National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/6837

TDMS Study 97006-01 Pathology Tables

NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20

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

                                                              Page   1


NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         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 [4.0]                                                                      
   Intestine Small, Duodenum                          (50)         (50)         (49)         (50)                                   
      Foreign Body                                     1                                                                            
   Intestine Small, Jejunum                           (50)         (49)         (49)         (49)                                   
      Necrosis                                         1 [4.0]                                                                      
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                                   1 [3.0]                                                         
      Basophilic Focus                                36           24           26           20                                     
      Clear Cell Focus                                11           10           11            7                                     
      Eosinophilic Focus                               3                         1            2                                     
      Hepatodiaphragmatic Nodule                       8 [4.0]     12 [4.0]      9 [4.0]      5 [4.0]                               
      Inflammation, Granulomatous                                   1 [2.0]                                                         
      Mixed Cell Focus                                 1            3                                                               
      Necrosis                                                                   2 [3.0]      3 [2.0]                               
      Vacuolization Cytoplasmic                        3 [2.7]      3 [2.3]      5 [2.8]      4 [2.0]                               
      Hepatocyte, Regeneration                         1 [4.0]      1 [4.0]      2 [3.0]      2 [4.0]                               
      Serosa, Fibrosis                                              1 [2.0]                                                         
   Mesentery                                          (18)         (17)         (15)         (15)                                   
      Fibrosis                                         1 [3.0]                                                                      
      Hemorrhage                                                    1 [3.0]                                                         
      Inflammation, Granulomatous                                                1 [2.0]                                            
      Necrosis                                        18 [3.0]     15 [3.0]     15 [3.0]     14 [2.9]                               
   Pancreas                                           (50)         (50)         (50)         (50)                                   
      Cyst                                                                                    1 [3.0]                               
      Acinus, Atrophy                                  1 [3.0]      1 [2.0]      1 [2.0]                                            
   Stomach, Forestomach                               (50)         (50)         (50)         (50)                                   
      Hyperkeratosis                                   1 [2.0]                                                                      
      Hyperplasia, Squamous                                         2 [2.0]      2 [2.5]                                            
                                                                                                                                    
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: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                      CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Necrosis                                                      1 [3.0]                                                         
      Ulcer                                            2 [4.0]                   1 [4.0]      1 [4.0]                               
   Tongue                                             (1)          (1)          (3)          (2)                                    
      Epithelium, Hyperplasia                          1 [4.0]      1 [1.0]      3 [2.0]      2 [2.5]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                   1 [2.0]      1 [3.0]      3 [2.0]      2 [2.0]                               
      Atrium, Thrombosis                                            1 [4.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                   1 [2.0]      1 [2.0]                                            
      Vacuolization Cytoplasmic                        9 [2.3]      4 [2.5]     13 [2.6]      9 [2.0]                               
   Adrenal Medulla                                    (50)         (50)         (50)         (50)                                   
      Atrophy                                                       1 [4.0]                                                         
      Hyperplasia                                                   2 [4.0]                                                         
      Necrosis                                                                                1 [4.0]                               
   Islets, Pancreatic                                 (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      1 [3.0]      1 [4.0]                   1 [4.0]                               
   Pituitary Gland                                    (49)         (50)         (50)         (50)                                   
      Cyst                                             3 [2.7]      6 [3.3]      4 [3.3]      3 [3.0]                               
      Hemorrhage                                                    2 [3.5]      2 [3.5]      3 [3.3]                               
      Hyperplasia                                     11 [3.2]     11 [3.5]      8 [3.3]     10 [3.2]                               
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      Cyst                                                                                    1 [2.0]                               
      C-Cell, Hyperplasia                              4 [2.8]      2 [3.0]      2 [3.0]      5 [2.6]                               
