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TDMS Study 88122-06 Pathology Tables

NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01
Route: GAVAGE                                                                                                     Time: 14:32:26

                                                           FINAL/RATS




       Facility:  Battelle Columbus Laboratory

       Chemical CAS #:  37319-17-8

       Lock Date:  06/01/00

       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: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   0 MG/KG      28 MG/KG     84 MG/KG     252                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Natural Death                                     13           10            9            6                                     
    Moribund Sacrifice                                 6            8           11           11                                     
    Dosing Accident                                    1                         2            5                                     
    Accidently Killed                                               1                         1                                     
  Survivors                                                                                                                         
    Natural Death                                                                             1                                     
    Terminal Sacrifice                                30           31           28           26                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Esophagus                                          (50)         (50)         (50)         (50)                                   
      Muscularis, Inflammation, Chronic                                                       1 (2%)                                
   Intestine Large, Colon                             (50)         (50)         (50)         (50)                                   
      Parasite Metazoan                                2 (4%)       3 (6%)       3 (6%)       3 (6%)                                
   Intestine Large, Rectum                            (46)         (43)         (44)         (42)                                   
      Infiltration Cellular, Histiocyte                                                      18 (43%)                               
      Inflammation, Acute, Focal                                                              1 (2%)                                
      Inflammation, Chronic                                                      1 (2%)       1 (2%)                                
      Myxomatous Change                                             1 (2%)      12 (27%)     35 (83%)                               
      Parasite Metazoan                                2 (4%)       3 (7%)       1 (2%)                                             
   Intestine Small, Jejunum                           (50)         (50)         (50)         (50)                                   
      Peyer's Patch, Hyperplasia, Lymphoid             1 (2%)                                                                       
   Intestine Small, Ileum                             (50)         (50)         (50)         (50)                                   
      Parasite Metazoan                                1 (2%)                                                                       
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                                                2 (4%)       1 (2%)                                
      Basophilic Focus                                39 (78%)     35 (70%)     40 (80%)     34 (68%)                               
      Clear Cell Focus                                 8 (16%)      4 (8%)       8 (16%)      6 (12%)                               
      Eosinophilic Focus                              12 (24%)     12 (24%)     14 (28%)     10 (20%)                               
      Fibrosis, Focal                                                            1 (2%)                                             
      Hepatodiaphragmatic Nodule                       9 (18%)      8 (16%)     11 (22%)     14 (28%)                               
      Inflammation, Granulomatous                     36 (72%)     31 (62%)     37 (74%)     39 (78%)                               
      Mixed Cell Focus                                19 (38%)     12 (24%)     10 (20%)      9 (18%)                               
      Necrosis, Focal                                                                         1 (2%)                                
      Regeneration                                                  1 (2%)       1 (2%)                                             
      Tension Lipidosis                                                          1 (2%)                                             
      Bile Duct, Hyperplasia                          13 (26%)     14 (28%)     11 (22%)     14 (28%)                               
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    2                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   0 MG/KG      28 MG/KG     84 MG/KG     252                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Bile Duct, Inflammation                                                    1 (2%)                                             
      Centrilobular, Fatty Change                      1 (2%)       2 (4%)                                                          
   Mesentery                                          (8)          (4)          (6)          (9)                                    
      Fat, Necrosis                                    7 (88%)      4 (100%)     6 (100%)     9 (100%)                              
   Oral Mucosa                                                     (1)          (1)                                                 
      Cyst                                                                       1 (100%)                                           
      Pharyngeal, Hyperplasia, Squamous                             1 (100%)                                                        
   Pancreas                                           (50)         (50)         (50)         (50)                                   
      Acinus, Atrophy                                  7 (14%)     12 (24%)     11 (22%)      8 (16%)                               
      Acinus, Hyperplasia, Focal                       1 (2%)       1 (2%)                                                          
   Salivary Glands                                    (50)         (50)         (50)         (50)                                   
      Parotid Gland, Atrophy, Diffuse                                                         1 (2%)                                
      Parotid Gland, Atrophy, Focal                    2 (4%)       1 (2%)                                                          
      Parotid Gland, Hyperplasia, Focal                1 (2%)                                                                       
   Stomach, Forestomach                               (50)         (50)         (50)         (50)                                   
      Inflammation, Acute                                                        1 (2%)                                             
      Inflammation, Chronic, Focal                                                            1 (2%)                                
      Epithelium, Hyperplasia, Squamous                                                       1 (2%)                                
      Epithelium, Inflammation, Focal, Suppurative                                            1 (2%)                                
   Stomach, Glandular                                 (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic, Focal                                                            1 (2%)                                
      Mineralization                                                1 (2%)                    1 (2%)                                
      Pigmentation, Hemosiderin                                                               1 (2%)                                
      Ulcer                                                                      1 (2%)       3 (6%)                                
      Epithelium, Ectasia                                           1 (2%)                                                          
   Tongue                                             (1)                                                                           
      Epithelium, Hyperplasia, Focal, Squamous         1 (100%)                                                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Blood Vessel                                       (50)         (50)         (50)         (50)                                   
