National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/20994

TDMS Study 91005-07 Pathology Tables

NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58

                                                         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
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)

                                                              Page   1


NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         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 [3.0]                                            
   Intestine Large, Colon                             (50)         (48)         (49)         (48)                                   
      Cyst                                                                                    1 [4.0]                               
   Intestine Small, Duodenum                          (49)         (48)         (49)         (48)                                   
      Ectopic Tissue                                                                          1 [2.0]                               
   Liver                                              (50)         (49)         (50)         (50)                                   
      Basophilic Focus                                37           34           38           40                                     
      Clear Cell Focus                                 8            5            9            8                                     
      Degeneration, Cystic                             1 [1.0]      1 [2.0]                   1 [1.0]                               
      Eosinophilic Focus                               3            2                                                               
      Hepatodiaphragmatic Nodule                       7 [0.0]      4 [2.0]      7 [0.0]      4 [2.0]                               
      Inflammation, Chronic                            6 [2.0]      4 [1.8]      4 [1.8]      5 [1.8]                               
      Necrosis, Focal                                  1 [2.0]                   1 [1.0]                                            
      Bile Duct, Hyperplasia                           7 [2.4]      5 [1.8]      6 [1.7]      2 [2.0]                               
      Centrilobular, Necrosis                          2 [1.5]                   1 [2.0]                                            
      Hepatocyte, Vacuolization Cytoplasmic            4 [2.3]      4 [1.8]                                                         
   Mesentery                                          (17)         (14)         (12)         (8)                                    
      Accessory Spleen                                              1 [2.0]                                                         
      Fat, Necrosis                                   17 [2.8]     14 [2.6]     11 [2.6]      8 [2.4]                               
   Oral Mucosa                                        (2)                                    (1)                                    
      Pharyngeal, Cyst                                 1 [3.0]                                1 [2.0]                               
   Pancreas                                           (49)         (48)         (48)         (49)                                   
      Atrophy                                         26 [1.5]     20 [1.4]     23 [1.3]     23 [1.5]                               
      Inflammation                                                  1 [1.0]                                                         
      Acinus, Hyperplasia, Focal                       3 [1.7]      1 [2.0]      2 [2.0]      1 [2.0]                               
   Salivary Glands                                    (50)         (49)         (50)         (50)                                   
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    2                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                      0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Inflammation                                                               1 [1.0]                                            
   Stomach, Forestomach                               (50)         (49)         (49)         (49)                                   
      Edema                                            2 [2.5]      3 [2.3]      1 [3.0]                                            
      Erosion                                                                                 1 [1.0]                               
      Inflammation, Chronic Active                     1 [1.0]                                2 [1.0]                               
      Ulcer                                            4 [2.3]      3 [3.0]      1 [3.0]      1 [2.0]                               
      Epithelium, Hyperplasia                          2 [2.0]      2 [2.0]      2 [1.5]      3 [1.3]                               
   Stomach, Glandular                                 (50)         (49)         (48)         (49)                                   
      Edema                                            2 [2.0]      1 [2.0]      1 [2.0]                                            
      Erosion                                          2 [2.5]      2 [2.5]                                                         
      Ulcer                                            2 [2.0]      1 [3.0]      1 [2.0]                                            
   Tongue                                             (1)          (1)          (1)          (1)                                    
      Cyst                                                          1 [2.0]                                                         
      Hyperplasia                                      1 [2.0]                                1 [2.0]                               
      Inflammation                                                  1 [3.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (49)         (50)         (50)                                   
      Cardiomyopathy                                  36 [1.3]     41 [1.2]     36 [1.2]     32 [1.2]                               
      Thrombosis                                                    1 [2.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (49)         (50)         (50)                                   
      Accessory Adrenal Cortical Nodule                9 [1.3]      7 [1.3]      8 [1.3]     12 [1.3]                               
      Degeneration, Fatty                             11 [1.4]     13 [1.8]     13 [1.9]      8 [1.4]                               
      Hyperplasia, Focal                               5 [1.4]      8 [1.6]      8 [1.4]      6 [2.0]                               
