National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/20583

TDMS Study 92013-06 Pathology Tables

NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56

                                                         FINAL #1 MICE




       Facility:  Southern Research Institute

       Chemical CAS #:  822-36-6

       Lock Date:  09/13/02

       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: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                 3            4            3            3                                     
    Natural Death                                      4            6            4            7                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                42           40           41           39                                     
    Natural Death                                      1                         2            1                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Large, Cecum                             (49)         (48)         (46)         (46)                                   
      Edema                                            3 [2.0]      4 [2.0]      2 [2.0]      2 [2.0]                               
   Intestine Small, Jejunum                           (50)         (48)         (47)         (47)                                   
      Hyperplasia, Lymphoid                            4 [3.3]      2 [3.5]      2 [2.5]                                            
   Intestine Small, Ileum                             (48)         (45)         (48)         (48)                                   
      Hyperplasia, Lymphoid                            1 [4.0]                                                                      
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                                                2 [2.5]                                            
      Basophilic Focus                                 1                         1            1                                     
      Cyst                                             3 [3.0]                                1 [3.0]                               
      Eosinophilic Focus                               1            2            1                                                  
      Hematopoietic Cell Proliferation                 6 [2.7]                   5 [3.4]      3 [2.3]                               
      Hemorrhage                                                                              1 [3.0]                               
      Hyperplasia, Lymphoid                            2 [2.0]      3 [3.0]      1 [4.0]                                            
      Infiltration Cellular, Mixed Cell                1 [4.0]      3 [2.0]      1 [3.0]      1 [2.0]                               
      Mixed Cell Focus                                 1                         1                                                  
      Necrosis, Focal                                  4 [3.3]      3 [1.3]      2 [2.0]      6 [2.7]                               
      Centrilobular, Necrosis                          1 [2.0]                   1 [3.0]      1 [4.0]                               
      Hepatocyte, Hypertrophy                          1 [3.0]                                                                      
      Hepatocyte, Vacuolization Cytoplasmic            1 [3.0]      1 [3.0]      1 [3.0]      1 [4.0]                               
      Kupffer Cell, Pigmentation                       1 [2.0]      1 [2.0]      2 [3.0]                                            
   Mesentery                                          (3)          (7)          (7)          (4)                                    
      Hemorrhage                                                                              1 [2.0]                               
      Fat, Necrosis                                    3 [2.7]      3 [3.0]      3 [3.0]      3 [2.7]                               
   Pancreas                                           (49)         (48)         (48)         (49)                                   
      Atrophy                                                       1 [4.0]                                                         
      Cyst                                             3 [3.0]      1 [3.0]                                                         
      Hyperplasia, Lymphoid                                         1 [2.0]                   1 [2.0]                               
      Necrosis                                         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    2                                                              
                                                                                                                                   
NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Acinus, Cytoplasmic Alteration                   1 [3.0]      1 [3.0]                                                         
   Salivary Glands                                    (50)         (48)         (50)         (49)                                   
      Atrophy                                                                                 2 [2.0]                               
      Hyperplasia, Lymphoid                            3 [2.7]      4 [2.5]      3 [2.0]      3 [2.7]                               
   Stomach, Forestomach                               (50)         (50)         (50)         (50)                                   
      Diverticulum                                     2                                                                            
      Hyperplasia, Squamous                                                      1 [4.0]                                            
      Inflammation, Chronic                                                      1 [2.0]      1 [2.0]                               
      Ulcer                                            1 [2.0]      1 [3.0]                                                         
      Epithelium, Hyperplasia                          3 [2.0]      5 [2.6]      2 [2.0]      5 [1.8]                               
   Stomach, Glandular                                 (49)         (49)         (50)         (49)                                   
      Erosion                                                                    2 [2.5]      1 [1.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic                            1 [2.0]                   1 [1.0]                                            
      Mineralization                                                                          4 [2.0]                               
      Thrombosis                                                                 1 [3.0]                                            
      Myocardium, Necrosis                                          1 [2.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Accessory Adrenal Cortical Nodule                9            9            9            5                                     
      Hyperplasia, Diffuse                             1 [3.0]                                                                      
      Hyperplasia, Focal                                                         1 [1.0]      2 [2.5]                               
      Capsule, Hyperplasia                                          2 [2.0]                                                         
   Adrenal Medulla                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                1 [2.0]      2 [2.5]                               
   Islets, Pancreatic                                 (49)         (48)         (47)         (49)                                   
      Hyperplasia                                      1 [2.0]                                2 [2.0]                               
   Parathyroid Gland                                  (49)         (49)         (48)         (47)                                   
      Cyst                                                          1 [3.0]      5 [3.0]      2 [3.0]                               
   Pituitary Gland                                    (49)         (46)         (49)         (50)                                   
      Pars Distalis, Cyst                              1 [3.0]      3 [3.0]      4 [3.0]                                            
      Pars Distalis, Hyperplasia, Focal                2 [3.0]      4 [2.0]      1 [2.0]                                            
   Thyroid Gland                                      (50)         (49)         (50)         (48)                                   
      Follicle, Cyst                                  20 [1.6]     22 [1.7]     29 [1.8]     30 [2.1]                               
      Follicular Cell, Hyperplasia                     1 [2.0]                   1 [4.0]      1 [1.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    3                                                              
                                                                                                                                   
NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (50)         (49)         (50)         (50)                                   
      Inflammation, Chronic                            1 [2.0]      3 [2.0]      5 [2.4]      3 [2.3]                               
   Ovary                                              (48)         (49)         (49)         (50)                                   
      Angiectasis                                      9 [2.4]      9 [2.4]      7 [2.9]      6 [2.5]                               
      Cyst                                            16 [3.0]     20 [3.0]     14 [3.0]     19 [3.0]                               
      Inflammation, Granulomatous                                   1 [3.0]                                                         
      Corpus Luteum, Hyperplasia                                                              1 [3.0]                               
      Granulosa Cell, Hyperplasia                      1 [2.0]      1 [3.0]                                                         
      Thecal Cell, Hyperplasia                                                   1 [3.0]                                            
   Uterus                                             (50)         (50)         (50)         (50)                                   
      Angiectasis                                                   3 [2.3]                   3 [2.0]                               
      Hyperplasia, Cystic                             45 [3.2]     47 [3.2]     46 [3.0]     47 [3.1]                               
      Inflammation, Chronic                            1 [2.0]      1 [3.0]      1 [3.0]      3 [2.7]                               
      Metaplasia, Squamous                             2 [2.5]      3 [2.7]      1 [3.0]      5 [2.2]                               
      Thrombosis                                                                 1 [4.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Hyperplasia                                     13 [2.9]     13 [2.6]     10 [3.2]     17 [2.4]                               
      Infiltration Cellular, Mast Cell                              1 [3.0]                                                         
   Lymph Node                                         (3)          (9)          (12)         (7)                                    
      Bronchial, Hyperplasia, Lymphoid                                           1 [2.0]                                            
      Iliac, Hemorrhage                                             1 [3.0]                   1 [2.0]                               
      Iliac, Hyperplasia, Lymphoid                                  2 [2.5]      1 [3.0]      1 [3.0]                               
      Iliac, Pigmentation                                                                     1 [3.0]                               
      Inguinal, Hyperplasia, Lymphoid                               2 [2.5]      1 [3.0]                                            
      Mediastinal, Hyperplasia, Lymphoid                            2 [2.5]                                                         
      Renal, Hematopoietic Cell Proliferation                                    1 [3.0]                                            
      Renal, Hyperplasia, Lymphoid                                               1 [2.0]      1 [3.0]                               
      Renal, Pigmentation                                                                     1 [3.0]                               
   Lymph Node, Mandibular                             (47)         (47)         (48)         (48)                                   
      Hematopoietic Cell Proliferation                 1 [2.0]                   2 [2.5]                                            
      Hemorrhage                                                                 1 [2.0]      3 [1.7]                               
      Hyperplasia, Lymphoid                            6 [2.5]      8 [2.3]      7 [2.7]     13 [2.4]                               
                                                                                                                                    
