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https://ntp.niehs.nih.gov/go/6821

TDMS Study 97006-01 Pathology Tables

NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57

                                                          FINAL#1/RATS




       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

                                                              Page   1


NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                14           14           20           15                                     
    Natural Death                                      1            2            4            3                                     
  Survivors                                                                                                                         
    Moribund Sacrifice                                              1                                                               
    Terminal Sacrifice                                35           33           26           32                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Large, Colon                             (50)         (49)         (49)         (50)                                   
      Foreign Body                                     1 (2%)                                                                       
   Intestine Small, Duodenum                          (50)         (50)         (49)         (50)                                   
      Foreign Body                                     1 (2%)                                                                       
   Intestine Small, Jejunum                           (50)         (49)         (49)         (49)                                   
      Necrosis                                         1 (2%)                                                                       
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                                   1 (2%)                                                          
      Basophilic Focus                                36 (72%)     24 (48%)     26 (52%)     20 (40%)                               
      Clear Cell Focus                                11 (22%)     10 (20%)     11 (22%)      7 (14%)                               
      Eosinophilic Focus                               3 (6%)                    1 (2%)       2 (4%)                                
      Hepatodiaphragmatic Nodule                       8 (16%)     12 (24%)      9 (18%)      5 (10%)                               
      Inflammation, Granulomatous                                   1 (2%)                                                          
      Mixed Cell Focus                                 1 (2%)       3 (6%)                                                          
      Necrosis                                                                   2 (4%)       3 (6%)                                
      Vacuolization Cytoplasmic                        3 (6%)       3 (6%)       5 (10%)      4 (8%)                                
      Hepatocyte, Regeneration                         1 (2%)       1 (2%)       2 (4%)       2 (4%)                                
      Serosa, Fibrosis                                              1 (2%)                                                          
   Mesentery                                          (18)         (17)         (15)         (15)                                   
      Fibrosis                                         1 (6%)                                                                       
      Hemorrhage                                                    1 (6%)                                                          
      Inflammation, Granulomatous                                                1 (7%)                                             
      Necrosis                                        18 (100%)    15 (88%)     15 (100%)    14 (93%)                               
   Pancreas                                           (50)         (50)         (50)         (50)                                   
      Cyst                                                                                    1 (2%)                                
      Acinus, Atrophy                                  1 (2%)       1 (2%)       1 (2%)                                             
   Stomach, Forestomach                               (50)         (50)         (50)         (50)                                   
      Hyperkeratosis                                   1 (2%)                                                                       
      Hyperplasia, Squamous                                         2 (4%)       2 (4%)                                             
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    2                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Necrosis                                                      1 (2%)                                                          
      Ulcer                                            2 (4%)                    1 (2%)       1 (2%)                                
   Tongue                                             (1)          (1)          (3)          (2)                                    
      Epithelium, Hyperplasia                          1 (100%)     1 (100%)     3 (100%)     2 (100%)                              
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                   1 (2%)       1 (2%)       3 (6%)       2 (4%)                                
      Atrium, Thrombosis                                            1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                   1 (2%)       1 (2%)                                             
      Vacuolization Cytoplasmic                        9 (18%)      4 (8%)      13 (26%)      9 (18%)                               
   Adrenal Medulla                                    (50)         (50)         (50)         (50)                                   
      Atrophy                                                       1 (2%)                                                          
      Hyperplasia                                                   2 (4%)                                                          
      Necrosis                                                                                1 (2%)                                
   Islets, Pancreatic                                 (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      1 (2%)       1 (2%)                    1 (2%)                                
   Pituitary Gland                                    (49)         (50)         (50)         (50)                                   
