National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/6857

TDMS Study 97006-02 Pathology Tables

NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48

                                                          FINAL#1 MICE




       Facility:  Battelle Northwest

       Chemical CAS #:  108-10-1

       Lock Date:  01/24/03

       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
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)

                                                              Page   1


NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                10            9            6            9                                     
    Natural Death                                      5            3            5            3                                     
    Accidently Killed                                               1                                                               
  Survivors                                                                                                                         
    Terminal Sacrifice                                35           37           39           38                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Large, Colon                             (48)         (48)         (49)         (49)                                   
      Artery, Inflammation, Chronic Active             1 [2.0]                                                                      
   Intestine Large, Rectum                            (47)         (48)         (48)         (49)                                   
      Artery, Inflammation, Chronic Active             1 [3.0]                                                                      
   Intestine Large, Cecum                             (46)         (48)         (47)         (49)                                   
      Artery, Inflammation, Chronic Active             1 [2.0]      1 [4.0]                                                         
   Intestine Small, Duodenum                          (47)         (48)         (47)         (48)                                   
      Ulcer                                                         1 [4.0]                                                         
      Peyer's Patch, Hyperplasia                                                              1 [2.0]                               
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                                                1 [2.0]                                            
      Basophilic Focus                                 3            2            1            3                                     
      Clear Cell Focus                                 3            4            5            2                                     
      Cyst                                                          1 [4.0]                                                         
      Eosinophilic Focus                               4           11           10           14                                     
      Fatty Change                                                               1 [2.0]                                            
      Hematopoietic Cell Proliferation                                           2 [2.0]                                            
      Infarct                                                       1                                                               
      Infiltration Cellular, Mast Cell                 1 [2.0]                                                                      
      Inflammation, Chronic                                         1 [1.0]                   2 [1.5]                               
      Mixed Cell Focus                                 1            1            1            1                                     
      Necrosis                                         3 [2.7]      1 [2.0]      5 [2.6]      1 [1.0]                               
      Tension Lipidosis                                1 [1.0]      2 [1.5]      3 [1.7]                                            
      Thrombosis                                       1 [2.0]                                                                      
      Bile Duct, Hyperplasia                           1 [2.0]                                                                      
   Mesentery                                          (11)         (11)         (13)         (8)                                    
      Artery, Inflammation, Chronic Active                          1 [4.0]                                                         
      Fat, Hemorrhage                                  1 [2.0]                                                                      
      Fat, Necrosis                                    9 [2.0]      9 [2.0]     11 [2.1]      7 [2.0]                               
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    2                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
   Pancreas                                           (50)         (50)         (49)         (50)                                   
      Atrophy                                          3 [2.7]                   1 [4.0]                                            
      Basophilic Focus                                                           1 [2.0]                                            
      Inflammation, Chronic Active                     1 [2.0]                   1 [2.0]                                            
      Necrosis, Fatty                                                            1 [3.0]                                            
      Artery, Inflammation, Chronic Active                          1 [3.0]                                                         
      Duct, Cyst                                       1 [3.0]                   1 [4.0]                                            
   Salivary Glands                                    (50)         (50)         (50)         (50)                                   
      Atrophy                                                                                 1 [2.0]                               
      Artery, Inflammation, Chronic Active                          1 [3.0]                                                         
   Stomach, Forestomach                               (50)         (50)         (50)         (50)                                   
      Hyperplasia, Squamous                            1 [1.0]      2 [1.0]      1 [1.0]      2 [2.0]                               
      Inflammation                                                  1 [1.0]                   2 [1.5]                               
      Artery, Inflammation, Chronic Active             2 [2.5]                                                                      
   Stomach, Glandular                                 (49)         (50)         (48)         (49)                                   
