TDMS Study 05075-01 Pathology Tables
INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)
DIPHENYLHYDANTOIN
NTP Experiment-Test: 05075-01 Report: PEIRPT03
Study Type: CHRONIC Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
Facility: Battelle Columbus Laboratory
Chemical CAS #: 57-41-0
Lock Date: None
Cage Range: All
Reasons For Removal: All
Removal Date Range: All
Treatment Groups: Include All
a Number of animals examined microscopically at site and number of animals with lesion
Page 1
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50 50 50 50 50
Early Deaths
Moribund Sacrifice 17 19 19 9 19 15
Natural Death 2 2 4 4 2 2
Survivors
Terminal Sacrifice 31 29 27 37 28 33
Moribund Sacrifice 1
Animals Examined Microscopically 50 50 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Cecum (48) (20) (20) (9) (19) (16)
Edema 1 (5%)
Inflammation, Chronic Active, Focal 1 (2%)
Ulcer 1 (2%) 1 (5%)
Submucosa, Edema 1 (2%) 1 (5%)
Intestine Large, Colon (49) (20) (20) (10) (20) (16)
Parasite Metazoan 1 (2%) 1 (5%) 1 (6%)
Intestine Large, Rectum (49) (20) (20) (9) (20) (16)
Parasite Metazoan 2 (4%)
Liver (50) (49) (50) (50) (50) (50)
Basophilic Focus 40 (80%) 35 (71%) 30 (60%) 33 (66%) 35 (70%) 31 (62%)
Clear Cell Focus 1 (2%) 2 (4%) 1 (2%) 1 (2%)
Cyst 1 (2%) 1 (2%) 1 (2%)
Eosinophilic Focus 3 (6%) 1 (2%) 1 (2%)
Fatty Change 5 (10%) 3 (6%) 3 (6%) 1 (2%) 2 (4%)
Fatty Change, Diffuse 2 (4%)
Granuloma, Multiple 1 (2%)
Hepatodiaphragmatic Nodule 1 (2%) 1 (2%)
Mixed Cell Focus 1 (2%) 1 (2%) 1 (2%) 2 (4%)
Necrosis, Coagulative, Focal 1 (2%)
Necrosis, Coagulative, Multifocal 1 (2%) 2 (4%) 1 (2%) 1 (2%) 1 (2%)
Necrosis, Caseous 1 (2%)
Necrosis, Caseous, Multifocal 1 (2%) 1 (2%)
Regeneration, Focal 2 (4%) 1 (2%) 2 (4%) 1 (2%)
Centrilobular, Cytomegaly 7 (14%) 22 (44%) 24 (48%) 29 (58%)
Sinusoid, Angiectasis 3 (6%) 1 (2%)
Sinusoid, Angiectasis, Multifocal 1 (2%)
Mesentery (3) (6) (3) (1) (1) (2)
Inflammation, Chronic 1 (33%) 1 (17%)
Artery, Inflammation, Chronic 1 (33%)
Fat, Necrosis 1 (33%) 3 (50%) 3 (100%) 1 (100%) 1 (50%)
Pancreas (50) (20) (23) (10) (21) (16)
Fibrosis, Focal 1 (4%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 2
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Acinus, Atrophy 21 (42%) 7 (35%) 13 (57%) 5 (50%) 5 (24%) 5 (31%)
Salivary Glands (50) (21) (22) (12) (22) (17)
Ectopic Tissue 1 (5%)
Acinus, Parotid Gland, Atrophy 1 (2%)
Parotid Gland, Inflammation, Chronic 1 (6%)
Stomach, Forestomach (49) (20) (23) (11) (22) (16)
Edema 1 (6%)
Inflammation, Chronic 1 (5%)
Epithelium, Acanthosis, Diffuse 1 (5%)
Epithelium, Hyperkeratosis, Diffuse 1 (5%)
Submucosa, Edema 1 (2%)
Stomach, Glandular (49) (20) (20) (11) (20) (16)
Inflammation, Chronic 1 (5%)
Inflammation, Subacute 1 (5%) 1 (5%)
Ulcer 1 (9%)
Mucosa, Inflammation, Multifocal, Necrotizing 1 (5%)
Mucosa, Proliferation, Focal 1 (5%)
Tooth (1)
Gingiva, Inflammation, Chronic 1 (100%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Blood Vessel (1)
Aorta, Inflammation, Chronic, Focal 1 (100%)
Heart (50) (21) (24) (13) (22) (17)
Autolysis 1 (4%)
Coronary Artery, Inflammation, Chronic 1 (2%) 1 (4%) 1 (6%)
Myocardium, Degeneration, Diffuse 1 (5%)
Myocardium, Degeneration, Multifocal 32 (64%) 13 (62%) 13 (54%) 6 (46%) 8 (36%) 5 (29%)
Myocardium, Fibrosis, Focal 1 (2%)
Myocardium, Inflammation, Chronic, Multifocal 2 (4%) 1 (4%)
Valve, Inflammation, Chronic 1 (4%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Gland, Cortex (50) (21) (23) (13) (20) (17)
Atrophy 1 (6%)
Atypia Cellular, Focal 1 (2%)
Congestion 1 (2%)
Hyperplasia, Nodular 19 (38%) 3 (14%) 7 (30%) 1 (8%) 9 (45%) 5 (29%)
Hypertrophy, Focal 3 (6%) 1 (5%) 2 (12%)
Hypertrophy, Multifocal 1 (5%)
Necrosis, Coagulative 1 (5%)
Vacuolization Cytoplasmic, Focal 1 (5%) 2 (15%) 1 (6%)
Adrenal Gland, Medulla (49) (21) (23) (13) (22) (17)
a Number of animals examined microscopically at site and number of animals with lesion
Page 3
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Hyperplasia, Nodular 4 (8%) 3 (14%) 6 (26%) 7 (32%) 4 (24%)
Necrosis, Coagulative 1 (5%)
Vacuolization Cytoplasmic, Focal 1 (5%)
Parathyroid Gland (45) (18) (21) (12) (19) (17)
Hyperplasia, Diffuse 1 (2%) 1 (5%) 1 (5%)
