the cross-sectionedbrainforapparent hydrocephaly.
Scheduled Sacrifice- F2 Generation Put)s:
On day 21 postpartum, pups willbe sacrificedand examined forgross lesions. Necropsy willincludea singlecross-sectionof the head at the levelof the frontal-parietsaulture and examination of the cross-sectionedbrainforapparent hydrocephaly.
418-008:PAGE F-23
Pmtocol 418-008 Page 23
PROPOSED STATISTICAL METHOD 16-12):
Averages and percentages willbe calculated.Liftevralues willbe used where appropriate.Additionalprocedures and/or analyses may be performed, ifappropriate.
jype ofTest'
1. Parametric' A. Bartleft'TsesV
11.Nonparametric-
A. Kruskal-WallisTest (s75% ties) I
Significantat p:gO.05 Not Significant
Significantat p.-@0.05 Not Significant
Nonparametdc
Analysis ofVariance
Dunn's Test
Significantat p.-50.05
1 Dunneff'sTest
Not Sic iificant B. Fishees Exact Test (>75% ties)
I11.Test for Pro ortionData
Variance Test forHomogeneity of the Binomial Distribution
a. Statisticalsliygnificanptrobabilitieasre reportedas eftherp-.@0.0o5rp:50.01. b. Used only to analyze data with homogeneity of variance. c. Proportiondata are not included inthiscategory. d. Test forhomogeneity of variance.
418-008:PAGE F-24
Pmtocol 418-008 Page 24
DATA ACQUISITION, VERIFICATION AND STORAGE:
Data willbe hand- and/or computer-recorded. Records willbe reviewed by the Study Directorand/or appropriatemanagement personnel within21 days aftergeneration.All originalrecordswillbe stored inthe archivesof the Testing FacilityA.lloriginaldata will be bound and indexed. A copy of allraw data willbe suppliedto the Sponsor upon request. Preserved tissueswillbe stored at the Testing Facilitayt no charge forone year aftermailingof the draftfinalreport,afterwhich time the Sponsor willbe contacted to determine the dispositionof these materials.
RECORDS TO BE MAINTAINED:
Protocoland Amendments. Test ArticleV,ehicle and/or Reagent Receipt,Preparationand Use. Animal Acquisition.
Randomization Schedules. Mating History. Treatment (ifprescribedby StaffVeterinarian). General Comments. ClinicalObservations and/or General Appearance. Blood Sample Collection,Processing and Shipment. Body Weights. Feed Consumption Values. Caesarean-Sectioning Observations. NaturalDeliveryObservations. LitterObservations. Reflex and Physical Development and Behavioral Observations - Fl Generation Pups. Gross Necropsy Observations. Organ Weights (ifrequired). Photographs (ifrequired). Study Maintenance (room and environmental records). Feed, Water and Bedding Analyses. Packing and/or Shipment Lists.
KEY PERSONNE
:
Executive Directorof Research: MildredS. Christian,Ph.D.,ATS Directorof Research: Alan M. Hoberman, Ph.D., DABT Associate Directorof Research and Study Director:Raymond G. York, Ph.D., DABT Directorof Laboratory Operations: John F. Barnett,B.S. Manager of Study Coordination: ValerieA. Sharper, M.S. Manager ofAnimal Operations and Member, InstitutionAanlimal Care and Use
Committee: Dena C. Lebo, V.M.D. Manager of Regulatory Compliance: Kathleen A. Moran, M.S. Consultant,VeterinaryPathology: W. Ray Brown, D.V.M., Ph.D.,ACVP
418-008:PAGE F--'!-z
PMtocol 418-008 Page 25
FINAL REPORT:
A comprehensive draftfinalreportwillbe prepared on completion of the study and will
be finalizefdollowingconsultationwith the Sponsor. The reportwillincludethe following:
Summary and Conclusion. Experimental Design and Method. Evaluationof Test Results. Appendices: Figures,Summary and IndividuaTlables Summarizing the Above Data, Protocoland Associated Amendments and Deviations,Study Director's GLP Compliance Statement, Reports of Supporting Data (ifappropriate)and QAU Statement.
INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE STATEMENT:
The procedures described inthisprotocolhave been reviewed by the Testing Facility's InstitutionAanlimal Care and Use Committee. Allprocedures described in thisprotocol thatinvolvestudy animals willbe conducted in a manner to avoid or minimize discomfort,distressor pain to the animals.
The Sponsoes signaturebelow documents the factthatinformationconcerning the necessityforconducting thisstudy and the factthatthisisnot an unnecessarily duplicativestudy may be obtained from the Sponsor. No aftemative (invitro) procedures were availableformeeting the statedpurposes of the study.
418-008:PAGE F-26
Pmtocol418-008 Page 26
REFERENCES:
1. ChristianM,.S. and Voytek,P.E.(1982).InVivoReproductiveand Mutagenicity
Tests. Environmental ProtectionAgency, Washington, D.C. National Technical InformationService,U.S. Department of Commerce, SpringfieldV,A 22161.
2. ChristianM,.S. (1984). Reproductive toxicitaynd teratologyevaluationsof 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). Embryo and Fetal Developmental Toxicity(Teratology) Control Data in the ChaHes River Cri.CDOBR Rat Charles River Laboratories, Inc.,Wilmington, MA 01887-0630. (Data base providedby Argus Research Laboratories,Inc.)
4. Instituteof Laboratory Animal Resources (1996). Guide forthe Care and Use of Laboratory Animals. National Academy Press, Washington, D.C.
5. Salewski,E. (1964). Frbemethode zum makroskopischen Nachweis von lmplantationsstelleanm Uterus der Rafte. Arch. Pathol.Exp. Pharmakol. 247:367.
6. Snedecor, G.W. and Cochran, W.G. (1967). Variance testforhomogeneity of the binomialdistributionS.tatisticaMlethods, 6th Edition,Iowa State University Press, Ames, pp. 240-241.
7. Sokal, R.R. and Rohlf,F.J.(1969). Bartieft'tsestof homogeneity of variances. Biometry,W.H. Freeman and Co., San Francisco,pp. 370-371.
B. Snedecor, G.W. and Cochran, W.G. (1967). Analysis of Variance. Statistical Methods, 6th Edition, Iowa State University Press, Ames, pp. 258-275.
9. Dunneft,C.W. (1955). A multiplecomparison procedure forcomparing several treatmentswith a control.J. Amer. Stat.Assoc. 50:1096-1129.
10. Sokal, R.R. and Rohff, F.J. (1969). Kruskal-Wallis Test. Biometry, W.H. Freeman and Co., San Francisco, pp. 388-389.
11. Dunn, O.J. (1964). Multiplecomparisons using rank sums. Technometrics 6(3):241-252.
12. Siegel, S. (1956). Nonparametric Statisticsfor the Behavioral Sciences, McGraw-Hill, New York, pp. 96-104.
PROTOCOL APPROVAL:
FOR THE TESTING FACILITY
418-008:PAGE F-27
Pmtocol41"08 Page 27
George E. Dearlove,Ph.D., [IKBT Associate Directorof Research
Date
Rkss)@mo@@G. York, Ph.Ds@DIIB
Ass * te Directorof Re
h
Study Director
Date
rbaraJ. Pafte@@ B.A. 0 hairperson,lnstiti@nalAnimal Care and ' Use Committee
Date
FOR THE SPONSOR
'-01a 01Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date
418-008:PAGE F-28
ATTACHMENT I STUDY SCHEDULE
ATTACHMENT I
-008:PAGEF--29
Pmtocol418408 Page 1 of2
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 untilsacrificeafter 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 littero)r day 20 postpartum (ratsthat deliver a lifter)).
Dosage Period Estrous Cycle Evaluation.
Cohabitation Period (Maximum Male 1 (07 days) Male 2 (07 days)
of 14 days).
FirstPossible 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 initiationdate is the day the Study Director signs the protocol.
ATTACHMENT 1
418-008:PAGE F-'@@"-
PMtocol 418-008 Page 2 of2
03 JUL 98
16 JUL 98 14 JUL 98 31 JUL 98 18JUL98 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
FirstPossibleDay 10 of Presumed Gestation
Caesarean-sectioning. Last Possible Day 10 of Presumed Gestation Caesarean-sectioning.
FirstPossible Delivery(Day 21 of presumed gestation). Last Possible Delivery(Day 25 of presumed gestation).