      Follicular Cell, Hyperplasia                                                            1 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (50)         (50)         (50)         (50)                                   
      Cyst                                             2 [2.5]      3 [2.7]      1 [3.0]      1 [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    3                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                      CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
GENITAL SYSTEM - CONT                                                                                                               
      Hyperplasia                                      1 [3.0]      3 [4.0]      1 [2.0]      1 [4.0]                               
      Inflammation, Chronic                            1 [3.0]      1 [3.0]                                                         
   Ovary                                              (50)         (50)         (50)         (50)                                   
      Cyst                                             6 [3.3]     10 [2.8]      7 [3.4]      4 [3.8]                               
      Cyst, Multiple                                   1 [3.0]                                                                      
   Uterus                                             (50)         (50)         (50)         (50)                                   
      Cyst                                             1 [4.0]                                                                      
      Decidual Reaction                                1 [3.0]                                                                      
      Hemorrhage                                       1 [4.0]                   1 [4.0]      2 [4.0]                               
      Necrosis                                         2 [4.0]                                1 [4.0]                               
      Thrombosis                                                                              1 [4.0]                               
      Endometrium, Hyperplasia                         1 [1.0]      2 [2.0]      3 [2.7]      3 [2.3]                               
      Endometrium, Inflammation, Suppurative           1 [3.0]                                                                      
      Myometrium, Hyperplasia                                                                 1 [3.0]                               
   Vagina                                             (2)                                    (1)                                    
      Muscularis, Hyperplasia                                                                 1 [4.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Myelofibrosis                                                                           1 [3.0]                               
   Lymph Node                                         (1)          (2)          (2)          (3)                                    
      Pancreatic, Hemorrhage                                        1 [3.0]                                                         
   Lymph Node, Bronchial                              (9)          (12)         (8)          (7)                                    
      Ectasia                                          2 [2.5]                                                                      
      Hemorrhage                                                    1 [2.0]                                                         
      Hyperplasia, Lymphoid                                         2 [3.0]                                                         
      Pigmentation                                     1 [3.0]      2 [2.5]                                                         
   Lymph Node, Mediastinal                            (46)         (44)         (46)         (49)                                   
      Angiectasis                                                   1 [4.0]                                                         
   Spleen                                             (50)         (50)         (50)         (50)                                   
      Accessory Spleen                                                           1            1                                     
      Fibrosis                                                      1 [2.0]                                                         
      Hemorrhage                                       1 [4.0]                   1 [4.0]                                            
      Inflammation, Granulomatous                                   1 [3.0]                                                         
      Necrosis                                         1 [4.0]                                1 [4.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (50)         (50)         (50)         (50)                                   
      Galactocele                                      1            1                         1                                     
                                                                                                                                    
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: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                      CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
INTEGUMENTARY SYSTEM - CONT                                                                                                         
      Epithelium, Hyperplasia                                       1 [3.0]                                                         
   Skin                                               (50)         (50)         (50)         (50)                                   
      Cyst Epithelial Inclusion                        1 [4.0]      1 [4.0]                   1 [4.0]                               
      Hyperkeratosis                                   1 [3.0]                                                                      
      Hyperplasia, Focal, Squamous                                  1 [2.0]                                                         
      Inflammation, Acute                                           2 [2.0]                                                         
      Ulcer                                            1 [3.0]      1 [4.0]                   2 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Compression                                      8 [3.4]     11 [3.7]     10 [3.9]      7 [3.7]                               
      Gliosis                                                                    1 [3.0]                                            