      Metaplasia, Hepatocyte                                                     1 [4.0]                                            
      Necrosis                                                                                1 [1.0]                               
      Artery, Inflammation, Chronic Active             2 [3.0]                                                                      
   Tooth                                              (1)                                    (1)                                    
      Malformation                                     1 [4.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                   3 [1.7]      6 [1.3]      5 [1.0]      3 [1.0]                               
      Inflammation, Suppurative                                                               1 [3.0]                               
      Artery, Inflammation, Chronic Active             1 [3.0]      2 [2.5]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Hematopoietic Cell Proliferation                                           1 [3.0]                                            
      Hyperplasia                                      4 [2.0]      3 [2.0]      1 [2.0]      2 [1.5]                               
      Hypertrophy                                      3 [2.3]                   3 [2.7]      3 [1.0]                               
      Infiltration Cellular, Mononuclear Cell                                                 1 [3.0]                               
      Necrosis                                                      1 [2.0]                                                         
   Adrenal Medulla                                    (50)         (50)         (49)         (49)                                   
      Hyperplasia                                      2 [3.0]      2 [3.0]      1 [2.0]                                            
   Islets, Pancreatic                                 (50)         (50)         (49)         (50)                                   
      Hyperplasia                                                                2 [2.0]      1 [2.0]                               
   Pituitary Gland                                    (50)         (49)         (48)         (49)                                   
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    3                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Pars Distalis, Angiectasis                       1 [1.0]      3 [2.3]      3 [2.3]      2 [1.5]                               
      Pars Distalis, Hyperplasia                      10 [2.4]      8 [2.6]     13 [2.5]     11 [2.6]                               
      Pars Intermedia, Hyperplasia                     1 [2.0]                                                                      
   Thyroid Gland                                      (50)         (50)         (49)         (48)                                   
      Cyst                                                          1 [3.0]                                                         
      Follicular Cell, Hyperplasia                     7 [2.1]      5 [1.4]     11 [1.5]      8 [1.6]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   Peritoneum                                                      (2)          (1)                                                 
      Inflammation, Suppurative                                                  1 [3.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Ovary                                              (49)         (50)         (48)         (50)                                   
      Angiectasis                                                   1 [2.0]                                                         
      Cyst                                            14 [2.4]     13 [2.2]     13 [2.6]      9 [2.2]                               
      Inflammation, Suppurative                                                               1 [1.0]                               
      Thrombosis                                       1 [3.0]                                                                      
      Artery, Inflammation, Chronic Active             1 [3.0]                                1 [3.0]                               
   Uterus                                             (50)         (50)         (49)         (50)                                   
      Amyloid Deposition                               1 [2.0]                                                                      
      Angiectasis                                      1 [4.0]      2 [3.0]      1 [4.0]      2 [3.0]                               
      Hyperplasia, Cystic                                           1 [3.0]                                                         
      Infiltration Cellular, Mixed Cell                                                       1 [2.0]                               
      Inflammation, Suppurative                                     1 [2.0]      1 [3.0]      1 [4.0]                               
      Metaplasia, Squamous                                                                    1 [2.0]                               
      Necrosis                                                      1 [3.0]                                                         
      Thrombosis                                                                 1 [2.0]                                            
      Endometrium, Hyperplasia, Cystic                49 [3.2]     48 [3.3]     46 [3.1]     49 [3.4]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (49)         (50)                                   
      Infiltration Cellular, Mast Cell                 1 [2.0]                                                                      
   Lymph Node                                         (7)          (3)          (9)          (5)                                    
      Iliac, Ectasia                                                1 [2.0]                                                         
      Iliac, Infiltration Cellular, Plasma Cell        1 [3.0]                                                                      
      Lumbar, Angiectasis                                           1 [3.0]                                                         
      Lumbar, Ectasia                                                            1 [3.0]                                            
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    4                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Lumbar, Infiltration Cellular, Plasma Cell                                              1 [4.0]                               
      Renal, Angiectasis                                            1 [3.0]      1 [3.0]                                            
      Renal, Ectasia                                   1 [3.0]                                                                      
      Renal, Infiltration Cellular, Plasma Cell                                               1 [3.0]                               