      Hypertrophy, Focal                              12 [1.9]     11 [2.1]     13 [2.2]      7 [2.0]                               
      Necrosis                                         2 [3.0]      1 [2.0]                                                         
   Adrenal Medulla                                    (50)         (49)         (50)         (50)                                   
      Hyperplasia                                      1 [2.0]      2 [1.0]      1 [3.0]                                            
   Islets, Pancreatic                                 (49)         (48)         (48)         (49)                                   
      Hyperplasia                                     13 [1.0]     15 [1.0]     15 [1.1]     15 [1.0]                               
      Metaplasia, Hepatocyte                           2 [1.5]                                                                      
   Pituitary Gland                                    (50)         (49)         (50)         (50)                                   
      Pars Distalis, Angiectasis                      28 [2.0]     27 [1.9]     29 [2.0]     21 [2.0]                               
      Pars Distalis, Cyst                             21 [2.1]     19 [1.6]     16 [1.7]     23 [2.0]                               
      Pars Distalis, Hyperplasia, Focal                5 [2.0]      8 [1.8]      6 [2.0]      6 [1.8]                               
      Pars Intermedia, Cyst                            1 [2.0]                                                                      
   Thyroid Gland                                      (50)         (49)         (50)         (50)                                   
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    3                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                      0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Ultimobranchial Cyst                             2 [1.5]                   1 [1.0]                                            
      C-Cell, Hyperplasia                             10 [2.1]     11 [1.4]      7 [1.9]      5 [2.0]                               
      Follicle, Cyst                                   2 [2.0]      1 [1.0]      2 [1.0]      4 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (50)         (48)         (50)         (50)                                   
      Cyst                                             4 [2.3]      7 [2.0]      4 [1.8]      6 [2.0]                               
      Inflammation, Chronic                            1 [2.0]      5 [1.6]      2 [3.0]      4 [2.3]                               
   Ovary                                              (50)         (49)         (50)         (50)                                   
      Cyst                                            11 [1.9]      4 [1.8]      9 [2.0]     10 [1.8]                               
   Uterus                                             (50)         (49)         (50)         (50)                                   
      Cyst                                             1            3            2            3                                     
      Hemorrhage                                       1 [2.0]                                1 [3.0]                               
      Hydrometra                                       1 [3.0]      4 [1.0]      2 [1.5]      1 [2.0]                               
      Cervix, Cyst                                     1                                                                            
      Endometrium, Hyperplasia, Cystic                 4 [2.5]      1 [1.0]                   2 [2.0]                               
   Vagina                                                                       (1)                                                 
      Cyst                                                                       1                                                  
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (49)         (50)         (50)                                   
      Hyperplasia                                      8 [2.4]      8 [2.8]      9 [2.6]      6 [2.5]                               
   Lymph Node                                         (15)         (8)          (11)         (3)                                    
      Mediastinal, Congestion                          1 [3.0]                                                                      
      Mediastinal, Hyperplasia, Lymphoid               5 [2.0]      7 [2.1]      8 [2.0]      2 [2.0]                               
      Pancreatic, Hyperplasia, Lymphoid                1 [2.0]                   1 [2.0]      1 [2.0]                               
   Lymph Node, Mesenteric                             (49)         (49)         (50)         (50)                                   
      Hyperplasia, Lymphoid                                         1 [2.0]      1 [1.0]                                            
   Spleen                                             (49)         (48)         (49)         (49)                                   
      Fibrosis                                         2 [2.0]                                                                      
      Hematopoietic Cell Proliferation                 3 [4.0]      5 [2.4]      7 [2.7]      8 [1.6]                               
      Necrosis                                         1 [3.0]                                                                      
      Capsule, Fibrosis                                8 [1.0]     17 [1.1]     12 [1.1]     20 [1.0]                               
      Lymphoid Follicle, Atrophy                                                 1 [3.0]                                            
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    4                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                      0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
      Lymphoid Follicle, Hyperplasia                   1 [3.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (50)         (49)         (50)         (50)                                   
      Cyst                                                                       2 [3.0]      1 [1.0]                               
      Galactocele                                                   1            1            1                                     
      Hyperplasia                                     18 [2.3]     19 [2.1]      9 [2.0]      7 [2.6]                               
      Hyperplasia, Atypical                            3 [1.3]      3 [2.0]      1 [2.0]                                            
