https://ntp.niehs.nih.gov/go/5455

TDMS Study 88122-07 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                                          ELMIRON                                        DATE: 04/23/01       
EXPERIMENT: 88122 TEST: 07                                                                                     TIME: 15:31:43       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: C88122       
PATHOLOGIST: GRUMBEIN, SONDRA                                                                                  CAS: 37319-17-8      
------------------------------------------------------------------------------------------------------------------------------------
                                                            final#1/Mice                                                            
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                                          ELMIRON                                        DATE: 04/23/01       
EXPERIMENT: 88122 TEST: 07                                                                                     TIME: 15:31:43       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: C88122       
PATHOLOGIST: GRUMBEIN, SONDRA                                                                                  CAS: 37319-17-8      
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                     ELMIRON                                                                                      
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Cortex                         Hyperplasia                                                                                  
                                       Hypertrophy                                                                                  
Intestine Large, Cecum                 Inflammation Chronic                                                                         
Intestine Large, Rectum                Infiltration Cellular Histiocyte                                                             
                                       Inflammation Chronic                                                                         
                                       Metaplasia                                                                                   
                                       Myxomatous Change                                                                            
                                       Necrosis                                                                                     
Kidney                                 Nephropathy                                                                                  
Liver                                  Basophilic Focus                                                                             
                                       Inflammation Chronic                                                                         
Liver: Centrilobular                   Degeneration                                                                                 
Lymph Node, Mesenteric                 Infiltration Cellular Histiocyte                                                             
Nose                                   Inflammation                                                                                 
Seminal Vesicle                        Dilatation                                                                                   
Spleen                                 Hematopoietic Cell Proliferation                                                             
                                       Infiltration Cellular Histiocyte                                                             
Stomach, Forestomach                   Hyperplasia                                                                                  
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex                         Hypertrophy                                                                                  
Intestine Large, Rectum                Infiltration Cellular Histiocyte                                                             
                                       Inflammation Chronic                                                                         
                                       Metaplasia                                                                                   
                                       Myxomatous Change                                                                            
                                       Necrosis                                                                                     
Kidney                                 Metaplasia Osseous                                                                           
                                       Nephropathy                                                                                  
Liver                                  Basophilic Focus                                                                             
                                       Clear Cell Focus                                                                             
                                       Eosinophilic Focus                                                                           
                                       Fatty Change                                                                                 
Lymph Node, Mandibular                 Infiltration Cellular Histiocyte                                                             
Lymph Node, Mesenteric                 Hemorrhage                                                                                   
                                       Infiltration Cellular Histiocyte                                                             
Spleen                                 Hematopoietic Cell Proliferation                                                             
                                       Infiltration Cellular Histiocyte                                                             
                                       Metaplasia Osseous                                                                           
===============================================================                                                                     
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 1       
                     Statistical Analysis of Non-neoplastic Lesions in        Mice(B6C3F1)  -                      ELMIRON          
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   8/50 (16%)   8/50 (16%)   13/49 (27%) |5/49 (10%)   3/49 (6%)    2/49 (4%)    2/48 (4%)    | 
|POLY-3 RATE (b)    |     5/45.56      8/44.27      8/45.36      13/41.34    |5/44.48      3/44.80      2/44.13      2/43.60      | 
|POLY-3 PERCENT (g) |     11.0%        18.1%        17.6%        31.5%       |11.2%        6.7%         4.5%         4.6%         | 
|TERMINAL (d)       |     5/39 (13%)   7/40 (18%)   8/38 (21%)   9/30 (30%)  |5/37 (14%)   2/38 (5%)    2/37 (5%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     730 (T)      707          730 (T)      621         |729 (T)      555          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.004 **   P=0.295      P=0.256      P=0.009 **  |P=0.255N     P=0.344N     P=0.215N     P=0.250N     | 
|POLY 3             |     P=0.014 *    P=0.256      P=0.272      P=0.016 *   |P=0.230N     P=0.352N     P=0.219N     P=0.224N     | 
|POLY 1.5           |     P=0.016 *    P=0.254      P=0.275      P=0.019 *   |P=0.227N     P=0.357N     P=0.216N     P=0.222N     | 
|POLY 6             |     P=0.011 *    P=0.270      P=0.267      P=0.014 *   |P=0.236N     P=0.347N     P=0.224N     P=0.228N     | 
|LOGISTIC REGRESSION|     P=0.007 **   P=0.292      P=0.256      P=0.014 *   |P=0.228N     P=0.359N     P=0.215N     P=0.250N     | 
|COCH-ARM / FISHERS |     P=0.024 *    P=0.277      P=0.277      P=0.030 *   |P=0.229N     P=0.357N     P=0.218N     P=0.226N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     27/50 (54%)  27/50 (54%)  23/50 (46%)  15/49 (31%) |1/49 (2%)    3/49 (6%)    3/49 (6%)    12/48 (25%)  | 
|POLY-3 RATE (b)    |     27/45.83     27/45.01     23/46.13     15/40.86    |1/44.48      3/44.24      3/44.13      12/44.29     | 
|POLY-3 PERCENT (g) |     58.9%        60.0%        49.9%        36.7%       |2.3%         6.8%         6.8%         27.1%        | 
|TERMINAL (d)       |     25/39 (64%)  24/40 (60%)  21/38 (55%)  13/30 (43%) |1/37 (3%)    3/38 (8%)    3/37 (8%)    10/34 (29%)  | 
|FIRST INCIDENCE    |     690          508          548          646         |729 (T)      729 (T)      729 (T)      517          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.073N     P=0.526N     P=0.310N     P=0.109N    |P<0.001 **   P=0.314      P=0.305      P<0.001 **   | 
|POLY 3             |     P=0.011N*    P=0.544      P=0.249N     P=0.027N*   |P<0.001 **   P=0.303      P=0.302      P<0.001 **   | 
|POLY 1.5           |     P=0.009N**   P=0.523      P=0.257N     P=0.024N*   |P<0.001 **   P=0.302      P=0.305      P<0.001 **   | 
|POLY 6             |     P=0.018N*    P=0.574N     P=0.247N     P=0.035N*   |P<0.001 **   P=0.304      P=0.298      P<0.001 **   | 
|LOGISTIC REGRESSION|     P=0.023N*    P=0.547      P=0.288N     P=0.060N    |P<0.001 **   P=0.314      P=0.305      P<0.001 **   | 
|COCH-ARM / FISHERS |     P=0.005N**   P=0.579N     P=0.274N     P=0.015N*   |P<0.001 **   P=0.309      P=0.309      P<0.001 **   | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    0/50 (0%)    1/49 (2%)   |0/49 (0%)    0/49 (0%)    0/47 (0%)    0/47 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      3/44.27      0/45.36      1/40.28     |0/44.48      0/44.24      0/42.51      0/42.86      | 
|POLY-3 PERCENT (g) |     0.0%         6.8%         0.0%         2.5%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    2/40 (5%)    0/38 (0%)    1/30 (3%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          707          ---          730 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.652      P=0.131      (e)          P=0.448     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.647N     P=0.114      (e)          P=0.475     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.642N     P=0.113      (e)          P=0.481     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.652N     P=0.117      (e)          P=0.468     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.673      P=0.117      (e)          P=0.448     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.621N     P=0.121      (e)          P=0.495     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone                                                                                                                             | 
|     Fibrous Osteodystrophy                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |4/50 (8%)    1/50 (2%)    5/50 (10%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/45.36      0/40.88     |4/44.88      1/45.21      5/44.89      5/45.21      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |8.9%         2.2%         11.1%        11.1%        | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |4/37 (11%)   1/38 (3%)    4/37 (11%)   5/34 (15%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      729 (T)      677          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.190      P=0.171N     P=0.497      P=0.446      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.239      P=0.176N     P=0.500      P=0.505      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.245      P=0.179N     P=0.503      P=0.507      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.229      P=0.173N     P=0.495      P=0.497      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.217      P=0.171N     P=0.484      P=0.446      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.238      P=0.181N     P=0.500      P=0.500      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Cornea                                                                                                                      | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     1/1 (100%)   2/2 (100%)   0/1 (0%)    |0/0 (0%)     0/0 (0%)     0/1 (0%)     1/2 (50%)    | 
|POLY-3 RATE (b)    |     0/0.00       1/1.00       2/2.00       0/0.51      |0/0.00       0/0.00       0/1.00       1/2.00       | 
|POLY-3 PERCENT (g) |     0.0%         100.0%       100.0%       0.0%        |0.0%         0.0%         0.0%         50.0%        | 
|TERMINAL (d)       |     0/0 (0%)     1/1 (100%)   2/2 (100%)   0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/1 (0%)     1/2 (50%)    | 