Hyperplasia, Nodular 1 (2%)
Pituitary Gland (50) (41) (43) (32) (35) (33)
Angiectasis, Focal 1 (3%)
Autolysis 1 (3%)
Pars Distalis, Angiectasis, Focal 2 (5%) 5 (12%) 2 (6%) 4 (11%) 6 (18%)
Pars Distalis, Angiectasis, Multifocal 1 (2%)
Pars Distalis, Cyst 3 (6%) 4 (10%) 5 (12%) 6 (19%) 2 (6%) 5 (15%)
Pars Distalis, Hyperplasia, Nodular 4 (8%) 3 (7%) 7 (16%) 3 (9%) 6 (17%) 2 (6%)
Pars Intermedia, Cyst 1 (3%)
Thyroid Gland (48) (20) (19) (9) (20) (17)
Cyst 1 (5%)
C-Cell, Hyperplasia 33 (69%) 14 (70%) 14 (74%) 8 (89%) 16 (80%) 16 (94%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Clitoral Gland (45) (21) (24) (14) (24) (20)
Autolysis 1 (4%)
Hyperplasia 2 (4%) 2 (10%)
Inflammation, Chronic 6 (13%) 4 (19%) 4 (17%) 4 (29%) 2 (8%) 4 (20%)
Inflammation, Chronic Active 3 (7%) 2 (10%) 1 (5%)
Duct, Dilatation 1 (2%) 1 (5%) 2 (8%) 3 (21%) 1 (4%) 2 (10%)
Ovary (49) (23) (26) (19) (26) (21)
Inflammation, Chronic 5 (10%) 1 (4%) 1 (5%)
Bilateral, Periovarian Tissue, Cyst 1 (4%)
Corpus Luteum, Congestion 1 (2%)
Follicle, Cyst 1 (2%) 1 (4%)
Periovarian Tissue, Cyst 5 (10%) 4 (17%) 5 (19%) 7 (37%) 4 (15%) 5 (24%)
Periovarian Tissue, Necrosis, Caseous 1 (5%)
Vein, Congestion 1 (5%)
Uterus (50) (26) (26) (25) (35) (31)
Dilatation 2 (8%) 1 (4%) 3 (12%) 2 (6%) 1 (3%)
Hemorrhage 1 (3%)
Hyperplasia 1 (4%)
Hyperplasia, Cystic 1 (3%)
Prolapse 3 (6%) 1 (4%)
Cervix, Inflammation, Suppurative 1 (4%) 2 (6%) 5 (16%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 4
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM - CONT
Endometrium, Bacterium 1 (2%)
Endometrium, Hyperplasia, Cystic 9 (18%) 2 (8%) 5 (20%) 6 (17%) 2 (6%)
Endometrium, Hyperplasia, Nodular 1 (3%)
Endometrium, Necrosis, Coagulative 1 (2%) 1 (3%)
Lumen, Hemorrhage 1 (3%)
Wall, Bacterium 1 (4%)
Wall, Cyst 1 (4%)
Wall, Inflammation, Chronic Active 2 (4%)
Wall, Inflammation, Necrotizing 1 (2%) 1 (4%)
Vagina (2) (1) (2) (4) (7)
Cyst 1 (100%) 1 (50%) 4 (100%) 7 (100%)
Lamina Propria, Inflammation, Necrotizing 1 (50%)
Lumen, Exudate 1 (50%)
Wall, Edema 1 (50%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Blood (1)
Polychromasia 1 (100%)
Bone Marrow (50) (21) (22) (12) (22) (17)
Femoral, Angiectasis 1 (2%)
Femoral, Hyperplasia 7 (14%) 8 (38%) 11 (50%) 4 (33%) 14 (64%) 8 (47%)
Femoral, Hyperplasia, Re Cell 1 (2%)
Femoral, Hypoplasia 2 (4%)
Femoral, Myelofibrosis 1 (8%) 2 (12%)
Lymph Node (49) (21) (26) (12) (23) (22)
Mandibular, Hemorrhage, Focal 1 (4%)
Mandibular, Infiltration Cellular,
Polymorphonuclear 1 (5%)
Mandibular, Infiltration Cellular, Histiocyte 1 (5%)
Mandibular, Inflammation, Chronic 1 (4%)
Mediastinal, Pigmentation, Hemosiderin 1 (4%)
Renal, Necrosis, Caseous 1 (5%)
Sinus, Ectasia 1 (4%)
Sinus, Mandibular, Ectasia 2 (9%) 1 (5%)
Lymph Node, Mesenteric (1) (1) (4) (1) (6) (6)
Sinus, Ectasia 1 (25%) 1 (17%) 3 (50%)
Spleen (50) (26) (29) (17) (22) (21)
Autolysis 1 (6%)
Fibrosis, Diffuse 1 (6%)
Fibrosis, Focal 1 (3%)
Granuloma, Single 1 (2%)
Hematopoietic Cell Proliferation 3 (6%) 2 (8%) 1 (3%) 1 (6%) 1 (5%) 1 (5%)
Necrosis, Coagulative 1 (2%) 1 (3%) 1 (5%)
Capsule, Cyst 1 (6%)
Capsule, Hemorrhage 1 (4%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 5
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Capsule, Inflammation, Focal, Subacute 1 (3%)
Thymus (46) (18) (21) (12) (19) (17)
Hemorrhage, Multifocal 1 (5%)
Arteriole, Inflammation, Chronic 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (24) (31) (19) (25) (23)
Hyperplasia, Cystic 32 (64%) 15 (63%) 12 (39%) 6 (32%) 15 (60%) 12 (52%)
Duct, Inflammation, Chronic Active 1 (2%)
Skin (50) (22) (23) (14) (26) (18)
Acanthosis 1 (2%) 1 (5%) 1 (4%) 1 (6%)
Hyperkeratosis 1 (2%) 1 (5%) 1 (4%) 1 (6%)
Inflammation, Chronic 1 (2%) 1 (5%)
Inflammation, Necrotizing 1 (5%)
Tail, Acanthosis, Focal 1 (4%)
Tail, Hyperkeratosis, Focal 1 (4%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (21) (24) (13) (22) (17)
Hyperostosis 1 (2%)
Femur, Osteopetrosis 2 (4%) 1 (8%)
Tibia, Proliferation 1 (4%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (21) (23) (13) (22) (17)
Infarct 1 (5%) 1 (4%)
Infarct, Multiple 1 (4%)
Inflammation, Multifocal, Necrotizing 1 (5%)
Hypothalamus, Compression 15 (30%) 8 (38%) 5 (22%) 4 (31%) 4 (18%) 5 (29%)
