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TDMS Study 91005-08 Pathology Tables

NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53

                                                   FINAL #1; REVISION #1 MICE




       Facility:  Southern Research Institute

       Chemical CAS #:  7220-79-3

       Lock Date:  09/05/03

       Cage Range:  All

       Reasons For Removal:    All

       Removal Date Range:     All

       Treatment Groups:       Include All

































a  Number of animals examined microscopically at site and number of animals with lesion
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)

                                                              Page   1


NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Natural Death                                      9            5            2            6                                     
    Moribund Sacrifice                                 7            4            5            1                                     
    Accidently Killed                                  1                                                                            
    Dosing Accident                                                 1            1                                                  
  Survivors                                                                                                                         
    Terminal Sacrifice                                29           40           41           41                                     
    Natural Death                                      2                         1            2                                     
    Moribund Sacrifice                                 2                                                                            
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Esophagus                                          (50)         (50)         (50)         (50)                                   
      Foreign Body                                                  1 [3.0]                                                         
      Inflammation                                                  1 [3.0]                                                         
      Perforation                                                   1 [3.0]                                                         
   Gallbladder                                        (42)         (45)         (47)         (44)                                   
      Cyst                                             2                         1            2                                     
   Intestine Large, Rectum                            (48)         (48)         (50)         (46)                                   
      Artery, Inflammation, Chronic, Focal                          1 [3.0]                                                         
   Intestine Large, Cecum                             (43)         (46)         (47)         (44)                                   
      Edema                                            1 [3.0]                                                                      
      Lymphoid Tissue, Hyperplasia, Lymphoid                                     1 [3.0]                                            
   Intestine Small, Duodenum                          (43)         (45)         (47)         (42)                                   
      Epithelium, Hyperplasia, Focal                                             1 [2.0]                                            
   Intestine Small, Jejunum                           (43)         (45)         (47)         (43)                                   
      Epithelium, Hyperplasia, Focal                                1 [2.0]                                                         
      Lymphoid Tissue, Hyperplasia                                               1 [4.0]                                            
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis, Focal                               2 [2.0]                                                                      
      Basophilic Focus                                              1                         3                                     
      Clear Cell Focus                                 3            3            4            2                                     
      Congestion                                       1 [3.0]      2 [2.5]      1 [1.0]      1 [3.0]                               
      Eosinophilic Focus                               1            1            3            1                                     
      Fibrosis, Focal                                  1 [1.0]                                                                      
      Hematopoietic Cell Proliferation                 4 [1.3]      1 [2.0]      6 [1.7]      2 [1.0]                               
      Hemorrhage                                       1 [3.0]                                1 [1.0]                               
      Hepatodiaphragmatic Nodule                       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    2                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Infarct                                                                    1 [3.0]                                            
      Infiltration Cellular, Mixed Cell               11 [1.5]     12 [1.2]     12 [1.5]     15 [1.1]                               
      Mixed Cell Focus                                 2            1                         1                                     
      Bile Duct, Cyst                                  1                                                                            
      Hepatocyte, Necrosis, Focal                      3 [1.7]      3 [1.7]      1 [2.0]                                            
      Hepatocyte, Vacuolization Cytoplasmic           12 [2.7]     11 [2.0]      8 [2.3]     15 [2.3]                               
      Kupffer Cell, Pigmentation                       1 [1.0]                   1 [1.0]                                            
   Mesentery                                          (18)         (14)         (15)         (13)                                   
      Hemorrhage                                                                 1 [3.0]      1 [2.0]                               
      Infiltration Cellular, Lymphoid                               1 [2.0]                                                         
      Artery, Inflammation, Chronic, Focal             1 [3.0]      1 [3.0]      1 [3.0]                                            
      Fat, Necrosis, Focal                            16 [2.4]     12 [2.8]     13 [2.3]      4 [2.5]                               
   Pancreas                                           (46)         (46)         (49)         (49)                                   
      Acinus, Atrophy, Diffuse                                                                1 [4.0]                               
      Acinus, Atrophy, Focal                           1 [4.0]      1 [4.0]                   1 [1.0]                               
      Acinus, Cytoplasmic Alteration                                             1 [1.0]                                            
      Duct, Cyst                                       2                         2            2                                     
   Salivary Glands                                    (50)         (50)         (50)         (49)                                   
      Hyperplasia, Lymphoid                                         1 [3.0]                                                         