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: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Pigmentation                                    12 [2.4]     19 [2.2]     18 [2.2]     19 [2.2]                               
   Lymph Node, Mesenteric                             (49)         (47)         (49)         (50)                                   
      Atrophy                                                       2 [2.5]                                                         
      Ectasia                                          1 [4.0]                   1 [2.0]                                            
      Hematopoietic Cell Proliferation                 2 [2.0]      1 [3.0]      2 [1.5]                                            
      Hyperplasia, Lymphoid                            3 [2.7]      8 [2.3]      9 [2.6]     10 [2.1]                               
   Spleen                                             (49)         (49)         (49)         (49)                                   
      Hematopoietic Cell Proliferation                15 [2.8]     16 [2.3]     13 [2.8]     11 [1.9]                               
      Hyperplasia, Lymphoid                            8 [3.5]     11 [3.5]      8 [3.8]     11 [3.3]                               
      Pigmentation                                                  1 [3.0]      1 [2.0]                                            
      Lymphoid Follicle, Atrophy                       1 [3.0]      1 [3.0]                   1 [2.0]                               
      Lymphoid Follicle, Hyperplasia                  14 [2.3]     12 [2.3]     12 [2.4]     13 [2.4]                               
      Red Pulp, Congestion                                                                    1 [3.0]                               
   Thymus                                             (49)         (49)         (50)         (48)                                   
      Atrophy                                          3 [3.0]      6 [2.7]      2 [3.5]      5 [2.8]                               
      Hyperplasia, Lymphoid                            3 [2.3]      1 [3.0]      2 [3.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (50)         (50)         (49)         (49)                                   
      Galactocele                                                                             1                                     
      Hyperplasia                                     16 [1.1]     10 [1.1]     14 [1.1]     24 [1.2]                               
   Skin                                               (50)         (50)         (50)         (50)                                   
      Edema                                                                      1 [2.0]      1 [2.0]                               
      Epidermis, Hyperplasia                                        1 [1.0]                                                         
      Subcutaneous Tissue, Inflammation,                                                                                            
        Granulomatous                                  1 [3.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Hyperostosis                                    10 [2.5]     12 [2.2]     10 [2.4]      6 [2.2]                               
   Skeletal Muscle                                    (1)          (1)          (2)          (2)                                    
      Mineralization                                                                          1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Compression                                                                             1 [4.0]                               
      Hemorrhage                                                    2 [3.0]      1 [2.0]      2 [1.5]                               
                                                                                                                                    