      Hemorrhage                                       5 [3.2]      4 [3.3]     10 [3.3]      5 [2.8]                               
      Necrosis                                                                   1 [4.0]      2 [4.0]                               
      Thrombosis                                       1 [4.0]                                                                      
      Cerebrum, Pigmentation                           1 [2.0]                                                                      
   Spinal Cord                                        (10)         (4)          (6)          (14)                                   
      Cyst Epithelial Inclusion                                                               1 [3.0]                               
      Hemorrhage                                                                              1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Larynx                                             (50)         (50)         (50)         (50)                                   
      Foreign Body                                     1 [4.0]      2 [4.0]      3 [4.0]      2 [4.0]                               
      Inflammation, Chronic                            1 [1.0]      1 [3.0]                                                         
      Inflammation, Suppurative                                                  1 [2.0]      2 [2.0]                               
      Epiglottis, Hyperplasia                                                    1 [2.0]                                            
      Epiglottis, Metaplasia, Squamous                              1 [2.0]      2 [1.5]      2 [1.5]                               
   Lung                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                                               1 [3.0]                                            
      Hemorrhage                                                                              1 [2.0]                               
      Inflammation, Chronic                            2 [1.0]     10 [1.8]      7 [1.9]      4 [1.3]                               
      Inflammation, Granulomatous                                                1 [3.0]                                            
      Alveolar Epithelium, Hyperplasia                 3 [1.3]      5 [2.0]      2 [2.0]      6 [1.3]                               
      Alveolar Epithelium, Metaplasia, Squamous                     1 [1.0]                   1 [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    5                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                      CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
RESPIRATORY SYSTEM - CONT                                                                                                           
      Alveolus, Emphysema                              1 [3.0]                                                                      
      Alveolus, Infiltration Cellular, Histiocyte     13 [1.2]      2 [1.0]      5 [1.4]     11 [1.1]                               
      Alveolus, Pigmentation                                                     1 [2.0]                                            
      Bronchiole, Hyperplasia                          1 [3.0]      2 [2.0]      2 [2.5]      3 [2.3]                               
      Interstitium, Fibrosis                           2 [1.0]      2 [2.0]      2 [2.5]      1 [1.0]                               
   Nose                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                                  2 [3.0]      2 [3.0]      1 [3.0]                               
      Inflammation, Suppurative                                     1 [2.0]      6 [1.2]                                            
      Goblet Cell, Hyperplasia                                                   2 [2.0]      1 [2.0]                               
      Nasolacrimal Duct, Inflammation, Suppurative     5 [1.8]      2 [2.0]      2 [1.0]                                            
      Olfactory Epithelium, Degeneration, Hyaline      1 [2.0]                   1 [2.0]      2 [1.5]                               
      Respiratory Epithelium, Degeneration, Hyaline    9 [1.4]      3 [1.7]      8 [2.0]      9 [2.1]                               
      Respiratory Epithelium, Hyperplasia                           2 [2.0]      2 [2.5]                                            
   Pleura                                             (50)         (50)         (50)         (50)                                   
      Fibrosis                                        12 [1.2]      7 [1.7]      4 [1.3]      5 [1.0]                               
      Inflammation, Chronic                            7 [1.6]      7 [1.7]      1 [1.0]      1 [1.0]                               
      Mesothelium, Hyperplasia                         1 [1.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (49)         (50)         (48)         (49)                                   
      Inflammation, Suppurative                                     1 [4.0]      2 [2.5]                                            
      Cornea, Inflammation, Suppurative                                          1 [3.0]                                            
      Lens, Cataract                                   2 [3.5]      3 [3.0]      4 [3.0]      4 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Infarct                                                                                 1                                     
      Nephropathy                                     19 [1.4]     35 [1.5]     38 [1.5]     44 [1.9]                               
      Papilla, Mineralization                          3 [1.0]      5 [1.0]      3 [1.0]      3 [1.0]                               
      Pelvis, Transitional Epithelium, Hyperplasia     1 [1.0]      1 [1.0]                   1 [1.0]                               
      Pelvis, Transitional Epithelium,                                                                                              
        Mineralization                                 9 [1.1]      6 [1.2]      7 [1.1]      2 [1.0]                               
      Renal Tubule, Cyst                                            1                         1                                     
      Renal Tubule, Hyperplasia                        1 [2.0]      1 [2.0]                   1 [3.0]                               
   Urinary Bladder                                    (50)         (50)         (50)         (50)                                   