   Stomach, Forestomach                               (50)         (50)         (50)         (49)                                   
      Diverticulum                                     1 [1.0]                   1 [1.0]      3 [1.0]                               
      Inflammation, Focal                              1 [1.0]                   1 [3.0]                                            
      Ulcer                                            2 [2.0]                   3 [2.0]      1 [1.0]                               
      Epithelium, Hyperplasia                          2 [2.0]      2 [2.0]      2 [2.5]      1 [2.0]                               
   Stomach, Glandular                                 (45)         (47)         (50)         (46)                                   
      Cyst                                             1                                      1                                     
      Epithelium, Cytoplasmic Alteration, Focal        1 [2.0]                                                                      
      Epithelium, Hyperplasia                          1 [2.0]                                                                      
   Tooth                                              (2)          (10)         (3)          (3)                                    
      Dysplasia                                        2 [1.5]     10 [1.2]      3 [1.3]      3 [1.3]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Blood Vessel                                                    (1)                                                              
      Aneurysm                                                      1 [4.0]                                                         
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                   1 [1.0]                                1 [1.0]                               
      Infiltration Cellular, Mixed Cell                                          1 [3.0]                                            
      Mineralization, Focal                                                                   1 [1.0]                               
      Thrombosis                                       1 [3.0]                                                                      
      Artery, Inflammation, Chronic                                              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    3                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Accessory Adrenal Cortical Nodule                2 [2.0]      2 [1.5]                                                         
      Angiectasis                                                                1 [2.0]                                            
      Cytoplasmic Alteration, Focal                    1 [1.0]                                                                      
      Degeneration, Cystic                             1 [1.0]                                                                      
      Hyperplasia, Focal                                                         1 [2.0]                                            
      Infiltration Cellular, Mixed Cell                1 [2.0]                                                                      
   Adrenal Medulla                                    (50)         (50)         (49)         (50)                                   
      Hyperplasia, Focal                                                         1 [1.0]                                            
   Parathyroid Gland                                  (48)         (48)         (46)         (49)                                   
      Cyst                                             1            1            1            1                                     
   Pituitary Gland                                    (46)         (49)         (48)         (47)                                   
      Angiectasis                                      2 [1.0]      1 [1.0]                                                         
      Cyst                                                                       1            1                                     
      Pars Distalis, Cytoplasmic Alteration, Focal     1 [1.0]      4 [1.5]      1 [2.0]      2 [2.0]                               
      Pars Distalis, Hyperplasia, Focal                1 [1.0]      1 [2.0]      1 [2.0]      1 [2.0]                               
   Thyroid Gland                                      (46)         (50)         (49)         (47)                                   
      Cyst                                             1                         1                                                  
      Inflammation, Chronic, Focal                     1 [2.0]      1 [2.0]      1 [2.0]                                            
      C-Cell, Hyperplasia                                           1 [2.0]                   1 [2.0]                               
      Follicle, Degeneration, Cystic, Focal           17 [1.8]     15 [1.5]     28 [1.6]     23 [1.7]                               
      Follicular Cell, Hyperplasia, Focal              5 [1.6]      2 [2.0]      4 [2.0]      5 [1.4]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   Tissue NOS                                         (3)                                    (3)                                    
      Pelvic, Fibrosis                                 1 [3.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (48)         (50)         (46)         (48)                                   
      Degeneration, Cystic                                          1 [2.0]      1 [2.0]                                            
   Ovary                                              (47)         (48)         (49)         (48)                                   
      Angiectasis                                      3 [3.3]      2 [3.0]                   2 [2.5]                               
      Cyst                                            11           12           16           13                                     
      Hemorrhage                                                                 1 [3.0]      1 [3.0]                               
      Pigmentation, Focal                                                                     1 [3.0]                               
      Thrombosis                                       3 [4.0]                                3 [3.3]                               
      Bilateral, Cyst                                  1                                                                            
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    4                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
GENITAL SYSTEM - CONT                                                                                                               
      Interstitial Cell, Hyperplasia                                1 [3.0]                                                         
   Uterus                                             (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 [3.0]      1 [3.0]      1 [3.0]                                            
      Hemorrhage                                                    1 [3.0]                                                         
      Inflammation, Chronic                                         1 [3.0]                                                         
      Inflammation, Suppurative                        1 [3.0]                                                                      
      Endometrium, Hyperplasia, Cystic                48 [2.8]     45 [2.7]     49 [2.8]     48 [2.8]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (49)         (50)                                   
