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TDMS Study 88122-06 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                                          ELMIRON                                        DATE: 06/12/01       
EXPERIMENT: 88122 TEST: 06                                                                                     TIME: 09:23:07       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: C88122       
PATHOLOGIST: RYAN, MICHAEL                                                                                     CAS: 37319-17-8      
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                                                              FINAL#1                                                               
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                                          ELMIRON                                        DATE: 06/12/01       
EXPERIMENT: 88122 TEST: 06                                                                                     TIME: 09:23:07       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: C88122       
PATHOLOGIST: RYAN, MICHAEL                                                                                     CAS: 37319-17-8      
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                     ELMIRON                                                                                      
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Intestine Large, Rectum                Infiltration Cellular Histiocyte                                                             
                                       Inflammation Chronic                                                                         
                                       Myxomatous Change                                                                            
Liver                                  Basophilic Focus                                                                             
                                       Eosinophilic Focus                                                                           
                                       Mixed Cell Focus                                                                             
Liver: Bile Duct                       Hyperplasia                                                                                  
Lung: Alveolar Epithelium              Hyperplasia                                                                                  
                                       Metaplasia                                                                                   
Lung: Alveolus                         Inflammation Chronic Focal                                                                   
Lymph Node, Mesenteric                 Infiltration Cellular Histiocyte                                                             
                                       Inflammation Granulomatous                                                                   
Mammary Gland                          Hyperplasia                                                                                  
Mammary Gland: Duct                    Dilatation                                                                                   
Pituitary Gland                        Hyperplasia                                                                                  
Preputial Gland                        Inflammation Chronic                                                                         
Spleen                                 Hyperplasia Lymphohistiocytic                                                                
Testes: Interstitial Cell              Hyperplasia                                                                                  
Thyroid Gland: C-Cell                  Hyperplasia                                                                                  
Trachea                                Inflammation Chronic                                                                         
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Heart: Myocardium                      Degeneration                                                                                 
Intestine Large, Rectum                Infiltration Cellular Histiocyte                                                             
                                       Myxomatous Change                                                                            
Liver                                  Inflammation Granulomatous                                                                   
                                       Mixed Cell Focus                                                                             
Lung                                   Congestion                                                                                   
Lung: Alveolus                         Inflammation Chronic Focal                                                                   
Lymph Node, Mesenteric                 Infiltration Cellular Histiocyte                                                             
Mammary Gland: Duct                    Dilatation                                                                                   
Mesentery: Fat                         Necrosis                                                                                     
Spleen                                 Hyperplasia Lymphohistiocytic                                                                
Stomach, Glandular                     Ulcer                                                                                        
===============================================================                                                                     
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 1       
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                      ELMIRON     
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/50 (28%)  16/50 (32%)  17/50 (34%)  17/50 (34%) |20/50 (40%)  17/50 (34%)  17/50 (34%)  19/50 (38%)  | 
|POLY-3 RATE (b)    |     14/41.37     16/43.03     17/42.96     17/41.46    |20/44.10     17/43.11     17/42.90     19/40.19     | 
|POLY-3 PERCENT (g) |     33.8%        37.2%        39.6%        41.0%       |45.4%        39.4%        39.6%        47.3%        | 
|TERMINAL (d)       |     13/26 (50%)  11/29 (38%)  9/25 (36%)   10/28 (36%) |14/30 (47%)  16/31 (52%)  11/28 (39%)  14/27 (52%)  | 
|FIRST INCIDENCE    |     686          577          484          622         |462          670          474          624          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.376      P=0.545      P=0.285      P=0.406     |P=0.338      P=0.296N     P=0.423N     P=0.515      | 
|POLY 3             |     P=0.317      P=0.462      P=0.373      P=0.326     |P=0.376      P=0.364N     P=0.372N     P=0.517      | 
|POLY 1.5           |     P=0.303      P=0.428      P=0.362      P=0.301     |P=0.403      P=0.353N     P=0.361N     P=0.547      | 
|POLY 6             |     P=0.360      P=0.520      P=0.388      P=0.385     |P=0.361      P=0.381N     P=0.387N     P=0.495      | 
|LOGISTIC REGRESSION|     P=0.297      P=0.475      P=0.289      P=0.318     |P=0.389      P=0.299N     P=0.350N     P=0.567      | 
|COCH-ARM / FISHERS |     P=0.348      P=0.414      P=0.333      P=0.333     |P=0.521      P=0.339N     P=0.339N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      3/40.43      0/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         7.4%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    2/25 (8%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          561          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.640N     (e)          P=0.119      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.665N     (e)          P=0.114      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.665N     (e)          P=0.118      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.661N     (e)          P=0.110      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.651N     (e)          P=0.120      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.646N     (e)          P=0.121      (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Hyperplasia Diffuse                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.53      0/41.91      0/39.89      0/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     4.8%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/26 (4%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     640          ---          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.239N     P=0.220N     P=0.256N     P=0.229N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.239N     P=0.235N     P=0.246N     P=0.245N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.237N     P=0.238N     P=0.240N     P=0.246N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.241N     P=0.230N     P=0.254N     P=0.242N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.242N     P=0.237N     P=0.240N     P=0.243N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.238N     P=0.247N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  17/50 (34%)  12/50 (24%)  13/50 (26%) |5/50 (10%)   2/50 (4%)    4/50 (8%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     10/42.22     17/43.67     12/42.54     13/40.50    |5/41.94      2/42.89      4/41.69      4/39.41      | 
|POLY-3 PERCENT (g) |     23.7%        38.9%        28.2%        32.1%       |11.9%        4.7%         9.6%         10.2%        | 
|TERMINAL (d)       |     3/26 (12%)   8/29 (28%)   5/25 (20%)   10/28 (36%) |5/30 (17%)   2/31 (7%)    3/28 (11%)   3/27 (11%)   | 
|FIRST INCIDENCE    |     589          478          526          661         |728 (T)      728 (T)      667          706          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.537      P=0.160      P=0.349      P=0.363     |P=0.479      P=0.200N     P=0.537N     P=0.566N     | 
|POLY 3             |     P=0.464      P=0.096      P=0.410      P=0.270     |P=0.504      P=0.206N     P=0.504N     P=0.539N     | 
|POLY 1.5           |     P=0.472      P=0.087      P=0.414      P=0.272     |P=0.512      P=0.211N     P=0.504N     P=0.535N     | 
|POLY 6             |     P=0.465      P=0.112      P=0.402      P=0.278     |P=0.500      P=0.200N     P=0.503N     P=0.539N     | 
|LOGISTIC REGRESSION|     P=0.493      P=0.090      P=0.396      P=0.299     |P=0.494      P=0.200N     P=0.517N     P=0.554N     | 
|COCH-ARM / FISHERS |     P=0.537      P=0.088      P=0.405      P=0.318     |P=0.554      P=0.218N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone                                                                                                                             | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.30      0/41.91      0/39.89      0/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     4.8%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/26 (4%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     707          ---          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.242N     P=0.218N     P=0.263N     P=0.232N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.239N     P=0.233N     P=0.244N     P=0.244N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.238N     P=0.237N     P=0.240N     P=0.245N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.242N     P=0.228N     P=0.252N     P=0.239N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.243N     P=0.225N     P=0.257N     P=0.237N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.238N     P=0.247N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.93      1/42.42      0/39.89      1/40.22     |0/41.94      1/43.55      1/41.74      0/39.32      | 
|POLY-3 PERCENT (g) |     4.8%         2.4%         0.0%         2.5%        |0.0%         2.3%         2.4%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     589          574          ---          679         |---          510          653          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.497N     P=0.488N     P=0.257N     P=0.494N    |P=0.553N     P=0.509      P=0.516      (e)          | 
|POLY 3             |     P=0.507N     P=0.496N     P=0.248N     P=0.515N    |P=0.557N     P=0.508      P=0.499      (e)          | 
|POLY 1.5           |     P=0.506N     P=0.500N     P=0.242N     P=0.515N    |P=0.555N     P=0.504      P=0.499      (e)          | 
|POLY 6             |     P=0.507N     P=0.489N     P=0.258N     P=0.510N    |P=0.557N     P=0.511      P=0.499      (e)          | 
|LOGISTIC REGRESSION|     P=0.482N     P=0.492N     P=0.242N     P=0.494N    |P=0.492N     P=0.495      P=0.502      (e)          | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.500N     P=0.247N     P=0.500N    |P=0.541N     P=0.500      P=0.500      (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Hydrocephalus                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   7/50 (14%)   9/50 (18%)   6/50 (12%)  |8/50 (16%)   6/50 (12%)   8/50 (16%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |     8/44.28      7/43.22      9/42.28      6/40.79     |8/43.60      6/43.12      8/42.16      10/40.85     | 
|POLY-3 PERCENT (g) |     18.1%        16.2%        21.3%        14.7%       |18.4%        13.9%        19.0%        24.5%        | 
|TERMINAL (d)       |     2/26 (8%)    3/29 (10%)   3/25 (12%)   3/28 (11%)  |2/30 (7%)    4/31 (13%)   3/28 (11%)   5/27 (19%)   | 
|FIRST INCIDENCE    |     503          478          462          629         |462          678          667          525          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.375N     P=0.458N     P=0.459      P=0.390N    |P=0.173      P=0.377N     P=0.562      P=0.326      | 
|POLY 3             |     P=0.423N     P=0.521N     P=0.458      P=0.451N    |P=0.189      P=0.394N     P=0.580      P=0.337      | 
|POLY 1.5           |     P=0.411N     P=0.519N     P=0.481      P=0.440N    |P=0.194      P=0.392N     P=0.588      P=0.344      | 
|POLY 6             |     P=0.427N     P=0.516N     P=0.429      P=0.452N    |P=0.189      P=0.398N     P=0.571      P=0.335      | 
|LOGISTIC REGRESSION|     P=0.342N     P=0.493N     P=0.495      P=0.373N    |P=0.196      P=0.381N     P=0.603      P=0.371      | 
|COCH-ARM / FISHERS |     P=0.356N     P=0.500N     P=0.500      P=0.387N    |P=0.236      P=0.387N     P=0.607N     P=0.398      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Hypothalamus                                                                                                              | 
|     Compression                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   2/50 (4%)    5/50 (10%)   4/50 (8%)   |5/50 (10%)   3/50 (6%)    5/50 (10%)   8/50 (16%)   | 
|POLY-3 RATE (b)    |     6/44.12      2/42.72      5/41.39      4/40.79     |5/43.14      3/43.12      5/42.01      8/40.65      | 
|POLY-3 PERCENT (g) |     13.6%        4.7%         12.1%        9.8%        |11.6%        7.0%         11.9%        19.7%        | 
|TERMINAL (d)       |     1/26 (4%)    0/29 (0%)    1/25 (4%)    1/28 (4%)   |0/30 (0%)    1/31 (3%)    1/28 (4%)    4/27 (15%)   | 
|FIRST INCIDENCE    |     503          478          462          629         |462          678          667          525          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.544N     P=0.137N     P=0.534N     P=0.385N    |P=0.080      P=0.348N     P=0.599      P=0.232      | 
|POLY 3             |     P=0.561N     P=0.143N     P=0.545N     P=0.419N    |P=0.085      P=0.356N     P=0.614      P=0.236      | 
|POLY 1.5           |     P=0.555N     P=0.142N     P=0.521N     P=0.412N    |P=0.088      P=0.357N     P=0.618      P=0.240      | 
|POLY 6             |     P=0.560N     P=0.142N     P=0.575N     P=0.418N    |P=0.085      P=0.355N     P=0.610      P=0.236      | 
|LOGISTIC REGRESSION|     P=0.471N     P=0.114N     P=0.522N     P=0.331N    |P=0.093      P=0.357N     P=0.629      P=0.263      | 
|COCH-ARM / FISHERS |     P=0.522N     P=0.134N     P=0.500N     P=0.370N    |P=0.108      P=0.357N     P=0.630N     P=0.277      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |4/50 (8%)    4/50 (8%)    4/50 (8%)    3/49 (6%)    | 
|POLY-3 RATE (b)    |                                                        |4/42.15      4/43.28      4/41.63      3/38.59      | 
|POLY-3 PERCENT (g) |                                                        |9.5%         9.2%         9.6%         7.8%         | 