FirstPossible Day 25 of Presumed Female Sacrifice. Last Possible Day 25 of Presumed Female Sacrifice.
Gestation Gestation
FirstPossible Day 21 Weaning (Dams and Fl generation pups not selectedforcontinued observation sacdficed). Last Possible Day 21 Weaning.
Fl Generation Postweaning Observations Begin (Detailsoftestscitedinprotocol).
Fl Generation CohabitationPeriod (Initiated when ratsare approximately 90 days of age approximate initiadlate).
Fl Generation Male Rats Sacrificedafter Completion of Cohabitation Period Approximate EarliestPossible Date.
DeliveryPeriod - Fl Generation Dams/F2 Generation Litters(Approximate dates).
Sacrificeof Fl Generation Dams and F2 Generation Litterson Day 21 Postpartum (Approximate dates).
DraftFinalReport.
I
418-008:PAGE F-31
ATTACHMENT 2 MATERIAL SAFETY DATA SHEET
418-008:PAGE F-32
MATERIAL SAFETY DATA SHEET
3M 3M Center St. Paul, Minnesota 551"-1000 1-800-364-3577 or (612)
737-6501
(24 hours)
Copyright, 1998, Minnesota Mining and Manufacturing Company. All rightsreserved. Copyingand/or downloadingof this information for the purpose of properlyutilizing3M products
is allowed provided that: 1) the information is copied in full with no changes unless
prior agreement is obtained from 3M, and 2) neither the copy nor the original is resold or otherwise
distributed with the intention of earning a profit thereon.
DIVISION: 3M CHEMICALS
TRADE NAME:
FC-95 FLUORAD Brand Fluorochemical
ID NUMBER/U.P.C.:
98-0207-0103-7 00-51135-09064-1
98-0211-0888-5 ZF-0002-10"-l
00-SI135-09362-7 -
ISSUED: January 29, 1998
SUPERSEDES: November OS, 1997
DOCUMENT: 10-3796-9
Surfactant
98-0207-0104-5 98-0211-3916-1
00-51135-09055-8 00-51135-02311-2
-----------------------------------------------------------------------------
1. INGREDIENT
C.A.S. NO.
PERCENT
-----------------------------------------------------------------------------
POTASSIUM PERFLUOROALKYL SULFONATE ...... 2795-39-3
82
POTASSIUM PERFLUOROALKYL
SULFONATE ...... 3871-99-6
3
POTASSIUM PERFLUOROALKYL
SULFONATE ...... 29420-49-3
3
POTASSIUM PERFLUOROALKYL
SULFONATE ...... 60270-55-5
2
POTASSIUM PERFLUOROALKYL
SULFONATE ...... 3872-25-1
1
- 86 -a -7 -6 -3
----------------------------------------------------------------------------2. PHYSICAL DATA
-----------------------------------------------------------------------------
BOILING POINT: ................N./A VAPOR PRESSURE: ...............N./A VAPOR DENSITY: ................N./A EVAPORATION RATE: .............N./A SOLUBILITY IN WATER: ...........slight SPECIFIC GRAVITY: .............c.a. 0.6
Water-1
(Bulk) PERCENT VOLATILE: .............0. % PH: .........................7..-. 8
(0.1% Aqueous) VISCOSITY: ...................N./.D
MELTING POINT: ................N./D
APPEARANCE AND ODOR: Light colored, free flowing powder.
----------------------------------------------------------------------------Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately
418-008:PAGE F-33
msDS: FC-95 FLUORAD Brand Fluarochosical Surfactant January 29, 1998
PAGE 2
-----------------------------------------------------------------------------
3. FIRE AND EXPLOSION HAZARD DATA -----------------------------------------------------------------------------
FLASH POINT: ................N.o.ne. FLAMMABLE LIMITS - LEL: ........N/A FLAMMABLE LIMITS - UEL: ........N/A AUTOIGNITION TEMPERATURE: ......N/A
EXTINGUISHING MEDIA: Water, Carbon dioxide, Dry chemical, Foam
SPECIAL FIRE FIGHTING PROCEDURES: Wear full protective clothing, including helmet, self-contained, positive pressure or pressure demand breathing apparatus, bunker coat and pants, bands around arms, waist and legs, face mask, and protective covering for exposed areas of the head.
UNUSUAL FIRE AND EXPLOSION HAZARDS: See Hazardous Decomposition section for products of combustion.
- ---------------------------------------------------------------------------
4. REACTIVITY DATA -----------------------------------------------------------------------------
STABILITY: Stable
INCOMPATIBILITY - MATERIALS/CONDITIONS Not applicable.
TO AVOID:
HAZARDOUS POLYMERIZATION: Hazardous polymerization will not occur.
HAZARDOUS DECOMPOSITION PRODUCTS: Carbon Monoxide and Carbon Dioxide, Oxides of Sulfur, Hydrogen Fluoride, Toxic Vapors, Gases or Particulates.
----------------------------------------------------------------------------S. ENVIRONMENTAL INFORMATION
-----------------------------------------------------------------------------
SPILL RESPONSE: Observe precautions from other sections. Vacuum, use wet sweeping compound or water to avoid dusting. CAUTIONI A vacuum cleaner could be an ignition source. Clean up residue with water. Place in an approved metal container. Seal the container.
RECOMMENDED DISPOSAL: Do not release to waterways or sewer. Do not use in products or processes that could result in aquatic concentrations greater than 1/10 of the lowest ECSO or LCSO concentration. Incinerate in an industrial or commercial facility in the presence of a combustible material. Combustion products will include HF. Disposal alternative: Dispose of waste product in a facility permitted to
----------------------------------------------------------------------------Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately
418-008:PAGE F-34
MSDS: FC-95 FLUORAD Brand Fluorachemir-al Surfactant January 29, 1998
PAGE 3
-----------------------------------------------------------------------------
5. ENVIRONMENTAL INFORMATION
(continued)
-----------------------------------------------------------------------------
accept chemical waste.
ENVIRONMENTAL DATA: 96-Hr. Aquatic Fish LC50, Fathead Minnow(Pimephales promelas)=38 mg/l, Bluegill Sunfish(Lepomis macrachirus)-66 mg/l, Rainbow Trout(Salmo gairdneri)-Il mg/l; 48-Hr. EC50, Daphnia Magna - 50 mg/l; COD=.004 gig; BOD20 - Nil.
REGULATORY INFORMATION: Volatile Organic Compounds: N/A. VOC Less H20 & Exempt Solvents: N/A.
Since regulations vary, consult applicable regulations or authorities before disposal. U.S. EPA Hazardous Waste Number = None (Not U.S. EPA Hazardous).
This product complies with the chemical registration requirements of TSCA, EINECS, CDSL, AICS, MITI and Korea.
EPCRA HAZARD CLASS: FIRE HAZARD: No PRESSURE: No REACTIVITY: No ACUTE: Yes CHRONIC: Yes
----------------------------------------------------------------------------6. SUGGESTED FIRST AID
-----------------------------------------------------------------------------
EYE CONTACT: Immediately flush eyes with large amounts of water for at least 15 minutes. Get immediate medical attention.
SKIN CONTACT: Immediately flush skin with large amounts of water. Remove contaminated clothing. If irritation persists, call a physician. Wash contaminated clothing before reuse.
INHALATION: If signs/symptoms occur, remove person to fresh air. If signs/symptoms continue, call a physician.
IF SWALLOWED: Drink two glasses of water. Call a physician.
----------------------------------------------------------------------------7. PRECAUTIONARY INFORMATION
-----------------------------------------------------------------------------
EYE PROTECTION: Avoid eye contact. Wear vented goggles.
----------------------------------------------------------------------------Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately
418-008:PAGE F-?-@
NSDS: FC-95 FLUORAD Brand Fluorochosical Surfactant January 29, 1998
PAGE 4
-----------------------------------------------------------------------------
7. PRECAUTIONARY INFORMATION
(continued)
-----------------------------------------------------------------------------
SKIN PROTECTION: Avoid skin contact. Wear appropriate gloves when handling this material. A pair of gloves made from the following material(s) are recommended: butyl rubber. Use one or more of the following personal protection items as necessary to prevent skin contact: head covering, coveralls. Protective garments (other than gloves) should be made of either of the following materials: polyethylene/polyvinylidenechloride (Saranex).