|FIRST INCIDENCE    |     ---          730 (T)      730 (T)      ---         |---          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=1.000      (e)          (e)          (e)         |P=0.638      (e)          (e)          P=1.000N     | 
|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)         |(e)          (e)          (e)          P=1.000N     | 
|COCH-ARM / FISHERS |     P=0.221N     (e)          (e)          (e)         |P=0.667      (e)          (e)          P=1.000      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Gallbladder                                                                                                                      | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/40 (0%)    1/38 (3%)    1/39 (3%)    0/34 (0%)   |0/39 (0%)    2/40 (5%)    1/38 (3%)    1/38 (3%)    | 
|POLY-3 RATE (b)    |     0/38.19      1/33.83      1/36.93      0/29.75     |0/36.77      2/37.97      1/35.38      1/35.22      | 
|POLY-3 PERCENT (g) |     0.0%         3.0%         2.7%         0.0%        |0.0%         5.3%         2.8%         2.8%         | 
|TERMINAL (d)       |     0/35 (0%)    1/32 (3%)    1/33 (3%)    0/26 (0%)   |0/34 (0%)    2/35 (6%)    0/33 (0%)    1/31 (3%)    | 
|FIRST INCIDENCE    |     ---          730 (T)      730 (T)      ---         |---          729 (T)      653          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.602N     P=0.482      P=0.488      (e)         |P=0.588      P=0.245      P=0.490      P=0.482      | 
|POLY 3             |     P=0.595N     P=0.476      P=0.493      (e)         |P=0.596      P=0.244      P=0.492      P=0.491      | 
|POLY 1.5           |     P=0.590N     P=0.478      P=0.494      (e)         |P=0.599      P=0.242      P=0.493      P=0.493      | 
|POLY 6             |     P=0.601N     P=0.476      P=0.492      (e)         |P=0.591      P=0.245      P=0.493      P=0.489      | 
|LOGISTIC REGRESSION|     (e)          P=0.482      P=0.488      (e)         |P=0.603      P=0.245      P=0.512      P=0.482      | 
|COCH-ARM / FISHERS |     P=0.574N     P=0.487      P=0.494      (e)         |P=0.603      P=0.253      P=0.494      P=0.494      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Gallbladder                                                                                                                      | 
|     Degeneration Hyaline                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/40 (8%)    1/38 (3%)    0/39 (0%)    1/34 (3%)   |1/39 (3%)    1/40 (3%)    3/38 (8%)    2/38 (5%)    | 
|POLY-3 RATE (b)    |     3/38.43      1/33.83      0/36.93      1/29.75     |1/36.77      1/37.97      3/35.10      2/35.22      | 
|POLY-3 PERCENT (g) |     7.8%         3.0%         0.0%         3.4%        |2.7%         2.6%         8.6%         5.7%         | 
|TERMINAL (d)       |     2/35 (6%)    1/32 (3%)    0/33 (0%)    1/26 (4%)   |1/34 (3%)    1/35 (3%)    3/33 (9%)    2/31 (7%)    | 
|FIRST INCIDENCE    |     664          730 (T)      ---          730 (T)     |729 (T)      729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.421N     P=0.328N     P=0.134N     P=0.414N    |P=0.356      P=0.755N     P=0.294      P=0.468      | 
|POLY 3             |     P=0.381N     P=0.352N     P=0.125N     P=0.401N    |P=0.376      P=0.753N     P=0.288      P=0.485      | 
|POLY 1.5           |     P=0.380N     P=0.347N     P=0.124N     P=0.391N    |P=0.382      P=0.755N     P=0.290      P=0.488      | 
|POLY 6             |     P=0.384N     P=0.354N     P=0.127N     P=0.412N    |P=0.368      P=0.752N     P=0.286      P=0.481      | 
|LOGISTIC REGRESSION|     P=0.396N     P=0.339N     P=0.123N     P=0.385N    |P=0.356      P=0.755N     P=0.294      P=0.468      | 
|COCH-ARM / FISHERS |     P=0.381N     P=0.327N     P=0.125N     P=0.371N    |P=0.386      P=0.747N     P=0.298      P=0.490      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/49 (2%)    1/48 (2%)    1/49 (2%)    1/48 (2%)   |3/48 (6%)    3/41 (7%)    2/50 (4%)    4/46 (9%)    | 
|POLY-3 RATE (b)    |     1/44.56      1/42.84      1/44.86      1/39.66     |3/43.37      3/36.80      2/44.70      4/41.57      | 
|POLY-3 PERCENT (g) |     2.2%         2.3%         2.2%         2.5%        |6.9%         8.2%         4.5%         9.6%         | 
|TERMINAL (d)       |     1/38 (3%)    1/39 (3%)    1/38 (3%)    1/30 (3%)   |2/35 (6%)    2/32 (6%)    2/37 (5%)    4/32 (13%)   | 
|FIRST INCIDENCE    |     730 (T)      730 (T)      730 (T)      730 (T)     |583          703          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.601      P=0.756N     P=0.762      P=0.708     |P=0.367      P=0.633      P=0.478N     P=0.458      | 
|POLY 3             |     P=0.633      P=0.752      P=0.759N     P=0.734     |P=0.408      P=0.585      P=0.486N     P=0.477      | 
|POLY 1.5           |     P=0.642      P=0.750      P=0.759N     P=0.740     |P=0.413      P=0.582      P=0.482N     P=0.481      | 
|POLY 6             |     P=0.618      P=0.758      P=0.759N     P=0.726     |P=0.399      P=0.590      P=0.494N     P=0.469      | 
|LOGISTIC REGRESSION|     P=0.601      P=0.756N     P=0.762      P=0.708     |P=0.411      P=0.587      P=0.480N     P=0.482      | 
|COCH-ARM / FISHERS |     P=0.665      P=0.747      P=0.753N     P=0.747     |P=0.406      P=0.583      P=0.480N     P=0.476      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Inflammation Acute                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    1/48 (2%)    2/49 (4%)    0/48 (0%)   |0/48 (0%)    0/41 (0%)    0/50 (0%)    0/46 (0%)    | 
|POLY-3 RATE (b)    |     0/44.56      1/42.84      2/44.88      0/39.66     |0/42.88      0/36.70      0/44.70      0/41.57      | 
|POLY-3 PERCENT (g) |     0.0%         2.3%         4.5%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/38 (0%)    1/39 (3%)    1/38 (3%)    0/30 (0%)   |0/35 (0%)    0/32 (0%)    0/37 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     ---          730 (T)      725          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.590N     P=0.505      P=0.240      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.556N     P=0.492      P=0.239      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.546N     P=0.490      P=0.238      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.571N     P=0.497      P=0.239      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.579N     P=0.505      P=0.239      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.520N     P=0.495      P=0.247      (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     3/45.56      0/44.17      1/45.36      2/40.88     |0/44.88      1/45.39      1/44.98      1/45.21      | 
|POLY-3 PERCENT (g) |     6.6%         0.0%         2.2%         4.9%        |0.0%         2.2%         2.2%         2.2%         | 
|TERMINAL (d)       |     3/39 (8%)    0/40 (0%)    1/38 (3%)    2/30 (7%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     730 (T)      ---          730 (T)      730 (T)     |---          681          653          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.465      P=0.117N     P=0.314N     P=0.619N    |P=0.472      P=0.514      P=0.490      P=0.483      | 
|POLY 3             |     P=0.543      P=0.124N     P=0.307N     P=0.549N    |P=0.486      P=0.502      P=0.500      P=0.501      | 
|POLY 1.5           |     P=0.555      P=0.125N     P=0.306N     P=0.535N    |P=0.488      P=0.500      P=0.501      P=0.502      | 
|POLY 6             |     P=0.523      P=0.120N     P=0.309N     P=0.569N    |P=0.480      P=0.505      P=0.499      P=0.499      | 
|LOGISTIC REGRESSION|     P=0.465      (e)          P=0.314N     P=0.619N    |P=0.481      P=0.501      P=0.492      P=0.483      | 
|COCH-ARM / FISHERS |     P=0.571      P=0.121N     P=0.309N     P=0.500N    |P=0.483      P=0.500      P=0.500      P=0.500      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    2/50 (4%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/45.36      0/40.88     |1/45.63      2/45.31      1/44.70      0/45.21      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.2%         4.4%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    1/38 (3%)    1/37 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |456          703          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.249N     P=0.509      P=0.758N     P=0.496N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.237N     P=0.498      P=0.756      P=0.502N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.235N     P=0.496      P=0.759      P=0.500N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.241N     P=0.500      P=0.752      P=0.505N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.247N     P=0.515      P=0.739      P=0.664N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.235N     P=0.500      P=0.753N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |1/50 (2%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/45.91      0/44.17      1/45.36      2/41.59     |1/45.21      1/45.21      1/45.08      1/45.32      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         2.2%         4.8%        |2.2%         2.2%         2.2%         2.2%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    0/30 (0%)   |0/37 (0%)    1/38 (3%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     632          ---          730 (T)      617         |636          729 (T)      621          701          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.191      P=0.505N     P=0.755      P=0.452     |P=0.658      P=0.757N     P=0.758      P=0.757      | 
|POLY 3             |     P=0.216      P=0.508N     P=0.758      P=0.466     |P=0.666N     P=0.761      P=0.760      P=0.760N     | 
|POLY 1.5           |     P=0.223      P=0.508N     P=0.759      P=0.475     |P=0.664N     P=0.759      P=0.760N     P=0.759N     | 
|POLY 6             |     P=0.204      P=0.505N     P=0.755      P=0.453     |P=0.662      P=0.760N     P=0.757      P=0.758      | 
|LOGISTIC REGRESSION|     P=0.256      P=0.469N     P=0.761      P=0.555     |P=0.660      P=0.762N     P=0.749      P=0.755      | 
|COCH-ARM / FISHERS |     P=0.235      P=0.500N     P=0.753N     P=0.500     |P=0.668N     P=0.753N     P=0.753N     P=0.753N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Artery                                                                                                                    | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|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)    |     0/45.56      0/44.17      3/45.81      0/40.88     |0/44.88      0/45.21      0/44.70      0/45.21      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         6.6%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    2/38 (5%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          597          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.691      (e)          P=0.119      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.686      (e)          P=0.120      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.676N     (e)          P=0.120      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.655      (e)          P=0.119      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.647N     (e)          P=0.119      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.646N     (e)          P=0.121      (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Cecum                                                                                                           | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/47 (0%)    0/46 (0%)    2/39 (5%)   |0/41 (0%)    0/43 (0%)    0/44 (0%)    0/43 (0%)    | 
|POLY-3 RATE (b)    |     0/44.72      0/42.17      0/43.31      2/35.39     |0/39.12      0/40.87      0/40.14      0/39.93      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         5.7%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    1/30 (3%)   |0/37 (0%)    0/37 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          584         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.030 *    (e)          (e)          P=0.200     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.026 *    (e)          (e)          P=0.186     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.026 *    (e)          (e)          P=0.185     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.026 *    (e)          (e)          P=0.187     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.030 *    (e)          (e)          P=0.201     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.027 *    (e)          (e)          P=0.194     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 8       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/47 (0%)    0/46 (0%)    6/44 (14%)  |0/45 (0%)    0/45 (0%)    2/44 (5%)    10/46 (22%)  | 