Hypothalamus, Hemorrhage, Multifocal 1 (4%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (22) (24) (13) (23) (18)
Congestion 1 (2%) 1 (4%)
Alveolar Epithelium, Hyperplasia 1 (2%)
Alveolus, Hemorrhage 3 (14%) 1 (6%)
Alveolus, Hemorrhage, Multifocal 2 (8%)
Alveolus, Inflammation, Multifocal,
Suppurative 1 (8%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 6
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM - CONT
Bronchus, Foreign Body 1 (2%) 1 (8%)
Bronchus, Inflammation, Multifocal,
Suppurative 1 (8%)
Interstitium, Inflammation, Chronic, Focal 3 (6%) 2 (9%)
Interstitium, Inflammation, Chronic,
Multifocal 1 (4%) 2 (15%) 1 (4%)
Nose (50) (21) (23) (13) (22) (17)
Nares, Inflammation, Chronic Active 1 (5%)
Sinus, Inflammation, Chronic Active 1 (5%)
Trachea (50) (21) (22) (12) (22) (17)
Inflammation, Subacute 1 (6%)
Lamina Propria, Inflammation, Chronic 1 (2%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Ear (3) (1) (1) (1)
Middle Ear, Inflammation, Chronic Active 1 (100%)
Eye (9) (6) (6) (7) (7) (9)
Anterior, Synechia 1 (14%)
Bilateral, Lens Crystalline, Cataract 1 (11%)
Cornea, Inflammation, Suppurative 1 (14%)
Lens Crystalline, Cataract 7 (78%) 5 (83%) 6 (100%) 6 (86%) 4 (57%) 8 (89%)
Lids, Inflammation, Suppurative 1 (11%)
Posterior Chamber, Inflammation, Chronic 3 (50%) 4 (67%) 4 (57%) 5 (71%) 8 (89%)
Retina, Atrophy 7 (78%) 2 (33%) 3 (50%) 1 (14%) 1 (14%)
Sclera, Mineralization, Multifocal 1 (17%) 1 (14%)
Harderian Gland (3) (1) (3) (1) (1)
Inflammation, Chronic, Multifocal 2 (67%) 2 (67%) 1 (100%) 1 (100%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (21) (23) (13) (22) (17)
Hydronephrosis 1 (2%)
Inflammation, Multifocal, Necrotizing 1 (2%) 1 (5%)
Nephropathy, Multifocal 32 (64%) 11 (52%) 10 (43%) 5 (38%) 9 (41%) 6 (35%)
Thrombosis 1 (8%)
Glomerulus, Inflammation,
Membranoproliferative 1 (5%)
Papilla, Bacterium 1 (5%)
Pelvis, Renal Tubule, Bacterium 1 (2%)
Urinary Bladder (50) (21) (20) (11) (20) (16)
Ectasia 1 (6%)
Inflammation, Acute 1 (5%)
Inflammation, Chronic 1 (5%)
Lumen, Hemorrhage 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 7
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT
Mucosa, Hyperplasia, Papillary 1 (5%)
Transitional Epithelium, Hyperplasia, Diffuse 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 8
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50
Early Deaths
Moribund Sacrifice 11 13
Natural Death 1 1
Drowned 5
Survivors
Terminal Sacrifice 37 31
Moribund Sacrifice 1
Animals Examined Microscopically 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Cecum (50) (49)
Ulcer 1 (2%)
Intestine Large, Colon (50) (50)
Dilatation 1 (2%)
Inflammation, Chronic, Focal 2 (4%)
Parasite Metazoan 3 (6%) 3 (6%)
Intestine Small, Ileum (48) (50)
Inflammation, Chronic Active, Focal 1 (2%)
Liver (50) (50)
Basophilic Focus 6 (12%) 3 (6%)
Clear Cell Focus 2 (4%) 3 (6%)
Eosinophilic Focus 5 (10%) 2 (4%)
Hepatodiaphragmatic Nodule 2 (4%)
Mixed Cell Focus 1 (2%) 4 (8%)
Necrosis, Coagulative, Multifocal 1 (2%)
Regeneration, Focal 1 (2%)
Centrilobular, Cytomegaly 42 (84%) 38 (76%)
Sinusoid, Angiectasis 1 (2%)
Pancreas (50) (50)
Ectopic Tissue 1 (2%)
Acinus, Atrophy 22 (44%) 14 (28%)
Acinus, Hypertrophy, Focal 1 (2%)
Salivary Glands (49) (50)
Acinus, Parotid Gland, Atrophy 1 (2%)
Stomach, Forestomach (50) (50)
Hyperkeratosis 1 (2%)
Inflammation, Subacute 1 (2%)
Inflammation, Suppurative 1 (2%)
Stomach, Glandular (50) (50)
Mucosa, Proliferation, Focal 1 (2%)
Tooth (3) (1)
Dysplasia 1 (33%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 9
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Gingiva, Inflammation, Chronic Active 1 (33%) 1 (100%)
Gingiva, Inflammation, Suppurative 1 (33%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50)
Atrium Left, Thrombosis 1 (2%) 1 (2%)
Coronary Artery, Inflammation, Chronic 1 (2%) 1 (2%)
Endocardium, Proliferation 1 (2%)
Epicardium, Inflammation, Chronic 2 (4%) 2 (4%)
Myocardium, Degeneration, Multifocal 27 (54%) 20 (40%)
Myocardium, Fibrosis, Focal 1 (2%)
Myocardium, Inflammation, Chronic, Multifocal 5 (10%)
Valve, Inflammation, Chronic 1 (2%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Gland, Cortex (50) (50)
