TDMS Study 05067-09 Pathology Tables
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
CORE STUDY
Facility: Southern Research Institute
Chemical CAS #: 58-55-9
Lock Date: 09/03/93
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: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially in Study 50 50 50 50
Early Deaths
Moribund Sacrifice 17 12 14 7
Natural Death 1 7 3 7
Dosing Accident 1 3
Survivors
Terminal Sacrifice 31 30 33 33
Natural Death 1
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Colon (50) (47) (50) (50)
Polyp Adenomatous 1 (2%)
Liver (50) (50) (50) (50)
Carcinoma, Metastatic, Islets, Pancreatic 1 (2%)
Hepatocellular Adenoma 1 (2%)
Sarcoma, Metastatic, Mesentery 1 (2%)
Mesentery (11) (12) (8) (4)
Carcinoma, Metastatic, Islets, Pancreatic 1 (8%)
Fibroma 1 (25%)
Sarcoma 1 (13%)
Oral Mucosa (1) (2)
Hemangiosarcoma 1 (100%)
Squamous Cell Papilloma 1 (50%)
Pancreas (50) (48) (49) (50)
Acinus, Adenoma 1 (2%) 1 (2%) 2 (4%)
Acinus, Sarcoma, Metastatic, Mesentery 1 (2%)
Salivary Glands (50) (49) (50) (50)
Stomach, Forestomach (50) (50) (50) (50)
Stomach, Glandular (50) (50) (50) (50)
Tongue (1) (1)
Squamous Cell Carcinoma 1 (100%) 1 (100%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
____________________________________________________________________________________________________________________________________
Page 2
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (50) (50) (50)
Adrenal Medulla (50) (49) (50) (49)
Pheochromocytoma Complex 1 (2%)
Pheochromocytoma Benign 2 (4%) 1 (2%)
Islets, Pancreatic (50) (49) (50) (50)
Adenoma 1 (2%) 1 (2%)
Carcinoma 1 (2%)
Pituitary Gland (47) (50) (49) (49)
Pars Distalis, Adenoma 22 (47%) 17 (34%) 17 (35%) 14 (29%)
Pars Distalis, Adenoma, Multiple 1 (2%)
Thyroid Gland (50) (50) (50) (50)
Bilateral, C-Cell, Adenoma 1 (2%)
C-Cell, Adenoma 3 (6%) 7 (14%) 5 (10%) 6 (12%)
C-Cell, Carcinoma 1 (2%)
Follicular Cell, Carcinoma 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Clitoral Gland (49) (50) (50) (50)
Adenoma 4 (8%) 3 (6%) 1 (2%) 1 (2%)
Carcinoma 2 (4%)
Ovary (50) (50) (50) (50)
Arrhenoblastoma Benign 1 (2%)
Uterus (50) (50) (50) (50)
Endometrium, Carcinoma 1 (2%)
Endometrium, Leiomyoma 1 (2%)
Endometrium, Polyp Stromal 9 (18%) 7 (14%) 11 (22%) 7 (14%)
Endometrium, Polyp Stromal, Multiple 1 (2%)
Endometrium, Sarcoma Stromal 1 (2%) 1 (2%) 3 (6%)
Vagina (1)
Schwannoma Malignant 1 (100%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (49) (50) (50)
Lymph Node (9) (10) (9) (8)
Mediastinal, Sarcoma, Metastatic, Mesentery 1 (11%)
Lymph Node, Mandibular (49) (48) (50) (50)
Lymph Node, Mesenteric (50) (50) (50) (50)
Page 3
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - cont
Spleen (50) (48) (50) (50)
Thymus (49) (49) (48) (50)
Thymoma Benign 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (50) (50) (50) (49)
Carcinoma 1 (2%) 1 (2%)
Fibroadenoma 17 (34%) 17 (34%) 11 (22%) 12 (24%)
Fibroadenoma, Multiple 5 (10%) 2 (4%) 1 (2%)
Skin (50) (50) (50) (50)
Basal Cell Adenoma 1 (2%)
Keratoacanthoma 1 (2%)
Sebaceous Gland, Adenoma 1 (2%)
Subcutaneous Tissue, Fibroma 2 (4%) 1 (2%) 1 (2%)
Subcutaneous Tissue, Fibrous Histiocytoma 1 (2%)
Subcutaneous Tissue, Melanoma Benign 1 (2%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Skeletal Muscle (1) (1)
Sarcoma, Metastatic, Mesentery 1 (100%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (50) (50) (50)
Glioma Malignant 1 (2%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Alveolar/Bronchiolar Adenoma 1 (2%) 1 (2%)
Nose (50) (50) (50) (50)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Zymbal's Gland (1)
Adenoma 1 (100%)
____________________________________________________________________________________________________________________________________
Page 4