|POLY-3 RATE (b)    |     0/44.56      0/42.17      0/43.31      6/38.29     |0/41.21      0/42.20      2/41.31      10/43.74     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         15.7%       |0.0%         0.0%         4.8%         22.9%        | 
|TERMINAL (d)       |     0/38 (0%)    0/40 (0%)    0/38 (0%)    3/30 (10%)  |0/37 (0%)    0/37 (0%)    0/37 (0%)    7/34 (21%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          498         |---          ---          509          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P=0.011 *   |P<0.001 **   (e)          P=0.244      P<0.001 **   | 
|POLY 3             |     P<0.001 **   (e)          (e)          P=0.008 **  |P<0.001 **   (e)          P=0.237      P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P=0.008 **  |P<0.001 **   (e)          P=0.236      P<0.001 **   | 
|POLY 6             |     P<0.001 **   (e)          (e)          P=0.008 **  |P<0.001 **   (e)          P=0.239      P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          P=0.014 *   |P<0.001 **   (e)          P=0.185      P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P=0.009 **  |P<0.001 **   (e)          P=0.242      P<0.001 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/47 (0%)    1/46 (2%)    8/44 (18%)  |0/45 (0%)    0/45 (0%)    2/44 (5%)    32/46 (70%)  | 
|POLY-3 RATE (b)    |     0/44.56      0/42.17      1/43.31      8/37.93     |0/41.21      0/42.20      2/40.55      32/45.04     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.3%         21.1%       |0.0%         0.0%         4.9%         71.1%        | 
|TERMINAL (d)       |     0/38 (0%)    0/40 (0%)    1/38 (3%)    5/30 (17%)  |0/37 (0%)    0/37 (0%)    1/37 (3%)    23/34 (68%)  | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      584         |---          ---          653          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          P=0.500      P=0.002 **  |P<0.001 **   (e)          P=0.235      P<0.001 **   | 
|POLY 3             |     P<0.001 **   (e)          P=0.494      P<0.001 **  |P<0.001 **   (e)          P=0.233      P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   (e)          P=0.492      P<0.001 **  |P<0.001 **   (e)          P=0.234      P<0.001 **   | 
|POLY 6             |     P<0.001 **   (e)          P=0.497      P<0.001 **  |P<0.001 **   (e)          P=0.233      P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          P=0.500      P=0.002 **  |P<0.001 **   (e)          P=0.231      P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          P=0.484      P=0.002 **  |P<0.001 **   (e)          P=0.242      P<0.001 **   | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 9       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/47 (0%)    0/46 (0%)    5/44 (11%)  |0/45 (0%)    0/45 (0%)    1/44 (2%)    26/46 (57%)  | 
|POLY-3 RATE (b)    |     0/44.56      0/42.17      0/43.31      5/37.45     |0/41.21      0/42.20      1/40.27      26/44.66     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         13.4%       |0.0%         0.0%         2.5%         58.2%        | 
|TERMINAL (d)       |     0/38 (0%)    0/40 (0%)    0/38 (0%)    3/30 (10%)  |0/37 (0%)    0/37 (0%)    1/37 (3%)    18/34 (53%)  | 
|FIRST INCIDENCE    |     ---          ---          ---          617         |---          ---          729 (T)      401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P=0.020 *   |P<0.001 **   (e)          P=0.500      P<0.001 **   | 
|POLY 3             |     P<0.001 **   (e)          (e)          P=0.018 *   |P<0.001 **   (e)          P=0.495      P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P=0.018 *   |P<0.001 **   (e)          P=0.496      P<0.001 **   | 
|POLY 6             |     P<0.001 **   (e)          (e)          P=0.017 *   |P<0.001 **   (e)          P=0.494      P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          P=0.021 *   |P<0.001 **   (e)          P=0.500      P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P=0.021 *   |P<0.001 **   (e)          P=0.494      P<0.001 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Myxomatous Change                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/47 (0%)    0/46 (0%)    13/44 (30%) |0/45 (0%)    3/45 (7%)    21/44 (48%)  31/46 (67%)  | 
|POLY-3 RATE (b)    |     0/44.56      0/42.17      0/43.31      13/39.27    |0/41.21      3/42.39      21/41.78     31/45.77     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         33.1%       |0.0%         7.1%         50.3%        67.7%        | 
|TERMINAL (d)       |     0/38 (0%)    0/40 (0%)    0/38 (0%)    8/30 (27%)  |0/37 (0%)    2/37 (5%)    18/37 (49%)  21/34 (62%)  | 
|FIRST INCIDENCE    |     ---          ---          ---          498         |---          681          509          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   P=0.127      P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   P=0.123      P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   P=0.121      P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   P=0.125      P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   P=0.122      P<0.001 **   P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   P=0.121      P<0.001 **   P<0.001 **   | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 10      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Rectum                                                                                                          | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/47 (0%)    0/46 (0%)    5/44 (11%)  |0/45 (0%)    0/45 (0%)    1/44 (2%)    24/46 (52%)  | 
|POLY-3 RATE (b)    |     0/44.56      0/42.17      0/43.31      5/37.54     |0/41.21      0/42.20      1/40.55      24/44.94     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         13.3%       |0.0%         0.0%         2.5%         53.4%        | 
|TERMINAL (d)       |     0/38 (0%)    0/40 (0%)    0/38 (0%)    3/30 (10%)  |0/37 (0%)    0/37 (0%)    0/37 (0%)    16/34 (47%)  | 
|FIRST INCIDENCE    |     ---          ---          ---          584         |---          ---          653          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P=0.020 *   |P<0.001 **   (e)          P=0.490      P<0.001 **   | 
|POLY 3             |     P<0.001 **   (e)          (e)          P=0.018 *   |P<0.001 **   (e)          P=0.497      P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P=0.018 *   |P<0.001 **   (e)          P=0.497      P<0.001 **   | 
|POLY 6             |     P<0.001 **   (e)          (e)          P=0.017 *   |P<0.001 **   (e)          P=0.496      P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          P=0.022 *   |P<0.001 **   (e)          P=0.487      P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P=0.021 *   |P<0.001 **   (e)          P=0.494      P<0.001 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    3/50 (6%)    1/49 (2%)   |0/48 (0%)    1/49 (2%)    0/48 (0%)    0/46 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      3/45.36      1/40.16     |0/44.46      1/44.91      0/43.18      0/41.91      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         6.6%         2.5%        |0.0%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    3/38 (8%)    1/30 (3%)   |0/37 (0%)    1/38 (3%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      730 (T)     |---          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.297      (e)          P=0.116      P=0.448     |P=0.602N     P=0.505      (e)          (e)          | 
|POLY 3             |     P=0.327      (e)          P=0.118      P=0.475     |P=0.596N     P=0.502      (e)          (e)          | 
|POLY 1.5           |     P=0.344      (e)          P=0.119      P=0.481     |P=0.596N     P=0.501      (e)          (e)          | 
|POLY 6             |     P=0.302      (e)          P=0.116      P=0.467     |P=0.595N     P=0.504      (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.116      P=0.448     |(e)          P=0.505      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.379      (e)          P=0.121      P=0.495     |P=0.594N     P=0.505      (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 11      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Infarct                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    4/50 (8%)    0/49 (0%)   |0/48 (0%)    1/49 (2%)    1/48 (2%)    1/46 (2%)    | 
|POLY-3 RATE (b)    |     1/45.56      3/44.17      4/45.81      0/40.16     |0/44.46      1/45.02      1/43.46      1/41.91      | 
|POLY-3 PERCENT (g) |     2.2%         6.8%         8.7%         0.0%        |0.0%         2.2%         2.3%         2.4%         | 
|TERMINAL (d)       |     1/39 (3%)    3/40 (8%)    3/38 (8%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     730 (T)      730 (T)      597          ---         |---          703          653          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.282N     P=0.314      P=0.174      P=0.552N    |P=0.465      P=0.510      P=0.490      P=0.483      | 
|POLY 3             |     P=0.255N     P=0.294      P=0.180      P=0.525N    |P=0.463      P=0.502      P=0.495      P=0.488      | 
|POLY 1.5           |     P=0.240N     P=0.293      P=0.180      P=0.519N    |P=0.466      P=0.501      P=0.497      P=0.490      | 
|POLY 6             |     P=0.277N     P=0.301      P=0.180      P=0.533N    |P=0.459      P=0.505      P=0.494      P=0.486      | 
|LOGISTIC REGRESSION|     P=0.237N     P=0.314      P=0.179      (e)         |P=0.468      P=0.503      P=0.518      P=0.483      | 
|COCH-ARM / FISHERS |     P=0.210N     P=0.309      P=0.181      P=0.505N    |P=0.469      P=0.505      P=0.500      P=0.489      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    3/50 (6%)    1/49 (2%)   |0/48 (0%)    0/49 (0%)    0/48 (0%)    0/46 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      3/44.27      3/46.84      1/40.75     |0/44.46      0/44.91      0/43.18      0/41.91      | 
|POLY-3 PERCENT (g) |     0.0%         6.8%         6.4%         2.5%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    1/40 (3%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          707          465          539         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.622N     P=0.133      P=0.124      P=0.487     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.610N     P=0.114      P=0.124      P=0.478     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.599N     P=0.113      P=0.122      P=0.482     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.623      P=0.117      P=0.125      P=0.471     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.500N     P=0.117      P=0.067      P=0.591     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.564N     P=0.121      P=0.121      P=0.495     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 12      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Metaplasia Osseous                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    0/50 (0%)    0/49 (0%)   |0/48 (0%)    0/49 (0%)    0/48 (0%)    3/46 (7%)    | 
|POLY-3 RATE (b)    |     1/45.56      1/44.17      0/45.36      0/40.16     |0/44.46      0/44.91      0/43.18      3/41.91      | 
|POLY-3 PERCENT (g) |     2.2%         2.3%         0.0%         0.0%        |0.0%         0.0%         0.0%         7.2%         | 
|TERMINAL (d)       |     1/39 (3%)    1/40 (3%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    3/34 (9%)    | 
|FIRST INCIDENCE    |     730 (T)      730 (T)      ---          ---         |---          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.351N     P=0.756N     P=0.505N     P=0.552N    |P=0.006 **   (e)          (e)          P=0.106      | 
|POLY 3             |     P=0.316N     P=0.754      P=0.501N     P=0.525N    |P=0.006 **   (e)          (e)          P=0.108      | 
|POLY 1.5           |     P=0.315N     P=0.753      P=0.500N     P=0.519N    |P=0.007 **   (e)          (e)          P=0.109      | 
|POLY 6             |     P=0.319N     P=0.758      P=0.502N     P=0.533N    |P=0.006 **   (e)          (e)          P=0.106      | 
|LOGISTIC REGRESSION|     P=0.351N     P=0.756N     (e)          (e)         |(e)          (e)          (e)          P=0.106      | 
|COCH-ARM / FISHERS |     P=0.309N     P=0.753N     P=0.500N     P=0.505N    |P=0.007 **   (e)          (e)          P=0.113      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |3/48 (6%)    2/49 (4%)    1/48 (2%)    1/46 (2%)    | 
