NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
CORE STUDY
Facility: Battelle Northwest
Chemical CAS #: 115-11-0007
Lock Date: 10/05/95
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: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially in Study 50 50 50 50
Early Deaths
Moribund Sacrifice 13 16 6 13
Natural Death 5 3 5 4
Survivors
Terminal Sacrifice 32 31 39 33
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Intestine Large, Colon (46) (48) (49) (50)
Intestine Large, Cecum (46) (47) (47) (48)
Intestine Small, Jejunum (46) (47) (46) (47)
Carcinoma 1 (2%)
Intestine Small, Ileum (46) (48) (46) (47)
Liver (47) (50) (50) (50)
Hepatoblastoma 1 (2%)
Hepatoblastoma, Multiple 1 (2%)
Hepatocellular Carcinoma 4 (9%) 8 (16%) 6 (12%) 9 (18%)
Hepatocellular Carcinoma, Multiple 1 (2%) 1 (2%) 2 (4%)
Hepatocellular Adenoma 15 (32%) 18 (36%) 11 (22%) 13 (26%)
Hepatocellular Adenoma, Multiple 5 (11%) 4 (8%) 8 (16%) 7 (14%)
Hepatocholangiocarcinoma 1 (2%)
Histiocytic Sarcoma 2 (4%) 4 (8%)
Mesentery (7) (8) (8) (10)
Histiocytic Sarcoma 1 (13%)
Lipoma 1 (13%)
Pancreas (47) (50) (48) (49)
Salivary Glands (48) (50) (50) (50)
Stomach, Forestomach (48) (49) (49) (49)
Squamous Cell Carcinoma 1 (2%)
Stomach, Glandular (46) (48) (48) (49)
Squamous Cell Carcinoma, Metastatic, Stomach,
Forestomach 1 (2%)
Tongue (1)
Squamous Cell Papilloma 1 (100%)
____________________________________________________________________________________________________________________________________
Page 2
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
Histiocytic Sarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (49) (50) (49) (50)
Hepatocellular Carcinoma, Metastatic, Liver 1 (2%)
Histiocytic Sarcoma 1 (2%)
Capsule, Adenoma 2 (4%) 1 (2%)
Adrenal Medulla (48) (49) (49) (49)
Pheochromocytoma Benign 1 (2%) 2 (4%) 2 (4%)
Bilateral, Pheochromocytoma Malignant 1 (2%)
Islets, Pancreatic (47) (49) (48) (49)
Adenoma 1 (2%) 1 (2%) 1 (2%)
Pituitary Gland (49) (49) (49) (49)
Pars Distalis, Adenoma 8 (16%) 13 (27%) 12 (24%) 12 (24%)
Pars Distalis, Carcinoma 1 (2%)
Pars Intermedia, Adenoma 1 (2%)
Thyroid Gland (48) (50) (49) (50)
Follicular Cell, Adenoma 1 (2%) 4 (8%) 3 (6%) 1 (2%)
Follicular Cell, Adenoma, Multiple 1 (2%)
Follicular Cell, Carcinoma 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Ovary (48) (50) (48) (50)
Cystadenoma 3 (6%) 1 (2%) 2 (4%)
Granulosa Cell Tumor Benign 1 (2%) 2 (4%)
Granulosa-Theca Tumor Benign 1 (2%)
Hemangioma 1 (2%) 1 (2%)
Hemangiosarcoma 1 (2%)
Histiocytic Sarcoma 2 (4%) 3 (6%) 1 (2%)
Luteoma 1 (2%)
Teratoma Benign 1 (2%)
Yolk Sac Carcinoma 1 (2%)
Uterus (49) (50) (50) (50)
Histiocytic Sarcoma 2 (4%) 1 (2%)
Polyp Stromal 2 (4%) 1 (2%) 1 (2%)
Polyp Stromal, Multiple 1 (2%)
Page 3
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (48) (49) (49) (50)
Hemangiosarcoma 1 (2%)
Histiocytic Sarcoma 2 (4%)
Lymph Node (7) (2) (5) (4)
Iliac, Histiocytic Sarcoma 1 (14%) 1 (50%)
Inguinal, Hemangiosarcoma 1 (20%)
Renal, Histiocytic Sarcoma 1 (14%) 2 (100%)
Lymph Node, Bronchial (38) (33) (44) (44)
Histiocytic Sarcoma 1 (3%)
Lymph Node, Mandibular (41) (42) (44) (38)
Histiocytic Sarcoma 2 (5%)
Lymph Node, Mesenteric (46) (48) (47) (49)
Histiocytic Sarcoma 2 (4%) 3 (6%)
Lymph Node, Mediastinal (38) (42) (36) (42)
Histiocytic Sarcoma 1 (3%) 2 (5%)
Spleen (49) (50) (50) (50)
Hemangiosarcoma 3 (6%) 1 (2%)
Hepatocholangiocarcinoma, Metastatic, Liver 1 (2%)
Histiocytic Sarcoma 1 (2%) 2 (4%)
Thymus (47) (44) (48) (46)
Histiocytic Sarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Mammary Gland (48) (49) (49) (50)
Carcinoma 2 (4%) 2 (4%)
Skin (49) (50) (49) (50)
Subcutaneous Tissue, Fibrosarcoma 2 (4%) 1 (2%) 1 (2%)
Subcutaneous Tissue, Fibrous Histiocytoma
