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TDMS Study 05211-05 Pathology Tables


NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                      EMODIN                                        DATE: 01/25/01       
EXPERIMENT: 05211 TEST: 05                                                                                     TIME: 13:06:07       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-85216                              ROUTE: DOSED FEED                                              NTP C#: C62408       
PATHOLOGIST: HEATH, JAMES                                                                                      CAS: 518-82-1        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                         FINAL#3;REVISION#1                                                         
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    25022 Accidently Killed                                                                      
                                       25019 Moribund Sacrifice                                                                     
                                       25020 Natural Death                                                                          
                                       25021 Terminal Sacrifice                                                                     
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                      EMODIN                                        DATE: 01/25/01       
EXPERIMENT: 05211 TEST: 05                                                                                     TIME: 13:06:07       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-85216                              ROUTE: DOSED FEED                                              NTP C#: C62408       
PATHOLOGIST: HEATH, JAMES                                                                                      CAS: 518-82-1        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                      EMODIN                                                                                      
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Cortex                         Accessory Adrenal Cortical Nodule                                                            
Adrenal Medulla                        Hyperplasia                                                                                  
Bone Marrow                            Hyperplasia                                                                                  
Heart                                  Thrombosis                                                                                   
Intestine Large, Cecum                 Inflammation Chronic                                                                         
Intestine Large, Cecum: Epithelium     Hyperplasia                                                                                  
Islets, Pancreatic                     Hyperplasia                                                                                  
Kidney                                 Hydronephrosis                                                                               
                                       Infarct                                                                                      
                                       Inflammation Chronic                                                                         
                                       Nephropathy                                                                                  
Kidney: Renal Tubule                   Hyaline Droplet                                                                              
                                       Pigmentation                                                                                 
Liver                                  Angiectasis                                                                                  
Liver: Bile Duct                       Hyperplasia                                                                                  
Lung                                   Infiltration Cellular Histiocyte                                                             
Lymph Node, Mesenteric                 Ectasia                                                                                      
Mammary Gland                          Hyperplasia                                                                                  
Mesentery                              Accessory Spleen                                                                             
Pituitary Gland: Pars Distalis         Hyperplasia Focal                                                                            
Prostate: Epithelium                   Hyperplasia                                                                                  
Spleen                                 Fibrosis                                                                                     
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex                         Atrophy                                                                                      
