Document NG5Em47g4JKkZdze7XwQeEJ6y
31NIrvlEDICALDEPART?vlAiNT
CORPORATE TOXICOLOGY
To: John Butenhoff Andrew Seacat
From: Marvin Case
Date: 5 April 2000
Subject:Liver SlideReview
I have completed my microscopicreview ofthe liversectionsofthe 14-week sacrificreatson thePFOS chronicstudy.My findingsarelistedb,y group,on attachedpages. My overall conclusionsare: 1)Centrolobularhepatocytehypertrophyispresentingroup 5 males and females. In the males, but not inthe females,the hepatocytehypertrophyisaccompanied by increased number ofcellswith lipidtypecytoplasmicvacuoles. 2) Centrolobularhepatocytehypertrophyispresentin group 4 males but thereisno increase incellswith lipidtypecytoplasmicvacuoles. 3) Centralobularhepatocvtehypertrophyisnot presentingroup 4 females. 4) Group 2 and 3 animals (maleand female)were notdifferenftrom controls. 5)The centrolobulahrepatocytehypertrophyisa compound-relatedchange but isan adaptive chan!zeand not necessarilayn adversechange. When increasednumber of cellswith lipid t.yPe cy.toplasmicvacuolesoccurr,Iwould considerthatan adversechan0ge. Thus, forliver histolooichan2es,m-...;N'OAELisgroup 4,male & female;and my compound-relatedNOEL is2roup 3 males and --roup4 females.
i&in T. Case,DVNI. PhD
Findingosn NEcroscopiRceviewofLiverSections From 14-weekSacrifiocfePFOS Rats
(reviedwonebyMarvinCaseM,arch2000)
Group1 Males
HistolozFiicnding
AnimalNumber
Foci of mononuclearcells
C92509 C92511 C92521 C92528 C92532
Hepatocyteswithcytoplasmvacuoles,
appearanceof hydrophilicdroplets
1
Hepatocteswith cytoplasmvacuoles,
appearanceof lipiddroplets
1
Grade key - 1= minimal(< 10% involvement) 2 = mild (<30% involvement) 3 = moderate(< 60% involvement 4 = marked (> 60% involvement) -= findincnyotobserved
Findingosn NflcroseoRpeivciewofLiverSections From 14-weekSacrificoefPFOS Rats
(reviedwone by MarvinCase,March 2000)
Group2 Males
Histolo2iFcindins!
AnimalNumber
Foci of mononuclear cells
C92593 C92600 C92616 C92621 C92627
1
-
1
1
Hepatocytes with cytoplasm vacuoles,
appearance of hydrophilicdroplets
1
1
1
Hepatoctes with cy-toplasmvacuoles,
appearance of lipiddroplets
-
-
1
Grade key - I 2
4
minimal (< 10% involvement) mild (< 30% involvement) moderate (< 60% involvement marked (> 60% involvement) findincn,ot obser-ved
Findingosn MicroscopiRceviewofLiverSections From 14-weekSacriflcoefPFOS Rats
(reviedwoneby MarvinCase,March 2000)
Group3 Males
HistologiFcinding Foci of mononuclear cells
Animal Number C92640 C92645 C92662 C92676 C92684
Hepatocytes with cytoplasm vacuoles,
appearance of hydrophilicdroplets
2
Hepatoctes with cytoplasm vacuoles, appearance of lipiddroplets
No histolo2ifcindin!zs
x
Grade ke,,-. I 2 3 4
minimal (< 10% involvement) niild(< 30% involvement) moderate (< 60% involvement marked (> 60% involvement) findincnyot observed
Findingosn MicroscopiRceviewofLiverSections From 14-weekSacrifiocfePFOS Rats
(reviedwonebyMarvinCase,March2000)
Group4 Males
HistolotFziincdin Fociof mononuclearcells
AnimalNumber
C92713 C92714 C92719 C92722 C92728
1
1
1
1
1
Hepatocyteswith cytoplasmvacuoles,
appearanceofhydrophilicdroplets
-
-
2
-
-
Hepatocteswith cytoplasmvacuoles,
appearanceof lipiddroplets
2
2
2
1
2
Hypertrophichepatocytes, generallycentrolobular
3
3
2
1)
3
Grade key - 1 minimal(< 10% involvement) '-) niild(<30% involvement) 3 moderate(< 60% involvement 4 marked (>60% involvement) findingnot observed