      Hyperplasia                                     10 [2.7]      4 [2.0]      9 [2.3]      4 [2.5]                               
   Lymph Node                                         (7)          (5)          (10)         (10)                                   
      Iliac, Angiectasis                               1 [3.0]                                                                      
      Iliac, Hyperplasia, Lymphoid                     1 [2.0]                   2 [2.5]      2 [2.5]                               
      Mediastinal, Hyperplasia, Lymphoid               2 [3.0]                                1 [3.0]                               
      Mediastinal, Inflammation                                                               1 [3.0]                               
      Pancreatic, Hyperplasia, Lymphoid                             1 [3.0]      1 [3.0]      1 [3.0]                               
      Renal, Hyperplasia, Lymphoid                     1 [2.0]                   1 [3.0]      1 [3.0]                               
   Lymph Node, Mandibular                             (48)         (49)         (48)         (46)                                   
      Hemorrhage                                       1 [3.0]                                                                      
      Hyperplasia, Lymphoid                            9 [2.0]     11 [2.6]     12 [2.3]     16 [2.2]                               
      Hyperplasia, Mast Cell                                                     1 [3.0]                                            
   Lymph Node, Mesenteric                             (46)         (49)         (49)         (48)                                   
      Ectasia                                                       1 [3.0]      2 [3.0]                                            
      Hemorrhage                                       1 [3.0]      2 [3.0]      2 [3.0]      1 [3.0]                               
      Hyperplasia, Histiocytic                                                   1 [3.0]                                            
      Hyperplasia, Lymphoid                            6 [2.3]      7 [2.3]     10 [2.6]      8 [2.3]                               
   Spleen                                             (47)         (47)         (49)         (50)                                   
      Angiectasis, Focal                                            1 [3.0]                                                         
      Congestion                                                    2 [3.0]                                                         
      Fibrosis, Focal                                               1 [3.0]      1 [3.0]                                            
      Hematopoietic Cell Proliferation                23 [2.7]     21 [2.5]     31 [2.4]     40 [2.3]                               
      Hyperplasia, Lymphoid                           17 [2.5]     15 [2.3]     17 [2.2]     11 [2.5]                               
   Thymus                                             (43)         (47)         (44)         (49)                                   
      Hyperplasia, Lymphoid                            8 [2.5]     13 [2.2]     11 [2.5]     14 [2.1]                               
      Inflammation                                                  1 [3.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Skin                                               (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    5                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
INTEGUMENTARY SYSTEM - CONT                                                                                                         
      Subcutaneous Tissue, Edema                                                              1 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Hyperostosis                                     5 [1.6]      5 [1.4]      4 [1.8]      5 [2.2]                               
      Vertebra, Hypertrophy, Focal                     3 [1.7]      2 [1.5]      1 [2.0]      1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (49)                                   
      Compression, Focal                               1 [3.0]                                1 [3.0]                               
      Artery, Meninges, Inflammation, Chronic          1 [2.0]                                                                      
   Spinal Cord                                        (1)          (2)          (1)          (1)                                    
      Demyelination, Focal                                          1 [3.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion                                       1 [3.0]                                                                      
      Foreign Body                                     1 [3.0]                   1 [4.0]                                            
      Hemorrhage                                       1 [3.0]      1 [2.0]                                                         
      Hyperplasia, Histiocytic                         1 [1.0]                                1 [3.0]                               
      Hyperplasia, Lymphoid                                                                   1 [3.0]                               
      Infiltration Cellular, Polymorphonuclear         1 [3.0]                                                                      
      Infiltration Cellular, Mixed Cell                1 [3.0]                                                                      
      Inflammation                                     1 [2.0]                   1 [4.0]                                            
      Metaplasia, Focal, Osseous                       1 [1.0]                                                                      
      Alveolar Epithelium, Hyperplasia, Focal          2 [1.5]                   1 [1.0]      1 [2.0]                               
      Mediastinum, Foreign Body                                     1            1                                                  
      Mediastinum, Inflammation                                     1 [3.0]      1 [3.0]                                            
      Serosa, Fibrosis                                                           1 [3.0]                                            
   Nose                                               (50)         (50)         (50)         (50)                                   
      Inflammation                                                  3 [2.0]      7 [2.0]     11 [1.9]                               
      Nasolacrimal Duct, Hyperplasia, Focal                                                   1 [2.0]                               
      Nasolacrimal Duct, Inflammation                               1 [2.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE FEMALE                           0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
SPECIAL SENSES SYSTEM - CONT                                                                                                        
   Eye                                                (43)         (48)         (47)         (47)                                   
      Atrophy                                                                                 1 [4.0]                               
      Cataract                                                                                1 [3.0]                               
      Anterior Chamber, Inflammation                   1 [3.0]                                                                      