      Duct, Dilatation                                31 [2.6]     28 [2.5]     29 [2.4]     24 [2.4]                               
      Duct, Hyperplasia                                2 [2.0]                                1 [2.0]                               
   Skin                                               (50)         (49)         (50)         (50)                                   
      Inflammation, Chronic                                         2 [1.5]                                                         
      Inflammation, Chronic Active                                  1 [4.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (49)         (50)         (50)                                   
      Inflammation                                                               1 [4.0]                                            
      Cranium, Osteopetrosis                           1 [2.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (49)         (50)         (50)                                   
      Compression                                      3 [2.3]      8 [2.1]      6 [2.2]      5 [2.0]                               
      Hemorrhage                                       1 [2.0]      1 [2.0]      1 [4.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (49)         (50)         (50)                                   
      Congestion                                       5 [1.2]      2 [1.0]      5 [1.0]      8 [1.5]                               
      Foreign Body                                                                            1 [3.0]                               
      Infiltration Cellular, Histiocyte               41 [1.0]     37 [1.0]     39 [1.0]     38 [1.0]                               
      Inflammation, Chronic                           29 [1.0]     33 [1.0]     29 [1.0]     33 [1.0]                               
      Inflammation, Suppurative                                                  1 [3.0]                                            
      Necrosis                                                                   1 [3.0]                                            
      Alveolar Epithelium, Hyperplasia                 1 [3.0]      4 [2.0]      3 [2.3]      2 [2.5]                               
   Nose                                               (50)         (49)         (50)         (50)                                   
      Foreign Body                                     4 [1.8]      3 [1.0]      1 [1.0]      3 [1.7]                               
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    5                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                      0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
RESPIRATORY SYSTEM - CONT                                                                                                           
      Inflammation, Chronic                            8 [1.9]      7 [1.0]      9 [1.8]      6 [1.7]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (50)         (49)         (50)         (50)                                   
      Cataract                                         1 [2.0]      2 [3.0]      5 [2.4]      3 [2.0]                               
      Inflammation, Chronic                                         2 [4.0]                                                         
      Anterior Chamber, Inflammation                                             1 [2.0]                                            
      Cornea, Inflammation, Chronic                    1 [2.0]                   1 [2.0]      2 [2.5]                               
      Retina, Degeneration                             2 [2.5]      2 [4.0]      4 [3.5]      2 [4.0]                               
   Harderian Gland                                    (50)         (49)         (50)         (50)                                   
      Inflammation, Chronic                            3 [1.7]      3 [1.3]      3 [1.3]      4 [1.0]                               
      Pigmentation                                     2 [2.0]      2 [2.0]      1 [2.0]      1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (49)         (50)         (50)                                   
      Cyst                                                                       1 [2.0]      1 [2.0]                               
      Infarct                                          1 [2.0]                   2 [1.5]      2 [2.0]                               
      Nephropathy                                     14 [1.0]     15 [1.1]     21 [1.2]     16 [1.0]                               
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         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 [3.5]                               
   Intestine Large, Colon                             (50)         (50)         (50)         (50)                                   
      Inflammation                                                                            1 [2.0]                               
   Intestine Large, Cecum                             (49)         (50)         (49)         (47)                                   
      Inflammation, Chronic                                                                   1 [2.0]                               
   Intestine Small, Duodenum                          (50)         (50)         (50)         (48)                                   
      Ectopic Tissue                                   1 [2.0]      1 [2.0]                                                         
      Ulcer                                                                      1 [2.0]                                            
   Intestine Small, Ileum                             (48)         (50)         (49)         (48)                                   
      Hyperplasia, Lymphoid                                                                   1 [3.0]                               
   Liver                                              (50)         (50)         (50)         (50)                                   
      Basophilic Focus                                 5            6            8            6                                     
      Clear Cell Focus                                14           13           16           12                                     
      Degeneration, Cystic                             5 [1.8]      3 [1.3]      2 [1.5]      1 [2.0]                               
      Eosinophilic Focus                               5            1            4            3                                     
      Hepatodiaphragmatic Nodule                       9 [2.1]      2 [2.0]      3 [2.5]      4 [2.0]                               