      Renal, Artery, Inflammation, Chronic Active                   1 [3.0]                                                         
   Lymph Node, Mandibular                             (40)         (42)         (39)         (38)                                   
      Hyperplasia, Lymphoid                                         2 [2.5]                                                         
      Infiltration Cellular, Plasma Cell                                                      1 [3.0]                               
   Lymph Node, Mesenteric                             (50)         (49)         (49)         (47)                                   
      Angiectasis                                                                             1 [2.0]                               
      Hyperplasia, Lymphoid                                         1 [3.0]                                                         
   Lymph Node, Mediastinal                            (46)         (40)         (38)         (41)                                   
      Hyperplasia, Lymphoid                                         1 [3.0]                                                         
      Infiltration Cellular, Mast Cell                 1 [2.0]                                                                      
   Spleen                                             (50)         (50)         (49)         (50)                                   
      Hematopoietic Cell Proliferation                 5 [2.4]      1 [2.0]      7 [2.9]      5 [3.0]                               
      Infiltration Cellular, Mast Cell                 1 [2.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (50)         (49)         (50)         (49)                                   
      Hyperplasia                                                   1 [3.0]                                                         
   Skin                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                                  1 [3.0]                                                         
      Hemorrhage                                       1 [4.0]                                                                      
      Inflammation, Chronic Active                     2 [1.5]      2 [1.5]      5 [2.0]      2 [2.5]                               
      Inflammation, Suppurative                                     1 [4.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Fracture                                                      1                                                               
      Hyperostosis                                                               1 [2.0]                                            
      Infiltration Cellular, Mast Cell                 1 [2.0]                                                                      
   Skeletal Muscle                                    (1)          (2)          (3)          (2)                                    
      Inflammation, Suppurative                                     1 [3.0]                                                         
      Artery, Inflammation, Chronic Active                                                    1 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    5                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
NERVOUS SYSTEM - CONT                                                                                                               
   Brain                                              (50)         (50)         (50)         (50)                                   
      Meninges, Infiltration Cellular, Mononuclear                                                                                  
        Cell                                                        1 [2.0]      2 [1.5]      2 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Larynx                                             (50)         (50)         (49)         (50)                                   
      Artery, Inflammation, Chronic Active             1 [3.0]                   1 [3.0]                                            
      Respiratory Epithelium, Degeneration, Hyaline                              1 [3.0]                                            
   Lung                                               (50)         (50)         (50)         (50)                                   
      Infiltration Cellular, Mononuclear Cell                                    1 [4.0]                                            
      Alveolar Epithelium, Hyperplasia                 1 [2.0]      5 [2.2]      3 [1.7]      5 [1.0]                               
      Alveolus, Infiltration Cellular, Histiocyte      1 [1.0]                   2 [2.0]                                            
      Artery, Mineralization                                        1 [3.0]                                                         
      Bronchiole, Hyperplasia                                       4 [1.0]      2 [2.0]                                            
   Nose                                               (50)         (50)         (50)         (49)                                   
      Infiltration Cellular, Mast Cell                 1 [4.0]                                                                      
      Inflammation, Suppurative                        4 [1.3]      3 [1.7]      2 [2.0]                                            
      Artery, Inflammation, Chronic Active             1 [2.0]                                                                      
      Glands, Hyperplasia                             23 [1.0]     30 [1.0]     23 [1.0]     20 [1.0]                               
      Olfactory Epithelium, Atrophy                                 1 [1.0]      1 [1.0]                                            
      Olfactory Epithelium, Degeneration, Hyaline      8 [1.5]      5 [1.0]      4 [1.5]      1 [1.0]                               
      Respiratory Epithelium, Degeneration, Hyaline   24 [1.8]     19 [1.9]     20 [1.8]     13 [1.3]                               
      Respiratory Epithelium, Metaplasia               3 [1.0]      3 [1.0]      6 [1.0]      1 [1.0]                               
      Respiratory Epithelium, Metaplasia, Squamous                               1 [1.0]                                            
      Turbinate, Necrosis                                                        2 [1.5]                                            
   Trachea                                            (50)         (50)         (49)         (50)                                   
      Degeneration, Hyaline                                                      1 [3.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (49)         (48)         (49)         (50)                                   
      Cataract                                                                   1 [3.0]                                            
      Degeneration                                                                            1 [4.0]                               