|TERMINAL (d)       |                                                        |3/30 (10%)   2/31 (7%)    3/28 (11%)   2/26 (8%)    | 
|FIRST INCIDENCE    |                                                        |673          677          685          656          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.504N     P=0.617N     P=0.610      P=0.564N     | 
|POLY 3             |                                                        |P=0.478N     P=0.629N     P=0.637      P=0.548N     | 
|POLY 1.5           |                                                        |P=0.470N     P=0.635N     P=0.638      P=0.544N     | 
|POLY 6             |                                                        |P=0.483N     P=0.621N     P=0.635      P=0.550N     | 
|LOGISTIC REGRESSION|                                                        |P=0.481N     P=0.630N     P=0.635      P=0.550N     | 
|COCH-ARM / FISHERS |                                                        |P=0.429N     P=0.643N     P=0.643N     P=0.511N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |5/50 (10%)   3/50 (6%)    2/50 (4%)    3/49 (6%)    | 
|POLY-3 RATE (b)    |                                                        |5/42.39      3/43.14      2/41.46      3/38.69      | 
|POLY-3 PERCENT (g) |                                                        |11.8%        7.0%         4.8%         7.8%         | 
|TERMINAL (d)       |                                                        |4/30 (13%)   1/31 (3%)    2/28 (7%)    2/26 (8%)    | 
|FIRST INCIDENCE    |                                                        |596          678          728 (T)      624          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.472N     P=0.342N     P=0.243N     P=0.424N     | 
|POLY 3             |                                                        |P=0.443N     P=0.346N     P=0.224N     P=0.407N     | 
|POLY 1.5           |                                                        |P=0.437N     P=0.351N     P=0.222N     P=0.402N     | 
|POLY 6             |                                                        |P=0.447N     P=0.340N     P=0.228N     P=0.408N     | 
|LOGISTIC REGRESSION|                                                        |P=0.450N     P=0.345N     P=0.221N     P=0.402N     | 
|COCH-ARM / FISHERS |                                                        |P=0.406N     P=0.357N     P=0.218N     P=0.369N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/50 (2%)    0/50 (0%)    1/50 (2%)    2/49 (4%)    | 
|POLY-3 RATE (b)    |                                                        |1/41.94      0/42.89      1/41.46      2/38.32      | 
|POLY-3 PERCENT (g) |                                                        |2.4%         0.0%         2.4%         5.2%         | 
|TERMINAL (d)       |                                                        |1/30 (3%)    0/31 (0%)    1/28 (4%)    2/26 (8%)    | 
|FIRST INCIDENCE    |                                                        |728 (T)      ---          728 (T)      728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.191      P=0.493N     P=0.747      P=0.450      | 
|POLY 3             |                                                        |P=0.207      P=0.496N     P=0.758      P=0.469      | 
|POLY 1.5           |                                                        |P=0.211      P=0.498N     P=0.759      P=0.472      | 
|POLY 6             |                                                        |P=0.204      P=0.493N     P=0.758      P=0.467      | 
|LOGISTIC REGRESSION|                                                        |P=0.191      (e)          P=0.747      P=0.450      | 
|COCH-ARM / FISHERS |                                                        |P=0.229      P=0.500N     P=0.753N     P=0.492      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |7/50 (14%)   10/50 (20%)  11/50 (22%)  8/49 (16%)   | 
|POLY-3 RATE (b)    |                                                        |7/42.42      10/43.59     11/42.41     8/38.80      | 
|POLY-3 PERCENT (g) |                                                        |16.5%        22.9%        25.9%        20.6%        | 
|TERMINAL (d)       |                                                        |5/30 (17%)   6/31 (19%)   7/28 (25%)   7/26 (27%)   | 
|FIRST INCIDENCE    |                                                        |651          653          491          588          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.464      P=0.334      P=0.190      P=0.396      | 
|POLY 3             |                                                        |P=0.492      P=0.316      P=0.212      P=0.424      | 
|POLY 1.5           |                                                        |P=0.507      P=0.307      P=0.212      P=0.432      | 
|POLY 6             |                                                        |P=0.478      P=0.329      P=0.208      P=0.419      | 
|LOGISTIC REGRESSION|                                                        |P=0.500      P=0.317      P=0.207      P=0.422      | 
|COCH-ARM / FISHERS |                                                        |P=0.543N     P=0.298      P=0.218      P=0.483      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye                                                                                                                              | 
|     Cataract                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     1/1 (100%)   0/0 (0%)     1/1 (100%)  |0/0 (0%)     1/3 (33%)    1/1 (100%)   2/3 (67%)    | 
|POLY-3 RATE (b)    |     0/0.00       1/1.00       0/0.00       1/1.00      |0/0.00       1/2.96       1/1.00       2/3.00       | 
|POLY-3 PERCENT (g) |     0.0%         100.0%       0.0%         100.0%      |0.0%         33.8%        100.0%       66.7%        | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     1/1 (100%)  |0/0 (0%)     0/1 (0%)     0/0 (0%)     2/3 (67%)    | 
|FIRST INCIDENCE    |     ---          713          ---          727 (T)     |---          653          685          728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.575      P=0.511      (e)          P=1.000      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.178      (e)          (e)          P=1.000      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.488      P=1.000      (e)          P=1.000      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye                                                                                                                              | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     0/1 (0%)     0/0 (0%)     0/1 (0%)    |0/0 (0%)     2/3 (67%)    0/1 (0%)     0/3 (0%)     | 
|POLY-3 RATE (b)    |     0/0.00       0/0.94       0/0.00       0/1.00      |0/0.00       2/2.72       0/0.83       0/3.00       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         73.5%        0.0%         0.0%         | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/1 (0%)    |0/0 (0%)     1/1 (100%)   0/0 (0%)     0/3 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          719          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.149N     P=0.513      (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.051N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.163N     P=1.000      (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 8       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Atrium                                                                                                                    | 
|     Thrombosis                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    4/50 (8%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.25      4/42.84      0/39.89      1/40.04     |0/41.94      1/43.11      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     4.9%         9.3%         0.0%         2.5%        |0.0%         2.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    1/28 (4%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     721          574          ---          727 (T)     |---          670          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.243N     P=0.372      P=0.277N     P=0.503N    |P=0.605N     P=0.516      (e)          (e)          | 
|POLY 3             |     P=0.233N     P=0.354      P=0.244N     P=0.510N    |P=0.585N     P=0.506      (e)          (e)          | 
|POLY 1.5           |     P=0.235N     P=0.343      P=0.240N     P=0.513N    |P=0.586N     P=0.503      (e)          (e)          | 
|POLY 6             |     P=0.227N     P=0.373      P=0.251N     P=0.504N    |P=0.583N     P=0.509      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.237N     P=0.337      P=0.262N     P=0.503N    |P=0.588N     P=0.500      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.228N     P=0.339      P=0.247N     P=0.500N    |P=0.585N     P=0.500      (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Myocardium                                                                                                                | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     41/50 (82%)  41/50 (82%)  42/50 (84%)  41/50 (82%) |38/50 (76%)  30/50 (60%)  31/50 (62%)  34/50 (68%)  | 
|POLY-3 RATE (b)    |     41/47.02     41/46.50     42/48.61     41/45.31    |38/47.00     30/44.84     31/44.50     34/46.40     | 
|POLY-3 PERCENT (g) |     87.2%        88.2%        86.4%        90.5%       |80.8%        66.9%        69.7%        73.3%        | 
|TERMINAL (d)       |     25/26 (96%)  27/29 (93%)  21/25 (84%)  24/28 (86%) |23/30 (77%)  22/31 (71%)  21/28 (75%)  20/27 (74%)  | 
|FIRST INCIDENCE    |     475          478          419          352         |427          526          375          139          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.520N     P=0.335N     P=0.380      P=0.465N    |P=0.322      P=0.086N     P=0.240N     P=0.513N     | 
|POLY 3             |     P=0.376      P=0.571      P=0.577N     P=0.429     |P=0.459N     P=0.090N     P=0.148N     P=0.261N     | 
|POLY 1.5           |     P=0.377      P=0.551      P=0.606N     P=0.421     |P=0.488N     P=0.076N     P=0.123N     P=0.267N     | 
|POLY 6             |     P=0.442      P=0.626      P=0.540N     P=0.515     |P=0.432N     P=0.110N     P=0.187N     P=0.260N     | 
|LOGISTIC REGRESSION|     P=0.387      P=0.574      P=0.504      P=0.410     |P=0.470      P=0.049N*    P=0.099N     P=0.301N     | 
|COCH-ARM / FISHERS |     P=0.558N     P=0.602N     P=0.500      P=0.602N    |P=0.496N     P=0.066N     P=0.097N     P=0.252N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 9       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Colon                                                                                                           | 
|     Parasite Metazoan                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    0/50 (0%)    3/50 (6%)   |2/50 (4%)    3/50 (6%)    3/50 (6%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     4/41.37      1/41.91      0/39.89      3/40.04     |2/41.94      3/42.94      3/41.71      3/40.32      | 
|POLY-3 PERCENT (g) |     9.7%         2.4%         0.0%         7.5%        |4.8%         7.0%         7.2%         7.4%         | 
|TERMINAL (d)       |     3/26 (12%)   1/29 (3%)    0/25 (0%)    3/28 (11%)  |2/30 (7%)    2/31 (7%)    1/28 (4%)    2/27 (7%)    | 
|FIRST INCIDENCE    |     686          727 (T)      ---          727 (T)     |728 (T)      716          667          139          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.553      P=0.152N     P=0.072N     P=0.465N    |P=0.437      P=0.515      P=0.478      P=0.460      | 
|POLY 3             |     P=0.528      P=0.174N     P=0.064N     P=0.518N    |P=0.462      P=0.511      P=0.497      P=0.482      | 
|POLY 1.5           |     P=0.530      P=0.178N     P=0.062N     P=0.521N    |P=0.467      P=0.506      P=0.497      P=0.484      | 
|POLY 6             |     P=0.528      P=0.167N     P=0.068N     P=0.509N    |P=0.460      P=0.517      P=0.498      P=0.482      | 
|LOGISTIC REGRESSION|     P=0.529      P=0.160N     P=0.073N     P=0.501N    |P=0.487      P=0.519      P=0.492      P=0.540      | 
|COCH-ARM / FISHERS |     P=0.541      P=0.181N     P=0.059N     P=0.500N    |P=0.491      P=0.500      P=0.500      P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Erosion                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    0/48 (0%)    2/49 (4%)    2/45 (4%)   |0/46 (0%)    0/43 (0%)    0/44 (0%)    0/42 (0%)    | 
|POLY-3 RATE (b)    |     0/39.46      0/40.92      2/40.89      2/36.89     |0/39.83      0/38.64      0/38.77      0/36.68      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.9%         5.4%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    2/28 (7%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          484          727 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.126      (e)          P=0.240      P=0.254     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.104      (e)          P=0.245      P=0.222     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.102      (e)          P=0.246      P=0.218     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.109      (e)          P=0.241      P=0.229     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.119      (e)          P=0.162      P=0.254     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.109      (e)          P=0.253      P=0.231     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 10      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    0/48 (0%)    0/49 (0%)    4/45 (9%)   |0/46 (0%)    0/43 (0%)    0/44 (0%)    18/42 (43%)  | 
|POLY-3 RATE (b)    |     0/39.46      0/40.92      0/39.70      4/37.40     |0/39.83      0/38.64      0/38.77      18/37.53     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         10.7%       |0.0%         0.0%         0.0%         48.0%        | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    2/28 (7%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    12/27 (44%)  | 
|FIRST INCIDENCE    |     ---          ---          ---          604         |---          ---          ---          588          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.002 **   (e)          (e)          P=0.074     |P<0.001 **   (e)          (e)          P<0.001 **   | 
|POLY 3             |     P<0.001 **   (e)          (e)          P=0.052     |P<0.001 **   (e)          (e)          P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P=0.050     |P<0.001 **   (e)          (e)          P<0.001 **   | 
|POLY 6             |     P<0.001 **   (e)          (e)          P=0.058     |P<0.001 **   (e)          (e)          P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          P=0.053     |P<0.001 **   (e)          (e)          P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P=0.051     |P<0.001 **   (e)          (e)          P<0.001 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/48 (2%)    0/48 (0%)    1/49 (2%)    5/45 (11%)  |0/46 (0%)    0/43 (0%)    0/44 (0%)    1/42 (2%)    | 
|POLY-3 RATE (b)    |     1/40.12      0/40.92      1/40.40      5/37.85     |0/39.83      0/38.64      0/38.77      1/36.77      | 
|POLY-3 PERCENT (g) |     2.5%         0.0%         2.5%         13.2%       |0.0%         0.0%         0.0%         2.7%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    4/28 (14%)  |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     505          ---          484          261         |---          ---          ---          706          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.007 **   P=0.509N     P=0.758      P=0.111     |P=0.198      (e)          (e)          P=0.482      | 
|POLY 3             |     P=0.004 **   P=0.496N     P=0.759N     P=0.087     |P=0.205      (e)          (e)          P=0.484      | 
|POLY 1.5           |     P=0.004 **   P=0.498N     P=0.756N     P=0.083     |P=0.205      (e)          (e)          P=0.483      | 
|POLY 6             |     P=0.005 **   P=0.493N     P=0.756      P=0.092     |P=0.205      (e)          (e)          P=0.486      | 
|LOGISTIC REGRESSION|     P=0.008 **   P=0.504N     P=0.687      P=0.097     |P=0.204      (e)          (e)          P=0.483      | 
|COCH-ARM / FISHERS |     P=0.005 **   P=0.500N     P=0.747N     P=0.088     |P=0.205      (e)          (e)          P=0.477      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 11      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Myxomatous Change                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    1/48 (2%)    3/49 (6%)    25/45 (56%) |0/46 (0%)    1/43 (2%)    12/44 (27%)  35/42 (83%)  | 
