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TDMS Study 88122-07 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                          ELMIRON                                        DATE: 04/23/01       
EXPERIMENT: 88122 TEST: 07                                                                                     TIME: 15:18:43       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: C88122       
PATHOLOGIST: GRUMBEIN, SONDRA                                                                                  CAS: 37319-17-8      
------------------------------------------------------------------------------------------------------------------------------------
                                                            final#1/Mice                                                            
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                          ELMIRON                                        DATE: 04/23/01       
EXPERIMENT: 88122 TEST: 07                                                                                     TIME: 15:18:43       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: C88122       
PATHOLOGIST: GRUMBEIN, SONDRA                                                                                  CAS: 37319-17-8      
Mice(B6C3F1)                                                                                                                        
-----------------------------                                                                                                       
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE                                                                   
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES                                                                 
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.                                                                                      
                                                 ---------------                                                                    
                                                 Adrenal Cortex                                                                     
                                                 Adrenal Medulla                                                                    
                                                 Bone Marrow                                                                        
                                                 Brain                                                                              
                                                 Clitoral/Preputial Gland                                                           
                                                 Heart                                                                              
                                                 Islets, Pancreatic                                                                 
                                                 Kidney                                                                             
                                                 Liver                                                                              
                                                 Lung                                                                               
                                                 Ovary                                                                              
                                                 Pituitary Gland                                                                    
                                                 Spleen                                                                             
                                                 Testes                                                                             
                                                 Thyroid Gland                                                                      
                                                 Urinary Bladder                                                                    
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Columbus                                          ELMIRON                                        DATE: 04/23/01       
EXPERIMENT: 88122 TEST: 07                                                                                     TIME: 15:18:43       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: C88122       
PATHOLOGIST: GRUMBEIN, SONDRA                                                                                  CAS: 37319-17-8      
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                     ELMIRON                                                                                      
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Liver                                  Hemangiosarcoma                                                                              
                                       Hepatocellular Carcinoma or Hepatocellular Adenoma                                           
                                       Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                          
Lung                                   Alveolar/Bronchiolar Adenoma                                                                 
                                       Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                               
All Organs                             Hemangiosarcoma                                                                              
                                       Hemangiosarcoma or Hemangioma                                                                
                                       Histiocytic Sarcoma                                                                          
                                       Malignant Tumors                                                                             
                                       Malignant and Benign Tumors                                                                  
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Liver                                  Hemangiosarcoma                                                                              
                                       Hepatocellular Adenoma                                                                       
                                       Hepatocellular Carcinoma or Hepatocellular Adenoma                                           
                                       Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                          
Ovary                                  Hemangioma                                                                                   
All Organs                             Hemangioma                                                                                   
                                       Hemangiosarcoma or Hemangioma                                                                
                                       Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type      
                                       Benign Tumors                                                                                
                                       Malignant Tumors                                                                             