|POLY-3 RATE (b)    |     1/46.28      0/44.17      0/45.36      0/40.16     |3/44.87      2/45.17      1/43.84      1/41.91      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         0.0%         0.0%        |6.7%         4.4%         2.3%         2.4%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     477          ---          ---          ---         |661          681          509          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.471N     P=0.513N     P=0.500N     P=0.504N    |P=0.284N     P=0.485N     P=0.322N     P=0.332N     | 
|POLY 3             |     P=0.464N     P=0.509N     P=0.504N     P=0.528N    |P=0.285N     P=0.497N     P=0.314N     P=0.330N     | 
|POLY 1.5           |     P=0.466N     P=0.509N     P=0.502N     P=0.521N    |P=0.281N     P=0.499N     P=0.310N     P=0.326N     | 
|POLY 6             |     P=0.463N     P=0.506N     P=0.506N     P=0.537N    |P=0.290N     P=0.494N     P=0.319N     P=0.336N     | 
|LOGISTIC REGRESSION|     P=0.384N     P=0.358N     P=0.667N     P=0.362N    |P=0.284N     P=0.488N     P=0.267N     P=0.320N     | 
|COCH-ARM / FISHERS |     P=0.475N     P=0.500N     P=0.500N     P=0.505N    |P=0.279N     P=0.490N     P=0.308N     P=0.325N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 13      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     43/50 (86%)  41/50 (82%)  47/50 (94%)  41/49 (84%) |19/48 (40%)  17/49 (35%)  22/48 (46%)  27/46 (59%)  | 
|POLY-3 RATE (b)    |     43/49.04     41/46.92     47/48.34     41/44.83    |19/45.89     17/45.76     22/46.22     27/44.12     | 
|POLY-3 PERCENT (g) |     87.7%        87.4%        97.2%        91.5%       |41.4%        37.2%        47.6%        61.2%        | 
|TERMINAL (d)       |     34/39 (87%)  37/40 (93%)  38/38 (100%) 29/30 (97%) |15/37 (41%)  14/38 (37%)  15/37 (41%)  20/34 (59%)  | 
|FIRST INCIDENCE    |     477          455          548          492         |456          555          481          509          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.020 *    P=0.357N     P=0.197      P=0.098     |P=0.016 *    P=0.383N     P=0.350      P=0.056      | 
|POLY 3             |     P=0.298      P=0.605N     P=0.067      P=0.393     |P=0.013 *    P=0.420N     P=0.349      P=0.045 *    | 
|POLY 1.5           |     P=0.380      P=0.577N     P=0.099      P=0.470     |P=0.013 *    P=0.423N     P=0.342      P=0.045 *    | 
|POLY 6             |     P=0.184      P=0.621N     P=0.039 *    P=0.286     |P=0.012 *    P=0.414N     P=0.360      P=0.044 *    | 
|LOGISTIC REGRESSION|     P=0.378      P=0.562N     P=0.155      P=0.447     |P=0.013 *    P=0.403N     P=0.355      P=0.049 *    | 
|COCH-ARM / FISHERS |     P=0.499N     P=0.393N     P=0.159      P=0.483N    |P=0.013 *    P=0.387N     P=0.340      P=0.050      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    0/49 (0%)   |0/48 (0%)    0/49 (0%)    0/48 (0%)    0/46 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      2/45.36      0/40.16     |0/44.46      0/44.91      0/43.18      0/41.91      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.4%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    2/38 (5%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.725      (e)          P=0.233      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.720      (e)          P=0.236      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.720N     (e)          P=0.237      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.698      (e)          P=0.235      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.233      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.700N     (e)          P=0.247      (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 14      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/50 (28%)  10/50 (20%)  5/50 (10%)   10/50 (20%) |5/50 (10%)   6/49 (12%)   8/50 (16%)   12/49 (24%)  | 
|POLY-3 RATE (b)    |     14/47.07     10/45.26     5/45.36      10/40.88    |5/44.88      6/44.91      8/44.89      12/44.29     | 
|POLY-3 PERCENT (g) |     29.8%        22.1%        11.0%        24.5%       |11.1%        13.4%        17.8%        27.1%        | 
|TERMINAL (d)       |     11/39 (28%)  8/40 (20%)   5/38 (13%)   10/30 (33%) |5/37 (14%)   6/38 (16%)   7/37 (19%)   12/34 (35%)  | 
|FIRST INCIDENCE    |     420          311          730 (T)      730 (T)     |729 (T)      729 (T)      677          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.533      P=0.235N     P=0.025N*    P=0.490N    |P=0.013 *    P=0.519      P=0.272      P=0.032 *    | 
|POLY 3             |     P=0.426N     P=0.274N     P=0.022N*    P=0.377N    |P=0.023 *    P=0.501      P=0.275      P=0.047 *    | 
|POLY 1.5           |     P=0.391N     P=0.274N     P=0.021N*    P=0.332N    |P=0.025 *    P=0.491      P=0.279      P=0.049 *    | 
|POLY 6             |     P=0.481N     P=0.263N     P=0.025N*    P=0.442N    |P=0.020 *    P=0.510      P=0.268      P=0.044 *    | 
|LOGISTIC REGRESSION|     P=0.390N     P=0.238N     P=0.021N*    P=0.339N    |P=0.016 *    P=0.519      P=0.254      P=0.032 *    | 
|COCH-ARM / FISHERS |     P=0.327N     P=0.241N     P=0.020N*    P=0.241N    |P=0.025 *    P=0.486      P=0.277      P=0.049 *    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Clear Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     21/50 (42%)  23/50 (46%)  19/50 (38%)  15/50 (30%) |0/50 (0%)    4/49 (8%)    1/50 (2%)    21/49 (43%)  | 
|POLY-3 RATE (b)    |     21/45.81     23/44.17     19/45.78     15/40.88    |0/44.88      4/45.02      1/44.70      21/45.13     | 
|POLY-3 PERCENT (g) |     45.8%        52.1%        41.5%        36.7%       |0.0%         8.9%         2.2%         46.5%        | 
|TERMINAL (d)       |     20/39 (51%)  23/40 (58%)  18/38 (47%)  15/30 (50%) |0/37 (0%)    3/38 (8%)    1/37 (3%)    20/34 (59%)  | 
|FIRST INCIDENCE    |     664          730 (T)      611          730 (T)     |---          703          729 (T)      401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.361N     P=0.461      P=0.459N     P=0.469N    |P<0.001 **   P=0.069      P=0.500      P<0.001 **   | 
|POLY 3             |     P=0.138N     P=0.351      P=0.417N     P=0.256N    |P<0.001 **   P=0.061      P=0.499      P<0.001 **   | 
|POLY 1.5           |     P=0.111N     P=0.351      P=0.416N     P=0.221N    |P<0.001 **   P=0.059      P=0.501      P<0.001 **   | 
|POLY 6             |     P=0.195N     P=0.377      P=0.424N     P=0.319N    |P<0.001 **   P=0.063      P=0.497      P<0.001 **   | 
|LOGISTIC REGRESSION|     P=0.291N     P=0.479      P=0.443N     P=0.412N    |P<0.001 **   P=0.064      P=0.500      P<0.001 **   | 
|COCH-ARM / FISHERS |     P=0.070N     P=0.420      P=0.419N     P=0.149N    |P<0.001 **   P=0.056      P=0.500      P<0.001 **   | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 15      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Eosinophilic Focus                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     13/50 (26%)  11/50 (22%)  9/50 (18%)   12/50 (24%) |10/50 (20%)  6/49 (12%)   7/50 (14%)   15/49 (31%)  | 
|POLY-3 RATE (b)    |     13/45.99     11/44.93     9/45.36      12/41.26    |10/45.26     6/44.91      7/44.70      15/44.45     | 
|POLY-3 PERCENT (g) |     28.3%        24.5%        19.8%        29.1%       |22.1%        13.4%        15.7%        33.8%        | 
|TERMINAL (d)       |     12/39 (31%)  10/40 (25%)  9/38 (24%)   9/30 (30%)  |7/37 (19%)   6/38 (16%)   7/37 (19%)   13/34 (38%)  | 
|FIRST INCIDENCE    |     606          455          730 (T)      676         |667          729 (T)      729 (T)      701          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.259      P=0.387N     P=0.252N     P=0.396     |P=0.017 *    P=0.194N     P=0.306N     P=0.129      | 
|POLY 3             |     P=0.450      P=0.432N     P=0.242N     P=0.561     |P=0.027 *    P=0.209N     P=0.305N     P=0.158      | 
|POLY 1.5           |     P=0.488      P=0.439N     P=0.238N     P=0.590N    |P=0.029 *    P=0.216N     P=0.298N     P=0.165      | 
|POLY 6             |     P=0.395      P=0.410N     P=0.251N     P=0.512     |P=0.023 *    P=0.204N     P=0.321N     P=0.145      | 
|LOGISTIC REGRESSION|     P=0.396      P=0.440N     P=0.242N     P=0.486     |P=0.021 *    P=0.194N     P=0.314N     P=0.146      | 
|COCH-ARM / FISHERS |     P=0.553N     P=0.408N     P=0.235N     P=0.500N    |P=0.030 *    P=0.220N     P=0.298N     P=0.163      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Fatty Change                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   12/50 (24%)  8/50 (16%)   13/50 (26%) |4/50 (8%)    2/49 (4%)    1/50 (2%)    12/49 (24%)  | 
|POLY-3 RATE (b)    |     9/46.28      12/45.86     8/46.68      13/41.39    |4/46.57      2/45.23      1/44.70      12/46.98     | 
|POLY-3 PERCENT (g) |     19.5%        26.2%        17.1%        31.4%       |8.6%         4.4%         2.2%         25.5%        | 
|TERMINAL (d)       |     8/39 (21%)   10/40 (25%)  6/38 (16%)   12/30 (40%) |0/37 (0%)    1/38 (3%)    1/37 (3%)    6/34 (18%)   | 
|FIRST INCIDENCE    |     477          311          465          576         |411          642          729 (T)      401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.081      P=0.329      P=0.517N     P=0.080     |P<0.001 **   P=0.341N     P=0.187N     P=0.033 *    | 
|POLY 3             |     P=0.161      P=0.302      P=0.492N     P=0.147     |P<0.001 **   P=0.351N     P=0.191N     P=0.026 *    | 
|POLY 1.5           |     P=0.187      P=0.294      P=0.494N     P=0.170     |P<0.001 **   P=0.352N     P=0.185N     P=0.026 *    | 
|POLY 6             |     P=0.129      P=0.321      P=0.493N     P=0.119     |P<0.001 **   P=0.349N     P=0.201N     P=0.026 *    | 
|LOGISTIC REGRESSION|     P=0.228      P=0.322      P=0.502N     P=0.145     |P<0.001 **   P=0.328N     P=0.199N     P=0.013 *    | 
|COCH-ARM / FISHERS |     P=0.251      P=0.312      P=0.500N     P=0.235     |P<0.001 **   P=0.349N     P=0.181N     P=0.024 *    | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 16      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    0/50 (0%)   |3/50 (6%)    7/49 (14%)   5/50 (10%)   7/49 (14%)   | 
|POLY-3 RATE (b)    |     0/45.56      1/45.10      1/45.36      0/40.88     |3/45.03      7/45.76      5/46.16      7/45.54      | 
|POLY-3 PERCENT (g) |     0.0%         2.2%         2.2%         0.0%        |6.7%         15.3%        10.8%        15.4%        | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    0/30 (0%)   |1/37 (3%)    4/38 (11%)   2/37 (5%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     ---          311          730 (T)      ---         |703          555          481          509          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.576N     P=0.496      P=0.495      (e)         |P=0.224      P=0.180      P=0.358      P=0.151      | 
|POLY 3             |     P=0.568N     P=0.498      P=0.499      (e)         |P=0.254      P=0.164      P=0.370      P=0.162      | 
|POLY 1.5           |     P=0.560N     P=0.496      P=0.500      (e)         |P=0.253      P=0.156      P=0.368      P=0.160      | 
|POLY 6             |     P=0.578N     P=0.503      P=0.498      (e)         |P=0.251      P=0.173      P=0.370      P=0.162      | 
|LOGISTIC REGRESSION|     P=0.438N     P=0.798      P=0.495      (e)         |P=0.227      P=0.151      P=0.345      P=0.146      | 
|COCH-ARM / FISHERS |     P=0.541N     P=0.500      P=0.500      (e)         |P=0.240      P=0.151      P=0.357      P=0.151      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  15/50 (30%)  23/50 (46%)  33/50 (66%) |40/50 (80%)  37/49 (76%)  40/50 (80%)  38/49 (78%)  | 
|POLY-3 RATE (b)    |     10/45.56     15/44.93     23/46.99     33/43.21    |40/46.83     37/45.31     40/46.76     38/47.64     | 
|POLY-3 PERCENT (g) |     22.0%        33.4%        49.0%        76.4%       |85.4%        81.7%        85.6%        79.8%        | 
|TERMINAL (d)       |     10/39 (26%)  14/40 (35%)  19/38 (50%)  28/30 (93%) |34/37 (92%)  34/38 (90%)  35/37 (95%)  30/34 (88%)  | 
|FIRST INCIDENCE    |     730 (T)      455          465          498         |456          681          313          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.190      P=0.004 **   P<0.001 **  |P=0.301      P=0.221N     P=0.588      P=0.520      | 
|POLY 3             |     P<0.001 **   P=0.162      P=0.005 **   P<0.001 **  |P=0.306N     P=0.415N     P=0.617      P=0.318N     | 
|POLY 1.5           |     P<0.001 **   P=0.157      P=0.005 **   P<0.001 **  |P=0.351N     P=0.419N     P=0.586N     P=0.353N     | 
|POLY 6             |     P<0.001 **   P=0.180      P=0.005 **   P<0.001 **  |P=0.286N     P=0.416N     P=0.554      P=0.307N     | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.156      P=0.005 **   P<0.001 **  |P=0.480N     P=0.272N     P=0.593N     P=0.426N     | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.178      P=0.005 **   P<0.001 **  |P=0.520N     P=0.384N     P=0.598N     P=0.479N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 17      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    5/50 (10%)  |0/50 (0%)    0/49 (0%)    0/50 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     2/46.28      2/44.18      2/45.94      5/42.68     |0/44.88      0/44.91      0/44.70      0/44.29      | 