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    5                                                              
                                                                                                                                   
NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
NERVOUS SYSTEM - CONT                                                                                                               
   Peripheral Nerve                                                (2)                       (2)                                    
      Atrophy                                                                                 1 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Hemorrhage                                       1 [1.0]      2 [1.5]      3 [1.7]      4 [1.8]                               
      Hyperplasia, Lymphoid                            6 [1.8]      6 [2.2]      8 [1.8]      8 [1.8]                               
      Infiltration Cellular, Histiocyte                1 [1.0]      5 [1.4]      1 [1.0]      8 [2.0]                               
      Metaplasia, Osseous                              1 [1.0]                                                                      
      Alveolar Epithelium, Hyperplasia                 3 [1.7]      2 [2.5]      3 [1.7]     11 [1.9]                               
   Nose                                               (50)         (49)         (50)         (50)                                   
      Inflammation, Chronic                            1 [3.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (50)         (50)         (50)         (50)                                   
      Cataract                                                                   2 [2.0]      1 [2.0]                               
      Inflammation, Chronic                                                      1 [2.0]      1 [1.0]                               
      Cornea, Hyperplasia                                                        1 [2.0]                                            
      Cornea, Mineralization                                                     1 [1.0]                                            
      Retina, Degeneration                                                       1 [2.0]                                            
   Harderian Gland                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                   1 [3.0]                                                         
      Hyperplasia, Focal                               2 [2.0]      3 [2.7]      2 [2.0]                                            
      Inflammation, Chronic                            1 [3.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (49)         (50)         (50)         (50)                                   
      Cyst                                             1 [3.0]      1 [3.0]                                                         
      Hydronephrosis                                                1 [2.0]                                                         
      Hyperplasia, Lymphoid                            1 [2.0]      2 [3.0]      6 [2.2]      3 [2.0]                               
      Metaplasia, Osseous                              1 [3.0]      1 [2.0]                   1 [2.0]                               
      Nephropathy                                     21 [1.2]     20 [1.3]     17 [1.0]     25 [1.0]                               
      Renal Tubule, Accumulation, Hyaline Droplet      3 [2.7]      2 [3.5]      1 [3.0]      2 [3.5]                               
      Renal Tubule, Hyperplasia                        1 [2.0]                                                                      
      Renal Tubule, Necrosis                                        1 [2.0]                                                         
   Urinary Bladder                                    (50)         (50)         (50)         (50)                                   
      Edema                                                                      1 [3.0]      1 [4.0]                               
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
URINARY SYSTEM - CONT                                                                                                               
      Hemorrhage                                                    1 [3.0]                                                         
      Hyperplasia, Lymphoid                            1 [3.0]      3 [2.0]      4 [2.0]      3 [2.0]                               
      Inflammation, Chronic                            1 [2.0]      1 [3.0]                                                         
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Natural Death                                      4            6            8                                                  
    Moribund Sacrifice                                 1                                      3                                     
  Survivors                                                                                                                         
    Natural Death                                      1                                                                            
    Terminal Sacrifice                                44           44           42           46                                     
  Other                                                                                       1                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Large, Cecum                             (50)         (49)         (47)         (50)                                   
      Edema                                            3 [2.0]      1 [2.0]      3 [2.0]      4 [2.0]                               
      Hyperplasia, Lymphoid                                                      1 [4.0]                                            
      Inflammation                                                               1 [4.0]                                            
      Ulcer                                            1 [4.0]                   1 [4.0]                                            
   Intestine Small, Jejunum                           (48)         (47)         (48)         (50)                                   
      Hemorrhage                                                                 1 [3.0]                                            
      Hyperplasia, Lymphoid                            2 [3.0]      2 [2.5]      3 [2.7]      1 [3.0]                               
   Intestine Small, Ileum                             (49)         (46)         (48)         (49)                                   
      Hyperplasia, Lymphoid                                         1 [3.0]                                                         
   Liver                                              (50)         (50)         (50)         (50)                                   
      Basophilic Focus                                 1                         1            1                                     
      Clear Cell Focus                                 3            3            2            3                                     
      Cyst                                                          1 [3.0]                   1 [3.0]                               
      Eosinophilic Focus                               5            2            1            1                                     
      Hyperplasia, Lymphoid                                                                   1 [4.0]                               
      Infiltration Cellular, Mixed Cell                                          3 [1.7]      1 [2.0]                               
      Mixed Cell Focus                                 3            7            2                                                  
      Necrosis, Focal                                  2 [2.0]      3 [1.0]      2 [2.0]                                            
      Tension Lipidosis                                1                         1                                                  
      Centrilobular, Necrosis                                                    1 [1.0]                                            
      Hepatocyte, Hypertrophy                                       1 [3.0]                   1 [3.0]                               
      Hepatocyte, Vacuolization Cytoplasmic            4 [3.0]      5 [3.4]      2 [3.5]                                            
   Mesentery                                          (4)          (7)          (2)          (3)                                    
      Hemorrhage                                       1 [4.0]                                                                      
      Fat, Necrosis                                    3 [2.7]      3 [2.0]      2 [2.5]      2 [2.0]                               
   Pancreas                                           (49)         (49)         (50)         (50)                                   
      Cyst                                                                       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    8                                                              
                                                                                                                                   
NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Acinus, Hyperplasia, Focal                                                              1 [2.0]                               
   Stomach, Forestomach                               (49)         (50)         (50)         (50)                                   
      Diverticulum                                                  2            1            1                                     
      Erosion                                                                    1 [1.0]                                            
      Hyperplasia                                                                             1 [4.0]                               
      Inflammation, Chronic                                                      2 [2.5]                                            
      Ulcer                                                         1 [3.0]      1 [3.0]                                            
      Epithelium, Hyperplasia                          3 [1.7]      2 [3.5]      4 [2.3]                                            
   Stomach, Glandular                                 (49)         (50)         (49)         (50)                                   
      Erosion                                          2 [2.0]                   1 [2.0]      1 [2.0]                               
      Glands, Hyperplasia                                                                     1 [3.0]                               
   Tooth                                              (4)                                    (3)                                    
      Inflammation, Chronic                            3 [2.3]                                2 [2.5]                               
      Malformation                                     1                                                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic                            2 [2.5]                   2 [1.5]      1 [2.0]                               
      Mineralization                                                             2 [2.0]                                            
      Thrombosis                                                                              1 [4.0]                               
      Myocardium, Necrosis                                                       1 [3.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Accessory Adrenal Cortical Nodule                2            4            6            8                                     
      Hyperplasia, Focal                               3 [1.7]      2 [2.0]      1 [1.0]      1 [1.0]                               
      Hypertrophy, Focal                              17 [1.5]     11 [1.9]     10 [1.5]     14 [1.9]                               
      Capsule, Hyperplasia                             1 [2.0]      1 [2.0]      2 [2.0]      5 [2.0]                               
   Islets, Pancreatic                                 (49)         (49)         (50)         (50)                                   
      Hyperplasia                                      4 [2.0]      2 [2.0]                   1 [2.0]                               
   Parathyroid Gland                                  (47)         (49)         (49)         (49)                                   
      Cyst                                             1 [3.0]                   1 [3.0]      1 [3.0]                               
   Pituitary Gland                                    (49)         (48)         (49)         (50)                                   
      Pars Distalis, Cyst                              1 [3.0]      3 [3.0]      3 [3.0]      2 [3.0]                               
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      Follicle, Cyst                                  13 [1.8]     13 [1.7]     13 [1.8]     14 [2.0]                               
      Follicular Cell, 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    9                                                              
                                                                                                                                   
NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Epididymis                                         (50)         (50)         (50)         (50)                                   
      Atypia Cellular                                  1 [2.0]      1 [3.0]                                                         
      Spermatocele                                     1 [2.0]                                1 [3.0]                               
   Preputial Gland                                    (50)         (50)         (50)         (50)                                   
      Cyst                                            29 [3.0]     27 [3.0]     31 [3.0]     36 [2.9]                               
      Inflammation, Chronic                           17 [2.1]     19 [2.1]     24 [2.1]     23 [2.1]                               
   Seminal Vesicle                                    (50)         (50)         (50)         (50)                                   
      Degeneration                                     1 [3.0]                                                                      
   Testes                                             (50)         (50)         (50)         (50)                                   
      Germinal Epithelium, Atrophy                                  3 [2.3]      1 [3.0]      3 [2.7]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Hyperplasia                                     13 [2.2]     15 [2.1]     14 [2.4]     15 [2.3]                               
   Lymph Node                                         (2)          (2)          (1)          (2)                                    
      Inguinal, Hyperplasia, Lymphoid                                                         1 [2.0]                               
      Inguinal, Pigmentation                           1 [3.0]                                                                      
      Pancreatic, Hyperplasia, Lymphoid                                                       1 [2.0]                               
   Lymph Node, Mandibular                             (48)         (50)         (48)         (45)                                   
      Hematopoietic Cell Proliferation                              2 [2.0]                   1 [2.0]                               
      Hyperplasia, Lymphoid                           10 [2.2]      8 [2.3]      9 [2.1]     12 [2.1]                               
      Pigmentation                                    10 [2.1]      5 [2.2]      7 [2.1]     12 [2.0]                               
   Lymph Node, Mesenteric                             (49)         (48)         (48)         (50)                                   
      Hematopoietic Cell Proliferation                                                        1 [2.0]                               
      Hemorrhage                                       4 [1.5]      7 [2.0]      4 [1.5]     14 [2.0]                               
      Hyperplasia, Lymphoid                            7 [2.6]      4 [2.8]      4 [2.8]      7 [2.6]                               
   Spleen                                             (49)         (49)         (50)         (50)                                   
      Angiectasis                                      1 [3.0]      1 [3.0]                   1 [3.0]                               
      Hematopoietic Cell Proliferation                10 [2.4]     14 [2.7]      9 [2.7]     12 [2.7]                               
      Hyperplasia, Lymphoid                            1 [4.0]      1 [3.0]      2 [3.0]      2 [4.0]                               
      Lymphoid Follicle, Atrophy                                    1 [3.0]      1 [4.0]      1 [3.0]                               
      Lymphoid Follicle, Hyperplasia                  10 [2.4]      8 [2.1]      2 [2.5]      7 [2.0]                               
   Thymus                                             (48)         (49)         (45)         (45)                                   
      Atrophy                                          7 [2.4]      7 [2.6]      5 [2.6]      8 [2.8]                               
                                                                                                                                    