                                       Malignant and Benign Tumors                                                                  
===============================================================                                                                     
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 1       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)        -                      ELMIRON                   
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    1/50 (2%)    0/49 (0%)   |0/49 (0%)    0/49 (0%)    0/49 (0%)    0/48 (0%)    | 
|POLY-3 RATE (b)    |     2/45.56      0/44.17      1/45.36      0/40.28     |0/44.48      0/44.24      0/44.13      0/43.60      | 
|POLY-3 PERCENT (g) |     4.4%         0.0%         2.2%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/39 (5%)    0/40 (0%)    1/38 (3%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     730 (T)      ---          730 (T)      ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.319N     P=0.233N     P=0.509N     P=0.298N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.281N     P=0.244N     P=0.502N     P=0.265N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.276N     P=0.245N     P=0.500N     P=0.259N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.291N     P=0.239N     P=0.504N     P=0.275N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.319N     (e)          P=0.509N     (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.270N     P=0.247N     P=0.500N     P=0.253N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    2/49 (4%)    1/50 (2%)   |0/50 (0%)    1/48 (2%)    0/50 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     2/46.04      0/44.17      2/45.38      1/40.88     |0/44.88      1/44.18      0/44.70      0/44.52      | 
|POLY-3 PERCENT (g) |     4.3%         0.0%         4.4%         2.5%        |0.0%         2.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/39 (3%)    0/40 (0%)    0/38 (0%)    1/30 (3%)   |0/37 (0%)    1/38 (3%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     590          ---          653          730 (T)     |---          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.653      P=0.249N     P=0.688      P=0.576N    |P=0.602N     P=0.505      (e)          (e)          | 
|POLY 3             |     P=0.618N     P=0.246N     P=0.689      P=0.541N    |P=0.582N     P=0.497      (e)          (e)          | 
|POLY 1.5           |     P=0.607N     P=0.247N     P=0.688      P=0.529N    |P=0.583N     P=0.495      (e)          (e)          | 
|POLY 6             |     P=0.637N     P=0.243N     P=0.690      P=0.559N    |P=0.580N     P=0.499      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.575N     P=0.217N     P=0.671      P=0.504N    |(e)          P=0.505      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.589N     P=0.247N     P=0.684      P=0.500N    |P=0.586N     P=0.490      (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 2       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   9/50 (18%)   5/50 (10%)   6/50 (12%)  |4/50 (8%)    3/50 (6%)    4/50 (8%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     6/45.99      9/44.35      5/45.36      6/42.08     |4/44.88      3/45.21      4/44.70      3/46.04      | 
|POLY-3 PERCENT (g) |     13.1%        20.3%        11.0%        14.3%       |8.9%         6.6%         9.0%         6.5%         | 
|TERMINAL (d)       |     5/39 (13%)   7/40 (18%)   5/38 (13%)   3/30 (10%)  |4/37 (11%)   3/38 (8%)    4/37 (11%)   2/34 (6%)    | 
|FIRST INCIDENCE    |     606          688          730 (T)      539         |729 (T)      729 (T)      729 (T)      401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.522      P=0.308      P=0.518N     P=0.465     |P=0.539N     P=0.485N     P=0.645      P=0.538N     | 
|POLY 3             |     P=0.480N     P=0.261      P=0.510N     P=0.557     |P=0.470N     P=0.496N     P=0.641      P=0.486N     | 
|POLY 1.5           |     P=0.462N     P=0.260      P=0.504N     P=0.573     |P=0.469N     P=0.500N     P=0.642N     P=0.487N     | 
|POLY 6             |     P=0.509N     P=0.273      P=0.519N     P=0.535     |P=0.477N     P=0.491N     P=0.635      P=0.490N     | 
|LOGISTIC REGRESSION|     P=0.487N     P=0.269      P=0.506N     P=0.600     |P=0.480N     P=0.485N     P=0.645      P=0.510N     | 
|COCH-ARM / FISHERS |     P=0.417N     P=0.288      P=0.500N     P=0.620N    |P=0.484N     P=0.500N     P=0.643N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    2/50 (4%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      1/45.36      2/41.37     |0/44.88      2/45.21      2/44.89      2/45.21      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         4.8%        |0.0%         4.4%         4.5%         4.4%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    1/30 (3%)   |0/37 (0%)    2/38 (5%)    1/37 (3%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      584         |---          729 (T)      677          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.058      (e)          P=0.495      P=0.200     |P=0.306      P=0.244      P=0.234      P=0.220      | 
|POLY 3             |     P=0.073      (e)          P=0.499      P=0.216     |P=0.342      P=0.239      P=0.237      P=0.239      | 
|POLY 1.5           |     P=0.077      (e)          P=0.500      P=0.222     |P=0.345      P=0.237      P=0.238      P=0.240      | 
|POLY 6             |     P=0.068      (e)          P=0.498      P=0.209     |P=0.336      P=0.241      P=0.235      P=0.236      | 
|LOGISTIC REGRESSION|     P=0.084      (e)          P=0.495      P=0.247     |P=0.334      P=0.244      P=0.238      P=0.220      | 
|COCH-ARM / FISHERS |     P=0.085      (e)          P=0.500      P=0.247     |P=0.339      P=0.247      P=0.247      P=0.247      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 3       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   9/50 (18%)   6/50 (12%)   8/50 (16%)  |4/50 (8%)    5/50 (10%)   6/50 (12%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     6/45.99      9/44.35      6/45.36      8/42.57     |4/44.88      5/45.21      6/44.89      5/46.04      | 
|POLY-3 PERCENT (g) |     13.1%        20.3%        13.2%        18.8%       |8.9%         11.1%        13.4%        10.9%        | 
|TERMINAL (d)       |     5/39 (13%)   7/40 (18%)   6/38 (16%)   4/30 (13%)  |4/37 (11%)   5/38 (13%)   5/37 (14%)   4/34 (12%)   | 
|FIRST INCIDENCE    |     606          688          730 (T)      539         |729 (T)      729 (T)      677          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.253      P=0.308      P=0.603      P=0.245     |P=0.434      P=0.517      P=0.366      P=0.454      | 
|POLY 3             |     P=0.398      P=0.261      P=0.611      P=0.327     |P=0.520      P=0.505      P=0.369      P=0.516      | 
|POLY 1.5           |     P=0.414      P=0.260      P=0.616      P=0.341     |P=0.521      P=0.500      P=0.373      P=0.515      | 
|POLY 6             |     P=0.372      P=0.273      P=0.603      P=0.309     |P=0.510      P=0.511      P=0.364      P=0.511      | 
|LOGISTIC REGRESSION|     P=0.394      P=0.269      P=0.615      P=0.372     |P=0.505      P=0.517      P=0.352      P=0.498      | 
|COCH-ARM / FISHERS |     P=0.460      P=0.288      P=0.620N     P=0.387     |P=0.500      P=0.500      P=0.370      P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Duodenum                                                                                                        | 