|POLY-3 PERCENT (g) |     4.3%         4.5%         4.4%         11.7%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/39 (3%)    1/40 (3%)    1/38 (3%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     477          728          548          539         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.067      P=0.689N     P=0.689      P=0.173     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.088      P=0.677      P=0.691      P=0.184     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.092      P=0.677      P=0.692      P=0.191     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.083      P=0.683      P=0.689      P=0.177     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.134      P=0.678N     P=0.671      P=0.288     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.103      P=0.691N     P=0.691N     P=0.218     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Tension Lipidosis                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    2/49 (4%)    1/50 (2%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     2/45.91      2/45.10      2/45.36      0/40.88     |0/44.88      2/45.47      1/44.70      0/44.29      | 
|POLY-3 PERCENT (g) |     4.4%         4.4%         4.4%         0.0%        |0.0%         4.4%         2.2%         0.0%         | 
|TERMINAL (d)       |     1/39 (3%)    0/40 (0%)    2/38 (5%)    0/30 (0%)   |0/37 (0%)    1/38 (3%)    1/37 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     632          455          730 (T)      ---         |---          555          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.202N     P=0.691N     P=0.684      P=0.289N    |P=0.400N     P=0.243      P=0.500      (e)          | 
|POLY 3             |     P=0.185N     P=0.687      P=0.690      P=0.264N    |P=0.384N     P=0.240      P=0.499      (e)          | 
|POLY 1.5           |     P=0.175N     P=0.684      P=0.692      P=0.256N    |P=0.384N     P=0.236      P=0.501      (e)          | 
|POLY 6             |     P=0.200N     P=0.692N     P=0.685      P=0.276N    |P=0.386N     P=0.245      P=0.497      (e)          | 
|LOGISTIC REGRESSION|     P=0.140N     P=0.640N     P=0.695      P=0.234N    |P=0.396N     P=0.237      P=0.500      (e)          | 
|COCH-ARM / FISHERS |     P=0.156N     P=0.691N     P=0.691N     P=0.247N    |P=0.388N     P=0.242      P=0.500      (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 18      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Centrilobular                                                                                                             | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    3/50 (6%)    4/50 (8%)   |0/50 (0%)    0/49 (0%)    1/50 (2%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |     0/45.56      1/44.18      3/46.01      4/42.50     |0/44.88      0/44.91      1/45.03      1/44.47      | 
|POLY-3 PERCENT (g) |     0.0%         2.3%         6.5%         9.4%        |0.0%         0.0%         2.2%         2.3%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          728          597          539         |---          ---          638          683          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.024 *    P=0.510      P=0.120      P=0.053     |P=0.308      (e)          P=0.500      P=0.500      | 
|POLY 3             |     P=0.032 *    P=0.494      P=0.120      P=0.052     |P=0.304      (e)          P=0.501      P=0.498      | 
|POLY 1.5           |     P=0.033 *    P=0.493      P=0.120      P=0.053     |P=0.306      (e)          P=0.501      P=0.499      | 
|POLY 6             |     P=0.029 *    P=0.498      P=0.121      P=0.050     |P=0.299      (e)          P=0.499      P=0.497      | 
|LOGISTIC REGRESSION|     P=0.051      P=0.505      P=0.116      P=0.081     |P=0.290      (e)          P=0.488      P=0.493      | 
|COCH-ARM / FISHERS |     P=0.039 *    P=0.500      P=0.121      P=0.059     |P=0.302      (e)          P=0.500      P=0.495      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    7/50 (14%)   4/50 (8%)    4/50 (8%)   |5/50 (10%)   3/50 (6%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     3/45.56      7/44.17      4/45.75      4/41.19     |5/44.93      3/45.21      1/44.70      1/45.26      | 
|POLY-3 PERCENT (g) |     6.6%         15.9%        8.7%         9.7%        |11.1%        6.6%         2.2%         2.2%         | 
|TERMINAL (d)       |     3/39 (8%)    7/40 (18%)   3/38 (8%)    3/30 (10%)  |4/37 (11%)   3/38 (8%)    1/37 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     730 (T)      730 (T)      620          646         |717          729 (T)      729 (T)      717          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.509      P=0.167      P=0.486      P=0.368     |P=0.107N     P=0.344N     P=0.106N     P=0.126N     | 
|POLY 3             |     P=0.553N     P=0.144      P=0.502      P=0.445     |P=0.087N     P=0.353N     P=0.102N     P=0.099N     | 
|POLY 1.5           |     P=0.534N     P=0.143      P=0.502      P=0.460     |P=0.086N     P=0.357N     P=0.101N     P=0.099N     | 
|POLY 6             |     P=0.580N     P=0.152      P=0.502      P=0.424     |P=0.089N     P=0.348N     P=0.105N     P=0.102N     | 
|LOGISTIC REGRESSION|     P=0.586N     P=0.167      P=0.497      P=0.415     |P=0.097N     P=0.339N     P=0.109N     P=0.108N     | 
|COCH-ARM / FISHERS |     P=0.486N     P=0.159      P=0.500      P=0.500     |P=0.089N     P=0.357N     P=0.102N     P=0.102N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 19      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/45.56      0/44.17      1/45.36      2/41.28     |0/44.88      0/45.21      2/44.70      2/45.31      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         2.2%         4.8%        |0.0%         0.0%         4.5%         4.4%         | 
|TERMINAL (d)       |     1/39 (3%)    0/40 (0%)    1/38 (3%)    1/30 (3%)   |0/37 (0%)    0/38 (0%)    2/37 (5%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     730 (T)      ---          730 (T)      617         |---          ---          729 (T)      703          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.174      P=0.495N     P=0.756      P=0.429     |P=0.106      (e)          P=0.238      P=0.225      | 
|POLY 3             |     P=0.214      P=0.506N     P=0.760      P=0.466     |P=0.125      (e)          P=0.236      P=0.239      | 
|POLY 1.5           |     P=0.222      P=0.507N     P=0.760      P=0.475     |P=0.126      (e)          P=0.238      P=0.240      | 
|POLY 6             |     P=0.202      P=0.502N     P=0.758      P=0.453     |P=0.121      (e)          P=0.233      P=0.237      | 
|LOGISTIC REGRESSION|     P=0.218      (e)          P=0.756      P=0.486     |P=0.119      (e)          P=0.238      P=0.238      | 
|COCH-ARM / FISHERS |     P=0.235      P=0.500N     P=0.753N     P=0.500     |P=0.124      (e)          P=0.247      P=0.247      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/28 (0%)    0/29 (0%)    0/30 (0%)    0/30 (0%)   |1/33 (3%)    1/38 (3%)    3/37 (8%)    0/39 (0%)    | 
|POLY-3 RATE (b)    |     0/25.34      0/25.75      0/28.35      0/24.22     |1/29.96      1/34.28      3/33.58      0/35.17      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |3.3%         2.9%         8.9%         0.0%         | 
|TERMINAL (d)       |     0/20 (0%)    0/24 (0%)    0/26 (0%)    0/18 (0%)   |1/25 (4%)    1/29 (3%)    3/29 (10%)   0/28 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      729 (T)      729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.319N     P=0.729N     P=0.358      P=0.477N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.304N     P=0.731N     P=0.346      P=0.468N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.301N     P=0.732N     P=0.347      P=0.467N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.308N     P=0.731N     P=0.341      P=0.470N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.319N     P=0.729N     P=0.358      (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.303N     P=0.717N     P=0.352      P=0.458N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 20      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/28 (0%)    0/29 (0%)    0/30 (0%)    0/30 (0%)   |0/33 (0%)    0/38 (0%)    0/37 (0%)    3/39 (8%)    | 
|POLY-3 RATE (b)    |     0/25.34      0/25.75      0/28.35      0/24.22     |0/29.96      0/34.28      0/33.58      3/35.91      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         8.4%         | 
|TERMINAL (d)       |     0/20 (0%)    0/24 (0%)    0/26 (0%)    0/18 (0%)   |0/25 (0%)    0/29 (0%)    0/29 (0%)    1/28 (4%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          517          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.009 **   (e)          (e)          P=0.129      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.010 *    (e)          (e)          P=0.151      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.010 *    (e)          (e)          P=0.151      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.010 *    (e)          (e)          P=0.151      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.009 **   (e)          (e)          P=0.146      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.011 *    (e)          (e)          P=0.153      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Infiltration Cellular Plasma Cell                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/28 (0%)    0/29 (0%)    0/30 (0%)    0/30 (0%)   |0/33 (0%)    1/38 (3%)    1/37 (3%)    2/39 (5%)    | 
|POLY-3 RATE (b)    |     0/25.34      0/25.75      0/28.35      0/24.22     |0/29.96      1/34.28      1/33.58      2/35.17      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         2.9%         3.0%         5.7%         | 
|TERMINAL (d)       |     0/20 (0%)    0/24 (0%)    0/26 (0%)    0/18 (0%)   |0/25 (0%)    1/29 (3%)    1/29 (3%)    2/28 (7%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.201      P=0.530      P=0.530      P=0.263      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.219      P=0.527      P=0.523      P=0.273      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.221      P=0.526      P=0.524      P=0.274      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.216      P=0.527      P=0.520      P=0.270      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          P=0.530      P=0.530      P=0.263      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.219      P=0.535      P=0.529      P=0.290      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 21      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/48 (6%)    0/46 (0%)    3/45 (7%)    0/41 (0%)   |0/47 (0%)    0/44 (0%)    0/42 (0%)    0/45 (0%)    | 
|POLY-3 RATE (b)    |     3/44.28      0/40.27      3/41.99      0/35.23     |0/43.27      0/41.79      0/38.98      0/41.14      | 
|POLY-3 PERCENT (g) |     6.8%         0.0%         7.1%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/37 (5%)    0/37 (0%)    2/37 (5%)    0/30 (0%)   |0/37 (0%)    0/37 (0%)    0/36 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     477          ---          725          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.231N     P=0.127N     P=0.661      P=0.150N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.229N     P=0.136N     P=0.638      P=0.163N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.223N     P=0.136N     P=0.635      P=0.159N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.239N     P=0.133N     P=0.642      P=0.167N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.219N     P=0.102N     P=0.614      P=0.120N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.220N     P=0.129N     P=0.630      P=0.152N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    0/46 (0%)    1/45 (2%)    0/41 (0%)   |0/47 (0%)    0/44 (0%)    1/42 (2%)    3/45 (7%)    | 
|POLY-3 RATE (b)    |     0/43.56      0/40.27      1/41.97      0/35.23     |0/43.27      0/41.79      1/38.98      3/41.36      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.4%         0.0%        |0.0%         0.0%         2.6%         7.3%         | 
|TERMINAL (d)       |     0/37 (0%)    0/37 (0%)    1/37 (3%)    0/30 (0%)   |0/37 (0%)    0/37 (0%)    1/36 (3%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      ---         |---          ---          729 (T)      683          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.814      (e)          P=0.500      (e)         |P=0.019 *    (e)          P=0.495      P=0.116      | 