Brain                                  Hydrocephalus                                                                                
Kidney                                 Infarct                                                                                      
Kidney: Renal Tubule                   Hyaline Droplet                                                                              
                                       Hyperplasia Oncocytic                                                                        
Liver                                  Angiectasis                                                                                  
                                       Clear Cell Focus                                                                             
                                       Eosinophilic Focus                                                                           
                                       Necrosis Focal                                                                               
Lymph Node, Mandibular                 Ectasia                                                                                      
                                       Pigmentation                                                                                 
Nose: Respiratory Epithelium           Hyperplasia                                                                                  
Pituitary Gland: Pars Distalis         Cyst                                                                                         
                                       Hyperplasia Focal                                                                            
Spleen                                 Fibrosis                                                                                     
                                       Hematopoietic Cell Proliferation                                                             
                                       Pigmentation                                                                                 
Thyroid Gland: C-Cell                  Hyperplasia                                                                                  
Uterus                                 Hyperplasia Cystic                                                                           
===============================================================                                                                     
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 1       
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                       EMODIN     
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Accessory Adrenal Cortical Nodule                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     13/50 (26%)  18/50 (36%)  16/50 (32%)  10/50 (20%) |6/49 (12%)   4/50 (8%)    7/50 (14%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |     13/42.15     18/41.41     16/41.38     10/43.75    |6/44.80      4/46.19      7/46.17      10/44.85     | 
|POLY-3 PERCENT (g) |     30.8%        43.5%        38.7%        22.9%       |13.4%        8.7%         15.2%        22.3%        | 
|TERMINAL (d)       |     10/30 (33%)  11/21 (52%)  9/21 (43%)   4/30 (13%)  |3/33 (9%)    3/39 (8%)    5/35 (14%)   8/34 (24%)   | 
|FIRST INCIDENCE    |     590          511          617          590         |610          600          527          602          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.070N     P=0.041 *    P=0.108      P=0.315N    |P=0.066      P=0.305N     P=0.541      P=0.219      | 
|POLY 3             |     P=0.076N     P=0.161      P=0.299      P=0.276N    |P=0.069      P=0.350N     P=0.523      P=0.204      | 
|POLY 1.5           |     P=0.088N     P=0.192      P=0.330      P=0.280N    |P=0.073      P=0.354N     P=0.517      P=0.210      | 
|POLY 6             |     P=0.064N     P=0.115      P=0.249      P=0.278N    |P=0.064      P=0.344N     P=0.532      P=0.197      | 
|LOGISTIC REGRESSION|     P=0.083N     P=0.146      P=0.278      P=0.285N    |P=0.080      P=0.360N     P=0.519      P=0.214      | 
|COCH-ARM / FISHERS |     P=0.119N     P=0.194      P=0.330      P=0.318N    |P=0.079      P=0.357N     P=0.516      P=0.220      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      0/42.44     |0/44.01      0/45.74      0/45.30      2/44.48      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         4.5%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          592          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.041 *    (e)          (e)          P=0.245      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.041 *    (e)          (e)          P=0.239      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.041 *    (e)          (e)          P=0.240      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.040 *    (e)          (e)          P=0.239      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.045 *    (e)          (e)          P=0.257      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.042 *    (e)          (e)          P=0.253      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Degeneration Fatty                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   9/50 (18%)   10/50 (20%)  8/50 (16%)  |12/49 (24%)  9/50 (18%)   14/50 (28%)  10/50 (20%)  | 