      Cyst                                             3 (6%)       6 (12%)      4 (8%)       3 (6%)                                
      Hemorrhage                                                    2 (4%)       2 (4%)       3 (6%)                                
      Hyperplasia                                     11 (22%)     11 (22%)      8 (16%)     10 (20%)                               
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      Cyst                                                                                    1 (2%)                                
      C-Cell, Hyperplasia                              4 (8%)       2 (4%)       2 (4%)       5 (10%)                               
      Follicular Cell, Hyperplasia                                                            1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (50)         (50)         (50)         (50)                                   
      Cyst                                             2 (4%)       3 (6%)       1 (2%)       1 (2%)                                
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    3                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
GENITAL SYSTEM - CONT                                                                                                               
      Hyperplasia                                      1 (2%)       3 (6%)       1 (2%)       1 (2%)                                
      Inflammation, Chronic                            1 (2%)       1 (2%)                                                          
   Ovary                                              (50)         (50)         (50)         (50)                                   
      Cyst                                             6 (12%)     10 (20%)      7 (14%)      4 (8%)                                
      Cyst, Multiple                                   1 (2%)                                                                       
   Uterus                                             (50)         (50)         (50)         (50)                                   
      Cyst                                             1 (2%)                                                                       
      Decidual Reaction                                1 (2%)                                                                       
      Hemorrhage                                       1 (2%)                    1 (2%)       2 (4%)                                
      Necrosis                                         2 (4%)                                 1 (2%)                                
      Thrombosis                                                                              1 (2%)                                
      Endometrium, Hyperplasia                         1 (2%)       2 (4%)       3 (6%)       3 (6%)                                
      Endometrium, Inflammation, Suppurative           1 (2%)                                                                       
      Myometrium, Hyperplasia                                                                 1 (2%)                                
   Vagina                                             (2)                                    (1)                                    
      Muscularis, Hyperplasia                                                                 1 (100%)                              
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Myelofibrosis                                                                           1 (2%)                                
   Lymph Node                                         (1)          (2)          (2)          (3)                                    
      Pancreatic, Hemorrhage                                        1 (50%)                                                         
   Lymph Node, Bronchial                              (9)          (12)         (8)          (7)                                    
      Ectasia                                          2 (22%)                                                                      
      Hemorrhage                                                    1 (8%)                                                          
      Hyperplasia, Lymphoid                                         2 (17%)                                                         
      Pigmentation                                     1 (11%)      2 (17%)                                                         
   Lymph Node, Mediastinal                            (46)         (44)         (46)         (49)                                   
      Angiectasis                                                   1 (2%)                                                          
   Spleen                                             (50)         (50)         (50)         (50)                                   
      Accessory Spleen                                                           1 (2%)       1 (2%)                                
      Fibrosis                                                      1 (2%)                                                          
      Hemorrhage                                       1 (2%)                    1 (2%)                                             
      Inflammation, Granulomatous                                   1 (2%)                                                          
      Necrosis                                         1 (2%)                                 1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (50)         (50)         (50)         (50)                                   
      Galactocele                                      1 (2%)       1 (2%)                    1 (2%)                                
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    4                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
INTEGUMENTARY SYSTEM - CONT                                                                                                         
      Epithelium, Hyperplasia                                       1 (2%)                                                          
   Skin                                               (50)         (50)         (50)         (50)                                   
      Cyst Epithelial Inclusion                        1 (2%)       1 (2%)                    1 (2%)                                
      Hyperkeratosis                                   1 (2%)                                                                       
      Hyperplasia, Focal, Squamous                                  1 (2%)                                                          
      Inflammation, Acute                                           2 (4%)                                                          
