https://ntp.niehs.nih.gov/go/21002

TDMS Study 91005-08 Pathology Tables

NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05
Route: GAVAGE                                                                                                     Time: 13:15:21
                                                   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
                                                              Page   1
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         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 (2%)                                                          
      Inflammation                                                  1 (2%)                                                          
      Perforation                                                   1 (2%)                                                          
   Gallbladder                                        (42)         (45)         (47)         (44)                                   
      Cyst                                             2 (5%)                    1 (2%)       2 (5%)                                
   Intestine Large, Rectum                            (48)         (48)         (50)         (46)                                   
      Artery, Inflammation, Chronic, Focal                          1 (2%)                                                          
   Intestine Large, Cecum                             (43)         (46)         (47)         (44)                                   
      Edema                                            1 (2%)                                                                       
      Lymphoid Tissue, Hyperplasia, Lymphoid                                     1 (2%)                                             
   Intestine Small, Duodenum                          (43)         (45)         (47)         (42)                                   
      Epithelium, Hyperplasia, Focal                                             1 (2%)                                             
   Intestine Small, Jejunum                           (43)         (45)         (47)         (43)                                   
      Epithelium, Hyperplasia, Focal                                1 (2%)                                                          
      Lymphoid Tissue, Hyperplasia                                               1 (2%)                                             
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis, Focal                               2 (4%)                                                                       
      Basophilic Focus                                              1 (2%)                    3 (6%)                                
      Clear Cell Focus                                 3 (6%)       3 (6%)       4 (8%)       2 (4%)                                
      Congestion                                       1 (2%)       2 (4%)       1 (2%)       1 (2%)                                
      Eosinophilic Focus                               1 (2%)       1 (2%)       3 (6%)       1 (2%)                                
      Fibrosis, Focal                                  1 (2%)                                                                       
      Hematopoietic Cell Proliferation                 4 (8%)       1 (2%)       6 (12%)      2 (4%)                                
      Hemorrhage                                       1 (2%)                                 1 (2%)                                
      Hepatodiaphragmatic Nodule                       1 (2%)                                                                       
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    2                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        0 MG/KG      2.5          12.5         25                                        
                                                                MG/KG        MG/KG        MG/KG                                     
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT                                                                                                            
      Infarct                                                                    1 (2%)                                             
      Infiltration Cellular, Mixed Cell               11 (22%)     12 (24%)     12 (24%)     15 (30%)                               
      Mixed Cell Focus                                 2 (4%)       1 (2%)                    1 (2%)                                
      Bile Duct, Cyst                                  1 (2%)                                                                       
      Hepatocyte, Necrosis, Focal                      3 (6%)       3 (6%)       1 (2%)                                             
      Hepatocyte, Vacuolization Cytoplasmic           12 (24%)     11 (22%)      8 (16%)     15 (30%)                               
      Kupffer Cell, Pigmentation                       1 (2%)                    1 (2%)                                             
   Mesentery                                          (18)         (14)         (15)         (13)                                   
      Hemorrhage                                                                 1 (7%)       1 (8%)                                
      Infiltration Cellular, Lymphoid                               1 (7%)                                                          
      Artery, Inflammation, Chronic, Focal             1 (6%)       1 (7%)       1 (7%)                                             
      Fat, Necrosis, Focal                            16 (89%)     12 (86%)     13 (87%)      4 (31%)                               
   Pancreas                                           (46)         (46)         (49)         (49)                                   
      Acinus, Atrophy, Diffuse                                                                1 (2%)                                
      Acinus, Atrophy, Focal                           1 (2%)       1 (2%)                    1 (2%)                                
      Acinus, Cytoplasmic Alteration                                             1 (2%)                                             
      Duct, Cyst                                       2 (4%)                    2 (4%)       2 (4%)                                
   Salivary Glands                                    (50)         (50)         (50)         (49)                                   
      Hyperplasia, Lymphoid                                         1 (2%)                                                          
   Stomach, Forestomach                               (50)         (50)         (50)         (49)                                   
      Diverticulum                                     1 (2%)                    1 (2%)       3 (6%)                                
      Inflammation, Focal                              1 (2%)                    1 (2%)                                             
      Ulcer                                            2 (4%)                    3 (6%)       1 (2%)                                
      Epithelium, Hyperplasia                          2 (4%)       2 (4%)       2 (4%)       1 (2%)                                
   Stomach, Glandular                                 (45)         (47)         (50)         (46)                                   
      Cyst                                             1 (2%)                                 1 (2%)                                
      Epithelium, Cytoplasmic Alteration, Focal        1 (2%)                                                                       
      Epithelium, Hyperplasia                          1 (2%)                                                                       