|POLY-3 RATE (b)    |     0/39.46      1/41.22      3/40.39      25/38.85    |0/39.83      1/39.36      12/39.71     35/39.32     | 
|POLY-3 PERCENT (g) |     0.0%         2.4%         7.4%         64.4%       |0.0%         2.5%         30.2%        89.0%        | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    2/25 (8%)    19/28 (68%) |0/30 (0%)    0/31 (0%)    9/28 (32%)   24/27 (89%)  | 
|FIRST INCIDENCE    |     ---          645          492          261         |---          474          483          525          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.526      P=0.117      P<0.001 **  |P<0.001 **   P=0.508      P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P=0.509      P=0.122      P<0.001 **  |P<0.001 **   P=0.498      P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.504      P=0.124      P<0.001 **  |P<0.001 **   P=0.493      P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.515      P=0.118      P<0.001 **  |P<0.001 **   P=0.503      P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.498      P=0.121      P<0.001 **  |P<0.001 **   P=0.470      P<0.001 **   P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.500      P=0.125      P<0.001 **  |P<0.001 **   P=0.483      P<0.001 **   P<0.001 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Parasite Metazoan                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/48 (10%)   8/48 (17%)   4/49 (8%)    3/45 (7%)   |2/46 (4%)    3/43 (7%)    1/44 (2%)    0/42 (0%)    | 
|POLY-3 RATE (b)    |     5/39.46      8/41.22      4/40.39      3/36.89     |2/39.83      3/38.64      1/38.77      0/36.68      | 
|POLY-3 PERCENT (g) |     12.7%        19.4%        9.9%         8.1%        |5.0%         7.8%         2.6%         0.0%         | 
|TERMINAL (d)       |     5/26 (19%)   7/29 (24%)   3/25 (12%)   3/28 (11%)  |2/30 (7%)    3/31 (10%)   1/28 (4%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     727 (T)      645          492          727 (T)     |728 (T)      728 (T)      728 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.141N     P=0.347      P=0.524N     P=0.311N    |P=0.123N     P=0.515      P=0.524N     P=0.261N     | 
|POLY 3             |     P=0.185N     P=0.302      P=0.485N     P=0.393N    |P=0.115N     P=0.486      P=0.509N     P=0.255N     | 
|POLY 1.5           |     P=0.193N     P=0.288      P=0.480N     P=0.404N    |P=0.115N     P=0.479      P=0.510N     P=0.256N     | 
|POLY 6             |     P=0.170N     P=0.322      P=0.498N     P=0.372N    |P=0.114N     P=0.496      P=0.509N     P=0.254N     | 
|LOGISTIC REGRESSION|     P=0.177N     P=0.322      P=0.503N     P=0.311N    |P=0.123N     P=0.515      P=0.524N     (e)          | 
|COCH-ARM / FISHERS |     P=0.182N     P=0.276      P=0.487N     P=0.394N    |P=0.116N     P=0.468      P=0.517N     P=0.270N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 12      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    1/50 (2%)    2/50 (4%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/41.23      1/42.41      1/39.93      2/41.38     |1/41.94      1/42.95      0/41.46      1/39.32      | 
|POLY-3 PERCENT (g) |     2.4%         2.4%         2.5%         4.8%        |2.4%         2.3%         0.0%         2.5%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |1/30 (3%)    0/31 (0%)    0/28 (0%)    1/27 (4%)    | 
|FIRST INCIDENCE    |     724          577          716          237         |728 (T)      714          ---          728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.357      P=0.754N     P=0.728      P=0.499     |P=0.647      P=0.747N     P=0.514N     P=0.739      | 
|POLY 3             |     P=0.359      P=0.755N     P=0.754      P=0.501     |P=0.659      P=0.756N     P=0.502N     P=0.746      | 
|POLY 1.5           |     P=0.356      P=0.759N     P=0.758      P=0.496     |P=0.661      P=0.758N     P=0.502N     P=0.748      | 
|POLY 6             |     P=0.364      P=0.747N     P=0.747      P=0.512     |P=0.658      P=0.753N     P=0.503N     P=0.746      | 
|LOGISTIC REGRESSION|     P=0.415      P=0.762N     P=0.740      P=0.572     |P=0.655      P=0.754N     (e)          P=0.739      | 
|COCH-ARM / FISHERS |     P=0.361      P=0.753N     P=0.753N     P=0.500     |P=0.677      P=0.753N     P=0.500N     P=0.753N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Hydronephrosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.46      0/41.91      0/39.89      0/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     4.8%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     685          ---          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.247N     P=0.227N     P=0.272N     P=0.243N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.239N     P=0.234N     P=0.245N     P=0.245N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.237N     P=0.237N     P=0.240N     P=0.246N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.241N     P=0.230N     P=0.254N     P=0.241N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.243N     P=0.235N     P=0.245N     P=0.243N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.238N     P=0.247N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 13      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Infarct                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     2/41.24      0/41.91      2/40.86      0/40.04     |2/42.39      0/42.89      0/41.46      1/39.32      | 
|POLY-3 PERCENT (g) |     4.9%         0.0%         4.9%         0.0%        |4.7%         0.0%         0.0%         2.5%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |1/30 (3%)    0/31 (0%)    0/28 (0%)    1/27 (4%)    | 
|FIRST INCIDENCE    |     724          ---          582          ---         |596          ---          ---          728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.287N     P=0.230N     P=0.666      P=0.246N    |P=0.674N     P=0.241N     P=0.253N     P=0.535N     | 
|POLY 3             |     P=0.293N     P=0.233N     P=0.691      P=0.243N    |P=0.654N     P=0.234N     P=0.242N     P=0.526N     | 
|POLY 1.5           |     P=0.292N     P=0.237N     P=0.694N     P=0.245N    |P=0.652N     P=0.236N     P=0.240N     P=0.522N     | 
|POLY 6             |     P=0.293N     P=0.227N     P=0.686      P=0.239N    |P=0.656N     P=0.233N     P=0.244N     P=0.529N     | 
|LOGISTIC REGRESSION|     P=0.278N     P=0.221N     P=0.695      P=0.238N    |P=0.658N     P=0.239N     P=0.237N     P=0.515N     | 
|COCH-ARM / FISHERS |     P=0.281N     P=0.247N     P=0.691N     P=0.247N    |P=0.646N     P=0.247N     P=0.247N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     40/50 (80%)  42/50 (84%)  41/50 (82%)  37/50 (74%) |16/50 (32%)  13/50 (26%)  11/50 (22%)  16/50 (32%)  | 
|POLY-3 RATE (b)    |     40/45.77     42/46.45     41/45.58     37/43.30    |16/43.17     13/43.50     11/42.61     16/40.59     | 
|POLY-3 PERCENT (g) |     87.4%        90.4%        90.0%        85.5%       |37.1%        29.9%        25.8%        39.4%        | 
|TERMINAL (d)       |     25/26 (96%)  25/29 (86%)  24/25 (96%)  26/28 (93%) |13/30 (43%)  10/31 (32%)  8/28 (29%)   13/27 (48%)  | 
|FIRST INCIDENCE    |     503          478          492          433         |462          622          474          525          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.235N     P=0.468N     P=0.352      P=0.254N    |P=0.266      P=0.298N     P=0.235N     P=0.449      | 
|POLY 3             |     P=0.353N     P=0.443      P=0.474      P=0.519N    |P=0.322      P=0.314N     P=0.184N     P=0.501      | 
|POLY 1.5           |     P=0.315N     P=0.367      P=0.509      P=0.498N    |P=0.334      P=0.323N     P=0.186N     P=0.508      | 
|POLY 6             |     P=0.362N     P=0.622      P=0.456      P=0.474N    |P=0.319      P=0.300N     P=0.182N     P=0.508      | 
|LOGISTIC REGRESSION|     P=0.299N     P=0.347      P=0.436      P=0.473N    |P=0.311      P=0.297N     P=0.189N     P=0.501      | 
|COCH-ARM / FISHERS |     P=0.168N     P=0.398      P=0.500      P=0.318N    |P=0.411      P=0.330N     P=0.184N     P=0.585N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 14      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    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)    |     2/41.46      1/42.19      2/40.05      0/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     4.8%         2.4%         5.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    1/25 (4%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     685          654          685          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.216N     P=0.477N     P=0.652      P=0.243N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.221N     P=0.494N     P=0.682      P=0.245N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.220N     P=0.499N     P=0.690      P=0.246N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.220N     P=0.485N     P=0.670      P=0.241N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.216N     P=0.499N     P=0.679      P=0.243N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.209N     P=0.500N     P=0.691N     P=0.247N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Pigmentation Lipofuscin                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    3/50 (6%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      1/41.96      3/41.07      0/40.04     |0/41.94      0/42.89      1/42.15      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         2.4%         7.3%         0.0%        |0.0%         0.0%         2.4%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          715          582          ---         |---          ---          491          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.505N     P=0.512      P=0.121      (e)         |P=0.793N     (e)          P=0.496      (e)          | 
|POLY 3             |     P=0.517N     P=0.504      P=0.117      (e)         |P=0.796N     (e)          P=0.501      (e)          | 
|POLY 1.5           |     P=0.518N     P=0.500      P=0.119      (e)         |P=0.794N     (e)          P=0.500      (e)          | 
|POLY 6             |     P=0.510N     P=0.509      P=0.115      (e)         |P=0.797N     (e)          P=0.502      (e)          | 
|LOGISTIC REGRESSION|     P=0.489N     P=0.510      P=0.111      (e)         |P=0.719N     (e)          P=0.530      (e)          | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.500      P=0.121      (e)         |P=0.785N     (e)          P=0.500      (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 15      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      0/39.89      1/40.04     |0/41.94      0/42.89      2/41.48      1/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         2.5%        |0.0%         0.0%         4.8%         2.5%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    1/28 (4%)   |0/30 (0%)    0/31 (0%)    1/28 (4%)    1/27 (4%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          727 (T)     |---          ---          723          728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.222      (e)          (e)          P=0.515     |P=0.327      (e)          P=0.225      P=0.479      | 
|POLY 3             |     P=0.210      (e)          (e)          P=0.494     |P=0.321      (e)          P=0.234      P=0.487      | 
|POLY 1.5           |     P=0.210      (e)          (e)          P=0.493     |P=0.326      (e)          P=0.235      P=0.489      | 
|POLY 6             |     P=0.211      (e)          (e)          P=0.498     |P=0.318      (e)          P=0.233      P=0.487      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.515     |P=0.325      (e)          P=0.224      P=0.479      | 
|COCH-ARM / FISHERS |     P=0.215      (e)          (e)          P=0.500     |P=0.354      (e)          P=0.247      P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     27/50 (54%)  27/50 (54%)  22/50 (44%)  19/50 (38%) |39/50 (78%)  35/50 (70%)  40/50 (80%)  34/50 (68%)  | 
|POLY-3 RATE (b)    |     27/42.66     27/42.45     22/41.05     19/40.36    |39/45.11     35/45.66     40/45.06     34/41.41     | 
|POLY-3 PERCENT (g) |     63.3%        63.6%        53.6%        47.1%       |86.5%        76.7%        88.8%        82.1%        | 
|TERMINAL (d)       |     22/26 (85%)  25/29 (86%)  19/25 (76%)  18/28 (64%) |27/30 (90%)  27/31 (87%)  27/28 (96%)  25/27 (93%)  | 
|FIRST INCIDENCE    |     475          577          533          640         |509          333          474          588          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.009N**   P=0.325N     P=0.236N     P=0.019N*   |P=0.506      P=0.212N     P=0.340      P=0.463N     | 
|POLY 3             |     P=0.050N     P=0.581      P=0.236N     P=0.093N    |P=0.551N     P=0.154N     P=0.494      P=0.387N     | 
|POLY 1.5           |     P=0.056N     P=0.562      P=0.212N     P=0.100N    |P=0.475N     P=0.177N     P=0.487      P=0.338N     | 
|POLY 6             |     P=0.039N*    P=0.584N     P=0.284N     P=0.077N    |P=0.581N     P=0.154N     P=0.491      P=0.415N     | 
|LOGISTIC REGRESSION|     P=0.031N*    P=0.467N     P=0.288N     P=0.053N    |P=0.451N     P=0.182N     P=0.448      P=0.304N     | 
|COCH-ARM / FISHERS |     P=0.045N*    P=0.579N     P=0.212N     P=0.080N    |P=0.216N     P=0.247N     P=0.500      P=0.184N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 16      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Clear Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     18/50 (36%)  22/50 (44%)  23/50 (46%)  16/50 (32%) |8/50 (16%)   4/50 (8%)    8/50 (16%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |     18/41.88     22/42.12     23/41.35     16/40.90    |8/42.49      4/42.89      8/42.89      6/39.51      | 
|POLY-3 PERCENT (g) |     43.0%        52.2%        55.6%        39.1%       |18.8%        9.3%         18.7%        15.2%        | 
|TERMINAL (d)       |     17/26 (65%)  21/29 (72%)  19/25 (76%)  14/28 (50%) |7/30 (23%)   4/31 (13%)   3/28 (11%)   5/27 (19%)   | 
|FIRST INCIDENCE    |     503          674          574          433         |559          728 (T)      483          680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.142N     P=0.403      P=0.111      P=0.309N    |P=0.537      P=0.160N     P=0.565      P=0.468N     | 
|POLY 3             |     P=0.235N     P=0.258      P=0.165      P=0.446N    |P=0.561      P=0.170N     P=0.601N     P=0.443N     | 
|POLY 1.5           |     P=0.251N     P=0.250      P=0.189      P=0.460N    |P=0.570N     P=0.173N     P=0.606N     P=0.435N     | 
|POLY 6             |     P=0.202N     P=0.285      P=0.137      P=0.411N    |P=0.555      P=0.166N     P=0.592N     P=0.446N     | 
|LOGISTIC REGRESSION|     P=0.223N     P=0.345      P=0.112      P=0.425N    |P=0.573N     P=0.160N     P=0.601      P=0.436N     | 
|COCH-ARM / FISHERS |     P=0.219N     P=0.270      P=0.208      P=0.417N    |P=0.512N     P=0.178N     P=0.607N     P=0.387N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Eosinophilic Focus                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   12/50 (24%)  5/50 (10%)   4/50 (8%)   |12/50 (24%)  12/50 (24%)  14/50 (28%)  10/50 (20%)  | 
|POLY-3 RATE (b)    |     9/41.58      12/41.91     5/40.40      4/40.30     |12/43.12     12/43.83     14/42.36     10/39.64     | 
|POLY-3 PERCENT (g) |     21.7%        28.6%        12.4%        9.9%        |27.8%        27.4%        33.1%        25.2%        | 
|TERMINAL (d)       |     7/26 (27%)   12/29 (41%)  3/25 (12%)   2/28 (7%)   |7/30 (23%)   8/31 (26%)   10/28 (36%)  7/27 (26%)   | 
|FIRST INCIDENCE    |     630          727 (T)      630          679         |601          510          545          672          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.033N*    P=0.405      P=0.227N     P=0.104N    |P=0.469N     P=0.557N     P=0.354      P=0.503N     | 
|POLY 3             |     P=0.038N*    P=0.314      P=0.204N     P=0.124N    |P=0.448N     P=0.577N     P=0.385      P=0.492N     | 
|POLY 1.5           |     P=0.040N*    P=0.305      P=0.196N     P=0.128N    |P=0.424N     P=0.583N     P=0.394      P=0.475N     | 
|POLY 6             |     P=0.033N*    P=0.329      P=0.218N     P=0.114N    |P=0.469N     P=0.574N     P=0.371      P=0.509N     | 
|LOGISTIC REGRESSION|     P=0.038N*    P=0.370      P=0.228N     P=0.115N    |P=0.421N     P=0.573N     P=0.395      P=0.471N     | 
|COCH-ARM / FISHERS |     P=0.037N*    P=0.312      P=0.194N     P=0.117N    |P=0.335N     P=0.592N     P=0.410      P=0.405N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 17      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   5/50 (10%)   7/50 (14%)   9/50 (18%)  |9/50 (18%)   8/50 (16%)   11/50 (22%)  14/50 (28%)  | 