|     Polyp Adenomatous                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/45.36      1/40.88     |0/44.88      2/45.21      0/44.70      1/45.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         2.5%        |0.0%         4.4%         0.0%         2.2%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    1/30 (3%)   |0/37 (0%)    2/38 (5%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          730 (T)     |---          729 (T)      ---          701          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.172      (e)          (e)          P=0.448     |P=0.594      P=0.244      (e)          P=0.495      | 
|POLY 3             |     P=0.201      (e)          (e)          P=0.478     |P=0.618      P=0.239      (e)          P=0.502      | 
|POLY 1.5           |     P=0.206      (e)          (e)          P=0.485     |P=0.618      P=0.237      (e)          P=0.503      | 
|POLY 6             |     P=0.194      (e)          (e)          P=0.470     |P=0.616      P=0.241      (e)          P=0.500      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.448     |P=0.612      P=0.244      (e)          P=0.501      | 
|COCH-ARM / FISHERS |     P=0.215      (e)          (e)          P=0.500     |P=0.615      P=0.247      (e)          P=0.500      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 4       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Jejunum                                                                                                         | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     4/46.04      1/44.17      0/45.36      0/40.88     |1/44.88      0/45.21      0/44.70      0/45.21      | 
|POLY-3 PERCENT (g) |     8.7%         2.3%         0.0%         0.0%        |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     3/39 (8%)    1/40 (3%)    0/38 (0%)    0/30 (0%)   |1/37 (3%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     590          730 (T)      ---          ---         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.074N     P=0.182N     P=0.068N     P=0.098N    |P=0.486N     P=0.495N     P=0.500N     P=0.517N     | 
|POLY 3             |     P=0.056N     P=0.191N     P=0.062N     P=0.077N    |P=0.472N     P=0.499N     P=0.501N     P=0.499N     | 
|POLY 1.5           |     P=0.054N     P=0.192N     P=0.061N     P=0.072N    |P=0.472N     P=0.500N     P=0.499N     P=0.498N     | 
|POLY 6             |     P=0.058N     P=0.187N     P=0.064N     P=0.085N    |P=0.473N     P=0.497N     P=0.503N     P=0.501N     | 
|LOGISTIC REGRESSION|     P=0.058N     P=0.185N     P=0.063N     P=0.067N    |P=0.486N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.056N     P=0.181N     P=0.059N     P=0.059N    |P=0.471N     P=0.500N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Site Unspecified                                                                                                | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    1/50 (2%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     4/46.04      1/44.17      1/45.36      0/40.88     |1/44.88      0/45.21      0/44.70      0/45.21      | 
|POLY-3 PERCENT (g) |     8.7%         2.3%         2.2%         0.0%        |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     3/39 (8%)    1/40 (3%)    1/38 (3%)    0/30 (0%)   |1/37 (3%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     590          730 (T)      730 (T)      ---         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.094N     P=0.182N     P=0.189N     P=0.098N    |P=0.486N     P=0.495N     P=0.500N     P=0.517N     | 
|POLY 3             |     P=0.074N     P=0.191N     P=0.183N     P=0.077N    |P=0.472N     P=0.499N     P=0.501N     P=0.499N     | 
|POLY 1.5           |     P=0.071N     P=0.192N     P=0.181N     P=0.072N    |P=0.472N     P=0.500N     P=0.499N     P=0.498N     | 
|POLY 6             |     P=0.080N     P=0.187N     P=0.187N     P=0.085N    |P=0.473N     P=0.497N     P=0.503N     P=0.501N     | 
|LOGISTIC REGRESSION|     P=0.074N     P=0.185N     P=0.179N     P=0.067N    |P=0.486N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.069N     P=0.181N     P=0.181N     P=0.059N    |P=0.471N     P=0.500N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 5       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Site Unspecified                                                                                                | 
|     Polyp Adenomatous                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/45.56      1/44.17      0/45.36      1/40.88     |0/44.88      2/45.21      0/44.70      1/45.32      | 
|POLY-3 PERCENT (g) |     0.0%         2.3%         0.0%         2.5%        |0.0%         4.4%         0.0%         2.2%         | 
|TERMINAL (d)       |     0/39 (0%)    1/40 (3%)    0/38 (0%)    1/30 (3%)   |0/37 (0%)    2/38 (5%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          730 (T)      ---          730 (T)     |---          729 (T)      ---          701          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.395      P=0.505      (e)          P=0.448     |P=0.594      P=0.244      (e)          P=0.495      | 
|POLY 3             |     P=0.432      P=0.494      (e)          P=0.478     |P=0.618      P=0.239      (e)          P=0.502      | 
|POLY 1.5           |     P=0.440      P=0.493      (e)          P=0.485     |P=0.618      P=0.237      (e)          P=0.503      | 
|POLY 6             |     P=0.422      P=0.498      (e)          P=0.470     |P=0.616      P=0.241      (e)          P=0.500      | 
|LOGISTIC REGRESSION|     (e)          P=0.505      (e)          P=0.448     |P=0.612      P=0.244      (e)          P=0.501      | 
|COCH-ARM / FISHERS |     P=0.459      P=0.500      (e)          P=0.500     |P=0.615      P=0.247      (e)          P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/49 (4%)    0/50 (0%)   |0/46 (0%)    0/45 (0%)    0/45 (0%)    0/46 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      2/45.14      0/40.88     |0/42.79      0/42.20      0/40.94      0/41.88      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.4%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    0/30 (0%)   |0/37 (0%)    0/37 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          653          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.732      (e)          P=0.237      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.722      (e)          P=0.235      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.715N     (e)          P=0.234      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.697      (e)          P=0.236      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.699N     (e)          P=0.231      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.694N     (e)          P=0.242      (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 6       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    4/50 (8%)    9/50 (18%)  |1/50 (2%)    1/49 (2%)    1/50 (2%)    4/49 (8%)    | 
|POLY-3 RATE (b)    |     2/45.87      0/44.17      4/45.36      9/42.54     |1/44.88      1/44.91      1/44.70      4/44.72      | 
|POLY-3 PERCENT (g) |     4.4%         0.0%         8.8%         21.2%       |2.2%         2.2%         2.2%         8.9%         | 
|TERMINAL (d)       |     1/39 (3%)    0/40 (0%)    4/38 (11%)   5/30 (17%)  |1/37 (3%)    1/38 (3%)    1/37 (3%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     646          ---          730 (T)      539         |729 (T)      729 (T)      729 (T)      645          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.237N     P=0.327      P=0.014 *   |P=0.049 *    P=0.756N     P=0.762      P=0.170      | 