   Tooth                                              (2)          (10)         (3)          (3)                                    
      Dysplasia                                        2 (100%)    10 (100%)     3 (100%)     3 (100%)                              
____________________________________________________________________________________________________________________________________
 CARDIOVASCULAR SYSTEM                                                                                                              
   Blood Vessel                                                    (1)                                                              
      Aneurysm                                                      1 (100%)                                                        
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                   1 (2%)                                 1 (2%)                                
      Infiltration Cellular, Mixed Cell                                          1 (2%)                                             
      Mineralization, Focal                                                                   1 (2%)                                
      Thrombosis                                       1 (2%)                                                                       
      Artery, Inflammation, Chronic                                              1 (2%)                                             
____________________________________________________________________________________________________________________________________
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    3                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         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 (4%)       2 (4%)                                                          
      Angiectasis                                                                1 (2%)                                             
      Cytoplasmic Alteration, Focal                    1 (2%)                                                                       
      Degeneration, Cystic                             1 (2%)                                                                       
      Hyperplasia, Focal                                                         1 (2%)                                             
      Infiltration Cellular, Mixed Cell                1 (2%)                                                                       
   Adrenal Medulla                                    (50)         (50)         (49)         (50)                                   
      Hyperplasia, Focal                                                         1 (2%)                                             
   Parathyroid Gland                                  (48)         (48)         (46)         (49)                                   
      Cyst                                             1 (2%)       1 (2%)       1 (2%)       1 (2%)                                
   Pituitary Gland                                    (46)         (49)         (48)         (47)                                   
      Angiectasis                                      2 (4%)       1 (2%)                                                          
      Cyst                                                                       1 (2%)       1 (2%)                                
      Pars Distalis, Cytoplasmic Alteration, Focal     1 (2%)       4 (8%)       1 (2%)       2 (4%)                                
      Pars Distalis, Hyperplasia, Focal                1 (2%)       1 (2%)       1 (2%)       1 (2%)                                
   Thyroid Gland                                      (46)         (50)         (49)         (47)                                   
      Cyst                                             1 (2%)                    1 (2%)                                             
      Inflammation, Chronic, Focal                     1 (2%)       1 (2%)       1 (2%)                                             
      C-Cell, Hyperplasia                                           1 (2%)                    1 (2%)                                
      Follicle, Degeneration, Cystic, Focal           17 (37%)     15 (30%)     28 (57%)     23 (49%)                               
      Follicular Cell, Hyperplasia, Focal              5 (11%)      2 (4%)       4 (8%)       5 (11%)                               
____________________________________________________________________________________________________________________________________
 GENERAL BODY SYSTEM                                                                                                                
   Tissue NOS                                         (3)                                    (3)                                    
      Pelvic, Fibrosis                                 1 (33%)                                                                      
____________________________________________________________________________________________________________________________________
 GENITAL SYSTEM                                                                                                                     
   Clitoral Gland                                     (48)         (50)         (46)         (48)                                   
      Degeneration, Cystic                                          1 (2%)       1 (2%)                                             
   Ovary                                              (47)         (48)         (49)         (48)                                   
      Angiectasis                                      3 (6%)       2 (4%)                    2 (4%)                                
      Cyst                                            11 (23%)     12 (25%)     16 (33%)     13 (27%)                               
      Hemorrhage                                                                 1 (2%)       1 (2%)                                
      Pigmentation, Focal                                                                     1 (2%)                                
      Thrombosis                                       3 (6%)                                 3 (6%)                                
      Bilateral, Cyst                                  1 (2%)                                                                       
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    4                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        0 MG/KG      2.5          12.5         25                                        
                                                                MG/KG        MG/KG        MG/KG                                     
____________________________________________________________________________________________________________________________________
GENITAL SYSTEM - CONT                                                                                                               
      Interstitial Cell, Hyperplasia                                1 (2%)                                                          
   Uterus                                             (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 (2%)       1 (2%)       1 (2%)                                             
      Hemorrhage                                                    1 (2%)                                                          
      Inflammation, Chronic                                         1 (2%)                                                          
      Inflammation, Suppurative                        1 (2%)                                                                       