RECOMMENDED VENTILATION: Use with appropriate local exhaust ventilation. Use in a wellventilated area. Provide sufficient ventilation to maintain emissions below recommended exposure limits. If exhaust ventilation is not adequate, use appropriate respiratory protection.
RESPIRATORY PROTECTION: Avoid breathing of dust. Select one of the following NIOSH approved respirators based on airborne concentration of contaminants and in accordance with OSHA regulations: half-mask dust and mist respirator, half-mask supplied air respirator, full-face dust and mist respirator, full-face supplied air respirator.
PREVENTION OF ACCIDENTAL INGESTION: Do not eat, drink or smoke when using this product. Wash exposed areas thoroughly with soap and water. Wash hands after handling and before eating.
RECOMMENDED STORAGE: Keep container dry. Keep container closed when not in use.
FIRE AND EXPLOSION AVOIDANCE: Nonflammable.
OTHER PRECAUTIONARY INFORMATION: No smoking: Smoking while using this product can result in contamination of the tobacco and/or smoke and lead to the formation of the hazardous decomposition products mentioned in section 4 of this MSDS.
MMIS HAZARD RATINGS:
HEALTH: 2 FLAMMABILITY: 0 REACTIVITY: 0 PERSONAL PROTECTION: X (See precautions, section 7.)
EXPOSURE LIMITS
INGREDIENT
VALUE UNIT
TYPE AUTH SKIN*
-----------------------------------------------------------------------------
POTASSIUM PERFLUOROALKYL SULFONATE ... 0.1 MG/M3
TWA
3M
y
POTASSIUM PERFLUOROALKYL SULFONATE ... 0.1
MG/M3
TWA
3M
y
POTASSIUM PERFLUOROALKYL SULFONATE ... 0.1 MG/M3
TWA
3M
y
POTASSIUM PERFLUOROALKYL SULFONATE ... 0.1 MGIM3-
TWA
3M
y
-----------------------------------------------------------------------------
Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately
418-008:PAGE F-36
MSDS: FC-9S FLUORAD Brand Fluorochomical Surfactant January 29, 1998
PAGE S
EXPOSURE LIMITS
(continued)
INGREDIENT
VALUE UNIT
TYPE AUTH SKIN*
-----------------------------------------------------------------------------
POTASSIUM PERFLUOROALKYL SULFONATE ... 0.1 MG/M3
TWA
3M
y
SKIN NOTATION: Listed substances indicated with 'Y' under SKIN refer to *the potential contribution to the overall exposure by the cutaneous route
including mucous membrane and eye, either by airborne or, more particularly, by direct contact with the substance. Vehicles can alter skin absorption.
SOURCE OF EXPOSURE LIMIT DATA:
- 3M:
3M Recommended Exposure Guidelines
-----------------------------------------------------------------------------
S. HEALTH HAZARD DATA -----------------------------------------------------------------------------
EYE CONTACT:
Mild Eye Irritation: signs/symptoms can include redness, swelling, pain, and tearing.
SKIN CONTACT: Mild Skin Irritation (after prolonged or repeated contact): signs/symptoms can include redness, swelling, and itching.
May be absorbed through the skin and persist in the body for an extended time.
INHALATION: May be harmful if inhaled.
May be absorbed by inhalation and persist in the body for an extended time.
Single overexposure, above recommended guidelines, way cause:
Irritation (upper respiratory): signs/symptoms can include soreness of the nose and throat, coughing and sneezing.
IF SWALLOWED: Ingestion is not a likely route of exposure to this product.
Illness may result from a single swallowing of a moderate quantity of this material.
May be harmful if swallowed.
MUTAGENICITY: Mutagenicity assays indicate the product is not autagenic.
----------------------------------------------------------------------------Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately
418-008:PAGE F-37
NSDS: FC-95 FLUORAD Brand Fluarachomical Surfactant january 29, 1998
PAGE 6
-----------------------------------------------------------------------------
B. HEALTH HAZARD DATA
(continued)
-----------------------------------------------------------------------------
REPRODUCTIVEIDEVELOPMENTAL
TOXINS:
Not toratogenic in the rat at oral doses below maternally toxic levels.
OTHER HEALTH KAZARD INFORMATION: This product is not known to contain any substances regulated under California Proposition 65.
A Product Toxicity Summary Sheet is available.
-----------------------------------------------------------------------------
SECTION CHANGE DATES -----------------------------------------------------------------------------
HEADING
SECTION CHANGED SINCE November OS, 1997 ISSUE
----------------------------------------------------------------------------Abbreviations: N/D - Not Determined N/A - Not Applicable CA - Approximately
-----------------------------------------------------------------------------
The information in this Material Safety Data Sheet (MSDS) is believed to be correct as of the date issued. 3M MAKES NO WARRANTIES, EXPRESSED OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR COURSE OF PERFORMANCE OR USAGE OF TRADE. User is responsible for determining whether the 3M product is fit for a particular purpose and suitable for user's method of use or application. Given the variety of factors that can affect the use and application of a 3M product, some of which are uniquely within the user's knowledge and control, it is essential that the user evaluate the 3M product to determine whether it is fit for a particular purpose and suitable for user's method of use or application.
3M provides information in electronic fare as a service to its customers. Due to the remote possibility that electronic transfer may have resulted in errors, omissions or alterations in this information, 3M makes no representations as to its completeness or accuracy. In addition, information obtained from a database may not be as current as the information in the MSDS available directly from 3M.
418-008:PAGE F-38
ATTACHMENT 3 TEST ARTICLE PREPARATION PROCEDURE
418-008:PAGE @:7-39
ATTACHMENT 3
TEST ARTICLE PREPARATION
Pmtocol 418-008 Version:418-008 (21 MAY 98)
Page I of3
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 articlefor oral administration to rats on Argus Study 418-008.
B. General Information:
1 . All suspension containers willbe labeled and color coded. Each label will specify the protocol number, test articleidentificationA,rgus batch number, concentration, dosage level,preparation date, expiration date and storage conditions.
2. Suspensions willbe prepared:
X Daily
-
Weekly
For
days of use
3. Suspensions willbe prepared at a finaldosage 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/Posftive 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.
418-008:PAGEF-4.1
A7rACHMENT 3
TEST ARTICLE PREPARATION
Pmtocol 418-008
Version4:1"08 (21MAY 98)
PROCEDURE
Page 2 of 3
NOTE:
Test articlewillbe prepared as a serialdilutionfrom the high dosage to the low dosage. Stirbars 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 ArticleSolution 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 stirbar and heat the preparation to 80 OC in a water bath for approximately 30 minutes (or untilthe test articlehas 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 stirbar and mix untiluniform.
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 stirbar and mix untiluniform.
418-008:PAGE F-41
A7rACHMENT 3
TEST ARTICLE PREPARATION
Pmtocol 418-008
Version:41 MOB (21 MAY 98)
PROCEDURE
Page 3 of3
7. To prepare group 11,(the0.02-mg/mL solution)a,dd 50 mL of group III solutionto an appropriatelylabeled container,then q.s.to 200 mL with vehicle.Add a stirbar and mix untiluniform.
Wdften by:
Approved b Clarification:
v No
ir, I/ Date: -21-1)& -91f
Yes (See attachedclarificatifoonrm.)
Initial/Date
-q5
418-008:PAGE F-42
TEST AM=ISMSTANCE
PROAUTTON
PROCEDMLE CLARMCATION
?rotor-al.: 41jk-009'
Date of
Preparation
Clarification Stop
-@-12
versiont-
.2co
Clarification eC Veli,cle, is 0 -t-.1
7"' Study Dirac
@@st
9 5r
Date
Study Director
Date
Study Director
Date
Reviewed by: C,
Stu.dy Director
Date
Data: O8.l5e97 T&SPPM-01-02
418-008:PAGE F-43
RESEA#?MI
Argus Reseamh LaboratoriesI,nc.
905 Sheehy Drive,BuildingA Homham, Pennsylvania 190"
T: (215)"34710 F:(215)"3-8587
PROTOCOL 418-008
COMBINED AND
ORAL(GAVAGE) FERTILITY, DEVELOPMENTAL
PERINATAUPOSTNATAL
REPRODUCTION
TOXICITY STUDY OF PFOS IN RATS
SPONSOR'S STUDY NUMBER: 6295.9
Amendment I -June 2,1998
1 Storaae(page 3 oftheprotocol):
[EffectiveDate: May 26, 1998] Prepared formulationswillbe storedat room temperature overnight,ratherthan frozen.
