National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/3183

TDMS Study 92012-06 Pathology Tables

NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43

                                                   FINAL #1; REVISION #2 MICE




       Facility:  Southern Research Institute

       Chemical CAS #:  693-98-1

       Lock Date:  10/16/01

       Cage Range:  All

       Reasons For Removal:    25019 Moribund Sacrifice                25020 Natural Death
                               25026 Other                             25021 Terminal Sacrifice

       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: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          60           60           60           60                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                 2            3            4            4                                     
    Natural Death                                      2            3            2            1                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                46           42           42           45                                     
    Moribund Sacrifice                                                           1                                                  
    Natural Death                                                   1                                                               
  Other                                                             1            1                                                  
                                                                                                                                    
  Animals Examined Microscopically                    50           49           49           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Large, Cecum                             (50)         (48)         (48)         (50)                                   
      Edema                                            2 [2.0]                   2 [2.0]      2 [2.0]                               
   Intestine Small, Jejunum                           (50)         (46)         (48)         (49)                                   
      Hyperplasia, Lymphoid                                         1 [3.0]                   1 [3.0]                               
      Peyer's Patch, Infiltration Cellular,                                                                                         
        Polymorphonuclear                                                                     1 [3.0]                               
   Intestine Small, Ileum                             (47)         (49)         (47)         (48)                                   
      Hyperplasia, Lymphoid                            1 [3.0]                                                                      
      Peyer's Patch, Infiltration Cellular,                                                                                         
        Polymorphonuclear                                                                     1 [3.0]                               
   Liver                                              (50)         (49)         (49)         (50)                                   
      Angiectasis                                      1 [3.0]                                                                      
      Basophilic Focus                                              4            1            1                                     
      Clear Cell Focus                                 1                         1            4                                     
      Eosinophilic Focus                                                         1                                                  
      Hematopoietic Cell Proliferation                 3 [3.0]      3 [2.0]      5 [1.8]      3 [3.0]                               
      Hemorrhage                                                    1 [3.0]                                                         
      Hepatodiaphragmatic Nodule                                                 1            2                                     
      Hyperplasia, Lymphoid                            3 [2.0]      3 [2.3]                   6 [2.2]                               
      Infarct                                                       1 [3.0]                                                         
      Infiltration Cellular, Mixed Cell               13 [1.7]      5 [1.6]     12 [1.3]     10 [1.1]                               
      Mixed Cell Focus                                 4            1            3                                                  
      Necrosis, Focal                                  5 [1.6]      2 [1.0]      3 [2.7]      4 [3.3]                               
      Tension Lipidosis                                                          2                                                  
      Bile Duct, Hyperplasia                                        1 [3.0]                                                         
      Hepatocyte, Vacuolization Cytoplasmic                                      1 [3.0]                                            
      Kupffer Cell, Pigmentation                                    2 [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    2                                                              
                                                                                                                                   
NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
   Mesentery                                          (3)          (4)          (6)          (6)                                    
      Inflammation, Chronic                            1 [4.0]      1 [3.0]                                                         
      Fat, Angiectasis                                                           1 [3.0]      1 [3.0]                               
      Fat, Necrosis                                    2 [3.0]      3 [2.3]      6 [1.8]      6 [2.8]                               
   Pancreas                                           (50)         (49)         (48)         (50)                                   
      Atrophy                                          1 [4.0]                                                                      
      Cyst                                             1 [3.0]      1 [3.0]      1 [3.0]      2 [3.0]                               
      Acinus, Cytoplasmic Alteration                                             2 [3.0]      1 [3.0]                               
   Salivary Glands                                    (50)         (49)         (49)         (49)                                   
      Atrophy                                          2 [2.0]                                1 [1.0]                               
      Hyperplasia, Lymphoid                                         5 [2.6]      3 [2.0]      2 [2.0]                               
   Stomach, Forestomach                               (50)         (49)         (49)         (50)                                   
      Diverticulum                                     1                                      5                                     
      Inflammation, Chronic Active                     1 [2.0]      1 [2.0]      2 [2.5]                                            
      Epithelium, Hyperplasia                          1 [2.0]                   4 [2.5]      1 [1.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (49)         (49)         (50)                                   
      Cardiomyopathy                                                                          2 [1.0]                               
      Thrombosis                                                                              1 [3.0]                               
      Myocardium, Necrosis                                                       1 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (49)         (49)         (50)                                   
      Accessory Adrenal Cortical Nodule                7 [3.0]      5 [3.0]      4 [3.0]      6 [3.0]                               
      Hyperplasia, Focal                                                                      2 [1.5]                               
      Capsule, Hyperplasia                             3 [2.0]                                                                      
   Adrenal Medulla                                    (50)         (49)         (49)         (50)                                   
      Hyperplasia                                                                1 [2.0]                                            
   Islets, Pancreatic                                 (50)         (48)         (48)         (50)                                   
      Hyperplasia                                      1 [2.0]      1 [2.0]                   1 [2.0]                               
   Parathyroid Gland                                  (48)         (46)         (45)         (48)                                   
      Cyst                                                          1 [3.0]      1 [3.0]      1 [3.0]                               
   Pituitary Gland                                    (50)         (49)         (47)         (49)                                   
      Pars Distalis, Angiectasis                                    3 [2.3]      1 [2.0]      1 [2.0]                               
      Pars Distalis, Cyst                              1 [3.0]      3 [3.0]      1 [2.0]                                            
      Pars Distalis, Hyperplasia, Focal                1 [3.0]      2 [1.5]      1 [1.0]      2 [2.0]                               
   Thyroid Gland                                      (49)         (48)         (48)         (50)                                   
      Degeneration, Cystic                            15 [2.1]     14 [1.8]     12 [1.7]      9 [1.2]                               
                                                                                                                                    
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: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Follicle, Cyst                                                             1 [3.0]      1 [3.0]                               
      Follicular Cell, Hyperplasia                     1 [1.0]      1 [2.0]      1 [1.0]      9 [1.6]                               
      Follicular Cell, Hypertrophy                     6 [1.2]      3 [1.0]     23 [1.1]     46 [1.7]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (50)         (48)         (48)         (50)                                   
      Inflammation, Chronic                                                                   1 [4.0]                               
   Ovary                                              (50)         (49)         (49)         (48)                                   
      Angiectasis                                     12 [2.3]      7 [2.4]      8 [2.8]      8 [2.6]                               
      Cyst                                            10 [3.0]     11 [3.0]     15 [3.0]     10 [3.0]                               
      Inflammation, Chronic                            3 [4.0]                   2 [3.0]                                            
      Thrombosis                                                                              1 [4.0]                               
      Corpus Luteum, Hyperplasia                                                              1 [3.0]                               
   Uterus                                             (50)         (49)         (49)         (50)                                   
      Angiectasis                                      3 [3.3]      2 [2.5]      2 [3.5]      6 [2.2]                               
      Inflammation, Chronic                            6 [2.8]      2 [2.0]      9 [2.7]      4 [3.3]                               
      Metaplasia, Squamous                             5 [3.0]                   5 [3.0]      1 [3.0]                               
      Cervix, Cyst Epithelial Inclusion                             1                                                               
      Endometrium, Fibrosis                                                                   1 [3.0]                               
      Endometrium, Hyperplasia, Cystic                48 [3.0]     47 [3.1]     46 [3.3]     45 [3.4]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (49)         (48)         (50)                                   
      Hyperplasia                                     10 [2.7]      5 [2.0]     13 [3.2]     16 [2.4]                               
   Lymph Node                                         (12)         (6)          (8)          (9)                                    
      Bronchial, Hyperplasia, Lymphoid                 1 [3.0]                                2 [2.5]                               
      Iliac, Ectasia                                                             1 [3.0]                                            
      Iliac, Hematopoietic Cell Proliferation          2 [2.5]      1 [2.0]      1 [2.0]                                            
      Iliac, Hyperplasia, Lymphoid                     5 [2.2]      3 [3.0]      4 [3.0]      2 [4.0]                               
      Iliac, Pigmentation                                           1 [2.0]                                                         
      Inguinal, Hyperplasia, Lymphoid                                            1 [2.0]                                            
      Lumbar, Hyperplasia, Lymphoid                    1 [2.0]      1 [2.0]      2 [3.0]      2 [3.0]                               
      Lumbar, Pigmentation                                          1 [2.0]                                                         
      Mediastinal, Hyperplasia, Lymphoid               1 [4.0]      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    4                                                              
                                                                                                                                   
NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Pancreatic, Hyperplasia, Lymphoid                                          1 [2.0]                                            
      Renal, Hematopoietic Cell Proliferation          1 [3.0]                   1 [2.0]                                            
      Renal, Hyperplasia, Lymphoid                     3 [2.7]      1 [4.0]      2 [2.5]                                            
   Lymph Node, Mandibular                             (48)         (48)         (46)         (48)                                   
      Atrophy                                                                    2 [2.5]                                            
      Hematopoietic Cell Proliferation                 3 [2.3]                                                                      
      Hemorrhage                                                                              1 [2.0]                               
      Hyperplasia, Lymphoid                           11 [2.0]     12 [1.8]     10 [2.0]     15 [1.7]                               
      Hyperplasia, Plasma Cell                         2 [2.0]      1 [3.0]      4 [1.8]                                            
      Pigmentation                                    24 [2.2]     20 [2.2]     21 [2.2]     21 [2.1]                               
   Lymph Node, Mesenteric                             (48)         (48)         (47)         (48)                                   
      Ectasia                                                                                 1 [2.0]                               
      Hematopoietic Cell Proliferation                 5 [2.2]      3 [2.3]                   3 [2.3]                               
      Hemorrhage                                                    1 [2.0]                   1 [2.0]                               
      Hyperplasia, Lymphoid                            3 [2.3]      7 [2.9]      4 [2.5]      6 [2.7]                               
      Hyperplasia, Plasma Cell                                      1 [3.0]                                                         
   Spleen                                             (50)         (49)         (49)         (50)                                   
      Angiectasis                                                                1 [2.0]                                            
      Atrophy                                                       1 [1.0]      1 [2.0]                                            
      Congestion                                       2 [2.0]                                                                      
      Hematopoietic Cell Proliferation                15 [2.1]     20 [2.2]     24 [2.5]     39 [2.4]                               
      Hyperplasia, Plasma Cell                                      1 [3.0]                                                         
      Pigmentation                                                  4 [1.3]     11 [1.5]     34 [1.7]                               
      Lymphoid Follicle, Atrophy                       1 [2.0]      3 [2.0]      5 [2.6]      4 [3.3]                               
      Lymphoid Follicle, Hyperplasia                  12 [1.8]     14 [1.8]     13 [2.3]     16 [2.2]                               
   Thymus                                             (50)         (48)         (48)         (50)                                   
      Atrophy                                          5 [2.6]      2 [2.0]      7 [3.1]      3 [3.0]                               
      Hyperplasia, Lymphoid                                                                   4 [2.5]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (49)         (49)         (49)         (50)                                   
      Hyperplasia                                                   2 [2.5]                   2 [1.0]                               
   Skin                                               (50)         (49)         (49)         (50)                                   
      Edema                                                                      1 [3.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (49)         (49)         (50)                                   
      Hyperostosis                                     9 [1.9]     13 [2.2]     10 [2.2]     11 [2.1]                               
   Skeletal Muscle                                                 (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    5                                                              
                                                                                                                                   
NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
MUSCULOSKELETAL SYSTEM - CONT                                                                                                       
      Necrosis                                                                   1 [4.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (49)         (49)         (50)                                   
      Hemorrhage                                                    1 [1.0]      1 [2.0]                                            
      Inflammation, Chronic Active                                  1 [2.0]                                                         
      Vacuolization Cytoplasmic                                                               1 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (49)         (49)         (50)                                   
      Edema                                            2 [2.0]                                1 [2.0]                               
      Foreign Body                                     2            2            2                                                  
      Hemorrhage                                       4 [1.3]      3 [1.3]      1 [2.0]      4 [1.5]                               
      Hyperplasia, Lymphoid                            9 [2.2]      6 [2.0]      3 [2.0]      7 [2.3]                               
      Infiltration Cellular, Histiocyte                2 [1.5]      2 [2.5]      3 [2.7]                                            
      Thrombosis                                                    1 [2.0]                   1 [1.0]                               
      Alveolar Epithelium, Hyperplasia                 1 [1.0]      2 [2.0]      3 [2.0]      2 [2.0]                               
   Nose                                               (50)         (49)         (49)         (50)                                   
      Foreign Body                                                  1                                                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (50)         (49)         (49)         (50)                                   
      Atrophy                                                                                 1 [4.0]                               
      Cataract                                                      1 [2.0]      2 [2.5]                                            
      Inflammation, Chronic                            1 [1.0]                   2 [2.5]                                            
   Harderian Gland                                    (50)         (49)         (49)         (50)                                   
      Hyperplasia                                      1 [2.0]                                                                      
      Hyperplasia, Focal                                            3 [3.0]      2 [2.0]      1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (49)         (49)         (50)                                   
      Cyst                                             1 [3.0]      2 [3.0]      1 [3.0]      1 [3.0]                               
      Hyperplasia, Lymphoid                            8 [2.0]     16 [2.1]      8 [2.1]      4 [2.3]                               
      Infarct                                                                    2 [1.5]      2 [3.0]                               
      Inflammation, Chronic                                                                   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    6                                                              
                                                                                                                                   
NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
URINARY SYSTEM - CONT                                                                                                               
      Metaplasia, Osseous                                           1 [2.0]                   2 [2.5]                               
      Nephropathy                                     27 [1.1]     17 [1.1]     21 [1.1]     19 [1.0]                               
      Papilla, Necrosis                                                                       1 [3.0]                               
      Renal Tubule, Accumulation, Hyaline Droplet                   1 [2.0]                   1 [4.0]                               
      Renal Tubule, Dilatation                                                   1 [2.0]                                            
      Renal Tubule, Necrosis                                                     1 [3.0]      1 [2.0]                               
      Renal Tubule, Pigmentation                                    2 [2.5]                                                         
   Urinary Bladder                                    (50)         (49)         (49)         (50)                                   
      Hyperplasia, Lymphoid                           16 [2.3]     16 [2.1]      6 [2.0]     11 [2.3]                               
      Inflammation, Chronic                            1 [1.0]      1 [2.0]                                                         
      Transitional Epithelium, Hyperplasia                          1 [1.0]                                                         
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          60           60           60           60                                     
  Early Deaths                                                                                                                      
    Moribund Sacrifice                                 4            1            5            5                                     
    Natural Death                                      3            3            9            5                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                43           46           36           40                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Intestine Large, Cecum                             (49)         (49)         (47)         (50)                                   
      Edema                                            2 [2.0]      1 [2.0]      1 [2.0]      1 [2.0]                               
   Intestine Small, Duodenum                          (49)         (49)         (45)         (50)                                   
      Epithelium, Hyperplasia                                                                 1 [3.0]                               
   Intestine Small, Jejunum                           (50)         (49)         (46)         (50)                                   
      Hyperplasia, Lymphoid                                         1 [2.0]      1 [3.0]                                            
      Infiltration Cellular, Polymorphonuclear                                   1 [3.0]                                            
   Intestine Small, Ileum                             (49)         (50)         (45)         (49)                                   
      Hyperplasia, Lymphoid                                         1 [2.0]                   1 [2.0]                               
      Infiltration Cellular, Polymorphonuclear                                                1 [2.0]                               
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                      2 [3.0]                   1 [4.0]                                            
      Basophilic Focus                                 2            3            1            3                                     
      Clear Cell Focus                                 6            9            6            8                                     
      Cyst                                                          1 [3.0]                                                         
      Eosinophilic Focus                               3            3            2            6                                     
      Hematopoietic Cell Proliferation                 1 [3.0]                   2 [1.5]      2 [2.0]                               
      Hepatodiaphragmatic Nodule                                                              1                                     
      Infarct                                          1                                                                            
      Infiltration Cellular, Mixed Cell                5 [1.4]      7 [1.1]      7 [1.3]      7 [1.4]                               
      Mixed Cell Focus                                 4            3            4            4                                     
      Necrosis, Diffuse                                                                       1 [3.0]                               
      Necrosis, Focal                                  2 [2.0]      6 [1.5]      2 [2.5]      6 [2.2]                               
      Tension Lipidosis                                             2            1                                                  
      Hepatocyte, Cytoplasmic Alteration                                        11 [1.2]     37 [1.8]                               
      Hepatocyte, Karyomegaly                                                   10 [1.0]     29 [1.3]                               
      Hepatocyte, Vacuolization Cytoplasmic                         1 [3.0]                   1 [2.0]                               
      Kupffer Cell, Pigmentation                                    1 [3.0]      1 [2.0]     19 [1.5]                               
   Mesentery                                          (6)          (2)          (5)          (2)                                    
      Angiectasis                                                   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    8                                                              
                                                                                                                                   
NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Inflammation, Chronic                                         1 [1.0]                                                         
      Fat, Necrosis                                    4 [2.3]      1 [2.0]      3 [2.3]      2 [2.5]                               
   Pancreas                                           (50)         (50)         (49)         (50)                                   
      Atrophy                                          1 [2.0]                   1 [4.0]                                            
      Cyst                                             2 [3.0]                   3 [3.0]      2 [3.0]                               
      Acinus, Cytoplasmic Alteration                                             2 [2.0]      1 [3.0]                               
   Salivary Glands                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia, Lymphoid                            2 [2.0]      2 [2.0]                                                         
   Stomach, Forestomach                               (50)         (49)         (50)         (50)                                   
      Diverticulum                                                  2                                                               
      Inflammation, Chronic Active                     1 [2.0]      1 [1.0]                                                         
      Ulcer                                                         1 [3.0]                   1 [3.0]                               
      Epithelium, Hyperplasia                          2 [2.0]      2 [1.5]      1 [2.0]      1 [3.0]                               
   Stomach, Glandular                                 (50)         (49)         (49)         (50)                                   
      Glands, Dysplasia                                1 [3.0]                                                                      
   Tooth                                                                                     (1)                                    
      Inflammation, Chronic                                                                   1 [4.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                   1 [1.0]                                1 [1.0]                               
      Perivascular, Inflammation, Chronic              3 [1.7]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Accessory Adrenal Cortical Nodule                2 [3.0]      6 [3.0]      8 [3.0]      6 [3.0]                               
      Hyperplasia, Focal                               2 [1.5]      4 [1.5]      3 [1.3]      1 [1.0]                               
      Hypertrophy, Focal                              13 [1.3]     18 [1.6]     10 [1.2]     10 [1.7]                               
      Capsule, Hyperplasia                             1 [1.0]      2 [1.5]      3 [1.3]      2 [1.5]                               
   Adrenal Medulla                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                2 [1.5]                                            
   Islets, Pancreatic                                 (50)         (50)         (49)         (50)                                   
      Hyperplasia                                                   2 [2.0]                   1 [2.0]                               
   Parathyroid Gland                                  (49)         (47)         (45)         (48)                                   
      Cyst                                             3 [3.0]      1 [3.0]      2 [3.0]      1 [3.0]                               
   Pituitary Gland                                    (49)         (48)         (48)         (50)                                   
      Pars Distalis, Cyst                              2 [3.0]      1 [3.0]      2 [3.0]      2 [3.0]                               
      Pars Distalis, Hyperplasia, Focal                             1 [4.0]                                                         
   Thyroid Gland                                      (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    9                                                              
                                                                                                                                   
NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Degeneration, Cystic                            10 [2.0]      2 [1.0]      3 [2.0]      4 [1.5]                               
      Follicular Cell, Hyperplasia                                  2 [1.5]      3 [1.7]     33 [1.9]                               
      Follicular Cell, Hypertrophy                     1 [1.0]                   6 [1.2]     25 [1.3]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Epididymis                                         (50)         (50)         (50)         (50)                                   
      Fibrosis                                         1 [2.0]                                                                      
      Granuloma Sperm                                                            3 [2.7]      6 [2.5]                               
      Hyperplasia, Lymphoid                                                      2 [2.5]      1 [3.0]                               
      Hypospermia                                                                1 [4.0]                                            
      Inflammation, Chronic Active                     1 [1.0]      3 [1.3]      7 [2.0]      8 [2.9]                               
   Penis                                              (1)                       (1)          (1)                                    
      Angiectasis                                                                1 [3.0]      1 [3.0]                               
   Preputial Gland                                    (50)         (50)         (50)         (50)                                   
      Cyst                                            18 [3.0]     23 [3.0]     16 [3.0]     21 [3.0]                               
      Inflammation, Chronic                           14 [2.4]     10 [2.2]     14 [2.1]      7 [2.4]                               
   Prostate                                           (49)         (50)         (49)         (50)                                   
      Inflammation, Chronic                                                                   2 [2.5]                               
   Seminal Vesicle                                    (50)         (50)         (50)         (50)                                   
      Atrophy                                          1 [2.0]                                                                      
   Testes                                             (50)         (50)         (50)         (50)                                   
      Germinal Epithelium, Atrophy                     1 [2.0]      4 [2.0]      8 [2.3]     14 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      4 [3.0]     10 [2.8]     20 [2.1]     42 [2.5]                               
   Lymph Node                                         (2)          (3)                       (1)                                    
      Bronchial, Hyperplasia, Lymphoid                              1 [2.0]                                                         
   Lymph Node, Mandibular                             (48)         (46)         (45)         (50)                                   
      Atrophy                                          1 [3.0]                   2 [2.0]      4 [2.8]                               
      Ectasia                                                                    1 [2.0]                                            
      Hyperplasia, Lymphoid                           10 [2.1]     14 [2.3]      9 [2.6]     13 [2.2]                               
      Pigmentation                                     8 [2.1]      6 [2.2]      9 [2.0]      6 [2.0]                               
   Lymph Node, Mesenteric                             (47)         (47)         (46)         (48)                                   
                                                                                                                                    
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: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Angiectasis                                                                             1 [3.0]                               
      Atrophy                                          1 [2.0]      1 [3.0]      2 [2.5]      2 [3.0]                               
      Hemorrhage                                       4 [1.8]      2 [1.5]      2 [2.0]                                            
      Hyperplasia, Lymphoid                            7 [2.4]      7 [2.1]     15 [2.4]     10 [2.3]                               
      Necrosis                                         1 [4.0]                                1 [3.0]                               
   Spleen                                             (50)         (50)         (49)         (50)                                   
      Angiectasis                                                                             1 [2.0]                               
      Atrophy                                                       1 [3.0]      4 [3.0]      3 [2.7]                               
      Hematopoietic Cell Proliferation                10 [2.2]     21 [2.3]     38 [2.5]     45 [2.9]                               
      Pigmentation                                     1 [2.0]     16 [1.1]     33 [1.6]     43 [2.2]                               
      Lymphoid Follicle, Atrophy                                    4 [3.3]     14 [1.6]     30 [1.8]                               
      Lymphoid Follicle, Hyperplasia                   5 [2.0]      2 [1.5]      2 [2.0]                                            
   Thymus                                             (47)         (46)         (46)         (47)                                   
      Atrophy                                          7 [2.6]      5 [2.2]      9 [3.4]      8 [3.1]                               
      Cyst                                             1 [3.0]                   1 [3.0]      1 [3.0]                               
      Hyperplasia, Lymphoid                                         1 [3.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Skin                                               (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic                                         1 [4.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Skeletal Muscle                                    (1)          (1)                       (2)                                    
      Atrophy                                                                                 1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Compression                                                   1 [3.0]                                                         
   Peripheral Nerve                                   (1)                                    (1)                                    
      Atrophy                                                                                 1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Edema                                            1 [2.0]      3 [2.0]      1 [2.0]      3 [2.0]                               
      Hemorrhage                                       4 [2.0]      8 [1.5]      4 [1.8]      2 [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   11                                                              
                                                                                                                                   
