NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
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 NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
____________________________________________________________________________________________________________________________________
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, Rectum (45) (45) (47) (48)
Artery, Inflammation, Chronic Active 1 (2%)
Intestine Small, Ileum (46) (48) (46) (47)
Inflammation, Chronic Active 1 (2%)
Liver (47) (50) (50) (50)
Angiectasis 1 (2%) 1 (2%) 1 (2%)
Basophilic Focus 4 (9%) 4 (8%) 2 (4%) 5 (10%)
Clear Cell Focus 4 (8%) 3 (6%) 4 (8%)
Cyst 1 (2%) 1 (2%)
Degeneration, Fatty 2 (4%) 1 (2%) 5 (10%) 1 (2%)
Eosinophilic Focus 17 (36%) 11 (22%) 12 (24%) 7 (14%)
Hematopoietic Cell Proliferation 1 (2%) 1 (2%)
Mixed Cell Focus 1 (2%)
Necrosis 2 (4%) 3 (6%) 1 (2%)
Tension Lipidosis 1 (2%) 3 (6%) 1 (2%)
Bile Duct, Hyperplasia 1 (2%)
Centrilobular, Necrosis 1 (2%) 3 (6%)
Mesentery (7) (8) (8) (10)
Artery, Inflammation 1 (13%) 1 (10%)
Fat, Inflammation, Chronic Active 1 (10%)
Fat, Necrosis 7 (100%) 6 (75%) 6 (75%) 10 (100%)
Pancreas (47) (50) (48) (49)
Atrophy 1 (2%)
Basophilic Focus 1 (2%) 2 (4%)
Lipomatosis 1 (2%) 1 (2%)
Duct, Cyst 1 (2%) 1 (2%)
Stomach, Forestomach (48) (49) (49) (49)
Hyperplasia 2 (4%) 4 (8%) 1 (2%) 1 (2%)
Inflammation, Acute 1 (2%) 2 (4%)
Stomach, Glandular (46) (48) (48) (49)
Necrosis 1 (2%)
Artery, Inflammation, Chronic Active 1 (2%)
Tooth (1) (1)
Malformation 1 (100%) 1 (100%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 2
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
Cardiomyopathy 10 (20%) 10 (20%) 12 (24%) 8 (16%)
Mineralization 1 (2%)
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (49) (50) (49) (50)
Hematopoietic Cell Proliferation 1 (2%) 1 (2%) 1 (2%)
Hyperplasia 3 (6%) 4 (8%) 3 (6%) 5 (10%)
Hypertrophy 3 (6%) 1 (2%) 4 (8%) 2 (4%)
Vacuolization Cytoplasmic 1 (2%) 2 (4%) 1 (2%) 2 (4%)
Adrenal Medulla (48) (49) (49) (49)
Hyperplasia 3 (6%)
Islets, Pancreatic (47) (49) (48) (49)
Hyperplasia 1 (2%) 1 (2%) 3 (6%)
Pituitary Gland (49) (49) (49) (49)
Pars Distalis, Hyperplasia 13 (27%) 15 (31%) 19 (39%) 14 (29%)
Thyroid Gland (48) (50) (49) (50)
Follicular Cell, Hyperplasia 25 (52%) 16 (32%) 29 (59%) 30 (60%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Ovary (48) (50) (48) (50)
Angiectasis 1 (2%) 3 (6%)
Cyst 13 (27%) 14 (28%) 11 (23%) 8 (16%)
Inflammation, Suppurative 1 (2%)
Uterus (49) (50) (50) (50)
Angiectasis 1 (2%)
Hydrometra 6 (12%) 7 (14%) 3 (6%) 4 (8%)
Inflammation, Suppurative 1 (2%) 1 (2%)
Necrosis 1 (2%)
Thrombosis 1 (2%)
Endometrium, Hyperplasia, Cystic 1 (2%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 3
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (48) (49) (49) (50)
Necrosis 1 (2%)
Lymph Node (7) (2) (5) (4)
Lumbar, Hemorrhage 1 (14%)
Lymph Node, Bronchial (38) (33) (44) (44)
Hyperplasia, Plasma Cell 1 (3%)
Lymph Node, Mandibular (41) (42) (44) (38)
Hyperplasia, Lymphoid 1 (2%)
Infiltration Cellular, Mixed Cell 1 (2%)
Lymph Node, Mesenteric (46) (48) (47) (49)
Angiectasis 1 (2%) 2 (4%)
Infiltration Cellular, Plasma Cell 1 (2%)
Infiltration Cellular, Mixed Cell 1 (2%)
Lymph Node, Mediastinal (38) (42) (36) (42)
Infiltration Cellular, Mixed Cell 1 (3%)
Spleen (49) (50) (50) (50)
Hematopoietic Cell Proliferation 4 (8%) 12 (24%) 6 (12%) 5 (10%)
Infarct 1 (2%)
Infiltration Cellular, Histiocyte 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Skin (49) (50) (49) (50)
Inflammation, Acute 1 (2%)
Inflammation, Chronic Active 1 (2%) 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Brain (49) (50) (50) (50)
Inflammation, Chronic Active 1 (2%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (49) (50) (50) (50)