Hyperplasia, Nodular 22 (44%) 15 (30%)
Hypertrophy, Focal 2 (4%)
Mineralization, Focal 1 (2%)
Vacuolization Cytoplasmic, Focal 1 (2%) 1 (2%)
Adrenal Gland, Medulla (50) (50)
Hyperplasia, Nodular 18 (36%) 15 (30%)
Pituitary Gland (50) (50)
Angiectasis, Focal 1 (2%)
Pars Distalis, Angiectasis, Focal 3 (6%) 2 (4%)
Pars Distalis, Cyst 4 (8%)
Pars Distalis, Hyperplasia, Nodular 10 (20%) 2 (4%)
Thyroid Gland (50) (49)
C-Cell, Hyperplasia 43 (86%) 39 (80%)
Follicle, Dilatation, Focal 2 (4%)
Follicle, Dilatation, Multifocal 2 (4%)
Follicle, Hyperplasia, Focal 1 (2%)
Follicular Cell, Hyperplasia, Focal 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 10
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Clitoral Gland (50) (49)
Hyperplasia 3 (6%) 1 (2%)
Inflammation, Chronic 7 (14%) 9 (18%)
Inflammation, Chronic Active 4 (8%) 1 (2%)
Duct, Dilatation 3 (6%)
Ovary (50) (50)
Inflammation, Chronic 2 (4%)
Follicle, Cyst 1 (2%) 1 (2%)
Periovarian Tissue, Cyst 2 (4%)
Uterus (50) (50)
Prolapse 1 (2%) 1 (2%)
Endometrium, Hyperplasia, Cystic 6 (12%) 10 (20%)
Endometrium, Necrosis, Coagulative 2 (4%) 1 (2%)
Wall, Bacterium 1 (2%)
Wall, Inflammation, Chronic Active 2 (4%) 3 (6%)
Vagina (2) (3)
Cyst 1 (50%) 3 (100%)
Prolapse 1 (50%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (50)
Femoral, Hyperplasia 8 (16%) 9 (18%)
Lymph Node (49) (50)
Sinus, Mandibular, Ectasia 3 (6%)
Lymph Node, Mesenteric (4) (3)
Sinus, Ectasia 1 (25%) 1 (33%)
Spleen (50) (50)
Fibrosis, Focal 2 (4%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (49)
Hyperplasia, Cystic 16 (32%) 21 (43%)
Necrosis, Coagulative 1 (2%)
Skin (50) (50)
Edema 1 (2%)
Infiltration Cellular, Polymorphonuclear 1 (2%)
Inflammation, Chronic 1 (2%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 11
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50)
Gliosis, Focal 1 (2%)
Infarct 1 (2%)
Hypothalamus, Compression 4 (8%) 2 (4%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50)
Congestion 3 (6%)
Alveolus, Hemorrhage 2 (4%)
Artery, Mineralization 1 (2%) 1 (2%)
Interstitium, Inflammation, Chronic,
Multifocal 1 (2%) 1 (2%)
Trachea (50) (50)
Lamina Propria, Inflammation, Chronic 2 (4%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Ear (4)
Canal, External Ear, Exudate, Subacute 1 (25%)
Middle Ear, Inflammation, Chronic 1 (25%)
Middle Ear, Inflammation, Chronic Active 1 (25%)
Middle Ear, Inflammation, Subacute 1 (25%)
Eye (8) (4)
Anterior Chamber, Inflammation, Suppurative 1 (13%)
Lens Crystalline, Cataract 6 (75%) 4 (100%)
Posterior Chamber, Inflammation, Chronic 2 (25%)
Retina, Atrophy 6 (75%) 3 (75%)
Sclera, Mineralization, Multifocal 1 (13%)
Harderian Gland (7) (2)
Inflammation, Chronic, Multifocal 5 (71%) 2 (100%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 12
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (50)
Infarct 1 (2%)
Inflammation, Multifocal, Necrotizing 1 (2%)
Nephropathy, Multifocal 15 (30%) 15 (30%)
Pelvis, Renal Tubule, Bacterium 1 (2%)
Urinary Bladder (50) (50)
Inflammation, Acute 1 (2%)
Inflammation, Chronic 2 (4%)
Transitional Epithelium, Hyperplasia, Diffuse 1 (2%)
Transitional Epithelium, Hyperplasia, Focal 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 13
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50 50 50 50 50
Early Deaths
Moribund Sacrifice 22 21 13 21 24 21
Natural Death 2 5 4 3 4 6
Survivors
Terminal Sacrifice 25 23 33 26 21 21
Moribund Sacrifice 1 1 1
Natural Death 2
Animals Examined Microscopically 50 50 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Cecum (49) (22) (13) (22) (26) (21)
Inflammation, Chronic, Focal 1 (5%)
Arteriole, Inflammation, Chronic 1 (2%)
Arteriole, Thrombosis 1 (2%)
Intestine Large, Colon (49) (24) (14) (22) (26) (23)
Diverticulum 1 (7%)
Parasite Metazoan 3 (6%) 2 (8%) 3 (12%) 2 (9%)
Intestine Large, Rectum (48) (24) (14) (22) (26) (22)
Parasite Metazoan 3 (6%) 1 (5%)
Ulcer 1 (5%)
Intestine Small, Ileum (46) (22) (13) (23) (26) (23)
Inflammation, Necrotizing 1 (4%) 1 (4%)
Ulcer 1 (2%) 1 (4%)
Intestine Small, Jejunum (48) (24) (13) (22) (26) (22)
Inflammation, Chronic, Focal 1 (2%)
Peyer's Patch, Inflammation, Suppurative 1 (4%)
Liver (50) (50) (49) (50) (49) (49)