      Hemorrhage                                       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    6                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         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 [4.0]                   2 [4.0]                               
   Intestine Small, Ileum                             (48)         (47)         (48)         (49)                                   
      Diverticulum                                                               1 [4.0]                                            
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 [2.0]                                1 [3.0]                               
      Basophilic Focus                                11            5           13            4                                     
      Clear Cell Focus                                14           13           17            9                                     
      Degeneration, Cystic                             1 [2.0]                   1 [4.0]      3 [3.0]                               
      Eosinophilic Focus                               2            6           10            9                                     
      Hemorrhage                                                                 1 [4.0]                                            
      Hepatodiaphragmatic Nodule                       3 [4.0]      6 [4.0]      7 [4.0]      7 [4.0]                               
      Inflammation, Granulomatous                                   1 [3.0]                                                         
      Mixed Cell Focus                                 1                         2            1                                     
      Necrosis                                         1 [4.0]      6 [3.3]      1 [3.0]                                            
      Vacuolization Cytoplasmic                        4 [2.5]      2 [2.5]      2 [3.5]                                            
      Bile Duct, Cyst                                  1 [3.0]                                                                      
      Bile Duct, Hyperplasia                                        3 [3.0]      4 [3.0]      4 [3.0]                               
      Bile Duct, Inflammation, Suppurative                          1 [4.0]                                                         
      Centrilobular, Necrosis                          1 [2.0]      1 [3.0]      1 [2.0]      4 [1.8]                               
      Hepatocyte, Regeneration                                      2 [4.0]      1 [3.0]      4 [3.8]                               
      Periportal, Inflammation, Chronic                             1 [3.0]                                                         
   Mesentery                                          (10)         (12)         (9)          (7)                                    
      Necrosis                                        10 [2.8]     12 [3.0]      9 [3.0]      7 [3.0]                               
   Oral Mucosa                                        (2)                                                                           
      Pharyngeal, Hyperplasia, Squamous                1 [4.0]                                                                      
   Pancreas                                           (50)         (48)         (50)         (50)                                   
      Hemorrhage                                                                 1 [4.0]                                            
      Necrosis                                                      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    7                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                        CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Acinus, Atrophy                                  4 [2.0]      7 [2.4]      5 [2.2]      2 [2.5]                               
      Artery, Thrombosis                                            1 [4.0]                                                         
   Salivary Glands                                    (50)         (48)         (50)         (50)                                   
      Hyperplasia                                                   1 [4.0]                                                         
   Stomach, Forestomach                               (50)         (48)         (50)         (50)                                   
      Hyperplasia, Squamous                                                      1 [2.0]      1 [4.0]                               
      Ulcer                                            3 [3.7]      1 [3.0]      6 [3.2]      6 [3.8]                               
   Stomach, Glandular                                 (50)         (48)         (50)         (50)                                   
      Erosion                                          1 [2.0]      1 [3.0]      2 [2.0]      3 [2.0]                               
      Ulcer                                                                                   1 [4.0]                               
      Serosa, Fibrosis                                                           1 [2.0]                                            
   Tongue                                             (1)          (1)                                                              
      Epithelium, Hyperplasia                          1 [2.0]      1 [3.0]                                                         
   Tooth                                              (1)                                                                           
      Peridontal Tissue, Inflammation                  1 [4.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (49)         (50)         (50)                                   
      Cardiomyopathy                                  14 [2.0]      9 [2.3]     12 [2.2]      8 [2.0]                               
      Atrium, Thrombosis                               2 [4.0]      4 [4.0]      3 [2.7]      1 [4.0]                               
      Myocardium, Mineralization                       1 [2.0]                                                                      
      Pericardium, Fibrosis                                                      1 [3.0]                                            
      Pericardium, Inflammation, Chronic                                         1 [4.0]                                            
      Valve, Inflammation, Suppurative                              1 [4.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (48)         (50)         (50)                                   