      Cornea, Inflammation, Chronic Active             1 [1.0]      1 [2.0]      3 [2.3]      2 [3.0]                               
      Cornea, Mineralization                           1 [1.0]                                                                      
      Retina, Atrophy                                  1 [3.0]                                                                      
   Harderian Gland                                    (49)         (49)         (49)         (50)                                   
      Hyperplasia                                      1 [2.0]      1 [1.0]      2 [3.0]      1 [1.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (49)         (50)                                   
      Amyloid Deposition                               1 [4.0]                                                                      
      Cyst                                                                       1 [3.0]                                            
      Metaplasia, Osseous                              2 [1.0]      2 [1.0]      3 [1.0]      2 [1.0]                               
      Nephropathy                                     22 [1.1]     28 [1.3]     26 [1.2]     27 [1.4]                               
      Artery, Inflammation, Chronic Active                                       1 [3.0]                                            
      Papilla, Necrosis                                1 [2.0]                                1 [2.0]                               
      Pelvis, Dilatation                                                         1 [2.0]                                            
      Renal Tubule, Hyperplasia                                                               1 [2.0]                               
   Urinary Bladder                                    (50)         (50)         (49)         (50)                                   
      Artery, Inflammation, Chronic Active             1 [3.0]                                                                      
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                 9            6           12            9                                     
    Natural Death                                      1            2            3            4                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                40           42           34           37                                     
    Natural Death                                                                1                                                  
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Gallbladder                                        (43)         (44)         (39)         (45)                                   
      Infiltration Cellular, Polymorphonuclear                      1 [2.0]                                                         
   Intestine Large, Rectum                            (50)         (48)         (49)         (49)                                   
      Hemorrhage                                                                 1 [2.0]                                            
      Inflammation, Acute                              1 [2.0]                                                                      
   Intestine Large, Cecum                             (49)         (48)         (47)         (47)                                   
      Hemorrhage                                                                 1 [3.0]                                            
   Intestine Small, Duodenum                          (49)         (48)         (45)         (47)                                   
      Ulcer                                            1 [3.0]                                                                      
   Intestine Small, Jejunum                           (49)         (48)         (47)         (47)                                   
      Cyst                                                                                    1 [2.0]                               
      Peyer's Patch, Hyperplasia                       1 [3.0]      1 [3.0]      2 [2.5]                                            
   Intestine Small, Ileum                             (49)         (48)         (48)         (47)                                   
      Inflammation, Acute                                                                     1 [3.0]                               
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 [2.0]                                1 [2.0]                               
      Basophilic Focus                                 8            5            4            8                                     
      Clear Cell Focus                                22           13           13           20                                     
      Eosinophilic Focus                               3            4            5            8                                     
      Hepatodiaphragmatic Nodule                                                 1                                                  
      Infarct                                                       1 [4.0]                                                         
      Inflammation, Chronic                                                                   1 [1.0]                               
      Inflammation, Granulomatous                      1 [2.0]                   1 [2.0]                                            
      Mixed Cell Focus                                 1                         1            1                                     
      Necrosis                                         5 [1.4]      1 [1.0]      2 [3.5]      7 [2.0]                               
      Tension Lipidosis                                4 [1.5]      3 [2.0]      3 [1.3]      1 [2.0]                               
      Thrombosis                                                                 1 [3.0]                                            
      Bile Duct, Cyst                                               1                                                               
      Bile Duct, Hyperplasia                           1 [1.0]                                                                      
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    8                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Hepatocyte, Erythrophagocytosis                                                         1 [1.0]                               
      Hepatocyte, Vacuolization Cytoplasmic            1 [2.0]                   2 [1.5]      1 [3.0]                               
   Mesentery                                          (9)          (3)          (3)          (4)                                    
      Fat, Necrosis                                    9 [2.1]      3 [2.0]      3 [2.0]      3 [2.0]                               
   Salivary Glands                                    (50)         (50)         (48)         (50)                                   