      Artery, Retrobulbar, Inflammation, Chronic,                                                                                   
         Focal                                                      1 [2.0]                                                         
      Cornea, Inflammation                             1 [3.0]      1 [3.0]      1 [2.0]      1 [3.0]                               
      Cornea, Necrosis, Focal                                       1 [3.0]                                                         
   Harderian Gland                                    (49)         (50)         (50)         (50)                                   
      Epithelium, Hyperplasia                          2 [1.5]      1 [1.0]                   3 [2.3]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (48)         (50)         (49)         (50)                                   
      Hemorrhage                                                                              1 [3.0]                               
      Hyperplasia, Lymphoid                            1 [2.0]                                                                      
      Infarct                                                       1 [3.0]      2 [2.5]      2 [2.0]                               
      Metaplasia, Focal, Osseous                       2 [2.0]      1 [1.0]      1 [2.0]                                            
      Nephropathy                                      6 [1.3]      5 [1.4]      9 [1.1]      5 [1.2]                               
      Bilateral, Infarct                                                                      1 [4.0]                               
      Capsule, Fibrosis, Focal                                      1 [2.0]                                                         
      Renal Tubule, Accumulation, Hyaline Droplet      2 [3.0]                                2 [2.5]                               
      Renal Tubule, Cyst                               1                         3                                                  
   Urinary Bladder                                    (45)         (47)         (49)         (48)                                   
      Hyperplasia, Lymphoid                                         1 [3.0]                                                         
      Inflammation                                     1 [2.0]                                                                      
      Transitional Epithelium, Hyperplasia             1 [2.0]                                1 [2.0]                               
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Natural Death                                     11            6            5            3                                     
    Moribund Sacrifice                                 4            4            7            4                                     
    Accidently Killed                                               1                                                               
    Dosing Accident                                                 1                         2                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                35           38           38           41                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Esophagus                                          (50)         (50)         (50)         (50)                                   
      Foreign Body                                                  1 [2.0]                   1 [3.0]                               
      Inflammation                                     1 [3.0]      1 [3.0]                   1 [3.0]                               
      Perforation                                                   1 [3.0]                   1 [3.0]                               
   Intestine Large, Cecum                             (45)         (46)         (46)         (47)                                   
      Edema                                                         1 [3.0]      1 [3.0]                                            
      Inflammation, Chronic, Focal                                                            1 [3.0]                               
   Intestine Small, Duodenum                          (42)         (46)         (46)         (46)                                   
      Epithelium, Cyst                                              1                                                               
   Intestine Small, Jejunum                           (45)         (45)         (47)         (47)                                   
      Inflammation                                     1 [2.0]                                                                      
      Lymphoid Tissue, Hyperplasia                     1 [3.0]                                                                      
      Peyer's Patch, Hyperplasia, Lymphoid                          1 [2.0]                                                         
   Liver                                              (50)         (50)         (50)         (49)                                   
      Basophilic Focus                                              1                                                               
      Clear Cell Focus                                20           19           22           16                                     
      Congestion                                                                              1 [3.0]                               
      Cyst                                                          1                         1                                     
      Eosinophilic Focus                                            2            2            2                                     
      Fibrosis, Focal                                  1 [3.0]                                                                      
      Hematopoietic Cell Proliferation                 1 [1.0]      2 [2.5]                                                         
      Hemorrhage                                                    1 [3.0]                                                         
      Hepatodiaphragmatic Nodule                                    1                         1                                     
      Infarct                                          1 [4.0]                                                                      
      Infiltration Cellular, Mixed Cell                3 [1.7]      1 [1.0]      2 [1.0]      6 [1.3]                               
      Mixed Cell Focus                                 3            1                                                               
      Thrombosis                                                    2 [3.0]      1 [3.0]      1 [3.0]                               
      Bile Duct, Hyperplasia                                        1 [1.0]                                                         
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    8                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Hepatocyte, Necrosis, Focal                      2 [2.5]      2 [3.0]      2 [3.0]      4 [2.0]                               
      Hepatocyte, Syncytial Alteration, Focal                                                 1 [1.0]                               
      Hepatocyte, Vacuolization Cytoplasmic           29 [2.3]     19 [2.6]     32 [2.5]     23 [2.2]                               
      Hepatocyte, Centrilobular, Necrosis                                        1 [3.0]                                            
   Mesentery                                          (5)          (11)         (5)          (4)                                    