      Aorta, Inflammation, Chronic                                               1 (2%)       1 (2%)                                
   Heart                                              (50)         (50)         (50)         (50)                                   
      Artery, Hyperplasia, Focal                                                              1 (2%)                                
      Atrium, Thrombosis                                            1 (2%)                                                          
      Myocardium, Degeneration                        38 (76%)     30 (60%)     31 (62%)     34 (68%)                               
      Myocardium, Inflammation, Chronic, Focal         1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    3                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   0 MG/KG      28 MG/KG     84 MG/KG     252                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ENDOCRINE SYSTEM - CONT                                                                                                             
      Hyperplasia, Focal                              20 (40%)     17 (34%)     17 (34%)     19 (38%)                               
   Adrenal Medulla                                    (50)         (50)         (50)         (50)                                   
      Hyperplasia, Focal                               5 (10%)      2 (4%)       4 (8%)       4 (8%)                                
      Necrosis                                                                                1 (2%)                                
   Islets, Pancreatic                                 (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      1 (2%)       1 (2%)                    1 (2%)                                
   Pituitary Gland                                    (50)         (50)         (50)         (50)                                   
      Angiectasis                                      1 (2%)       2 (4%)       2 (4%)       2 (4%)                                
      Cyst                                            20 (40%)     21 (42%)     18 (36%)     22 (44%)                               
      Hemorrhage                                       1 (2%)                                                                       
      Pars Distalis, Hyperplasia, Focal               16 (32%)     15 (30%)     10 (20%)     13 (26%)                               
      Pars Distalis, Mineralization                                                           1 (2%)                                
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      Hemorrhage                                                                 1 (2%)       1 (2%)                                
      C-Cell, Hyperplasia                             33 (66%)     38 (76%)     34 (68%)     31 (62%)                               
      Follicle, Hyperplasia                                                      2 (4%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   None                                                                                                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Clitoral Gland                                     (50)         (50)         (50)         (49)                                   
      Cyst                                             4 (8%)       4 (8%)       4 (8%)       3 (6%)                                
      Fibrosis                                         1 (2%)                                                                       
      Hyperplasia                                      1 (2%)                                                                       
      Hyperplasia, Focal                               5 (10%)      3 (6%)       2 (4%)       3 (6%)                                
      Inflammation, Chronic                            7 (14%)     10 (20%)     11 (22%)      8 (16%)                               
      Inflammation, Suppurative                        1 (2%)                    1 (2%)       2 (4%)                                
   Ovary                                              (50)         (50)         (50)         (50)                                   
      Cyst                                             4 (8%)       5 (10%)      7 (14%)      5 (10%)                               
      Inflammation, Granulomatous                                                             1 (2%)                                
   Oviduct                                                         (1)                                                              
      Cyst                                                          1 (100%)                                                        
   Uterus                                             (50)         (50)         (50)         (50)                                   
      Inflammation, Suppurative                                                               1 (2%)                                
      Ulcer                                                         1 (2%)                                                          
      Cervix, Endometrium, Hyperplasia                                                        1 (2%)                                
      Endometrium, Hyperplasia, Cystic                 4 (8%)       5 (10%)      3 (6%)       6 (12%)                               
      Endometrium, Inflammation, Chronic                                         1 (2%)                                             
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    4                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   0 MG/KG      28 MG/KG     84 MG/KG     252                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
GENITAL SYSTEM - CONT                                                                                                               
   Vagina                                                                       (2)          (2)                                    
      Hyperplasia                                                                1 (50%)                                            
      Infiltration Cellular, Polymorphonuclear                                                1 (50%)                               
      Epithelium, Vacuolization Cytoplasmic                                                   1 (50%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Fibrosis                                                      1 (2%)       1 (2%)                                             
   Lymph Node                                         (7)          (19)         (14)         (13)                                   
      Deep Cervical, Hemorrhage                                                               1 (8%)                                
      Deep Cervical, Hyperplasia, Lymphoid                          1 (5%)                    1 (8%)                                
      Deep Cervical, Infiltration Cellular,                                                                                         
          Histiocyte                                   1 (14%)                                                                      
      Mediastinal, Congestion                                                                 1 (8%)                                
      Mediastinal, Ectasia                                          2 (11%)      3 (21%)      1 (8%)                                
      Mediastinal, Hemorrhage                                       3 (16%)      2 (14%)      3 (23%)                               
      Mediastinal, Hyperplasia, Lymphoid               2 (29%)      3 (16%)      3 (21%)      6 (46%)                               
      Mediastinal, Infiltration Cellular, Mast Cell                                           1 (8%)                                
      Mediastinal, Infiltration Cellular, Plasma                                                                                    
          Cell                                         1 (14%)                                1 (8%)                                
      Mediastinal, Infiltration Cellular,                                                                                           
          Histiocyte                                   1 (14%)                   4 (29%)                                            
      Mediastinal, Necrosis, Lymphoid                               1 (5%)                                                          
      Pancreatic, Infiltration Cellular, Histiocyte                                           1 (8%)                                
      Pancreatic, Pigmentation, Hemosiderin                                                   1 (8%)                                
   Lymph Node, Mandibular                             (3)          (8)          (3)          (2)                                    