|POLY-3 RATE (b)    |     7/41.44      9/41.31      10/40.09     8/42.44     |12/44.43     9/45.90      14/45.34     10/45.01     | 
|POLY-3 PERCENT (g) |     16.9%        21.8%        25.0%        18.9%       |27.0%        19.6%        30.9%        22.2%        | 
|TERMINAL (d)       |     5/30 (17%)   2/21 (10%)   6/21 (29%)   8/30 (27%)  |9/33 (27%)   8/39 (21%)   12/35 (34%)  7/34 (21%)   | 
|FIRST INCIDENCE    |     599          506          644          729 (T)     |648          690          725          603          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.449N     P=0.230      P=0.118      P=0.504     |P=0.509N     P=0.193N     P=0.480      P=0.391N     | 
|POLY 3             |     P=0.547N     P=0.388      P=0.266      P=0.520     |P=0.458N     P=0.280N     P=0.432      P=0.390N     | 
|POLY 1.5           |     P=0.550N     P=0.406      P=0.293      P=0.524     |P=0.452N     P=0.287N     P=0.427      P=0.389N     | 
|POLY 6             |     P=0.551N     P=0.354      P=0.221      P=0.506     |P=0.465N     P=0.268N     P=0.439      P=0.389N     | 
|LOGISTIC REGRESSION|     P=0.507N     P=0.382      P=0.216      P=0.520     |P=0.499N     P=0.251N     P=0.474      P=0.406N     | 
|COCH-ARM / FISHERS |     P=0.554      P=0.393      P=0.298      P=0.500     |P=0.442N     P=0.294N     P=0.433      P=0.384N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Diffuse                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    1/50 (2%)    1/50 (2%)   |1/49 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      2/39.60      1/39.86      1/42.86     |1/44.11      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         5.1%         2.5%         2.3%        |2.3%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          690          609          607         |704          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.638      P=0.178      P=0.505      P=0.515     |P=0.486N     P=0.484N     P=0.495N     P=0.511N     | 
|POLY 3             |     P=0.633      P=0.230      P=0.495      P=0.509     |P=0.472N     P=0.493N     P=0.495N     P=0.500N     | 
|POLY 1.5           |     P=0.630      P=0.237      P=0.501      P=0.508     |P=0.471N     P=0.494N     P=0.496N     P=0.499N     | 
|POLY 6             |     P=0.633      P=0.216      P=0.484      P=0.509     |P=0.474N     P=0.490N     P=0.492N     P=0.503N     | 
|LOGISTIC REGRESSION|     P=0.610      P=0.211      P=0.487      P=0.474     |P=0.472N     P=0.495N     P=0.496N     P=0.498N     | 
|COCH-ARM / FISHERS |     P=0.614      P=0.247      P=0.500      P=0.500     |P=0.470N     P=0.495N     P=0.495N     P=0.495N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    4/50 (8%)    2/50 (4%)   |3/49 (6%)    3/50 (6%)    8/50 (16%)   7/50 (14%)   | 
|POLY-3 RATE (b)    |     3/40.99      0/39.45      4/39.88      2/42.44     |3/44.03      3/46.09      8/46.01      7/44.65      | 
|POLY-3 PERCENT (g) |     7.3%         0.0%         10.0%        4.7%        |6.8%         6.5%         17.4%        15.7%        | 
|TERMINAL (d)       |     2/30 (7%)    0/21 (0%)    3/21 (14%)   2/30 (7%)   |2/33 (6%)    2/39 (5%)    3/35 (9%)    5/34 (15%)   | 
|FIRST INCIDENCE    |     704          ---          605          729 (T)     |725          634          665          610          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.570N     P=0.184N     P=0.347      P=0.500N    |P=0.095      P=0.597N     P=0.132      P=0.168      | 
|POLY 3             |     P=0.610N     P=0.125N     P=0.485      P=0.484N    |P=0.103      P=0.641N     P=0.112      P=0.162      | 
|POLY 1.5           |     P=0.610      P=0.119N     P=0.501      P=0.484N    |P=0.106      P=0.647N     P=0.107      P=0.163      | 
|POLY 6             |     P=0.591N     P=0.138N     P=0.454      P=0.489N    |P=0.098      P=0.631N     P=0.121      P=0.162      | 
|LOGISTIC REGRESSION|     P=0.600N     P=0.153N     P=0.450      P=0.494N    |P=0.105      P=0.646N     P=0.109      P=0.157      | 
|COCH-ARM / FISHERS |     P=0.589      P=0.121N     P=0.500      P=0.500N    |P=0.113      P=0.651N     P=0.106      P=0.167      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   9/50 (18%)   7/50 (14%)   3/50 (6%)   |12/49 (24%)  7/50 (14%)   12/50 (24%)  10/50 (20%)  | 
|POLY-3 RATE (b)    |     6/41.79      9/41.88      7/41.33      3/42.44     |12/45.06     7/46.42      12/45.46     10/44.94     | 
|POLY-3 PERCENT (g) |     14.4%        21.5%        16.9%        7.1%        |26.6%        15.1%        26.4%        22.3%        | 
|TERMINAL (d)       |     4/30 (13%)   2/21 (10%)   2/21 (10%)   3/30 (10%)  |9/33 (27%)   5/39 (13%)   9/35 (26%)   8/34 (24%)   | 
|FIRST INCIDENCE    |     597          506          483          729 (T)     |544          572          702          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.079N     P=0.184      P=0.369      P=0.236N    |P=0.517      P=0.095N     P=0.533N     P=0.386N     | 
|POLY 3             |     P=0.086N     P=0.285      P=0.491      P=0.233N    |P=0.547      P=0.134N     P=0.584N     P=0.406N     | 