      Inflammation                                                  1 [3.0]                   1 [2.0]                               
      Fat, Necrosis, Focal                             4 [3.0]      7 [2.3]      4 [2.5]                                            
   Pancreas                                           (48)         (50)         (49)         (48)                                   
      Acinus, Atrophy, Diffuse                         1 [4.0]                                                                      
      Acinus, Atrophy, Focal                           1 [2.0]      1 [1.0]      2 [2.0]      1 [1.0]                               
      Acinus, Cytoplasmic Alteration                   1 [1.0]      1 [2.0]                                                         
      Acinus, Inflammation                                                       1 [2.0]                                            
      Duct, Cyst                                                                 1                                                  
   Stomach, Forestomach                               (50)         (50)         (50)         (48)                                   
      Ulcer                                                         3 [2.0]                   1 [2.0]                               
      Epithelium, Hyperplasia                          3 [2.0]      2 [2.0]      3 [1.7]      2 [2.5]                               
   Stomach, Glandular                                 (47)         (47)         (47)         (48)                                   
      Erosion                                          2 [2.0]      1 [2.0]      2 [2.0]      1 [2.0]                               
      Ulcer                                            1 [3.0]                                                                      
   Tooth                                              (43)         (37)         (33)         (35)                                   
      Dysplasia                                       43 [2.7]     37 [2.5]     33 [2.4]     35 [2.6]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Infiltration Cellular, Mixed Cell                1 [2.0]      1 [2.0]      1 [2.0]                                            
      Mineralization, Focal                                                      1 [3.0]      1 [1.0]                               
      Artery, Inflammation, Chronic                                 1 [2.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (48)         (50)         (50)         (48)                                   
      Accessory Adrenal Cortical Nodule                1 [1.0]                   1 [1.0]                                            
      Cytoplasmic Alteration, Focal                    4 [1.5]                   5 [1.6]      5 [1.8]                               
      Degeneration, Cystic                             1 [2.0]                   1 [2.0]                                            
      Hyperplasia, Focal                                                                      1 [2.0]                               
      Hypertrophy                                      1 [1.0]                                                                      
      Hypertrophy, Focal                                            1 [3.0]                                                         
      Inflammation                                     1 [3.0]                                                                      
   Adrenal Medulla                                    (48)         (50)         (50)         (48)                                   
      Hyperplasia, Focal                               2 [1.5]      1 [1.0]      1 [2.0]      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    9                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
   Islets, Pancreatic                                 (50)         (50)         (49)         (48)                                   
      Hyperplasia                                     17 [2.1]     17 [1.8]      7 [1.6]     13 [2.1]                               
   Parathyroid Gland                                  (46)         (50)         (48)         (46)                                   
      Cyst                                                          3            3            2                                     
   Pituitary Gland                                    (50)         (49)         (49)         (50)                                   
      Cyst                                             3            1            1            3                                     
      Pars Distalis, Hyperplasia, Focal                             1 [2.0]                                                         
   Thyroid Gland                                      (50)         (50)         (49)         (48)                                   
      Follicle, Degeneration, Cystic, Focal            6 [1.5]     12 [1.3]     11 [1.5]      7 [1.3]                               
      Follicular Cell, Hyperplasia, Focal             14 [1.7]      5 [1.6]     11 [1.7]     11 [1.5]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   Tissue NOS                                         (1)          (2)                       (1)                                    
      Foreign Body                                                                            1 [3.0]                               
      Abdominal, Fibrosis                                           2 [3.0]                                                         
      Abdominal, Inflammation                                       1 [3.0]                                                         
      Pelvic, Inflammation                             1 [3.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Preputial Gland                                    (50)         (50)         (50)         (48)                                   
      Degeneration, Cystic                            11 [3.0]     11 [2.9]     16 [2.9]     11 [3.0]                               
      Inflammation, Chronic                            2 [3.0]      1 [3.0]      2 [3.0]      3 [3.0]                               
   Prostate                                           (49)         (50)         (50)         (50)                                   
      Inflammation                                     1 [2.0]      1 [3.0]                   1 [2.0]                               
      Epithelium, Hyperplasia                          1 [3.0]      1 [3.0]      1 [2.0]                                            
   Seminal Vesicle                                    (49)         (50)         (50)         (49)                                   
      Dilatation                                       2 [3.0]      2 [3.0]                                                         
      Epithelium, Hyperplasia                                                    1 [1.0]                                            
   Testes                                             (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 [2.0]                                                                      
      Atrophy                                          1 [2.0]                   1 [3.0]                                            
      Thrombosis                                       1 [2.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      2 [3.0]      3 [3.0]      3 [3.0]      2 [3.0]                               
   Lymph Node                                         (5)          (3)          (3)          (6)                                    
                                                                                                                                    
