https://ntp.niehs.nih.gov/go/20969

TDMS Study 91005-07 Pathology Tables

NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05
Route: GAVAGE                                                                                                     Time: 10:00:58
                                                         FINAL #1 RATS
       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: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                   0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY                                                                                                                 
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Natural Death                                      6            4            9           11                                     
    Moribund Sacrifice                                 9           13            5            3                                     
    Dosing Accident                                                                           1                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                35           32           34           35                                     
    Natural Death                                                                2                                                  
  Other                                                             1                                                               
  Animals Examined Microscopically                    50           49           50           50                                     
____________________________________________________________________________________________________________________________________
 ALIMENTARY SYSTEM                                                                                                                  
   Esophagus                                          (50)         (49)         (50)         (50)                                   
      Perforation                                                                1 (2%)                                             
   Intestine Large, Colon                             (50)         (48)         (49)         (48)                                   
      Cyst                                                                                    1 (2%)                                
   Intestine Small, Duodenum                          (49)         (48)         (49)         (48)                                   
      Ectopic Tissue                                                                          1 (2%)                                
   Liver                                              (50)         (49)         (50)         (50)                                   
      Basophilic Focus                                37 (74%)     34 (69%)     38 (76%)     40 (80%)                               
      Clear Cell Focus                                 8 (16%)      5 (10%)      9 (18%)      8 (16%)                               
      Degeneration, Cystic                             1 (2%)       1 (2%)                    1 (2%)                                
      Eosinophilic Focus                               3 (6%)       2 (4%)                                                          
      Hepatodiaphragmatic Nodule                       7 (14%)      4 (8%)       7 (14%)      4 (8%)                                
      Inflammation, Chronic                            6 (12%)      4 (8%)       4 (8%)       5 (10%)                               
      Necrosis, Focal                                  1 (2%)                    1 (2%)                                             
      Bile Duct, Hyperplasia                           7 (14%)      5 (10%)      6 (12%)      2 (4%)                                
      Centrilobular, Necrosis                          2 (4%)                    1 (2%)                                             
      Hepatocyte, Vacuolization Cytoplasmic            4 (8%)       4 (8%)                                                          
   Mesentery                                          (17)         (14)         (12)         (8)                                    
      Accessory Spleen                                              1 (7%)                                                          
      Fat, Necrosis                                   17 (100%)    14 (100%)    11 (92%)      8 (100%)                              
   Oral Mucosa                                        (2)                                    (1)                                    
      Pharyngeal, Cyst                                 1 (50%)                                1 (100%)                              
   Pancreas                                           (49)         (48)         (48)         (49)                                   
      Atrophy                                         26 (53%)     20 (42%)     23 (48%)     23 (47%)                               
      Inflammation                                                  1 (2%)                                                          
      Acinus, Hyperplasia, Focal                       3 (6%)       1 (2%)       2 (4%)       1 (2%)                                
   Salivary Glands                                    (50)         (49)         (50)         (50)                                   
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    2                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                   0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT                                                                                                            
      Inflammation                                                               1 (2%)                                             
   Stomach, Forestomach                               (50)         (49)         (49)         (49)                                   
      Edema                                            2 (4%)       3 (6%)       1 (2%)                                             
      Erosion                                                                                 1 (2%)                                
      Inflammation, Chronic Active                     1 (2%)                                 2 (4%)                                
      Ulcer                                            4 (8%)       3 (6%)       1 (2%)       1 (2%)                                
      Epithelium, Hyperplasia                          2 (4%)       2 (4%)       2 (4%)       3 (6%)                                
   Stomach, Glandular                                 (50)         (49)         (48)         (49)                                   
      Edema                                            2 (4%)       1 (2%)       1 (2%)                                             
      Erosion                                          2 (4%)       2 (4%)                                                          