|POLY 1.5           |     P=0.087N     P=0.300      P=0.508      P=0.230N    |P=0.560N     P=0.138N     P=0.583N     P=0.398N     | 
|POLY 6             |     P=0.088N     P=0.258      P=0.458      P=0.242N    |P=0.527      P=0.126N     P=0.582N     P=0.417N     | 
|LOGISTIC REGRESSION|     P=0.096N     P=0.288      P=0.501      P=0.226N    |P=0.556      P=0.141N     P=0.556N     P=0.393N     | 
|COCH-ARM / FISHERS |     P=0.097N     P=0.288      P=0.500      P=0.243N    |P=0.541N     P=0.142N     P=0.570N     P=0.384N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/49 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      1/40.11      0/39.45      0/42.44     |0/44.01      2/46.62      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         2.5%         0.0%         0.0%        |0.0%         4.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          506          ---          ---         |---          600          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.583N     P=0.509      (e)          (e)         |P=0.389N     P=0.247      (e)          (e)          | 
|POLY 3             |     P=0.586N     P=0.496      (e)          (e)         |P=0.376N     P=0.250      (e)          (e)          | 
|POLY 1.5           |     P=0.583N     P=0.502      (e)          (e)         |P=0.378N     P=0.246      (e)          (e)          | 
|POLY 6             |     P=0.591N     P=0.485      (e)          (e)         |P=0.373N     P=0.257      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.654N     P=0.407      (e)          (e)         |P=0.350N     P=0.257      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.587N     P=0.500      (e)          (e)         |P=0.379N     P=0.253      (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  9/49 (18%)   7/50 (14%)   17/50 (34%) |2/47 (4%)    2/50 (4%)    2/50 (4%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     10/41.49     9/39.51      7/40.01      17/43.51    |2/42.97      2/45.74      2/45.30      3/44.02      | 
|POLY-3 PERCENT (g) |     24.1%        22.8%        17.5%        39.1%       |4.7%         4.4%         4.4%         6.8%         | 
|TERMINAL (d)       |     6/30 (20%)   4/20 (20%)   4/21 (19%)   11/30 (37%) |1/33 (3%)    2/39 (5%)    2/35 (6%)    3/34 (9%)    | 
|FIRST INCIDENCE    |     617          596          638          605         |686          730 (T)      730 (T)      730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.081      P=0.415      P=0.549N     P=0.108     |P=0.372      P=0.641N     P=0.675N     P=0.508      | 
|POLY 3             |     P=0.030 *    P=0.549N     P=0.322N     P=0.102     |P=0.393      P=0.671N     P=0.675N     P=0.511      | 
|POLY 1.5           |     P=0.028 *    P=0.517N     P=0.297N     P=0.102     |P=0.401      P=0.672N     P=0.675N     P=0.518      | 
|POLY 6             |     P=0.034 *    P=0.605      P=0.371N     P=0.099     |P=0.382      P=0.669N     P=0.674N     P=0.503      | 
|LOGISTIC REGRESSION|     P=0.040 *    P=0.602      P=0.380N     P=0.097     |P=0.372      P=0.668N     P=0.672N     P=0.503      | 
|COCH-ARM / FISHERS |     P=0.025 *    P=0.520N     P=0.298N     P=0.088     |P=0.411      P=0.668N     P=0.668N     P=0.530      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    5/50 (10%)   3/50 (6%)    11/50 (22%) |5/49 (10%)   3/50 (6%)    4/50 (8%)    6/50 (12%)   | 
|POLY-3 RATE (b)    |     3/43.19      5/40.25      3/40.41      11/44.90    |5/44.64      3/46.58      4/46.35      6/46.26      | 
|POLY-3 PERCENT (g) |     7.0%         12.4%        7.4%         24.5%       |11.2%        6.4%         8.6%         13.0%        | 
|TERMINAL (d)       |     0/30 (0%)    2/21 (10%)   0/21 (0%)    5/30 (17%)  |2/33 (6%)    2/39 (5%)    2/35 (6%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     122          610          603          590         |630          396          232          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.017 *    P=0.292      P=0.647      P=0.033 *   |P=0.283      P=0.307N     P=0.475N     P=0.498      | 
|POLY 3             |     P=0.007 **   P=0.317      P=0.632      P=0.023 *   |P=0.307      P=0.333N     P=0.477N     P=0.525      | 
|POLY 1.5           |     P=0.007 **   P=0.340      P=0.648      P=0.022 *   |P=0.307      P=0.338N     P=0.481N     P=0.521      | 
|POLY 6             |     P=0.009 **   P=0.284      P=0.605      P=0.024 *   |P=0.306      P=0.328N     P=0.473N     P=0.528      | 
|LOGISTIC REGRESSION|     P=0.003 **   P=0.253      P=0.525      P=0.009 **  |P=0.370      P=0.348N     P=0.450N     P=0.580      | 
|COCH-ARM / FISHERS |     P=0.006 **   P=0.357      P=0.661N     P=0.020 *   |P=0.305      P=0.346N     P=0.487N     P=0.514      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/49 (0%)    2/50 (4%)    4/50 (8%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      0/42.44     |0/44.01      2/45.74      4/45.70      2/44.18      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         4.4%         8.8%         4.5%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    2/39 (5%)    3/35 (9%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          730 (T)      617          689          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.359      P=0.276      P=0.072      P=0.243      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.370      P=0.246      P=0.065      P=0.238      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.376      P=0.244      P=0.064      P=0.239      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.364      P=0.249      P=0.067      P=0.237      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.373      P=0.276      P=0.065      P=0.238      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.385      P=0.253      P=0.061      P=0.253      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone: Cranium                                                                                                                    | 