|POLY 3             |     P=0.803      (e)          P=0.493      (e)         |P=0.020 *    (e)          P=0.479      P=0.110      | 
|POLY 1.5           |     P=0.807      (e)          P=0.490      (e)         |P=0.021 *    (e)          P=0.478      P=0.111      | 
|POLY 6             |     P=0.796      (e)          P=0.495      (e)         |P=0.020 *    (e)          P=0.481      P=0.110      | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.500      (e)         |P=0.021 *    (e)          P=0.495      P=0.112      | 
|COCH-ARM / FISHERS |     P=0.807N     (e)          P=0.484      (e)         |P=0.022 *    (e)          P=0.472      P=0.113      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 22      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    0/46 (0%)    0/45 (0%)    0/41 (0%)   |3/47 (6%)    1/44 (2%)    3/42 (7%)    0/45 (0%)    | 
|POLY-3 RATE (b)    |     0/43.56      0/40.27      0/41.97      0/35.23     |3/43.27      1/41.79      3/39.28      0/41.14      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |6.9%         2.4%         7.6%         0.0%         | 
|TERMINAL (d)       |     0/37 (0%)    0/37 (0%)    0/37 (0%)    0/30 (0%)   |3/37 (8%)    1/37 (3%)    2/36 (6%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      729 (T)      647          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.157N     P=0.305N     P=0.648      P=0.136N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.153N     P=0.318N     P=0.617      P=0.127N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.149N     P=0.325N     P=0.613      P=0.127N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.158N     P=0.311N     P=0.624      P=0.128N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.149N     P=0.305N     P=0.613      (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.146N     P=0.334N     P=0.606      P=0.129N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    15/46 (33%)  33/45 (73%)  34/41 (83%) |0/47 (0%)    23/44 (52%)  35/42 (83%)  25/45 (56%)  | 
|POLY-3 RATE (b)    |     0/43.56      15/41.59     33/44.27     34/38.95    |0/43.27      23/43.54     35/40.40     25/43.77     | 
|POLY-3 PERCENT (g) |     0.0%         36.1%        74.5%        87.3%       |0.0%         52.8%        86.6%        57.1%        | 
|TERMINAL (d)       |     0/37 (0%)    13/37 (35%)  28/37 (76%)  26/30 (87%) |0/37 (0%)    20/37 (54%)  32/36 (89%)  19/34 (56%)  | 
|FIRST INCIDENCE    |     ---          508          465          483         |---          18           509          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P<0.001 **   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<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   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<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 23      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Infiltration Cellular Plasma Cell                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    0/46 (0%)    0/45 (0%)    0/41 (0%)   |1/47 (2%)    0/44 (0%)    1/42 (2%)    2/45 (4%)    | 
|POLY-3 RATE (b)    |     0/43.56      0/40.27      0/41.97      0/35.23     |1/43.27      0/41.79      1/38.98      2/41.24      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.3%         0.0%         2.6%         4.9%         | 
|TERMINAL (d)       |     0/37 (0%)    0/37 (0%)    0/37 (0%)    0/30 (0%)   |1/37 (3%)    0/37 (0%)    1/36 (3%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      ---          729 (T)      703          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.211      P=0.500N     P=0.756      P=0.471      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.227      P=0.507N     P=0.737      P=0.483      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.231      P=0.511N     P=0.736      P=0.484      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.223      P=0.503N     P=0.739      P=0.482      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.223      (e)          P=0.756      P=0.481      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.233      P=0.516N     P=0.724      P=0.484      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/10 (100%) 3/4 (75%)    19/20 (95%)  10/10 (100%)|29/30 (97%)  33/34 (97%)  31/32 (97%)  41/42 (98%)  | 
|POLY-3 RATE (b)    |     10/10.00     3/3.84       19/19.61     10/10.00    |29/29.25     33/33.41     31/31.67     41/42.00     | 
|POLY-3 PERCENT (g) |     100.0%       78.2%        96.9%        100.0%      |99.2%        98.8%        97.9%        97.6%        | 
|TERMINAL (d)       |     9/9 (100%)   3/3 (100%)   18/18 (100%) 9/9 (100%)  |21/21 (100%) 27/27 (100%) 25/25 (100%) 29/30 (97%)  | 
|FIRST INCIDENCE    |     477          730 (T)      680          631         |411          681          589          579          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.494      P=0.513N     P=0.753      (e)         |P=0.147      P=0.376N     P=0.413N     P=0.301      | 
|POLY 3             |     P=0.580      P=0.385N     P=0.840N     (e)         |P=0.520N     P=0.965N     P=0.801N     P=0.677N     | 
|POLY 1.5           |     P=0.537      P=0.343N     P=0.736N     (e)         |P=0.629N     P=0.872N     P=0.774N     P=0.753N     | 
|POLY 6             |     P=0.681      P=0.485N     P=0.979N     (e)         |P=0.381N     P=1.000N     P=0.915N     P=0.601N     | 
|LOGISTIC REGRESSION|     P=0.626      P=0.290N     P=0.440N     (e)         |P=0.481N     P=0.354N     P=0.517N     P=0.669N     | 
|COCH-ARM / FISHERS |     P=0.500      P=0.286N     P=0.667N     (e)         |P=0.570      P=0.722      P=0.738      P=0.663      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 24      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   0/50 (0%)    11/50 (22%)  2/47 (4%)   |2/50 (4%)    0/50 (0%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     5/46.47      0/44.17      11/46.23     2/39.33     |2/44.90      0/45.21      2/45.55      2/45.21      | 
|POLY-3 PERCENT (g) |     10.8%        0.0%         23.8%        5.1%        |4.5%         0.0%         4.4%         4.4%         | 
|TERMINAL (d)       |     2/39 (5%)    0/40 (0%)    8/38 (21%)   2/30 (7%)   |1/37 (3%)    0/38 (0%)    0/37 (0%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     599          ---          620          730 (T)     |723          ---          509          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.539N     P=0.037N*    P=0.088      P=0.322N    |P=0.406      P=0.237N     P=0.687      P=0.663      | 
|POLY 3             |     P=0.489N     P=0.035N*    P=0.081      P=0.289N    |P=0.430      P=0.236N     P=0.689N     P=0.691N     | 
|POLY 1.5           |     P=0.454N     P=0.035N*    P=0.083      P=0.272N    |P=0.435      P=0.237N     P=0.689N     P=0.690N     | 
|POLY 6             |     P=0.545N     P=0.034N*    P=0.078      P=0.314N    |P=0.422      P=0.234N     P=0.690N     P=0.692      | 
|LOGISTIC REGRESSION|     P=0.440N     P=0.030N*    P=0.086      P=0.248N    |P=0.424      P=0.231N     P=0.686      P=0.678      | 
|COCH-ARM / FISHERS |     P=0.417N     P=0.028N*    P=0.086      P=0.244N    |P=0.429      P=0.247N     P=0.691N     P=0.691N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Olfactory Epithelium                                                                                                       | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    1/50 (2%)    0/47 (0%)   |0/50 (0%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/45.56      3/44.17      1/45.36      0/39.33     |0/44.88      1/45.21      1/44.70      1/45.21      | 
|POLY-3 PERCENT (g) |     0.0%         6.8%         2.2%         0.0%        |0.0%         2.2%         2.2%         2.2%         | 
|TERMINAL (d)       |     0/39 (0%)    3/40 (8%)    1/38 (3%)    0/30 (0%)   |0/37 (0%)    1/38 (3%)    1/37 (3%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          730 (T)      730 (T)      ---         |---          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.348N     P=0.126      P=0.495      (e)         |P=0.456      P=0.505      P=0.500      P=0.483      | 
|POLY 3             |     P=0.322N     P=0.113      P=0.499      (e)         |P=0.486      P=0.501      P=0.499      P=0.501      | 
|POLY 1.5           |     P=0.315N     P=0.113      P=0.500      (e)         |P=0.488      P=0.500      P=0.501      P=0.502      | 
|POLY 6             |     P=0.332N     P=0.117      P=0.498      (e)         |P=0.480      P=0.503      P=0.497      P=0.499      | 
|LOGISTIC REGRESSION|     (e)          P=0.126      P=0.495      (e)         |(e)          P=0.505      P=0.500      P=0.483      | 
|COCH-ARM / FISHERS |     P=0.296N     P=0.121      P=0.500      (e)         |P=0.483      P=0.500      P=0.500      P=0.500      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 25      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Olfactory Epithelium                                                                                                       | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    1/50 (2%)    1/47 (2%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/45.56      3/44.17      1/45.36      1/39.33     |0/44.88      2/45.21      0/44.70      1/45.21      | 
|POLY-3 PERCENT (g) |     0.0%         6.8%         2.2%         2.5%        |0.0%         4.4%         0.0%         2.2%         | 
|TERMINAL (d)       |     0/39 (0%)    3/40 (8%)    1/38 (3%)    1/30 (3%)   |0/37 (0%)    2/38 (5%)    0/37 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          730 (T)      730 (T)      730 (T)     |---          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.631      P=0.126      P=0.495      P=0.448     |P=0.591      P=0.244      (e)          P=0.483      | 
|POLY 3             |     P=0.643N     P=0.113      P=0.499      P=0.471     |P=0.617      P=0.239      (e)          P=0.501      | 
|POLY 1.5           |     P=0.634N     P=0.113      P=0.500      P=0.476     |P=0.618      P=0.237      (e)          P=0.502      | 
|POLY 6             |     P=0.643      P=0.117      P=0.498      P=0.463     |P=0.615      P=0.241      (e)          P=0.499      | 
|LOGISTIC REGRESSION|     (e)          P=0.126      P=0.495      P=0.448     |(e)          P=0.244      (e)          P=0.483      | 
|COCH-ARM / FISHERS |     P=0.613N     P=0.121      P=0.500      P=0.485     |P=0.615      P=0.247      (e)          P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/47 (2%)    0/46 (0%)    0/47 (0%)    2/48 (4%)    | 
|POLY-3 RATE (b)    |                                                        |1/42.97      0/41.53      0/41.98      2/43.54      | 
|POLY-3 PERCENT (g) |                                                        |2.3%         0.0%         0.0%         4.6%         | 
|TERMINAL (d)       |                                                        |0/36 (0%)    0/35 (0%)    0/36 (0%)    2/34 (6%)    | 
|FIRST INCIDENCE    |                                                        |456          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.186      P=0.500N     P=0.496N     P=0.489      | 
|POLY 3             |                                                        |P=0.199      P=0.507N     P=0.505N     P=0.505      | 
|POLY 1.5           |                                                        |P=0.200      P=0.507N     P=0.502N     P=0.508      | 
|POLY 6             |                                                        |P=0.195      P=0.506N     P=0.509N     P=0.499      | 
|LOGISTIC REGRESSION|                                                        |P=0.172      P=0.443N     P=0.595N     P=0.465      | 
|COCH-ARM / FISHERS |                                                        |P=0.198      P=0.505N     P=0.500N     P=0.508      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 26      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |10/47 (21%)  12/46 (26%)  8/47 (17%)   7/48 (15%)   | 
|POLY-3 RATE (b)    |                                                        |10/44.49     12/41.81     8/42.65      7/43.54      | 
|POLY-3 PERCENT (g) |                                                        |22.5%        28.7%        18.8%        16.1%        | 
|TERMINAL (d)       |                                                        |6/36 (17%)   10/35 (29%)  6/36 (17%)   7/34 (21%)   | 
|FIRST INCIDENCE    |                                                        |183          681          589          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.202N     P=0.393      P=0.403N     P=0.338N     | 
|POLY 3             |                                                        |P=0.166N     P=0.339      P=0.435N     P=0.312N     | 