Malignant 1 (2%)
Subcutaneous Tissue, Hemangiosarcoma 1 (2%) 1 (2%)
Subcutaneous Tissue, Sarcoma 2 (4%) 2 (4%) 2 (4%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
Page 4
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (49) (50) (50) (50)
Astrocytoma Benign 1 (2%)
Carcinoma, Metastatic, Pituitary Gland 1 (2%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (49) (50) (50) (50)
Alveolar/Bronchiolar Adenoma 2 (4%) 2 (4%) 2 (4%) 2 (4%)
Alveolar/Bronchiolar Carcinoma 4 (8%) 2 (4%) 2 (4%) 1 (2%)
Alveolar/Bronchiolar Carcinoma, Metastatic,
Lung 1 (2%)
Carcinoma, Metastatic, Mammary Gland 1 (2%)
Hepatoblastoma, Metastatic, Liver 1 (2%)
Hepatocellular Carcinoma, Metastatic, Liver 1 (2%) 4 (8%) 2 (4%) 1 (2%)
Histiocytic Sarcoma 2 (4%) 4 (8%)
Pheochromocytoma Malignant, Metastatic,
Adrenal Medulla 1 (2%)
Sarcoma, Metastatic, Skin 1 (2%)
Nose (47) (50) (49) (50)
Pleura (1)
Hepatoblastoma, Metastatic, Liver 1 (100%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Harderian Gland (2) (2) (1) (2)
Adenoma 1 (50%) 1 (50%) 1 (100%) 1 (50%)
Carcinoma 1 (50%) 1 (50%)
Bilateral, Carcinoma 1 (50%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (49) (50) (49) (50)
Histiocytic Sarcoma 3 (6%)
Urinary Bladder (45) (49) (49) (50)
Histiocytic Sarcoma 1 (2%)
____________________________________________________________________________________________________________________________________
SYSTEMIC LESIONS
Multiple Organs *(50) *(50) *(50) *(50)
Histiocytic Sarcoma 2 (4%) 4 (8%) 2 (4%)
Lymphoma Malignant 16 (32%) 9 (18%) 17 (34%) 19 (38%)
____________________________________________________________________________________________________________________________________
* Number of animals with any tissue examined microscopically
Page 5
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
TUMOR SUMMARY
Total Animals with Primary Neoplasms (b) 43 45 44 44
Total Primary Neoplasms 77 86 83 82
Total Animals with Benign Neoplasms 29 35 33 32
Total Benign Neoplasms 39 53 46 44
Total Animals with Malignant Neoplasms 29 29 30 31
Total Malignant Neoplasms 38 33 37 38
Total Animals with Metastatic Neoplasms 3 7 4 2
Total Metastatic Neoplasm 3 8 5 2
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: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY
Animals Initially in Study 50 50 50 50
Early Deaths
Natural Death 6 9 3 9
Moribund Sacrifice 16 9 20 13
Survivors
Terminal Sacrifice 28 32 27 28
Animals Examined Microscopically 50 50 50 50
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM
Gallbladder (46) (40) (45) (34)
Intestine Large, Cecum (47) (45) (49) (42)
Leiomyoma 1 (2%)
Intestine Small, Duodenum (46) (45) (48) (42)
Histiocytic Sarcoma 1 (2%)
Intestine Small, Jejunum (45) (43) (48) (43)
Carcinoma 1 (2%) 1 (2%)
Intestine Small, Ileum (46) (43) (48) (42)
Liver (50) (50) (50) (49)
Hemangiosarcoma 1 (2%) 2 (4%) 2 (4%)
Hepatoblastoma 1 (2%)
Hepatocellular Carcinoma 12 (24%) 12 (24%) 10 (20%) 7 (14%)
Hepatocellular Carcinoma, Multiple 1 (2%) 1 (2%) 4 (8%) 7 (14%)
Hepatocellular Adenoma 15 (30%) 20 (40%) 13 (26%) 10 (20%)
Hepatocellular Adenoma, Multiple 5 (10%) 4 (8%) 5 (10%) 7 (14%)
Histiocytic Sarcoma 1 (2%)
Pancreas (50) (48) (50) (47)
Salivary Glands (50) (49) (50) (50)
Stomach, Forestomach (50) (49) (50) (48)
Squamous Cell Papilloma 1 (2%)
Tooth (7) (14) (9) (16)
Odontoma 1 (14%) 3 (21%) 2 (22%) 2 (13%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
Hemangiosarcoma 1 (2%)
Pheochromocytoma Malignant, Metastatic,
Adrenal Medulla 1 (2%)
____________________________________________________________________________________________________________________________________
Page 7
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (49) (49) (50) (49)
