TDMS Study 92013-05 Pathology Tables
NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 FINAL #1 RATS Facility: Southern Research Institute Chemical CAS #: 822-36-6 Lock Date: 09/13/02 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: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially in Study 50 50 50 50 Early Deaths Natural Death 2 6 11 6 Moribund Sacrifice 5 5 5 9 Survivors Terminal Sacrifice 40 39 34 33 Natural Death 3 2 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Colon (49) (48) (45) (46) Histiocytic Sarcoma 1 (2%) Intestine Large, Cecum (48) (46) (43) (43) Intestine Small, Duodenum (49) (48) (43) (45) Intestine Small, Ileum (45) (47) (42) (43) Liver (50) (50) (48) (50) Cholangiocarcinoma 1 (2%) Hepatocellular Adenoma 1 (2%) 2 (4%) Histiocytic Sarcoma 2 (4%) Osteosarcoma, Metastatic, Uncertain Primary Site 1 (2%) Mesentery (9) (7) (11) (8) Fibrosarcoma 1 (11%) Histiocytic Sarcoma 1 (11%) Pancreas (49) (49) (47) (47) Histiocytic Sarcoma 1 (2%) Salivary Glands (50) (50) (50) (50) Stomach, Forestomach (50) (50) (49) (50) Stomach, Glandular (50) (50) (49) (49) Tongue (5) (4) (3) Squamous Cell Papilloma 1 (20%) 1 (25%) 1 (33%) ____________________________________________________________________________________________________________________________________ Page 2 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (48) (50) Schwannoma Benign 1 (2%) 1 (2%) 3 (6%) Schwannoma Benign, Multiple 1 (2%) Schwannoma Malignant 1 (2%) Epicardium, Alveolar/Bronchiolar Carcinoma, Metastatic, Lung 1 (2%) ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (49) (50) (50) (50) Adenoma 1 (2%) 1 (2%) 1 (2%) Carcinoma 1 (2%) Adrenal Medulla (48) (50) (50) (50) Pheochromocytoma Malignant 1 (2%) Pheochromocytoma Benign 1 (2%) 1 (2%) 2 (4%) 2 (4%) Bilateral, Pheochromocytoma Benign 1 (2%) Islets, Pancreatic (49) (50) (48) (47) Adenoma 1 (2%) Mixed Tumor Benign 1 (2%) Pituitary Gland (48) (50) (50) (50) Pars Distalis, Adenoma 29 (60%) 19 (38%) 20 (40%) 9 (18%) Pars Distalis, Carcinoma 1 (2%) Thyroid Gland (47) (44) (40) (45) Bilateral, C-Cell, Adenoma 1 (3%) C-Cell, Adenoma 10 (21%) 8 (18%) 5 (13%) 8 (18%) C-Cell, Carcinoma 1 (2%) 2 (5%) Follicular Cell, Adenoma 2 (4%) 3 (7%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Tissue NOS (5) (3) (6) (6) Neoplasm NOS 1 (17%) Mediastinum, Alveolar/Bronchiolar Carcinoma, Metastatic, Lung 1 (33%) Mediastinum, Schwannoma Malignant 1 (20%) ____________________________________________________________________________________________________________________________________ Page 3 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Clitoral Gland (50) (50) (50) (50) Adenoma 8 (16%) 1 (2%) Carcinoma 2 (4%) 1 (2%) Ovary (50) (50) (48) (50) Granulosa-Theca Tumor Malignant 1 (2%) Histiocytic Sarcoma 1 (2%) Oviduct (2) (1) Uterus (50) (50) (48) (50) Carcinoma 1 (2%) Endometrium, Polyp Stromal 16 (32%) 5 (10%) 2 (4%) 2 (4%) Endometrium, Sarcoma Stromal 1 (2%) ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (50) (48) (49) (48) Osteosarcoma, Metastatic, Bone 1 (2%) Lymph Node (24) (11) (24) (35) Mediastinal, Carcinoma, Metastatic, Thyroid Gland 1 (4%) Pancreatic, Histiocytic Sarcoma 2 (8%) Lymph Node, Mandibular (1) (3) (1) (4) Lymph Node, Mesenteric (49) (49) (49) (47) Spleen (50) (48) (47) (48) Histiocytic Sarcoma 1 (2%) Thymus (47) (50) (48) (48) Alveolar/Bronchiolar Carcinoma, Metastatic, Lung 1 (2%) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (50) (49) (50) (50) Carcinoma 2 (4%) 1 (2%) 2 (4%) Fibroadenoma 20 (40%) 5 (10%) 3 (6%) 1 (2%) Fibroadenoma, Multiple 4 (8%) 1 (2%) 1 (2%) Skin (50) (50) (50) (50) Basal Cell Adenoma 1 (2%) Squamous Cell Papilloma 1 (2%) Trichoepithelioma 1 (2%) Pinna, Neural Crest Tumor 1 (2%) Subcutaneous Tissue, Fibroma 1 (2%) 1 (2%) 5 (10%) Page 4 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM - cont Subcutaneous Tissue, Histiocytic Sarcoma 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Bone (50) (50) (50) (50) Osteosarcoma 1 (2%) 1 (2%) Maxilla, Sarcoma 1 (2%) Skeletal Muscle (1) (1) Alveolar/Bronchiolar Carcinoma, Metastatic, Lung 1 (100%) Carcinoma, Metastatic, Thyroid Gland 1 (100%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Astrocytoma Malignant 1 (2%) Carcinoma, Metastatic, Pituitary Gland 1 (2%) Spinal Cord (7) (3) (24) (50) ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Larynx (1) Carcinoma, Metastatic, Thyroid Gland 1 (100%) Lung (50) (50) (50) (50) Alveolar/Bronchiolar Carcinoma 2 (4%) Histiocytic Sarcoma, Metastatic, Uncertain Primary Site 1 (2%) Osteosarcoma, Metastatic, Bone 1 (2%) Nose (49) (50) (50) (50) Trachea (50) (50) (50) (50) Carcinoma, Metastatic, Thyroid Gland 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Eye (48) (45) (40) (45) Lids, Neural Crest Tumor 1 (2%) 1 (3%) Harderian Gland (50) (50) (50) (50) Zymbal's Gland (3) (1) Carcinoma 1 (33%) 1 (100%) Page 5 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM - cont Carcinosarcoma 1 (33%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (48) (48) (43) (43) Bilateral, Renal Tubule, Adenoma 1 (2%) Pelvis, Transitional Epithelium, Papilloma 1 (2%) Urinary Bladder (49) (50) (49) (48) ____________________________________________________________________________________________________________________________________ SYSTEMIC LESIONS Multiple Organs *(50) *(50) *(50) *(50) Histiocytic Sarcoma 2 (4%) Leukemia Mononuclear 9 (18%) 7 (14%) 16 (32%) 20 (40%) ____________________________________________________________________________________________________________________________________ * Number of animals with any tissue examined microscopically Page 6 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS FEMALE 0 PPM 1250 PPM 2500 PPM 5000 PPM ____________________________________________________________________________________________________________________________________ TUMOR SUMMARY Total Animals with Primary Neoplasms (b) 48 39 42 36 Total Primary Neoplasms 118 67 73 49 Total Animals with Benign Neoplasms 48 32 29 20 Total Benign Neoplasms 97 49 46 27 Total Animals with Malignant Neoplasms 19 15 24 21 Total Malignant Neoplasms 21 17 25 21 Total Animals with Metastatic Neoplasms 3 3 2 Total Metastatic Neoplasm 3 6 4 Total Animals with Malignant Neoplasms 1 1 Uncertain Primary Site Total Animals with Neoplasms Uncertain- Benign or Malignant 1 2 1 Total Uncertain Neoplasms 1 2 1 ____________________________________________________________________________________________________________________________________ a Number of animals examined microscopically at site and number of animals with lesion b Primary tumors: all tumors except metastatic tumors Page 7 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM ____________________________________________________________________________________________________________________________________ DISPOSITION SUMMARY Animals Initially in Study 50 50 50 50 Early Deaths Moribund Sacrifice 13 11 12 10 Natural Death 6 5 5 8 Survivors Terminal Sacrifice 31 34 33 32 Animals Examined Microscopically 50 50 50 50 ____________________________________________________________________________________________________________________________________ ALIMENTARY SYSTEM Intestine Large, Colon (48) (49) (49) (46) Intestine Large, Cecum (46) (46) (46) (46) Intestine Small, Duodenum (49) (48) (47) (47) Intestine Small, Jejunum (47) (45) (45) (43) Intestine Small, Ileum (46) (45) (45) (44) Liver (50) (50) (50) (50) Basal Cell Carcinoma, Metastatic, Skin 1 (2%) Histiocytic Sarcoma 1 (2%) Ito Cell Tumor Benign 1 (2%) Mesentery (13) (10) (11) (10) Basal Cell Carcinoma, Metastatic, Skin 1 (9%) Histiocytic Sarcoma 1 (10%) Pancreas (50) (48) (48) (49) Acinus, Adenoma 1 (2%) 2 (4%) Salivary Glands (50) (50) (50) (50) Fibrosarcoma 1 (2%) Stomach, Forestomach (50) (50) (50) (49) Stomach, Glandular (50) (50) (49) (49) Tongue (3) (1) (1) Squamous Cell Carcinoma 1 (33%) Squamous Cell Papilloma 1 (33%) ____________________________________________________________________________________________________________________________________ CARDIOVASCULAR SYSTEM Heart (50) (50) (50) (50) ____________________________________________________________________________________________________________________________________ Page 8 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM ____________________________________________________________________________________________________________________________________ ENDOCRINE SYSTEM Adrenal Cortex (50) (50) (50) (50) Adenoma 1 (2%) Adrenal Medulla (50) (50) (50) (50) Pheochromocytoma Malignant 2 (4%) Pheochromocytoma Complex 2 (4%) Pheochromocytoma Benign 6 (12%) 3 (6%) 3 (6%) 3 (6%) Bilateral, Pheochromocytoma Benign 2 (4%) 2 (4%) Islets, Pancreatic (50) (49) (49) (49) Adenoma 3 (6%) 2 (4%) 1 (2%) 1 (2%) Carcinoma 1 (2%) Parathyroid Gland (48) (50) (48) (50) Adenoma 1 (2%) Pituitary Gland (49) (49) (48) (48) Pars Distalis, Adenoma 16 (33%) 13 (27%) 10 (21%) 7 (15%) Pars Intermedia, Adenoma 1 (2%) Thyroid Gland (47) (46) (48) (44) Chemodectoma Benign 1 (2%) Bilateral, C-Cell, Adenoma 1 (2%) 1 (2%) C-Cell, Adenoma 11 (23%) 6 (13%) 3 (6%) 9 (20%) C-Cell, Carcinoma 2 (4%) Follicular Cell, Adenoma 1 (2%) ____________________________________________________________________________________________________________________________________ GENERAL BODY SYSTEM Peritoneum (2) (3) (1) Tissue NOS (6) (4) (6) (5) ____________________________________________________________________________________________________________________________________ GENITAL SYSTEM Epididymis (50) (50) (50) (50) Preputial Gland (50) (50) (50) (49) Adenoma 2 (4%) 1 (2%) Carcinoma 1 (2%) Prostate (50) (50) (50) (49) Seminal Vesicle (50) (50) (50) (50) Testes (50) (50) (50) (50) Bilateral, Interstitial Cell, Adenoma 40 (80%) 40 (80%) 34 (68%) 31 (62%) Interstitial Cell, Adenoma 6 (12%) 4 (8%) 13 (26%) 14 (28%) ____________________________________________________________________________________________________________________________________ Page 9 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM ____________________________________________________________________________________________________________________________________ HEMATOPOIETIC SYSTEM Bone Marrow (47) (50) (48) (50) Lymph Node (19) (18) (26) (27) Lymph Node, Mandibular (1) (1) (2) Lymph Node, Mesenteric (50) (48) (48) (49) Spleen (50) (48) (48) (49) Fibroma 1 (2%) Thymus (48) (49) (46) (45) ____________________________________________________________________________________________________________________________________ INTEGUMENTARY SYSTEM Mammary Gland (47) (46) (41) (45) Fibroadenoma 3 (6%) 1 (2%) 1 (2%) 1 (2%) Skin (50) (50) (50) (50) Basal Cell Adenoma 1 (2%) 1 (2%) 2 (4%) Basal Cell Carcinoma 1 (2%) Keratoacanthoma 1 (2%) 3 (6%) Squamous Cell Carcinoma 1 (2%) Subcutaneous Tissue, Fibroma 7 (14%) 2 (4%) 4 (8%) 3 (6%) Subcutaneous Tissue, Fibroma, Multiple 1 (2%) Subcutaneous Tissue, Hemangioma 1 (2%) Subcutaneous Tissue, Histiocytic Sarcoma 1 (2%) Subcutaneous Tissue, Lipoma 1 (2%) Subcutaneous Tissue, Sarcoma 1 (2%) ____________________________________________________________________________________________________________________________________ MUSCULOSKELETAL SYSTEM Skeletal Muscle (2) (2) Histiocytic Sarcoma 1 (50%) ____________________________________________________________________________________________________________________________________ NERVOUS SYSTEM Brain (50) (50) (50) (50) Astrocytoma Malignant 1 (2%) Glioma Malignant 1 (2%) 1 (2%) Pineal Gland, Neoplasm NOS 1 (2%) Spinal Cord (2) (3) (2) (3) ____________________________________________________________________________________________________________________________________ Page 10 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM ____________________________________________________________________________________________________________________________________ RESPIRATORY SYSTEM Lung (50) (50) (50) (50) Alveolar/Bronchiolar Adenoma 1 (2%) 1 (2%) Alveolar/Bronchiolar Carcinoma 1 (2%) Basal Cell Carcinoma, Metastatic, Skin 1 (2%) Chordoma, Metastatic, Uncertain Primary Site 1 (2%) Nose (49) (50) (50) (50) Olfactory Epithelium, Carcinoma 1 (2%) ____________________________________________________________________________________________________________________________________ SPECIAL SENSES SYSTEM Harderian Gland (50) (50) (50) (50) Zymbal's Gland (3) (1) (2) Carcinoma 3 (100%) 1 (100%) 2 (100%) ____________________________________________________________________________________________________________________________________ URINARY SYSTEM Kidney (48) (49) (48) (50) Histiocytic Sarcoma 1 (2%) Sarcoma 1 (2%) Urinary Bladder (49) (50) (50) (50) Transitional Epithelium, Papilloma 1 (2%) ____________________________________________________________________________________________________________________________________ SYSTEMIC LESIONS Multiple Organs *(50) *(50) *(50) *(50) Histiocytic Sarcoma 1 (2%) 1 (2%) Leukemia Mononuclear 15 (30%) 18 (36%) 22 (44%) 20 (40%) Lymphoma Malignant 1 (2%) Mesothelioma Malignant 2 (4%) 3 (6%) 1 (2%) ____________________________________________________________________________________________________________________________________ * Number of animals with any tissue examined microscopically Page 11 NTP Experiment-Test: 92013-05 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05 Study Type: CHRONIC 4-METHYLIMIDAZOLE Date: 12/06/04 Route: DOSED FEED Time: 08:36:54 ____________________________________________________________________________________________________________________________________ FISCHER 344 RATS MALE 0 PPM 625 PPM 1250 PPM 2500 PPM ____________________________________________________________________________________________________________________________________ TUMOR SUMMARY Total Animals with Primary Neoplasms (b) 50 49 50 50 Total Primary Neoplasms 124 104 114 103 Total Animals with Benign Neoplasms 50 49 48 47 Total Benign Neoplasms 102 79 76 78 Total Animals with Malignant Neoplasms 22 21 30 23 Total Malignant Neoplasms 22 24 38 25 Total Animals with Metastatic Neoplasms 2 1 Total Metastatic Neoplasm 19 1 Total Animals with Malignant Neoplasms 1 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 12 ------------------------------------------------------------ ---------- 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