      Inflammation, Chronic                                         1 [1.0]                   1 [1.0]                               
      Necrosis, Focal                                  1 [2.0]      1 [1.0]                                                         
      Bile Duct, Hyperplasia                          41 [2.5]     35 [2.3]     38 [1.9]     37 [2.0]                               
      Centrilobular, Necrosis                          2 [1.5]                   1 [2.0]      2 [2.0]                               
      Hepatocyte, Vacuolization Cytoplasmic            5 [2.2]      1 [2.0]      2 [2.5]      3 [2.3]                               
      Serosa, Inflammation                                                                    1 [2.0]                               
   Mesentery                                          (16)         (11)         (9)          (12)                                   
      Accessory Spleen                                                                        1 [2.0]                               
      Fibrosis                                         1 [2.0]                                                                      
      Fat, Necrosis                                   14 [2.6]      9 [2.3]      8 [3.0]      7 [2.6]                               
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         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 [4.0]                               
      Pharyngeal, Inflammation                                                                2 [2.5]                               
   Pancreas                                           (50)         (50)         (50)         (50)                                   
      Atrophy                                         43 [2.1]     31 [1.8]     35 [2.0]     32 [1.9]                               
      Atrophy, Focal                                                                          1 [1.0]                               
      Cyst                                                                                    1 [2.0]                               
      Inflammation, Chronic                                                                   1 [2.0]                               
      Acinus, Hyperplasia, Focal                       4 [2.0]      6 [1.7]     15 [1.9]     12 [1.8]                               
   Salivary Glands                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                             1 [2.0]                               
   Stomach, Forestomach                               (50)         (50)         (50)         (50)                                   
      Edema                                            6 [2.5]                   1 [2.0]      2 [2.5]                               
      Erosion                                          3 [2.3]                                1 [1.0]                               
      Ulcer                                            4 [3.5]      1 [2.0]      2 [2.5]      2 [2.5]                               
      Epithelium, Hyperplasia                          4 [2.3]                   3 [1.7]      3 [1.3]                               
   Stomach, Glandular                                 (50)         (50)         (50)         (50)                                   
      Edema                                            1 [2.0]                                2 [2.0]                               
      Erosion                                          4 [2.0]      2 [3.0]      1 [3.0]      1 [2.0]                               
      Hyperplasia                                      1 [2.0]                                                                      
      Inflammation                                     1 [2.0]                                                                      
      Mineralization                                                1 [2.0]                                                         
      Ulcer                                            2 [3.5]      1 [2.0]      2 [2.0]      1 [4.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Heart                                              (50)         (50)         (50)         (50)                                   
      Cardiomyopathy                                  47 [1.6]     46 [1.5]     47 [1.4]     45 [1.7]                               
      Mineralization                                                1 [3.0]                                                         
      Thrombosis                                                    1 [2.0]      1 [1.0]                                            
      Pericardium, Inflammation, Granulomatous         1 [3.0]                                                                      
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Accessory Adrenal Cortical Nodule               23 [1.1]     23 [1.2]     28 [1.3]     25 [1.2]                               
      Degeneration, Fatty                              7 [1.9]      6 [1.3]      7 [1.7]      2 [1.5]                               
      Hyperplasia, Focal                               6 [1.2]      5 [1.6]      5 [1.6]      5 [1.2]                               
      Hypertrophy, Focal                               6 [2.3]      5 [1.6]      9 [1.9]      8 [2.0]                               
      Necrosis                                         1 [2.0]                                1 [3.0]                               
   Adrenal Medulla                                    (50)         (50)         (50)         (50)                                   
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    8                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                        0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Hyperplasia                                      7 [2.0]     12 [1.8]      8 [1.6]      2 [2.0]                               
      Thrombosis                                                                 1 [3.0]                                            
   Islets, Pancreatic                                 (50)         (50)         (50)         (50)                                   
      Hyperplasia                                     13 [1.2]     13 [1.7]     17 [1.8]     26 [1.4]                               
      Metaplasia, Hepatocyte                                                     1 [2.0]                                            
   Pituitary Gland                                    (50)         (50)         (50)         (50)                                   