      Ulcer                                            2 (4%)       1 (2%)       1 (2%)                                             
   Tongue                                             (1)          (1)          (1)          (1)                                    
      Cyst                                                          1 (100%)                                                        
      Hyperplasia                                      1 (100%)                               1 (100%)                              
      Inflammation                                                  1 (100%)                                                        
____________________________________________________________________________________________________________________________________
 CARDIOVASCULAR SYSTEM                                                                                                              
   Heart                                              (50)         (49)         (50)         (50)                                   
      Cardiomyopathy                                  36 (72%)     41 (84%)     36 (72%)     32 (64%)                               
      Thrombosis                                                    1 (2%)                                                          
____________________________________________________________________________________________________________________________________
 ENDOCRINE SYSTEM                                                                                                                   
   Adrenal Cortex                                     (50)         (49)         (50)         (50)                                   
      Accessory Adrenal Cortical Nodule                9 (18%)      7 (14%)      8 (16%)     12 (24%)                               
      Degeneration, Fatty                             11 (22%)     13 (27%)     13 (26%)      8 (16%)                               
      Hyperplasia, Focal                               5 (10%)      8 (16%)      8 (16%)      6 (12%)                               
      Hypertrophy, Focal                              12 (24%)     11 (22%)     13 (26%)      7 (14%)                               
      Necrosis                                         2 (4%)       1 (2%)                                                          
   Adrenal Medulla                                    (50)         (49)         (50)         (50)                                   
      Hyperplasia                                      1 (2%)       2 (4%)       1 (2%)                                             
   Islets, Pancreatic                                 (49)         (48)         (48)         (49)                                   
      Hyperplasia                                     13 (27%)     15 (31%)     15 (31%)     15 (31%)                               
      Metaplasia, Hepatocyte                           2 (4%)                                                                       
   Pituitary Gland                                    (50)         (49)         (50)         (50)                                   
      Pars Distalis, Angiectasis                      28 (56%)     27 (55%)     29 (58%)     21 (42%)                               
      Pars Distalis, Cyst                             21 (42%)     19 (39%)     16 (32%)     23 (46%)                               
      Pars Distalis, Hyperplasia, Focal                5 (10%)      8 (16%)      6 (12%)      6 (12%)                               
      Pars Intermedia, Cyst                            1 (2%)                                                                       
   Thyroid Gland                                      (50)         (49)         (50)         (50)                                   
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    3                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                   0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT                                                                                                             
      Ultimobranchial Cyst                             2 (4%)                    1 (2%)                                             
      C-Cell, Hyperplasia                             10 (20%)     11 (22%)      7 (14%)      5 (10%)                               
      Follicle, Cyst                                   2 (4%)       1 (2%)       2 (4%)       4 (8%)                                
____________________________________________________________________________________________________________________________________
 GENERAL BODY SYSTEM                                                                                                                
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
 GENITAL SYSTEM                                                                                                                     
   Clitoral Gland                                     (50)         (48)         (50)         (50)                                   
      Cyst                                             4 (8%)       7 (15%)      4 (8%)       6 (12%)                               
      Inflammation, Chronic                            1 (2%)       5 (10%)      2 (4%)       4 (8%)                                
   Ovary                                              (50)         (49)         (50)         (50)                                   
      Cyst                                            11 (22%)      4 (8%)       9 (18%)     10 (20%)                               
   Uterus                                             (50)         (49)         (50)         (50)                                   
      Cyst                                             1 (2%)       3 (6%)       2 (4%)       3 (6%)                                
      Hemorrhage                                       1 (2%)                                 1 (2%)                                
      Hydrometra                                       1 (2%)       4 (8%)       2 (4%)       1 (2%)                                
      Cervix, Cyst                                     1 (2%)                                                                       
      Endometrium, Hyperplasia, Cystic                 4 (8%)       1 (2%)                    2 (4%)                                
   Vagina                                                                       (1)                                                 
      Cyst                                                                       1 (100%)                                           
____________________________________________________________________________________________________________________________________
 HEMATOPOIETIC SYSTEM                                                                                                               
   Bone Marrow                                        (50)         (49)         (50)         (50)                                   