|POLY-3 RATE (b)    |     5/43.04      5/43.09      7/41.87      9/42.56     |9/44.37      8/44.23      11/44.18     14/42.88     | 
|POLY-3 PERCENT (g) |     11.6%        11.6%        16.7%        21.2%       |20.3%        18.1%        24.9%        32.7%        | 
|TERMINAL (d)       |     2/26 (8%)    3/29 (10%)   3/25 (12%)   5/28 (18%)  |5/30 (17%)   4/31 (13%)   5/28 (18%)   7/27 (26%)   | 
|FIRST INCIDENCE    |     111          503          419          120         |191          589          111          273          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.131      P=0.593N     P=0.359      P=0.220     |P=0.059      P=0.476N     P=0.366      P=0.138      | 
|POLY 3             |     P=0.112      P=0.630N     P=0.358      P=0.183     |P=0.066      P=0.503N     P=0.396      P=0.141      | 
|POLY 1.5           |     P=0.111      P=0.621      P=0.368      P=0.179     |P=0.067      P=0.509N     P=0.398      P=0.141      | 
|POLY 6             |     P=0.116      P=0.614N     P=0.345      P=0.194     |P=0.065      P=0.489N     P=0.392      P=0.144      | 
|LOGISTIC REGRESSION|     P=0.162      P=0.616N     P=0.358      P=0.255     |P=0.122      P=0.511N     P=0.422      P=0.210      | 
|COCH-ARM / FISHERS |     P=0.120      P=0.630N     P=0.380      P=0.194     |P=0.086      P=0.500N     P=0.402      P=0.171      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Granulomatous                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     30/50 (60%)  26/50 (52%)  32/50 (64%)  27/50 (54%) |36/50 (72%)  31/50 (62%)  37/50 (74%)  39/50 (78%)  | 
|POLY-3 RATE (b)    |     30/45.00     26/43.47     32/42.93     27/41.94    |36/46.63     31/46.42     37/44.40     39/46.28     | 
|POLY-3 PERCENT (g) |     66.7%        59.8%        74.5%        64.4%       |77.2%        66.8%        83.3%        84.3%        | 
|TERMINAL (d)       |     23/26 (89%)  22/29 (76%)  24/25 (96%)  19/28 (68%) |24/30 (80%)  23/31 (74%)  27/28 (96%)  25/27 (93%)  | 
|FIRST INCIDENCE    |     475          478          462          604         |406          197          375          111          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.355N     P=0.105N     P=0.297      P=0.246N    |P=0.038 *    P=0.189N     P=0.339      P=0.170      | 
|POLY 3             |     P=0.548      P=0.321N     P=0.268      P=0.501N    |P=0.076      P=0.176N     P=0.304      P=0.261      | 
|POLY 1.5           |     P=0.550N     P=0.316N     P=0.346      P=0.484N    |P=0.090      P=0.174N     P=0.377      P=0.283      | 
|POLY 6             |     P=0.525N     P=0.309N     P=0.183      P=0.464N    |P=0.068      P=0.183N     P=0.221      P=0.248      | 
|LOGISTIC REGRESSION|     P=0.499N     P=0.255N     P=0.352      P=0.414N    |P=0.073      P=0.189N     P=0.469      P=0.266      | 
|COCH-ARM / FISHERS |     P=0.407N     P=0.273N     P=0.418      P=0.343N    |P=0.129      P=0.198N     P=0.500      P=0.322      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 18      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Mixed Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   17/50 (34%)  13/50 (26%)  11/50 (22%) |19/50 (38%)  12/50 (24%)  10/50 (20%)  9/50 (18%)   | 
|POLY-3 RATE (b)    |     8/41.85      17/41.95     13/40.07     11/40.29    |19/42.42     12/43.17     10/41.76     9/39.83      | 
|POLY-3 PERCENT (g) |     19.1%        40.5%        32.4%        27.3%       |44.8%        27.8%        24.0%        22.6%        | 
|TERMINAL (d)       |     7/26 (27%)   16/29 (55%)  12/25 (48%)  10/28 (36%) |17/30 (57%)  9/31 (29%)   7/28 (25%)   7/27 (26%)   | 
|FIRST INCIDENCE    |     519          719          679          661         |596          678          667          588          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.436N     P=0.044 *    P=0.120      P=0.353     |P=0.083N     P=0.077N     P=0.055N     P=0.038N*    | 
|POLY 3             |     P=0.530N     P=0.025 *    P=0.126      P=0.267     |P=0.057N     P=0.074N     P=0.033N*    P=0.026N*    | 
|POLY 1.5           |     P=0.532N     P=0.025 *    P=0.145      P=0.267     |P=0.056N     P=0.083N     P=0.035N*    P=0.027N*    | 
|POLY 6             |     P=0.509N     P=0.026 *    P=0.103      P=0.280     |P=0.056N     P=0.065N     P=0.031N*    P=0.023N*    | 
|LOGISTIC REGRESSION|     P=0.504N     P=0.039 *    P=0.105      P=0.293     |P=0.064N     P=0.062N     P=0.035N*    P=0.028N*    | 
|COCH-ARM / FISHERS |     P=0.477N     P=0.032 *    P=0.163      P=0.306     |P=0.044N*    P=0.097N     P=0.038N*    P=0.022N*    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Bile Duct                                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     44/50 (88%)  41/50 (82%)  32/50 (64%)  39/50 (78%) |13/50 (26%)  14/50 (28%)  11/50 (22%)  14/50 (28%)  | 
|POLY-3 RATE (b)    |     44/47.17     41/45.36     32/43.58     39/44.71    |13/43.99     14/44.12     11/42.88     14/41.20     | 
|POLY-3 PERCENT (g) |     93.3%        90.4%        73.4%        87.2%       |29.6%        31.7%        25.7%        34.0%        | 
|TERMINAL (d)       |     26/26 (100%) 27/29 (93%)  22/25 (88%)  24/28 (86%) |7/30 (23%)   8/31 (26%)   5/28 (18%)   7/27 (26%)   | 
|FIRST INCIDENCE    |     475          478          484          433         |191          510          491          379          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.265N     P=0.170N     P=0.053N     P=0.182N    |P=0.361      P=0.533      P=0.464N     P=0.403      | 
|POLY 3             |     P=0.274N     P=0.444N     P=0.004N**   P=0.249N    |P=0.393      P=0.504      P=0.434N     P=0.418      | 
|POLY 1.5           |     P=0.295N     P=0.403N     P=0.003N**   P=0.249N    |P=0.402      P=0.495      P=0.431N     P=0.424      | 
|POLY 6             |     P=0.206N     P=0.447N     P=0.009N**   P=0.192N    |P=0.391      P=0.515      P=0.436N     P=0.421      | 
|LOGISTIC REGRESSION|     P=0.362N     P=0.301N     P=0.003N**   P=0.265N    |P=0.425      P=0.505      P=0.410N     P=0.465      | 
|COCH-ARM / FISHERS |     P=0.217N     P=0.288N     P=0.005N**   P=0.143N    |P=0.482      P=0.500      P=0.408N     P=0.500      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 19      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Centrilobular                                                                                                             | 
|     Fatty Change                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |1/50 (2%)    2/50 (4%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      1/40.07      1/40.41     |1/42.39      2/43.49      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.5%         2.5%        |2.4%         4.6%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          679          622         |596          622          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.311      (e)          P=0.482      P=0.510     |P=0.228N     P=0.512      P=0.509N     P=0.519N     | 
|POLY 3             |     P=0.297      (e)          P=0.494      P=0.496     |P=0.222N     P=0.509      P=0.504N     P=0.515N     | 
|POLY 1.5           |     P=0.296      (e)          P=0.498      P=0.494     |P=0.221N     P=0.505      P=0.503N     P=0.513N     | 
|POLY 6             |     P=0.302      (e)          P=0.489      P=0.502     |P=0.223N     P=0.515      P=0.507N     P=0.517N     | 
|LOGISTIC REGRESSION|     P=0.308      (e)          P=0.498      P=0.509     |P=0.198N     P=0.495      P=0.491N     P=0.476N     | 
|COCH-ARM / FISHERS |     P=0.305      (e)          P=0.500      P=0.500     |P=0.214N     P=0.500      P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Centrilobular                                                                                                             | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    3/50 (6%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/41.33      1/42.19      2/40.59      3/41.76     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     2.4%         2.4%         4.9%         7.2%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     699          654          561          352         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.175      P=0.742N     P=0.466      P=0.291     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.182      P=0.756N     P=0.494      P=0.308     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.179      P=0.760N     P=0.499      P=0.302     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.188      P=0.750N     P=0.486      P=0.319     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.222      P=0.762N     P=0.499      P=0.358     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.182      P=0.753N     P=0.500      P=0.309     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 20      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |5/50 (10%)   3/50 (6%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      0/39.89      0/40.04     |5/45.26      3/45.40      1/41.86      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |11.1%        6.6%         2.4%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |191          197          614          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.030N*    P=0.356N     P=0.111N     P=0.042N*    | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.030N*    P=0.354N     P=0.120N     P=0.044N*    | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.029N*    P=0.355N     P=0.115N     P=0.041N*    | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.032N*    P=0.356N     P=0.126N     P=0.047N*    | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.002N**   P=0.369N     P=0.062N     P=0.005N**   | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.024N*    P=0.357N     P=0.102N     P=0.028N*    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    1/50 (2%)    4/50 (8%)   |2/50 (4%)    1/50 (2%)    1/50 (2%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     2/42.21      1/42.88      1/40.36      4/42.85     |2/42.06      1/43.80      1/42.04      4/42.44      | 
|POLY-3 PERCENT (g) |     4.7%         2.3%         2.5%         9.3%        |4.8%         2.3%         2.4%         9.4%         | 
|TERMINAL (d)       |     1/26 (4%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     111          223          587          120         |707          333          545          111          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.129      P=0.487N     P=0.513N     P=0.338     |P=0.114      P=0.497N     P=0.524N     P=0.314      | 
|POLY 3             |     P=0.129      P=0.494N     P=0.516N     P=0.344     |P=0.124      P=0.486N     P=0.500N     P=0.341      | 
|POLY 1.5           |     P=0.127      P=0.500N     P=0.509N     P=0.335     |P=0.125      P=0.491N     P=0.501N     P=0.339      | 
|POLY 6             |     P=0.133      P=0.485N     P=0.524N     P=0.357     |P=0.123      P=0.481N     P=0.500N     P=0.344      | 
|LOGISTIC REGRESSION|     P=0.314      P=0.392N     P=0.627N     P=0.613     |P=0.339      P=0.508N     P=0.498N     P=0.577      | 
|COCH-ARM / FISHERS |     P=0.128      P=0.500N     P=0.500N     P=0.339     |P=0.128      P=0.500N     P=0.500N     P=0.339      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 21      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Metaplasia Osseous                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/41.22      3/41.91      0/39.89      0/40.04     |2/41.94      0/42.89      1/41.46      1/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         7.2%         0.0%         0.0%        |4.8%         0.0%         2.4%         2.5%         | 
|TERMINAL (d)       |     0/26 (0%)    3/29 (10%)   0/25 (0%)    0/28 (0%)   |2/30 (7%)    0/31 (0%)    1/28 (4%)    1/27 (4%)    | 
|FIRST INCIDENCE    |     ---          727 (T)      ---          ---         |728 (T)      ---          728 (T)      728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.261N     P=0.140      (e)          (e)         |P=0.653N     P=0.231N     P=0.524N     P=0.537N     | 
|POLY 3             |     P=0.265N     P=0.121      (e)          (e)         |P=0.633N     P=0.232N     P=0.504N     P=0.522N     | 
|POLY 1.5           |     P=0.269N     P=0.119      (e)          (e)         |P=0.629N     P=0.234N     P=0.503N     P=0.520N     | 
|POLY 6             |     P=0.256N     P=0.126      (e)          (e)         |P=0.636N     P=0.229N     P=0.505N     P=0.523N     | 
|LOGISTIC REGRESSION|     (e)          P=0.140      (e)          (e)         |P=0.653N     (e)          P=0.524N     P=0.537N     | 
|COCH-ARM / FISHERS |     P=0.266N     P=0.121      (e)          (e)         |P=0.614N     P=0.247N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   0/50 (0%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     6/41.94      0/41.91      0/39.89      1/40.04     |1/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     14.3%        0.0%         0.0%         2.5%        |2.4%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     5/26 (19%)   0/29 (0%)    0/25 (0%)    1/28 (4%)   |1/30 (3%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     475          ---          ---          727 (T)     |728 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.117N     P=0.013N*    P=0.019N*    P=0.050N    |P=0.490N     P=0.493N     P=0.514N     P=0.521N     | 
|POLY 3             |     P=0.114N     P=0.015N*    P=0.017N*    P=0.062N    |P=0.472N     P=0.496N     P=0.502N     P=0.513N     | 
|POLY 1.5           |     P=0.113N     P=0.016N*    P=0.016N*    P=0.063N    |P=0.471N     P=0.498N     P=0.502N     P=0.511N     | 
|POLY 6             |     P=0.115N     P=0.014N*    P=0.019N*    P=0.059N    |P=0.474N     P=0.493N     P=0.503N     P=0.513N     | 
|LOGISTIC REGRESSION|     P=0.123N     P=0.017N*    P=0.018N*    P=0.062N    |P=0.490N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.118N     P=0.013N*    P=0.013N*    P=0.056N    |P=0.471N     P=0.500N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 22      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    4/50 (8%)    3/50 (6%)    3/50 (6%)   |3/50 (6%)    4/50 (8%)    5/50 (10%)   3/50 (6%)    | 
|POLY-3 RATE (b)    |     3/41.85      4/41.91      3/40.52      3/40.79     |3/41.94      4/42.89      5/41.54      3/39.80      | 
|POLY-3 PERCENT (g) |     7.2%         9.5%         7.4%         7.4%        |7.2%         9.3%         12.0%        7.5%         | 
|TERMINAL (d)       |     2/26 (8%)    4/29 (14%)   2/25 (8%)    2/28 (7%)   |3/30 (10%)   4/31 (13%)   3/28 (11%)   1/27 (4%)    | 
|FIRST INCIDENCE    |     519          727 (T)      521          456         |728 (T)      728 (T)      713          656          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.520N     P=0.550      P=0.653      P=0.654N    |P=0.578N     P=0.518      P=0.321      P=0.622      | 
|POLY 3             |     P=0.539N     P=0.501      P=0.648      P=0.651     |P=0.550N     P=0.512      P=0.350      P=0.639      | 
|POLY 1.5           |     P=0.542N     P=0.496      P=0.657      P=0.647     |P=0.546N     P=0.507      P=0.351      P=0.639      | 
|POLY 6             |     P=0.530N     P=0.511      P=0.634      P=0.661     |P=0.546N     P=0.519      P=0.349      P=0.644      | 
|LOGISTIC REGRESSION|     P=0.535N     P=0.507      P=0.663N     P=0.659N    |P=0.563N     P=0.518      P=0.323      P=0.634      | 
|COCH-ARM / FISHERS |     P=0.525N     P=0.500      P=0.661N     P=0.661N    |P=0.508N     P=0.500      P=0.357      P=0.661N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      0/39.89      2/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         5.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    2/28 (7%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          727 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.045 *    (e)          (e)          P=0.254     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.039 *    (e)          (e)          P=0.230     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.039 *    (e)          (e)          P=0.229     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.039 *    (e)          (e)          P=0.235     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.254     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.042 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 23      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Inflammation Acute                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/41.65      1/42.48      0/39.89      2/41.00     |0/41.94      1/43.27      0/41.46      1/39.51      | 