      Atrophy                                          1 [4.0]                   1 [3.0]                                            
      Hyperplasia                                                                1 [3.0]                                            
      Necrosis                                                                                1 [2.0]                               
      Vacuolization Cytoplasmic                        7 [1.9]      3 [2.7]      6 [1.7]      3 [2.0]                               
   Adrenal Medulla                                    (50)         (48)         (50)         (50)                                   
      Atrophy                                          1 [4.0]                                                                      
      Hemorrhage                                       1 [4.0]                                                                      
      Hyperplasia                                     13 [2.2]     18 [2.8]     18 [2.3]     24 [2.8]                               
      Thrombosis                                                                 1 [4.0]                                            
   Islets, Pancreatic                                 (50)         (48)         (50)         (50)                                   
      Hyperplasia                                                   1 [4.0]                   1 [4.0]                               
   Parathyroid Gland                                  (49)         (48)         (49)         (50)                                   
                                                                                                                                    
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: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                        CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Hyperplasia                                                   1 [3.0]                                                         
   Pituitary Gland                                    (50)         (49)         (50)         (50)                                   
      Angiectasis                                                                1 [4.0]                                            
      Atrophy                                          1 [4.0]                                                                      
      Cyst                                             1 [4.0]      1 [4.0]                   1 [2.0]                               
      Hemorrhage                                       4 [3.5]      1 [4.0]                   1 [3.0]                               
      Hyperplasia                                      8 [3.8]      8 [3.1]      9 [3.3]      9 [3.8]                               
   Thyroid Gland                                      (50)         (48)         (50)         (50)                                   
      C-Cell, Hyperplasia                              4 [1.8]      3 [1.7]      5 [1.8]      1 [2.0]                               
      Follicle, Cyst                                   1 [2.0]      1 [2.0]                   1 [4.0]                               
      Follicular Cell, Hyperplasia                     1 [1.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Preputial Gland                                    (50)         (49)         (50)         (50)                                   
      Cyst                                             1 [2.0]      2 [4.0]                                                         
      Hyperplasia                                      1 [4.0]      2 [3.5]                   3 [3.7]                               
      Inflammation, Granulomatous                                                             1 [2.0]                               
      Inflammation, Suppurative                                                  1 [3.0]                                            
   Prostate                                           (50)         (49)         (50)         (50)                                   
      Inflammation, Suppurative                        3 [3.0]      1 [2.0]                   2 [2.5]                               
   Seminal Vesicle                                    (50)         (49)         (50)         (50)                                   
      Hyperplasia                                                   1 [3.0]                                                         
   Testes                                             (50)         (50)         (50)         (50)                                   
      Germinal Epithelium, Atrophy                    10 [3.7]      8 [3.8]      8 [3.5]     15 [3.7]                               
      Interstitial Cell, Hyperplasia                   4 [3.0]      3 [3.0]      1 [3.0]      3 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (49)         (50)         (50)                                   
      Hyperplasia, Reticulum Cell                                   1 [4.0]                                                         
      Myelofibrosis                                                 1 [3.0]                                                         
   Lymph Node                                         (7)          (7)          (12)         (15)                                   
      Infiltration Cellular, Histiocyte                                          1 [3.0]                                            
      Deep Cervical, Hemorrhage                                     1 [3.0]                                                         
      Deep Cervical, Infiltration Cellular,                                                                                         
                                                                                                                                    
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: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                        CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
        Histiocyte                                     1 [2.0]                                                                      
      Deep Cervical, Pigmentation                                                             1 [2.0]                               
      Pancreatic, Ectasia                              2 [3.5]                                                                      
      Pancreatic, Pigmentation                                                   1 [3.0]                                            
      Renal, Ectasia                                                             1 [3.0]                                            