|     Osteopetrosis                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |7/49 (14%)   5/50 (10%)   6/50 (12%)   8/50 (16%)   | 
|POLY-3 RATE (b)    |     1/41.51      0/39.45      0/39.45      0/42.44     |7/45.09      5/45.74      6/46.98      8/44.17      | 
|POLY-3 PERCENT (g) |     2.4%         0.0%         0.0%         0.0%        |15.5%        10.9%        12.8%        18.1%        | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |4/33 (12%)   5/39 (13%)   2/35 (6%)    7/34 (21%)   | 
|FIRST INCIDENCE    |     528          ---          ---          ---         |610          730 (T)      539          690          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.465N     P=0.500N     P=0.496N     P=0.491N    |P=0.297      P=0.296N     P=0.463N     P=0.510      | 
|POLY 3             |     P=0.464N     P=0.510N     P=0.510N     P=0.496N    |P=0.304      P=0.369N     P=0.468N     P=0.483      | 
|POLY 1.5           |     P=0.471N     P=0.502N     P=0.502N     P=0.495N    |P=0.318      P=0.368N     P=0.479N     P=0.497      | 
|POLY 6             |     P=0.451N     P=0.525N     P=0.524N     P=0.499N    |P=0.287      P=0.369N     P=0.455N     P=0.463      | 
|LOGISTIC REGRESSION|     P=0.524N     P=0.573N     P=0.558N     P=0.569N    |P=0.337      P=0.362N     P=0.461N     P=0.504      | 
|COCH-ARM / FISHERS |     P=0.472N     P=0.500N     P=0.500N     P=0.500N    |P=0.335      P=0.365N     P=0.484N     P=0.517      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone: Femur                                                                                                                      | 
|     Osteopetrosis                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |6/49 (12%)   8/50 (16%)   7/50 (14%)   7/50 (14%)   | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      0/42.44     |6/44.67      8/46.02      7/45.81      7/44.33      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |13.4%        17.4%        15.3%        15.8%        | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |4/33 (12%)   7/39 (18%)   5/35 (14%)   5/34 (15%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |630          656          617          689          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.506      P=0.497      P=0.543      P=0.510      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.527      P=0.409      P=0.519      P=0.494      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.539      P=0.405      P=0.514      P=0.502      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.511      P=0.417      P=0.528      P=0.484      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.532      P=0.413      P=0.516      P=0.501      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.557      P=0.403      P=0.516      P=0.516      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Compression                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    2/50 (4%)    5/50 (10%)   5/50 (10%)  |8/49 (16%)   7/50 (14%)   10/50 (20%)  7/50 (14%)   | 
|POLY-3 RATE (b)    |     4/41.82      2/40.18      5/40.70      5/42.74     |8/45.84      7/46.96      10/46.31     7/45.26      | 
|POLY-3 PERCENT (g) |     9.6%         5.0%         12.3%        11.7%       |17.5%        14.9%        21.6%        15.5%        | 
|TERMINAL (d)       |     1/30 (3%)    0/21 (0%)    1/21 (5%)    4/30 (13%)  |3/33 (9%)    4/39 (10%)   6/35 (17%)   2/34 (6%)    | 
|FIRST INCIDENCE    |     604          561          483          645         |497          572          648          610          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.378      P=0.404N     P=0.406      P=0.510     |P=0.515N     P=0.421N     P=0.458      P=0.504N     | 
|POLY 3             |     P=0.329      P=0.355N     P=0.483      P=0.514     |P=0.502N     P=0.480N     P=0.406      P=0.511N     | 
|POLY 1.5           |     P=0.320      P=0.338N     P=0.502      P=0.517     |P=0.488N     P=0.483N     P=0.405      P=0.501N     | 
|POLY 6             |     P=0.339      P=0.387N     P=0.446      P=0.502     |P=0.518N     P=0.472N     P=0.413      P=0.520N     | 
|LOGISTIC REGRESSION|     P=0.304      P=0.341N     P=0.499      P=0.517     |P=0.439N     P=0.501N     P=0.424      P=0.444N     | 
|COCH-ARM / FISHERS |     P=0.301      P=0.339N     P=0.500      P=0.500     |P=0.466N     P=0.483N     P=0.416      P=0.483N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Hydrocephalus                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |3/49 (6%)    0/50 (0%)    3/50 (6%)    7/50 (14%)   | 