Hemorrhage 1 (2%)
Infiltration Cellular, Histiocyte 1 (2%) 1 (2%)
Inflammation, Granulomatous 1 (2%)
Metaplasia, Osseous 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 4
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
____________________________________________________________________________________________________________________________________
B6C3F1 MICE FEMALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM - CONT
Alveolar Epithelium, Hyperplasia 4 (8%) 3 (6%) 3 (6%) 1 (2%)
Nose (47) (50) (49) (50)
Inflammation, Chronic 1 (2%)
Inflammation, Suppurative 1 (2%) 1 (2%)
Olfactory Epithelium, Atrophy 1 (2%)
Olfactory Epithelium, Degeneration, Hyaline 17 (36%) 19 (38%) 24 (49%) 27 (54%)
Respiratory Epithelium, Degeneration, Hyaline 21 (45%) 39 (78%) 41 (84%) 48 (96%)
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (1) (1) (1)
Degeneration 1 (100%)
Cornea, Metaplasia, Squamous 1 (100%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (49) (50) (49) (50)
Amyloid Deposition 1 (2%)
Cyst 1 (2%)
Infarct 1 (2%) 2 (4%) 1 (2%)
Metaplasia, Osseous 1 (2%) 1 (2%) 2 (4%)
Mineralization 1 (2%)
Nephropathy 13 (27%) 14 (28%) 18 (37%) 12 (24%)
Renal Tubule, Necrosis 1 (2%)
Urinary Bladder (45) (49) (49) (50)
Artery, Inflammation, Chronic Active 1 (2%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 5
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
____________________________________________________________________________________________________________________________________
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
Liver (50) (50) (50) (49)
Basophilic Focus 7 (14%) 8 (16%) 6 (12%) 5 (10%)
Clear Cell Focus 9 (18%) 4 (8%) 6 (12%) 10 (20%)
Cyst 1 (2%) 1 (2%)
Degeneration, Fatty 2 (4%) 1 (2%) 2 (4%) 5 (10%)
Eosinophilic Focus 5 (10%) 4 (8%) 11 (22%) 7 (14%)
Mixed Cell Focus 2 (4%) 1 (2%)
Necrosis 1 (2%) 5 (10%) 2 (4%) 1 (2%)
Vacuolization Cytoplasmic, Focal 1 (2%) 1 (2%) 1 (2%)
Centrilobular, Necrosis 2 (4%)
Mesentery (4) (2) (4) (2)
Fat, Inflammation, Chronic Active 1 (25%)
Fat, Necrosis 3 (75%) 2 (100%) 4 (100%) 2 (100%)
Pancreas (50) (48) (50) (47)
Atrophy 1 (2%)
Basophilic Focus 1 (2%)
Stomach, Forestomach (50) (49) (50) (48)
Hyperplasia 2 (4%) 1 (2%) 1 (2%)
Inflammation, Acute 1 (2%) 1 (2%)
Stomach, Glandular (49) (47) (49) (46)
Inflammation, Acute 1 (2%)
Necrosis 2 (4%) 1 (2%)
Tooth (7) (14) (9) (16)
Malformation 6 (86%) 12 (86%) 7 (78%) 14 (88%)
____________________________________________________________________________________________________________________________________
CARDIOVASCULAR SYSTEM
Heart (50) (50) (50) (50)
Cardiomyopathy 21 (42%) 18 (36%) 16 (32%) 19 (38%)
Inflammation, Chronic 1 (2%)
Thrombosis 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 6
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM
Adrenal Cortex (49) (49) (50) (49)
Hyperplasia 14 (29%) 10 (20%) 15 (30%) 16 (33%)
Hypertrophy 32 (65%) 24 (49%) 24 (48%) 29 (59%)
Adrenal Medulla (49) (49) (50) (49)
Hyperplasia 1 (2%) 1 (2%)
Islets, Pancreatic (50) (48) (50) (48)
Hyperplasia 1 (2%) 1 (2%) 1 (2%)
Pituitary Gland (50) (48) (49) (48)
Pars Distalis, Hyperplasia 1 (2%) 4 (8%) 3 (6%) 4 (8%)
Thyroid Gland (50) (50) (50) (49)
Follicular Cell, Hyperplasia 5 (10%) 6 (12%) 3 (6%) 3 (6%)
____________________________________________________________________________________________________________________________________
GENERAL BODY SYSTEM
None
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM
Epididymis (50) (50) (50) (50)
Granuloma Sperm 1 (2%) 1 (2%) 5 (10%)
Penis (2)
Inflammation, Acute 1 (50%)
Preputial Gland (50) (48) (50) (50)
Cyst 2 (4%) 1 (2%)
Inflammation, Chronic Active 2 (4%) 3 (6%)
Prostate (48) (46) (47) (48)
