TDMS Study 05075-02 Pathology Tables
INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) DIPHENYLHYDANTOIN NTP Experiment-Test: 05075-02 Report: PEIRPT03 Study Type: CHRONIC Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 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: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 PPM 0 PPM 60 PPM 200 PPM 200 PPM 200 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 50 50 Early Deaths Natural Death 6 5 6 7 6 4 Moribund Sacrifice 8 11 9 6 6 8 Survivors Terminal Sacrifice 36 34 35 37 38 38 Animals Examined Microscopically 50 50 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Cecum (46) (15) (20) (13) (10) (11) Fibrosis 1 (9%) Parasite Metazoan 1 (10%) Intestine Small, Duodenum (47) (14) (14) (12) (10) (10) Inflammation, Acute, Necrotizing 1 (7%) 1 (10%) 2 (20%) Intestine Small, Ileum (46) (15) (14) (14) (11) (11) Inflammation, Acute, Necrotizing 1 (9%) Intestine Small, Jejunum (48) (16) (14) (15) (12) (11) Hyperplasia, Lymphoid 1 (2%) Liver (48) (49) (50) (50) (50) (49) Basophilic Focus 1 (2%) 2 (4%) 3 (6%) 2 (4%) 1 (2%) Clear Cell Focus 1 (2%) 1 (2%) Degeneration, Cystic 1 (2%) 1 (2%) Eosinophilic Focus 1 (2%) 3 (6%) 5 (10%) 4 (8%) 3 (6%) Fatty Change 2 (4%) 6 (12%) 26 (52%) 27 (54%) 23 (47%) Hematopoietic Cell Proliferation 2 (4%) 2 (4%) 1 (2%) 1 (2%) Infarct, Multifocal 6 (13%) 5 (10%) 3 (6%) 2 (4%) 2 (4%) 3 (6%) Infiltration Cellular, Lymphocyte 1 (2%) Inflammation, Chronic 5 (10%) 1 (2%) Mixed Cell Focus 1 (2%) Necrosis, Focal 1 (2%) Regeneration, Diffuse 1 (2%) Bile Duct, Hyperplasia 1 (2%) Centrilobular, Congestion, Chronic 1 (2%) Centrilobular, Cytomegaly 3 (6%) 26 (52%) 25 (50%) 25 (51%) Hepatocyte, Necrosis 1 (2%) 1 (2%) Mesentery (8) (2) (5) (4) (4) (2) Inflammation, Suppurative 1 (20%) 1 (25%) 1 (25%) Artery, Inflammation, Chronic Active 1 (20%) 1 (25%) Fat, Necrosis 1 (13%) 2 (40%) 1 (25%) 1 (25%) Pancreas (47) (15) (15) (12) (12) (11) Inflammation, Chronic 1 (7%) 1 (9%) Acinus, Atrophy 6 (13%) 2 (13%) 2 (17%) 2 (18%) Acinus, Focal Cellular Change 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 2 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 PPM 0 PPM 60 PPM 200 PPM 200 PPM 200 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Duct, Dilatation 1 (2%) 1 (7%) 1 (8%) Duct, Hyperplasia 1 (9%) Salivary Glands (49) (15) (14) (14) (12) (11) Necrosis 1 (7%) Stomach, Forestomach (48) (20) (20) (20) (12) (16) Cyst 1 (5%) 1 (8%) Hyperplasia, Squamous 4 (20%) 3 (19%) Epithelium, Hyperplasia 2 (10%) 2 (10%) 2 (13%) Stomach, Glandular (48) (16) (16) (15) (11) (13) Cyst 1 (6%) Artery, Inflammation, Chronic Active 1 (7%) Tooth (5) (1) (1) Incisor, Upper, Dysplasia 3 (60%) 1 (100%) 1 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (16) (15) (13) (12) (13) Bacterium 1 (8%) 1 (8%) Cardiomyopathy, Chronic Active 2 (4%) 1 (8%) Mineralization 1 (6%) Artery, Inflammation, Chronic Active 2 (13%) 2 (15%) Atrium, Thrombosis 1 (8%) Valve, Inflammation, Suppurative 1 (8%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Gland, Cortex (48) (16) (14) (13) (12) (11) Hematopoietic Cell Proliferation 1 (8%) Hypertrophy 3 (6%) Necrosis 1 (2%) Corticomedullary