      Ulcer                                            1 (2%)       1 (2%)                    2 (4%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Compression                                      8 (16%)     11 (22%)     10 (20%)      7 (14%)                               
      Gliosis                                                                    1 (2%)                                             
      Hemorrhage                                       5 (10%)      4 (8%)      10 (20%)      5 (10%)                               
      Necrosis                                                                   1 (2%)       2 (4%)                                
      Thrombosis                                       1 (2%)                                                                       
      Cerebrum, Pigmentation                           1 (2%)                                                                       
   Spinal Cord                                        (10)         (4)          (6)          (14)                                   
      Cyst Epithelial Inclusion                                                               1 (7%)                                
      Hemorrhage                                                                              1 (7%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Larynx                                             (50)         (50)         (50)         (50)                                   
      Foreign Body                                     1 (2%)       2 (4%)       3 (6%)       2 (4%)                                
      Inflammation, Chronic                            1 (2%)       1 (2%)                                                          
      Inflammation, Suppurative                                                  1 (2%)       2 (4%)                                
      Epiglottis, Hyperplasia                                                    1 (2%)                                             
      Epiglottis, Metaplasia, Squamous                              1 (2%)       2 (4%)       2 (4%)                                
   Lung                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                                               1 (2%)                                             
      Hemorrhage                                                                              1 (2%)                                
      Inflammation, Chronic                            2 (4%)      10 (20%)      7 (14%)      4 (8%)                                
      Inflammation, Granulomatous                                                1 (2%)                                             
      Alveolar Epithelium, Hyperplasia                 3 (6%)       5 (10%)      2 (4%)       6 (12%)                               
      Alveolar Epithelium, Metaplasia, Squamous                     1 (2%)                    1 (2%)                                
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    5                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
RESPIRATORY SYSTEM - CONT                                                                                                           
      Alveolus, Emphysema                              1 (2%)                                                                       
      Alveolus, Infiltration Cellular, Histiocyte     13 (26%)      2 (4%)       5 (10%)     11 (22%)                               
      Alveolus, Pigmentation                                                     1 (2%)                                             
      Bronchiole, Hyperplasia                          1 (2%)       2 (4%)       2 (4%)       3 (6%)                                
      Interstitium, Fibrosis                           2 (4%)       2 (4%)       2 (4%)       1 (2%)                                
   Nose                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                                  2 (4%)       2 (4%)       1 (2%)                                
      Inflammation, Suppurative                                     1 (2%)       6 (12%)                                            
      Goblet Cell, Hyperplasia                                                   2 (4%)       1 (2%)                                
      Nasolacrimal Duct, Inflammation, Suppurative     5 (10%)      2 (4%)       2 (4%)                                             
      Olfactory Epithelium, Degeneration, Hyaline      1 (2%)                    1 (2%)       2 (4%)                                
      Respiratory Epithelium, Degeneration, Hyaline    9 (18%)      3 (6%)       8 (16%)      9 (18%)                               
      Respiratory Epithelium, Hyperplasia                           2 (4%)       2 (4%)                                             
   Pleura                                             (50)         (50)         (50)         (50)                                   
      Fibrosis                                        12 (24%)      7 (14%)      4 (8%)       5 (10%)                               
      Inflammation, Chronic                            7 (14%)      7 (14%)      1 (2%)       1 (2%)                                
      Mesothelium, Hyperplasia                         1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (49)         (50)         (48)         (49)                                   
      Inflammation, Suppurative                                     1 (2%)       2 (4%)                                             
      Cornea, Inflammation, Suppurative                                          1 (2%)                                             
      Lens, Cataract                                   2 (4%)       3 (6%)       4 (8%)       4 (8%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Infarct                                                                                 1 (2%)                                
      Nephropathy                                     19 (38%)     35 (70%)     38 (76%)     44 (88%)                               
      Papilla, Mineralization                          3 (6%)       5 (10%)      3 (6%)       3 (6%)                                
      Pelvis, Transitional Epithelium, Hyperplasia     1 (2%)       1 (2%)                    1 (2%)                                
      Pelvis, Transitional Epithelium,                                                                                              
        Mineralization                                 9 (18%)      6 (12%)      7 (14%)      2 (4%)                                
      Renal Tubule, Cyst                                            1 (2%)                    1 (2%)                                