Basophilic Focus 17 (34%) 17 (34%) 24 (49%) 15 (30%) 12 (24%) 26 (53%)
Clear Cell Focus 2 (4%) 5 (10%) 10 (20%) 8 (16%) 6 (12%) 3 (6%)
Congestion 1 (2%)
Degeneration, Cystic 6 (12%) 5 (10%) 9 (18%) 3 (6%) 5 (10%) 2 (4%)
Eosinophilic Focus 5 (10%) 2 (4%) 5 (10%) 6 (12%) 8 (16%) 11 (22%)
Fatty Change 3 (6%) 1 (2%) 1 (2%) 1 (2%) 3 (6%) 3 (6%)
Hepatodiaphragmatic Nodule 1 (2%) 1 (2%) 1 (2%)
Mixed Cell Focus 2 (4%) 1 (2%) 5 (10%)
Necrosis, Coagulative, Focal 1 (2%) 2 (4%) 1 (2%)
Necrosis, Coagulative, Multifocal 4 (8%) 5 (10%) 1 (2%) 1 (2%) 1 (2%)
Necrosis, Caseous, Focal 1 (2%)
Regeneration, Focal 1 (2%) 2 (4%) 2 (4%)
Regeneration, Multifocal 1 (2%)
Centrilobular, Cytomegaly 24 (49%) 13 (26%) 14 (29%) 29 (59%)
Centrilobular, Hemorrhage 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 14
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Centrilobular, Necrosis, Coagulative 1 (2%) 2 (4%) 2 (4%) 1 (2%)
Centrilobular, Necrosis, Caseous 1 (2%)
Periportal, Vacuolization Cytoplasmic 1 (2%)
Sinusoid, Angiectasis 1 (2%) 4 (8%) 3 (6%) 1 (2%) 3 (6%) 5 (10%)
Sinusoid, Angiectasis, Focal 1 (2%) 1 (2%)
Sinusoid, Angiectasis, Multifocal 1 (2%)
Mesentery (7) (3) (3) (3) (7) (2)
Inflammation, Chronic 2 (29%)
Fat, Necrosis 2 (29%) 2 (67%) 2 (29%) 1 (50%)
Pancreas (50) (27) (16) (23) (28) (25)
Autolysis 1 (4%)
Acinus, Atrophy 27 (54%) 14 (52%) 11 (69%) 13 (57%) 17 (61%) 14 (56%)
Acinus, Hyperplasia 1 (4%)
Acinus, Hypertrophy, Focal 1 (6%)
Artery, Inflammation, Acute 1 (4%)
Artery, Inflammation, Chronic 1 (2%) 1 (4%) 2 (7%) 2 (8%)
Duct, Concretion 1 (2%)
Duct, Ectasia 1 (2%) 2 (7%) 1 (4%)
Salivary Glands (48) (27) (16) (23) (27) (28)
Autolysis 1 (6%)
Acinus, Submandibular Gland, Atrophy 1 (2%) 1 (4%)
Parotid Gland, Inflammation, Chronic 1 (2%)
Stomach, Forestomach (49) (26) (15) (24) (27) (26)
Edema 1 (4%)
Ulcer 2 (4%) 1 (4%) 2 (8%) 3 (11%)
Epithelium, Acanthosis, Diffuse 1 (4%)
Stomach, Glandular (49) (25) (15) (23) (26) (23)
Edema 1 (4%)
Ulcer 3 (6%) 1 (4%) 1 (4%)
Arteriole, Submucosa, Thrombosis 1 (2%)
Mucosa, Mineralization, Multifocal 1 (4%)
Tongue (1) (2)
Cyst 1 (50%)
Tooth (1)
Peridontal Tissue, Inflammation, Chronic
Active 1 (100%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (28) (18) (25) (29) (29)
Dilatation 1 (6%)
Infarct 1 (3%)
Atrium, Dilatation 2 (11%) 1 (3%)
Atrium Left, Thrombosis 1 (2%) 1 (4%) 1 (6%) 3 (12%) 2 (7%) 2 (7%)
Endocardium, Proliferation 1 (3%)
Mitral Valve, Thrombosis 1 (4%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 15
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM - CONT
Myocardium, Degeneration, Multifocal 39 (78%) 22 (79%) 14 (78%) 16 (64%) 25 (86%) 27 (93%)
Myocardium, Fibrosis, Focal 1 (2%)
Myocardium, Inflammation, Chronic, Focal 1 (2%) 2 (11%)
Myocardium, Inflammation, Chronic, Multifocal 1 (2%) 2 (11%)
Myocardium, Inflammation, Chronic Active,
Multifocal 1 (4%)
Myocardium, Inflammation, Multifocal,
Necrotizing 1 (2%)
Myocardium, Mineralization, Focal 1 (4%)
Valve, Bacterium 2 (4%) 1 (3%)
Valve, Inflammation, Chronic Active 2 (4%)
Valve, Thrombosis 1 (2%) 1 (3%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Gland, Cortex (50) (50) (48) (49) (47) (49)
Hyperplasia, Nodular 20 (40%) 10 (20%) 13 (27%) 8 (16%) 10 (21%) 19 (39%)
Hypertrophy, Focal 1 (2%) 1 (2%) 2 (4%) 3 (6%) 3 (6%)
Inflammation, Necrotizing 1 (2%)
Mineralization, Multifocal 1 (2%)
Necrosis, Coagulative, Diffuse 1 (2%)
Vacuolization Cytoplasmic, Focal 1 (2%) 1 (2%)
Adrenal Gland, Medulla (50) (50) (50) (49) (48) (49)
Hyperplasia 1 (2%) 1 (2%)
Hyperplasia, Nodular 14 (28%) 25 (50%) 26 (52%) 24 (49%) 30 (63%) 21 (43%)
Inflammation, Necrotizing 1 (2%)
Necrosis, Coagulative, Diffuse 1 (2%)
Parathyroid Gland (47) (26) (17) (24) (26) (29)
Hyperplasia, Diffuse 2 (4%)
Pituitary Gland (50) (34) (20) (31) (30) (27)
Pars Distalis, Angiectasis, Focal 1 (2%) 1 (3%) 1 (3%)
Pars Distalis, Cyst 1 (2%) 2 (6%) 1 (3%)
Pars Distalis, Hyperplasia 1 (2%)
Pars Distalis, Hyperplasia, Nodular 6 (12%) 2 (6%) 1 (5%) 4 (13%) 3 (10%) 2 (7%)
Pars Nervosa, Inflammation, Multifocal,
Subacute 1 (2%)
Thyroid Gland (49) (26) (14) (22) (27) (23)
Necrosis, Caseous, Focal 1 (2%)
C-Cell, Hyperplasia 37 (76%) 13 (50%) 7 (50%) 17 (77%) 19 (70%) 16 (70%)