Reason forChanae:
This change was made to clariftyhe protocoland facilitatdeose formulation preparation.
2. Freauency of Prer)aratio(npage 4 of the protocol):
[EffectiveDate: May 26, 1998] The vehicle(0.5% Tween 800 inR.O. Deionized Water) willbe prepared weekly by adding 15 mLs of Tween 80(Dto 2985 mL of R.O. Deionized Water.
Reason forChange:
This change was made to clariftyhe protocoland facilitatdeose formulation preparation.
3. Stabilil(ypage 4 ofthe protocol):
[EffectivDeate: May 27, 1998] The Sponsor has confirmed a 48-hour stability on the testarticlein 0.5% Tween 804D solutions.This allows forpreparationsto be made one day priortothe day ofdose administration.Due tothe lengthy
418-008:PAGE!:---44
Pmtocol 418-008 Amendment 1 Page 2
preparationprocedure,dose solutionsmay be made one day priortothe day of dosing.
Reason for hange:
This change was made to clariftyhe protocoland facilitatdeose formulation preparation.
Alan M. Hoberman, Ph.D., DABT Date Directorof Research
@Na-@f-fUnd G. York, Ph..D. DABT Associate Directorof es@larch
and Study Director
Date
Dena C. Lebo, V.M.D.
Date
Member, InstitutionAanlimal Care
and Use Committee
T(:,
Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date
418-008:PAGE F-2,,,--
rgm,.i
REMARCH
Argus Research Laboratories,Inc.
905 Sheehy Drive,Building A Horsham, Pennsylvania 19044
T: (215)443-8710 F: (215)4434587
PROTOCOL 418-008
COMBINED AND
ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL
PERINATAUPOSTNATAL
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 ofthe protocol):
[EffectiveDate: May 26, 1998] Body weights and feed consumption values will also be collectedon Fo generation females on postpartum day 10.
Reason forChange:
This informationwas added to the protocolto match data collectionon Fl generationfemales.
2. Scheduled Sacrificeof Male Rats (page 14 ofthe protocol):
[EffectiveDate: May 26, 1998] At scheduled sacrificoefFo male rats,allorgans willbe weighed individually.
Reason forChange:
This change clarifietshe protocol.
3. Scheduled Sacrifice- Female Rats Assigned to Caesarea n-Sectioning (page 15 of the protocol):
[EffectiveDate: May 26, 19981 Uteriof non-pregnant ratswillnot be retained.
418-008:PAGE F-46
ProtoCol418-008 Amendment 2 Page 2
Reason forChange:
Thischange was made atthe requestofthe Sponsor.
4. Scheduled Sacrifice- Fl Generation Male Rats (page 20 ofthe protocol):
[EffectivDeate:May 26, 1998] Seminalvesicles(withand withoutfluidsa)nd
prostates,willbe weighed at scheduled sacrificeof allFl generation male rats. Reason forChange:
This informationwas added to the protocolto match data collectionon Fo generation males.
Alan M. Hoberman, Ph.D.,DABT Date Directorof Research
4.asy@Qond G. York, As ciateDirectoro and Study Director
D, NABT search
Date
Dena C. Lebo, V.M.D.
Tt,"/. Date
Member, InstitutionAanlimal Care
and Use Committee
Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date
418-008:PAGE F-47
rgm,.i
REMACH
Argus Reseamh Laboratories,Inc. 905 Sheehy Drive,BuildingA
Horsham, Pennsylvania 19044
T: (215)4434710 F: (215)"3-W87
PROTOCOL 418-008
COMBINED ORAL(GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATALIPOSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS
SPONSOR'S STUDY NUMBER: 6295.9
Amendment 3 - June 25, 1998
Administration.Method and FregueD-CY (Page 10 of the protocol):
[EffectivDeate: June 19, 1998] Due to a programming errorin dosage calculationthe dosage period willbe extended foran additional2 weeks and the cohabitationperiod willoccur two weeks laterthan originallsycheduled. The errorindosage calculationscaused the male ratsto receiveapproximately 89% to 90% of the targeted dosage and female ratsto receiveapproximately 95% to 99% of the targeted dosage. This occurred forsixof the seven days in the second and thirdweeks and two days of the fourthweek of the dosage period.
Reason forChange:
This change was made to ensure thatallratsreceivethe correctdosage before cohabitation.
418-008:PAGEF-48
.Pmtoco4l18-008 Amendment 3 Page 2
2. Schedule (Attachment1 ofthe 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 20JUL98 03 AUG 98
17JUL98 30 JUL 98
Start of Dosage Period - Fo Generation Male. Rats (42 days before cohabitation and continuing through a 14-day cohabitation period untilsacrifice aftersuccessful 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 liftero)r day 20 postpartum (ratsthat deliver a lifter)].
Dosage Period Estrous Cycle Evaluation.
Cohabitation Period (Maximum Male 1 (07 days) Male 2 (07 days)
of 14 days).
FirstPossible Day 0 of Presumed Last Possible Day 0 of Presumed
Gestation. Gestation.
Fo Generation Male Rats Sacrificed after Completion of the Cohabitation Period (Earliest possible date).
FirstPossible Day 10 of Presumed Caesarean-sectioning. Last Possible Day 10 of Presumed Caesarean-sectioning.
Gestation Gestation
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
418-008:PAGEF49
Protoco4l18-008 Amendment3 Page3
FirsPtossiblDeeliver(yDay21 ofpresumed
gestation). LastPossibleDelivery(Day 25 ofpresumed gestation).
FirstPossibleDay 25 ofPresumed Gestation Female Sacrifice. LastPossibleDay 25 ofPresumed Gestation Female Sacrifice.
FirstPossibleDay 21 Weaning (Dams and Fl generationpups notselectedforcontinued observationsacrificed). LastPossibleDay 21 Weaning.
Fl GenerationPostweaningObservations Begin(Detailosftestscitedinprotocol).
Fl GenerationCohabitationPeriod(initiated when ratsareapproximately90 days ofage approximateinitidaalte).
Fl GenerationMale Rats Sacrificeadfter CompletionofCohabitationPeriodApproximateEarliesPtossibleDate.
DeliveryPeriod-Fl GenerationDams/F2 GenerationLifter(sApproximatedates).
SacrificoefFl GenerationDams and F2 GenerationLifterosn Day 21 Postpartum (Approximatedates).
DraftFinal
418-008:PAGE F-l'i-W
Pmtocol 418-008 Amendffient 3 Page 4
Reason forChange:
Thisschedulewas changed due tothe extensionofthe dosingperiodby two weeks and the cohabitatiopneriodoccurringtwo weeks laterthan scheduled.
Alan M. Hoberman, Ph.D.,DABT Date Directorof Research
R.)k@@'nd G. rk, h.D.,DABT Date AssociateDirect f esearch and Study Director
Dena C. Lebo,V.M.D.
Date
Member, InstitutioAnnailmal Care
and Use Committee
Marvin T.Case, D.V.M.,Ph.D. Date Study Monitor
irjPIZIXIMICA
. 418-008:PAGE F-51
Argus Rcscmh LaboratoriesI,nc. 905 Sheehy Drive,BuildingA Horsham, PA 19044 Telephone:(215) 443-8710 Telefax:(215)443-8597
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAUPOSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS.
SPONSOR'S STUDY NUMBER: 6295.9 Amendment 4 -July14, 1998
1 . TestArticlPereparationProcedure (Version29 JUN 98 ofAttachment 3 tothe protocol):
[EffectivDeate: June 29,1998] The volume ofthetestarticlseolutions preparedeach day willbe increased.The new Test ArticlPereparation Procedure isattachedtothisamendment.
Reason forChanae:
Itisnecessarytoincreasethe volume ofthe testarticlseolutionspreparedeach 1433 da because oftheincreasingbody weightsoftherats.
eotge E. Dearlove(PJ.D.,DABT AssociateDirectorof Research
Date RayModd G. York,P4@., DABT AssociateDirectorof Research Study Director
9
Date
@@B@aarrbara J.p@k4wo on, B.A.
Date MarvinT. Case, D.V.M.,Ph.D.
Date
Chairperson,I titutionAanlimal Care Study Monitor
and Use 'Oomriftee
418-008:PAGEF-52
ATTACHMENT 3
TEST ARTICLE PREPARATION
Pmtocol 418-008
Version:418-OO8l22jUN_98 j
PROCEDURE
Page 1 of3
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 articlefor oral administration to rats on Argus Study 418-008.