      Pars Distalis, Angiectasis                      14 [2.1]     30 [2.0]     16 [2.1]     15 [2.2]                               
      Pars Distalis, Cyst                              6 [2.4]      3 [1.3]      6 [1.8]      5 [2.0]                               
      Pars Distalis, Hyperplasia, Focal                9 [2.1]      8 [2.0]      9 [1.8]     13 [2.3]                               
      Pars Distalis, Hyperplasia, Multifocal                        1 [3.0]                                                         
      Pars Intermedia, Cyst                            1 [1.0]                                                                      
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      Ultimobranchial Cyst                             3 [1.7]      1 [1.0]                   2 [1.5]                               
      C-Cell, Hyperplasia                              8 [2.4]      2 [2.0]      9 [1.8]      4 [2.3]                               
      Follicle, Cyst                                   1 [1.0]      2 [2.0]      4 [1.0]      1 [1.0]                               
      Follicular Cell, Hyperplasia                                               1 [3.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Coagulating Gland                                  (1)                       (2)                                                 
      Inflammation                                                               1 [4.0]                                            
   Penis                                              (1)                                                                           
      Fibrosis                                         1 [2.0]                                                                      
   Preputial Gland                                    (50)         (50)         (50)         (50)                                   
      Cyst                                             4 [2.5]                                3 [1.7]                               
      Inflammation, Chronic                            5 [2.0]      5 [1.4]      4 [2.0]      4 [1.8]                               
   Prostate                                           (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic                           31 [2.0]     28 [1.8]     27 [2.0]     26 [2.1]                               
   Testes                                             (50)         (50)         (50)         (50)                                   
      Bilateral, Germinal Epithelium, Atrophy          1 [4.0]                   2 [3.0]                                            
      Germinal Epithelium, Atrophy                     1 [1.0]                                1 [3.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      7 [2.4]      7 [2.9]      4 [2.5]      9 [2.7]                               
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page    9                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         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 [3.0]      1 [4.0]                                            
      Deep Cervical, Inflammation, Granulomatous       1 [2.0]                                                                      
      Mediastinal, Hyperplasia, Lymphoid               9 [2.0]      9 [2.0]     10 [2.2]     15 [2.0]                               
      Mediastinal, Inflammation, Granulomatous         1 [3.0]                                                                      
      Pancreatic, Hyperplasia, Lymphoid                2 [2.0]      4 [2.0]      1 [2.0]      1 [2.0]                               
   Lymph Node, Mesenteric                             (50)         (50)         (50)         (50)                                   
      Hyperplasia, Lymphoid                            7 [2.3]      3 [2.0]      4 [2.0]      9 [2.1]                               
   Spleen                                             (50)         (50)         (50)         (50)                                   
      Fibrosis                                         1 [2.0]      2 [1.5]      2 [2.0]      2 [2.0]                               
      Hematopoietic Cell Proliferation                11 [1.5]     12 [2.0]     17 [1.5]     20 [1.7]                               
      Hemorrhage                                                                              2 [2.5]                               
      Necrosis                                         2 [3.0]                                                                      
      Capsule, Fibrosis                                1 [1.0]      7 [1.3]     12 [1.5]     30 [1.8]                               
      Lymphoid Follicle, Hyperplasia                                1 [2.0]      1 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (50)         (50)         (50)         (50)                                   
      Cyst                                            23 [1.8]     18 [1.7]     20 [1.8]     20 [1.9]                               
      Hyperplasia                                      1 [2.0]                   1 [1.0]                                            
   Skin                                               (50)         (50)         (50)         (50)                                   
      Hyperkeratosis                                                                          1 [2.0]                               
      Inflammation, Chronic                                                      5 [2.6]      1 [2.0]                               
      Lip, Inflammation                                1 [4.0]                                                                      
      Subcutaneous Tissue, Mineralization                                                     1 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Cyst                                             1                                                                            
      Cranium, Osteopetrosis                                        1 [2.0]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Compression                                      7 [3.0]     10 [2.0]      9 [2.2]      6 [2.3]                               
      Hemorrhage                                       1 [3.0]      2 [1.5]                                                         
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page   10                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         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 [1.7]      4 [1.5]      3 [1.3]      7 [1.9]                               
      Foreign Body                                                               1 [2.0]      2 [2.0]                               