Follicle, Dilatation, Focal 1 (4%)
Follicle, Dilatation, Multifocal 1 (5%) 1 (4%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 16
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (48) (27) (17) (24) (27) (30)
Granuloma Sperm 1 (2%) 1 (4%)
Inflammation, Chronic 1 (6%)
Preputial Gland (49) (27) (18) (24) (33) (29)
Autolysis, Diffuse 1 (3%)
Hyperplasia 1 (2%) 1 (4%) 1 (6%) 1 (3%)
Inflammation, Chronic 28 (57%) 18 (67%) 15 (83%) 21 (88%) 25 (76%) 21 (72%)
Inflammation, Chronic Active 4 (8%) 5 (19%) 2 (11%) 2 (8%) 4 (12%) 7 (24%)
Duct, Ectasia 1 (4%) 2 (6%) 1 (3%)
Prostate (49) (27) (17) (24) (28) (29)
Granuloma 1 (2%) 1 (3%)
Hemorrhage 1 (2%)
Seminal Vesicle (3) (1) (1)
Hemorrhage 1 (33%)
Testes (50) (50) (50) (48) (50) (49)
Autolysis, Diffuse 1 (2%)
Granuloma Sperm 1 (2%)
Necrosis 2 (4%)
Artery, Inflammation, Chronic 1 (2%)
Interstitial Cell, Hyperplasia 1 (2%) 1 (2%) 2 (4%) 1 (2%)
Seminiferous Tubule, Atrophy 4 (8%) 9 (18%) 15 (30%) 12 (25%) 13 (26%) 9 (18%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (26) (16) (23) (28) (29)
Femoral, Hyperplasia 21 (42%) 20 (77%) 11 (69%) 15 (65%) 16 (57%) 16 (55%)
Femoral, Myelofibrosis 1 (2%) 1 (4%)
Lymph Node (50) (27) (19) (26) (29) (29)
Lumbar, Sinus, Ectasia 1 (4%)
Mandibular, Hyperplasia, Lymphoid 1 (5%)
Mandibular, Hyperplasia, Plasma Cell 1 (3%)
Mandibular, Inflammation, Necrotizing 1 (4%)
Mediastinal, Hematopoietic Cell Proliferation 1 (2%)
Mediastinal, Hyperplasia, Lymphoid 1 (5%) 1 (3%)
Mediastinal, Infiltration Cellular,
Histiocyte 1 (3%)
Mediastinal, Medulla, Fibrosis 1 (2%)
Mediastinal, Sinus, Ectasia 1 (2%) 1 (5%) 1 (4%) 1 (3%)
Sinus, Mandibular, Ectasia 1 (2%) 1 (5%) 1 (3%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 17
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Lymph Node, Mesenteric (5) (7) (4) (5) (8) (4)
Infiltration Cellular, Histiocyte 1 (14%)
Sinus, Ectasia 2 (40%) 2 (50%) 2 (40%) 1 (13%) 1 (25%)
Spleen (49) (33) (29) (31) (35) (29)
Fibrosis, Diffuse 1 (3%)
Fibrosis, Focal 2 (4%) 2 (6%) 3 (10%) 1 (3%) 3 (9%)
Hematopoietic Cell Proliferation 3 (6%) 1 (3%) 2 (7%) 1 (3%) 1 (3%)
Necrosis, Focal 1 (3%)
Capsule, Fibrosis, Focal 1 (3%)
Capsule, Pigmentation, Focal, Hemosiderin 1 (2%)
Red Pulp, Pigmentation, Diffuse, Hemosiderin 1 (3%)
Thymus (40) (23) (15) (23) (28) (25)
Ectopic Parathyroid Gland 1 (3%)
Mediastinum, Inflammation, Chronic,
Multifocal 1 (4%)
Vein, Congestion 1 (4%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (23) (12) (8) (7) (14) (7)
Granuloma 1 (4%)
Hyperplasia, Cystic 20 (87%) 11 (92%) 5 (63%) 5 (71%) 12 (86%) 6 (86%)
Skin (49) (29) (20) (31) (29) (30)
Acanthosis 1 (3%)
Cyst Epithelial Inclusion 1 (5%)
Fungus 1 (3%)
Hyperkeratosis 1 (2%) 1 (3%) 1 (3%)
Inflammation, Chronic 2 (4%) 1 (5%) 1 (3%)
Inflammation, Granulomatous 1 (5%) 1 (3%)
Inflammation, Necrotizing 1 (3%)
Thrombosis 1 (5%)
Subcutaneous Tissue, Edema 1 (3%)
Tail, Necrosis, Coagulative, Diffuse 1 (3%)
Tail, Dermis, Epidermis, Bacterium 1 (3%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (49) (27) (18) (25) (29) (27)
Cranium, Inflammation, Chronic, Focal 1 (4%)
Femur, Fibrous Osteodystrophy 1 (2%)
Femur, Osteopetrosis 1 (3%)
Tibia, Fracture Healed 1 (6%)
Skeletal Muscle (1) (1) (1)
Hindlimb, Inflammation, Subacute 1 (100%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 18
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (27) (17) (24) (29) (29)
Abscess 1 (3%)
Hemorrhage 1 (4%)
Infarct 2 (4%) 4 (15%) 2 (12%)
Mineralization, Focal 1 (2%)
Artery, Bacterium 1 (3%)
Cerebellum, Neuron, Necrosis, Focal 1 (3%)
Hypothalamus, Compression 8 (16%) 4 (15%) 1 (6%) 3 (13%) 5 (17%) 2 (7%)
Ventricle, Hydrocephalus 1 (3%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (27) (18) (24) (30) (29)
Bacterium 1 (6%)
Congestion 2 (7%) 2 (11%) 2 (7%)
Alveolar Epithelium, Hyperplasia 1 (4%)
Alveolus, Hemorrhage 1 (4%) 4 (22%) 3 (13%) 1 (3%)
Alveolus, Hemorrhage, Multifocal 1 (3%)
Artery, Mineralization 2 (4%) 2 (8%)
Interstitium, Hemorrhage, Chronic, Multifocal 1 (3%)
Interstitium, Inflammation, Chronic 1 (3%)
Interstitium, Inflammation, Chronic, Focal 2 (4%) 1 (4%) 2 (11%) 1 (3%)
Interstitium, Inflammation, Chronic,