B. General Information:
1 . All suspension containers willbe labeled and color coded. Each label will specify the protocol number, test articleidentification,Argus batch number, concentration, dosage level,preparation date, expiration date and storage conditions.
2. Suspensions willbe prepared:
X Daily
-
Weekly
For
days of use
3. Suspensions willbe prepared at a finaldosage 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/Posftive Pressure Hood
Tyvek SuiVApron
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.
418-008:PAGE F-53
ATTACHMENT 3
TEST ARTICLE PREPARATION
Protocol418-008
Version:418-OO8l22jUN 981
PROCEDURE
Page 2 of3
NOTE:
Test articlewillbe prepared as a serialdilutionfrom the high dosage to the low dosage. Stirbars are to be added to the containers;mixing should occur during sampling and/or dosage administration.
C. Preparationof the Control Group:
1 . Add the requiredamount ofvehicleto an appropriatevessel. (See TEST ARTICLE CALCULATIONS forexact quantities.)
D. Test ArticleSolutionPreparation:
1 . To prepare the 0.64-mg/mL, (group V) solution,add 224 mg oftestarticle intoan appropriatelysized,labeledcontainer.
2. Q. S. to 350 mL with the vehicle.
3. Add a stirbar and heat the preparationto 80 *C in a water bath for approximately 30 minutes (oruntilthe testarticlehas dissolved).
4. Remove the solutionfrom the water bath,and spin while the solution equilibratesto room temperature.
5. To prepare group IV,(the0.32-mg/mL solution)a,dd 150 mL ofgroup V solutionto an appropriatelylabeledcontainer,then q.s.to 300 mL with vehicle.Add a stirbar and mix untiluniform.
6. To prepare group 111(,the0.08-mg/mL solution)a,dd 65 mL of group IV solutionto an appropriatelylabeledcontainer,then q.s.to 260 mL with vehicle.Add a stirbar and mix untiluniform.
B-QOB: PAGE .@@-54
ATTACHMENT 3
TEST ARTICLE PREPARATION
PMtocol 418-008 Version:418-008agjUN 981
PROCEDURE
Page 3 of3
7. To prepare group 11,(the0.02-mg/mL solution)a,dd 50 mL of group III solutionto an appropriatelylabeledcontainer,then q.s.to 200 mL with vehicle.Add a stirbar and mix untilunfform.
Written by:
Approvedby:@@4@-\
Date:/3-dUo?
'Lo Clarification,:/ No
U Yes (See attached clarificatifoonrm.)
Initial/Date
@rPjP-J'MMICA
418-008:PAGE
Argus Research LaboratoriesI,nc. 905 Sheehy Drive,BuildingA Horshazn,PA 19044 Telephone: (215)443-97 1C Telefax:(215)443-8597
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAUPOSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS.
SPONSOR'S STUDY NUMBER: 6295.9 Amendment 5 -July17, 1998
1 ConcentrationAnalyses(page 5 oftheprotocol):
Samples (5mL each)fromeach concentratiownillbe takenduringthefirsatnd lastweek ofthe Fl dosage administratiotnoverifyconcentrationosfthe prepared testarticlfeormulations.
Reason forChange:
Thischange was made because dosage administratiownas extended toinclude theFl generationmale and femalerats.
2. Sex (page 6 oftheprotocol):
The Fl generationmale and female pups willbe giventhe testarticloervehicle.
Reason forChange:
These changes were made atthe requestofthe Sponsor inordertoprovide informatioanbout the effectsofthetestarticloen the second generation.
3. Method and Freguencv (page 10 oftheprotocol):
The Fl generationmale and femalepups willbe administeredthetestarticle orall(ygavage)on day 1 postweaningthroughthe day beforesacrifice. F2 generationpups willnot be directlgyiventhe testarticleb,ut may be possibly exposed tothe testarticldeuringmatemal gestation(inuteroexposure)orvia matemal milkduringthe lactatiopneriod.
418-008:PAGEF-56
Pmtocol418-008 Amendment 5 Page 2
Reason for Change:
These changes were made at the request of the Sponsor of exposure to Fo generation.
and follow the method
4.
Dosage Levels, Concentrations and Volumes (page 11 of the protocol):
Dosage Group
1 11 [if L: lVvt 1
Number of Fo Generation Rats Per Sex
Number of
Fl Generation
Rats Per Sex
Dosage (mg&Wday)
Concentration (mg/mL)
35
25
0 (Vehicle)
0
35
25
0.1
0.02
35
25
0.4
0.08
35
25
1.6
0.32
25
3.2
0.64
Reason for Change:
Dosage Volume
(mLJkg)
Argus BatchNumber
5
B-418-008-A(DayM.onntthh..Year
5
.Y. B-41B-008-B(DayM.oonntth.Year)
h YYeeaarr
5
B-418-008-C(Dayo.@0Mnotnthh@.Yaerar)
5
B-41B-008-D(DayM.onth.Year) I
5
B41&00:ELDay. onth.Yearl
This change was made because dosage administration was extended the Fl generation male and female rats.
to include
5.
Tests, Analyses and Measurements
- Fl Generation (page 16 of the protocol):
Clinical Observations and/or General AE)Dearance-
Preweaning Period:
Once daily.
Dosage Period: Matemal Behavior:
Twice daily. Prior to dosage administration and once approximately one hour postdosage.
Days 1, 4, 7, 14 and 21 postpartum. Any observed abnormal behavior will be recorded daily
418-008:PAGE F-57
Protocol418-008 Amendment 5 Page 3
Body Weights - Male: Preweaning Period: Dosage Period: Sacrifice: Body Weiahts - Female: Preweaning Period: Dosage Period:
Sacdfice: Reason forChan-ge:
Days 1 (birth)4,, 7, 14 and 21 postpartum. Weekly. Terminal weight.
Days 1 (birth)4,, 7, 14 and 21 postpartum. Weekly to cohabitation.Dailyduring presumed gestationand on Days 1,4, 7 and 14 postpartum (ratsassigned to naturaldelivery). Terminal weight.
These changes were made because dosage administrationwas extended to includethe Fl generation male and female rats.
6. Fl/F2 Generation Pur)s Not Selected forContinued Observation (page 22 ofthe protocol):
On day 4 postpartum, the stomach contents (milkcurd)willbe collectedfrom culledpups from Groups 1,11and V (orhighestdosage group available). Samples willbe collectedfrom allpups from four to fiveof the largestlifterisn these three dosage groups. Individualpup samples willbe combined by lifter intopolypropylene tubes and frozenat -20*C. Aftercompletion of sample collections,amples willbe shipped (frozenon dry ice)to KrisJ.Hansen, Ph.D. at 3M Environmental Technology and Safety Services,935 Bush Avenue, Building2-3E-09,,St.Paul,Minnesota 55133-3331 foranalysis.Both the recipientand the Study Monitor willbe notifiedinadvance of sample shipment.
418-008:PAGE F-58
Pmtocol 41 M08 Amendment 5 Page 4
Reason forChanue:
Collectionof milk samples were requested by the Sponsor to determine ifthe testarticleisreaching the pups via lactation.
.,."C.@@
/7---4--qA9,
--@rGe"*'D@Ee. Dearlov P sD.,DABT Associate Directoroo@ e@eeseaa'rrrc,h
Date
@4
Ray-?n@nd G. York .41h.D., DABT Associate Directorof Research Study Director
Date
Barbara J. Pafterson,4B.A.
Date
Chairperson,InstitutionAanlimal Care
and Use Committee
Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date
ir.0-@PPJAEDICA
418-008:PAGE t':7-59
Argus ResearchLaboratoriesl,nc. 905 Sheehy Drive,BuildingA Homhatn, PA 19044 Telephone: (215)443-97 1C Telefax:(215)443-9597
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAUPOSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS
SPONSOR'S STUDY NUMBER: 6295.9 Amendment 6 - 13 August 1998
1 . Necropsy (page 20 oftheprotocol): On postpartumday 21,the 1.6mg/kg/day dosage group (Group IV)dams and lifterwsillbe sacrificed. Reason forChange:
Group IVwas terminatedatweaning because ofthe severe pup toxicitdyuring lactatio(nmortalitaynd reduced body weightsand delayeddevelopment).
