TDMS Study 05075-02 Pathology Tables
INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) DIPHENYLHYDANTOIN NTP Experiment-Test: 05075-02 Report: PEIRPT05 Study Type: CHRONIC Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 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 NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 Gallbladder (45) (14) (14) (12) (11) (11) Intestine Large, Cecum (46) (15) (20) (13) (10) (11) Leiomyosarcoma 1 (8%) Intestine Large, Colon (48) (16) (15) (13) (12) (11) Leiomyoma 1 (2%) Leiomyosarcoma 1 (8%) Intestine Small, Ileum (46) (15) (14) (14) (11) (11) Intestine Small, Jejunum (48) (16) (14) (15) (12) (11) Adenocarcinoma 1 (8%) Liver (48) (49) (50) (50) (50) (49) Hemangiosarcoma 2 (4%) 2 (4%) Hemangiosarcoma, Multiple 1 (2%) Hepatocellular Carcinoma 1 (2%) 4 (8%) 4 (8%) 3 (6%) 1 (2%) Hepatocellular Adenoma 5 (10%) 8 (16%) 10 (20%) 7 (14%) 20 (40%) 8 (16%) Hepatocellular Adenoma, Multiple 3 (6%) 1 (2%) 5 (10%) 5 (10%) 5 (10%) Mesentery (8) (2) (5) (4) (4) (2) Pancreas (47) (15) (15) (12) (12) (11) Salivary Glands (49) (15) (14) (14) (12) (11) Stomach, Forestomach (48) (20) (20) (20) (12) (16) Squamous Cell Papilloma 2 (4%) 3 (15%) 3 (15%) 2 (10%) Squamous Cell Papilloma, Multiple 1 (5%) Stomach, Glandular (48) (16) (16) (15) (11) (13) Tongue (1) Squamous Cell Carcinoma 1 (100%) Tooth (5) (1) (1) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (16) (15) (13) (12) (13) ____________________________________________________________________________________________________________________________________ Page 2 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Gland, Cortex (48) (16) (14) (13) (12) (11) Adrenal Gland, Medulla (48) (16) (14) (13) (12) (11) Pheochromocytoma Malignant 1 (2%) Pheochromocytoma Complex 1 (2%) Pheochromocytoma Benign 2 (4%) 2 (13%) 1 (7%) 1 (8%) Islets, Pancreatic (47) (15) (14) (12) (11) (11) Pituitary Gland (44) (19) (17) (17) (14) (15) Pars Distalis, Adenoma 6 (14%) 8 (42%) 3 (18%) 2 (12%) 3 (21%) 8 (53%) Pars Distalis, Carcinoma 1 (2%) Pars Intermedia, Adenoma 1 (5%) Thyroid Gland (47) (16) (15) (14) (12) (11) C-Cell, Carcinoma 1 (7%) Follicular Cell, Adenoma 4 (9%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Ovary (49) (28) (36) (28) (25) (30) Choriocarcinoma 1 (4%) Cystadenoma 1 (2%) 1 (3%) 3 (11%) 1 (4%) 1 (3%) Granulosa Cell Tumor Benign 1 (2%) Hemangioma 1 (4%) Luteoma 1 (2%) Periovarian Tissue, Hemangiosarcoma 1 (2%) Uterus (49) (36) (31) (33) (33) (32) Hemangiosarcoma 1 (3%) Polyp Stromal 1 (2%) 1 (3%) Sarcoma Stromal 1 (3%) 2 (6%) Sarcoma Stromal, Multiple 1 (2%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Blood (2) Bone Marrow (48) (16) (15) (13) (12) (11) Femoral, Hemangiosarcoma 1 (2%) 2 (13%) Lymph Node (50) (18) (16) (20) (15) (20) Mandibular, Adenocarcinoma, Metastatic, Harderian Gland 1 (5%) Mediastinal, Alveolar/Bronchiolar Carcinoma, Metastatic, Lung 1 (5%) Page 3 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - cont Mediastinal, Osteosarcoma, Metastatic, Uncertain Primary Site 1 (5%) Mediastinal, Mandibular, Sarcoma, Metastatic, Eye 1 (6%) Lymph Node, Mesenteric (12) (7) (5) (6) (4) (9) Hemangiosarcoma 1 (14%) Spleen (48) (23) (27) (23) (23) (27) Hemangiosarcoma 3 (6%) 4 (17%) Thymus (42) (12) (11) (9) (11) (10) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (46) (15) (12) (13) (9) (5) Adenocarcinoma 1 (2%) 1 (7%) 2 (17%) 2 (15%) Skin (49) (16) (17) (13) (12) (13) Squamous Cell Carcinoma 1 (8%) Subcutaneous Tissue, Fibrosarcoma 