Junction, Degeneration, Fatty 5 (10%) 1 (8%) Adrenal Gland, Medulla (48) (16) (14) (13) (12) (11) Hyperplasia 1 (2%) 1 (6%) 1 (9%) Pituitary Gland (44) (19) (17) (17) (14) (15) Pars Distalis, Hyperplasia 19 (43%) 1 (6%) 2 (12%) 1 (7%) 2 (13%) Thyroid Gland (47) (16) (15) (14) (12) (11) Inflammation, Chronic Active 3 (6%) Follicular Cell, Hyperplasia 4 (9%) 1 (6%) 1 (7%) 1 (8%) 2 (18%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 3 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 PPM 0 PPM 60 PPM 200 PPM 200 PPM 200 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (1) (1) Duct, Dilatation 1 (100%) 1 (100%) Ovary (49) (28) (36) (28) (25) (30) Angiectasis 1 (2%) 1 (4%) 1 (3%) Cyst 25 (51%) 17 (61%) 29 (81%) 16 (57%) 15 (60%) 24 (80%) Fibrosis 1 (3%) Inflammation, Chronic Active 6 (21%) 2 (8%) 1 (3%) Mineralization 1 (2%) Thrombosis 2 (4%) 1 (3%) 1 (4%) 1 (3%) Uterus (49) (36) (31) (33) (33) (32) Dilatation 2 (6%) 1 (3%) 1 (3%) 2 (6%) Fibrosis 1 (3%) Inflammation, Chronic Active 2 (6%) Inflammation, Suppurative 1 (2%) 2 (6%) 2 (6%) 3 (9%) 1 (3%) Thrombosis 1 (3%) Endometrium, Hyperplasia, Cystic 15 (31%) 18 (50%) 16 (52%) 20 (61%) 24 (73%) 25 (78%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (48) (16) (15) (13) (12) (11) Myelofibrosis 1 (2%) Femoral, Myelofibrosis 2 (4%) 1 (9%) Lymph Node (50) (18) (16) (20) (15) (20) Lumbar, Edema 1 (5%) Mandibular, Edema 1 (5%) 1 (5%) Mandibular, Hyperplasia, Lymphoid 1 (5%) Mediastinal, Inflammation, Suppurative 2 (13%) Pancreatic, Hyperplasia, Lymphoid 1 (5%) Lymph Node, Mesenteric (12) (7) (5) (6) (4) (9) Angiectasis 3 (25%) 2 (29%) 1 (20%) 1 (11%) Necrosis 1 (14%) Spleen (48) (23) (27) (23) (23) (27) Hematopoietic Cell Proliferation 6 (13%) 1 (4%) 5 (19%) 4 (17%) 6 (26%) 3 (11%) Hyperplasia, Lymphoid 2 (9%) 3 (11%) 3 (13%) 2 (7%) Necrosis 1 (4%) Thymus (42) (12) (11) (9) (11) (10) Necrosis 1 (2%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 4 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 PPM 0 PPM 60 PPM 200 PPM 200 PPM 200 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (46) (15) (12) (13) (9) (5) Hyperplasia, Cystic 1 (2%) Skin (49) (16) (17) (13) (12) (13) Inflammation, Chronic Active 1 (2%) 1 (8%) Subcutaneous Tissue, Fibrosis 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM None ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (16) (15) (13) (13) (12) Compression 1 (2%) 1 (6%) Hemorrhage 2 (4%) Necrosis 1 (2%) 1 (7%) Artery, Inflammation, Chronic Active 1 (7%) Meninges, Infiltration Cellular, Lymphocyte 1 (8%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (20) (20) (15) (13) (13) Bacterium 1 (8%) Hemorrhage, Chronic 1 (7%) Hyperplasia, Lymphoid 1 (8%) Inflammation, Acute 1 (8%) Inflammation, Chronic Active 3 (6%) 2 (10%) 3 (20%) 2 (15%) Alveolar Epithelium, Hyperplasia 4 (8%) 1 (5%) Nose (50) (16) (15) (13) (12) (12) Mucosa, Inflammation, Suppurative 1 (2%) Nasolacrimal Duct, Inflammation, Suppurative 1 (7%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (2) (2) (1) (2) (1) (3) Degeneration 2 (100%) 2 (100%) 1 (100%) 3 (100%) Cornea, Inflammation, Chronic Active 2 (100%) Harderian Gland (8) (4) (4) (3) (4) (4) Hyperplasia 