|POLY-3 PERCENT (g) |     2.4%         2.4%         0.0%         4.9%        |0.0%         2.3%         0.0%         2.5%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     600          551          ---          352         |---          622          ---          680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.329      P=0.752N     P=0.516N     P=0.498     |P=0.444      P=0.515      (e)          P=0.482      | 
|POLY 3             |     P=0.327      P=0.757N     P=0.509N     P=0.494     |P=0.444      P=0.506      (e)          P=0.488      | 
|POLY 1.5           |     P=0.326      P=0.760N     P=0.503N     P=0.491     |P=0.446      P=0.503      (e)          P=0.489      | 
|POLY 6             |     P=0.330      P=0.751N     P=0.516N     P=0.501     |P=0.445      P=0.510      (e)          P=0.489      | 
|LOGISTIC REGRESSION|     P=0.395      P=0.755N     P=0.514N     P=0.556     |P=0.466      P=0.497      (e)          P=0.493      | 
|COCH-ARM / FISHERS |     P=0.332      P=0.753N     P=0.500N     P=0.500     |P=0.459      P=0.500      (e)          P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Inflammation Chronic Focal                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    6/50 (12%)   11/50 (22%)  14/50 (28%) |2/50 (4%)    25/50 (50%)  27/50 (54%)  34/50 (68%)  | 
|POLY-3 RATE (b)    |     0/41.22      6/41.97      11/41.70     14/41.63    |2/41.94      25/45.19     27/43.59     34/42.81     | 
|POLY-3 PERCENT (g) |     0.0%         14.3%        26.4%        33.6%       |4.8%         55.3%        61.9%        79.4%        | 
|TERMINAL (d)       |     0/26 (0%)    5/29 (17%)   6/25 (24%)   9/28 (32%)  |2/30 (7%)    17/31 (55%)  21/28 (75%)  23/27 (85%)  | 
|FIRST INCIDENCE    |     ---          713          484          433         |728 (T)      510          483          495          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.024 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P=0.016 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.015 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.017 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.020 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.013 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 24      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Ectasia                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    2/50 (4%)    3/50 (6%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/41.22      2/41.91      2/39.89      1/40.04     |0/41.94      2/42.89      3/41.46      1/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         4.8%         5.0%         2.5%        |0.0%         4.7%         7.2%         2.5%         | 
|TERMINAL (d)       |     0/26 (0%)    2/29 (7%)    2/25 (8%)    1/28 (4%)   |0/30 (0%)    2/31 (7%)    3/28 (11%)   1/27 (4%)    | 
|FIRST INCIDENCE    |     ---          727 (T)      727 (T)      727 (T)     |---          728 (T)      728 (T)      728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.626      P=0.262      P=0.229      P=0.515     |P=0.573      P=0.245      P=0.108      P=0.479      | 
|POLY 3             |     P=0.599      P=0.241      P=0.229      P=0.494     |P=0.577      P=0.242      P=0.116      P=0.487      | 
|POLY 1.5           |     P=0.597      P=0.237      P=0.234      P=0.493     |P=0.582      P=0.240      P=0.117      P=0.489      | 
|POLY 6             |     P=0.608      P=0.246      P=0.222      P=0.498     |P=0.575      P=0.245      P=0.115      P=0.487      | 
|LOGISTIC REGRESSION|     (e)          P=0.262      P=0.229      P=0.515     |(e)          P=0.245      P=0.108      P=0.479      | 
|COCH-ARM / FISHERS |     P=0.615      P=0.247      P=0.247      P=0.500     |P=0.617      P=0.247      P=0.121      P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    3/50 (6%)    2/50 (4%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     2/41.71      0/41.91      0/39.89      1/41.00     |0/41.94      3/42.94      2/42.06      3/40.18      | 
|POLY-3 PERCENT (g) |     4.8%         0.0%         0.0%         2.4%        |0.0%         7.0%         4.8%         7.5%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    2/31 (7%)    0/28 (0%)    1/27 (4%)    | 
|FIRST INCIDENCE    |     589          ---          ---          237         |---          716          545          525          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.648N     P=0.240N     P=0.272N     P=0.508N    |P=0.202      P=0.128      P=0.230      P=0.111      | 
|POLY 3             |     P=0.648N     P=0.236N     P=0.247N     P=0.506N    |P=0.215      P=0.123      P=0.237      P=0.111      | 
|POLY 1.5           |     P=0.647N     P=0.238N     P=0.241N     P=0.508N    |P=0.215      P=0.121      P=0.237      P=0.111      | 
|POLY 6             |     P=0.649N     P=0.232N     P=0.256N     P=0.501N    |P=0.218      P=0.125      P=0.238      P=0.112      | 
|LOGISTIC REGRESSION|     P=0.569N     P=0.237N     P=0.237N     P=0.420N    |P=0.229      P=0.127      P=0.241      P=0.123      | 
|COCH-ARM / FISHERS |     P=0.646N     P=0.247N     P=0.247N     P=0.500N    |P=0.235      P=0.121      P=0.247      P=0.121      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 25      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    7/50 (14%)   2/50 (4%)    1/50 (2%)   |2/50 (4%)    3/50 (6%)    3/50 (6%)    6/50 (12%)   | 
|POLY-3 RATE (b)    |     2/41.22      7/42.91      2/39.89      1/40.04     |2/41.95      3/42.94      3/41.48      6/39.55      | 
|POLY-3 PERCENT (g) |     4.9%         16.3%        5.0%         2.5%        |4.8%         7.0%         7.2%         15.2%        | 
|TERMINAL (d)       |     2/26 (8%)    6/29 (21%)   2/25 (8%)    1/28 (4%)   |1/30 (3%)    2/31 (7%)    2/28 (7%)    5/27 (19%)   | 
|FIRST INCIDENCE    |     727 (T)      131          727 (T)      727 (T)     |726          716          723          667          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.107N     P=0.104      P=0.683      P=0.474N    |P=0.058      P=0.512      P=0.466      P=0.107      | 
|POLY 3             |     P=0.119N     P=0.087      P=0.683      P=0.510N    |P=0.066      P=0.511      P=0.495      P=0.113      | 
|POLY 1.5           |     P=0.122N     P=0.083      P=0.690      P=0.513N    |P=0.068      P=0.506      P=0.496      P=0.115      | 
|POLY 6             |     P=0.112N     P=0.093      P=0.672      P=0.503N    |P=0.065      P=0.517      P=0.493      P=0.113      | 
|LOGISTIC REGRESSION|     P=0.121N     P=0.081      P=0.683      P=0.474N    |P=0.057      P=0.519      P=0.468      P=0.110      | 
|COCH-ARM / FISHERS |     P=0.116N     P=0.080      P=0.691N     P=0.500N    |P=0.082      P=0.500      P=0.500      P=0.134      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    4/50 (8%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      1/39.89      0/40.04     |1/41.94      0/42.89      4/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.5%         0.0%        |2.4%         0.0%         9.7%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    1/25 (4%)    0/28 (0%)   |1/30 (3%)    0/31 (0%)    4/28 (14%)   0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          727 (T)      ---         |728 (T)      ---          728 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.778N     (e)          P=0.492      (e)         |P=0.477N     P=0.493N     P=0.157      P=0.521N     | 
|POLY 3             |     P=0.790N     (e)          P=0.493      (e)         |P=0.477N     P=0.496N     P=0.174      P=0.513N     | 
|POLY 1.5           |     P=0.790N     (e)          P=0.498      (e)         |P=0.470N     P=0.498N     P=0.175      P=0.511N     | 
|POLY 6             |     P=0.789N     (e)          P=0.487      (e)         |P=0.481N     P=0.493N     P=0.172      P=0.513N     | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.492      (e)         |P=0.477N     (e)          P=0.157      (e)          | 
|COCH-ARM / FISHERS |     P=0.785N     (e)          P=0.500      (e)         |P=0.436N     P=0.500N     P=0.181      P=0.500N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 26      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Ectasia                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/50 (4%)    0/49 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |     0/41.22      2/42.19      2/39.89      0/39.18     |0/41.94      0/42.89      0/41.46      1/38.51      | 
|POLY-3 PERCENT (g) |     0.0%         4.7%         5.0%         0.0%        |0.0%         0.0%         0.0%         2.6%         | 
|TERMINAL (d)       |     0/26 (0%)    1/29 (3%)    2/25 (8%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/26 (0%)    | 
|FIRST INCIDENCE    |     ---          654          727 (T)      ---         |---          ---          ---          680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.378N     P=0.261      P=0.229      (e)         |P=0.200      (e)          (e)          P=0.482      | 
|POLY 3             |     P=0.404N     P=0.242      P=0.229      (e)         |P=0.201      (e)          (e)          P=0.483      | 
|POLY 1.5           |     P=0.407N     P=0.238      P=0.234      (e)         |P=0.202      (e)          (e)          P=0.484      | 
|POLY 6             |     P=0.396N     P=0.249      P=0.222      (e)         |P=0.200      (e)          (e)          P=0.483      | 
|LOGISTIC REGRESSION|     P=0.400N     P=0.239      P=0.229      (e)         |P=0.205      (e)          (e)          P=0.488      | 
|COCH-ARM / FISHERS |     P=0.392N     P=0.247      P=0.247      (e)         |P=0.211      (e)          (e)          P=0.495      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    1/49 (2%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    2/49 (4%)    | 
|POLY-3 RATE (b)    |     0/41.22      1/42.41      1/40.59      1/40.07     |0/41.94      0/42.89      2/41.75      2/39.50      | 
|POLY-3 PERCENT (g) |     0.0%         2.4%         2.5%         2.5%        |0.0%         0.0%         4.8%         5.1%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/26 (0%)    | 
|FIRST INCIDENCE    |     ---          577          484          352         |---          ---          667          139          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.472      P=0.505      P=0.500      P=0.487     |P=0.109      (e)          P=0.236      P=0.228      | 
|POLY 3             |     P=0.472      P=0.506      P=0.497      P=0.494     |P=0.107      (e)          P=0.236      P=0.224      | 
|POLY 1.5           |     P=0.468      P=0.502      P=0.500      P=0.492     |P=0.109      (e)          P=0.236      P=0.224      | 
|POLY 6             |     P=0.480      P=0.512      P=0.492      P=0.500     |P=0.106      (e)          P=0.236      P=0.224      | 
|LOGISTIC REGRESSION|     P=0.582      P=0.509      P=0.417      P=0.604     |P=0.179      (e)          P=0.236      P=0.358      | 
|COCH-ARM / FISHERS |     P=0.478      P=0.500      P=0.500      P=0.495     |P=0.119      (e)          P=0.247      P=0.242      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 27      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    18/50 (36%)  39/49 (80%) |0/50 (0%)    3/50 (6%)    27/50 (54%)  41/49 (84%)  | 
|POLY-3 RATE (b)    |     1/41.24      1/41.91      18/42.35     39/46.11    |0/41.94      3/43.87      27/43.55     41/43.68     | 
|POLY-3 PERCENT (g) |     2.4%         2.4%         42.5%        84.6%       |0.0%         6.8%         62.0%        93.9%        | 
|TERMINAL (d)       |     0/26 (0%)    1/29 (3%)    10/25 (40%)  24/28 (86%) |0/30 (0%)    2/31 (7%)    21/28 (75%)  26/26 (100%) | 
|FIRST INCIDENCE    |     721          727 (T)      492          237         |---          197          405          111          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.748N     P<0.001 **   P<0.001 **  |P<0.001 **   P=0.128      P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P=0.757N     P<0.001 **   P<0.001 **  |P<0.001 **   P=0.127      P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.760N     P<0.001 **   P<0.001 **  |P<0.001 **   P=0.124      P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.752N     P<0.001 **   P<0.001 **  |P<0.001 **   P=0.129      P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.747N     P<0.001 **   P<0.001 **  |P<0.001 **   P=0.110      P<0.001 **   P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.753N     P<0.001 **   P<0.001 **  |P<0.001 **   P=0.121      P<0.001 **   P<0.001 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Inflammation Granulomatous                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    3/49 (6%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      0/39.89      3/39.61     |0/41.94      0/42.89      0/41.46      0/38.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         7.6%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    2/28 (7%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/26 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          604         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.011 *    (e)          (e)          P=0.136     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.007 **   (e)          (e)          P=0.111     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.007 **   (e)          (e)          P=0.109     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.007 **   (e)          (e)          P=0.116     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.008 **   (e)          (e)          P=0.112     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.008 **   (e)          (e)          P=0.117     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 28      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     25/49 (51%)  37/49 (76%)  31/50 (62%)  17/48 (35%) |2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     25/45.36     37/47.83     31/46.70     17/43.03    |2/42.42      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     55.1%        77.4%        66.4%        39.5%       |4.7%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     12/26 (46%)  19/28 (68%)  15/25 (60%)  8/28 (29%)  |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     475          131          419          237         |596          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.012N*    P=0.083      P=0.161      P=0.102N    |P=0.252N     P=0.248N     P=0.256N     P=0.261N     | 
|POLY 3             |     P=0.003N**   P=0.016 *    P=0.180      P=0.101N    |P=0.240N     P=0.234N     P=0.242N     P=0.254N     | 
|POLY 1.5           |     P=0.003N**   P=0.012 *    P=0.182      P=0.105N    |P=0.239N     P=0.236N     P=0.241N     P=0.251N     | 
|POLY 6             |     P=0.003N**   P=0.023 *    P=0.176      P=0.096N    |P=0.241N     P=0.233N     P=0.244N     P=0.256N     | 
|LOGISTIC REGRESSION|     P=0.002N**   P=0.012 *    P=0.198      P=0.083N    |P=0.235N     P=0.239N     P=0.236N     P=0.237N     | 
|COCH-ARM / FISHERS |     P=0.002N**   P=0.010 *    P=0.184      P=0.089N    |P=0.238N     P=0.247N     P=0.247N     P=0.247N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/49 (0%)    0/50 (0%)    0/48 (0%)   |6/50 (12%)   3/50 (6%)    3/50 (6%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/41.21      0/40.91      0/39.89      0/39.24     |6/43.58      3/42.95      3/42.62      2/40.15      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |13.8%        7.0%         7.0%         5.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/28 (0%)    0/25 (0%)    0/28 (0%)   |3/30 (10%)   2/31 (7%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |462          714          483          518          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.203N     P=0.236N     P=0.264N     P=0.171N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.184N     P=0.248N     P=0.252N     P=0.160N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.181N     P=0.246N     P=0.250N     P=0.155N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.185N     P=0.250N     P=0.255N     P=0.162N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.143N     P=0.244N     P=0.231N     P=0.117N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.161N     P=0.243N     P=0.243N     P=0.134N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 29      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland: Duct                                                                                                              | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     12/49 (24%)  24/49 (49%)  27/50 (54%)  15/48 (31%) |29/50 (58%)  15/50 (30%)  20/50 (40%)  23/50 (46%)  | 