      Endometrium, Hyperplasia, Cystic                48 (96%)     45 (90%)     49 (98%)     48 (96%)                               
____________________________________________________________________________________________________________________________________
 HEMATOPOIETIC SYSTEM                                                                                                               
   Bone Marrow                                        (50)         (50)         (49)         (50)                                   
      Hyperplasia                                     10 (20%)      4 (8%)       9 (18%)      4 (8%)                                
   Lymph Node                                         (7)          (5)          (10)         (10)                                   
      Iliac, Angiectasis                               1 (14%)                                                                      
      Iliac, Hyperplasia, Lymphoid                     1 (14%)                   2 (20%)      2 (20%)                               
      Mediastinal, Hyperplasia, Lymphoid               2 (29%)                                1 (10%)                               
      Mediastinal, Inflammation                                                               1 (10%)                               
      Pancreatic, Hyperplasia, Lymphoid                             1 (20%)      1 (10%)      1 (10%)                               
      Renal, Hyperplasia, Lymphoid                     1 (14%)                   1 (10%)      1 (10%)                               
   Lymph Node, Mandibular                             (48)         (49)         (48)         (46)                                   
      Hemorrhage                                       1 (2%)                                                                       
      Hyperplasia, Lymphoid                            9 (19%)     11 (22%)     12 (25%)     16 (35%)                               
      Hyperplasia, Mast Cell                                                     1 (2%)                                             
   Lymph Node, Mesenteric                             (46)         (49)         (49)         (48)                                   
      Ectasia                                                       1 (2%)       2 (4%)                                             
      Hemorrhage                                       1 (2%)       2 (4%)       2 (4%)       1 (2%)                                
      Hyperplasia, Histiocytic                                                   1 (2%)                                             
      Hyperplasia, Lymphoid                            6 (13%)      7 (14%)     10 (20%)      8 (17%)                               
   Spleen                                             (47)         (47)         (49)         (50)                                   
      Angiectasis, Focal                                            1 (2%)                                                          
      Congestion                                                    2 (4%)                                                          
      Fibrosis, Focal                                               1 (2%)       1 (2%)                                             
      Hematopoietic Cell Proliferation                23 (49%)     21 (45%)     31 (63%)     40 (80%)                               
      Hyperplasia, Lymphoid                           17 (36%)     15 (32%)     17 (35%)     11 (22%)                               
   Thymus                                             (43)         (47)         (44)         (49)                                   
      Hyperplasia, Lymphoid                            8 (19%)     13 (28%)     11 (25%)     14 (29%)                               
      Inflammation                                                  1 (2%)                                                          
____________________________________________________________________________________________________________________________________
 INTEGUMENTARY SYSTEM                                                                                                               
   Skin                                               (50)         (50)         (50)         (50)                                   
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    5                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE FEMALE                        0 MG/KG      2.5          12.5         25                                        
                                                                MG/KG        MG/KG        MG/KG                                     
____________________________________________________________________________________________________________________________________
INTEGUMENTARY SYSTEM - CONT                                                                                                         
      Subcutaneous Tissue, Edema                                                              1 (2%)                                
____________________________________________________________________________________________________________________________________
 MUSCULOSKELETAL SYSTEM                                                                                                             
   Bone                                               (50)         (50)         (50)         (50)                                   
      Hyperostosis                                     5 (10%)      5 (10%)      4 (8%)       5 (10%)                               
      Vertebra, Hypertrophy, Focal                     3 (6%)       2 (4%)       1 (2%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
 NERVOUS SYSTEM                                                                                                                     
   Brain                                              (50)         (50)         (50)         (49)                                   
      Compression, Focal                               1 (2%)                                 1 (2%)                                
      Artery, Meninges, Inflammation, Chronic          1 (2%)                                                                       
   Spinal Cord                                        (1)          (2)          (1)          (1)                                    
      Demyelination, Focal                                          1 (50%)                                                         
____________________________________________________________________________________________________________________________________
 RESPIRATORY SYSTEM                                                                                                                 
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion                                       1 (2%)                                                                       
      Foreign Body                                     1 (2%)                    1 (2%)                                             
      Hemorrhage                                       1 (2%)       1 (2%)                                                          
      Hyperplasia, Histiocytic                         1 (2%)                                 1 (2%)                                
      Hyperplasia, Lymphoid                                                                   1 (2%)                                
      Infiltration Cellular, Polymorphonuclear         1 (2%)                                                                       
      Infiltration Cellular, Mixed Cell                1 (2%)                                                                       