|POLY 3             |     P<0.001 **   P=0.246N     P=0.332      P=0.017 *   |P=0.056      P=0.760N     P=0.760      P=0.177      | 
|POLY 1.5           |     P<0.001 **   P=0.246N     P=0.335      P=0.019 *   |P=0.057      P=0.758      P=0.760N     P=0.178      | 
|POLY 6             |     P<0.001 **   P=0.242N     P=0.326      P=0.015 *   |P=0.055      P=0.757N     P=0.757      P=0.176      | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.235N     P=0.334      P=0.026 *   |P=0.056      P=0.756N     P=0.762      P=0.175      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.247N     P=0.339      P=0.026 *   |P=0.056      P=0.747      P=0.753N     P=0.175      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Adenoma                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     19/50 (38%)  15/50 (30%)  15/50 (30%)  20/50 (40%) |7/50 (14%)   5/49 (10%)   4/50 (8%)    15/49 (31%)  | 
|POLY-3 RATE (b)    |     19/47.46     15/44.93     15/46.67     20/43.05    |7/45.48      5/44.91      4/45.00      15/45.68     | 
|POLY-3 PERCENT (g) |     40.0%        33.4%        32.1%        46.5%       |15.4%        11.1%        8.9%         32.8%        | 
|TERMINAL (d)       |     15/39 (39%)  14/40 (35%)  12/38 (32%)  15/30 (50%) |6/37 (16%)   5/38 (13%)   3/37 (8%)    11/34 (32%)  | 
|FIRST INCIDENCE    |     420          455          592          483         |536          729 (T)      647          517          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.064      P=0.251N     P=0.303N     P=0.191     |P=0.002 **   P=0.362N     P=0.266N     P=0.035 *    | 
|POLY 3             |     P=0.195      P=0.328N     P=0.280N     P=0.342     |P=0.003 **   P=0.388N     P=0.267N     P=0.042 *    | 
|POLY 1.5           |     P=0.223      P=0.321N     P=0.273N     P=0.383     |P=0.003 **   P=0.394N     P=0.262N     P=0.042 *    | 
|POLY 6             |     P=0.157      P=0.319N     P=0.288N     P=0.290     |P=0.003 **   P=0.382N     P=0.274N     P=0.041 *    | 
|LOGISTIC REGRESSION|     P=0.223      P=0.289N     P=0.263N     P=0.409     |P=0.003 **   P=0.384N     P=0.261N     P=0.041 *    | 
|COCH-ARM / FISHERS |     P=0.293      P=0.263N     P=0.263N     P=0.500     |P=0.003 **   P=0.394N     P=0.262N     P=0.040 *    | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 7       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/50 (22%)  13/50 (26%)  15/50 (30%)  13/50 (26%) |3/50 (6%)    3/49 (6%)    5/50 (10%)   3/49 (6%)    | 
|POLY-3 RATE (b)    |     11/46.87     13/45.09     15/48.23     13/45.10    |3/45.05      3/44.94      5/44.70      3/44.70      | 
|POLY-3 PERCENT (g) |     23.5%        28.8%        31.1%        28.8%       |6.7%         6.7%         11.2%        6.7%         | 
|TERMINAL (d)       |     8/39 (21%)   10/40 (25%)  7/38 (18%)   4/30 (13%)  |2/37 (5%)    2/38 (5%)    5/37 (14%)   0/34 (0%)    | 
|FIRST INCIDENCE    |     590          508          548          483         |685          722          729 (T)      660          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.223      P=0.424      P=0.251      P=0.245     |P=0.562      P=0.649N     P=0.352      P=0.638      | 
|POLY 3             |     P=0.407      P=0.365      P=0.273      P=0.365     |P=0.583N     P=0.661      P=0.352      P=0.659      | 
|POLY 1.5           |     P=0.411      P=0.365      P=0.263      P=0.367     |P=0.579N     P=0.656      P=0.357      P=0.659      | 
|POLY 6             |     P=0.390      P=0.379      P=0.286      P=0.356     |P=0.590N     P=0.658N     P=0.343      P=0.656      | 
|LOGISTIC REGRESSION|     P=0.482      P=0.385      P=0.243      P=0.481     |P=0.593N     P=0.660N     P=0.341      P=0.657      | 
|COCH-ARM / FISHERS |     P=0.445      P=0.408      P=0.247      P=0.408     |P=0.587N     P=0.651      P=0.357      P=0.651      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     12/50 (24%)  14/50 (28%)  15/50 (30%)  13/50 (26%) |3/50 (6%)    3/49 (6%)    5/50 (10%)   3/49 (6%)    | 
|POLY-3 RATE (b)    |     12/46.87     14/45.99     15/48.23     13/45.10    |3/45.05      3/44.94      5/44.70      3/44.70      | 
|POLY-3 PERCENT (g) |     25.6%        30.4%        31.1%        28.8%       |6.7%         6.7%         11.2%        6.7%         | 
|TERMINAL (d)       |     9/39 (23%)   10/40 (25%)  7/38 (18%)   4/30 (13%)  |2/37 (5%)    2/38 (5%)    5/37 (14%)   0/34 (0%)    | 
|FIRST INCIDENCE    |     590          346          548          483         |685          722          729 (T)      660          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.299      P=0.426      P=0.323      P=0.310     |P=0.562      P=0.649N     P=0.352      P=0.638      | 
|POLY 3             |     P=0.498      P=0.387      P=0.357      P=0.455     |P=0.583N     P=0.661      P=0.352      P=0.659      | 
|POLY 1.5           |     P=0.504      P=0.381      P=0.345      P=0.458     |P=0.579N     P=0.656      P=0.357      P=0.659      | 
|POLY 6             |     P=0.478      P=0.405      P=0.373      P=0.446     |P=0.590N     P=0.658N     P=0.343      P=0.656      | 
|LOGISTIC REGRESSION|     P=0.505N     P=0.412      P=0.323      P=0.569     |P=0.593N     P=0.660N     P=0.341      P=0.657      | 
|COCH-ARM / FISHERS |     P=0.545      P=0.410      P=0.326      P=0.500     |P=0.587N     P=0.651      P=0.357      P=0.651      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 8       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     23/50 (46%)  23/50 (46%)  26/50 (52%)  31/50 (62%) |10/50 (20%)  8/49 (16%)   9/50 (18%)   18/49 (37%)  | 
|POLY-3 RATE (b)    |     23/47.93     23/45.85     26/49.07     31/46.55    |10/45.65     8/44.94      9/45.00      18/46.09     | 
|POLY-3 PERCENT (g) |     48.0%        50.2%        53.0%        66.6%       |21.9%        17.8%        20.0%        39.1%        | 
|TERMINAL (d)       |     18/39 (46%)  19/40 (48%)  16/38 (42%)  18/30 (60%) |8/37 (22%)   7/38 (18%)   8/37 (22%)   11/34 (32%)  | 
|FIRST INCIDENCE    |     420          455          548          483         |536          722          647          517          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.004 **   P=0.548N     P=0.333      P=0.016 *   |P=0.006 **   P=0.377N     P=0.506N     P=0.051      | 
|POLY 3             |     P=0.031 *    P=0.498      P=0.386      P=0.049 *   |P=0.010 *    P=0.411N     P=0.514N     P=0.057      | 
|POLY 1.5           |     P=0.030 *    P=0.502      P=0.367      P=0.049 *   |P=0.010 *    P=0.417N     P=0.503N     P=0.056      | 
|POLY 6             |     P=0.030 *    P=0.517      P=0.417      P=0.050     |P=0.010 *    P=0.406N     P=0.531N     P=0.058      | 
|LOGISTIC REGRESSION|     P=0.036 *    P=0.544      P=0.346      P=0.068     |P=0.009 **   P=0.400N     P=0.503N     P=0.054      | 
|COCH-ARM / FISHERS |     P=0.043 *    P=0.579N     P=0.345      P=0.080     |P=0.009 **   P=0.416N     P=0.500N     P=0.052      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma, Hepatocellular Adenoma,                                                                           | 
|     or Hepatoblastoma                                                                                                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     24/50 (48%)  24/50 (48%)  26/50 (52%)  31/50 (62%) |10/50 (20%)  8/49 (16%)   9/50 (18%)   18/49 (37%)  | 
|POLY-3 RATE (b)    |     24/47.93     24/46.74     26/49.07     31/46.55    |10/45.65     8/44.94      9/45.00      18/46.09     | 
|POLY-3 PERCENT (g) |     50.1%        51.3%        53.0%        66.6%       |21.9%        17.8%        20.0%        39.1%        | 
|TERMINAL (d)       |     19/39 (49%)  19/40 (48%)  16/38 (42%)  18/30 (60%) |8/37 (22%)   7/38 (18%)   8/37 (22%)   11/34 (32%)  | 