2. Male and Female Rats Assigned toPharmacokineticSample Collectio(npage 14 ofthe protocol):
On postpartumDay 21, the liverosfthe pups from fivelifterisneach ofthe remaininggroups willbe excised,pooledper liftefrr,ozenand retainedat-70*C untislhipmenttothe Sponsor. Reason forChange:
This change was made atthe requestofthe Sponsor forpossibleanalysis.
3. Scheduled Sacrific-eFemale Rats Assigned to NaturalDelivervand Dams with No SurvivingPups (page 15 ofthe protocol): Ovarieswillbe retainedinneutralbuffered10% formalin.
418-008:PAGE F-r.-l-
Amendment 6 Page 2
Reason forChange:
This cha was made to clariftyhe protoc
Th
4 ee@ororIE E. Dearlove,Ph.D.,DABT Date Associate Directorof Research
B a rbar--- atterson,@JA.
Date
Chairpitrisn, InstitutionAanlimal Care
and Use Committee
R
nd G. York, F@h-;D.e,a@ABT
Associate Director@fR earch
Stuoy Director
7
Marvin T. Case, D.V.M., Ph.D. Study Monitor
Date Date
418-008:PAGE F-61
Argus Research LaboratoriesI,nc. 905 Sheehy DTive,BuildingA Horshan36 PA 19044 Telephone:(215) 443-97 1C Telefax:(215)443-9591
PROTOCOL 418-008 COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAUPOSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS
SPONSOR'S STUDY NUMBER: 6295.9 Amendment 7 -24 November 1998
1. NaturalDeliverv(page 13 ofthe protocol):
The Length ofParturitio(ntimeofdeliveryoflastpup minus the time ofdelivery ofthefirsptup dividedby N-1 pups ineach littewri)llnot be calculated. Reason forChanae: A littweartch was notrequiredby the Sponsor.
-rgrorgek Dearlove,Ph.D.,DABT Date AssociateDirectorof Research
2
Ra @ Ld G. York,P
ArBT
AssociateDirector %@JarchTB
Study Director
-gz
Date
Dena C. Lebo, V.M.D.
Date MarvinT. Case, D.V.M.,Ph.D.
Date
Chairperson,InstitutioAnnailmal Care
Study Monitor
and Use Committee
ir.o-*PRLMMIC,,4,.
418-008:PAGE F-62
Argw Rescirch LaboraforiesI,nc. 905 Sheehy Drive,Budding A Horsham, PA 19044 Telephone:(215)443-87 10 Telefax:(215)443-8597
PROTOCOL 418-008
COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND
PERINATAUPOSTNATAL
REPRODUCTION TOXICITY STUDY OF PFOS IN RATS
SPONSOR'S STUDY NUMBER: 6295.9
Amendment 8 - 18 May 1999
1 ConcentrationAnalyses (page5 oftheprotocol):
The concentrationsamples were senttotheSponsor. Sample analyseswillbe conducted atthediscretioonfthe Sponsor and no reportwillbe senttothe TestingFacility.
Reason forChange:
Thischange was made atthe requestoftheSponsor toclariftyheprotocol. 2. Male and Female Rats AssignedtoPharmacokineticSample Collectio(npage 14
ofthe protocol):
The livearnd serum samples were senttotheSponsor. Samples willbe analyzed at the discretioonf the Sponsor.
Reason forChange:
Thischange was made attherequestofthe Sponsor toclariftyheprotocol. 3. Fl/F2 Generabon Pul2sNot SelectedforContinued Observation(page 22 and
Amendment 5 ofthe protocol):
The stomach contentsofthese pups were senttotheSponsor foranalysis. Stomach contentswillbe analyzedatthe discretioonfthe Sponsor.
41MOB:PAGE F-63
Reason forChange:
Protocol418-008
Amendment 8
Page 2
This change was made atthe requestofthe Sponsor to clariftyhe protocol.
or04 E. Dearlove,Ph.D.,DABT Date Ray ond G. York, h.D, DABT
@ate
AssociateDirectorof Research
AssociateDirectorof esearch
Study Director
7
4en@a C.L@e@@24
ODfate Marvin T. Case, D.V.M.,Ph.D.
Date
Chairperson,InstitutionAanlimal Care
Study Monitor
and Use Committee
APPENDIX G
DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY
418-008:PAGE G-1
DEVIATIONS FROM THE PROTOCOL AND THE STANDARD OPERATING PROCEDURES OF THE TESTING FACILITY
1 On 8 August 1998, the 5 mL concentrationsample was nottaken duringthe firswteek ofdosage administratiofnorthe Fl generation rats.This deviationdid not adverselyaffecthe outcome or interpretatiofnthe study because sufficiendtata were collectedto accuratelyevaluatethisparameter.
2. On 3 to 8 June 1998 [studydays (DSs) 9 to 14],10 to 15 June 1998 (DSs 16 to21),17 June 1998 (DS 23) and 18 June 1998 (DS 24),all Fo generationmale and female ratswere dosed withthe dosage volumes based on body weights recordedon DS 1 (26 May 1998), ratherthan on weekly body weights.As a resultofthiserror,male rats were administeredapproximately89% to 90% ofthe targeteddosages and female ratswere administeredapproximately95% to99% ofthe targeteddosages. This deviationdidnot adverselyaffecthe outcome or interpretatiofnthe study because the precohabitatiodnosage periodwas extended foran additionatlwo weeks to ensure thatallrats were administeredthe correctdosages before cohabitation.
3. On 21 August 1998 (postweaningday 1),Fl generationmale rats 13158 and 13159 inthe 0.4 mg/kg/day dosage group were neither weighed nor dosed. The dosage volume forthe restofthe week was based on the postweaning day 2 body weight.This deviationdidnot adverselyaffectthe outcome or interpretatioofnthe study because a sufficientumber of postweaning day 1 body weights were collectedto evaluatethisparameter,and the dosage volumes were based on the
day 2 postweaning weight were presumed to be very similartodosage volumes based on the day 1 postweaning weight.
Alldeviationsa documented inthe raw data. /
-
il@fi
// --
/@Ra ndd G. Y@oorrkloohf .,DABT Associate Directo esearch
Date
and Study Director
TEMPERATURE
APPENDIX H AND RELATIVE HUMIDITY REPORTS
418-008:PAGE H-1
ARGUS
Temperature and RelativeHumidity Report Location:Room 17
Protocol Number. 418-008
Range of Dates: 12-May-1998 12:00 to 12-Jun-1998 09:46
TargetRange: Species:Rat
TotalNumber ofDays: TotalNumber ofHours: TotalNumber ofDataPoints:
Temperature 64*F to 79OF
32 741.5 742
RelativeHumidity 30% to70%
32 741.5 742
Mean (SD):
Maximum: Median: Minimum:
Number of PointsinRange (%): Number ofPointsHigh (%): Number ofPointsLow (%):
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-1998at13:18
COMMENTS:
REVIEWED BY:
DATE: ?1,.Ili
Cumulativeby Location(v04.01.97)
ARGUS
418-008:PAGE H-2
Temperature and RelativeHumidity Report Location:Room 03
ProtocolNumber. 418-008
Range of Dates: 12-Jun-1998 09:46 to 21-Sep-1998 13:40
TargetRange: Species:Rat
TotalNumber ofDays: TotalNumber ofHours: TotalNumber of DataPoints:
Temperature 64OF to79OF
102 2427.74
2423
RelativeHumidity 30% to70%
102 2427.74
2423
Mean (:SkD):
69.0
Maximum:
75.3
Median:
69.1
Minimum:
62.0
Number ofPointsinRange (%):
2405
Number ofPointsHigh (%):
0
Number ofPointsLow (%):
is
Report Generated: 31-Mar-1999 at09:02
(:2t.0) 61.6
72.3 63.1 45.7
(99.3) 2404 (0-0) 19 (0.7) 0
(t4.8)
(99.2) (0-8) (0.0)
COMMENTS:
REVIEWED BY: -t,-
DATE:
Cumulativeby Location(vD4.01.97)
418-008:PAGE H-3
ARGUS
Temperature and RelativeHumidity Report Location:Room 05
Protocol Number. 418-008
Range of Dates: 27-Jul-199812:50to 28-Dec-1998 08:29
Target Range: Species:Rat
TotalNumber ofDays: TotalNumber ofHours: TotalNumber ofData Points:
Temperature 64"F to79*F
155 3691.26
3677
RelativeHumidity 30% to70%
155 3691.26
3677
Mean (.StD):
69.3
Maximum:
82.7
Median:
69.7
Minimum:
64.6
Number ofPointsinRange (%):
3661
Number ofPointsHigh (%):
16
Number ofPointsLow
0
Report Generated:31-Mar-1999 at09:22
(.t1.8) 56.3
71.3 58.1 34.3
(gg.e) 3667 (0.4) 10 (0-0) 0
(:6t-7)
(gg.7) (0.3) (0-0)
COMMENTS:
REVIEWED BY:
DATE:-
-'-Ict
Cumulativeby Location(vO4.01.97)
ARGUS
418-008:PAGE H-'T
Temperature and RelativeHumidity 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
TotalNumber of Days: TotalNumber of Hours: TotalNumber of Data Points:
Temperature 54OF to 79*F
99 2346.52
2336
RelativeHumidity 30% to70%
99 2346.52
2336
Mean (SD):
Maximum: Median: Minimum:
Number of Points in Range (%): Number of Points High (%): Number of Points Low (%):
69.7
73.0 69.7 67.8
2336 0 0
Report Generated: 31-Mar-1999 at09:52
0.7) 52.5
69.5 51.7 23.6
(100.0) (0-0) (0-0)
2332 0 4
(:4t.0)
(99-8) (0-0) (0.2)
COMMENTS:
REVIEWED BY:
DATE:
Cumulative by Location(vO4.01.97)
ARGUS
418-008:PAGE H-5
Temperature DeviationsReport Location:Room 03
ProtocolNumber. 418-008
Range of Dates: 12-Jun-1998 09:46 to 21-Sep-1998 13:40
Temperature Target Range: Species: Rat
64OF to 79*F
Date
17-jun-I998
17-Jun-1998 17-Jun-1998 17-Jun-1998 17-Jun-1998
28-Jun-1998 28-Jun-I998 08-Jul-I998 08-Jul-1998 08-Jul-1998 09-Jul-1998 09-Jul-1998 09-Jul-1998 09-Jul-1998 09-Jul-1998 09-Jul-I998 09-Jul-1998
rime
03:00 04:00 05:C)O
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
Date
09-Jul-I998
Time
07:00
Temp.