      Hemorrhage                                       1 [2.0]                                                                      
      Infiltration Cellular, Histiocyte               28 [1.1]     29 [1.0]     36 [1.1]     26 [1.0]                               
      Inflammation, Chronic                           29 [1.1]     23 [1.0]     36 [1.0]     30 [1.2]                               
      Inflammation, Suppurative                                                               1 [3.0]                               
      Necrosis                                                                   1 [3.0]      1 [2.0]                               
      Alveolar Epithelium, Hyperplasia                 7 [2.0]      9 [2.2]      4 [2.3]      6 [2.2]                               
      Mediastinum, Inflammation, Granulomatous         1 [3.0]                                                                      
   Nose                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                     7 [2.0]      4 [1.0]     12 [1.7]      7 [1.7]                               
      Inflammation, Chronic                           12 [2.0]      3 [1.3]     20 [1.7]     15 [1.9]                               
   Pleura                                             (1)                                                                           
      Inflammation, Granulomatous                      1 [3.0]                                                                      
   Trachea                                            (50)         (50)         (50)         (50)                                   
      Foreign Body                                                                            1 [2.0]                               
      Inflammation                                     1 [3.0]                   1 [2.0]                                            
      Necrosis                                                                                1 [2.0]                               
      Perforation                                                                1 [2.0]                                            
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                (50)         (49)         (48)         (48)                                   
      Cataract                                         1 [2.0]      3 [2.7]      4 [2.8]      3 [2.7]                               
      Inflammation, Chronic                            1 [4.0]                   1 [2.0]      1 [4.0]                               
      Phthisis Bulbi                                                                          1                                     
      Anterior Chamber, Inflammation, Acute                                                   1 [2.0]                               
      Bilateral, Anterior Chamber, Inflammation,                                                                                    
         Acute                                                      1 [2.0]                                                         
      Retina, Degeneration                             1 [2.0]      2 [3.0]      4 [3.5]      3 [3.7]                               
   Harderian Gland                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                1 [2.0]      1 [2.0]                               
      Inflammation, Chronic                            2 [2.0]      3 [1.0]      1 [1.0]      4 [1.0]                               
      Pigmentation                                     2 [2.0]      1 [2.0]      1 [2.0]      3 [2.0]                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Cyst                                                                       1 [3.0]                                            
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                             Page   11                                                              
                                                                                                                                   
NTP Experiment-Test: 91005-07         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT18  
Study Type: CHRONIC                                  WITH AVERAGE SEVERITY GRADES[b]                              Date: 03/25/05    
Route: GAVAGE                                             METHYLENE BLUE TRIHYDRATE                               Time: 10:16:58    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                        0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG                               
                                                                                                                                    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
URINARY SYSTEM - CONT                                                                                                               
      Hydronephrosis                                                1 [3.0]                   2 [2.5]                               
      Infarct                                          2 [1.5]                                                                      
      Nephropathy                                     35 [1.7]     39 [1.8]     33 [1.3]     34 [1.3]                               
   Urethra                                                                                   (1)                                    
      Inflammation                                                                            1 [3.0]                               
   Urinary Bladder                                    (50)         (50)         (50)         (49)                                   
      Hemorrhage                                       1 [2.0]                                1 [2.0]                               
      Hyperplasia                                                                1 [3.0]                                            
      Inflammation, Chronic                                         2 [3.0]                   1 [3.0]                               
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
b  Average severity grade (1-minimal;2-mild;3-moderate;4-marked)                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page   12                                                              
                                                                                                                                   
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                             ----------              END OF REPORT             ----------                                           
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NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.