|POLY 1.5           |                                                        |P=0.156N     P=0.344      P=0.421N     P=0.299N     | 
|POLY 6             |                                                        |P=0.182N     P=0.339      P=0.451N     P=0.333N     | 
|LOGISTIC REGRESSION|                                                        |P=0.148N     P=0.384      P=0.410N     P=0.306N     | 
|COCH-ARM / FISHERS |                                                        |P=0.150N     P=0.382      P=0.397N     P=0.280N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)   |0/46 (0%)    2/45 (4%)    0/46 (0%)    1/46 (2%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/44.86      0/40.88     |0/42.79      2/42.20      0/41.89      1/41.88      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         4.7%         0.0%         2.4%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    2/37 (5%)    0/37 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.593      P=0.238      (e)          P=0.483      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.612      P=0.234      (e)          P=0.496      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.614      P=0.232      (e)          P=0.498      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.608      P=0.236      (e)          P=0.493      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          P=0.238      (e)          P=0.483      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.617      P=0.242      (e)          P=0.500      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 27      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/47 (0%)    0/48 (0%)    3/49 (6%)    2/48 (4%)   |11/48 (23%)  8/47 (17%)   10/45 (22%)  11/48 (23%)  | 
|POLY-3 RATE (b)    |     0/43.37      0/42.17      3/44.36      2/39.13     |11/43.21     8/42.52      10/41.65     11/43.65     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         6.8%         5.1%        |25.5%        18.8%        24.0%        25.2%        | 
|TERMINAL (d)       |     0/37 (0%)    0/38 (0%)    3/37 (8%)    2/30 (7%)   |11/36 (31%)  7/37 (19%)   8/36 (22%)   10/34 (29%)  | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      730 (T)     |729 (T)      703          638          701          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.103      (e)          P=0.121      P=0.193     |P=0.346      P=0.277N     P=0.504N     P=0.539      | 
|POLY 3             |     P=0.125      (e)          P=0.122      P=0.215     |P=0.440      P=0.316N     P=0.539N     P=0.587N     | 
|POLY 1.5           |     P=0.135      (e)          P=0.124      P=0.222     |P=0.448      P=0.324N     P=0.546N     P=0.583N     | 
|POLY 6             |     P=0.110      (e)          P=0.121      P=0.206     |P=0.422      P=0.306N     P=0.531N     P=0.597N     | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.121      P=0.193     |P=0.411      P=0.295N     P=0.558N     P=0.547      | 
|COCH-ARM / FISHERS |     P=0.159      (e)          P=0.129      P=0.253     |P=0.433      P=0.323N     P=0.567N     P=0.596N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Ectasia                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/49 (6%)    3/50 (6%)    5/49 (10%)   3/50 (6%)   |                                                    | 
|POLY-3 RATE (b)    |     3/45.04      3/44.34      5/44.84      3/41.44     |                                                    | 
|POLY-3 PERCENT (g) |     6.7%         6.8%         11.2%        7.2%        |                                                    | 
|TERMINAL (d)       |     2/38 (5%)    2/40 (5%)    4/38 (11%)   1/30 (3%)   |                                                    | 
|FIRST INCIDENCE    |     590          688          653          631         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.473      P=0.650N     P=0.357      P=0.566     |                                                    | 
|POLY 3             |     P=0.553      P=0.655      P=0.354      P=0.624     |                                                    | 
|POLY 1.5           |     P=0.573      P=0.654      P=0.356      P=0.637     |                                                    | 
|POLY 6             |     P=0.520      P=0.661N     P=0.351      P=0.605     |                                                    | 
|LOGISTIC REGRESSION|     P=0.590      P=0.661N     P=0.356      P=0.658N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.571N     P=0.651N     P=0.357      P=0.651N    |                                                    | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 28      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/49 (2%)    2/50 (4%)    2/49 (4%)    3/50 (6%)   |                                                    | 
|POLY-3 RATE (b)    |     1/44.56      2/44.17      2/44.55      3/40.88     |                                                    | 
|POLY-3 PERCENT (g) |     2.2%         4.5%         4.5%         7.3%        |                                                    | 
|TERMINAL (d)       |     1/38 (3%)    2/40 (5%)    2/38 (5%)    3/30 (10%)  |                                                    | 
|FIRST INCIDENCE    |     730 (T)      730 (T)      730 (T)      730 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.167      P=0.518      P=0.500      P=0.224     |                                                    | 
|POLY 3             |     P=0.234      P=0.497      P=0.500      P=0.275     |                                                    | 
|POLY 1.5           |     P=0.246      P=0.495      P=0.500      P=0.285     |                                                    | 
|POLY 6             |     P=0.215      P=0.505      P=0.499      P=0.260     |                                                    | 
|LOGISTIC REGRESSION|     P=0.167      P=0.518      P=0.500      P=0.224     |                                                    | 
|COCH-ARM / FISHERS |     P=0.273      P=0.508      P=0.500      P=0.316     |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |0/49 (0%)    0/49 (0%)    2/50 (4%)    0/48 (0%)    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      0/45.36      0/40.09     |0/44.21      0/44.24      2/45.36      0/43.60      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         4.4%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    1/37 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          509          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.700N     (e)          P=0.242      (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.699N     (e)          P=0.243      (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.697N     (e)          P=0.244      (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.704N     (e)          P=0.240      (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.735N     (e)          P=0.219      (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.700N     (e)          P=0.253      (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 29      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Seminal Vesicle                                                                                                                  | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    5/50 (10%)   0/49 (0%)   |                                                    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      5/45.36      0/40.28     |                                                    | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         11.0%        0.0%        |                                                    | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    5/38 (13%)   0/30 (0%)   |                                                    | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      ---         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.631      (e)          P=0.031 *    (e)         |                                                    | 
|POLY 3             |     P=0.646      (e)          P=0.030 *    (e)         |                                                    | 
|POLY 1.5           |     P=0.640N     (e)          P=0.031 *    (e)         |                                                    | 
|POLY 6             |     P=0.610      (e)          P=0.029 *    (e)         |                                                    | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.031 *    (e)         |                                                    | 
|COCH-ARM / FISHERS |     P=0.597N     (e)          P=0.028 *    (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Seminal Vesicle                                                                                                                  | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    2/49 (4%)   |                                                    | 
|POLY-3 RATE (b)    |     0/45.56      0/44.17      1/45.36      2/40.51     |                                                    | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         4.9%        |                                                    | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    1/38 (3%)    1/30 (3%)   |                                                    | 
|FIRST INCIDENCE    |     ---          ---          730 (T)      668         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.052      (e)          P=0.495      P=0.192     |                                                    | 
|POLY 3             |     P=0.070      (e)          P=0.499      P=0.212     |                                                    | 
|POLY 1.5           |     P=0.074      (e)          P=0.500      P=0.217     |                                                    | 
|POLY 6             |     P=0.065      (e)          P=0.498      P=0.205     |                                                    | 
|LOGISTIC REGRESSION|     P=0.069      (e)          P=0.495      P=0.218     |                                                    | 
|COCH-ARM / FISHERS |     P=0.081      (e)          P=0.500      P=0.242     |                                                    | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 30      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/49 (20%)  8/50 (16%)   15/49 (31%)  15/49 (31%) |10/47 (21%)  19/48 (40%)  15/47 (32%)  18/46 (39%)  | 
|POLY-3 RATE (b)    |     10/46.45     8/46.66      15/48.52     15/42.40    |10/45.28     19/45.25     15/44.02     18/43.75     | 
|POLY-3 PERCENT (g) |     21.5%        17.1%        30.9%        35.4%       |22.1%        42.0%        34.1%        41.1%        | 
|TERMINAL (d)       |     6/39 (15%)   4/40 (10%)   6/38 (16%)   7/30 (23%)  |5/37 (14%)   13/38 (34%)  10/37 (27%)  11/34 (32%)  | 
|FIRST INCIDENCE    |     590          311          465          590         |456          541          589          509          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.031 *    P=0.409N     P=0.191      P=0.081     |P=0.135      P=0.064      P=0.189      P=0.059      | 
|POLY 3             |     P=0.042 *    P=0.393N     P=0.211      P=0.111     |P=0.130      P=0.034 *    P=0.152      P=0.042 *    | 
|POLY 1.5           |     P=0.050      P=0.395N     P=0.198      P=0.125     |P=0.136      P=0.033 *    P=0.159      P=0.044 *    | 
|POLY 6             |     P=0.034 *    P=0.388N     P=0.224      P=0.097     |P=0.123      P=0.035 *    P=0.147      P=0.039 *    | 
|LOGISTIC REGRESSION|     P=0.115      P=0.284N     P=0.152      P=0.162     |P=0.140      P=0.044 *    P=0.188      P=0.053      | 
|COCH-ARM / FISHERS |     P=0.080      P=0.379N     P=0.177      P=0.177     |P=0.140      P=0.043 *    P=0.175      P=0.049 *    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)   |1/47 (2%)    3/48 (6%)    0/47 (0%)    0/46 (0%)    | 
|POLY-3 RATE (b)    |     0/44.72      0/44.17      0/44.81      0/40.16     |1/43.70      3/43.55      0/42.46      0/41.88      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.3%         6.9%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |1/37 (3%)    3/38 (8%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.170N     P=0.314      P=0.500N     P=0.517N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.162N     P=0.304      P=0.506N     P=0.508N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.161N     P=0.304      P=0.504N     P=0.507N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.163N     P=0.306      P=0.508N     P=0.511N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.170N     P=0.314      (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.160N     P=0.316      P=0.500N     P=0.505N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 31      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    1/50 (2%)    1/49 (2%)    22/49 (45%) |0/47 (0%)    3/48 (6%)    12/47 (26%)  28/46 (61%)  | 