      Hyperplasia                                      8 (16%)      8 (16%)      9 (18%)      6 (12%)                               
   Lymph Node                                         (15)         (8)          (11)         (3)                                    
      Mediastinal, Congestion                          1 (7%)                                                                       
      Mediastinal, Hyperplasia, Lymphoid               5 (33%)      7 (88%)      8 (73%)      2 (67%)                               
      Pancreatic, Hyperplasia, Lymphoid                1 (7%)                    1 (9%)       1 (33%)                               
   Lymph Node, Mesenteric                             (49)         (49)         (50)         (50)                                   
      Hyperplasia, Lymphoid                                         1 (2%)       1 (2%)                                             
   Spleen                                             (49)         (48)         (49)         (49)                                   
      Fibrosis                                         2 (4%)                                                                       
      Hematopoietic Cell Proliferation                 3 (6%)       5 (10%)      7 (14%)      8 (16%)                               
      Necrosis                                         1 (2%)                                                                       
      Capsule, Fibrosis                                8 (16%)     17 (35%)     12 (24%)     20 (41%)                               
      Lymphoid Follicle, Atrophy                                                 1 (2%)                                             
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    4                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                   0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Lymphoid Follicle, Hyperplasia                   1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
 INTEGUMENTARY SYSTEM                                                                                                               
   Mammary Gland                                      (50)         (49)         (50)         (50)                                   
      Cyst                                                                       2 (4%)       1 (2%)                                
      Galactocele                                                   1 (2%)       1 (2%)       1 (2%)                                
      Hyperplasia                                     18 (36%)     19 (39%)      9 (18%)      7 (14%)                               
      Hyperplasia, Atypical                            3 (6%)       3 (6%)       1 (2%)                                             
      Duct, Dilatation                                31 (62%)     28 (57%)     29 (58%)     24 (48%)                               
      Duct, Hyperplasia                                2 (4%)                                 1 (2%)                                
   Skin                                               (50)         (49)         (50)         (50)                                   
      Inflammation, Chronic                                         2 (4%)                                                          
      Inflammation, Chronic Active                                  1 (2%)                                                          
____________________________________________________________________________________________________________________________________
 MUSCULOSKELETAL SYSTEM                                                                                                             
   Bone                                               (50)         (49)         (50)         (50)                                   
      Inflammation                                                               1 (2%)                                             
      Cranium, Osteopetrosis                           1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
 NERVOUS SYSTEM                                                                                                                     
   Brain                                              (50)         (49)         (50)         (50)                                   
      Compression                                      3 (6%)       8 (16%)      6 (12%)      5 (10%)                               
      Hemorrhage                                       1 (2%)       1 (2%)       1 (2%)                                             
____________________________________________________________________________________________________________________________________
 RESPIRATORY SYSTEM                                                                                                                 
   Lung                                               (50)         (49)         (50)         (50)                                   
      Congestion                                       5 (10%)      2 (4%)       5 (10%)      8 (16%)                               
      Foreign Body                                                                            1 (2%)                                
      Infiltration Cellular, Histiocyte               41 (82%)     37 (76%)     39 (78%)     38 (76%)                               
      Inflammation, Chronic                           29 (58%)     33 (67%)     29 (58%)     33 (66%)                               
      Inflammation, Suppurative                                                  1 (2%)                                             
      Necrosis                                                                   1 (2%)                                             
      Alveolar Epithelium, Hyperplasia                 1 (2%)       4 (8%)       3 (6%)       2 (4%)                                
   Nose                                               (50)         (49)         (50)         (50)                                   
      Foreign Body                                     4 (8%)       3 (6%)       1 (2%)       3 (6%)                                
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    5                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS FEMALE                   0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
RESPIRATORY SYSTEM - CONT                                                                                                           
      Inflammation, Chronic                            8 (16%)      7 (14%)      9 (18%)      6 (12%)                               
____________________________________________________________________________________________________________________________________
 SPECIAL SENSES SYSTEM                                                                                                              
   Eye                                                (50)         (49)         (50)         (50)                                   