      Inflammation, Acute                              1 [3.0]                                                                      
   Stomach, Forestomach                               (50)         (49)         (49)         (50)                                   
      Hyperplasia, Squamous                            3 [2.7]      3 [2.7]      2 [1.5]      1 [2.0]                               
      Inflammation                                     1 [1.0]      2 [2.0]      3 [1.3]                                            
      Ulcer                                            2 [2.0]      1 [3.0]                   2 [2.0]                               
   Stomach, Glandular                                 (49)         (49)         (49)         (49)                                   
      Hyperplasia                                      1 [2.0]                                                                      
      Necrosis                                         1 [2.0]                   1 [2.0]                                            
   Tooth                                                                        (1)                                                 
      Malformation                                                               1 [4.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                  10 [1.2]      8 [1.0]      2 [2.0]     10 [1.1]                               
      Inflammation, Suppurative                                                               1 [3.0]                               
      Thrombosis                                       2 [4.0]                   3 [3.0]      1 [3.0]                               
      Artery, Inflammation, Chronic Active             2 [2.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (49)         (50)                                   
      Hyperplasia                                     13 [2.0]     18 [1.9]     13 [2.1]      9 [2.1]                               
      Hypertrophy                                     26 [2.0]     30 [1.9]     26 [1.8]     14 [1.9]                               
   Adrenal Medulla                                    (50)         (50)         (49)         (50)                                   
      Hyperplasia                                      1 [2.0]      1 [3.0]      3 [1.7]                                            
   Islets, Pancreatic                                 (49)         (50)         (49)         (50)                                   
      Hyperplasia                                      1 [2.0]      2 [2.0]                   1 [2.0]                               
   Pituitary Gland                                    (50)         (47)         (48)         (49)                                   
      Pars Distalis, Hyperplasia                       1 [4.0]                   2 [2.0]                                            
   Thyroid Gland                                      (50)         (49)         (50)         (50)                                   
      Follicular Cell, Hyperplasia                     4 [1.5]      4 [2.0]      6 [1.5]      8 [1.8]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    9                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Epididymis                                         (50)         (50)         (50)         (50)                                   
      Granuloma Sperm                                  2 [3.0]                   2 [1.5]      1 [3.0]                               
      Infiltration Cellular, Polymorphonuclear                      1 [2.0]                                                         
      Inflammation, Granulomatous                                   1 [3.0]                                                         
   Penis                                              (1)          (1)                       (1)                                    
      Inflammation, Acute                                           1 [3.0]                   1 [4.0]                               
   Preputial Gland                                    (50)         (50)         (50)         (50)                                   
      Ectasia                                          2 [2.0]      3 [3.0]                   1 [3.0]                               
      Inflammation, Chronic Active                                  1 [3.0]                   2 [2.5]                               
   Prostate                                           (50)         (49)         (49)         (50)                                   
      Inflammation, Suppurative                        1 [3.0]      1 [4.0]                                                         
   Seminal Vesicle                                    (50)         (50)         (49)         (50)                                   
      Dilatation                                       1 [3.0]                                                                      
      Inflammation, Chronic Active                     1 [1.0]      1 [4.0]                   1 [2.0]                               
   Testes                                             (50)         (50)         (50)         (50)                                   
      Atrophy                                          2 [2.5]      2 [2.0]      3 [1.3]      1 [2.0]                               
      Thrombosis                                                                 1 [2.0]                                            
      Interstitial Cell, Hyperplasia                   1 [2.0]                   1 [1.0]      2 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Lymph Node, Bronchial                              (39)         (35)         (37)         (39)                                   
      Hyperplasia, Lymphoid                                                      1 [3.0]                                            
   Lymph Node, Mandibular                             (37)         (36)         (32)         (34)                                   
      Hyperplasia, Lymphoid                                                      1 [3.0]                                            
   Lymph Node, Mesenteric                             (49)         (48)         (48)         (48)                                   
      Infiltration Cellular, Histiocyte                                                       1 [2.0]                               
   Lymph Node, Mediastinal                            (42)         (38)         (36)         (38)                                   
      Hyperplasia, Lymphoid                                                      1 [3.0]                                            
   Spleen                                             (50)         (50)         (49)         (49)                                   
      Hematopoietic Cell Proliferation                 2 [2.0]      1 [3.0]      1 [3.0]      3 [2.7]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Skin                                               (50)         (50)         (49)         (50)                                   