|POLY-3 RATE (b)    |     1/41.29      1/39.45      2/40.32      1/42.44     |3/44.77      0/45.74      3/45.76      7/44.86      | 
|POLY-3 PERCENT (g) |     2.4%         2.5%         5.0%         2.4%        |6.7%         0.0%         6.6%         15.6%        | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    1/21 (5%)    1/30 (3%)   |1/33 (3%)    0/39 (0%)    1/35 (3%)    3/34 (9%)    | 
|FIRST INCIDENCE    |     617          729 (T)      368          729 (T)     |596          ---          665          610          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.597N     P=0.718      P=0.466      P=0.755N    |P=0.013 *    P=0.110N     P=0.628N     P=0.171      | 
|POLY 3             |     P=0.621N     P=0.751      P=0.492      P=0.755N    |P=0.012 *    P=0.115N     P=0.652N     P=0.157      | 
|POLY 1.5           |     P=0.626N     P=0.760      P=0.502      P=0.754N    |P=0.013 *    P=0.115N     P=0.655N     P=0.161      | 
|POLY 6             |     P=0.616N     P=0.734      P=0.470      P=0.758N    |P=0.012 *    P=0.114N     P=0.648N     P=0.154      | 
|LOGISTIC REGRESSION|     P=0.645      P=0.763N     P=0.448      P=0.762N    |P=0.016 *    P=0.113N     P=0.641N     P=0.174      | 
|COCH-ARM / FISHERS |     P=0.639N     P=0.753N     P=0.500      P=0.753N    |P=0.015 *    P=0.117N     P=0.651N     P=0.167      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 8       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/49 (2%)    0/50 (0%)    4/49 (8%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |                                                        |1/44.32      0/45.74      4/44.41      1/43.02      | 
|POLY-3 PERCENT (g) |                                                        |2.3%         0.0%         9.0%         2.3%         | 
|TERMINAL (d)       |                                                        |0/33 (0%)    0/39 (0%)    3/34 (9%)    1/33 (3%)    | 
|FIRST INCIDENCE    |                                                        |645          ---          702          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.547      P=0.495N     P=0.196      P=0.758      | 
|POLY 3             |                                                        |P=0.548      P=0.494N     P=0.179      P=0.754      | 
|POLY 1.5           |                                                        |P=0.557      P=0.495N     P=0.178      P=0.757      | 
|POLY 6             |                                                        |P=0.534      P=0.492N     P=0.181      P=0.751      | 
|LOGISTIC REGRESSION|                                                        |P=0.560      P=0.489N     P=0.179      P=0.760N     | 
|COCH-ARM / FISHERS |                                                        |P=0.570      P=0.495N     P=0.181      P=0.753N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |3/49 (6%)    2/50 (4%)    6/49 (12%)   3/49 (6%)    | 
|POLY-3 RATE (b)    |                                                        |3/44.01      2/45.74      6/44.30      3/43.17      | 
|POLY-3 PERCENT (g) |                                                        |6.8%         4.4%         13.5%        7.0%         | 
|TERMINAL (d)       |                                                        |3/33 (9%)    2/39 (5%)    6/34 (18%)   2/33 (6%)    | 
|FIRST INCIDENCE    |                                                        |730 (T)      730 (T)      730 (T)      690          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.505      P=0.424N     P=0.254      P=0.660      | 
|POLY 3             |                                                        |P=0.522      P=0.482N     P=0.244      P=0.654      | 
|POLY 1.5           |                                                        |P=0.531      P=0.487N     P=0.241      P=0.656      | 
|POLY 6             |                                                        |P=0.511      P=0.475N     P=0.250      P=0.651      | 
|LOGISTIC REGRESSION|                                                        |P=0.497      P=0.424N     P=0.254      P=0.645      | 
|COCH-ARM / FISHERS |                                                        |P=0.544      P=0.490N     P=0.243      P=0.661N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 9       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |5/49 (10%)   5/50 (10%)   6/49 (12%)   5/49 (10%)   | 
|POLY-3 RATE (b)    |                                                        |5/44.49      5/45.74      6/44.77      5/43.02      | 
|POLY-3 PERCENT (g) |                                                        |11.2%        10.9%        13.4%        11.6%        | 
|TERMINAL (d)       |                                                        |3/33 (9%)    5/39 (13%)   5/34 (15%)   5/33 (15%)   | 
|FIRST INCIDENCE    |                                                        |645          730 (T)      592          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.537      P=0.537N     P=0.522      P=0.626      | 
|POLY 3             |                                                        |P=0.549      P=0.613N     P=0.504      P=0.609      | 
|POLY 1.5           |                                                        |P=0.562      P=0.615N     P=0.499      P=0.618      | 