      Infiltration Cellular, Histiocyte                             1 (13%)                                                         
      Necrosis, Lymphoid                                            1 (13%)                                                         
   Lymph Node, Mesenteric                             (50)         (50)         (50)         (49)                                   
      Ectasia                                                                                 1 (2%)                                
      Hyperplasia, Lymphoid                                                      2 (4%)       2 (4%)                                
      Infiltration Cellular, Histiocyte                             3 (6%)      27 (54%)     42 (86%)                               
   Spleen                                             (50)         (50)         (50)         (50)                                   
      Hematopoietic Cell Proliferation                 6 (12%)      2 (4%)       4 (8%)       5 (10%)                               
      Hemorrhage                                                                 1 (2%)                                             
      Hyperplasia, Lymphohistiocytic                                1 (2%)       2 (4%)       4 (8%)                                
      Necrosis, Focal                                  1 (2%)                                                                       
      Lymphoid Follicle, Atrophy                      35 (70%)     32 (64%)     31 (62%)     28 (56%)                               
      Lymphoid Follicle, Hyperplasia                                                          1 (2%)                                
   Thymus                                             (45)         (41)         (46)         (41)                                   
      Epithelial Cell, Hyperplasia                     1 (2%)                                                                       
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    5                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   0 MG/KG      28 MG/KG     84 MG/KG     252                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      2 (4%)                                                                       
      Hyperplasia, Focal                               6 (12%)      3 (6%)       3 (6%)       2 (4%)                                
      Duct, Dilatation                                29 (58%)     15 (30%)     20 (40%)     23 (46%)                               
   Skin                                               (50)         (50)         (50)         (50)                                   
      Ulcer                                                                                   1 (2%)                                
      Subcutaneous Tissue, Pigmentation,                                                                                            
          Hemosiderin                                               1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
   Bone                                               (50)         (50)         (50)         (50)                                   
      Osteopetrosis                                                 1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Hydrocephalus                                    8 (16%)      6 (12%)      8 (16%)     10 (20%)                               
      Cerebrum, Degeneration, Focal                                              1 (2%)                                             
      Cerebrum, Gliosis, Focal                                                   1 (2%)                                             
      Cerebrum, Necrosis, Focal                        1 (2%)                                                                       
      Hypothalamus, Compression                        5 (10%)      3 (6%)       5 (10%)      8 (16%)                               
      Medulla, Compression                                          1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Lung                                               (50)         (50)         (50)         (50)                                   
      Congestion                                       5 (10%)      3 (6%)       1 (2%)                                             
      Hemorrhage                                       2 (4%)       1 (2%)       1 (2%)       4 (8%)                                
      Infiltration Cellular, Histiocyte                                          1 (2%)                                             
      Inflammation, Chronic Active, Focal                                        1 (2%)                                             
      Inflammation, Granulomatous, Multifocal          1 (2%)                                                                       
      Metaplasia, Osseous                              2 (4%)                    1 (2%)       1 (2%)                                
      Alveolar Epithelium, Hyperplasia                 1 (2%)                                                                       
      Alveolar Epithelium, Hyperplasia, Focal          3 (6%)       4 (8%)       5 (10%)      3 (6%)                                
      Alveolus, Emphysema, Focal                       1 (2%)                                                                       
      Alveolus, Inflammation, Acute                                 1 (2%)                    1 (2%)                                
      Alveolus, Inflammation, Chronic Active, Focal    2 (4%)      25 (50%)     27 (54%)     34 (68%)                               
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    6                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS FEMALE                   0 MG/KG      28 MG/KG     84 MG/KG     252                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
RESPIRATORY SYSTEM - CONT                                                                                                           
   Nose                                               (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic                            6 (12%)      3 (6%)       7 (14%)      5 (10%)                               
   Trachea                                            (50)         (50)         (50)         (50)                                   
      Hemorrhage                                                                 1 (2%)                                             
      Inflammation, Chronic                                         1 (2%)                                                          
      Peritracheal Tissue, Hemorrhage                               1 (2%)                                                          
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                             (3)          (1)          (3)                                    
      Cataract                                                      1 (33%)      1 (100%)     2 (67%)                               
      Degeneration                                                  2 (67%)                                                         
      Cornea, Fibrosis                                                                        1 (33%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Infarct                                          2 (4%)                                 1 (2%)                                
      Inflammation, Focal, Suppurative                              1 (2%)                                                          
      Nephropathy                                     16 (32%)     13 (26%)     11 (22%)     16 (32%)                               
      Pelvis, Inflammation, Suppurative                                          1 (2%)                                             
      Renal Tubule, Cyst                                            1 (2%)                                                          
      Renal Tubule, Necrosis                                                                  1 (2%)                                
      Renal Tubule, Pigmentation, Lipofuscin                                     1 (2%)                                             
   Urinary Bladder                                    (50)         (50)         (50)         (50)                                   
      Hemorrhage                                                                              1 (2%)                                
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page    7                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     0 MG/KG      14 MG/KG     42 MG/KG     126                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
DISPOSITION SUMMARY                                                                                                                 
                                                                                                                                    