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: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Iliac, Hyperplasia, Lymphoid                                  1 [2.0]                                                         
      Inguinal, Hyperplasia, Lymphoid                  1 [3.0]                                                                      
      Mediastinal, Hemorrhage                                                    1 [3.0]                                            
      Mediastinal, Hyperplasia, Lymphoid                                                      1 [3.0]                               
   Lymph Node, Mandibular                             (43)         (46)         (48)         (47)                                   
      Hemorrhage                                                                 1 [3.0]                                            
      Hyperplasia, Lymphoid                            2 [3.0]      1 [3.0]                   2 [3.0]                               
   Lymph Node, Mesenteric                             (47)         (50)         (48)         (48)                                   
      Hematopoietic Cell Proliferation                                                        1 [3.0]                               
      Hemorrhage                                                                 3 [3.0]                                            
      Hyperplasia, Lymphoid                            2 [3.5]      2 [3.0]      2 [3.0]                                            
   Spleen                                             (49)         (50)         (49)         (48)                                   
      Atrophy                                                                    1 [3.0]                                            
      Fibrosis, Focal                                                                         1 [2.0]                               
      Hematopoietic Cell Proliferation                14 [2.6]     16 [2.7]     25 [2.8]     29 [2.5]                               
      Hyperplasia, Lymphoid                            7 [2.0]      6 [2.2]      2 [2.0]      3 [2.0]                               
      Hyperplasia, Mast Cell                           1 [2.0]                                                                      
      Lymphoid Follicle, Necrosis                      1 [3.0]                   1 [2.0]                                            
   Thymus                                             (38)         (47)         (40)         (44)                                   
      Angiectasis                                                   1 [3.0]                                                         
      Hyperplasia, Lymphoid                                         1 [3.0]                                                         
      Epithelial Cell, Hyperplasia                                  1 [3.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Skin                                               (50)         (50)         (50)         (50)                                   
      Cyst Epithelial Inclusion                        1                                                                            
      Ulcer                                                                                   2 [3.0]                               
      Pinna, Inflammation, Focal                                                              1 [2.0]                               
      Subcutaneous Tissue, Edema                       1 [2.0]      1 [3.0]      2 [3.0]      1 [3.0]                               
      Subcutaneous Tissue, Inflammation, Focal,                                                                                     
         Suppurative                                                                          1 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Hyperostosis                                                                            2 [1.5]                               
      Vertebra, Fracture                                            1 [3.0]                                                         
   Skeletal Muscle                                                 (4)          (1)          (1)                                    
      Fibrosis, Focal                                               1 [1.0]                                                         
      Inflammation                                                  1 [2.0]                                                         
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page   11                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Compression, Focal                                                         1 [3.0]                                            
   Spinal Cord                                        (4)          (4)          (1)          (2)                                    
      Hemorrhage                                                    2 [3.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion                                       1 [2.0]      1 [3.0]                   1 [3.0]                               
      Hemorrhage                                                                 1 [2.0]      1 [3.0]                               
      Hyperplasia, Histiocytic                         1 [2.0]                   3 [3.0]      2 [1.5]                               
      Inflammation                                     1 [2.0]                                                                      