|FIRST INCIDENCE    |     420          346          548          483         |536          722          647          517          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.007 **   P=0.548N     P=0.397      P=0.022 *   |P=0.006 **   P=0.377N     P=0.506N     P=0.051      | 
|POLY 3             |     P=0.047 *    P=0.533      P=0.467      P=0.074     |P=0.010 *    P=0.411N     P=0.514N     P=0.057      | 
|POLY 1.5           |     P=0.047 *    P=0.527      P=0.445      P=0.074     |P=0.010 *    P=0.417N     P=0.503N     P=0.056      | 
|POLY 6             |     P=0.046 *    P=0.557      P=0.500      P=0.075     |P=0.010 *    P=0.406N     P=0.531N     P=0.058      | 
|LOGISTIC REGRESSION|     P=0.063      P=0.566      P=0.423      P=0.095     |P=0.009 **   P=0.400N     P=0.503N     P=0.054      | 
|COCH-ARM / FISHERS |     P=0.068      P=0.579N     P=0.421      P=0.114     |P=0.009 **   P=0.416N     P=0.500N     P=0.052      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 9       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Adenoma                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  3/50 (6%)    8/50 (16%)   5/50 (10%)  |2/50 (4%)    3/50 (6%)    2/50 (4%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     10/46.26     3/44.17      8/45.86      5/42.08     |2/44.88      3/45.80      2/44.70      1/45.21      | 
|POLY-3 PERCENT (g) |     21.6%        6.8%         17.5%        11.9%       |4.5%         6.6%         4.5%         2.2%         | 
|TERMINAL (d)       |     8/39 (21%)   3/40 (8%)    7/38 (18%)   1/30 (3%)   |2/37 (5%)    2/38 (5%)    2/37 (5%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     599          730 (T)      581          631         |729 (T)      541          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.472N     P=0.036N*    P=0.423N     P=0.264N    |P=0.334N     P=0.512      P=0.695      P=0.530N     | 
|POLY 3             |     P=0.331N     P=0.042N*    P=0.405N     P=0.175N    |P=0.303N     P=0.509      P=0.692      P=0.497N     | 
|POLY 1.5           |     P=0.315N     P=0.042N*    P=0.400N     P=0.163N    |P=0.300N     P=0.503      P=0.693N     P=0.496N     | 
|POLY 6             |     P=0.359N     P=0.040N*    P=0.414N     P=0.192N    |P=0.308N     P=0.516      P=0.688      P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.326N     P=0.041N*    P=0.399N     P=0.151N    |P=0.300N     P=0.500      P=0.695      P=0.530N     | 
|COCH-ARM / FISHERS |     P=0.284N     P=0.036N*    P=0.398N     P=0.131N    |P=0.303N     P=0.500      P=0.691N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   3/50 (6%)    5/50 (10%)   4/50 (8%)   |1/50 (2%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     5/45.99      3/44.17      5/45.75      4/41.32     |1/44.88      1/45.24      1/45.41      1/45.21      | 
|POLY-3 PERCENT (g) |     10.9%        6.8%         10.9%        9.7%        |2.2%         2.2%         2.2%         2.2%         | 
|TERMINAL (d)       |     4/39 (10%)   3/40 (8%)    4/38 (11%)   2/30 (7%)   |1/37 (3%)    0/38 (0%)    0/37 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     606          730 (T)      620          668         |729 (T)      722          481          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.459      P=0.350N     P=0.613      P=0.629     |P=0.650      P=0.754N     P=0.756N     P=0.743      | 
|POLY 3             |     P=0.559      P=0.379N     P=0.627      P=0.567N    |P=0.666N     P=0.759N     P=0.758N     P=0.759N     | 
|POLY 1.5           |     P=0.580      P=0.379N     P=0.629      P=0.548N    |P=0.664N     P=0.760      P=0.758N     P=0.758N     | 
|POLY 6             |     P=0.526      P=0.370N     P=0.623      P=0.592N    |P=0.663      P=0.757N     P=0.760N     P=0.760      | 
|LOGISTIC REGRESSION|     P=0.569      P=0.371N     P=0.630      P=0.551N    |P=0.657      P=0.757N     P=0.742      P=0.743      | 
|COCH-ARM / FISHERS |     P=0.551N     P=0.357N     P=0.630N     P=0.500N    |P=0.668N     P=0.753N     P=0.753N     P=0.753N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 10      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar                                                                      | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/50 (28%)  5/50 (10%)   13/50 (26%)  9/50 (18%)  |3/50 (6%)    4/50 (8%)    3/50 (6%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     14/46.69     5/44.17      13/46.25     9/42.52     |3/44.88      4/45.83      3/45.41      2/45.21      | 
|POLY-3 PERCENT (g) |     30.0%        11.3%        28.1%        21.2%       |6.7%         8.7%         6.6%         4.4%         | 
|TERMINAL (d)       |     11/39 (28%)  5/40 (13%)   11/38 (29%)  3/30 (10%)  |3/37 (8%)    2/38 (5%)    2/37 (5%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     599          730 (T)      581          631         |729 (T)      541          481          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.459      P=0.021N*    P=0.531N     P=0.375N    |P=0.374N     P=0.514      P=0.659N     P=0.539N     | 
|POLY 3             |     P=0.466N     P=0.025N*    P=0.512N     P=0.239N    |P=0.335N     P=0.511      P=0.657N     P=0.497N     | 
|POLY 1.5           |     P=0.444N     P=0.024N*    P=0.504N     P=0.221N    |P=0.331N     P=0.504      P=0.656N     P=0.495N     | 
|POLY 6             |     P=0.500N     P=0.024N*    P=0.525N     P=0.262N    |P=0.344N     P=0.520      P=0.660N     P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.465N     P=0.024N*    P=0.501N     P=0.209N    |P=0.335N     P=0.499      P=0.662      P=0.539N     | 
|COCH-ARM / FISHERS |     P=0.396N     P=0.020N*    P=0.500N     P=0.171N    |P=0.335N     P=0.500      P=0.661N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cystadenoma                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/47 (2%)    1/46 (2%)    2/47 (4%)    0/48 (0%)    | 
|POLY-3 RATE (b)    |                                                        |1/42.21      1/41.53      2/42.26      0/43.54      | 
|POLY-3 PERCENT (g) |                                                        |2.4%         2.4%         4.7%         0.0%         | 
|TERMINAL (d)       |                                                        |1/36 (3%)    1/35 (3%)    1/36 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      729 (T)      653          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.343N     P=0.756      P=0.494      P=0.511N     | 
|POLY 3             |                                                        |P=0.322N     P=0.757      P=0.500      P=0.494N     | 
|POLY 1.5           |                                                        |P=0.320N     P=0.755      P=0.502      P=0.493N     | 
|POLY 6             |                                                        |P=0.327N     P=0.759      P=0.497      P=0.496N     | 
|LOGISTIC REGRESSION|                                                        |P=0.322N     P=0.756      P=0.500      (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.324N     P=0.747      P=0.500      P=0.495N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 11      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Hemangioma                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |0/47 (0%)    0/46 (0%)    0/47 (0%)    2/48 (4%)    | 
|POLY-3 RATE (b)    |                                                        |0/42.21      0/41.53      0/41.98      2/43.54      | 
|POLY-3 PERCENT (g) |                                                        |0.0%         0.0%         0.0%         4.6%         | 