  Animals Initially In Study                          50           50           50           50                                     
  Early Deaths                                                                                                                      
    Natural Death                                      7            9            8            5                                     
    Moribund Sacrifice                                15           10           17           12                                     
    Dosing Accident                                    2            2                         5                                     
  Survivors                                                                                                                         
    Terminal Sacrifice                                26           29           25           28                                     
                                                                                                                                    
  Animals Examined Microscopically                    50           50           50           50                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ALIMENTARY SYSTEM                                                                                                                  
                                                                                                                                    
   Esophagus                                          (50)         (50)         (50)         (50)                                   
      Muscularis, Periesophageal Tissue,                                                                                            
          Inflammation, Chronic                                     1 (2%)                                                          
      Periesophageal Tissue, Hemorrhage                1 (2%)                                 1 (2%)                                
   Intestine Large, Colon                             (50)         (50)         (50)         (50)                                   
      Parasite Metazoan                                4 (8%)       1 (2%)                    3 (6%)                                
   Intestine Large, Rectum                            (48)         (48)         (49)         (45)                                   
      Erosion                                                                    2 (4%)       2 (4%)                                
      Infiltration Cellular, Histiocyte                                                       4 (9%)                                
      Inflammation, Chronic                            1 (2%)                    1 (2%)       5 (11%)                               
      Myxomatous Change                                             1 (2%)       3 (6%)      25 (56%)                               
      Parasite Metazoan                                5 (10%)      8 (17%)      4 (8%)       3 (7%)                                
      Ulcer                                                                                   1 (2%)                                
   Intestine Small, Duodenum                          (50)         (50)         (50)         (50)                                   
      Epithelium, Cyst                                              1 (2%)                                                          
      Epithelium, Necrosis                                          1 (2%)                                                          
   Intestine Small, Jejunum                           (50)         (50)         (50)         (50)                                   
      Inflammation, Chronic, Focal                                               1 (2%)                                             
      Peyer's Patch, Hyperplasia                                    1 (2%)                                                          
   Intestine Small, Ileum                             (50)         (50)         (50)         (50)                                   
      Parasite Metazoan                                                          1 (2%)                                             
   Liver                                              (50)         (50)         (50)         (50)                                   
      Angiectasis                                                                             1 (2%)                                
      Basophilic Focus                                27 (54%)     27 (54%)     22 (44%)     19 (38%)                               
      Clear Cell Focus                                18 (36%)     22 (44%)     23 (46%)     16 (32%)                               
      Eosinophilic Focus                               9 (18%)     12 (24%)      5 (10%)      4 (8%)                                
      Fatty Change, Focal                                                        1 (2%)                                             
      Fibrosis, Focal                                               1 (2%)       1 (2%)       1 (2%)                                
      Hepatodiaphragmatic Nodule                       5 (10%)      5 (10%)      7 (14%)      9 (18%)                               
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    8                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     0 MG/KG      14 MG/KG     42 MG/KG     126                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
ALIMENTARY SYSTEM - CONT                                                                                                            
      Inflammation, Granulomatous                     30 (60%)     26 (52%)     32 (64%)     27 (54%)                               
      Mixed Cell Focus                                 8 (16%)     17 (34%)     13 (26%)     11 (22%)                               
      Necrosis, Focal                                  1 (2%)                                                                       
      Artery, Hyperplasia, Focal                                    1 (2%)                                                          