3 (38%) 1 (25%) 1 (33%) Inflammation, Chronic Active 1 (13%) Zymbal's Gland (1) Dilatation 1 (100%) a Number of animals examined microscopically at site and number of animals with lesion Page 5 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 0 PPM 0 PPM 60 PPM 200 PPM 200 PPM 200 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (48) (16) (16) (13) (14) (12) Cyst 2 (13%) Nephropathy, Chronic 14 (29%) 4 (25%) 4 (31%) 1 (7%) 1 (8%) Artery, Inflammation, Chronic Active 1 (8%) Glomerulus, Inflammation, Membranoproliferative 1 (2%) 1 (6%) 1 (8%) Pelvis, Inflammation, Suppurative 1 (8%) Renal Tubule, Necrosis 1 (2%) 1 (6%) 1 (8%) Renal Tubule, Regeneration 1 (6%) Urinary Bladder (48) (15) (15) (13) (11) (11) Artery, Inflammation, Chronic Active 1 (8%) 1 (9%) 1 (9%) a Number of animals examined microscopically at site and number of animals with lesion Page 6 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 600 PPM 600 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 Early Deaths Natural Death 4 5 Moribund Sacrifice 6 8 Survivors Terminal Sacrifice 40 37 Animals Examined Microscopically 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Colon (49) (48) Parasite Metazoan 1 (2%) Intestine Small, Jejunum (48) (48) Edema 1 (2%) Inflammation, Acute, Necrotizing 1 (2%) 1 (2%) Liver (50) (50) Basophilic Focus 3 (6%) 4 (8%) Clear Cell Focus 5 (10%) 1 (2%) Degeneration, Cystic 5 (10%) Eosinophilic Focus 8 (16%) 8 (16%) Fibrosis, Multifocal 1 (2%) Hematopoietic Cell Proliferation 1 (2%) Infarct, Multifocal 6 (12%) 11 (22%) Inflammation, Chronic 2 (4%) Mixed Cell Focus 2 (4%) Vacuolization Cytoplasmic 1 (2%) Centrilobular, Cytomegaly 37 (74%) 31 (62%) Mesentery (6) (6) Artery, Inflammation, Chronic Active 1 (17%) Pancreas (49) (48) Inflammation, Chronic 1 (2%) Acinus, Atrophy 5 (10%) 3 (6%) Acinus, Depletion Secretory 1 (2%) 1 (2%) Artery, Inflammation, Chronic Active 2 (4%) Stomach, Forestomach (49) (48) Diverticulum 1 (2%) Inflammation, Chronic Active 1 (2%) Tooth (12) (9) Incisor, Upper, Dysplasia 10 (83%) 7 (78%) Peridontal Tissue, Inflammation, Suppurative 1 (8%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 7 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 600 PPM 600 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) Artery, Inflammation, Chronic Active 2 (4%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Gland, Cortex (50) (48) Hematopoietic Cell Proliferation 1 (2%) 1 (2%) Hyperplasia 1 (2%) Hypertrophy 2 (4%) Thrombosis 1 (2%) Adrenal Gland, Medulla (50) (48) Hyperplasia 1 (2%) Pituitary Gland (44) (41) Pars Distalis, Hyperplasia 17 (39%) 17 (41%) Thyroid Gland (49) (50) Inflammation, Chronic Active 4 (8%) Follicular Cell, Hyperplasia 15 (31%) 13 (26%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Ovary (50) (49) Angiectasis 2 (4%) 2 (4%) Cyst 13 (26%) 18 (37%) Thrombosis 1 (2%) 1 (2%) Uterus (50) (50) Dilatation 3 (6%) 3 (6%) Inflammation, Suppurative 2 (4%) 1 (2%) Endometrium, Hyperplasia, Cystic 8 (16%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (49) (50) Femoral, Myelofibrosis 2 (4%) 3 (6%) Lymph Node, Mesenteric (6) (6) Angiectasis 1 (17%) Hyperplasia, Lymphoid 