|POLY-3 RATE (b)    |     12/43.36     24/42.70     27/42.98     15/40.74    |29/45.21     15/43.74     20/45.16     23/42.79     | 
|POLY-3 PERCENT (g) |     27.7%        56.2%        62.8%        36.8%       |64.2%        34.3%        44.3%        53.8%        | 
|TERMINAL (d)       |     4/26 (15%)   15/28 (54%)  17/25 (68%)  10/28 (36%) |19/30 (63%)  11/31 (36%)  9/28 (32%)   14/27 (52%)  | 
|FIRST INCIDENCE    |     505          478          462          433         |462          589          483          495          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.329N     P=0.035 *    P=0.003 **   P=0.367     |P=0.378      P=0.006N**   P=0.126N     P=0.321N     | 
|POLY 3             |     P=0.435N     P=0.005 **   P<0.001 **   P=0.252     |P=0.490      P=0.003N**   P=0.042N*    P=0.215N     | 
|POLY 1.5           |     P=0.446N     P=0.005 **   P<0.001 **   P=0.249     |P=0.482      P=0.003N**   P=0.046N*    P=0.216N     | 
|POLY 6             |     P=0.409N     P=0.006 **   P<0.001 **   P=0.266     |P=0.515      P=0.003N**   P=0.036N*    P=0.203N     | 
|LOGISTIC REGRESSION|     P=0.411N     P=0.008 **   P<0.001 **   P=0.272     |P=0.461      P=0.003N**   P=0.057N     P=0.222N     | 
|COCH-ARM / FISHERS |     P=0.366N     P=0.010 *    P=0.002 **   P=0.303     |P=0.537N     P=0.004N**   P=0.055N     P=0.158N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Inflammation Granulomatous                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/9 (0%)     0/11 (0%)    0/9 (0%)     2/13 (15%)  |0/8 (0%)     0/4 (0%)     0/6 (0%)     0/9 (0%)     | 
|POLY-3 RATE (b)    |     0/7.11       0/10.79      0/6.86       2/10.93     |0/6.66       0/3.28       0/3.89       0/6.50       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         18.3%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/4 (0%)     0/7 (0%)     0/3 (0%)     2/7 (29%)   |0/6 (0%)     0/3 (0%)     0/1 (0%)     0/3 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          727 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.077      (e)          (e)          P=0.362     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.059      (e)          (e)          P=0.331     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.062      (e)          (e)          P=0.326     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.055      (e)          (e)          P=0.335     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.362     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.068      (e)          (e)          P=0.338     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 30      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/9 (78%)    10/11 (91%)  9/9 (100%)   8/13 (62%)  |7/8 (88%)    4/4 (100%)   6/6 (100%)   9/9 (100%)   | 
|POLY-3 RATE (b)    |     7/8.86       10/11.00     9/9.00       8/12.63     |7/7.45       4/4.00       6/6.00       9/9.00       | 
|POLY-3 PERCENT (g) |     79.0%        90.9%        100.0%       63.4%       |93.9%        100.0%       100.0%       100.0%       | 
|TERMINAL (d)       |     4/4 (100%)   6/7 (86%)    3/3 (100%)   3/7 (43%)   |6/6 (100%)   3/3 (100%)   1/1 (100%)   3/3 (100%)   | 
|FIRST INCIDENCE    |     503          705          484          484         |427          474          483          273          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.363N     P=0.634      P=0.226      P=0.515N    |P=0.018 *    P=0.753N     P=0.105      P=0.056      | 
|POLY 3             |     P=0.081N     P=0.457      P=0.240      P=0.384N    |P=0.775      P=0.932      P=0.897      P=0.861      | 
|POLY 1.5           |     P=0.076N     P=0.442      P=0.232      P=0.379N    |P=0.573      P=0.790      P=0.724      P=0.656      | 
|POLY 6             |     P=0.087N     P=0.486      P=0.257      P=0.387N    |P=0.998      P=1.000      P=1.000      P=1.000      | 
|LOGISTIC REGRESSION|     P=0.060N     P=0.309      P=0.250      P=0.412N    |P=0.353      P=0.643      P=0.512      P=0.421      | 
|COCH-ARM / FISHERS |     P=0.076N     P=0.421      P=0.235      P=0.372N    |P=0.414      P=0.667      P=0.571      P=0.471      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   7/50 (14%)   8/50 (16%)   9/50 (18%)  |6/50 (12%)   3/50 (6%)    7/50 (14%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     9/42.45      7/43.28      8/40.77      9/40.97     |6/42.30      3/43.17      7/42.48      5/39.33      | 
|POLY-3 PERCENT (g) |     21.2%        16.2%        19.6%        22.0%       |14.2%        7.0%         16.5%        12.7%        | 
|TERMINAL (d)       |     4/26 (15%)   1/29 (3%)    4/25 (16%)   7/28 (25%)  |5/30 (17%)   2/31 (7%)    5/28 (18%)   4/27 (15%)   | 
|FIRST INCIDENCE    |     547          577          586          433         |629          653          111          727          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.465      P=0.343N     P=0.561N     P=0.571N    |P=0.481      P=0.223N     P=0.458      P=0.566N     | 
|POLY 3             |     P=0.417      P=0.375N     P=0.537N     P=0.572     |P=0.488      P=0.231N     P=0.503      P=0.551N     | 
|POLY 1.5           |     P=0.422      P=0.390N     P=0.515N     P=0.569     |P=0.501      P=0.236N     P=0.506      P=0.543N     | 
|POLY 6             |     P=0.412      P=0.348N     P=0.567N     P=0.583     |P=0.476      P=0.224N     P=0.497      P=0.557N     | 
|LOGISTIC REGRESSION|     P=0.433      P=0.392N     P=0.523N     P=0.578     |P=0.520      P=0.228N     P=0.499      P=0.549N     | 
|COCH-ARM / FISHERS |     P=0.462      P=0.393N     P=0.500N     P=0.602N    |P=0.559      P=0.243N     P=0.500      P=0.500N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 31      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.33      1/41.97      0/39.89      0/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     4.8%         2.4%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/26 (4%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     699          713          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.180N     P=0.463N     P=0.266N     P=0.235N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.172N     P=0.495N     P=0.245N     P=0.244N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.171N     P=0.500N     P=0.240N     P=0.245N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.172N     P=0.486N     P=0.252N     P=0.240N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.174N     P=0.485N     P=0.254N     P=0.239N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.169N     P=0.500N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |4/50 (8%)    5/50 (10%)   7/50 (14%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |                                                        |4/43.47      5/43.27      7/42.34      5/40.50      | 
|POLY-3 PERCENT (g) |                                                        |9.2%         11.6%        16.5%        12.3%        | 
|TERMINAL (d)       |                                                        |2/30 (7%)    4/31 (13%)   5/28 (18%)   3/27 (11%)   | 
|FIRST INCIDENCE    |                                                        |191          622          405          111          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.429      P=0.517      P=0.233      P=0.449      | 
|POLY 3             |                                                        |P=0.445      P=0.497      P=0.244      P=0.456      | 
|POLY 1.5           |                                                        |P=0.457      P=0.494      P=0.248      P=0.463      | 
|POLY 6             |                                                        |P=0.438      P=0.503      P=0.239      P=0.453      | 
|LOGISTIC REGRESSION|                                                        |P=0.547      P=0.491      P=0.270      P=0.600      | 
|COCH-ARM / FISHERS |                                                        |P=0.507      P=0.500      P=0.262      P=0.500      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 32      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas: Acinus                                                                                                                 | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     12/50 (24%)  14/50 (28%)  14/50 (28%)  16/50 (32%) |7/50 (14%)   12/50 (24%)  11/50 (22%)  8/50 (16%)   | 
|POLY-3 RATE (b)    |     12/42.89     14/43.56     14/40.87     16/41.13    |7/42.68      12/43.77     11/44.11     8/41.24      | 
|POLY-3 PERCENT (g) |     28.0%        32.1%        34.3%        38.9%       |16.4%        27.4%        24.9%        19.4%        | 
|TERMINAL (d)       |     7/26 (27%)   9/29 (31%)   12/25 (48%)  11/28 (39%) |6/30 (20%)   10/31 (32%)  5/28 (18%)   5/27 (19%)   | 
|FIRST INCIDENCE    |     503          551          574          622         |462          539          375          379          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.277      P=0.511      P=0.354      P=0.303     |P=0.542N     P=0.171      P=0.193      P=0.424      | 
|POLY 3             |     P=0.187      P=0.425      P=0.349      P=0.201     |P=0.477N     P=0.163      P=0.236      P=0.471      | 
|POLY 1.5           |     P=0.194      P=0.407      P=0.383      P=0.201     |P=0.478N     P=0.157      P=0.229      P=0.467      | 
|POLY 6             |     P=0.193      P=0.464      P=0.304      P=0.217     |P=0.470N     P=0.172      P=0.243      P=0.481      | 
|LOGISTIC REGRESSION|     P=0.208      P=0.413      P=0.371      P=0.220     |P=0.442N     P=0.162      P=0.221      P=0.487      | 
|COCH-ARM / FISHERS |     P=0.249      P=0.410      P=0.410      P=0.252     |P=0.428N     P=0.154      P=0.218      P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas: Acinus                                                                                                                 | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    1/50 (2%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      2/41.91      1/39.89      0/40.04     |1/41.94      1/42.93      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         4.8%         2.5%         0.0%        |2.4%         2.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    2/29 (7%)    1/25 (4%)    0/28 (0%)   |1/30 (3%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          727 (T)      727 (T)      ---         |728 (T)      719          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.378N     P=0.262      P=0.492      (e)         |P=0.325N     P=0.760N     P=0.514N     P=0.521N     | 
|POLY 3             |     P=0.392N     P=0.241      P=0.493      (e)         |P=0.311N     P=0.756N     P=0.502N     P=0.513N     | 
|POLY 1.5           |     P=0.395N     P=0.237      P=0.498      (e)         |P=0.311N     P=0.758N     P=0.502N     P=0.511N     | 
|POLY 6             |     P=0.384N     P=0.246      P=0.487      (e)         |P=0.312N     P=0.753N     P=0.503N     P=0.513N     | 
|LOGISTIC REGRESSION|     (e)          P=0.262      P=0.492      (e)         |P=0.322N     P=0.754N     (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.385N     P=0.247      P=0.500      (e)         |P=0.305N     P=0.753N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 33      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    2/50 (4%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/41.22      1/41.91      0/39.89      1/40.04     |1/41.94      2/43.32      2/41.46      2/39.69      | 
|POLY-3 PERCENT (g) |     0.0%         2.4%         0.0%         2.5%        |2.4%         4.6%         4.8%         5.0%         | 
|TERMINAL (d)       |     0/26 (0%)    1/29 (3%)    0/25 (0%)    1/28 (4%)   |1/30 (3%)    0/31 (0%)    2/28 (7%)    1/27 (4%)    | 
|FIRST INCIDENCE    |     ---          727 (T)      ---          727 (T)     |728 (T)      622          728 (T)      624          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.467      P=0.522      (e)          P=0.515     |P=0.450      P=0.519      P=0.476      P=0.476      | 
|POLY 3             |     P=0.452      P=0.503      (e)          P=0.494     |P=0.456      P=0.511      P=0.496      P=0.481      | 
|POLY 1.5           |     P=0.450      P=0.500      (e)          P=0.493     |P=0.460      P=0.506      P=0.497      P=0.482      | 
|POLY 6             |     P=0.458      P=0.509      (e)          P=0.498     |P=0.456      P=0.518      P=0.495      P=0.483      | 
|LOGISTIC REGRESSION|     (e)          P=0.522      (e)          P=0.515     |P=0.463      P=0.503      P=0.476      P=0.482      | 
|COCH-ARM / FISHERS |     P=0.459      P=0.500      (e)          P=0.500     |P=0.489      P=0.500      P=0.500      P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    3/50 (6%)    5/50 (10%)   2/50 (4%)   |20/50 (40%)  21/50 (42%)  18/50 (36%)  22/50 (44%)  | 
|POLY-3 RATE (b)    |     3/41.58      3/41.91      5/40.86      2/40.47     |20/44.24     21/44.37     18/43.58     22/42.21     | 
|POLY-3 PERCENT (g) |     7.2%         7.2%         12.2%        4.9%        |45.2%        47.3%        41.3%        52.1%        | 
|TERMINAL (d)       |     1/26 (4%)    3/29 (10%)   3/25 (12%)   1/28 (4%)   |13/30 (43%)  15/31 (48%)  12/28 (43%)  14/27 (52%)  | 
|FIRST INCIDENCE    |     630          727 (T)      526          604         |427          474          483          495          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.389N     P=0.621N     P=0.334      P=0.483N    |P=0.238      P=0.547      P=0.500N     P=0.301      | 
|POLY 3             |     P=0.414N     P=0.659N     P=0.346      P=0.512N    |P=0.297      P=0.505      P=0.438N     P=0.333      | 
|POLY 1.5           |     P=0.417N     P=0.661      P=0.354      P=0.516N    |P=0.299      P=0.502      P=0.434N     P=0.333      | 
|POLY 6             |     P=0.405N     P=0.651N     P=0.332      P=0.503N    |P=0.313      P=0.509      P=0.448N     P=0.350      | 
|LOGISTIC REGRESSION|     P=0.411N     P=0.648N     P=0.352      P=0.511N    |P=0.283      P=0.526      P=0.430N     P=0.333      | 
|COCH-ARM / FISHERS |     P=0.395N     P=0.661N     P=0.357      P=0.500N    |P=0.390      P=0.500      P=0.418N     P=0.420      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 34      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      0/39.89      2/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         5.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    2/28 (7%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          727 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.045 *    (e)          (e)          P=0.254     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.039 *    (e)          (e)          P=0.230     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.039 *    (e)          (e)          P=0.229     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.039 *    (e)          (e)          P=0.235     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.254     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.042 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/50 (22%)  12/50 (24%)  17/50 (34%)  9/50 (18%)  |16/50 (32%)  15/50 (30%)  10/50 (20%)  13/50 (26%)  | 
|POLY-3 RATE (b)    |     11/42.30     12/42.77     17/42.98     9/42.73     |16/43.43     15/44.54     10/42.69     13/40.86     | 
|POLY-3 PERCENT (g) |     26.0%        28.1%        39.6%        21.1%       |36.9%        33.7%        23.4%        31.8%        | 
|TERMINAL (d)       |     6/26 (23%)   9/29 (31%)   10/25 (40%)  5/28 (18%)  |14/30 (47%)  11/31 (36%)  7/28 (25%)   8/27 (30%)   | 
|FIRST INCIDENCE    |     519          577          419          261         |406          474          491          518          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.285N     P=0.585N     P=0.117      P=0.387N    |P=0.452N     P=0.457N     P=0.161N     P=0.441N     | 
|POLY 3             |     P=0.267N     P=0.512      P=0.131      P=0.389N    |P=0.395N     P=0.465N     P=0.128N     P=0.398N     | 
|POLY 1.5           |     P=0.285N     P=0.498      P=0.136      P=0.407N    |P=0.387N     P=0.483N     P=0.130N     P=0.397N     | 
|POLY 6             |     P=0.245N     P=0.538      P=0.124      P=0.365N    |P=0.387N     P=0.437N     P=0.122N     P=0.379N     | 
|LOGISTIC REGRESSION|     P=0.300N     P=0.520      P=0.125      P=0.403N    |P=0.385N     P=0.485N     P=0.131N     P=0.393N     | 