      Bile Duct, Hyperplasia                          44 (88%)     41 (82%)     32 (64%)     39 (78%)                               
      Centrilobular, Degeneration                      1 (2%)       1 (2%)       1 (2%)       1 (2%)                                
      Centrilobular, Fatty Change                                                1 (2%)       1 (2%)                                
      Centrilobular, Necrosis                          1 (2%)       1 (2%)       2 (4%)       3 (6%)                                
   Mesentery                                          (9)          (11)         (9)          (13)                                   
      Accessory Spleen                                                                        1 (8%)                                
      Hemorrhage                                                                              1 (8%)                                
      Fat, Inflammation, Granulomatous                                                        2 (15%)                               
      Fat, Necrosis                                    7 (78%)     10 (91%)      9 (100%)     8 (62%)                               
   Pancreas                                           (50)         (50)         (50)         (50)                                   
      Fibrosis                                                      1 (2%)                                                          
      Acinus, Atrophy                                 12 (24%)     14 (28%)     14 (28%)     16 (32%)                               
      Acinus, Hyperplasia, Focal                                    2 (4%)       1 (2%)                                             
      Duct, Necrosis                                                             1 (2%)                                             
   Salivary Glands                                    (50)         (50)         (49)         (50)                                   
      Duct, Parotid Gland, Sublingual Gland,                                                                                        
          Mineralization                                                         1 (2%)                                             
      Parotid Gland, Atrophy, Focal                    1 (2%)                    1 (2%)                                             
      Sublingual Gland, Atrophy, Focal                                           1 (2%)                                             
      Sublingual Gland, Hypertrophy, Focal             1 (2%)                                                                       
   Stomach, Forestomach                               (50)         (50)         (50)         (50)                                   
      Edema                                                         1 (2%)                                                          
      Hyperplasia, Focal, Squamous                                               2 (4%)       1 (2%)                                
      Inflammation, Acute                                           1 (2%)                                                          
      Inflammation, Chronic                                                      1 (2%)                                             
      Mineralization                                   1 (2%)                                                                       
      Ulcer                                            1 (2%)       2 (4%)       4 (8%)       1 (2%)                                
   Stomach, Glandular                                 (50)         (50)         (50)         (50)                                   
      Mineralization                                   2 (4%)                    1 (2%)       1 (2%)                                
      Ulcer                                            1 (2%)       3 (6%)       5 (10%)      2 (4%)                                
      Epithelium, Hyperplasia, Focal                   1 (2%)                    2 (4%)       1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 CARDIOVASCULAR SYSTEM                                                                                                              
                                                                                                                                    
   Blood Vessel                                       (50)         (50)         (50)         (50)                                   
      Aorta, Mineralization                            1 (2%)                                                                       
   Heart                                              (50)         (50)         (50)         (50)                                   
      Atrium, Inflammation, Chronic                                              1 (2%)                                             
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page    9                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     0 MG/KG      14 MG/KG     42 MG/KG     126                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
CARDIOVASCULAR SYSTEM - CONT                                                                                                        
      Atrium, Thrombosis                               2 (4%)       4 (8%)                    1 (2%)                                
      Myocardium, Degeneration                        41 (82%)     41 (82%)     42 (84%)     41 (82%)                               
      Myocardium, Necrosis, Focal                                   1 (2%)                                                          
      Vein, Thrombosis                                                                        1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 ENDOCRINE SYSTEM                                                                                                                   
                                                                                                                                    