      Renal Tubule, Hyperplasia                        1 (2%)       1 (2%)                    1 (2%)                                
   Urinary Bladder                                    (50)         (50)         (50)         (50)                                   
      Hemorrhage                                       1 (2%)                                                                       
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                14           16           21           29                                     
    Natural Death                                      4            5            4            2                                     
    Accidently Killed                                               1                                                               
  Survivors                                                                                                                         
    Terminal Sacrifice                                32           28           25           19                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Large, Cecum                             (48)         (48)         (50)         (50)                                   
      Ulcer                                                         1 (2%)                    2 (4%)                                
   Intestine Small, Ileum                             (48)         (47)         (48)         (49)                                   
      Diverticulum                                                               1 (2%)                                             
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 (2%)                                 1 (2%)                                
      Basophilic Focus                                11 (22%)      5 (10%)     13 (26%)      4 (8%)                                
      Clear Cell Focus                                14 (28%)     13 (26%)     17 (34%)      9 (18%)                               
      Degeneration, Cystic                             1 (2%)                    1 (2%)       3 (6%)                                
      Eosinophilic Focus                               2 (4%)       6 (12%)     10 (20%)      9 (18%)                               
      Hemorrhage                                                                 1 (2%)                                             
      Hepatodiaphragmatic Nodule                       3 (6%)       6 (12%)      7 (14%)      7 (14%)                               
      Inflammation, Granulomatous                                   1 (2%)                                                          
      Mixed Cell Focus                                 1 (2%)                    2 (4%)       1 (2%)                                
      Necrosis                                         1 (2%)       6 (12%)      1 (2%)                                             
      Vacuolization Cytoplasmic                        4 (8%)       2 (4%)       2 (4%)                                             
      Bile Duct, Cyst                                  1 (2%)                                                                       
      Bile Duct, Hyperplasia                                        3 (6%)       4 (8%)       4 (8%)                                
      Bile Duct, Inflammation, Suppurative                          1 (2%)                                                          
      Centrilobular, Necrosis                          1 (2%)       1 (2%)       1 (2%)       4 (8%)                                
      Hepatocyte, Regeneration                                      2 (4%)       1 (2%)       4 (8%)                                
      Periportal, Inflammation, Chronic                             1 (2%)                                                          
   Mesentery                                          (10)         (12)         (9)          (7)                                    
      Necrosis                                        10 (100%)    12 (100%)     9 (100%)     7 (100%)                              
   Oral Mucosa                                        (2)                                                                           
      Pharyngeal, Hyperplasia, Squamous                1 (50%)                                                                      
   Pancreas                                           (50)         (48)         (50)         (50)                                   
      Hemorrhage                                                                 1 (2%)                                             
      Necrosis                                                      1 (2%)                                                          
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Acinus, Atrophy                                  4 (8%)       7 (15%)      5 (10%)      2 (4%)                                
      Artery, Thrombosis                                            1 (2%)                                                          
   Salivary Glands                                    (50)         (48)         (50)         (50)                                   
      Hyperplasia                                                   1 (2%)                                                          
   Stomach, Forestomach                               (50)         (48)         (50)         (50)                                   
      Hyperplasia, Squamous                                                      1 (2%)       1 (2%)                                
      Ulcer                                            3 (6%)       1 (2%)       6 (12%)      6 (12%)                               
   Stomach, Glandular                                 (50)         (48)         (50)         (50)                                   
      Erosion                                          1 (2%)       1 (2%)       2 (4%)       3 (6%)                                
      Ulcer                                                                                   1 (2%)                                
      Serosa, Fibrosis                                                           1 (2%)                                             
   Tongue                                             (1)          (1)                                                              
      Epithelium, Hyperplasia                          1 (100%)     1 (100%)                                                        
   Tooth                                              (1)                                                                           
      Peridontal Tissue, Inflammation                  1 (100%)                                                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (49)         (50)         (50)                                   