      Inflammation                                     1 (2%)                    1 (2%)                                             
      Metaplasia, Focal, Osseous                       1 (2%)                                                                       
      Alveolar Epithelium, Hyperplasia, Focal          2 (4%)                    1 (2%)       1 (2%)                                
      Mediastinum, Foreign Body                                     1 (2%)       1 (2%)                                             
      Mediastinum, Inflammation                                     1 (2%)       1 (2%)                                             
      Serosa, Fibrosis                                                           1 (2%)                                             
   Nose                                               (50)         (50)         (50)         (50)                                   
      Inflammation                                                  3 (6%)       7 (14%)     11 (22%)                               
      Nasolacrimal Duct, Hyperplasia, Focal                                                   1 (2%)                                
      Nasolacrimal Duct, Inflammation                               1 (2%)                                                          
____________________________________________________________________________________________________________________________________
 SPECIAL SENSES SYSTEM                                                                                                              
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    6                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         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 (2%)                                
      Cataract                                                                                1 (2%)                                
      Anterior Chamber, Inflammation                   1 (2%)                                                                       
      Artery, Retrobulbar, Inflammation, Chronic,                                                                                   
         Focal                                                      1 (2%)                                                          
      Cornea, Inflammation                             1 (2%)       1 (2%)       1 (2%)       1 (2%)                                
      Cornea, Necrosis, Focal                                       1 (2%)                                                          
   Harderian Gland                                    (49)         (50)         (50)         (50)                                   
      Epithelium, Hyperplasia                          2 (4%)       1 (2%)                    3 (6%)                                
____________________________________________________________________________________________________________________________________
 URINARY SYSTEM                                                                                                                     
   Kidney                                             (48)         (50)         (49)         (50)                                   
      Hemorrhage                                                                              1 (2%)                                
      Hyperplasia, Lymphoid                            1 (2%)                                                                       
      Infarct                                                       1 (2%)       2 (4%)       2 (4%)                                
      Metaplasia, Focal, Osseous                       2 (4%)       1 (2%)       1 (2%)                                             
      Nephropathy                                      6 (13%)      5 (10%)      9 (18%)      5 (10%)                               
      Bilateral, Infarct                                                                      1 (2%)                                
      Capsule, Fibrosis, Focal                                      1 (2%)                                                          
      Renal Tubule, Accumulation, Hyaline Droplet      2 (4%)                                 2 (4%)                                
      Renal Tubule, Cyst                               1 (2%)                    3 (6%)                                             
   Urinary Bladder                                    (45)         (47)         (49)         (48)                                   
      Hyperplasia, Lymphoid                                         1 (2%)                                                          
      Inflammation                                     1 (2%)                                                                       
      Transitional Epithelium, Hyperplasia             1 (2%)                                 1 (2%)                                
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    7                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         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%)                    1 (2%)                                
      Inflammation                                     1 (2%)       1 (2%)                    1 (2%)                                
      Perforation                                                   1 (2%)                    1 (2%)                                
   Intestine Large, Cecum                             (45)         (46)         (46)         (47)                                   
      Edema                                                         1 (2%)       1 (2%)                                             
      Inflammation, Chronic, Focal                                                            1 (2%)                                
   Intestine Small, Duodenum                          (42)         (46)         (46)         (46)                                   
      Epithelium, Cyst                                              1 (2%)                                                          
   Intestine Small, Jejunum                           (45)         (45)         (47)         (47)                                   
      Inflammation                                     1 (2%)                                                                       
      Lymphoid Tissue, Hyperplasia                     1 (2%)                                                                       
      Peyer's Patch, Hyperplasia, Lymphoid                          1 (2%)                                                          
   Liver                                              (50)         (50)         (50)         (49)                                   
      Basophilic Focus                                              1 (2%)                                                          
      Clear Cell Focus                                20 (40%)     19 (38%)     22 (44%)     16 (33%)                               
      Congestion                                                                              1 (2%)                                
      Cyst                                                          1 (2%)                    1 (2%)                                
      Eosinophilic Focus                                            2 (4%)       2 (4%)       2 (4%)                                
      Fibrosis, Focal                                  1 (2%)                                                                       
      Hematopoietic Cell Proliferation                 1 (2%)       2 (4%)                                                          
      Hemorrhage                                                    1 (2%)                                                          