FindingosnNhcroscopiRceviewofLiverSections From 14-weekSacrificoefPFOS Rats
(reviedwoneby MarvinCase,March2000)
Group 5 Males
HistoloizFiicndin
AnimalNumber
Foci of mononuclear cells
C92765 C92777 C92789 C92799 C92812
1
1
1
1
1
Hepatocyteswith cytoplasm vacuoles,
appearance of hydrophilicdroplets
2
-
-
-
-
Hepatoctes with cvtoplasm vacuoles,
appearance of lipiadroplets
1
3
2
3
3
Hypertrophichepatocytes, c,enerallcyentrolobular
3
4
4
3
4
Grade key - I = minimal (< 10% involvement) 2 = n-iil(d< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = findincn,ot observed
Findingson NficroscopiRceview ofLiverSections From 14-week Sacrificeof PFOS Rats
(reviewdone by Marvin Case,March 2000)
Group 1 Females
HistoloeicFindin2
Animal Number
Foci of mononuclear cells
C92880 C92887 C92898 C92903 C92905
Hepatocytes with cytoplasm vacuoles,
appearance of hydrophilicdroplets
I
Hepatocteswith cytoplasm vacuoles, appearance of lipiddroplets
Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) = moderate (< 60% involvement 4 = marked (> 60% involvement) findincn,ot observed
Findingosn NEcroscopiRceviewofLiverSections From 14-weekSacrifiocfePFOS Rats
(reviedwonebyMarvinCaseM,arch2000)
Group 2 Females
HistoloLF,iincdinEr
AnimalNumber
Foci ofmononuclear cells
C92944 C92962 C92967 C92978 C92987
Hepatocyteswith cytoplasmvacuoles, appearanceof hydrophilicdroplets
Hepatocteswith c,,-topslmavacuoles, appearanceof lipi@droplets
No histologifcindings
x
Grade key - 1 2 3 4
minimal(< 10% involvement) mild(<30% involvement) moderate(<60% involvement marked (> 60% involvement) findincn,ot observed
Findingosn NEcroscopiRceviewofLiverSections From 14-weekSacrifiocfePFOS Rats
(reviedwonebyMarvinCase,March2000)
Group3 Females
HistolosF!iincdin Foci of mononuclearcells
AnimalNumber
C92993 C93000 C93018 C93023 C93035 1
Hepatocyteswith cytoplasmvacuoles, appearanceof hydrophilicdroplets
1
1
Hepatocteswith cytoplasmvacuoles, appearanceof lipiddroplets
-
-
No histologifcindings
x
x
no slidesentforreview
Grade key - I 2 0 4
minimal(< 10% involvement) mild(<30% involvement) moderate(< 60% in;volvement marked (>60% involvement) findincn,ot observed
Findingson NEcroscopicReview ofLiverSections From 14-weekSacrificoefPFOS Rats
(reviewdone by Marvin Case,March 2000)
Group 4 Females
Histolos!iFcindinL3, Fociof mononuclear cells
Animal Number C93051 C93064 C93071 C93085 C93109
Hepatocyteswith cytoplasmvacuoles, appearanceofhydrophilicdroplets
Hepatocteswith cytoplasmvacuoles,
appearanceof lipiddroplets
1
No histolocifcindincrs
x
Grade key - 1 2 3 4
minimal (< 10% involvement) mild (<30% involvement) moderate(<60% involvement marked (>60% involvement) findincn,ot observed
FindingosnNEcroscopiRceviewofLiverSections From 14-weekSacrifiocfePFOS Rats
(reviedwonebyMarvinCase,March2000)
Group 5 Females
HistoloLyiFcindini!
Animal Number
Foci of mononuclearcells
C93111 C93127 C93143 C93155 C93169
-
1
Hepatocyteswith cytoplasm vacuoles, appearanceof hydrophilicdroplets
2
2
Hepatocteswith cytoplasmvacuoles,
appearanceof lipiddroplets
-
-
1
1
Hypertrophichepatocytes, generallycentrolobular
3
4
3
2
3
Grade key - I = minimal(< 10% involvement) 2 = mild (<30% involvement) 3 = moderate(<60% involvement 4 = marked (> 60% involvement) - = findincnyotobserved