      Cataract                                         1 (2%)       2 (4%)       5 (10%)      3 (6%)                                
      Inflammation, Chronic                                         2 (4%)                                                          
      Anterior Chamber, Inflammation                                             1 (2%)                                             
      Cornea, Inflammation, Chronic                    1 (2%)                    1 (2%)       2 (4%)                                
      Retina, Degeneration                             2 (4%)       2 (4%)       4 (8%)       2 (4%)                                
   Harderian Gland                                    (50)         (49)         (50)         (50)                                   
      Inflammation, Chronic                            3 (6%)       3 (6%)       3 (6%)       4 (8%)                                
      Pigmentation                                     2 (4%)       2 (4%)       1 (2%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
 URINARY SYSTEM                                                                                                                     
   Kidney                                             (50)         (49)         (50)         (50)                                   
      Cyst                                                                       1 (2%)       1 (2%)                                
      Infarct                                          1 (2%)                    2 (4%)       2 (4%)                                
      Nephropathy                                     14 (28%)     15 (31%)     21 (42%)     16 (32%)                               
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    6                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
DISPOSITION SUMMARY                                                                                                                 
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Natural Death                                      6           10            5            7                                     
    Moribund Sacrifice                                13            7            5           10                                     
    Dosing Accident                                                              1            2                                     
  Survivors                                                                                                                         
    Natural Death                                      1                                                                            
    Terminal Sacrifice                                29           33           39           30                                     
    Moribund Sacrifice                                 1                                      1                                     
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
 ALIMENTARY SYSTEM                                                                                                                  
   Esophagus                                          (50)         (50)         (50)         (50)                                   
      Perforation                                                                             2 (4%)                                
   Intestine Large, Colon                             (50)         (50)         (50)         (50)                                   
      Inflammation                                                                            1 (2%)                                
   Intestine Large, Cecum                             (49)         (50)         (49)         (47)                                   
      Inflammation, Chronic                                                                   1 (2%)                                
   Intestine Small, Duodenum                          (50)         (50)         (50)         (48)                                   
      Ectopic Tissue                                   1 (2%)       1 (2%)                                                          
      Ulcer                                                                      1 (2%)                                             
   Intestine Small, Ileum                             (48)         (50)         (49)         (48)                                   
      Hyperplasia, Lymphoid                                                                   1 (2%)                                
   Liver                                              (50)         (50)         (50)         (50)                                   
      Basophilic Focus                                 5 (10%)      6 (12%)      8 (16%)      6 (12%)                               
      Clear Cell Focus                                14 (28%)     13 (26%)     16 (32%)     12 (24%)                               
      Degeneration, Cystic                             5 (10%)      3 (6%)       2 (4%)       1 (2%)                                
      Eosinophilic Focus                               5 (10%)      1 (2%)       4 (8%)       3 (6%)                                
      Hepatodiaphragmatic Nodule                       9 (18%)      2 (4%)       3 (6%)       4 (8%)                                
      Inflammation, Chronic                                         1 (2%)                    1 (2%)                                
      Necrosis, Focal                                  1 (2%)       1 (2%)                                                          
      Bile Duct, Hyperplasia                          41 (82%)     35 (70%)     38 (76%)     37 (74%)                               
      Centrilobular, Necrosis                          2 (4%)                    1 (2%)       2 (4%)                                
      Hepatocyte, Vacuolization Cytoplasmic            5 (10%)      1 (2%)       2 (4%)       3 (6%)                                
      Serosa, Inflammation                                                                    1 (2%)                                
   Mesentery                                          (16)         (11)         (9)          (12)                                   
      Accessory Spleen                                                                        1 (8%)                                
      Fibrosis                                         1 (6%)                                                                       
      Fat, Necrosis                                   14 (88%)      9 (82%)      8 (89%)      7 (58%)                               
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    7                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
ALIMENTARY SYSTEM - CONT                                                                                                            
   Oral Mucosa                                        (1)                                    (4)                                    