1 (2%) 1 (6%) 1 (6%) 1 (8%) 1 (8%) Subcutaneous Tissue, Hemangiosarcoma 3 (19%) Subcutaneous Tissue, Myxoma 1 (2%) Subcutaneous Tissue, Myxosarcoma 1 (6%) Subcutaneous Tissue, Sarcoma 1 (6%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (16) (16) (13) (12) (12) Femur, Osteoma 1 (6%) Skeletal Muscle (1) (1) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (16) (15) (13) (13) (12) Adenocarcinoma, Metastatic, Harderian Gland 1 (8%) Carcinoma, Metastatic, Pituitary Gland 1 (2%) Spinal Cord (1) (1) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (20) (20) (15) (13) (13) Adenocarcinoma, Metastatic, Harderian Gland 1 (5%) 1 (8%) Alveolar/Bronchiolar Adenoma 5 (10%) 2 (10%) 1 (5%) 2 (13%) 2 (15%) Alveolar/Bronchiolar Carcinoma 1 (5%) 1 (5%) 1 (7%) 1 (8%) 1 (8%) Hepatocellular Carcinoma, Metastatic, Liver 1 (5%) 2 (10%) 1 (8%) Osteosarcoma, Metastatic, Uncertain Primary Page 4 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - cont Site 1 (5%) 1 (8%) Pheochromocytoma Malignant, Metastatic, Adrenal Gland 1 (2%) Sarcoma, Metastatic, Eye 1 (5%) Mediastinum, Alveolar/Bronchiolar Carcinoma, Metastatic, Lung 1 (8%) Nose (50) (16) (15) (13) (12) (12) Adenocarcinoma, Metastatic, Harderian Gland 1 (6%) 1 (8%) Sarcoma, Metastatic, Eye 1 (7%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (2) (2) (1) (2) (1) (3) Adenocarcinoma, Metastatic, Harderian Gland 1 (33%) Sarcoma 1 (100%) Harderian Gland (8) (4) (4) (3) (4) (4) Adenocarcinoma 1 (13%) 3 (75%) 1 (33%) 1 (25%) 2 (50%) Adenoma 3 (38%) 1 (25%) 2 (50%) 1 (33%) 3 (75%) 2 (50%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (48) (16) (16) (13) (14) (12) Osteosarcoma, Metastatic, Uncertain Primary Site 1 (8%) Urinary Bladder (48) (15) (15) (13) (11) (11) ____________________________________________________________________________________________________________________________________ SYSTEMIC LESIONS Multiple Organs *(50) *(50) *(50) *(50) *(50) *(50) Lymphoma Malignant Histiocytic 5 (10%) 3 (6%) 6 (12%) 4 (8%) 2 (4%) Lymphoma Malignant Lymphocytic 9 (18%) 2 (4%) 2 (4%) 1 (2%) Lymphoma Malignant Mixed 9 (18%) 8 (16%) 3 (6%) 11 (22%) 10 (20%) 12 (24%) Lymphoma Malignant Undifferentiated Cell 1 (2%) 2 (4%) ____________________________________________________________________________________________________________________________________ * Number of animals with any tissue examined microscopically Page 5 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 ____________________________________________________________________________________________________________________________________ TUMOR SUMMARY Total Animals with Primary Neoplasms (b) 40 36 27 36 39 36 Total Primary Neoplasms 69 65 47 50 55 47 Total Animals with Benign Neoplasms 23 22 18 22 29 24 Total Benign Neoplasms 33 28 23 25 33 26 Total Animals with Malignant Neoplasms 29 28 21 23 21 20 Total Malignant Neoplasms 36 37 24 25 22 21 Total Animals with Metastatic Neoplasms 2 2 4 1 4 Total Metastatic Neoplasm 2 3 6 1 10 Total Animals with Malignant Neoplasms 1 1 Uncertain Primary Site Total Animals with Neoplasms Uncertain- Benign or Malignant Total Uncertain Neoplasms ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Primary tumors: all tumors except metastatic tumors Page 6 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 Gallbladder (45) (45) Intestine Large, Rectum (50) (47) Intestine Small, Duodenum (49) (48) Intestine Small, Jejunum (48) (48) Liver (50) (50) Hepatoblastoma 1 (2%) Hepatocellular Carcinoma 10 (20%) 9 (18%) Hepatocellular Carcinoma, Multiple 2 (4%) Hepatocellular Adenoma 19 (38%) 16 (32%) Hepatocellular Adenoma, Multiple 7 (14%) 6 (12%) Mesentery (6) (6) Pancreas (49) (48) Salivary Glands (50) (49) Stomach, Forestomach (49) (48) Mast Cell Tumor NOS 1 (2%) Stomach, Glandular (49) (48) Mast Cell Tumor NOS 1 (2%) Tooth (12) (9) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Gland, Cortex (50) (48) Adrenal Gland, Medulla (50) (48) Pheochromocytoma Malignant 1 (2%) Pheochromocytoma Benign 2 (4%) Pituitary Gland (44) (41) Pars Distalis, Adenoma 3 (7%) 3 (7%) Page 7 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 600 PPM 600 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM - cont Thyroid Gland (49) (50) Follicular Cell, Adenoma 4 (8%) 2 (4%) Follicular Cell, Adenoma, Multiple 2 (4%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Ovary (50) (49) Cystadenoma 1 (2%) 2 (4%) Luteoma 1 (2%) Teratoma 1 (2%) Uterus (50) (50) Adenocarcinoma 1 (2%) Polyp Stromal 1 (2%) Vagina (1) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Blood (3) (1) Bone Marrow (49) (50) Lymph Node (48) (49) Lymph Node, Mesenteric (6) (6) Spleen (50) (48) Thymus (42) (45) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (39) (40) Skin (49) (50) Subcutaneous Tissue, Fibrosarcoma 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Skeletal Muscle (1) ____________________________________________________________________________________________________________________________________ Page 8 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 600 PPM 600 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (49) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) Alveolar/Bronchiolar Adenoma 1 (2%) 2 (4%) Hepatocellular Carcinoma, Metastatic, Liver 2 (4%) 2 (4%) Osteosarcoma, Metastatic, Uncertain Primary Site 1 (2%) Mediastinum, Hepatocellular Carcinoma, Metastatic, Liver 1 (2%) Trachea (49) (50) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Harderian Gland (2) Adenoma 1 (50%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) Urinary Bladder (49) (49) ____________________________________________________________________________________________________________________________________ SYSTEMIC LESIONS Multiple Organs *(50) *(50) Lymphoma Malignant Histiocytic 4 (8%) 6 (12%) Lymphoma Malignant Lymphocytic 3 (6%) 5 (10%) Lymphoma Malignant Mixed 5 (10%) 4 (8%) Lymphoma Malignant Undifferentiated Cell 1 (2%) ____________________________________________________________________________________________________________________________________ * Number of animals with any tissue examined microscopically Page 9 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE FEMALE 600 PPM 600 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ TUMOR SUMMARY Total Animals with Primary Neoplasms (b) 46 42 Total Primary Neoplasms 64 65 Total Animals with Benign Neoplasms 33 28 Total Benign Neoplasms 39 35 Total Animals with Malignant Neoplasms 21 26 Total Malignant Neoplasms 23 30 Total Animals with Metastatic Neoplasms 3 3 Total Metastatic Neoplasm 3 3 Total Animals with Malignant Neoplasms 1 Uncertain Primary Site Total Animals with Neoplasms Uncertain- Benign or Malignant 1 Total Uncertain Neoplasms 2 ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Primary tumors: all tumors except metastatic tumors Page 10 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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) Intestine Large, Rectum (47) (13) (11) (12) (15) (8) Intestine Small, Duodenum (48) (12) (9) (10) (15) (7) Intestine Small, Ileum (48) (11) (13) (11) (14) (6) Intestine Small, Jejunum (50) (12) (17) (10) (16) (8) Liver (50) (50) (50) (49) (50) (49) Cholangiocarcinoma 1 (2%) Hemangiosarcoma 4 (8%) 1 (2%) 1 (2%) Hemangiosarcoma, Multiple 1 (2%) 2 (4%) 4 (8%) 1 (2%) 1 (2%) Hepatoblastoma 1 (2%) 1 (2%) Hepatoblastoma, Multiple 1 (2%) Hepatocellular Carcinoma 11 (22%) 10 (20%) 11 (22%) 11 (22%) 14 (28%) 11 (22%) Hepatocellular Carcinoma, Multiple 2 (4%) 4 (8%) 2 (4%) 7 (14%) 4 (8%) 3 (6%) Hepatocellular Adenoma 14 (28%) 11 (22%) 10 (20%) 10 (20%) 15 (30%) 11 (22%) Hepatocellular Adenoma, Multiple 5 (10%) 12 (24%) 6 (12%) 13 (27%) 5 (10%) 8 (16%) Hepatocholangiocarcinoma 1 (2%) Osteosarcoma, Metastatic, Uncertain Primary Site 1 (2%) Mesentery (3) (2) (2) (3) Hepatocholangiocarcinoma, Metastatic 1 (50%) Sarcoma 1 (50%) Pancreas (50) (13) (11) (13) (17) (8) Sarcoma, Metastatic, Mesentery 1 (9%) Salivary Glands (50) (13) (12) (13) (17) (9) Stomach, Forestomach (50) (16) (11) (18) (15) (9) Squamous Cell Papilloma 2 (13%) 2 (13%) Stomach, Glandular (50) (15) (9) (16) (13) (9) Adenoma 1 (11%) Tongue (1) Squamous Cell Carcinoma 1 (100%) Page 11 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 ____________________________________________________________________________________________________________________________________ ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (14) (12) (13) (17) (10) Alveolar/Bronchiolar Carcinoma, Metastatic, Lung 1 (8%) Cholangiocarcinoma, Metastatic, Liver 1 (8%) Hemangiosarcoma 1 (2%) 2 (15%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Gland (50) (14) (11) (12) (17) (9) Corticomedullary Junction, Hepatocellular Carcinoma, Metastatic, Liver 1 (2%) Adrenal Gland, Cortex (50) (14) (11) (12) (17) (9) Adenoma 1 (7%) Adrenal Gland, Medulla (50) (14) (11) (11) (17) (9) Pheochromocytoma Benign 1 (2%) Islets, Pancreatic (50) (13) (10) (12) (17) (8) Adenoma 1 (2%) Pituitary Gland (45) (11) (4) (10) (14) (7) Pars Distalis, Carcinoma 1 (25%) Pars Intermedia, Carcinoma 1 (10%) Thyroid Gland (49) (14) (11) (13) (17) (9) Follicular Cell, Adenoma 1 (7%) 1 (9%) 1 (11%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Preputial Gland (5) (2) (4) (2) (3) (8) Adenoma 1 (20%) Hemangiosarcoma 1 (13%) Prostate (50) (14) (12) (13) (17) (9) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (14) (11) (13) (18) (9) Femoral, Hemangiosarcoma 2 (4%) Lymph Node (50) (30) (32) (27) (31) (23) Deep Cervical, Carcinoma, Metastatic, Ear 1 (3%) Page 12 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM - cont Mandibular, Fibrosarcoma, Metastatic, Skin 1 (2%) Mediastinal, Alveolar/Bronchiolar Carcinoma, Metastatic, Lung 1 (4%) Mediastinal, Cholangiocarcinoma, Metastatic, Liver 1 (3%) Lymph Node, Mesenteric (22) (22) (20) (16) (20) (15) Hemangiosarcoma 1 (5%) 1 (7%) Spleen (49) (21) (18) (20) (25) (17) Hemangiosarcoma 4 (8%) 2 (10%) 3 (15%) Thymus (37) (8) (7) (7) (10) (7) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (50) (15) (13) (14) (20) (9) Squamous Cell Carcinoma 1 (7%) Subcutaneous Tissue, Fibroma 2 (13%) Subcutaneous Tissue, Fibrosarcoma 1 (2%) 1 (7%) 1 (7%) 1 (5%) 1 (11%) Subcutaneous Tissue, Lipoma 1 (8%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (30) (40) (30) (37) (35) Osteosarcoma 1 (3%) Skeletal Muscle (1) (1) (1) Hemangiosarcoma 1 (100%) 1 (100%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (14) (12) (13) (18) (10) Carcinoma, Metastatic, Pituitary