1 (17%) Spleen (50) (48) Hematopoietic Cell Proliferation 2 (4%) a Number of animals examined microscopically at site and number of animals with lesion Page 8 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 600 PPM 600 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (49) (50) Cyst 1 (2%) Mineralization 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM None ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (49) Hemorrhage 1 (2%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) Inflammation, Chronic Active 1 (2%) 4 (8%) Alveolar Epithelium, Hyperplasia 2 (4%) Nose (50) (50) Mucosa, Inflammation, Suppurative 1 (2%) Nasolacrimal Duct, Inflammation, Suppurative 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM None ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) Metaplasia, Osseous 1 (2%) Nephropathy, Chronic 14 (28%) 17 (34%) Urinary Bladder (49) (49) Artery, Inflammation, Chronic Active 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 9 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 PPM O PPM 30 PPM 100 PPM 100 PPM 100 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 50 50 50 50 Early Deaths Moribund Sacrifice 6 8 2 7 10 3 Natural Death 5 5 9 6 7 6 Survivors Terminal Sacrifice 38 36 38 36 33 39 Moribund Sacrifice 1 Natural Death 1 1 1 Missing 1 1 Animals Examined Microscopically 50 50 50 49 50 49 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Gallbladder (46) (11) (8) (11) (10) (5) Inflammation, Suppurative 1 (13%) Intestine Large, Cecum (49) (13) (11) (12) (16) (7) Parasite Metazoan 1 (2%) Intestine Large, Colon (49) (13) (12) (13) (15) (7) Parasite Metazoan 1 (2%) 1 (8%) Intestine Large, Rectum (47) (13) (11) (12) (15) (8) Parasite Metazoan 1 (2%) 1 (7%) Prolapse 1 (13%) Intestine Small, Duodenum (48) (12) (9) (10) (15) (7) Hyperplasia, Atypical 1 (7%) Inflammation, Acute, Necrotizing 1 (7%) Inflammation, Chronic Active 1 (14%) Intestine Small, Jejunum (50) (12) (17) (10) (16) (8) Inflammation, Acute, Necrotizing 2 (4%) 1 (6%) 1 (6%) Inflammation, Chronic Active 1 (6%) Liver (50) (50) (50) (49) (50) (49) Angiectasis 1 (2%) Basophilic Focus 4 (8%) 3 (6%) 5 (10%) 1 (2%) 6 (12%) Clear Cell Focus 7 (14%) 7 (14%) 2 (4%) 3 (6%) 4 (8%) 5 (10%) Clear Cell Focus, Multiple 1 (2%) Cyst 1 (2%) 1 (2%) 1 (2%) 2 (4%) Degeneration, Cystic 3 (6%) 2 (4%) 9 (18%) 7 (14%) 9 (18%) Eosinophilic Focus 3 (6%) 2 (4%) 3 (6%) 3 (6%) 5 (10%) Fatty Change 5 (10%) 2 (4%) 7 (14%) 4 (8%) 2 (4%) Fibrosis, Focal 1 (2%) Hematopoietic Cell Proliferation 2 (4%) 1 (2%) Hepatodiaphragmatic Nodule 1 (2%) 1 (2%) Infarct, Multifocal 4 (8%) 8 (16%) 5 (10%) 11 (22%) 7 (14%) 6 (12%) Inflammation, Chronic 1 (2%) Mineralization 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 10 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 PPM O PPM 30 PPM 100 PPM 100 PPM 100 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Mixed Cell Focus 3 (6%) 1 (2%) 1 (2%) 2 (4%) 1 (2%) Necrosis 2 (4%) Necrosis, Multifocal 1 (2%) Regeneration, Diffuse 1 (2%) Bile Duct, Hyperplasia 2 (4%) 1 (2%) Centrilobular, Congestion, Chronic 1 (2%) Centrilobular, Cytomegaly 16 (32%) 5 (10%) 33 (67%) 20 (40%) 19 (39%) Mesentery (3) (2) (2) (3) Inflammation, Suppurative 1 (33%) 2 (67%) Artery, Inflammation, Chronic Active 1 (33%) 1 (50%) Fat, Necrosis 1 (50%) Pancreas (50) (13) (11) (13) (17) (8) Acinus, Atrophy 4 (8%) 1 (8%) 1 (9%) 1 (8%) Acinus, Focal Cellular Change 1 (2%) 1 (8%) Artery, Inflammation, Chronic Active 1 (8%) Duct, Dilatation 1 (8%) Stomach, Forestomach (50) (16) (11) (18) (15) (9) Diverticulum 1 (6%) Hyperplasia, Squamous 4 (22%) 1 (11%) Epithelium, Hyperplasia 1 (2%) 2 (18%) 2 (11%) Stomach, Glandular (50) (15) (9) (16) (13) (9) Inflammation, Acute, Necrotizing 1 (2%) Mineralization 1 (7%) Tooth (36) (1) (5) (1) (2) (2) Incisor, Upper, Dysplasia 36 (100%) 1 (100%) 5 (100%) 1 (100%) 2 (100%) 2 (100%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (14) (12) (13) (17) (10) Bacterium 1 (10%) Cardiomyopathy, Chronic Active 1 (8%) 1 (10%) Atrium, Thrombosis 1 (8%) Valve, Inflammation, Suppurative 1 (10%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Gland, Cortex (50) (14) (11) (12) (17) (9) Hyperplasia 4 (8%) 1 (7%) 1 (9%) 1 (6%) Hypertrophy 17 (34%) 1 (7%) 2 (18%) 4 (33%) Necrosis 1 (9%) Adrenal Gland, Medulla (50) (14) (11) (11) (17) (9) Hyperplasia 5 (10%) Necrosis 1 (9%) Islets, Pancreatic (50) (13) (10) (12) (17) (8) Hyperplasia 1 (2%) 1 (8%) 1 (6%) a Number of animals examined microscopically at site and number of animals with lesion Page 11 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 PPM O PPM 30 PPM 100 PPM 100 PPM 100 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - CONT Pituitary Gland (45) (11) (4) (10) (14) (7) Pars Distalis, Hyperplasia 2 (4%) Thyroid Gland (49) (14) (11) (13) (17) (9) Follicle, Cyst Multilocular 1 (2%) 1 (7%) Follicular Cell, Hyperplasia 2 (4%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Preputial Gland (5) (2) (4) (2) (3) (8) Inflammation, Chronic Active 1 (20%) 1 (50%) 1 (25%) 2 (67%) 3 (38%) Duct, Dilatation 4 (80%) 1 (50%) 4 (100%) 2 (100%) 1 (33%) 4 (50%) Prostate (50) (14) (12) (13) (17) (9) Inflammation, Suppurative 2 (22%) Artery, Inflammation, Chronic Active 1 (2%) Seminal Vesicle (1) (1) (2) (1) Inflammation, Chronic Active 1 (100%) Testes (50) (14) (12) (13) (17) (9) Degeneration 1 (8%) 1 (6%) Inflammation, Acute, Necrotizing 1 (11%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Lymph Node (50) (30) (32) (27) (31) (23) Deep Cervical, Edema 1 (4%) Lumbar, Edema 1 (4%) Mandibular, Angiectasis 1 (3%) 1 (4%) 1 (3%) Mandibular, Edema 1 (3%) 1 (3%) 2 (6%) Mandibular, Hyperplasia, Lymphoid 2 (6%) 1 (4%) 2 (6%) Renal, Edema 1 (4%) Lymph Node, Mesenteric (22) (22) (20) (16) (20) (15) Angiectasis 15 (68%) 12 (55%) 15 (75%) 11 (69%) 9 (45%) 11 (73%) Edema 2 (9%) 1 (6%) Hyperplasia, Lymphoid 1 (5%) 1 (5%) 1 (6%) 2 (10%) Spleen (49) (21) (18) (20) (25) (17) Angiectasis, Focal 1 (2%) Hematopoietic Cell Proliferation 4 (8%) 1 (5%) 3 (17%) 3 (15%) 4 (16%) 1 (6%) Hyperplasia, Lymphoid 1 (5%) 3 (18%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 12 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 PPM O PPM 30 PPM 100 PPM 100 PPM 100 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (50) (15) (13) (14) (20) (9) Cyst Epithelial Inclusion 1 (8%) Inflammation, Acute 