      Pharyngeal, Cyst                                                                        2 (50%)                               
      Pharyngeal, Inflammation                                                                2 (50%)                               
   Pancreas                                           (50)         (50)         (50)         (50)                                   
      Atrophy                                         43 (86%)     31 (62%)     35 (70%)     32 (64%)                               
      Atrophy, Focal                                                                          1 (2%)                                
      Cyst                                                                                    1 (2%)                                
      Inflammation, Chronic                                                                   1 (2%)                                
      Acinus, Hyperplasia, Focal                       4 (8%)       6 (12%)     15 (30%)     12 (24%)                               
   Salivary Glands                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                             1 (2%)                                
   Stomach, Forestomach                               (50)         (50)         (50)         (50)                                   
      Edema                                            6 (12%)                   1 (2%)       2 (4%)                                
      Erosion                                          3 (6%)                                 1 (2%)                                
      Ulcer                                            4 (8%)       1 (2%)       2 (4%)       2 (4%)                                
      Epithelium, Hyperplasia                          4 (8%)                    3 (6%)       3 (6%)                                
   Stomach, Glandular                                 (50)         (50)         (50)         (50)                                   
      Edema                                            1 (2%)                                 2 (4%)                                
      Erosion                                          4 (8%)       2 (4%)       1 (2%)       1 (2%)                                
      Hyperplasia                                      1 (2%)                                                                       
      Inflammation                                     1 (2%)                                                                       
      Mineralization                                                1 (2%)                                                          
      Ulcer                                            2 (4%)       1 (2%)       2 (4%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
 CARDIOVASCULAR SYSTEM                                                                                                              
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                  47 (94%)     46 (92%)     47 (94%)     45 (90%)                               
      Mineralization                                                1 (2%)                                                          
      Thrombosis                                                    1 (2%)       1 (2%)                                             
      Pericardium, Inflammation, Granulomatous         1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
 ENDOCRINE SYSTEM                                                                                                                   
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Accessory Adrenal Cortical Nodule               23 (46%)     23 (46%)     28 (56%)     25 (50%)                               
      Degeneration, Fatty                              7 (14%)      6 (12%)      7 (14%)      2 (4%)                                
      Hyperplasia, Focal                               6 (12%)      5 (10%)      5 (10%)      5 (10%)                               
      Hypertrophy, Focal                               6 (12%)      5 (10%)      9 (18%)      8 (16%)                               
      Necrosis                                         1 (2%)                                 1 (2%)                                
   Adrenal Medulla                                    (50)         (50)         (50)         (50)                                   
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    8                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
ENDOCRINE SYSTEM - CONT                                                                                                             
      Hyperplasia                                      7 (14%)     12 (24%)      8 (16%)      2 (4%)                                
      Thrombosis                                                                 1 (2%)                                             
   Islets, Pancreatic                                 (50)         (50)         (50)         (50)                                   
      Hyperplasia                                     13 (26%)     13 (26%)     17 (34%)     26 (52%)                               
      Metaplasia, Hepatocyte                                                     1 (2%)                                             
   Pituitary Gland                                    (50)         (50)         (50)         (50)                                   
      Pars Distalis, Angiectasis                      14 (28%)     30 (60%)     16 (32%)     15 (30%)                               
      Pars Distalis, Cyst                              6 (12%)      3 (6%)       6 (12%)      5 (10%)                               
      Pars Distalis, Hyperplasia, Focal                9 (18%)      8 (16%)      9 (18%)     13 (26%)                               
      Pars Distalis, Hyperplasia, Multifocal                        1 (2%)                                                          
      Pars Intermedia, Cyst                            1 (2%)                                                                       
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      Ultimobranchial Cyst                             3 (6%)       1 (2%)                    2 (4%)                                
      C-Cell, Hyperplasia                              8 (16%)      2 (4%)       9 (18%)      4 (8%)                                
      Follicle, Cyst                                   1 (2%)       2 (4%)       4 (8%)       1 (2%)                                
      Follicular Cell, Hyperplasia                                               1 (2%)                                             
____________________________________________________________________________________________________________________________________
 GENERAL BODY SYSTEM                                                                                                                
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
