Document DDRM56nwVxB9bvdEQeRbbMjbn
3M MEDICAL DEPARTMANT CORPORATE TOXICOLOGY
To: John Butenhoff Andrew Seacat
From: Marvin Case
Date: 5 April 2000
Subject: Liver Slide Review
conclusons re 1 have completed
the PFOS chronic
mstyudmyi.crMosycofpiincdirnegvsiaerweofltishteed,lbivyergrsoeucpt,ioonns
of the 14-week
attached pages.
sacrifice rats
My overall
on
1) Centrolobular hepatocyte hypertrophy is present in group 5 males and females. In the
`males, but not in the females, the hepatocyte hypertrophy is accompanied by increased.
number of cells with lipid type cytoplasmic vacuoles.
2) Centrolobular hepatocyte hypertrophisy present in group 4 males but there is no increase
in 3)
cells with lipid type cytoplasmic vacuoles. Centrolobular hepatocyte hypertrophy is not
present
in
group
4
females.
4)
5)
Group 2 and 3 animals (male
The centrolobular hepatocyte
and female)
hypertrophy
were not different from controls.
is a compound-related change but
is
an
adaptive:
change and not necessarily an adverse change. When increased number of cells with lipid
htiyspteoclyogtiocplcahsamnigcesv.amcuyolNesOoAcEcuLrri,s
1 would consider
group 4, male &
that an adverse
female; and my
change. Thus, for
compound-related
liver
NOEL
is group 3 males and group 4 females.
/Wes --Cag. arvin T. Case, DVM. PhD
002364
Findings on Microscopic Review of Liver.Sections From 14-week Sacrifice of PFOS Rats
(review done by Marvin Case, March 2000)
Group 1 Males
Histologic Finding
Animal Number
Foci of mononuclear cells
92509 C92511 C92521 C92528 C92532
1
1
1
1
1
Hepatocytes with cytoplasm vacuoles,
appearance of hydrophilic droplets.
1
2
1
1
-
`Hepatoctes with cytoplasm vacuoles,
`appearance of lipid droplets
1
-
1
1-
Grade key -- 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement)
- = finding not observed
002365
FindinFgrsoomn 1Mdi-cwreoseckoSpaiccriRfeivceieowf PofFLOiSveRratSesctions (review done by Marvin Case, March 2000) Group 2 Males
Histologic Finding
Animal Number
Foci of mononuclear cells
C92593 92600 C9266 C92621 C92627
1-
1
-1
Hepatocytes with cytoplasm vacuoles,
appearance of hydrophilic droplets
1
1
1
--
Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets
-
-
1
1-
Grade key
1 = minimal (< 10% involvement) 2 = mild (< 30% involvement)
3 = moderate (< 60% involvement
4= marked (> 60% involvement)
-= finding not observed
.
002366
FindinFgrsoomn 1Mdi-crwoeseckoSpaiccriRfeivceieowf PofFLOiSveRratSesctions (review done by Marvin Case, March 2000) Group 3 Males
Histologic Finding
Animal Number
Foci of mononuclear cells
92640 C92645 C92662 C92676 C92684
11
1-1
Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets
2
1
1-2
aHepppaetaorcatnecse woiftlhipciydtdorpolplaestms.vacuoles, - - - - -
No histologic findings
x
Grade key
21 == mmiilndim(a<l3(0<%1i0n%voilnvveomlevnetm)ent) 3 = moderate (< 60% involvement 4= marked (> 60% involvement) - = finding not observed
:
002367
FindinFgrsoomn M1i4c-rwoeseckoSpaiccriRfeivceieowf PofFLOiSveRraStesctions (review done by Marvin Case, March 2000) Group 4 Males
Histologic Finding
Animal Number
Foci of mononuclear cells
C92713 C92714 C2719 C9222 C9228
11
1
11
Haepppaetaorcayntceesofwihtyhdrcoypthoiplliacsdmrovpalceutosles, - -
2--
Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets
2
2
2
12
Hypertrophic hepatocytes, generally centrolobular
3 3 2 23