Multifocal 2 (4%) 3 (11%) 1 (6%) 2 (8%) 1 (3%) 2 (7%)
Nose (50) (27) (17) (24) (29) (29)
Sinus, Inflammation, Suppurative 1 (3%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Ear (1) (1) (2) (3)
External Ear, Inflammation, Chronic Active 1 (100%)
Middle Ear, Inflammation, Chronic 1 (50%)
Pinna, Acanthosis 1 (33%)
Pinna, Inflammation, Necrotizing 1 (100%) 1 (50%)
Eye (9) (3) (6) (4) (3) (6)
Anterior, Synechia 1 (17%)
Anterior Chamber, Hemorrhage 1 (11%)
Lens Capsule, Cataract 1 (33%)
Lens Crystalline, Cataract 9 (100%) 2 (67%) 6 (100%) 4 (100%) 2 (67%) 5 (83%)
Posterior Chamber, Inflammation, Chronic 1 (11%) 2 (67%) 2 (50%) 2 (67%) 2 (33%)
Retina, Atrophy 7 (78%) 1 (33%) 6 (100%) 2 (50%) 3 (50%)
Sclera, Mineralization, Multifocal 1 (17%) 2 (67%)
Harderian Gland (2) (1) (1) (1) (1)
a Number of animals examined microscopically at site and number of animals with lesion
Page 19
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 0 PPM 0 PPM 240 PPM 800 PPM 800 PPM 800 PPM
0-0 10-0 1-1 0-3 3-3 10-3
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM - CONT
Inflammation, Chronic, Multifocal 1 (100%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (28) (21) (28) (31) (30)
Hemorrhage, Focal 1 (3%)
Infarct 1 (4%)
Inflammation, Multifocal, Necrotizing 1 (3%)
Nephropathy, Multifocal 50 (100%) 26 (93%) 20 (95%) 26 (93%) 28 (90%) 27 (90%)
Pelvis, Inflammation, Suppurative 1 (3%)
Renal Tubule, Bacterium 1 (3%)
Renal Tubule, Cyst 1 (3%)
Renal Tubule, Cytoplasmic Alteration 1 (2%)
Urinary Bladder (48) (26) (15) (23) (27) (24)
Dilatation 1 (4%)
Inflammation, Acute 1 (4%)
Lamina Propria, Edema 1 (4%)
Mucosa, Inflammation, Proliferative 1 (4%)
Transitional Epithelium, Metaplasia, Focal,
Squamous 1 (4%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 20
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially In Study 50 50
Early Deaths
Moribund Sacrifice 25 17
Natural Death 3 2
Survivors
Moribund Sacrifice 1 1
Terminal Sacrifice 21 30
Animals Examined Microscopically 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Cecum (47) (48)
Ulcer 1 (2%)
Submucosa, Edema 1 (2%) 1 (2%)
Intestine Large, Colon (46) (48)
Inflammation, Chronic Active, Focal 1 (2%)
Parasite Metazoan 6 (13%) 8 (17%)
Ulcer 1 (2%)
Intestine Large, Rectum (47) (49)
Parasite Metazoan 2 (4%) 3 (6%)
Intestine Small, Ileum (47) (48)
Inflammation, Chronic, Diffuse 1 (2%)
Inflammation, Chronic, Focal 2 (4%)
Ulcer 1 (2%)
Intestine Small, Jejunum (48) (48)
Inflammation, Chronic, Focal 2 (4%)
Peyer's Patch, Hyperplasia 2 (4%)
Liver (50) (49)
Basophilic Focus 4 (8%) 7 (14%)
Clear Cell Focus 1 (2%) 7 (14%)
Degeneration, Cystic 4 (8%) 7 (14%)
Eosinophilic Focus 8 (16%) 7 (14%)
Fatty Change 2 (4%) 3 (6%)
Hepatodiaphragmatic Nodule 1 (2%)
Mixed Cell Focus 3 (6%) 6 (12%)
Necrosis, Coagulative, Focal 2 (4%) 1 (2%)
Necrosis, Coagulative, Multifocal 2 (4%) 2 (4%)
Regeneration, Focal 1 (2%)
Regeneration, Multifocal 2 (4%)
Centrilobular, Congestion 1 (2%)
Centrilobular, Cytomegaly 27 (54%) 31 (63%)
Serosa, Inflammation, Chronic, Multifocal 1 (2%)
Mesentery (6) (4)
Inflammation, Chronic 1 (25%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 21
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT
Inflammation, Chronic Active 1 (17%)
Necrosis 1 (17%) 1 (25%)
Fat, Necrosis 1 (17%) 1 (25%)
Pancreas (48) (50)
Acinus, Atrophy 18 (38%) 24 (48%)
Artery, Inflammation, Chronic 2 (4%) 2 (4%)
Salivary Glands (49) (50)
Acinus, Sublingual Gland, Atrophy 1 (2%)
Arteriole, Thrombosis 1 (2%)
Parotid Gland, Hyperplasia, Lobular 1 (2%)
Parotid Gland, Inflammation, Chronic 1 (2%)
Submandibular Gland, Necrosis, Caseous 1 (2%)
Stomach, Forestomach (49) (48)
Hyperkeratosis 1 (2%) 3 (6%)
Ulcer 2 (4%) 1 (2%)
Submucosa, Edema 1 (2%) 1 (2%)
Stomach, Glandular (49) (48)
Inflammation, Acute 1 (2%)
Inflammation, Chronic 1 (2%)
Ulcer 2 (4%)
Submucosa, Edema 1 (2%)
Tooth (1)
Gingiva, Inflammation, Necrotizing 1 (100%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50)
Arteriole, Coronary Artery, Intima, Necrosis,
Fibrinoid 1 (2%)
Atrium, Dilatation 2 (4%) 1 (2%)
Atrium Left, Thrombosis 1 (2%) 1 (2%)
Coronary Artery, Inflammation, Chronic 1 (2%)
Endocardium, Proliferation 1 (2%)
Myocardium, Degeneration, Multifocal 34 (68%) 40 (80%)