      Inflammation, Acute                              1 [4.0]                                                                      
      Inflammation, Chronic Active                                  2 [4.0]      1 [4.0]                                            
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page   10                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Atrophy                                                                    1 [3.0]                                            
      Hyperostosis                                     1 [2.0]                                                                      
      Joint, Cartilage, Hyperplasia                    1 [3.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Hemorrhage                                                                              1 [3.0]                               
      Hydrocephalus                                                              1 [3.0]                                            
      Necrosis                                         2 [1.5]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion, Chronic                              1 [4.0]                                                                      
      Hemorrhage                                                    1 [2.0]                                                         
      Hyperplasia                                                   1 [2.0]                                                         
      Inflammation, Chronic Active                                               1 [3.0]                                            
      Pigmentation                                                               1 [3.0]                                            
      Thrombosis                                                                 1 [4.0]                                            
      Alveolar Epithelium, Hyperplasia                 7 [2.3]      5 [2.2]      5 [2.2]      2 [1.5]                               
      Alveolus, Infiltration Cellular, Histiocyte      1 [3.0]      1 [3.0]      3 [3.3]                                            
      Bronchiole, Hyperplasia                          1 [3.0]      2 [2.5]      3 [1.0]      2 [1.0]                               
   Nose                                               (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      1 [1.0]                                                                      
      Inflammation, Suppurative                        4 [1.0]      1 [1.0]      3 [2.0]      2 [2.5]                               
      Glands, Hyperplasia                             33 [1.0]     32 [1.0]     24 [1.0]     26 [1.0]                               
      Olfactory Epithelium, Atrophy                                              1 [1.0]                                            
      Olfactory Epithelium, Degeneration, Hyaline      1 [1.0]      1 [1.0]      2 [2.0]                                            
      Olfactory Epithelium, Necrosis                                             1 [2.0]                                            
      Respiratory Epithelium, Degeneration, Hyaline                 1 [1.0]      3 [1.3]                                            
      Respiratory Epithelium, Hyperplasia                                        1 [2.0]                                            
      Respiratory Epithelium, Metaplasia               9 [1.0]     11 [1.0]     13 [1.1]      6 [1.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (49)         (48)         (49)         (49)                                   
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page   11                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-02         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 04/29/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 07:55:48    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
SPECIAL SENSES SYSTEM - CONT                                                                                                        
      Cataract                                                                                1 [2.0]                               
      Degeneration                                                               1 [2.0]      1 [3.0]                               
      Cornea, Inflammation, Acute                                   1 [2.0]                                                         
      Cornea, Inflammation, Chronic Active                          2 [3.0]                                                         
      Cornea, Mineralization                                                                  1 [1.0]                               
      Retina, Atrophy                                  1 [3.0]                                                                      
   Harderian Gland                                    (50)         (49)         (50)         (50)                                   
      Hyperplasia                                      3 [2.3]      4 [2.5]      1 [3.0]      2 [2.0]                               
      Hypertrophy                                      1 [2.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (49)         (50)                                   
      Cyst                                                                       1 [3.0]                                            
      Inflammation, Suppurative                        1 [3.0]      1 [1.0]      1 [2.0]      3 [2.7]                               
      Metaplasia, Osseous                              2 [1.0]      2 [1.0]      3 [1.0]      1 [1.0]                               
      Nephropathy                                     41 [1.4]     45 [1.4]     40 [1.5]     43 [1.3]                               
      Renal Tubule, Hyperplasia                        2 [1.0]      2 [1.5]      1 [2.0]                                            
   Urinary Bladder                                    (50)         (49)         (49)         (50)                                   
      Hemorrhage                                                                              1 [3.0]                               
      Inflammation, Chronic Active                     1 [2.0]                                                                      
      Inflammation, Suppurative                                     1 [4.0]                                                         
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page   12                                                              
                                                                                                                                   
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                             ----------              END OF REPORT             ----------                                           
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NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.