|TERMINAL (d)       |                                                        |0/36 (0%)    0/35 (0%)    0/36 (0%)    2/34 (6%)    | 
|FIRST INCIDENCE    |                                                        |---          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.038 *    (e)          (e)          P=0.226      | 
|POLY 3             |                                                        |P=0.044 *    (e)          (e)          P=0.244      | 
|POLY 1.5           |                                                        |P=0.044 *    (e)          (e)          P=0.245      | 
|POLY 6             |                                                        |P=0.043 *    (e)          (e)          P=0.241      | 
|LOGISTIC REGRESSION|                                                        |(e)          (e)          (e)          P=0.226      | 
|COCH-ARM / FISHERS |                                                        |P=0.044 *    (e)          (e)          P=0.253      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/47 (0%)    0/48 (0%)    0/49 (0%)    0/48 (0%)   |2/48 (4%)    3/47 (6%)    4/45 (9%)    2/48 (4%)    | 
|POLY-3 RATE (b)    |     0/43.37      0/42.17      0/44.36      0/39.13     |2/43.21      3/42.52      4/41.03      2/43.72      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.6%         7.1%         9.8%         4.6%         | 
|TERMINAL (d)       |     0/37 (0%)    0/38 (0%)    0/37 (0%)    0/30 (0%)   |2/36 (6%)    2/37 (5%)    4/36 (11%)   1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      703          729 (T)      683          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.544N     P=0.514      P=0.336      P=0.678      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.497N     P=0.493      P=0.313      P=0.690N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.494N     P=0.489      P=0.313      P=0.689N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.504N     P=0.497      P=0.311      P=0.693N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.510N     P=0.496      P=0.336      P=0.695N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.503N     P=0.490      P=0.308      P=0.692N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 12      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma,                                                                        | 
|     or Fibrous Histiocytoma                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |3/50 (6%)    4/50 (8%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/45.36      1/40.88     |3/45.18      4/46.06      2/44.74      2/45.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         2.5%        |6.6%         8.7%         4.5%         4.4%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    1/30 (3%)   |1/37 (3%)    1/38 (3%)    1/37 (3%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          730 (T)     |661          555          717          701          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.172      (e)          (e)          P=0.448     |P=0.370N     P=0.515      P=0.511N     P=0.527N     | 
|POLY 3             |     P=0.201      (e)          (e)          P=0.478     |P=0.338N     P=0.510      P=0.504N     P=0.499N     | 
|POLY 1.5           |     P=0.206      (e)          (e)          P=0.485     |P=0.334N     P=0.503      P=0.500N     P=0.496N     | 
|POLY 6             |     P=0.194      (e)          (e)          P=0.470     |P=0.346N     P=0.519      P=0.512N     P=0.506N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.448     |P=0.335N     P=0.501      P=0.501N     P=0.497N     | 
|COCH-ARM / FISHERS |     P=0.215      (e)          (e)          P=0.500     |P=0.337N     P=0.500      P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |3/50 (6%)    4/50 (8%)    2/50 (4%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/45.36      1/40.88     |3/45.18      4/46.06      2/44.74      1/45.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         2.5%        |6.6%         8.7%         4.5%         2.2%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    1/30 (3%)   |1/37 (3%)    1/38 (3%)    1/37 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          730 (T)     |661          555          717          701          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.172      (e)          (e)          P=0.448     |P=0.188N     P=0.515      P=0.511N     P=0.327N     | 
|POLY 3             |     P=0.201      (e)          (e)          P=0.478     |P=0.165N     P=0.510      P=0.504N     P=0.304N     | 
|POLY 1.5           |     P=0.206      (e)          (e)          P=0.485     |P=0.163N     P=0.503      P=0.500N     P=0.302N     | 
|POLY 6             |     P=0.194      (e)          (e)          P=0.470     |P=0.171N     P=0.519      P=0.512N     P=0.309N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.448     |P=0.165N     P=0.501      P=0.501N     P=0.303N     | 
|COCH-ARM / FISHERS |     P=0.215      (e)          (e)          P=0.500     |P=0.165N     P=0.500      P=0.500N     P=0.309N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 13      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Sarcoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |3/50 (6%)    4/50 (8%)    2/50 (4%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/45.36      0/40.88     |3/45.18      4/46.06      2/44.74      1/45.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |6.6%         8.7%         4.5%         2.2%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |1/37 (3%)    1/38 (3%)    1/37 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |661          555          717          701          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.188N     P=0.515      P=0.511N     P=0.327N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.165N     P=0.510      P=0.504N     P=0.304N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.163N     P=0.503      P=0.500N     P=0.302N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.171N     P=0.519      P=0.512N     P=0.309N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.165N     P=0.501      P=0.501N     P=0.303N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.165N     P=0.500      P=0.500N     P=0.309N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    1/49 (2%)    2/49 (4%)   |0/47 (0%)    1/48 (2%)    0/47 (0%)    0/46 (0%)    | 
|POLY-3 RATE (b)    |     0/44.72      0/44.17      1/44.81      2/40.75     |0/43.70      1/43.55      0/42.46      0/41.88      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         4.9%        |0.0%         2.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    1/30 (3%)   |0/37 (0%)    1/38 (3%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      539         |---          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.060      (e)          P=0.495      P=0.204     |P=0.602N     P=0.505      (e)          (e)          | 
|POLY 3             |     P=0.073      (e)          P=0.500      P=0.217     |P=0.594N     P=0.499      (e)          (e)          | 
|POLY 1.5           |     P=0.076      (e)          P=0.501      P=0.222     |P=0.594N     P=0.499      (e)          (e)          | 
|POLY 6             |     P=0.067      (e)          P=0.500      P=0.210     |P=0.594N     P=0.500      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.089      (e)          P=0.495      P=0.260     |(e)          P=0.505      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.083      (e)          P=0.500      P=0.247     |P=0.591N     P=0.505      (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 14      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      1/45.10      2/45.75      0/40.88     |0/44.88      0/45.21      0/44.70      0/45.21      | 