   Lymph Node, Bronchial                              (11)         (13)         (12)         (7)                                    
      Angiectasis                                      1 [4.0]                                                                      
      Ectasia                                          3 [3.7]      2 [4.0]      1 [3.0]                                            
      Hemorrhage                                                    1 [3.0]                                                         
      Infiltration Cellular, Histiocyte                1 [2.0]      1 [2.0]                                                         
      Pigmentation                                     1 [3.0]      1 [1.0]                                                         
   Lymph Node, Mesenteric                             (50)         (48)         (50)         (50)                                   
      Hyperplasia, Lymphoid                            1 [4.0]                   1 [3.0]                                            
   Lymph Node, Mediastinal                            (41)         (44)         (46)         (44)                                   
      Angiectasis                                                   1 [3.0]                                                         
      Hemorrhage                                       1 [4.0]                                                                      
      Hyperplasia, Lymphoid                                                      1 [3.0]      1 [4.0]                               
      Infiltration Cellular, Histiocyte                                          1 [4.0]                                            
      Pigmentation                                                  1 [1.0]                   1 [4.0]                               
   Spleen                                             (50)         (50)         (50)         (50)                                   
      Accessory Spleen                                 2            1                         1                                     
      Fibrosis                                         2 [3.0]      5 [2.8]      3 [3.0]      8 [3.6]                               
      Hemorrhage                                       2 [4.0]      2 [4.0]      2 [4.0]      1 [4.0]                               
      Necrosis                                         4 [4.0]      4 [4.0]      6 [4.0]      4 [4.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (49)         (49)         (50)         (50)                                   
      Galactocele                                      5 [3.0]                   1 [3.0]      3 [4.0]                               
   Skin                                               (50)         (49)         (50)         (50)                                   
      Cyst Epithelial Inclusion                        3 [4.0]      3 [4.0]                   4 [4.0]                               
      Hyperkeratosis                                   1 [4.0]      1 [4.0]      1 [4.0]      3 [2.3]                               
      Hyperplasia, Focal, Squamous                                               1 [2.0]                                            
      Inflammation, Acute                                           1 [2.0]                                                         
      Inflammation, Granulomatous                                                1 [3.0]      2 [2.5]                               
      Sebaceous Gland, Hyperplasia                     1 [3.0]                                                                      
      Subcutaneous Tissue, Fibrosis                                 1 [3.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
                                                                                                                                    
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: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                        CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
MUSCULOSKELETAL SYSTEM - CONT                                                                                                       
      Hyperostosis                                     1 [2.0]                                                                      
      Cranium, Maxilla, Fracture                                    1 [4.0]                                                         
      Tibia, Fracture                                                                         1                                     
   Skeletal Muscle                                    (3)          (3)          (4)          (6)                                    
      Hemorrhage                                                                              1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (49)         (50)         (50)                                   
      Compression                                      8 [3.4]      8 [3.0]      3 [2.3]      6 [2.8]                               
      Hemorrhage                                       5 [3.8]      3 [3.7]      6 [3.2]      4 [3.5]                               
   Spinal Cord                                        (2)          (3)          (5)          (5)                                    
      Gliosis                                                                    1 [2.0]                                            
      Inflammation                                                               1 [3.0]                                            
      Neuron, Degeneration                                                       1 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Larynx                                             (50)         (48)         (50)         (50)                                   
      Foreign Body                                     2 [4.0]      3 [4.0]      6 [3.7]      4 [4.0]                               
      Inflammation, Suppurative                                     2 [2.5]      2 [1.5]      2 [1.5]                               
      Epiglottis, Hyperplasia                                                    1 [2.0]                                            
      Epiglottis, Metaplasia, Squamous                              1 [2.0]                                                         
   Lung                                               (50)         (49)         (50)         (50)                                   
      Hemorrhage                                       2 [2.5]      5 [3.2]      5 [2.6]                                            
      Inflammation, Chronic                            4 [2.0]                   2 [1.5]                                            