      Cardiomyopathy                                  14 (28%)      9 (18%)     12 (24%)      8 (16%)                               
      Atrium, Thrombosis                               2 (4%)       4 (8%)       3 (6%)       1 (2%)                                
      Myocardium, Mineralization                       1 (2%)                                                                       
      Pericardium, Fibrosis                                                      1 (2%)                                             
      Pericardium, Inflammation, Chronic                                         1 (2%)                                             
      Valve, Inflammation, Suppurative                              1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (48)         (50)         (50)                                   
      Atrophy                                          1 (2%)                    1 (2%)                                             
      Hyperplasia                                                                1 (2%)                                             
      Necrosis                                                                                1 (2%)                                
      Vacuolization Cytoplasmic                        7 (14%)      3 (6%)       6 (12%)      3 (6%)                                
   Adrenal Medulla                                    (50)         (48)         (50)         (50)                                   
      Atrophy                                          1 (2%)                                                                       
      Hemorrhage                                       1 (2%)                                                                       
      Hyperplasia                                     13 (26%)     18 (38%)     18 (36%)     24 (48%)                               
      Thrombosis                                                                 1 (2%)                                             
   Islets, Pancreatic                                 (50)         (48)         (50)         (50)                                   
      Hyperplasia                                                   1 (2%)                    1 (2%)                                
   Parathyroid Gland                                  (49)         (48)         (49)         (50)                                   
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    8                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Hyperplasia                                                   1 (2%)                                                          
   Pituitary Gland                                    (50)         (49)         (50)         (50)                                   
      Angiectasis                                                                1 (2%)                                             
      Atrophy                                          1 (2%)                                                                       
      Cyst                                             1 (2%)       1 (2%)                    1 (2%)                                
      Hemorrhage                                       4 (8%)       1 (2%)                    1 (2%)                                
      Hyperplasia                                      8 (16%)      8 (16%)      9 (18%)      9 (18%)                               
   Thyroid Gland                                      (50)         (48)         (50)         (50)                                   
      C-Cell, Hyperplasia                              4 (8%)       3 (6%)       5 (10%)      1 (2%)                                
      Follicle, Cyst                                   1 (2%)       1 (2%)                    1 (2%)                                
      Follicular Cell, Hyperplasia                     1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Preputial Gland                                    (50)         (49)         (50)         (50)                                   
      Cyst                                             1 (2%)       2 (4%)                                                          
      Hyperplasia                                      1 (2%)       2 (4%)                    3 (6%)                                
      Inflammation, Granulomatous                                                             1 (2%)                                
      Inflammation, Suppurative                                                  1 (2%)                                             
   Prostate                                           (50)         (49)         (50)         (50)                                   
      Inflammation, Suppurative                        3 (6%)       1 (2%)                    2 (4%)                                
   Seminal Vesicle                                    (50)         (49)         (50)         (50)                                   
      Hyperplasia                                                   1 (2%)                                                          
   Testes                                             (50)         (50)         (50)         (50)                                   
      Germinal Epithelium, Atrophy                    10 (20%)      8 (16%)      8 (16%)     15 (30%)                               
      Interstitial Cell, Hyperplasia                   4 (8%)       3 (6%)       1 (2%)       3 (6%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (49)         (50)         (50)                                   
      Hyperplasia, Reticulum Cell                                   1 (2%)                                                          
      Myelofibrosis                                                 1 (2%)                                                          
   Lymph Node                                         (7)          (7)          (12)         (15)                                   
      Infiltration Cellular, Histiocyte                                          1 (8%)                                             
      Deep Cervical, Hemorrhage                                     1 (14%)                                                         
      Deep Cervical, Infiltration Cellular,                                                                                         
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    9                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
        Histiocyte                                     1 (14%)                                                                      