|POLY-3 PERCENT (g) |     0.0%         2.2%         4.4%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          311          620          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.554N     P=0.496      P=0.234      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.558N     P=0.498      P=0.238      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.545N     P=0.496      P=0.238      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.577N     P=0.503      P=0.238      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.417N     P=0.798      P=0.234      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.517N     P=0.500      P=0.247      (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      2/45.75      0/40.88     |0/44.88      0/45.21      0/44.70      0/45.21      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.4%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          620          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.736      (e)          P=0.234      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.722      (e)          P=0.238      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.716N     (e)          P=0.238      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.698      (e)          P=0.238      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.689N     (e)          P=0.234      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.695N     (e)          P=0.247      (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 15      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Polyp Stromal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |3/50 (6%)    1/50 (2%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |                                                        |3/44.88      1/45.21      2/44.70      2/45.21      | 
|POLY-3 PERCENT (g) |                                                        |6.7%         2.2%         4.5%         4.4%         | 
|TERMINAL (d)       |                                                        |3/37 (8%)    1/38 (3%)    2/37 (5%)    2/34 (6%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.622      P=0.295N     P=0.500N     P=0.539N     | 
|POLY 3             |                                                        |P=0.580N     P=0.303N     P=0.502N     P=0.497N     | 
|POLY 1.5           |                                                        |P=0.577N     P=0.306N     P=0.499N     P=0.495N     | 
|POLY 6             |                                                        |P=0.588N     P=0.299N     P=0.508N     P=0.502N     | 
|LOGISTIC REGRESSION|                                                        |P=0.622      P=0.295N     P=0.500N     P=0.539N     | 
|COCH-ARM / FISHERS |                                                        |P=0.582N     P=0.309N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangioma                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/45.36      0/40.88     |0/44.88      0/45.21      0/44.70      3/45.47      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         6.6%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          660          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.007 **   (e)          (e)          P=0.113      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.008 **   (e)          (e)          P=0.121      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.008 **   (e)          (e)          P=0.121      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.008 **   (e)          (e)          P=0.119      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.009 **   (e)          (e)          P=0.122      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.009 **   (e)          (e)          P=0.121      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 16      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   0/50 (0%)    7/50 (14%)   9/50 (18%)  |1/50 (2%)    1/50 (2%)    3/50 (6%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     6/46.34      0/44.17      7/45.93      9/42.54     |1/44.88      1/45.21      3/45.36      4/45.64      | 
|POLY-3 PERCENT (g) |     13.0%        0.0%         15.2%        21.2%       |2.2%         2.2%         6.6%         8.8%         | 
|TERMINAL (d)       |     4/39 (10%)   0/40 (0%)    5/38 (13%)   5/30 (17%)  |1/37 (3%)    1/38 (3%)    2/37 (5%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     590          ---          653          539         |729 (T)      729 (T)      509          645          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.013 *    P=0.019N*    P=0.484      P=0.171     |P=0.079      P=0.756N     P=0.309      P=0.170      | 
|POLY 3             |     P=0.026 *    P=0.018N*    P=0.493      P=0.227     |P=0.093      P=0.759N     P=0.309      P=0.184      | 
|POLY 1.5           |     P=0.029 *    P=0.018N*    P=0.497      P=0.242     |P=0.094      P=0.760      P=0.310      P=0.184      | 
|POLY 6             |     P=0.022 *    P=0.017N*    P=0.487      P=0.208     |P=0.090      P=0.757N     P=0.306      P=0.182      | 
|LOGISTIC REGRESSION|     P=0.034 *    P=0.017N*    P=0.500      P=0.279     |P=0.089      P=0.756N     P=0.300      P=0.182      | 
|COCH-ARM / FISHERS |     P=0.038 *    P=0.013N*    P=0.500      P=0.288     |P=0.090      P=0.753N     P=0.309      P=0.181      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangiosarcoma or Hemangioma                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   0/50 (0%)    7/50 (14%)   9/50 (18%)  |1/50 (2%)    1/50 (2%)    3/50 (6%)    6/50 (12%)   | 
|POLY-3 RATE (b)    |     6/46.34      0/44.17      7/45.93      9/42.54     |1/44.88      1/45.21      3/45.36      6/45.90      | 
|POLY-3 PERCENT (g) |     13.0%        0.0%         15.2%        21.2%       |2.2%         2.2%         6.6%         13.1%        | 
|TERMINAL (d)       |     4/39 (10%)   0/40 (0%)    5/38 (13%)   5/30 (17%)  |1/37 (3%)    1/38 (3%)    2/37 (5%)    3/34 (9%)    | 
|FIRST INCIDENCE    |     590          ---          653          539         |729 (T)      729 (T)      509          645          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.013 *    P=0.019N*    P=0.484      P=0.171     |P=0.010 *    P=0.756N     P=0.309      P=0.056      | 
|POLY 3             |     P=0.026 *    P=0.018N*    P=0.493      P=0.227     |P=0.013 *    P=0.759N     P=0.309      P=0.059      | 
|POLY 1.5           |     P=0.029 *    P=0.018N*    P=0.497      P=0.242     |P=0.013 *    P=0.760      P=0.310      P=0.059      | 
|POLY 6             |     P=0.022 *    P=0.017N*    P=0.487      P=0.208     |P=0.012 *    P=0.757N     P=0.306      P=0.059      | 
|LOGISTIC REGRESSION|     P=0.034 *    P=0.017N*    P=0.500      P=0.279     |P=0.012 *    P=0.756N     P=0.300      P=0.059      | 
|COCH-ARM / FISHERS |     P=0.038 *    P=0.013N*    P=0.500      P=0.288     |P=0.012 *    P=0.753N     P=0.309      P=0.056      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 17      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Histiocytic Sarcoma                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    3/50 (6%)   |0/50 (0%)    4/50 (8%)    1/50 (2%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     1/45.72      0/44.17      0/45.36      3/41.37     |0/44.88      4/46.01      1/44.70      3/45.39      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         0.0%         7.3%        |0.0%         8.7%         2.2%         6.6%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    1/38 (3%)    1/37 (3%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     690          ---          ---          646         |---          541          729 (T)      703          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.033 *    P=0.495N     P=0.510N     P=0.237     |P=0.278      P=0.072      P=0.500      P=0.113      | 