Gland 1 (8%) 1 (8%) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (19) (19) (21) (20) (22) Adenocarcinoma, Metastatic, Harderian Gland 1 (5%) Alveolar/Bronchiolar Adenoma 6 (12%) 8 (42%) 5 (26%) 5 (24%) 3 (15%) 2 (9%) Alveolar/Bronchiolar Carcinoma 4 (8%) 3 (16%) 2 (11%) 3 (14%) 1 (5%) 6 (27%) Alveolar/Bronchiolar Carcinoma, Multiple 2 (11%) 2 (11%) 1 (5%) 1 (5%) 3 (14%) Carcinoma, Metastatic, Ear 1 (5%) Cholangiocarcinoma, Metastatic, Liver 1 (5%) Hepatocellular Carcinoma, Metastatic, Liver 6 (12%) 2 (11%) 3 (16%) 5 (24%) 4 (20%) 2 (9%) Hepatocholangiocarcinoma, Metastatic 1 (5%) Osteosarcoma, Metastatic, Uncertain Primary Page 13 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM - cont Site 1 (5%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Ear (1) Basal Cell Carcinoma 1 (100%) Harderian Gland (9) (2) (2) (2) (3) (4) Adenocarcinoma 1 (11%) 1 (50%) 1 (33%) Adenoma 5 (56%) 2 (100%) 1 (50%) 1 (50%) 2 (67%) 4 (100%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (16) (12) (13) (18) (9) Hepatocellular Carcinoma, Metastatic, Liver 1 (2%) 1 (8%) Osteosarcoma, Metastatic, Uncertain Primary Site 1 (11%) Sarcoma, Metastatic, Mesentery 1 (8%) Renal Tubule, Carcinoma 1 (6%) ____________________________________________________________________________________________________________________________________ SYSTEMIC LESIONS Multiple Organs *(50) *(50) *(50) *(49) *(50) *(49) Lymphoma Malignant Histiocytic 2 (4%) 2 (4%) 1 (2%) 2 (4%) 4 (8%) 2 (4%) Lymphoma Malignant Lymphocytic 5 (10%) 2 (4%) 2 (4%) Lymphoma Malignant Mixed 5 (10%) 8 (16%) 5 (10%) 3 (6%) 5 (10%) 5 (10%) Lymphoma Malignant Undifferentiated Cell 1 (2%) ____________________________________________________________________________________________________________________________________ * Number of animals with any tissue examined microscopically Page 14 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 ____________________________________________________________________________________________________________________________________ TUMOR SUMMARY Total Animals with Primary Neoplasms (b) 43 43 33 42 45 39 Total Primary Neoplasms 77 79 53 70 64 63 Total Animals with Benign Neoplasms 25 32 20 26 24 22 Total Benign Neoplasms 33 39 24 29 27 27 Total Animals with Malignant Neoplasms 29 31 24 29 34 31 Total Malignant Neoplasms 44 40 29 41 37 36 Total Animals with Metastatic Neoplasms 7 4 7 6 5 3 Total Metastatic Neoplasm 9 6 10 8 5 5 Total Animals with Malignant Neoplasms 1 Uncertain Primary Site Total Animals with Neoplasms Uncertain- Benign or Malignant Total Uncertain Neoplasms ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Primary tumors: all tumors except metastatic tumors Page 15 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ 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 Gallbladder (44) (46) Intestine Large, Cecum (47) (47) Intestine Large, Colon (48) (50) Intestine Small, Duodenum (49) (48) Intestine Small, Ileum (49) (46) Intestine Small, Jejunum (48) (48) Liver (50) (49) Hemangiosarcoma 1 (2%) 1 (2%) Hemangiosarcoma, Multiple 2 (4%) Hepatocellular Carcinoma 18 (36%) 7 (14%) Hepatocellular Carcinoma, Multiple 2 (4%) Hepatocellular Adenoma 12 (24%) 11 (22%) Hepatocellular Adenoma, Multiple 19 (38%) 11 (22%) Sarcoma, Metastatic, Uncertain Primary Site 1 (2%) Mesentery (3) (4) Sarcoma, Metastatic, Uncertain Primary Site 1 (33%) Pancreas (49) (49) Tooth (44) (39) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (49) Hepatocellular