 GENITAL SYSTEM                                                                                                                     
   Coagulating Gland                                  (1)                       (2)                                                 
      Inflammation                                                               1 (50%)                                            
   Penis                                              (1)                                                                           
      Fibrosis                                         1 (100%)                                                                     
   Preputial Gland                                    (50)         (50)         (50)         (50)                                   
      Cyst                                             4 (8%)                                 3 (6%)                                
      Inflammation, Chronic                            5 (10%)      5 (10%)      4 (8%)       4 (8%)                                
   Prostate                                           (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic                           31 (62%)     28 (56%)     27 (54%)     26 (52%)                               
   Testes                                             (50)         (50)         (50)         (50)                                   
      Bilateral, Germinal Epithelium, Atrophy          1 (2%)                    2 (4%)                                             
      Germinal Epithelium, Atrophy                     1 (2%)                                 1 (2%)                                
____________________________________________________________________________________________________________________________________
 HEMATOPOIETIC SYSTEM                                                                                                               
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      7 (14%)      7 (14%)      4 (8%)       9 (18%)                               
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page    9                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
   Lymph Node                                         (21)         (17)         (10)         (18)                                   
      Deep Cervical, Hyperplasia, Lymphoid                          1 (6%)       1 (10%)                                            
      Deep Cervical, Inflammation, Granulomatous       1 (5%)                                                                       
      Mediastinal, Hyperplasia, Lymphoid               9 (43%)      9 (53%)     10 (100%)    15 (83%)                               
      Mediastinal, Inflammation, Granulomatous         1 (5%)                                                                       
      Pancreatic, Hyperplasia, Lymphoid                2 (10%)      4 (24%)      1 (10%)      1 (6%)                                
   Lymph Node, Mesenteric                             (50)         (50)         (50)         (50)                                   
      Hyperplasia, Lymphoid                            7 (14%)      3 (6%)       4 (8%)       9 (18%)                               
   Spleen                                             (50)         (50)         (50)         (50)                                   
      Fibrosis                                         1 (2%)       2 (4%)       2 (4%)       2 (4%)                                
      Hematopoietic Cell Proliferation                11 (22%)     12 (24%)     17 (34%)     20 (40%)                               
      Hemorrhage                                                                              2 (4%)                                
      Necrosis                                         2 (4%)                                                                       
      Capsule, Fibrosis                                1 (2%)       7 (14%)     12 (24%)     30 (60%)                               
      Lymphoid Follicle, Hyperplasia                                1 (2%)       1 (2%)                                             
____________________________________________________________________________________________________________________________________
 INTEGUMENTARY SYSTEM                                                                                                               
   Mammary Gland                                      (50)         (50)         (50)         (50)                                   
      Cyst                                            23 (46%)     18 (36%)     20 (40%)     20 (40%)                               
      Hyperplasia                                      1 (2%)                    1 (2%)                                             
   Skin                                               (50)         (50)         (50)         (50)                                   
      Hyperkeratosis                                                                          1 (2%)                                
      Inflammation, Chronic                                                      5 (10%)      1 (2%)                                
      Lip, Inflammation                                1 (2%)                                                                       
      Subcutaneous Tissue, Mineralization                                                     1 (2%)                                
____________________________________________________________________________________________________________________________________
 MUSCULOSKELETAL SYSTEM                                                                                                             
   Bone                                               (50)         (50)         (50)         (50)                                   
      Cyst                                             1 (2%)                                                                       
      Cranium, Osteopetrosis                                        1 (2%)                                                          
____________________________________________________________________________________________________________________________________
 NERVOUS SYSTEM                                                                                                                     
   Brain                                              (50)         (50)         (50)         (50)                                   
      Compression                                      7 (14%)     10 (20%)      9 (18%)      6 (12%)                               
      Hemorrhage                                       1 (2%)       2 (4%)                                                          
____________________________________________________________________________________________________________________________________
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   10                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