Inflammation, Chronic Active 2 (4%) 4 (9%) 4 (8%)
Seminal Vesicle (49) (47) (50) (47)
Necrosis 1 (2%)
Testes (50) (50) (50) (50)
Atrophy 1 (2%) 1 (2%)
Mineralization 1 (2%)
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM
Bone Marrow (50) (49) (50) (49)
Congestion 1 (2%)
Hemorrhage 1 (2%)
Lymph Node (4) (3) (7) (1)
Iliac, Infiltration Cellular, Plasma Cell 1 (33%) 2 (29%) 1 (100%)
Iliac, Infiltration Cellular,
Polymorphonuclear 1 (14%)
Lumbar, Infiltration Cellular, Plasma Cell 1 (33%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 7
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT
Pancreatic, Infiltration Cellular, Plasma
Cell 1 (25%)
Lymph Node, Mesenteric (48) (49) (48) (49)
Angiectasis 1 (2%) 1 (2%)
Infiltration Cellular, Plasma Cell 1 (2%)
Spleen (50) (49) (50) (48)
Hematopoietic Cell Proliferation 4 (8%) 3 (6%) 5 (10%) 4 (8%)
Infiltration Cellular, Histiocyte 1 (2%) 1 (2%)
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM
Skin (49) (50) (50) (50)
Cyst 1 (2%)
Prepuce, Inflammation, Chronic Active 7 (14%) 6 (12%) 13 (26%) 9 (18%)
Subcutaneous Tissue, Edema 1 (2%)
____________________________________________________________________________________________________________________________________
MUSCULOSKELETAL SYSTEM
None
____________________________________________________________________________________________________________________________________
NERVOUS SYSTEM
Peripheral Nerve (1)
Sciatic, Degeneration 1 (100%)
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM
Lung (50) (50) (50) (50)
Hemorrhage 3 (6%)
Thrombosis 1 (2%) 1 (2%)
Alveolar Epithelium, Hyperplasia 5 (10%) 6 (12%) 4 (8%) 3 (6%)
Nose (50) (49) (50) (48)
Inflammation, Suppurative 1 (2%) 2 (4%) 2 (4%)
Polyp, Inflammatory 1 (2%) 1 (2%)
Nasolacrimal Duct, Polyp, Inflammatory 1 (2%)
Olfactory Epithelium, Atrophy 1 (2%) 1 (2%) 1 (2%) 2 (4%)
Olfactory Epithelium, Degeneration, Hyaline 6 (12%) 7 (14%) 16 (32%) 17 (35%)
Respiratory Epithelium, Degeneration, Hyaline 6 (12%) 19 (39%) 29 (58%) 39 (81%)
____________________________________________________________________________________________________________________________________
a Number of animals examined microscopically at site and number of animals with lesion
Page 8
NTP Experiment-Test: 88070-04 INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a) Report: PEIRPT03
Study Type: CHRONIC ISOBUTENE Date: 06/20/97
Route: RESPIRATORY EXPOSURE WHOLE BODY Time: 12:10:34
____________________________________________________________________________________________________________________________________
B6C3F1 MICE MALE CONTROL 500 PPM 2000 PPM 8000 PPM
____________________________________________________________________________________________________________________________________
SPECIAL SENSES SYSTEM
Eye (2) (2)
Cataract 1 (50%)
Cornea, Inflammation, Chronic Active 1 (50%)
Harderian Gland (4) (4) (4) (4)
Hyperplasia 1 (25%)
____________________________________________________________________________________________________________________________________
URINARY SYSTEM
Kidney (50) (49) (50) (50)
Cyst 1 (2%) 1 (2%)
Infarct 1 (2%) 2 (4%) 4 (8%)
Inflammation, Chronic Active 1 (2%)
Metaplasia, Osseous 1 (2%) 2 (4%)
Mineralization 1 (2%) 1 (2%)
Nephropathy 36 (72%) 39 (80%) 38 (76%) 40 (80%)
Capsule, Inflammation, Chronic 1 (2%)
Papilla, Inflammation, Suppurative 3 (6%) 3 (6%) 6 (12%) 5 (10%)
Pelvis, Dilatation 3 (6%) 2 (4%) 4 (8%) 4 (8%)
Renal Tubule, Hyperplasia 1 (2%) 1 (2%)
Urinary Bladder (49) (47) (49) (46)
Calculus Gross Observation 1 (2%)
Inflammation, Chronic Active 4 (8%) 3 (6%) 7 (14%) 6 (13%)
a Number of animals examined microscopically at site and number of animals with lesion
Page 9
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