|POLY 3             |     P=0.049 *    P=0.507N     P=0.502N     P=0.270     |P=0.307      P=0.064      P=0.499      P=0.121      | 
|POLY 1.5           |     P=0.051      P=0.507N     P=0.501N     P=0.280     |P=0.308      P=0.062      P=0.501      P=0.121      | 
|POLY 6             |     P=0.046 *    P=0.503N     P=0.504N     P=0.258     |P=0.304      P=0.066      P=0.497      P=0.119      | 
|LOGISTIC REGRESSION|     P=0.053      P=0.500N     P=0.501N     P=0.293     |P=0.302      P=0.064      P=0.500      P=0.121      | 
|COCH-ARM / FISHERS |     P=0.056      P=0.500N     P=0.500N     P=0.309     |P=0.303      P=0.059      P=0.500      P=0.121      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        | 
|     NOS, or Undifferentiated Cell Type                                                                                          | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    2/50 (4%)    4/50 (8%)   |7/50 (14%)   8/50 (16%)   6/50 (12%)   16/50 (32%)  | 
|POLY-3 RATE (b)    |     3/45.56      1/44.17      2/45.36      4/40.88     |7/44.90      8/46.93      6/45.97      16/45.85     | 
|POLY-3 PERCENT (g) |     6.6%         2.3%         4.4%         9.8%        |15.6%        17.1%        13.1%        34.9%        | 
|TERMINAL (d)       |     3/39 (8%)    1/40 (3%)    2/38 (5%)    4/30 (13%)  |6/37 (16%)   5/38 (13%)   3/37 (8%)    14/34 (41%)  | 
|FIRST INCIDENCE    |     730 (T)      730 (T)      730 (T)      730 (T)     |723          281          509          621          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.134      P=0.296N     P=0.512N     P=0.358     |P=0.005 **   P=0.518      P=0.503N     P=0.017 *    | 
|POLY 3             |     P=0.210      P=0.316N     P=0.502N     P=0.441     |P=0.006 **   P=0.537      P=0.482N     P=0.028 *    | 
|POLY 1.5           |     P=0.222      P=0.318N     P=0.500N     P=0.458     |P=0.007 **   P=0.521      P=0.486N     P=0.029 *    | 
|POLY 6             |     P=0.191      P=0.309N     P=0.505N     P=0.417     |P=0.006 **   P=0.552      P=0.479N     P=0.027 *    | 
|LOGISTIC REGRESSION|     P=0.134      P=0.296N     P=0.512N     P=0.358     |P=0.007 **   P=0.502      P=0.499N     P=0.025 *    | 
|COCH-ARM / FISHERS |     P=0.243      P=0.309N     P=0.500N     P=0.500     |P=0.007 **   P=0.500      P=0.500N     P=0.028 *    | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 18      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     29/50 (58%)  24/50 (48%)  29/50 (58%)  27/50 (54%) |17/50 (34%)  16/50 (32%)  14/50 (28%)  26/50 (52%)  | 
|POLY-3 RATE (b)    |     29/47.88     24/45.10     29/47.45     27/44.89    |17/45.82     16/45.90     14/45.28     26/47.87     | 
|POLY-3 PERCENT (g) |     60.6%        53.2%        61.1%        60.2%       |37.1%        34.9%        30.9%        54.3%        | 
|TERMINAL (d)       |     24/39 (62%)  21/40 (53%)  24/38 (63%)  17/30 (57%) |15/37 (41%)  14/38 (37%)  12/37 (32%)  19/34 (56%)  | 
|FIRST INCIDENCE    |     420          455          581          483         |536          541          647          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.106      P=0.197N     P=0.521      P=0.281     |P=0.006 **   P=0.464N     P=0.337N     P=0.035 *    | 
|POLY 3             |     P=0.450      P=0.305N     P=0.562      P=0.569N    |P=0.019 *    P=0.497N     P=0.344N     P=0.068      | 
|POLY 1.5           |     P=0.467      P=0.292N     P=0.569      P=0.545N    |P=0.018 *    P=0.505N     P=0.333N     P=0.065      | 
|POLY 6             |     P=0.418      P=0.297N     P=0.554      P=0.579     |P=0.019 *    P=0.488N     P=0.360N     P=0.070      | 
|LOGISTIC REGRESSION|     P=0.419      P=0.261N     P=0.580      P=0.532N    |P=0.016 *    P=0.494N     P=0.337N     P=0.056      | 
|COCH-ARM / FISHERS |     P=0.545N     P=0.212N     P=0.580N     P=0.420N    |P=0.015 *    P=0.500N     P=0.333N     P=0.053      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     24/50 (48%)  20/50 (40%)  27/50 (54%)  30/50 (60%) |17/50 (34%)  22/50 (44%)  20/50 (40%)  28/50 (56%)  | 
|POLY-3 RATE (b)    |     24/47.76     20/46.91     27/48.81     30/47.14    |17/45.68     22/48.58     20/47.73     28/47.15     | 
|POLY-3 PERCENT (g) |     50.3%        42.6%        55.3%        63.6%       |37.2%        45.3%        41.9%        59.4%        | 
|TERMINAL (d)       |     18/39 (46%)  15/40 (38%)  17/38 (45%)  14/30 (47%) |12/37 (32%)  13/38 (34%)  12/37 (32%)  18/34 (53%)  | 
|FIRST INCIDENCE    |     590          311          548          483         |647          281          481          579          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.007 **   P=0.276N     P=0.333      P=0.044 *   |P=0.022 *    P=0.264      P=0.347      P=0.022 *    | 
|POLY 3             |     P=0.044 *    P=0.296N     P=0.384      P=0.132     |P=0.023 *    P=0.279      P=0.401      P=0.024 *    | 
|POLY 1.5           |     P=0.041 *    P=0.299N     P=0.369      P=0.123     |P=0.024 *    P=0.247      P=0.383      P=0.023 *    | 
|POLY 6             |     P=0.047 *    P=0.288N     P=0.402      P=0.140     |P=0.021 *    P=0.311      P=0.415      P=0.024 *    | 
|LOGISTIC REGRESSION|     P=0.054      P=0.272N     P=0.345      P=0.142     |P=0.025 *    P=0.205      P=0.341      P=0.023 *    | 
|COCH-ARM / FISHERS |     P=0.054      P=0.273N     P=0.345      P=0.158     |P=0.024 *    P=0.206      P=0.339      P=0.022 *    | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 19      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                      ELMIRON                    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     38/50 (76%)  32/50 (64%)  41/50 (82%)  42/50 (84%) |29/50 (58%)  34/50 (68%)  30/50 (60%)  40/50 (80%)  | 
|POLY-3 RATE (b)    |     38/48.82     32/47.67     41/49.26     42/48.00    |29/46.61     34/48.68     30/48.32     40/49.06     | 
|POLY-3 PERCENT (g) |     77.8%        67.1%        83.2%        87.5%       |62.2%        69.8%        62.1%        81.5%        | 
|TERMINAL (d)       |     30/39 (77%)  25/40 (63%)  30/38 (79%)  24/30 (80%) |22/37 (60%)  24/38 (63%)  20/37 (54%)  26/34 (77%)  | 
|FIRST INCIDENCE    |     420          311          548          483         |536          281          481          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.002 **   P=0.163N     P=0.304      P=0.028 *   |P=0.019 *    P=0.294      P=0.487      P=0.022 *    | 
|POLY 3             |     P=0.039 *    P=0.168N     P=0.336      P=0.159     |P=0.027 *    P=0.284      P=0.579N     P=0.026 *    | 
|POLY 1.5           |     P=0.032 *    P=0.170N     P=0.323      P=0.139     |P=0.025 *    P=0.247      P=0.565      P=0.022 *    | 
|POLY 6             |     P=0.048 *    P=0.163N     P=0.361      P=0.187     |P=0.028 *    P=0.316      P=0.561N     P=0.030 *    | 
|LOGISTIC REGRESSION|     P=0.036 *    P=0.154N     P=0.312      P=0.133     |P=0.020 *    P=0.197      P=0.507      P=0.017 *    | 
|COCH-ARM / FISHERS |     P=0.059      P=0.138N     P=0.312      P=0.227     |P=0.018 *    P=0.204      P=0.500      P=0.015 *    | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).