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (48) (50) (49)
Lipoma 1 (2%)
Sarcoma 1 (2%)
Urinary Bladder (50) (49) (50) (50)
Leiomyosarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
SYSTEMIC LESIONS
Multiple Organs *(50) *(50) *(50) *(50)
Leukemia Mononuclear 10 (20%) 8 (16%) 9 (18%) 12 (24%)
____________________________________________________________________________________________________________________________________
* Number of animals with any tissue examined microscopically
Page 5
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS FEMALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
TUMOR SUMMARY
Total Animals with Primary Neoplasms (b) 44 41 40 36
Total Primary Neoplasms 87 72 69 65
Total Animals with Benign Neoplasms 37 39 32 30
Total Benign Neoplasms 69 59 51 51
Total Animals with Malignant Neoplasms 18 11 16 14
Total Malignant Neoplasms 18 13 18 14
Total Animals with Metastatic Neoplasms 1 1
Total Metastatic Neoplasm 2 4
Total Animals with Malignant Neoplasms
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: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially in Study 50 50 50 50
Early Deaths
Moribund Sacrifice 21 11 18 13
Natural Death 5 5 2 13
Dosing Accident 1 1 1
Survivors
Terminal Sacrifice 23 33 29 24
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Small, Jejunum (49) (48) (50) (49)
Polyp Adenomatous 1 (2%)
Intestine Small, Ileum (49) (48) (50) (49)
Liver (50) (50) (50) (50)
Fibrous Histiocytoma 1 (2%)
Hepatocellular Adenoma 1 (2%) 2 (4%) 1 (2%)
Hepatocellular Adenoma, Multiple 1 (2%)
Histiocytic Sarcoma 2 (4%)
Osteosarcoma, Metastatic, Bone 1 (2%)
Mesentery (16) (16) (17) (27)
Histiocytic Sarcoma 1 (6%)
Oral Mucosa (1) (1)
Squamous Cell Papilloma 1 (100%)
Pancreas (50) (50) (50) (50)
Histiocytic Sarcoma 1 (2%)
Acinus, Adenoma 8 (16%) 6 (12%) 4 (8%) 4 (8%)
Acinus, Adenoma, Multiple 2 (4%) 1 (2%)
Salivary Glands (50) (50) (50) (50)
Schwannoma Malignant, Metastatic, Skin 1 (2%)
Tongue (1) (1) (1)
Squamous Cell Papilloma 1 (100%) 1 (100%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
None
____________________________________________________________________________________________________________________________________
Page 7
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (50) (50) (50) (50)
Adenoma 1 (2%)
Carcinoma 1 (2%)
Adrenal Medulla (50) (49) (50) (50)
Fibrous Histiocytoma 1 (2%)
Pheochromocytoma Malignant 2 (4%)
Pheochromocytoma Malignant, Multiple 1 (2%)
Pheochromocytoma Complex 1 (2%)
Pheochromocytoma Benign 5 (10%) 5 (10%) 6 (12%) 9 (18%)
Bilateral, Pheochromocytoma Benign 2 (4%) 1 (2%) 1 (2%)
Islets, Pancreatic (50) (50) (50) (50)
Carcinoma 2 (4%) 1 (2%)
Carcinoma, Multiple 1 (2%)
Pituitary Gland (50) (49) (50) (48)
Pars Distalis, Adenoma 19 (38%) 18 (37%) 16 (32%) 10 (21%)
Thyroid Gland (50) (50) (50) (50)
C-Cell, Adenoma 5 (10%) 1 (2%) 3 (6%) 1 (2%)
C-Cell, Carcinoma 1 (2%) 2 (4%)
Follicular Cell, Adenoma 1 (2%)
Follicular Cell, Carcinoma 2 (4%) 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
Peritoneum (2) (2) (3) (3)
Fibrosarcoma, Metastatic, Spleen 1 (50%)
Tissue NOS (2) (1)
Mediastinum, Hemangioma 1 (50%)
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (50) (50) (50) (50)
Preputial Gland (50) (49) (50) (50)
Adenoma 2 (4%) 4 (8%) 3 (6%)
Carcinoma 3 (6%) 2 (4%) 3 (6%)
Bilateral, Carcinoma 1 (2%)
Prostate (50) (50) (50) (50)
Histiocytic Sarcoma 1 (2%)
Seminal Vesicle (50) (50) (50) (50)
Testes (50) (50) (50) (50)
Bilateral, Interstitial Cell, Adenoma 42 (84%) 38 (76%) 41 (82%) 43 (86%)
Interstitial Cell, Adenoma 4 (8%) 4 (8%) 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
Page 8
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (50) (50) (50)