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: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Skin                                               (50)         (50)         (50)         (49)                                   
      Cyst Epithelial Inclusion                                                               1                                     
      Edema                                                         2 [2.5]                                                         
      Ulcer                                                                      1 [4.0]                                            
      Epidermis, Hyperplasia                           2 [1.0]                   2 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Fibrous Osteodystrophy                                        1 [2.0]                   1 [2.0]                               
   Skeletal Muscle                                    (1)          (2)          (1)          (1)                                    
      Atrophy                                                                                 1 [2.0]                               
      Necrosis                                                      1 [3.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Hemorrhage                                       1 [2.0]                                                                      
      Inflammation, Chronic                            1 [3.0]                                                                      
   Peripheral Nerve                                                                          (2)                                    
      Atrophy                                                                                 1 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion                                                                 1 [2.0]      1 [4.0]                               
      Hemorrhage                                       3 [1.7]      2 [2.0]      1 [2.0]      5 [1.2]                               
      Hyperplasia, Lymphoid                            3 [1.7]      2 [2.0]      6 [1.8]      2 [2.0]                               
      Infiltration Cellular, Histiocyte                5 [2.2]      6 [1.7]      5 [1.8]     11 [1.7]                               
      Metaplasia, Osseous                                                        1 [1.0]                                            
      Thrombosis                                       1 [2.0]                                                                      
      Alveolar Epithelium, Hyperplasia                 7 [2.0]      3 [1.0]      1 [2.0]      9 [1.9]                               
      Bronchiole, Epithelium, Hyperplasia                                        1 [1.0]      1 [1.0]                               
   Nose                                               (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic                            1 [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   11                                                              
                                                                                                                                   
NTP Experiment-Test: 92013-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 01/12/04    
Route: DOSED FEED                                             4-METHYLIMIDAZOLE                                   Time: 15:11:56    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 PPM        312 PPM      625 PPM      1250 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (50)         (50)         (50)         (50)                                   
      Cataract                                         1 [3.0]                                2 [1.5]                               
      Inflammation, Chronic                            1 [1.0]                                1 [2.0]                               
   Harderian Gland                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia, Focal                               1 [3.0]      1 [2.0]      1 [3.0]      3 [2.3]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Cyst                                            13 [3.0]     12 [3.0]     12 [3.0]      7 [3.0]                               
      Hydronephrosis                                                             1 [2.0]      1 [2.0]                               
      Hyperplasia, Lymphoid                            2 [2.0]      2 [3.0]                   2 [2.0]                               
      Inflammation, Chronic Active                                  1 [3.0]                                                         
      Metaplasia, Osseous                              2 [2.0]      3 [1.7]                   2 [2.0]                               
      Mineralization                                                             2 [3.0]                                            
      Nephropathy                                     34 [1.4]     40 [1.2]     38 [1.3]     35 [1.6]                               
      Renal Tubule, Necrosis                                                     1 [2.0]                                            
   Urinary Bladder                                    (50)         (49)         (49)         (50)                                   
      Edema                                            1 [3.0]      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                                                              
                                                                                                                                   
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                             ----------              END OF REPORT             ----------                                           
                             ------------------------------------------------------------                                           
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.