Grade key - 21 == mmiilndim(a<l3(0<%1i0n%voilnvveomlevnetm)ent) 34== mmoadrekreadte(>(<606%0%inivnovlovlevmeemnetn)t - = finding not observed
002368
Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 5 Males
Histologic Finding
Animal Number
Foci of mononuclear cells
C2765 C92777 C92789 C9279 C92812
11
1
11
Hepatocytes with cytoplasm vacuoles,
appearance of hydrophilic droplets
2
-
---
Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets
1
3
2
33
Hypertrophic hepatocytes, `generally centrolobular
3 4 4 34
Grade key - 21 == mmiilndim(a<l3(0<%1i0n%voilnvveomlevnetm)ent) 3 = moderate (< 60% involvement 4= marked (> 60% involvement) - = finding not observed
002369
FindinFgrsoomn 1M4i-cwreoeskcoSpaiccriRfeivcieeowf PofFLOiSveRraStesctions (review done by Marvin Case, March 2000) Group 1 Females
Histologic Finding
Animal Number
Foci of mononuclear cells
92880 92887 C92898 C92903 C92905
11
-1-
Haepppaetaorcayntceesofwihtyhdrcoypthoiplliacsdmrovpalceutosles, 1 -
-
1
1
`Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets
1
1
1
1-
Grade key 21 == mmiilndim(a<l3(0<%1i0n%voilnvveomlevnetm)ent) 34== mmoadrekreadte(>(<606%0%inivnovlovlevmeemnetn)t - = finding not observed
002370
Findings on Microscopic Review of Liver Sections From 1d-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000)
Group 2 Females
`Histologic Finding
Animal Number
Foci of mononuclear cells
C9244 C92962 C92967 C92978 C92987
--
-
11
Haepppaetaorcanycteesofwihtyhdrcoypthoiplliacsdmrovpalceutosles, - 1
-
1
-
Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets
1
-
-
1-
No histologic findings
x
Grade key - 21 == mmiilndim(a<l3(0<%1i0n%voilnvveomlevnetm)ent) 3 = moderate (< 60% involvement 4-== mfainrdkiendg n(>ot6o0b%seirnvveodlvement)
}
002371
FindinFgrsoomn 1Mi4c-rwoeseckoSpaiccriRfeivceieowf PofFLOiSveRraStesctions (review done by Marvin Case, March 2000) Group 3 Females
Histologic Finding
Animal Number
Foci of mononuclear cells
C92993 C9300 C93018 C93023 C93035
--
1 - o-
aHepppaetaorcayntceesofwihtyhdrcoypthoiplliacsdmrovpalceutosles, - -
1
1
Haepppaetaorcatnecse woiftlhipciydtdorpolpalsetmsvacuoles, -
-
-
n.
No histologic findings
Xx + no slide sent for review
Grade
key
-
1 2.=
=
mmiilndim(a<l3(0<%1i0n%voilnvveomlevnetm)ent)
3 = moderate (< 60% involvement
+= marked (> 60% involvement)
- = finding not observed
002372
FindinFgrsoomn 1Mdi-cwroeseckoSpaiccriRfeivceieowf PofFLOiSveRratSesctions (review done by Marvin Case, March 2000) Group 4 Females
Histologic Finding
Animal Number
Foci of mononuclear cells
Co3051 C93064 C93071 C93085 C93109
11
-
1-
Haepppaetaorcayntceesofwihtyhdrcoypthoiplliacsdmrovpalceutosles, 1 -
--
1
Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets
-
-
-
1-
No histologic findings
x
Grade
key
-
1 2
= =
minimal (< 10% involvement) mild (< 30% involvement)
3 = moderate (< 60% involvement
4-== mfainrdkiendg n(o>t6o0bs%erivnevdo.lvement)
002373
FindinFgrsoomn 1Mi4c-rwoeseckoSpaiccriRfeivceieowf PofFLOiSveRratSesctions (review done by Marvin Case, March 2000) Group 5 Females
Histologic Finding
Animal Number
Foci of mononuclear cells
C3111 93127 C93143 C931SS C3169
--
1
--
Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets
-
2
2- -
Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets
-
-
1
-1
Hypertrophic hepatocytes, generally centrolobular
34
3
23
Grade key - 21 == mmiilndim(a<l3(0<%1i0n%voilnvveomlevnetm)ent) 3 = moderate (< 60% involvement 4= marked (> 60% involvement) - = finding not observed
:
002374