62.4 L
H = Value out of range -High L Value out of range - Low Temp. =Temperature *F
Report Generated: 31-Mar-1999 at 09:09
,.,-@These deviationsdid not adverselyaffectthe outcome or interpretatiofnthe study. The followingdeviation(si)mpacted on the outcome ofthe studyas described:
Study Directo. ,-i
_Date: 3,(-Mft75@9
Deviationsby Location(vO4.01.97)
418-008:PAGE H-6
ARGUS
RelativeHumidity DeviationsReport Location:Room 03
ProtocolNumber. 418-008
Range of Dates: 12-Jun-1998 09:46 to 21-Sep-1998 13:40
Humidity Target Range: Species: Rat
30% to70%
Date
26-Jun-1998 26-Jun-1998 09-Jul-1998 09-Jul-9I98 09-Jul-1998 21-Jul-1998 24-Jul-1998 16-Aug-1998
16-Aug-1998 18-Aug-1998 24-Aug-1998 25-Aug-1998 27-Aug-1998 3D-Aug-1998 31-Aug-1998
15-Sep-1998 16-Sep-1998
rime 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
MH. 70.7H 71.0 H 70.1 H 70.2 H 70.6 H 70.2 H 70.1 H 72.0H 71.0H 70.2H
70.3H 70.6H 72.3H 70.6H 71.2H 70.2H 72.1H
Date
rime
kH.
H u Value out ofrange- High L Value outof range- Low R.H.u RelativeHumidity
Report Generated:31-Mar-1999at09:15
C,-T@hese deviationdsidnotadverselyaffectheoutcome orinterpretatioofnthestudy. The followindgeviation(ism)pactedon theotacome ofthestudyas described:
/7
Study Director,
-Date: 3 M,6t -99
DeviatiboynLsocati(ovnO4.01.97)
418-008:PAGE H-7
ARGUS
Temperature DeviationsReport Location:Room 05
Protocol Number. 418-008
Range of Dates: 27-Jul-I998 12:50 to 28-Dec-I998 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-I998 19-Sep-I998 19-Sep-1998 20-Sep-1998 20-Sep-1 998 20-Sep-1998 20-Sep-1998 20-Sep-1998 2D-Sep-1998 20-Sep-1998 20-Sep-I998
rime
16:W 17:00 18:00 19:00 20:00 21:00 22:00 23:00 00:DO 01:00 02:00 03:00
D4:00 05:00 06:00 07:00
Temp.
80.8 H $1.7 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
ai.0H
81.1 H
al.1H
64OF to79*F
Date
rime Temp.
H z Value out of range - High L Value out of range - Low Temp. a Temperature "F
Report Generated: 31-Mar-I999 at 09:36
',@/These deviationsdid not adverselyaffectthe outcome or interpretationfthe study. The followingdeviation(si)mpacted on the outcome of thestudy as described:
Study Directo
L
Date:
Deviationsby Location(vO4.01.97)
418-008:PAGE H-8
ARGUS
RelativeHurrddityDeviationsReport Location:Room 05
Pmtocal Number. 418-008
Range of Dates:27-Jul-I998 12:50 to 28-Dec-I998 08:29
Humidity Target Range: Species: Rat
Date
25-Sep-I998 26-Sep-19913 28-Sep-1998 30-Sep-1998 09-Oct-1998 14-Oct-1998 14-Oct-1998 03-Nov-1998 07-DOC-1998
Time
14:00 16:00 19:00 17:W Ck2:00 07:00 11:00 191:00 08:00
R.H.
70.7 H 70.1H 70.1H 70.1 H
70.5 H 70.4 H 70.1 H 70.3 H 71.3 H
30% to70%
Date rime
R.H.
H - Value out ofrange -High L Value out of range -Low ILH.- RelativeHumidity
Report Generated: 31-Mar-1999at09:45
--'These deviationsdidnotadverselyaffectheoutcome orInterpretatioofnthe sti The followindgeviation(si)mpactedon the outcome ofthestudyas described:
Study Director.
Date:31-PIP& ,)i
Deviationsby Location(vO4.01.97)
418-008:PAGE H-9
ARGUS
RelativeHumidity DeviationsReport 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-I998 23-Sep-1998 23-Sep-1998 23-Sep-1998
Time 10:00 11:00 12:00 13:00
kH.
29.3L 27.3 L 28.2L 23.6L
30% to70%
Date
rime
RH.
H m Value out of range -High L = Value outof range -Low R.H.- RelativeHumidity
ReportGenerated:31-Mar-1999at10:12
---@ese deviationdsidnotadverselyaffectheoutcome orinterpretatiooftnhestudy. The follovandgeviation(ism)pactedon theoutcome ofthestudyas described:
StudyDirector
Date:
-99
Deviationbsy Location(vD4.01.97)
STATEMENT
APPENDIX I OF THE STUDY DIRECTOR
RESEARCH rg
418-008:PAGE 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 PERINATAUPOSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS SPONSOR'S STUDY NUMBER: 6295.9
IN RATS
STATEMENT OF THE STUDY DIRECTOR
This finalreport accurately reflectsthe raw data obtained during the performance of the study. No deviationsfrom the U.S. Food and Drug Administration(FDA) Good Laboratory PracticeRegulations; FinalRule a ,the Japanese Ministryof Health and Welfare (MHW) Good Laboratory Practice Standard forSafety Studies on Drugs' and the European Economic Community (EEC) Counc# decision on 28 July 1989 on the acceptance by the European Economic Community of an OECD decisionlrecommendation on compliance with principlesof good laboratorypracticecoccurred thataffectedthe qualityor integritoyf the study.
Raa"-tirinqdLn G. York, 0,h.D., DABT Date Associate Directorof Research and Study Director I Argus Research Laboratories,Inc.
---------------------
a.
U.S. Food and Drug Administration. Good Laboratory Practice
Regulations; FinalRule. 21 CFR Part 58.
b.
Japanese Ministry of Health and Welfare (1997). Good Laboratory
Practice Standard for Safety Studies on Drugs, MHW Ordinance Number
21, March 26, 1997.
C.