|POLY-3 RATE (b)    |     0/44.72      1/44.84      1/45.28      22/42.62    |0/43.70      3/43.55      12/43.17     28/44.08     | 
|POLY-3 PERCENT (g) |     0.0%         2.2%         2.2%         51.6%       |0.0%         6.9%         27.8%        63.5%        | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    18/30 (60%) |0/37 (0%)    3/38 (8%)    11/37 (30%)  23/34 (68%)  | 
|FIRST INCIDENCE    |     ---          508          592          17          |---          729 (T)      481          401          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.492      P=0.496      P<0.001 **  |P<0.001 **   P=0.126      P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P=0.501      P=0.502      P<0.001 **  |P<0.001 **   P=0.118      P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.499      P=0.502      P<0.001 **  |P<0.001 **   P=0.118      P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.505      P=0.503      P<0.001 **  |P<0.001 **   P=0.119      P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.621      P=0.454      P<0.001 **  |P<0.001 **   P=0.126      P<0.001 **   P<0.001 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.505      P=0.500      P<0.001 **  |P<0.001 **   P=0.125      P<0.001 **   P<0.001 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Metaplasia Osseous                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)   |0/47 (0%)    0/48 (0%)    0/47 (0%)    2/46 (4%)    | 
|POLY-3 RATE (b)    |     0/44.72      0/44.17      0/44.81      0/40.16     |0/43.70      0/43.55      0/42.46      2/41.88      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         4.8%         | 
|TERMINAL (d)       |     0/39 (0%)    0/40 (0%)    0/38 (0%)    0/30 (0%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.034 *    (e)          (e)          P=0.220      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.038 *    (e)          (e)          P=0.228      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.038 *    (e)          (e)          P=0.230      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.037 *    (e)          (e)          P=0.225      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          P=0.220      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.039 *    (e)          (e)          P=0.242      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 32      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/49 (12%)   0/50 (0%)    2/50 (4%)    3/50 (6%)   |2/47 (4%)    2/48 (4%)    2/49 (4%)    0/48 (0%)    | 
|POLY-3 RATE (b)    |     6/47.48      0/44.17      2/45.65      3/41.73     |2/43.74      2/44.26      2/43.93      0/43.54      | 
|POLY-3 PERCENT (g) |     12.6%        0.0%         4.4%         7.2%        |4.6%         4.5%         4.6%         0.0%         | 
|TERMINAL (d)       |     1/39 (3%)    0/40 (0%)    1/38 (3%)    1/30 (3%)   |1/37 (3%)    1/38 (3%)    2/37 (5%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     477          ---          653          483         |661          642          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.596N     P=0.023N*    P=0.152N     P=0.334N    |P=0.173N     P=0.683N     P=0.687      P=0.252N     | 
|POLY 3             |     P=0.522N     P=0.020N*    P=0.146N     P=0.310N    |P=0.159N     P=0.690N     P=0.692N     P=0.238N     | 
|POLY 1.5           |     P=0.512N     P=0.018N*    P=0.138N     P=0.285N    |P=0.156N     P=0.692N     P=0.687N     P=0.236N     | 
|POLY 6             |     P=0.542N     P=0.020N*    P=0.156N     P=0.345N    |P=0.164N     P=0.686N     P=0.689      P=0.242N     | 
|LOGISTIC REGRESSION|     P=0.424N     P=0.005N**   P=0.075N     P=0.135N    |P=0.153N     P=0.684N     P=0.689N     P=0.231N     | 
|COCH-ARM / FISHERS |     P=0.502N     P=0.012N*    P=0.128N     P=0.233N    |P=0.153N     P=0.684N     P=0.676N     P=0.242N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |3/47 (6%)    0/48 (0%)    0/49 (0%)    0/48 (0%)    | 
|POLY-3 RATE (b)    |     0/45.37      1/44.17      0/45.36      1/40.88     |3/44.38      0/43.94      0/43.93      0/43.54      | 
|POLY-3 PERCENT (g) |     0.0%         2.3%         0.0%         2.5%        |6.8%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/39 (0%)    1/40 (3%)    0/38 (0%)    1/30 (3%)   |0/37 (0%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          730 (T)      ---          730 (T)     |636          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.395      P=0.505      (e)          P=0.448     |P=0.134N     P=0.123N     P=0.133N     P=0.125N     | 
|POLY 3             |     P=0.431      P=0.495      (e)          P=0.479     |P=0.121N     P=0.120N     P=0.120N     P=0.122N     | 
|POLY 1.5           |     P=0.440      P=0.495      (e)          P=0.486     |P=0.121N     P=0.120N     P=0.117N     P=0.119N     | 
|POLY 6             |     P=0.420      P=0.498      (e)          P=0.470     |P=0.121N     P=0.121N     P=0.126N     P=0.127N     | 
|LOGISTIC REGRESSION|     (e)          P=0.505      (e)          P=0.448     |P=0.131N     P=0.095N     P=0.094N     P=0.108N     | 
|COCH-ARM / FISHERS |     P=0.462      P=0.505      (e)          P=0.505     |P=0.128N     P=0.117N     P=0.113N     P=0.117N     | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 33      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Tooth                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/33 (18%)   6/27 (22%)   5/30 (17%)   6/23 (26%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|POLY-3 RATE (b)    |     6/32.23      6/26.99      5/29.52      6/22.31     |0/0.00       0/0.00       0/0.00       0/0.00       | 
|POLY-3 PERCENT (g) |     18.6%        22.2%        16.9%        26.9%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     6/30 (20%)   6/26 (23%)   5/28 (18%)   6/20 (30%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     730 (T)      730 (T)      730 (T)      730 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.284      P=0.518      P=0.550N     P=0.320     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.326      P=0.492      P=0.563N     P=0.349     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.331      P=0.484      P=0.565N     P=0.351     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.319      P=0.505      P=0.560N     P=0.345     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.284      P=0.518      P=0.550N     P=0.320     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.334      P=0.472      P=0.570N     P=0.350     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Tooth                                                                                                                            | 
|     Malformation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     29/33 (88%)  22/27 (81%)  27/30 (90%)  20/23 (87%) |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|POLY-3 RATE (b)    |     29/33.00     22/27.00     27/30.00     20/23.00    |0/0.00       0/0.00       0/0.00       0/0.00       | 
|POLY-3 PERCENT (g) |     87.9%        81.5%        90.0%        87.0%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     26/30 (87%)  21/26 (81%)  25/28 (89%)  17/20 (85%) |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     632          728          653          621         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.366      P=0.217N     P=0.596N     P=0.592     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.533      P=0.373N     P=0.552      P=0.619N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.533      P=0.373N     P=0.552      P=0.619N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.533      P=0.373N     P=0.552      P=0.619N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.533      P=0.370N     P=0.555      P=0.613N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 34      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hydrometra                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |27/48 (56%)  21/49 (43%)  25/50 (50%)  20/50 (40%)  | 
|POLY-3 RATE (b)    |                                                        |27/44.27     21/44.63     25/46.24     20/45.54     | 
|POLY-3 PERCENT (g) |                                                        |61.0%        47.1%        54.1%        43.9%        | 
|TERMINAL (d)       |                                                        |24/37 (65%)  18/38 (47%)  19/37 (51%)  17/34 (50%)  | 
|FIRST INCIDENCE    |                                                        |667          681          621          683          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.312N     P=0.126N     P=0.435N     P=0.197N     | 
|POLY 3             |                                                        |P=0.126N     P=0.130N     P=0.323N     P=0.074N     | 
|POLY 1.5           |                                                        |P=0.120N     P=0.142N     P=0.333N     P=0.074N     | 
|POLY 6             |                                                        |P=0.143N     P=0.116N     P=0.307N     P=0.078N     | 
|LOGISTIC REGRESSION|                                                        |P=0.144N     P=0.111N     P=0.395N     P=0.092N     | 
|COCH-ARM / FISHERS |                                                        |P=0.132N     P=0.132N     P=0.338N     P=0.079N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |8/48 (17%)   9/49 (18%)   8/50 (16%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |                                                        |8/44.48      9/44.24      8/44.93      10/45.46     | 
|POLY-3 PERCENT (g) |                                                        |18.0%        20.4%        17.8%        22.0%        | 
|TERMINAL (d)       |                                                        |6/37 (16%)   9/38 (24%)   7/37 (19%)   9/34 (27%)   | 
|FIRST INCIDENCE    |                                                        |636          729 (T)      667          661          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.283      P=0.522      P=0.598      P=0.334      | 
|POLY 3             |                                                        |P=0.392      P=0.495      P=0.600N     P=0.417      | 
|POLY 1.5           |                                                        |P=0.402      P=0.495      P=0.588N     P=0.426      | 
|POLY 6             |                                                        |P=0.375      P=0.494      P=0.602      P=0.400      | 
|LOGISTIC REGRESSION|                                                        |P=0.379      P=0.511      P=0.594N     P=0.420      | 
|COCH-ARM / FISHERS |                                                        |P=0.401      P=0.519      P=0.572N     P=0.435      | 
|=================================================================================================================================| 
       Date:  04/23/01                           EXPERIMENT: 88122 TEST: 07                                            Page 35      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                      ELMIRON           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      56 MG/KG     168          504         |0 MG/KG      56 MG/KG     168          504          | 
|                   |                               MG/KG        MG/KG       |                          MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |2/48 (4%)    0/49 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |                                                        |2/43.89      0/44.24      0/44.70      0/45.21      | 
|POLY-3 PERCENT (g) |                                                        |4.6%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |                                                        |2/37 (5%)    0/38 (0%)    0/37 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.251N     P=0.232N     P=0.238N     P=0.257N     | 
|POLY 3             |                                                        |P=0.229N     P=0.235N     P=0.233N     P=0.230N     | 
|POLY 1.5           |                                                        |P=0.228N     P=0.237N     P=0.231N     P=0.229N     | 
|POLY 6             |                                                        |P=0.231N     P=0.233N     P=0.236N     P=0.233N     | 
|LOGISTIC REGRESSION|                                                        |P=0.251N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.233N     P=0.242N     P=0.237N     P=0.237N     | 
|=================================================================================================================================| 
(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).