      Hepatodiaphragmatic Nodule                                    1 (2%)                    1 (2%)                                
      Infarct                                          1 (2%)                                                                       
      Infiltration Cellular, Mixed Cell                3 (6%)       1 (2%)       2 (4%)       6 (12%)                               
      Mixed Cell Focus                                 3 (6%)       1 (2%)                                                          
      Thrombosis                                                    2 (4%)       1 (2%)       1 (2%)                                
      Bile Duct, Hyperplasia                                        1 (2%)                                                          
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    8                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE MALE                          0 MG/KG      2.5          12.5         25                                        
                                                                MG/KG        MG/KG        MG/KG                                     
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT                                                                                                            
      Hepatocyte, Necrosis, Focal                      2 (4%)       2 (4%)       2 (4%)       4 (8%)                                
      Hepatocyte, Syncytial Alteration, Focal                                                 1 (2%)                                
      Hepatocyte, Vacuolization Cytoplasmic           29 (58%)     19 (38%)     32 (64%)     23 (47%)                               
      Hepatocyte, Centrilobular, Necrosis                                        1 (2%)                                             
   Mesentery                                          (5)          (11)         (5)          (4)                                    
      Inflammation                                                  1 (9%)                    1 (25%)                               
      Fat, Necrosis, Focal                             4 (80%)      7 (64%)      4 (80%)                                            
   Pancreas                                           (48)         (50)         (49)         (48)                                   
      Acinus, Atrophy, Diffuse                         1 (2%)                                                                       
      Acinus, Atrophy, Focal                           1 (2%)       1 (2%)       2 (4%)       1 (2%)                                
      Acinus, Cytoplasmic Alteration                   1 (2%)       1 (2%)                                                          
      Acinus, Inflammation                                                       1 (2%)                                             
      Duct, Cyst                                                                 1 (2%)                                             
   Stomach, Forestomach                               (50)         (50)         (50)         (48)                                   
      Ulcer                                                         3 (6%)                    1 (2%)                                
      Epithelium, Hyperplasia                          3 (6%)       2 (4%)       3 (6%)       2 (4%)                                
   Stomach, Glandular                                 (47)         (47)         (47)         (48)                                   
      Erosion                                          2 (4%)       1 (2%)       2 (4%)       1 (2%)                                
      Ulcer                                            1 (2%)                                                                       
   Tooth                                              (43)         (37)         (33)         (35)                                   
      Dysplasia                                       43 (100%)    37 (100%)    33 (100%)    35 (100%)                              
____________________________________________________________________________________________________________________________________
 CARDIOVASCULAR SYSTEM                                                                                                              
   Heart                                              (50)         (50)         (50)         (50)                                   
      Infiltration Cellular, Mixed Cell                1 (2%)       1 (2%)       1 (2%)                                             
      Mineralization, Focal                                                      1 (2%)       1 (2%)                                
      Artery, Inflammation, Chronic                                 1 (2%)                                                          
____________________________________________________________________________________________________________________________________
 ENDOCRINE SYSTEM                                                                                                                   
   Adrenal Cortex                                     (48)         (50)         (50)         (48)                                   
      Accessory Adrenal Cortical Nodule                1 (2%)                    1 (2%)                                             
      Cytoplasmic Alteration, Focal                    4 (8%)                    5 (10%)      5 (10%)                               
      Degeneration, Cystic                             1 (2%)                    1 (2%)                                             
      Hyperplasia, Focal                                                                      1 (2%)                                
      Hypertrophy                                      1 (2%)                                                                       
      Hypertrophy, Focal                                            1 (2%)                                                          
      Inflammation                                     1 (2%)                                                                       
   Adrenal Medulla                                    (48)         (50)         (50)         (48)                                   
      Hyperplasia, Focal                               2 (4%)       1 (2%)       1 (2%)       1 (2%)                                
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    9                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         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 (34%)     17 (34%)      7 (14%)     13 (27%)                               
   Parathyroid Gland                                  (46)         (50)         (48)         (46)                                   
      Cyst                                                          3 (6%)       3 (6%)       2 (4%)                                
   Pituitary Gland                                    (50)         (49)         (49)         (50)                                   
      Cyst                                             3 (6%)       1 (2%)       1 (2%)       3 (6%)                                
      Pars Distalis, Hyperplasia, Focal                             1 (2%)                                                          
   Thyroid Gland                                      (50)         (50)         (49)         (48)                                   
      Follicle, Degeneration, Cystic, Focal            6 (12%)     12 (24%)     11 (22%)      7 (15%)                               
      Follicular Cell, Hyperplasia, Focal             14 (28%)      5 (10%)     11 (22%)     11 (23%)                               