 RESPIRATORY SYSTEM                                                                                                                 
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion                                       3 (6%)       4 (8%)       3 (6%)       7 (14%)                               
      Foreign Body                                                               1 (2%)       2 (4%)                                
      Hemorrhage                                       1 (2%)                                                                       
      Infiltration Cellular, Histiocyte               28 (56%)     29 (58%)     36 (72%)     26 (52%)                               
      Inflammation, Chronic                           29 (58%)     23 (46%)     36 (72%)     30 (60%)                               
      Inflammation, Suppurative                                                               1 (2%)                                
      Necrosis                                                                   1 (2%)       1 (2%)                                
      Alveolar Epithelium, Hyperplasia                 7 (14%)      9 (18%)      4 (8%)       6 (12%)                               
      Mediastinum, Inflammation, Granulomatous         1 (2%)                                                                       
   Nose                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                     7 (14%)      4 (8%)      12 (24%)      7 (14%)                               
      Inflammation, Chronic                           12 (24%)      3 (6%)      20 (40%)     15 (30%)                               
   Pleura                                             (1)                                                                           
      Inflammation, Granulomatous                      1 (100%)                                                                     
   Trachea                                            (50)         (50)         (50)         (50)                                   
      Foreign Body                                                                            1 (2%)                                
      Inflammation                                     1 (2%)                    1 (2%)                                             
      Necrosis                                                                                1 (2%)                                
      Perforation                                                                1 (2%)                                             
____________________________________________________________________________________________________________________________________
 SPECIAL SENSES SYSTEM                                                                                                              
   Eye                                                (50)         (49)         (48)         (48)                                   
      Cataract                                         1 (2%)       3 (6%)       4 (8%)       3 (6%)                                
      Inflammation, Chronic                            1 (2%)                    1 (2%)       1 (2%)                                
      Phthisis Bulbi                                                                          1 (2%)                                
      Anterior Chamber, Inflammation, Acute                                                   1 (2%)                                
      Bilateral, Anterior Chamber, Inflammation,                                                                                    
         Acute                                                      1 (2%)                                                          
      Retina, Degeneration                             1 (2%)       2 (4%)       4 (8%)       3 (6%)                                
   Harderian Gland                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                1 (2%)       1 (2%)                                
      Inflammation, Chronic                            2 (4%)       3 (6%)       1 (2%)       4 (8%)                                
      Pigmentation                                     2 (4%)       1 (2%)       1 (2%)       3 (6%)                                
____________________________________________________________________________________________________________________________________
 URINARY SYSTEM                                                                                                                     
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Cyst                                                                       1 (2%)                                             
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   11                                                              
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                     METHYLENE BLUE TRIHYDRATE                                 Date: 03/25/05    
Route: GAVAGE                                                                                                     Time: 10:00:58    
____________________________________________________________________________________________________________________________________
         FISCHER 344 RATS MALE                     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                                  
____________________________________________________________________________________________________________________________________
URINARY SYSTEM - CONT                                                                                                               
      Hydronephrosis                                                1 (2%)                    2 (4%)                                
      Infarct                                          2 (4%)                                                                       
      Nephropathy                                     35 (70%)     39 (78%)     33 (66%)     34 (68%)                               
   Urethra                                                                                   (1)                                    
      Inflammation                                                                            1 (100%)                              
   Urinary Bladder                                    (50)         (50)         (50)         (49)                                   
      Hemorrhage                                       1 (2%)                                 1 (2%)                                
      Hyperplasia                                                                1 (2%)                                             
      Inflammation, Chronic                                         2 (4%)                    1 (2%)                                
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                             Page   12                                                              
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