      Deep Cervical, Pigmentation                                                             1 (7%)                                
      Pancreatic, Ectasia                              2 (29%)                                                                      
      Pancreatic, Pigmentation                                                   1 (8%)                                             
      Renal, Ectasia                                                             1 (8%)                                             
   Lymph Node, Bronchial                              (11)         (13)         (12)         (7)                                    
      Angiectasis                                      1 (9%)                                                                       
      Ectasia                                          3 (27%)      2 (15%)      1 (8%)                                             
      Hemorrhage                                                    1 (8%)                                                          
      Infiltration Cellular, Histiocyte                1 (9%)       1 (8%)                                                          
      Pigmentation                                     1 (9%)       1 (8%)                                                          
   Lymph Node, Mesenteric                             (50)         (48)         (50)         (50)                                   
      Hyperplasia, Lymphoid                            1 (2%)                    1 (2%)                                             
   Lymph Node, Mediastinal                            (41)         (44)         (46)         (44)                                   
      Angiectasis                                                   1 (2%)                                                          
      Hemorrhage                                       1 (2%)                                                                       
      Hyperplasia, Lymphoid                                                      1 (2%)       1 (2%)                                
      Infiltration Cellular, Histiocyte                                          1 (2%)                                             
      Pigmentation                                                  1 (2%)                    1 (2%)                                
   Spleen                                             (50)         (50)         (50)         (50)                                   
      Accessory Spleen                                 2 (4%)       1 (2%)                    1 (2%)                                
      Fibrosis                                         2 (4%)       5 (10%)      3 (6%)       8 (16%)                               
      Hemorrhage                                       2 (4%)       2 (4%)       2 (4%)       1 (2%)                                
      Necrosis                                         4 (8%)       4 (8%)       6 (12%)      4 (8%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (49)         (49)         (50)         (50)                                   
      Galactocele                                      5 (10%)                   1 (2%)       3 (6%)                                
   Skin                                               (50)         (49)         (50)         (50)                                   
      Cyst Epithelial Inclusion                        3 (6%)       3 (6%)                    4 (8%)                                
      Hyperkeratosis                                   1 (2%)       1 (2%)       1 (2%)       3 (6%)                                
      Hyperplasia, Focal, Squamous                                               1 (2%)                                             
      Inflammation, Acute                                           1 (2%)                                                          
      Inflammation, Granulomatous                                                1 (2%)       2 (4%)                                
      Sebaceous Gland, Hyperplasia                     1 (2%)                                                                       
      Subcutaneous Tissue, Fibrosis                                 1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page   10                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
MUSCULOSKELETAL SYSTEM - CONT                                                                                                       
      Hyperostosis                                     1 (2%)                                                                       
      Cranium, Maxilla, Fracture                                    1 (2%)                                                          
      Tibia, Fracture                                                                         1 (2%)                                
   Skeletal Muscle                                    (3)          (3)          (4)          (6)                                    
      Hemorrhage                                                                              1 (17%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (49)         (50)         (50)                                   
      Compression                                      8 (16%)      8 (16%)      3 (6%)       6 (12%)                               
      Hemorrhage                                       5 (10%)      3 (6%)       6 (12%)      4 (8%)                                
   Spinal Cord                                        (2)          (3)          (5)          (5)                                    
      Gliosis                                                                    1 (20%)                                            
      Inflammation                                                               1 (20%)                                            
      Neuron, Degeneration                                                       1 (20%)                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Larynx                                             (50)         (48)         (50)         (50)                                   
      Foreign Body                                     2 (4%)       3 (6%)       6 (12%)      4 (8%)                                
      Inflammation, Suppurative                                     2 (4%)       2 (4%)       2 (4%)                                
      Epiglottis, Hyperplasia                                                    1 (2%)                                             
      Epiglottis, Metaplasia, Squamous                              1 (2%)                                                          
   Lung                                               (50)         (49)         (50)         (50)                                   