European Economic Community (1989). Council decision on 28 July
1989 on the acceptance by the European Economic Community of an
OECD decisionlrecommendation
on compliance with principles of good
laboratory practice. Official Journal of the European Communities:
Legislation.32(No. L 315; 28 October): 1-17.
QUALITY ASSURANCE
APPENDIX J UNIT FINAL REPORT STATEMENT
418-008:PAGE J-1
ArgtLsResearch Laboratories,Inc. 905 Sheehy Drive,BuildingA 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
ExecutiveDirectorof Research: MildredS. ChristianP,h.D.,Fellow,ATS
Protocol418-008:
Combined Oral (Gavage) FertilitDye,velopmental and Perinatal/PostantalReproduction ToxicityStudy of PFOS in Rats
Sponsor'sStudy Number: 6295.9
The draftprotocolforthisstudy was auditedforadherence to U.S. Food and Drug Administratio(nFDA) Good LaboratoryPracticeRegulations,Japanese MinistryofHealthand Welfare (MHW); Good LaboratoryPracticeStandard for SafetyStudieson Drugs,and European Economic Community (1989)council decisionon 28 July1989 on the acceptance by the European Economic Community ofan OECD decision/recommendationon compliance withprinciples ofgood laboratorypracticeon 13 MAY 98.
Criticaplhases ofthisstudy were inspected24 times;study information and raw data were auditedsixtimes (see tables1 and 2 fordates and phases/data).
The draftfinalreportand the raw data forthisstudywere compared and auditedforaccuracy,foradherence to protocolrequirements,and foradherence to U.S. Food and Drug Administratio(nFDA) Good LaboratoryPractice Regulations,Japanese Ministryof Healthand Welfare (MHW); Good Laboratory PracticeStandard forSafetyStudieson Drugs, and European Economic Community (1989)councildecisionon 28 July1989 on the acceptance by the European Economic Community of an OECD decision/recommendationon compliance withprincipleosfgood laboratorypracticebetween 05 DEC 98 and 29 APR 99, and forrevisionsrequestedby the Sponsor 18 MAY 99, 7 JUN 99, 9 JUN 99, and forfinalizatioonn 10 JUN 99.
418-008:PAGE J-2
This study was conducted accordingto U.S. Food and Drug Administratio(nFDA) Good LaboratoryPracticeRegulations,Japanese Ministry of Healthand Welfafe (MHW); Good LaboratoryPracticeStandardforSafety Studieson Drugs,and European Economic Community (1989)councildecision on 28 July1989 on the acceptance by the European Economic Community of an OECD decision/recommendationon compliance withprincipleosfgood laboratorypractice.
Nancy J.Gongliewski
Date
QualityAssurance Manager
Heather L.Ra@
M.S.
Date
QualityAssurance Supervisor
and PrincipaAluditor
TABLE 1 CRITICAL PHASES INSPECTED
418-008:PAGE J-3
Test ArticlAedministratio-nGaygqe Dates of inspection:28 IVIAY98,02 JUN 98, 03 SEP 98 Dates resultsreportedtothe Study Directorand Management: 15 JUN 98,15 JUN 98,18 SEP 98
EstrousCycle Evaluation Date ofinspection:11 JUN 98 Date resultsreportedto the Study Directorand Management: 11 JUN 98
Cohabitation
Dates of inspection:08 JUL 98, 04 NOV 98
Dates resultsreportedtothe Study Directorand Management: 14 JUL 98,12 NOV 98
Scheduled Sacrifice-Day 10 Date ofinspection:17 JUL 98 Date resultsreportedto the Study Directorand Management: 03 AUG 98
Test ArticlePreparation
Dates ofinspection:29 JUL 98, 16 SEP 98
Dates resultsreportedtothe Study Directorand Management: 14 AUG 98,24 SEP 98
NaturalDelivM
Dates of inspection:31 JUL 98, 25 NOV 98
Dates resultsreportedtothe Study Directorand Management: 14 AUG 98, 02 DEC 98
Blood Collection
418-008:PAGE J-4 Dates ofinspection:31 JUL 98, 18 AUG 98 Dates resultsreportedtothe Study Directorand Management:
14 AUG 98, 21 AUG 98
Physicaland ReflexDevelopment - Surface Ri-ghtingP,inna Unfoldin-Cl. Eye Opening, Audito[yStartleA,irRighting,PupilConstriction, Sexual Maturation Dates of inspection:31 JUL 98, 13 AUG 98, 18 AUG 98, 28 AUG 98, 11 SEP 98 Dates resultsreportedto the Study Directorand Management: 14 AUG 98, 03 SEP 98, 08 SEP 98, 11 SEP 98,12 SEP 98
Male Necrgpsy Date of inspection:31 JUL 98 Date resultsreportedtothe Study Directorand Management: 14 AUG 98
Necropsy -Dam and LifteSracrifice Dates ofinspection:18 AUG 98, 15 DEC 98 Dates resultsreportedtothe Study Directorand Management: 21 AUG 98,18 DEC 98
Day 21 Wean'Lng Date ofinspection:18 AUG 98 Date resultsreportedto the Study Directorand Management: 08 SEP 98
BehavioralTestinQ-Passive Avoidance, Watermaze, Dates of inspection:25 AUG 98, 08 OCT 98 Dates resultsreportedtothe Study Directorand Management: 12 SEP 98,12 OCT 98
418-008:PAGE J-5
TABLE 2
RAW DATA AUDIT(S)
The followingstudy informationand raw data were audited on 29 SEP 98, 01 OCT 98, 04 OCT 98 TO 05 OCT 98:
Protocol. Protocolamendments. Listofpersonneland computer operatorcodes. Errorcodes and codes forclinicasligh observations. Animal receipt,randomization,physicalexaminationand acclimation. In-lifteransactionrecord. Feed consumption. Necropsy. Organ weights. Tissue packing lists. Editrequests. Deviations. Data reviewpage/pages. Blood collectiodnata and packing lists. Key fortestingfacilitcyomputer backup recordabbreviations.
The resultsofthisauditwere reportedtothe Study Directorand Management on 06 OCT 98.
418-008:PAGE J-6
The followingstudy informationand raw data were audited on 06 OCT 98,12 OCT 98, 02 NOV 98 TO 06 NOV 98:
Animal receiptr,andomization,physicalexaminationand In-lifteransactionrecord. Feed consumption. Estruscycleevaluation. Cohabitation. Caesarean-sectioning. Maternalgross observations Naturaldeliveryobservations. Lifteorbservations. Pup body weights and status. Table of random units. Necropsy. Tissue packing lists. General comments. Reflexand physicaldevelopment. Study maintenance records. Temperature and relativheumidityreports. Feed, water and bedding analyses. Editrequests. Data review page. Blood collectiodnata and packing lists. Pup stomach contents.
acclimation.
The resultsofthisauditwere reportedto the Study Directorand Management on 08 NOV 98.
418-008:PAGE J-7
The followingstudy informationand raw data were audited on 08 NOV 98 to09 NOV 98:
Vehiclereceiptp,reparationand use. Test articlreeceiptp,reparationand use. Test articlpeacking lists.
The resultsofthisauditwere reportedtothe Study Directorand Management on 12 NOV 98.
The followingstudy informationand raw data were audited on 26 JAN 99 to 28 JAN 99:
In-lifteransactionrecord. Feed consumption. Passive avoidance. Watermaze. Genealogy chart. Necropsy. Organ weights. Tissue packing lists. Sexual Maturation. Editrequest.
The resultsofthisauditwere reportedtothe Study Directorand Management on 28 JAN 99.
418-008:PAGE J-8
The followingstudy informationand raw data were audited on 28 JAN 99 to 01 FEB 99:
In-lifteransactionrecord. Feed consumption. Cohabitation. Naturaldeliveryobservations. Lifteorbservations. Pup body weights and status. Passive avoidance. Watermaze. Table ofrandom units. Necropsy. Tissue packing lists. General comments. Sexual maturation. Study maintenance records. Temperature and relativheumidityreports. Feed, water and bedding analyses. Editrequests. Dosage volumes. Data reviewpages.
The resultsofthisauditwere reportedtothe Study Directorand Management on 01 FEB 99.
The followingstudy informationand raw data were audited on 25 JAN 99:
Vehiclereceipt,preparationand use. Test articlreeceipt,preparationand use. Test articlpeacking lists.
The resultsofthisaudi*wLere reportedtothe Study Directorand Management on 28 JAN 99.