|COCH-ARM / FISHERS |     P=0.282N     P=0.500      P=0.133      P=0.402N    |P=0.316N     P=0.500N     P=0.127N     P=0.330N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 35      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    3/50 (6%)    2/50 (4%)   |                                                    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      3/40.43      2/40.04     |                                                    | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         7.4%         5.0%        |                                                    | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    2/25 (8%)    2/28 (7%)   |                                                    | 
|FIRST INCIDENCE    |     ---          ---          561          727 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.165      (e)          P=0.119      P=0.254     |                                                    | 
|POLY 3             |     P=0.143      (e)          P=0.114      P=0.230     |                                                    | 
|POLY 1.5           |     P=0.143      (e)          P=0.118      P=0.229     |                                                    | 
|POLY 6             |     P=0.145      (e)          P=0.110      P=0.235     |                                                    | 
|LOGISTIC REGRESSION|     P=0.150      (e)          P=0.120      P=0.254     |                                                    | 
|COCH-ARM / FISHERS |     P=0.157      (e)          P=0.121      P=0.247     |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |                                                    | 
|POLY-3 RATE (b)    |     1/41.22      2/41.91      0/39.89      0/40.04     |                                                    | 
|POLY-3 PERCENT (g) |     2.4%         4.8%         0.0%         0.0%        |                                                    | 
|TERMINAL (d)       |     1/26 (4%)    2/29 (7%)    0/25 (0%)    0/28 (0%)   |                                                    | 
|FIRST INCIDENCE    |     727 (T)      727 (T)      ---          ---         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.210N     P=0.538      P=0.508N     P=0.485N    |                                                    | 
|POLY 3             |     P=0.216N     P=0.506      P=0.507N     P=0.506N    |                                                    | 
|POLY 1.5           |     P=0.218N     P=0.500      P=0.502N     P=0.507N    |                                                    | 
|POLY 6             |     P=0.213N     P=0.515      P=0.513N     P=0.502N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.210N     P=0.538      (e)          (e)         |                                                    | 
|COCH-ARM / FISHERS |     P=0.214N     P=0.500      P=0.500N     P=0.500N    |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 36      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    2/50 (4%)    1/50 (2%)   |                                                    | 
|POLY-3 RATE (b)    |     1/41.85      0/41.91      2/39.89      1/40.04     |                                                    | 
|POLY-3 PERCENT (g) |     2.4%         0.0%         5.0%         2.5%        |                                                    | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    2/25 (8%)    1/28 (4%)   |                                                    | 
|FIRST INCIDENCE    |     519          ---          727 (T)      727 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.558      P=0.504N     P=0.491      P=0.759     |                                                    | 
|POLY 3             |     P=0.537      P=0.500N     P=0.483      P=0.751     |                                                    | 
|POLY 1.5           |     P=0.539      P=0.502N     P=0.493      P=0.751     |                                                    | 
|POLY 6             |     P=0.538      P=0.496N     P=0.470      P=0.754     |                                                    | 
|LOGISTIC REGRESSION|     P=0.552      P=0.483N     P=0.500      P=0.755N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.558      P=0.500N     P=0.500      P=0.753N    |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     35/50 (70%)  44/50 (88%)  42/50 (84%)  37/50 (74%) |                                                    | 
|POLY-3 RATE (b)    |     35/45.89     44/47.42     42/48.28     37/45.20    |                                                    | 
|POLY-3 PERCENT (g) |     76.3%        92.8%        87.0%        81.9%       |                                                    | 
|TERMINAL (d)       |     20/26 (77%)  26/29 (90%)  21/25 (84%)  24/28 (86%) |                                                    | 
|FIRST INCIDENCE    |     503          223          462          161         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.393N     P=0.230      P=0.115      P=0.521     |                                                    | 
|POLY 3             |     P=0.477N     P=0.019 *    P=0.128      P=0.339     |                                                    | 
|POLY 1.5           |     P=0.466N     P=0.016 *    P=0.109      P=0.332     |                                                    | 
|POLY 6             |     P=0.472N     P=0.033 *    P=0.161      P=0.369     |                                                    | 
|LOGISTIC REGRESSION|     P=0.477N     P=0.016 *    P=0.073      P=0.307     |                                                    | 
|COCH-ARM / FISHERS |     P=0.355N     P=0.024 *    P=0.077      P=0.412     |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 37      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     18/50 (36%)  16/50 (32%)  19/50 (38%)  18/49 (37%) |                                                    | 
|POLY-3 RATE (b)    |     18/43.92     16/44.15     19/43.66     18/42.17    |                                                    | 
|POLY-3 PERCENT (g) |     41.0%        36.2%        43.5%        42.7%       |                                                    | 
|TERMINAL (d)       |     10/26 (39%)  7/29 (24%)   8/25 (32%)   10/28 (36%) |                                                    | 
|FIRST INCIDENCE    |     503          478          462          352         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.473      P=0.335N     P=0.419      P=0.534N    |                                                    | 
|POLY 3             |     P=0.401      P=0.406N     P=0.490      P=0.523     |                                                    | 
|POLY 1.5           |     P=0.394      P=0.421N     P=0.504      P=0.509     |                                                    | 
|POLY 6             |     P=0.425      P=0.379N     P=0.474      P=0.557     |                                                    | 
|LOGISTIC REGRESSION|     P=0.410      P=0.415N     P=0.495      P=0.520     |                                                    | 
|COCH-ARM / FISHERS |     P=0.444      P=0.417N     P=0.500      P=0.553     |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands: Parotid Gland                                                                                                   | 
|     Atrophy Focal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    1/49 (2%)    0/50 (0%)   |2/50 (4%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/41.22      0/41.91      1/39.56      0/40.04     |2/41.94      1/42.93      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     2.4%         0.0%         2.5%         0.0%        |4.8%         2.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/26 (4%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |2/30 (7%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     727 (T)      ---          561          ---         |728 (T)      719          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.457N     P=0.478N     P=0.759      P=0.485N    |P=0.186N     P=0.496N     P=0.253N     P=0.261N     | 
|POLY 3             |     P=0.468N     P=0.497N     P=0.752      P=0.506N    |P=0.175N     P=0.492N     P=0.239N     P=0.251N     | 
|POLY 1.5           |     P=0.467N     P=0.500N     P=0.755      P=0.507N    |P=0.174N     P=0.496N     P=0.239N     P=0.250N     | 
|POLY 6             |     P=0.469N     P=0.491N     P=0.747      P=0.502N    |P=0.176N     P=0.487N     P=0.240N     P=0.252N     | 
|LOGISTIC REGRESSION|     P=0.454N     (e)          P=0.758      (e)         |P=0.183N     P=0.485N     (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.459N     P=0.500N     P=0.747      P=0.500N    |P=0.169N     P=0.500N     P=0.247N     P=0.247N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 38      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Seminal Vesicle                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    0/50 (0%)    2/50 (4%)    2/49 (4%)   |                                                    | 
|POLY-3 RATE (b)    |     4/42.05      0/41.91      2/41.32      2/40.18     |                                                    | 
|POLY-3 PERCENT (g) |     9.5%         0.0%         4.8%         5.0%        |                                                    | 
|TERMINAL (d)       |     2/26 (8%)    0/29 (0%)    0/25 (0%)    1/28 (4%)   |                                                    | 
|FIRST INCIDENCE    |     503          ---          462          120         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.556N     P=0.059N     P=0.361N     P=0.334N    |                                                    | 
|POLY 3             |     P=0.559N     P=0.060N     P=0.344N     P=0.358N    |                                                    | 
|POLY 1.5           |     P=0.558N     P=0.061N     P=0.338N     P=0.359N    |                                                    | 
|POLY 6             |     P=0.559N     P=0.058N     P=0.357N     P=0.351N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.459N     P=0.063N     P=0.358N     P=0.292N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.551N     P=0.059N     P=0.339N     P=0.349N    |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Fibrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      2/42.48      0/39.89      1/40.04     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         4.7%         0.0%         2.5%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    1/28 (4%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          574          ---          727 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.607      P=0.258      (e)          P=0.515     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.608      P=0.244      (e)          P=0.494     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.605      P=0.239      (e)          P=0.493     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.616      P=0.251      (e)          P=0.498     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.611      P=0.239      (e)          P=0.515     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.615      P=0.247      (e)          P=0.500     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 39      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    3/50 (6%)    4/50 (8%)   |6/50 (12%)   2/50 (4%)    4/50 (8%)    5/50 (10%)   | 
|POLY-3 RATE (b)    |     2/41.32      2/42.41      3/41.55      4/41.80     |6/43.41      2/42.89      4/42.47      5/40.12      | 
|POLY-3 PERCENT (g) |     4.8%         4.7%         7.2%         9.6%        |13.8%        4.7%         9.4%         12.5%        | 
|TERMINAL (d)       |     0/26 (0%)    1/29 (3%)    0/25 (0%)    0/28 (0%)   |3/30 (10%)   2/31 (7%)    0/28 (0%)    1/27 (4%)    | 
|FIRST INCIDENCE    |     707          577          484          352         |406          728 (T)      483          588          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.231      P=0.672N     P=0.466      P=0.341     |P=0.419      P=0.133N     P=0.403N     P=0.555N     | 
|POLY 3             |     P=0.232      P=0.685N     P=0.503      P=0.342     |P=0.431      P=0.136N     P=0.383N     P=0.555N     | 
|POLY 1.5           |     P=0.226      P=0.692N     P=0.505      P=0.332     |P=0.437      P=0.135N     P=0.380N     P=0.547N     | 
|POLY 6             |     P=0.243      P=0.674N     P=0.498      P=0.359     |P=0.431      P=0.136N     P=0.386N     P=0.558N     | 
|LOGISTIC REGRESSION|     P=0.273      P=0.694N     P=0.485      P=0.359     |P=0.475      P=0.136N     P=0.362N     P=0.507N     | 
|COCH-ARM / FISHERS |     P=0.232      P=0.691N     P=0.500      P=0.339     |P=0.478      P=0.134N     P=0.370N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hyperplasia Lymphohistiocytic                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    8/50 (16%)  |0/50 (0%)    1/50 (2%)    2/50 (4%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     2/41.22      2/41.96      2/40.24      8/40.07     |0/41.94      1/42.89      2/41.46      4/39.32      | 
|POLY-3 PERCENT (g) |     4.9%         4.8%         5.0%         20.0%       |0.0%         2.3%         4.8%         10.2%        | 
|TERMINAL (d)       |     2/26 (8%)    1/29 (3%)    1/25 (4%)    7/28 (25%)  |0/30 (0%)    1/31 (3%)    2/28 (7%)    4/27 (15%)   | 
|FIRST INCIDENCE    |     727 (T)      715          630          720         |---          728 (T)      728 (T)      728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.007 **   P=0.659N     P=0.679      P=0.055     |P=0.019 *    P=0.507      P=0.223      P=0.049 *    | 
|POLY 3             |     P=0.004 **   P=0.688N     P=0.686      P=0.039 *   |P=0.022 *    P=0.504      P=0.234      P=0.052      | 
|POLY 1.5           |     P=0.005 **   P=0.693N     P=0.692      P=0.038 *   |P=0.023 *    P=0.502      P=0.235      P=0.053      | 
|POLY 6             |     P=0.004 **   P=0.678N     P=0.678      P=0.041 *   |P=0.022 *    P=0.507      P=0.233      P=0.051      | 
|LOGISTIC REGRESSION|     P=0.005 **   P=0.671N     P=0.678      P=0.039 *   |(e)          P=0.507      P=0.223      P=0.049 *    | 
|COCH-ARM / FISHERS |     P=0.006 **   P=0.691N     P=0.691N     P=0.046 *   |P=0.029 *    P=0.500      P=0.247      P=0.059      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 40      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen: Lymphoid Follicle                                                                                                        | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     20/50 (40%)  25/50 (50%)  29/50 (58%)  25/50 (50%) |35/50 (70%)  32/50 (64%)  31/50 (62%)  28/50 (56%)  | 
|POLY-3 RATE (b)    |     20/44.80     25/44.28     29/46.10     25/47.39    |35/47.36     32/47.62     31/44.19     28/45.46     | 
|POLY-3 PERCENT (g) |     44.7%        56.5%        62.9%        52.8%       |73.9%        67.2%        70.2%        61.6%        | 
|TERMINAL (d)       |     12/26 (46%)  20/29 (69%)  16/25 (64%)  14/28 (50%) |23/30 (77%)  21/31 (68%)  23/28 (82%)  16/27 (59%)  | 
|FIRST INCIDENCE    |     503          131          419          120         |191          197          375          111          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.345      P=0.343      P=0.060      P=0.280     |P=0.347N     P=0.310N     P=0.418N     P=0.301N     | 
|POLY 3             |     P=0.445      P=0.178      P=0.056      P=0.282     |P=0.149N     P=0.307N     P=0.431N     P=0.139N     | 
|POLY 1.5           |     P=0.404      P=0.189      P=0.059      P=0.262     |P=0.132N     P=0.316N     P=0.374N     P=0.125N     | 
|POLY 6             |     P=0.480      P=0.172      P=0.049 *    P=0.300     |P=0.168N     P=0.299N     P=0.503N     P=0.154N     | 
|LOGISTIC REGRESSION|     P=0.333      P=0.209      P=0.055      P=0.250     |P=0.118N     P=0.339N     P=0.274N     P=0.095N     | 
|COCH-ARM / FISHERS |     P=0.310      P=0.211      P=0.055      P=0.211     |P=0.108N     P=0.335N     P=0.263N     P=0.107N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      2/40.47      1/40.99     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.9%         2.4%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          561          261         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.344      (e)          P=0.227      P=0.492     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.348      (e)          P=0.233      P=0.499     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.345      (e)          P=0.236      P=0.496     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.352      (e)          P=0.228      P=0.504     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.432      (e)          P=0.235      P=0.638     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.354      (e)          P=0.247      P=0.500     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 41      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    4/50 (8%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/41.24      2/42.85      4/41.43      1/40.83     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     2.4%         4.7%         9.7%         2.5%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     721          478          484          433         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.519N     P=0.507      P=0.162      P=0.743     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.513N     P=0.513      P=0.179      P=0.759     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.517N     P=0.505      P=0.181      P=0.755     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.506N     P=0.526      P=0.176      P=0.758N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.444N     P=0.505      P=0.173      P=0.740N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.500      P=0.181      P=0.753N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     2/41.46      0/41.91      1/39.89      1/40.47     |0/41.94      1/42.89      0/41.46      1/39.32      | 
