Document K6e5Vp4Mdo5KYYekaxRwYayxo

ARa%-olHl 3M MEDICAL DEPARTMANT CORPORATE TOXICOLOGY To: John Butenhoff Andrew Seacat From: Marvin Case Date: 5 April 2000 Subject: Liver Slide Review I have completed my microscopic review of the liver sections of the 14-week sacrifice rats on the PFOS chronic study. My findings are listed, by group, on attached pages. My overall conclusions are: 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 hypertrophy is present in group 4 males but there is no increase in cells with lipid type cytoplasmic vacuoles. 3) Centrolobular hepatocyte hypertrophy is not present in group 4 females. 4) Group 2 and 3 animals (male and female) were not different from controls. 5) The centrolobular hepatocyte hypertrophy is a compound-related change but is an adaptive change and not necessarily an adverse change. When increased number of cells with lipid type cytoplasmic vacuoles occurr, I would consider that an adverse change. Thus, for liver histologic changes, my NOAEL is group 4, male & female; and my compound-related NOEL is group 3 males and group 4 females. Marvin 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 C92509 C92511 C92521 C92528 C92532 11 111 Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets 1 2 11- Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets 1-11 Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = finding not observed 002365 Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 2 Males Histologic Finding Animal Number Foci of mononuclear cells C92593 C92600 C92616 C92621 C92627 1-1-1 Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets 11 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 Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 3 Males Histologic Finding Animal Number Foci of mononuclear cells C92640 C92645 C92662 C92676 C92684 11 1 -1 Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets 2 1 1 -2 Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets No histologic findings X Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = finding not observed 002367 Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 4 Males Histologic Finding Animal Number Foci of mononuclear cells C92713 C92714 C92719 C92722 C92728 11 1 11 Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets - - 2- Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets 222 12 Hypertrophic hepatocytes, generally centrolobular 332 23 Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = 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 C92765 C92777 C92789 C92799 C92812 11 1 11 Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets 2 - -- - Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets 13 2 33 Hypertrophic hepatocytes, generally centrolobular 344 34 Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = finding not observed 002369 Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 1 Females Histologic Finding Animal Number Foci of mononuclear cells C92880 C92887 C92898 C92903 C92905 11 -1 Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets 1 - -1 1 Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets 11 11- Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = finding not observed 002370 Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 2 Females Histologic Finding Animal Number Foci of mononuclear cells C92944 C92962 C92967 C92978 C92987 11 Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets - 1 1 Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets 1- - 1 No histologic findings X Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = finding not observed 002371 Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 3 Females Histologic Finding Animal Number Foci of mononuclear cells C92993 C93000 C93018 C93023 C93035 - 1 *** Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets - 11 Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets No histologic findings XX *** no slide sent for review Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = finding not observed 002372 Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 4 Females Histoloeic Finding Animal Number Foci of mononuclear cells C93051 C93064 C93071 C93085 C93109 11 - 1- Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets 1 1 Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets 1 No histologic findings X Grade key - 1 = minimal (<10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = finding not observed 002373 Findings on Microscopic Review of Liver Sections From 14-week Sacrifice of PFOS Rats (review done by Marvin Case, March 2000) Group 5 Females Histologie Finding Animal Number Foci of mononuclear cells C93111 C93127 C93143 C93155 C93169 1 Hepatocytes with cytoplasm vacuoles, appearance of hydrophilic droplets 22 Hepatoctes with cytoplasm vacuoles, appearance of lipid droplets 1 -1 Hypertrophic hepatocytes, generally centrolobular 34 3 23 Grade key - 1 = minimal (< 10% involvement) 2 = mild (< 30% involvement) 3 = moderate (< 60% involvement 4 = marked (> 60% involvement) - = finding not observed 002374