Lymph Node (13) (11) (12) (9)
Inguinal, Fibrous Histiocytoma 1 (9%)
Mediastinal, Fibrous Histiocytoma 1 (9%)
Mediastinal, Histiocytic Sarcoma 1 (8%)
Lymph Node, Mandibular (48) (49) (50) (50)
Osteosarcoma, Metastatic, Bone 1 (2%)
Lymph Node, Mesenteric (50) (49) (50) (49)
Fibrous Histiocytoma 1 (2%)
Histiocytic Sarcoma 1 (2%)
Spleen (49) (50) (50) (49)
Fibroma 2 (4%) 1 (2%)
Fibrosarcoma 1 (2%)
Fibrous Histiocytoma 1 (2%)
Hemangiosarcoma 1 (2%)
Thymus (49) (47) (47) (50)
Thymoma Benign 1 (2%)
Thymoma Malignant 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (48) (49) (47) (48)
Carcinoma 1 (2%)
Fibroadenoma 3 (6%) 2 (4%) 1 (2%) 1 (2%)
Skin (50) (50) (50) (50)
Basal Cell Adenoma 1 (2%)
Keratoacanthoma 2 (4%) 1 (2%)
Squamous Cell Papilloma 1 (2%)
Trichoepithelioma 1 (2%)
Subcutaneous Tissue, Fibroma 5 (10%) 1 (2%) 6 (12%) 4 (8%)
Subcutaneous Tissue, Fibroma, Multiple 1 (2%) 1 (2%)
Subcutaneous Tissue, Fibrosarcoma 1 (2%)
Subcutaneous Tissue, Fibrous Histiocytoma 1 (2%)
Subcutaneous Tissue, Histiocytic Sarcoma 1 (2%)
Subcutaneous Tissue, Lipoma 1 (2%)
Subcutaneous Tissue, Melanoma Benign 1 (2%)
Subcutaneous Tissue, Melanoma Malignant 2 (4%)
Subcutaneous Tissue, Schwannoma Malignant 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
Page 9
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
Bone (50) (50) (50) (50)
Osteosarcoma 1 (2%) 1 (2%)
Skeletal Muscle (4) (1) (1)
Fibrosarcoma, Metastatic, Spleen 1 (25%)
Histiocytic Sarcoma 1 (25%)
Sarcoma 1 (100%)
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (50) (49) (50) (49)
Astrocytoma Malignant 1 (2%)
Glioma Malignant 1 (2%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Alveolar/Bronchiolar Adenoma 2 (4%) 1 (2%) 2 (4%)
Alveolar/Bronchiolar Carcinoma 1 (2%)
Fibrous Histiocytoma 1 (2%)
Histiocytic Sarcoma 2 (4%)
Osteosarcoma, Metastatic, Bone 1 (2%)
Osteosarcoma, Metastatic, Uncertain Primary
Site 1 (2%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Zymbal's Gland (2)
Carcinoma 2 (100%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (49) (49) (50) (49)
Fibrous Histiocytoma 1 (2%)
Histiocytic Sarcoma 1 (2%)
Artery, Osteosarcoma, Metastatic, Bone 1 (2%)
____________________________________________________________________________________________________________________________________
SYSTEMIC LESIONS
Multiple Organs *(50) *(50) *(50) *(50)
Histiocytic Sarcoma 2 (4%)
* Number of animals with any tissue examined microscopically
Page 10
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
SYSTEMIC LESIONS - cont
Multiple Organs *(50) *(50) *(50) *(50)
Leukemia Mononuclear 15 (30%) 5 (10%) 6 (12%) 6 (12%)
Mesothelioma Malignant 1 (2%) 2 (4%) 4 (8%) 3 (6%)
____________________________________________________________________________________________________________________________________
Page 11
NTP Experiment-Test: 05067-09 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC THEOPHYLLINE Date: 07/11/96
Route: GAVAGE Time: 17:04:03
____________________________________________________________________________________________________________________________________
FISCHER 344 RATS MALE VEHICLE 7.5 25 MG/KG 75 MG/KG
CONTROL MG/KG
____________________________________________________________________________________________________________________________________
TUMOR SUMMARY
Total Animals with Primary Neoplasms (b) 49 49 48 47
Total Primary Neoplasms 134 118 106 100
Total Animals with Benign Neoplasms 49 49 48 46
Total Benign Neoplasms 104 87 89 84
Total Animals with Malignant Neoplasms 23 18 14 14
Total Malignant Neoplasms 30 31 17 16
Total Animals with Metastatic Neoplasms 2 2 1
Total Metastatic Neoplasm 5 4 1
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
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