Adenoma 1 (2%) 1 (2%) 1 (2%)
Capsule, Adenoma 1 (2%) 2 (4%) 3 (6%)
Adrenal Medulla (49) (49) (50) (49)
Pheochromocytoma Malignant 1 (2%)
Pheochromocytoma Benign 1 (2%) 1 (2%) 2 (4%)
Islets, Pancreatic (50) (48) (50) (48)
Adenoma 1 (2%)
Pituitary Gland (50) (48) (49) (48)
Pars Intermedia, Adenoma 1 (2%)
Thyroid Gland (50) (50) (50) (49)
Follicular Cell, Adenoma 1 (2%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (50) (50) (50) (50)
Prostate (48) (46) (47) (48)
Seminal Vesicle (49) (47) (50) (47)
Testes (50) (50) (50) (50)
Interstitial Cell, Adenoma 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (49) (50) (49)
Histiocytic Sarcoma 1 (2%)
Lymph Node (4) (3) (7) (1)
Renal, Histiocytic Sarcoma 1 (25%)
Lymph Node, Bronchial (30) (33) (32) (32)
Pheochromocytoma Malignant, Metastatic,
Adrenal Medulla 1 (3%)
Lymph Node, Mandibular (34) (29) (33) (35)
Lymph Node, Mesenteric (48) (49) (48) (49)
Histiocytic Sarcoma 1 (2%) 1 (2%)
Lymph Node, Mediastinal (37) (38) (36) (31)
Histiocytic Sarcoma 1 (3%)
Pheochromocytoma Malignant, Metastatic,
Adrenal Medulla 1 (3%)
Spleen (50) (49) (50) (48)
Hemangiosarcoma 1 (2%) 1 (2%)
Page 8
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - cont
Histiocytic Sarcoma 1 (2%) 1 (2%) 1 (2%)
Thymus (41) (42) (38) (41)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Skin (49) (50) (50) (50)
Subcutaneous Tissue, Hemangioma 1 (2%)
Subcutaneous Tissue, Sarcoma 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
None
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Alveolar/Bronchiolar Adenoma 9 (18%) 5 (10%) 5 (10%) 3 (6%)
Alveolar/Bronchiolar Adenoma, Multiple 3 (6%) 2 (4%)
Alveolar/Bronchiolar Carcinoma 6 (12%) 5 (10%) 4 (8%) 3 (6%)
Alveolar/Bronchiolar Carcinoma, Multiple 1 (2%) 3 (6%)
Hepatocellular Carcinoma, Metastatic, Liver 4 (8%) 4 (8%) 2 (4%) 3 (6%)
Histiocytic Sarcoma 1 (2%)
Pheochromocytoma Malignant, Metastatic,
Adrenal Medulla 1 (2%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Harderian Gland (4) (4) (4) (4)
Adenoma 2 (50%) 3 (75%) 4 (100%) 2 (50%)
Carcinoma 1 (25%) 2 (50%)
Bilateral, Adenoma 1 (25%)
____________________________________________________________________________________________________________________________________
Page 9
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (49) (50) (50)
Hepatocellular Carcinoma, Metastatic, Liver 1 (2%)
Histiocytic Sarcoma 1 (2%)
Pheochromocytoma Malignant, Metastatic,
Adrenal Medulla 1 (2%)
Renal Tubule, Adenoma 1 (2%) 2 (4%)
____________________________________________________________________________________________________________________________________
SYSTEMIC LESIONS
Multiple Organs *(50) *(50) *(50) *(50)
Histiocytic Sarcoma 1 (2%) 1 (2%) 1 (2%)
Lymphoma Malignant 4 (8%) 2 (4%) 5 (10%) 5 (10%)
____________________________________________________________________________________________________________________________________
* Number of animals with any tissue examined microscopically
Page 10
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NEOPLASMS BY ANATOMIC SITE (SYSTEMIC LESIONS ABRIDGED) (a) Report: PEIRPT05
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:23:18
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
TUMOR SUMMARY
Total Animals with Primary Neoplasms (b) 41 41 36 38
Total Primary Neoplasms 66 66 64 66
Total Animals with Benign Neoplasms 30 32 27 23
Total Benign Neoplasms 40 42 36 32
Total Animals with Malignant Neoplasms 21 19 23 23
Total Malignant Neoplasms 26 24 28 34
Total Animals with Metastatic Neoplasms 4 5 2 3
Total Metastatic Neoplasm 4 10 2 3
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 11
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