NTP Experiment-Test: 92012-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 08/06/04    
Route: DOSED FEED                                             2-METHYLIMIDAZOLE                                   Time: 09:44:43    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0PPM         625 PPM      1250 PPM     2500 PPM                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
RESPIRATORY SYSTEM - CONT                                                                                                           
      Hyperplasia, Lymphoid                            1 [2.0]      2 [2.0]      2 [2.0]      4 [2.0]                               
      Infiltration Cellular, Histiocyte                4 [2.8]      4 [3.0]      4 [2.0]      2 [3.0]                               
      Inflammation, Chronic                                                      1 [1.0]      2 [1.5]                               
      Metaplasia, Osseous                                                        2 [1.0]                                            
      Thrombosis                                       1 [1.0]                                1 [2.0]                               
      Alveolar Epithelium, Hyperplasia                 5 [3.2]      3 [2.0]      1 [1.0]      3 [2.3]                               
      Alveolar Epithelium, Hyperplasia, Multifocal     1 [3.0]                                                                      
   Nose                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                     1            3            3            2                                     
      Inflammation, Chronic                            1 [1.0]      4 [2.5]      3 [1.7]      2 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (50)         (50)         (50)         (50)                                   
      Cataract                                                                   1 [3.0]      1 [2.0]                               
      Inflammation, Chronic                            1 [3.0]      2 [3.0]      2 [2.0]      2 [3.0]                               
      Cornea, Hyperplasia                              1 [2.0]                   1 [2.0]                                            
   Harderian Gland                                    (50)         (50)         (48)         (50)                                   
      Hyperplasia, Focal                               1 [2.0]                   2 [2.5]                                            
      Inflammation, Chronic                            3 [1.7]      4 [1.8]                   2 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Cyst                                            13 [3.0]     11 [3.0]     12 [3.0]     19 [3.0]                               
      Hydronephrosis                                   1 [2.0]                                                                      
      Hyperplasia, Lymphoid                            1 [2.0]      3 [2.0]      3 [2.0]      3 [2.0]                               
      Infarct                                          6 [1.8]      6 [1.8]      6 [2.2]      1 [2.0]                               
      Inflammation, Suppurative                                                               1 [4.0]                               
      Metaplasia, Osseous                              5 [1.8]      3 [1.3]      2 [1.0]      3 [1.7]                               
      Nephropathy                                     34 [1.2]     43 [1.5]     32 [1.5]     31 [1.1]                               
      Papilla, Necrosis                                                                       1 [2.0]                               
      Renal Tubule, Hyperplasia                        1 [1.0]      1 [1.0]      2 [1.0]      3 [1.7]                               
      Renal Tubule, Pigmentation                       1 [2.0]                   2 [1.5]     45 [2.5]                               
   Urethra                                                                                   (1)                                    
      Angiectasis                                                                             1 [4.0]                               
      Inflammation, Suppurative                                                               1 [3.0]                               
   Urinary Bladder                                    (50)         (50)         (50)         (50)                                   
      Transitional Epithelium, Hyperplasia                                                    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   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.