      Hemorrhage                                       2 (4%)       5 (10%)      5 (10%)                                            
      Inflammation, Chronic                            4 (8%)                    2 (4%)                                             
      Inflammation, Suppurative                                     2 (4%)       1 (2%)                                             
      Thrombosis                                                    1 (2%)                                                          
      Alveolar Epithelium, Hyperplasia                 4 (8%)       7 (14%)      4 (8%)       4 (8%)                                
      Alveolar Epithelium, Metaplasia, Squamous        1 (2%)                                                                       
      Alveolus, Emphysema                              2 (4%)                                                                       
      Alveolus, Infiltration Cellular, Histiocyte     10 (20%)      5 (10%)      6 (12%)      6 (12%)                               
      Alveolus, Pigmentation                                        1 (2%)                                                          
      Bronchiole, Hyperplasia                                                                 1 (2%)                                
      Bronchiole, Alveolus, Foreign Body                            1 (2%)                                                          
      Interstitium, Fibrosis                           2 (4%)                    3 (6%)       1 (2%)                                
   Nose                                               (50)         (49)         (50)         (50)                                   
      Foreign Body                                     1 (2%)       3 (6%)       4 (8%)       7 (14%)                               
      Inflammation, Suppurative                        4 (8%)       8 (16%)      4 (8%)      10 (20%)                               
      Goblet Cell, Hyperplasia                         1 (2%)       1 (2%)                    5 (10%)                               
      Nasolacrimal Duct, Inflammation, Suppurative                  1 (2%)       1 (2%)       1 (2%)                                
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page   11                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                       METHYL ISOBUTYL KETONE                                  Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                                                                            Time: 08:44:57    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     CONTROL      450 PPM      900 PPM      1800 PPM                                  
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
RESPIRATORY SYSTEM - CONT                                                                                                           
      Respiratory Epithelium, Hyperplasia              4 (8%)       1 (2%)       3 (6%)       3 (6%)                                
   Pleura                                             (50)         (49)         (50)         (50)                                   
      Fibrosis                                         3 (6%)                                                                       
      Inflammation, Chronic                            6 (12%)                   6 (12%)      4 (8%)                                
      Mesothelium, Hyperplasia                                                   1 (2%)       1 (2%)                                
   Trachea                                            (50)         (48)         (50)         (50)                                   
      Inflammation, Suppurative                                     2 (4%)                                                          
      Epithelium, Hyperplasia                                       1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (49)         (45)         (46)         (48)                                   
      Anterior Chamber, Hemorrhage                                  1 (2%)                                                          
      Anterior Chamber, Inflammation, Suppurative                   1 (2%)                                                          
      Cornea, Hyperplasia                                                                     1 (2%)                                
      Lens, Cataract                                   7 (14%)      6 (13%)      3 (7%)       2 (4%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Infarct                                                                    4 (8%)       3 (6%)                                
      Nephropathy                                     42 (84%)     45 (90%)     47 (94%)     50 (100%)                              
      Papilla, Mineralization                          1 (2%)       6 (12%)     22 (44%)     29 (58%)                               
      Pelvis, Dilatation                                            1 (2%)                                                          
      Pelvis, Transitional Epithelium, Hyperplasia     1 (2%)       5 (10%)      6 (12%)     19 (38%)                               
      Renal Tubule, Accumulation, Hyaline Droplet                                2 (4%)       2 (4%)                                
      Renal Tubule, Cyst                               1 (2%)       1 (2%)       1 (2%)                                             
      Renal Tubule, Hyperplasia                        1 (2%)      11 (22%)      3 (6%)      18 (36%)                               
      Renal Tubule, Pigmentation                                                              1 (2%)                                
      Transitional Epithelium, Hyperplasia                                                    1 (2%)                                
   Urinary Bladder                                    (50)         (48)         (50)         (50)                                   
      Calculus Micro Observation Only                  1 (2%)       2 (4%)       2 (4%)                                             
      Transitional Epithelium, Hyperplasia                          1 (2%)                                                          
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page   12                                                              
                                                                                                                                   
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                             ----------              END OF REPORT             ----------                                           
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