____________________________________________________________________________________________________________________________________
 GENERAL BODY SYSTEM                                                                                                                
   Tissue NOS                                         (1)          (2)                       (1)                                    
      Foreign Body                                                                            1 (100%)                              
      Abdominal, Fibrosis                                           2 (100%)                                                        
      Abdominal, Inflammation                                       1 (50%)                                                         
      Pelvic, Inflammation                             1 (100%)                                                                     
____________________________________________________________________________________________________________________________________
 GENITAL SYSTEM                                                                                                                     
   Preputial Gland                                    (50)         (50)         (50)         (48)                                   
      Degeneration, Cystic                            11 (22%)     11 (22%)     16 (32%)     11 (23%)                               
      Inflammation, Chronic                            2 (4%)       1 (2%)       2 (4%)       3 (6%)                                
   Prostate                                           (49)         (50)         (50)         (50)                                   
      Inflammation                                     1 (2%)       1 (2%)                    1 (2%)                                
      Epithelium, Hyperplasia                          1 (2%)       1 (2%)       1 (2%)                                             
   Seminal Vesicle                                    (49)         (50)         (50)         (49)                                   
      Dilatation                                       2 (4%)       2 (4%)                                                          
      Epithelium, Hyperplasia                                                    1 (2%)                                             
   Testes                                             (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 (2%)                                                                       
      Atrophy                                          1 (2%)                    1 (2%)                                             
      Thrombosis                                       1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
 HEMATOPOIETIC SYSTEM                                                                                                               
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      2 (4%)       3 (6%)       3 (6%)       2 (4%)                                
   Lymph Node                                         (5)          (3)          (3)          (6)                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   10                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         B6C3F1 MICE MALE                          0 MG/KG      2.5          12.5         25                                        
                                                                MG/KG        MG/KG        MG/KG                                     
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Iliac, Hyperplasia, Lymphoid                                  1 (33%)                                                         
      Inguinal, Hyperplasia, Lymphoid                  1 (20%)                                                                      
      Mediastinal, Hemorrhage                                                    1 (33%)                                            
      Mediastinal, Hyperplasia, Lymphoid                                                      1 (17%)                               
   Lymph Node, Mandibular                             (43)         (46)         (48)         (47)                                   
      Hemorrhage                                                                 1 (2%)                                             
      Hyperplasia, Lymphoid                            2 (5%)       1 (2%)                    2 (4%)                                
   Lymph Node, Mesenteric                             (47)         (50)         (48)         (48)                                   
      Hematopoietic Cell Proliferation                                                        1 (2%)                                
      Hemorrhage                                                                 3 (6%)                                             
      Hyperplasia, Lymphoid                            2 (4%)       2 (4%)       2 (4%)                                             
   Spleen                                             (49)         (50)         (49)         (48)                                   
      Atrophy                                                                    1 (2%)                                             
      Fibrosis, Focal                                                                         1 (2%)                                
      Hematopoietic Cell Proliferation                14 (29%)     16 (32%)     25 (51%)     29 (60%)                               
      Hyperplasia, Lymphoid                            7 (14%)      6 (12%)      2 (4%)       3 (6%)                                
      Hyperplasia, Mast Cell                           1 (2%)                                                                       
      Lymphoid Follicle, Necrosis                      1 (2%)                    1 (2%)                                             
   Thymus                                             (38)         (47)         (40)         (44)                                   
      Angiectasis                                                   1 (2%)                                                          
      Hyperplasia, Lymphoid                                         1 (2%)                                                          
      Epithelial Cell, Hyperplasia                                  1 (2%)                                                          
____________________________________________________________________________________________________________________________________
 INTEGUMENTARY SYSTEM                                                                                                               
   Skin                                               (50)         (50)         (50)         (50)                                   
      Cyst Epithelial Inclusion                        1 (2%)                                                                       
      Ulcer                                                                                   2 (4%)                                
      Pinna, Inflammation, Focal                                                              1 (2%)                                
      Subcutaneous Tissue, Edema                       1 (2%)       1 (2%)       2 (4%)       1 (2%)                                
      Subcutaneous Tissue, Inflammation, Focal,                                                                                     
         Suppurative                                                                          1 (2%)                                
____________________________________________________________________________________________________________________________________
 MUSCULOSKELETAL SYSTEM                                                                                                             