Myocardium, Fibrosis, Focal 1 (2%)
Myocardium, Infarct 1 (2%)
Myocardium, Inflammation, Chronic, Multifocal 1 (2%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Gland, Cortex (49) (50)
Hyperplasia, Nodular 10 (20%) 11 (22%)
Adrenal Gland, Medulla (48) (50)
Hyperplasia 1 (2%)
Hyperplasia, Nodular 17 (35%) 15 (30%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 22
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT
Parathyroid Gland (49) (44)
Hyperplasia, Diffuse 2 (4%) 2 (5%)
Pituitary Gland (48) (49)
Pars Distalis, Hyperplasia, Nodular 4 (8%) 4 (8%)
Pars Nervosa, Inflammation, Chronic 4 (8%) 1 (2%)
Thyroid Gland (48) (49)
C-Cell, Hyperplasia 36 (75%) 30 (61%)
C-Cell, Mineralization, Multifocal 1 (2%)
Follicle, Dilatation, Multifocal 1 (2%) 1 (2%)
Follicular Cell, Hyperplasia, Nodular 1 (2%)
Follicular Cell, Vacuolization Cytoplasmic,
Focal 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (49) (48)
Granuloma Sperm 1 (2%)
Inflammation, Chronic 1 (2%)
Preputial Gland (49) (50)
Hyperplasia 3 (6%) 2 (4%)
Inflammation, Chronic 44 (90%) 29 (58%)
Inflammation, Chronic Active 1 (2%) 5 (10%)
Duct, Ectasia 3 (6%) 2 (4%)
Testes (49) (49)
Artery, Inflammation, Chronic 1 (2%)
Interstitial Cell, Hyperplasia 4 (8%) 5 (10%)
Seminiferous Tubule, Atrophy 1 (2%) 3 (6%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (49) (50)
Femoral, Hyperplasia 22 (45%) 26 (52%)
Lymph Node (50) (50)
Inguinal, Sinus, Ectasia 1 (2%)
Lumbar, Necrosis, Caseous 1 (2%)
Mandibular, Hyperplasia, Plasma Cell 1 (2%)
Mandibular, Necrosis, Caseous 1 (2%)
Mediastinal, Sinus, Ectasia 1 (2%)
Renal, Sinus, Ectasia 3 (6%)
Lymph Node, Mesenteric (8) (8)
a Number of animals examined microscopically at site and number of animals with lesion
Page 23
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Fibrosis 1 (13%)
Giant Cell 1 (13%)
Metaplasia, Focal, Osseous 1 (13%)
Thrombosis 1 (13%)
Sinus, Ectasia 2 (25%) 3 (38%)
Spleen (50) (50)
Fibrosis, Focal 3 (6%) 2 (4%)
Hematopoietic Cell Proliferation 1 (2%)
Thymus (35) (39)
Cyst 1 (3%)
Ectopic Parathyroid Gland 1 (3%)
Arteriole, Inflammation, Chronic 1 (3%) 1 (3%)
Arteriole, Thrombosis 1 (3%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (19) (18)
Hyperplasia, Cystic 17 (89%) 16 (89%)
Skin (49) (50)
Acanthosis 1 (2%)
Inflammation, Chronic 1 (2%)
Inflammation, Necrotizing 2 (4%)
Sebaceous Gland, Hyperplasia 1 (2%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (50)
Femur, Fibrous Osteodystrophy 1 (2%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50)
Infarct 2 (4%) 2 (4%)
Mineralization, Focal 1 (2%)
Fourth Ventricle, Hydrocephalus 1 (2%)
Hypothalamus, Compression 3 (6%) 2 (4%)
Third Ventricle, Hydrocephalus 1 (2%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 24
NTP Experiment-Test: 05075-01 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94
Route: DOSED FEED Time: 09:05:49
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE 2400 PPM 2400 PPM
0-10 10-10
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50)
Inflammation, Focal, Subacute 1 (2%)
Artery, Mineralization 3 (6%)
Interstitium, Inflammation, Chronic, Diffuse 1 (2%) 1 (2%)
Interstitium, Inflammation, Chronic, Focal 2 (4%)
Interstitium, Inflammation, Chronic,
Multifocal 1 (2%) 1 (2%)
Trachea (50) (50)
Lamina Propria, Inflammation, Chronic 1 (2%) 2 (4%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Ear (3)
Middle Ear, Inflammation, Chronic 1 (33%)
Eye (6) (8)
Lens Crystalline, Cataract 4 (67%) 7 (88%)
Posterior Chamber, Inflammation, Chronic 1 (17%) 3 (38%)
Retina, Atrophy 2 (33%) 5 (63%)
Retina, Mineralization, Focal 1 (13%)
Harderian Gland (4)
Inflammation, Chronic, Multifocal 2 (50%)
Zymbal's Gland (1)
Inflammation, Suppurative 1 (100%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (50)
Cyst 2 (4%)
Hemorrhage 1 (2%)
Nephropathy, Multifocal 48 (96%) 49 (98%)
Fat, Hematopoietic Cell Proliferation 1 (2%)
Urinary Bladder (49) (49)
Dilatation 2 (4%)
Inflammation, Chronic 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 25
------------------------------------------------------------
---------- END OF REPORT ----------
------------------------------------------------------------