2 (22%) Inflammation, Chronic Active 2 (4%) Subcutaneous Tissue, Fibrosis 1 (5%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (30) (40) (30) (37) (35) Femur, Fibrosis, Focal 1 (2%) Tarsal, Hyperostosis 28 (56%) 16 (53%) 31 (78%) 19 (63%) 22 (59%) 27 (77%) Tarsal, Inflammation, Chronic Active 1 (3%) Skeletal Muscle (1) (1) (1) Artery, Inflammation, Chronic Active 1 (100%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (14) (12) (13) (18) (10) Compression 1 (8%) Hemorrhage 1 (8%) 1 (6%) Hydrocephalus 1 (6%) Necrosis 1 (6%) Artery, Inflammation, Chronic Active 1 (2%) 1 (8%) Meninges, Infiltration Cellular, Lymphocyte 1 (2%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (19) (19) (21) (20) (22) Inflammation, Chronic Active 2 (4%) 3 (16%) 3 (14%) Metaplasia, Focal, Squamous 1 (2%) Alveolar Epithelium, Hyperplasia 11 (22%) 1 (5%) 2 (10%) 1 (5%) 2 (9%) Alveolus, Infiltration Cellular, Histiocyte 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (2) (3) (2) (3) Degeneration 1 (50%) 1 (33%) 2 (100%) 3 (100%) Cornea, Inflammation, Chronic Active 1 (50%) 1 (33%) Harderian Gland (9) (2) (2) (2) (3) (4) Hyperplasia 3 (33%) Inflammation, Suppurative 1 (11%) 1 (50%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 13 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 0 PPM O PPM 30 PPM 100 PPM 100 PPM 100 PPM 0-0 10-0 1-1 10-3 3-3 0-3 ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (16) (12) (13) (18) (9) Cyst 1 (2%) Hydronephrosis 1 (2%) Infiltration Cellular, Lymphocyte 1 (2%) Metaplasia, Osseous 1 (2%) Nephropathy, Chronic 36 (72%) 4 (25%) 6 (50%) 4 (31%) 9 (50%) 1 (11%) Artery, Inflammation, Chronic Active 1 (2%) 1 (8%) Pelvis, Inflammation, Suppurative 1 (2%) 2 (22%) Renal Tubule, Hyperplasia 1 (11%) Urinary Bladder (49) (13) (12) (13) (18) (8) Inflammation, Chronic Active 1 (2%) 2 (11%) 2 (25%) a Number of animals examined microscopically at site and number of animals with lesion Page 14 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 300 PPM 300 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially In Study 50 50 Early Deaths Moribund Sacrifice 4 9 Natural Death 2 7 Survivors Terminal Sacrifice 44 34 Animals Examined Microscopically 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Colon (48) (50) Inflammation, Acute, Necrotizing 1 (2%) Intestine Large, Rectum (49) (48) Parasite Metazoan 2 (4%) 1 (2%) Intestine Small, Ileum (49) (46) Inflammation, Acute, Necrotizing 1 (2%) 1 (2%) Intestine Small, Jejunum (48) (48) Inflammation, Chronic Active 1 (2%) Parasite Metazoan 1 (2%) Liver (50) (49) Basophilic Focus 1 (2%) 3 (6%) Clear Cell Focus 26 (52%) 20 (41%) Degeneration, Cystic 39 (78%) 29 (59%) Eosinophilic Focus 5 (10%) 2 (4%) Hematopoietic Cell Proliferation 1 (2%) Infarct, Multifocal 3 (6%) 2 (4%) Inflammation, Chronic 1 (2%) 1 (2%) Mixed Cell Focus 3 (6%) Centrilobular, Cytomegaly 46 (92%) 37 (76%) Mesentery (3) (4) Artery, Inflammation, Chronic Active 1 (33%) Pancreas (49) (49) Acinus, Atrophy 6 (12%) Acinus, Depletion Secretory 1 (2%) Acinus, Focal Cellular Change 2 (4%) Salivary Glands (50) (49) Inflammation, Granulomatous 1 (2%) Necrosis 1 (2%) Acinus, Atrophy 1 (2%) Stomach, Forestomach (49) (48) Ulcer 1 (2%) Epithelium, Hyperplasia 1 (2%) 2 (4%) Stomach, Glandular (49) (47) Inflammation, Acute, Necrotizing 4 (9%) a Number of animals examined microscopically at site and number of animals with lesion Page 15 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 300 PPM 300 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM - CONT Tooth (44) (39) Incisor, Upper, Dysplasia 44 (100%) 38 (97%) Peridontal Tissue, Inflammation, Suppurative 1 (2%) 1 (3%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (49) Artery, Inflammation, Chronic Active 2 (4%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Gland, Cortex (49) (49) Hyperplasia 2 (4%) 4 (8%) Hypertrophy 15 (31%) 7 (14%) Islets, Pancreatic (49) (49) Hyperplasia 1 (2%) Thyroid Gland (50) (49) Inflammation, Chronic Active 1 (2%) Follicle, Cyst Multilocular 1 (2%) Follicular Cell, Hyperplasia 4 (8%) 6 (12%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Epididymis (49) (50) Inflammation, Chronic Active 1 (2%) Preputial Gland (4) (8) Inflammation, Chronic Active 3 (38%) Duct, Dilatation 4 (100%) 7 (88%) Prostate (50) (50) Inflammation, Suppurative 3 (6%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) Femoral, Thrombosis 1 (2%) Lymph Node (50) (47) Mandibular, Angiectasis 1 (2%) Mandibular, Edema 1 (2%) a Number of animals examined microscopically at site and number of animals with lesion Page 16 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 300 PPM 300 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - CONT Mediastinal, Angiectasis 1 (2%) Lymph Node, Mesenteric (18) (24) Angiectasis 13 (72%) 13 (54%) Spleen (49) (47) Cyst 1 (2%) Depletion Lymphoid 1 (2%) Hematopoietic Cell Proliferation 2 (4%) 2 (4%) Thymus (43) (41) Atrophy 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (50) (50) Inflammation, Acute 1 (2%) Inflammation, Chronic Active 2 (4%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) Femur, Hyperostosis 1 (2%) Tarsal, Hyperostosis 9 (18%) 13 (26%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM None ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (49) Inflammation, Acute 2 (4%) Inflammation, Chronic Active 1 (2%) 2 (4%) Alveolar Epithelium, Hyperplasia 1 (2%) 6 (12%) Artery, Mediastinum, Inflammation, Chronic Active 1 (2%) Nose (50) (50) Mucosa, Inflammation, Suppurative 1 (2%) Nasolacrimal Duct, Inflammation, Suppurative 1 (2%) ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion Page 17 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:41:56 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 300 PPM 300 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (2) (1) Degeneration 2 (100%) 1 (100%) Harderian Gland (4) (5) Hyperplasia 1 (25%) 1 (20%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) Embolus Bacterial 1 (2%) Nephropathy, Chronic 39 (78%) 35 (70%) Artery, Inflammation, Chronic Active 1 (2%) Pelvis, Inflammation, Suppurative 2 (4%) Urinary Bladder (50) (50) Concretion 1 (2%) Inflammation, Chronic Active 5 (10%) a Number of animals examined microscopically at site and number of animals with lesion Page 18 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