   Adrenal Cortex                                     (50)         (50)         (50)         (50)                                   
      Hyperplasia                                                                             1 (2%)                                
      Hyperplasia, Diffuse                             1 (2%)                                                                       
      Hyperplasia, Focal                              14 (28%)     16 (32%)     17 (34%)     17 (34%)                               
      Necrosis, Acute                                                            1 (2%)                                             
      Necrosis, Focal                                               1 (2%)                                                          
   Adrenal Medulla                                    (50)         (50)         (50)         (50)                                   
      Fibrosis                                                                   3 (6%)                                             
      Hyperplasia, Diffuse                             2 (4%)                                                                       
      Hyperplasia, Focal                              10 (20%)     17 (34%)     12 (24%)     13 (26%)                               
      Necrosis, Acute                                  1 (2%)                                                                       
      Necrosis, Focal                                                            1 (2%)                                             
   Islets, Pancreatic                                 (50)         (50)         (50)         (50)                                   
      Hyperplasia                                      1 (2%)       1 (2%)       1 (2%)       2 (4%)                                
   Parathyroid Gland                                  (46)         (44)         (45)         (47)                                   
      Cyst, Multiple                                   1 (2%)                                                                       
   Pituitary Gland                                    (50)         (50)         (50)         (50)                                   
      Angiectasis                                                   1 (2%)                    1 (2%)                                
      Cyst                                             3 (6%)       3 (6%)       5 (10%)      2 (4%)                                
      Hyperplasia                                                                             2 (4%)                                
      Necrosis, Focal                                                                         1 (2%)                                
      Pars Distalis, Hyperplasia, Focal               12 (24%)     12 (24%)     17 (34%)      9 (18%)                               
   Thyroid Gland                                      (50)         (50)         (50)         (50)                                   
      C-Cell, Hyperplasia                             31 (62%)     36 (72%)     40 (80%)     35 (70%)                               
      Follicle, Cyst                                                             1 (2%)                                             
      Follicle, Hyperplasia                                                                   1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENERAL BODY SYSTEM                                                                                                                
                                                                                                                                    
   Peritoneum                                                                   (1)                                                 
      Inflammation, Chronic                                                      1 (100%)                                           
____________________________________________________________________________________________________________________________________
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                                                                                                    
                                                             Page   10                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     0 MG/KG      14 MG/KG     42 MG/KG     126                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 GENITAL SYSTEM                                                                                                                     
                                                                                                                                    
   Coagulating Gland                                  (1)                                    (1)                                    
      Inflammation, Chronic                                                                   1 (100%)                              
   Epididymis                                         (50)         (50)         (50)         (50)                                   
      Fibrosis                                                                                1 (2%)                                
      Granuloma Sperm                                  1 (2%)                    1 (2%)       1 (2%)                                
      Inflammation, Acute                                                                     1 (2%)                                
   Preputial Gland                                    (50)         (50)         (50)         (50)                                   
      Cyst                                                                       3 (6%)       2 (4%)                                
      Hyperplasia                                      1 (2%)       2 (4%)                                                          
      Inflammation, Chronic                           35 (70%)     44 (88%)     42 (84%)     37 (74%)                               
      Inflammation, Suppurative                        1 (2%)                    2 (4%)       1 (2%)                                
   Prostate, NOS                                      (50)         (50)         (50)         (49)                                   
      Hyperplasia                                      1 (2%)                                                                       
      Hyperplasia, Focal                                                         1 (2%)                                             
      Inflammation, Acute                              1 (2%)                                                                       
      Inflammation, Chronic Active                    18 (36%)     16 (32%)     19 (38%)     18 (37%)                               
   Seminal Vesicle                                    (50)         (50)         (50)         (49)                                   
      Atrophy                                          1 (2%)       1 (2%)                                                          
      Fibrosis                                                      1 (2%)       1 (2%)                                             
      Hyperplasia                                      4 (8%)                    2 (4%)       2 (4%)                                
   Testes                                             (50)         (50)         (50)         (50)                                   
      Cyst                                                                       2 (4%)                                             
      Artery, Necrosis                                                           1 (2%)                                             
      Germinal Epithelium, Atrophy                     3 (6%)       1 (2%)       1 (2%)       1 (2%)                                
      Interstitial Cell, Hyperplasia                   5 (10%)                   1 (2%)       2 (4%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 HEMATOPOIETIC SYSTEM                                                                                                               
                                                                                                                                    