   Bone                                               (50)         (50)         (50)         (50)                                   
      Hyperostosis                                                                            2 (4%)                                
      Vertebra, Fracture                                            1 (2%)                                                          
   Skeletal Muscle                                                 (4)          (1)          (1)                                    
      Fibrosis, Focal                                               1 (25%)                                                         
      Inflammation                                                  1 (25%)                                                         
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   11                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         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 (2%)                                             
   Spinal Cord                                        (4)          (4)          (1)          (2)                                    
      Hemorrhage                                                    2 (50%)                                                         
____________________________________________________________________________________________________________________________________
 RESPIRATORY SYSTEM                                                                                                                 
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion                                       1 (2%)       1 (2%)                    1 (2%)                                
      Hemorrhage                                                                 1 (2%)       1 (2%)                                
      Hyperplasia, Histiocytic                         1 (2%)                    3 (6%)       2 (4%)                                
      Inflammation                                     1 (2%)                                                                       
      Thrombosis                                                                 1 (2%)                                             
      Alveolar Epithelium, Hyperplasia, Focal          4 (8%)       3 (6%)       2 (4%)       4 (8%)                                
      Mediastinum, Foreign Body                        1 (2%)                                                                       
      Mediastinum, Inflammation, Suppurative           1 (2%)                                                                       
      Mediastinum, Thrombosis                          1 (2%)                                                                       
   Nose                                               (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                             1 (2%)                                
      Inflammation                                     1 (2%)       3 (6%)       3 (6%)       6 (12%)                               
      Nasolacrimal Duct, Hyperplasia, Focal                         1 (2%)                    1 (2%)                                
      Nasolacrimal Duct, Inflammation                  3 (6%)                    1 (2%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
 SPECIAL SENSES SYSTEM                                                                                                              
   Eye                                                (45)         (49)         (49)         (47)                                   
      Atrophy                                                                    1 (2%)                                             
      Cataract                                                                                1 (2%)                                
      Cornea, Inflammation                             2 (4%)                                 1 (2%)                                
      Cornea, Necrosis, Focal                          1 (2%)                                                                       
      Retrobulbar, Inflammation, Chronic, Focal                                               1 (2%)                                
   Harderian Gland                                    (50)         (50)         (50)         (50)                                   
      Cyst                                                                                    1 (2%)                                
      Inflammation                                     1 (2%)                                 1 (2%)                                
      Epithelium, Hyperplasia                          2 (4%)                    2 (4%)                                             
____________________________________________________________________________________________________________________________________
 URINARY SYSTEM                                                                                                                     
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   12                                                              
NTP Experiment-Test: 91005-08         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 06/02/05    
Route: GAVAGE                                                                                                     Time: 13:15:21    
____________________________________________________________________________________________________________________________________
         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 (4%)                                                                       
      Hyperplasia, Lymphoid                                                      1 (2%)                                             
      Infarct                                                       1 (2%)                    1 (2%)                                
      Metaplasia, Focal, Osseous                       3 (6%)                    3 (6%)       4 (8%)                                
      Mineralization, Focal                                                      1 (2%)                                             
      Nephropathy                                     40 (82%)     44 (90%)     44 (88%)     43 (90%)                               
      Artery, Inflammation, Chronic                                              1 (2%)                                             
      Renal Tubule, Accumulation, Hyaline Droplet                                1 (2%)                                             
      Renal Tubule, Cyst                               4 (8%)       2 (4%)       3 (6%)       2 (4%)                                
      Renal Tubule, Hyperplasia, Atypical                           1 (2%)                                                          
      Renal Tubule, Hyperplasia, Focal                 3 (6%)       2 (4%)       1 (2%)       2 (4%)                                
      Renal Tubule, Pigmentation                                                 1 (2%)                                             
   Urethra                                            (1)                                                                           
      Inflammation, Chronic                            1 (100%)                                                                     
   Urinary Bladder                                    (48)         (50)         (50)         (48)                                   
      Transitional Epithelium, Hyperplasia             1 (2%)                                                                       
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   13                                                              
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