Carcinoma, Metastatic, Liver 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Gland (49) (48) Capsule, Adenoma 1 (2%) Adrenal Gland, Cortex (49) (49) Adrenal Gland, Medulla (49) (45) Pheochromocytoma Benign 1 (2%) Page 16 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 300 PPM 300 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM None ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Prostate (50) (50) Testes (50) (50) Interstitial Cell, Adenoma 2 (4%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (50) Femoral, Mast Cell Tumor NOS 1 (2%) Lymph Node (50) (47) Lymph Node, Mesenteric (18) (24) Sarcoma, Metastatic, Uncertain Primary Site 1 (6%) Spleen (49) (47) Hemangiosarcoma 2 (4%) Thymus (43) (41) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Skin (50) (50) Subcutaneous Tissue, Fibrous Histiocytoma 1 (2%) Subcutaneous Tissue, Hemangiosarcoma 1 (2%) Subcutaneous Tissue, Sarcoma 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM None ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM None ____________________________________________________________________________________________________________________________________ Page 17 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 300 PPM 300 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (49) Adenocarcinoma, Metastatic, Harderian Gland 1 (2%) Alveolar/Bronchiolar Adenoma 7 (14%) 4 (8%) Alveolar/Bronchiolar Carcinoma 4 (8%) 2 (4%) Hepatocellular Carcinoma, Metastatic, Liver 7 (14%) 1 (2%) Sarcoma, Metastatic, Uncertain Primary Site 1 (2%) Mediastinum, Hepatocellular Carcinoma, Metastatic, Liver 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Harderian Gland (4) (5) Adenocarcinoma 1 (20%) Adenoma 3 (75%) 3 (60%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (50) (50) ____________________________________________________________________________________________________________________________________ SYSTEMIC LESIONS Multiple Organs *(50) *(50) Lymphoma Malignant Histiocytic 3 (6%) Lymphoma Malignant Lymphocytic 3 (6%) 3 (6%) Lymphoma Malignant Mixed 3 (6%) 2 (4%) ____________________________________________________________________________________________________________________________________ * Number of animals with any tissue examined microscopically Page 18 NTP Experiment-Test: 05075-02 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC DIPHENYLHYDANTOIN Date: 09/09/94 Route: DOSED FEED Time: 15:42:01 ____________________________________________________________________________________________________________________________________ B6C3F1 MICE MALE 300 PPM 300 PPM 10-10 0-10 ____________________________________________________________________________________________________________________________________ TUMOR SUMMARY Total Animals with Primary Neoplasms (b) 45 36 Total Primary Neoplasms 79 53 Total Animals with Benign Neoplasms 36 26 Total Benign Neoplasms 41 33 Total Animals with Malignant Neoplasms 26 16 Total Malignant Neoplasms 37 20 Total Animals with Metastatic Neoplasms 9 2 Total Metastatic Neoplasm 13 2 Total Animals with Malignant Neoplasms 1 Uncertain Primary Site Total Animals with Neoplasms Uncertain- Benign or Malignant 1 Total Uncertain Neoplasms 1 ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Primary tumors: all tumors except metastatic tumors Page 19 ------------------------------------------------------------ ---------- END OF REPORT ---------- ------------------------------------------------------------