      Thrombosis                                                                 1 [2.0]                                            
      Alveolar Epithelium, Hyperplasia, Focal          4 [1.5]      3 [1.7]      2 [1.0]      4 [1.3]                               
      Mediastinum, Foreign Body                        1                                                                            
      Mediastinum, Inflammation, Suppurative           1 [3.0]                                                                      
      Mediastinum, Thrombosis                          1 [4.0]                                                                      
   Nose                                               (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                             1 [3.0]                               
      Inflammation                                     1 [2.0]      3 [1.3]      3 [2.3]      6 [1.8]                               
      Nasolacrimal Duct, Hyperplasia, Focal                         1 [3.0]                   1 [2.0]                               
      Nasolacrimal Duct, Inflammation                  3 [2.0]                   1 [2.0]      1 [1.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (45)         (49)         (49)         (47)                                   
      Atrophy                                                                    1 [4.0]                                            
      Cataract                                                                                1 [2.0]                               
      Cornea, Inflammation                             2 [2.0]                                1 [2.0]                               
      Cornea, Necrosis, Focal                          1 [2.0]                                                                      
      Retrobulbar, Inflammation, Chronic, Focal                                               1 [3.0]                               
   Harderian Gland                                    (50)         (50)         (50)         (50)                                   
      Cyst                                                                                    1                                     
      Inflammation                                     1 [3.0]                                1 [1.0]                               
      Epithelium, Hyperplasia                          2 [2.0]                   2 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page   12                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 06/02/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 13:15:53    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         B6C3F1 MICE MALE                             0 MG/KG      2.5          12.5         25                                     
                                                                   MG/KG        MG/KG        MG/KG                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
URINARY SYSTEM - CONT                                                                                                               
   Kidney                                             (49)         (49)         (50)         (48)                                   
      Hydronephrosis                                   2 [3.0]                                                                      
      Hyperplasia, Lymphoid                                                      1 [3.0]                                            
      Infarct                                                       1 [2.0]                   1 [2.0]                               
      Metaplasia, Focal, Osseous                       3 [1.3]                   3 [1.0]      4 [1.3]                               
      Mineralization, Focal                                                      1 [2.0]                                            
      Nephropathy                                     40 [1.5]     44 [1.7]     44 [1.7]     43 [1.5]                               
      Artery, Inflammation, Chronic                                              1 [2.0]                                            
      Renal Tubule, Accumulation, Hyaline Droplet                                1 [2.0]                                            
      Renal Tubule, Cyst                               4            2            3            2                                     
      Renal Tubule, Hyperplasia, Atypical                           1 [2.0]                                                         
      Renal Tubule, Hyperplasia, Focal                 3 [1.3]      2 [2.5]      1 [1.0]      2 [1.5]                               
      Renal Tubule, Pigmentation                                                 1 [2.0]                                            
   Urethra                                            (1)                                                                           
      Inflammation, Chronic                            1 [3.0]                                                                      
   Urinary Bladder                                    (48)         (50)         (50)         (48)                                   
      Transitional Epithelium, Hyperplasia             1 [3.0]                                                                      
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page   13                                                              
                                                                                                                                   
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