      Inflammation, Suppurative                                     2 [2.5]      1 [2.0]                                            
      Thrombosis                                                    1 [3.0]                                                         
      Alveolar Epithelium, Hyperplasia                 4 [1.8]      7 [2.0]      4 [1.8]      4 [2.0]                               
      Alveolar Epithelium, Metaplasia, Squamous        1 [1.0]                                                                      
      Alveolus, Emphysema                              2 [2.5]                                                                      
      Alveolus, Infiltration Cellular, Histiocyte     10 [1.9]      5 [2.0]      6 [1.8]      6 [2.0]                               
      Alveolus, Pigmentation                                        1 [3.0]                                                         
      Bronchiole, Hyperplasia                                                                 1 [3.0]                               
      Bronchiole, Alveolus, Foreign Body                            1 [3.0]                                                         
      Interstitium, Fibrosis                           2 [2.5]                   3 [1.7]      1 [1.0]                               
   Nose                                               (50)         (49)         (50)         (50)                                   
      Foreign Body                                     1 [3.0]      3 [3.0]      4 [3.0]      7 [3.0]                               
      Inflammation, Suppurative                        4 [2.0]      8 [1.9]      4 [1.8]     10 [1.3]                               
      Goblet Cell, Hyperplasia                         1 [2.0]      1 [1.0]                   5 [2.4]                               
      Nasolacrimal Duct, Inflammation, Suppurative                  1 [2.0]      1 [2.0]      1 [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   11                                                              
                                                                                                                                   
NTP Experiment-Test: 97006-01         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 05/11/04    
Route: RESPIRATORY EXPOSURE WHOLE BODY                      METHYL ISOBUTYL KETONE                                Time: 09:05:20    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                        CONTROL      450 PPM      900 PPM      1800 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
RESPIRATORY SYSTEM - CONT                                                                                                           
      Respiratory Epithelium, Hyperplasia              4 [2.3]      1 [1.0]      3 [2.0]      3 [2.0]                               
   Pleura                                             (50)         (49)         (50)         (50)                                   
      Fibrosis                                         3 [1.7]                                                                      
      Inflammation, Chronic                            6 [1.8]                   6 [1.5]      4 [1.5]                               
      Mesothelium, Hyperplasia                                                   1 [2.0]      1 [4.0]                               
   Trachea                                            (50)         (48)         (50)         (50)                                   
      Inflammation, Suppurative                                     2 [2.5]                                                         
      Epithelium, Hyperplasia                                       1 [4.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (49)         (45)         (46)         (48)                                   
      Anterior Chamber, Hemorrhage                                  1 [3.0]                                                         
      Anterior Chamber, Inflammation, Suppurative                   1 [2.0]                                                         
      Cornea, Hyperplasia                                                                     1 [2.0]                               
      Lens, Cataract                                   7 [2.7]      6 [2.7]      3 [2.7]      2 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Infarct                                                                    4            3                                     
      Nephropathy                                     42 [2.0]     45 [2.6]     47 [2.4]     50 [3.1]                               
      Papilla, Mineralization                          1 [1.0]      6 [1.2]     22 [1.6]     29 [1.5]                               
      Pelvis, Dilatation                                            1 [1.0]                                                         
      Pelvis, Transitional Epithelium, Hyperplasia     1 [1.0]      5 [1.8]      6 [1.2]     19 [1.4]                               
      Renal Tubule, Accumulation, Hyaline Droplet                                2 [1.5]      2 [1.0]                               
      Renal Tubule, Cyst                               1            1            1                                                  
      Renal Tubule, Hyperplasia                        1 [2.0]     11 [3.2]      3 [2.0]     18 [2.7]                               
      Renal Tubule, Pigmentation                                                              1 [3.0]                               
      Transitional Epithelium, Hyperplasia                                                    1 [3.0]                               
   Urinary Bladder                                    (50)         (48)         (50)         (50)                                   
      Calculus Micro Observation Only                  1 [2.0]      2 [3.0]      2 [2.0]                                            
      Transitional Epithelium, Hyperplasia                          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   12                                                              
                                                                                                                                   
                             ------------------------------------------------------------                                           
                             ----------              END OF REPORT             ----------                                           
                             ------------------------------------------------------------                                           
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.