   Bone Marrow                                        (50)         (50)         (50)         (50)                                   
      Fibrosis                                         2 (4%)       1 (2%)                    1 (2%)                                
      Infiltration Cellular, Lymphocyte                1 (2%)                                                                       
      Infiltration Cellular, Histiocyte                1 (2%)                                                                       
   Lymph Node                                         (11)         (17)         (10)         (13)                                   
      Deep Cervical, Angiectasis                                                              1 (8%)                                
      Deep Cervical, Hyperplasia, Lymphoid             1 (9%)                                                                       
      Mediastinal, Angiectasis                                                                1 (8%)                                
      Mediastinal, Ectasia                                          2 (12%)      2 (20%)      1 (8%)                                
      Mediastinal, Hemorrhage                          2 (18%)                                1 (8%)                                
      Mediastinal, Hyperplasia, Lymphoid               2 (18%)      7 (41%)      2 (20%)      1 (8%)                                
      Mediastinal, Hyperplasia, Plasma Cell                                                   1 (8%)                                
      Mediastinal, Infiltration Cellular,                                                                                           
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page   11                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     0 MG/KG      14 MG/KG     42 MG/KG     126                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
HEMATOPOIETIC SYSTEM - CONT                                                                                                         
          Histiocyte                                                             1 (10%)                                            
      Pancreatic, Ectasia                                           1 (6%)                                                          
      Pancreatic, Hemorrhage                                        1 (6%)                                                          
      Renal, Ectasia                                                             1 (10%)                                            
      Renal, Infiltration Cellular, Plasma Cell                                  1 (10%)                                            
   Lymph Node, Mandibular                             (5)          (5)          (9)          (2)                                    
      Ectasia                                                                    1 (11%)      1 (50%)                               
      Infiltration Cellular, Plasma Cell               1 (20%)                                                                      
   Lymph Node, Mesenteric                             (50)         (50)         (50)         (49)                                   
      Ectasia                                                       2 (4%)       2 (4%)                                             
      Fibrosis                                                      1 (2%)                                                          
      Hemorrhage                                                    1 (2%)       1 (2%)       1 (2%)                                
      Hyperplasia, Lymphoid                                         1 (2%)       1 (2%)       1 (2%)                                
      Infiltration Cellular, Histiocyte                1 (2%)       1 (2%)      18 (36%)     39 (80%)                               
      Inflammation, Granulomatous                                                             3 (6%)                                
      Necrosis, Lymphoid                                            1 (2%)                                                          
      Endothelial Cell, Hyperplasia                                 1 (2%)                                                          
   Spleen                                             (50)         (50)         (50)         (50)                                   
      Fibrosis, Focal                                               2 (4%)                    1 (2%)                                
      Hematopoietic Cell Proliferation                 2 (4%)       2 (4%)       3 (6%)       4 (8%)                                
      Hyperplasia, Lymphohistiocytic                   2 (4%)       2 (4%)       2 (4%)       8 (16%)                               
      Necrosis, Focal                                               1 (2%)                                                          
      Capsule, Fibrosis, Focal                         1 (2%)                                 1 (2%)                                
      Lymphoid Follicle, Atrophy                      20 (40%)     25 (50%)     29 (58%)     25 (50%)                               
      Lymphoid Follicle, Hyperplasia                   1 (2%)       1 (2%)       1 (2%)                                             
      Lymphoid Follicle, Necrosis                      1 (2%)                                                                       
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 INTEGUMENTARY SYSTEM                                                                                                               
                                                                                                                                    
   Mammary Gland                                      (49)         (49)         (50)         (48)                                   
      Hyperplasia                                     25 (51%)     37 (76%)     31 (62%)     17 (35%)                               
      Duct, Dilatation                                12 (24%)     24 (49%)     27 (54%)     15 (31%)                               
      Duct, Dilatation, Diffuse                                     1 (2%)                                                          
   Skin                                               (50)         (50)         (50)         (50)                                   
      Metaplasia, Osseous                                           1 (2%)                                                          
      Epidermis, Cyst, Squamous                        1 (2%)                                                                       
      Epidermis, Epidermis, Cyst                       1 (2%)                                                                       
      Sebaceous Gland, Hyperplasia, Focal                                                     1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 MUSCULOSKELETAL SYSTEM                                                                                                             
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page   12                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     0 MG/KG      14 MG/KG     42 MG/KG     126                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
MUSCULOSKELETAL SYSTEM - CONT                                                                                                       
   Bone                                               (50)         (50)         (50)         (50)                                   
      Cyst                                             2 (4%)                                                                       
      Femur, Hyperostosis                              1 (2%)                                                                       
   Skeletal Muscle                                                              (1)          (2)                                    
      Hemorrhage                                                                              1 (50%)                               
      Inflammation, Acute                                                                     1 (50%)                               
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 NERVOUS SYSTEM                                                                                                                     
                                                                                                                                    
   Brain                                              (50)         (50)         (50)         (50)                                   
      Hydrocephalus                                    8 (16%)      7 (14%)      9 (18%)      6 (12%)                               
      Cerebrum, Degeneration, Focal                                              1 (2%)                                             
      Hippocampus, Cerebrum, Degeneration                           1 (2%)                                                          
      Hypothalamus, Compression                        6 (12%)      2 (4%)       5 (10%)      4 (8%)                                
      Medulla, Degeneration, Focal                                               1 (2%)                                             
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 RESPIRATORY SYSTEM                                                                                                                 
                                                                                                                                    