|POLY-3 PERCENT (g) |     4.8%         0.0%         2.5%         2.5%        |0.0%         2.3%         0.0%         2.5%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    1/25 (4%)    0/28 (0%)   |0/30 (0%)    1/31 (3%)    0/28 (0%)    1/27 (4%)    | 
|FIRST INCIDENCE    |     685          ---          727 (T)      604         |---          728 (T)      ---          728 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.610N     P=0.227N     P=0.538N     P=0.495N    |P=0.432      P=0.507      (e)          P=0.479      | 
|POLY 3             |     P=0.621N     P=0.234N     P=0.514N     P=0.508N    |P=0.443      P=0.504      (e)          P=0.487      | 
|POLY 1.5           |     P=0.621N     P=0.237N     P=0.505N     P=0.512N    |P=0.445      P=0.502      (e)          P=0.489      | 
|POLY 6             |     P=0.621N     P=0.230N     P=0.527N     P=0.501N    |P=0.443      P=0.507      (e)          P=0.487      | 
|LOGISTIC REGRESSION|     P=0.622N     P=0.235N     P=0.521N     P=0.504N    |(e)          P=0.507      (e)          P=0.479      | 
|COCH-ARM / FISHERS |     P=0.614N     P=0.247N     P=0.500N     P=0.500N    |P=0.459      P=0.500      (e)          P=0.500      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 42      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    5/50 (10%)   2/50 (4%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     1/41.24      3/43.02      5/41.61      2/40.12     |0/41.94      0/42.89      1/41.60      3/40.30      | 
|POLY-3 PERCENT (g) |     2.4%         7.0%         12.0%        5.0%        |0.0%         0.0%         2.4%         7.4%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    1/28 (4%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     721          533          561          708         |---          ---          691          495          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.585      P=0.327      P=0.094      P=0.501     |P=0.019 *    (e)          P=0.494      P=0.118      | 
|POLY 3             |     P=0.568      P=0.320      P=0.102      P=0.490     |P=0.018 *    (e)          P=0.498      P=0.111      | 
|POLY 1.5           |     P=0.568      P=0.311      P=0.103      P=0.488     |P=0.018 *    (e)          P=0.498      P=0.111      | 
|POLY 6             |     P=0.574      P=0.336      P=0.101      P=0.498     |P=0.018 *    (e)          P=0.498      P=0.113      | 
|LOGISTIC REGRESSION|     P=0.605N     P=0.307      P=0.101      P=0.500     |P=0.023 *    (e)          P=0.498      P=0.127      | 
|COCH-ARM / FISHERS |     P=0.597      P=0.309      P=0.102      P=0.500     |P=0.021 *    (e)          P=0.500      P=0.121      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular: Epithelium                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/41.22      0/41.91      2/40.38      1/40.19     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     2.4%         0.0%         5.0%         2.5%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/26 (4%)    0/29 (0%)    1/25 (4%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     727 (T)      ---          582          689         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.564      P=0.478N     P=0.491      P=0.749N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.541      P=0.497N     P=0.493      P=0.755     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.541      P=0.500N     P=0.498      P=0.753     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.545      P=0.491N     P=0.485      P=0.761     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.550      (e)          P=0.497      P=0.759     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.558      P=0.500N     P=0.500      P=0.753N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 43      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |                                                    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      2/39.89      0/40.04     |                                                    | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         5.0%         0.0%        |                                                    | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    2/25 (8%)    0/28 (0%)   |                                                    | 
|FIRST INCIDENCE    |     ---          ---          727 (T)      ---         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.686N     (e)          P=0.229      (e)         |                                                    | 
|POLY 3             |     P=0.708N     (e)          P=0.229      (e)         |                                                    | 
|POLY 1.5           |     P=0.708N     (e)          P=0.234      (e)         |                                                    | 
|POLY 6             |     P=0.705N     (e)          P=0.222      (e)         |                                                    | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.229      (e)         |                                                    | 
|COCH-ARM / FISHERS |     P=0.695N     (e)          P=0.247      (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    1/50 (2%)    1/50 (2%)   |                                                    | 
|POLY-3 RATE (b)    |     3/41.42      1/41.95      1/40.05      1/40.83     |                                                    | 
|POLY-3 PERCENT (g) |     7.2%         2.4%         2.5%         2.5%        |                                                    | 
|TERMINAL (d)       |     1/26 (4%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |                                                    | 
|FIRST INCIDENCE    |     685          717          686          433         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.356N     P=0.290N     P=0.350N     P=0.318N    |                                                    | 
|POLY 3             |     P=0.345N     P=0.300N     P=0.317N     P=0.310N    |                                                    | 
|POLY 1.5           |     P=0.346N     P=0.305N     P=0.309N     P=0.314N    |                                                    | 
|POLY 6             |     P=0.343N     P=0.292N     P=0.328N     P=0.302N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.339N     P=0.290N     P=0.323N     P=0.297N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.339N     P=0.309N     P=0.309N     P=0.309N    |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 44      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Interstitial Cell                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   0/50 (0%)    1/50 (2%)    2/50 (4%)   |                                                    | 
|POLY-3 RATE (b)    |     5/42.79      0/41.91      1/40.05      2/40.39     |                                                    | 
|POLY-3 PERCENT (g) |     11.7%        0.0%         2.5%         5.0%        |                                                    | 
|TERMINAL (d)       |     2/26 (8%)    0/29 (0%)    0/25 (0%)    1/28 (4%)   |                                                    | 
|FIRST INCIDENCE    |     519          ---          686          629         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.423N     P=0.031N*    P=0.121N     P=0.215N    |                                                    | 
|POLY 3             |     P=0.425N     P=0.032N*    P=0.116N     P=0.239N    |                                                    | 
|POLY 1.5           |     P=0.424N     P=0.032N*    P=0.108N     P=0.238N    |                                                    | 
|POLY 6             |     P=0.424N     P=0.031N*    P=0.128N     P=0.235N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.410N     P=0.032N*    P=0.104N     P=0.209N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.418N     P=0.028N*    P=0.102N     P=0.218N    |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: C-Cell                                                                                                            | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     31/50 (62%)  36/50 (72%)  40/50 (80%)  35/50 (70%) |33/50 (66%)  38/50 (76%)  34/50 (68%)  31/50 (62%)  | 
|POLY-3 RATE (b)    |     31/45.75     36/46.19     40/48.54     35/44.87    |33/46.32     38/47.51     34/46.36     31/42.42     | 
|POLY-3 PERCENT (g) |     67.8%        77.9%        82.4%        78.0%       |71.3%        80.0%        73.3%        73.1%        | 
|TERMINAL (d)       |     16/26 (62%)  22/29 (76%)  18/25 (72%)  22/28 (79%) |20/30 (67%)  25/31 (81%)  22/28 (79%)  22/27 (82%)  | 
|FIRST INCIDENCE    |     475          313          462          261         |462          197          405          139          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.423      P=0.417      P=0.077      P=0.379     |P=0.496N     P=0.319      P=0.398      P=0.503      | 
|POLY 3             |     P=0.273      P=0.185      P=0.071      P=0.187     |P=0.470N     P=0.222      P=0.503      P=0.519      | 
|POLY 1.5           |     P=0.269      P=0.175      P=0.057      P=0.180     |P=0.381N     P=0.216      P=0.501      P=0.588      | 
|POLY 6             |     P=0.314      P=0.215      P=0.100      P=0.224     |P=0.554      P=0.227      P=0.490      P=0.442      | 
|LOGISTIC REGRESSION|     P=0.301      P=0.186      P=0.038 *    P=0.192     |P=0.310N     P=0.197      P=0.482      P=0.558N     | 
|COCH-ARM / FISHERS |     P=0.386      P=0.198      P=0.038 *    P=0.263     |P=0.193N     P=0.189      P=0.500      P=0.418N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 45      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicle                                                                                                          | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/41.22      0/41.91      0/39.89      1/40.04     |0/41.94      0/42.89      2/41.48      0/39.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         2.5%        |0.0%         0.0%         4.8%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    1/28 (4%)   |0/30 (0%)    0/31 (0%)    1/28 (4%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          727 (T)     |---          ---          723          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.222      (e)          (e)          P=0.515     |P=0.714N     (e)          P=0.225      (e)          | 
|POLY 3             |     P=0.210      (e)          (e)          P=0.494     |P=0.720N     (e)          P=0.234      (e)          | 
|POLY 1.5           |     P=0.210      (e)          (e)          P=0.493     |P=0.716N     (e)          P=0.235      (e)          | 
|POLY 6             |     P=0.211      (e)          (e)          P=0.498     |P=0.722N     (e)          P=0.233      (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.515     |P=0.718N     (e)          P=0.224      (e)          | 
|COCH-ARM / FISHERS |     P=0.215      (e)          (e)          P=0.500     |P=0.695N     (e)          P=0.247      (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Trachea                                                                                                                          | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    4/50 (8%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/41.65      0/41.91      0/39.89      4/41.24     |0/41.94      1/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     2.4%         0.0%         0.0%         9.7%        |0.0%         2.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    2/28 (7%)   |0/30 (0%)    1/31 (3%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     600          ---          ---          352         |---          728 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.017 *    P=0.495N     P=0.516N     P=0.194     |P=0.605N     P=0.507      (e)          (e)          | 
|POLY 3             |     P=0.013 *    P=0.499N     P=0.509N     P=0.175     |P=0.585N     P=0.504      (e)          (e)          | 
|POLY 1.5           |     P=0.013 *    P=0.501N     P=0.503N     P=0.171     |P=0.586N     P=0.502      (e)          (e)          | 
|POLY 6             |     P=0.014 *    P=0.495N     P=0.516N     P=0.181     |P=0.584N     P=0.507      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.019 *    P=0.494N     P=0.514N     P=0.196     |(e)          P=0.507      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.015 *    P=0.500N     P=0.500N     P=0.181     |P=0.585N     P=0.500      (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/12/01                           EXPERIMENT: 88122 TEST: 06                                            Page 46      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      ELMIRON      
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Urinary Bladder                                                                                                                  | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.46      0/41.91      0/39.89      0/39.19     |0/41.94      0/42.89      0/41.46      0/39.32      | 
|POLY-3 PERCENT (g) |     4.8%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/26 (0%)    0/29 (0%)    0/25 (0%)    0/28 (0%)   |0/30 (0%)    0/31 (0%)    0/28 (0%)    0/27 (0%)    | 
|FIRST INCIDENCE    |     685          ---          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.247N     P=0.227N     P=0.272N     P=0.243N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.242N     P=0.234N     P=0.245N     P=0.249N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.240N     P=0.237N     P=0.240N     P=0.251N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.244N     P=0.230N     P=0.254N     P=0.245N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.246N     P=0.235N     P=0.245N     P=0.248N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.241N     P=0.247N     P=0.247N     P=0.253N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      14 MG/KG     42 MG/KG     126         |0 MG/KG      28 MG/KG     84 MG/KG     252          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |4/50 (8%)    5/50 (10%)   3/50 (6%)    6/50 (12%)   | 
|POLY-3 RATE (b)    |                                                        |4/41.94      5/42.93      3/41.46      6/40.52      | 
|POLY-3 PERCENT (g) |                                                        |9.5%         11.7%        7.2%         14.8%        | 
|TERMINAL (d)       |                                                        |4/30 (13%)   4/31 (13%)   3/28 (11%)   3/27 (11%)   | 
|FIRST INCIDENCE    |                                                        |728 (T)      719          728 (T)      273          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.255      P=0.516      P=0.538N     P=0.317      | 
|POLY 3             |                                                        |P=0.296      P=0.515      P=0.506N     P=0.347      | 
|POLY 1.5           |                                                        |P=0.298      P=0.508      P=0.505N     P=0.346      | 
|POLY 6             |                                                        |P=0.297      P=0.523      P=0.508N     P=0.351      | 
|LOGISTIC REGRESSION|                                                        |P=0.280      P=0.519      P=0.538N     P=0.349      | 
|COCH-ARM / FISHERS |                                                        |P=0.323      P=0.500      P=0.500N     P=0.370      | 
|=================================================================================================================================| 
(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).