   Larynx                                                                                    (1)                                    
      Hemorrhage                                                                              1 (100%)                              
   Lung                                               (50)         (50)         (50)         (50)                                   
      Emphysema, Focal                                              1 (2%)                                                          
      Hemorrhage                                       2 (4%)       1 (2%)       1 (2%)       4 (8%)                                
      Infiltration Cellular, Histiocyte                                                       1 (2%)                                
      Metaplasia, Osseous                                           3 (6%)                                                          
      Myxomatous Change                                                                       1 (2%)                                
      Thrombosis                                                    1 (2%)                                                          
      Alveolar Epithelium, Hyperplasia                 6 (12%)                                1 (2%)                                
      Alveolar Epithelium, Hyperplasia, Focal          3 (6%)       4 (8%)       3 (6%)       3 (6%)                                
      Alveolar Epithelium, Metaplasia, Squamous                                               2 (4%)                                
      Alveolus, Emphysema, Focal                                    1 (2%)                    1 (2%)                                
      Alveolus, Inflammation, Acute                    1 (2%)       1 (2%)                    2 (4%)                                
      Alveolus, Inflammation, Chronic Active, Focal                 6 (12%)     11 (22%)     14 (28%)                               
      Artery, Thrombosis                                                                      1 (2%)                                
      Interstitium, Fibrosis, Focal                                                           1 (2%)                                
      Interstitium, Alveolus, Inflammation                                                    1 (2%)                                
      Mediastinum, Inflammation, Chronic                            1 (2%)                                                          
   Nose                                               (50)         (50)         (50)         (50)                                   
      Foreign Body                                     1 (2%)                                                                       
      Inflammation, Chronic                            9 (18%)      7 (14%)      8 (16%)      9 (18%)                               
      Thrombosis                                                                              1 (2%)                                
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                             Page   13                                                              
                                                                                                                                   
NTP Experiment-Test: 88122-06         INCIDENCE RATES OF NONNEOPLASTIC LESIONS BY ANATOMIC SITE (a)               Report: PEIRPT03  
Study Type: CHRONIC                                              ELMIRON                                          Date: 09/26/01    
Route: GAVAGE                                                                                                     Time: 14:32:26    
____________________________________________________________________________________________________________________________________
                                                                                                                                    
         FISCHER 344 RATS MALE                     0 MG/KG      14 MG/KG     42 MG/KG     126                                       
                                                                                          MG/KG                                     
____________________________________________________________________________________________________________________________________
                                                                                                                                    
RESPIRATORY SYSTEM - CONT                                                                                                           
      Ulcer                                            2 (4%)       1 (2%)                                                          
   Trachea                                            (50)         (50)         (50)         (50)                                   
      Hemorrhage                                                                              1 (2%)                                
      Inflammation, Chronic                            1 (2%)                                 4 (8%)                                
      Ulcer                                                                                   1 (2%)                                
      Epithelium, Metaplasia, Squamous                 1 (2%)                                 1 (2%)                                
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 SPECIAL SENSES SYSTEM                                                                                                              
                                                                                                                                    
   Eye                                                             (1)                       (1)                                    
      Cataract                                                      1 (100%)                  1 (100%)                              
____________________________________________________________________________________________________________________________________
                                                                                                                                    
 URINARY SYSTEM                                                                                                                     
                                                                                                                                    
   Kidney                                             (50)         (50)         (50)         (50)                                   
      Glomerulosclerosis                                            1 (2%)                                                          
      Hemorrhage                                                                 1 (2%)                                             
      Hydronephrosis                                   2 (4%)                                                                       
      Infarct                                          2 (4%)                    2 (4%)                                             
      Nephropathy                                     40 (80%)     42 (84%)     41 (82%)     37 (74%)                               
      Artery, Thrombosis                               1 (2%)                                                                       
      Pelvis, Inflammation, Suppurative                                          1 (2%)                                             
      Renal Tubule, Necrosis, Focal                    2 (4%)       1 (2%)       2 (4%)                                             
      Renal Tubule, Pigmentation, Lipofuscin                        1 (2%)       3 (6%)                                             
      Vein, Inflammation, Chronic                      1 (2%)                                                                       
   Urethra                                                                                   (1)                                    
      Inflammation, Suppurative                                                               1 (100%)                              
   Urinary Bladder                                    (50)         (50)         (50)         (49)                                   
      Hemorrhage                                                    1 (2%)                                                          
      Inflammation, Acute                              1 (2%)                                                                       
      Mineralization                                   1 (2%)                                                                       
      Ulcer                                            2 (4%)                                                                       
                                                                                                                                    
                                                                                                                                    
a  Number of animals examined microscopically at site and number of animals with lesion                                             
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                             Page   14                                                              
                                                                                                                                   
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                             ----------              END OF REPORT             ----------                                           
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