|POLY 6             |                                                        |P=0.530      P=0.609N     P=0.511      P=0.597      | 
|LOGISTIC REGRESSION|                                                        |P=0.547      P=0.601N     P=0.500      P=0.611      | 
|COCH-ARM / FISHERS |                                                        |P=0.578N     P=0.617N     P=0.500      P=0.630N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis                                                                                                                       | 
|     Atypia Cellular                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     29/50 (58%)  26/50 (52%)  25/50 (50%)  29/50 (58%) |                                                    | 
|POLY-3 RATE (b)    |     29/44.66     26/42.58     25/43.18     29/46.03    |                                                    | 
|POLY-3 PERCENT (g) |     64.9%        61.1%        57.9%        63.0%       |                                                    | 
|TERMINAL (d)       |     19/30 (63%)  15/21 (71%)  12/21 (57%)  19/30 (63%) |                                                    | 
|FIRST INCIDENCE    |     528          555          575          539         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.385N     P=0.290      P=0.403      P=0.539N    |                                                    | 
|POLY 3             |     P=0.552N     P=0.437N     P=0.319N     P=0.511N    |                                                    | 
|POLY 1.5           |     P=0.512      P=0.350N     P=0.266N     P=0.508N    |                                                    | 
|POLY 6             |     P=0.508N     P=0.594N     P=0.415N     P=0.536N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.532      P=0.367N     P=0.280N     P=0.507N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.423      P=0.344N     P=0.274N     P=0.580N    |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 10      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye                                                                                                                              | 
|     Cataract                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/3 (67%)    1/1 (100%)   1/1 (100%)   0/0 (0%)    |4/5 (80%)    2/2 (100%)   3/4 (75%)    1/2 (50%)    | 
|POLY-3 RATE (b)    |     2/3.00       1/1.00       1/1.00       0/0.00      |4/4.54       2/2.00       3/4.00       1/1.58       | 
|POLY-3 PERCENT (g) |     66.7%        100.0%       100.0%       0.0%        |88.0%        100.0%       75.0%        63.2%        | 
|TERMINAL (d)       |     1/2 (50%)    0/0 (0%)     1/1 (100%)   0/0 (0%)    |3/3 (100%)   2/2 (100%)   2/3 (67%)    0/0 (0%)     | 
|FIRST INCIDENCE    |     679          631          729 (T)      ---         |646          730 (T)      725          603          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.373N     P=0.700      P=0.736N     P=0.507N    |P=0.639      P=0.484N     P=0.487N     P=0.751      | 
|POLY 3             |     (e)          P=0.691      P=0.691      (e)         |P=0.442N     P=0.885      P=0.649N     P=0.703N     | 
|POLY 1.5           |     (e)          P=0.691      P=0.691      (e)         |P=0.412N     P=0.778      P=0.680N     P=0.615N     | 
|POLY 6             |     (e)          P=0.691      P=0.691      (e)         |P=0.487N     P=0.995      P=0.593N     P=0.903N     | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.736N     (e)         |P=0.721N     P=0.484N     P=0.484N     P=0.803      | 
|COCH-ARM / FISHERS |     P=0.983      P=0.750      P=0.750      P=1.000     |P=0.365N     P=0.714      P=0.722N     P=0.524N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye                                                                                                                              | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/3 (0%)     0/1 (0%)     0/1 (0%)     0/0 (0%)    |0/5 (0%)     0/2 (0%)     2/4 (50%)    0/2 (0%)     | 
|POLY-3 RATE (b)    |     0/2.81       0/0.65       0/1.00       0/0.00      |0/4.24       0/2.00       2/4.00       0/1.15       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         50.0%        0.0%         | 
|TERMINAL (d)       |     0/2 (0%)     0/0 (0%)     0/1 (0%)     0/0 (0%)    |0/3 (0%)     0/2 (0%)     1/3 (33%)    0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          725          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.668      (e)          P=0.249      (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.403      (e)          P=0.176      (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.566      (e)          P=0.158      (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.201      (e)          P=0.207      (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.534      (e)          P=0.254      (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.688      (e)          P=0.167      (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 11      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Retina                                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/3 (67%)    1/1 (100%)   1/1 (100%)   0/0 (0%)    |4/5 (80%)    2/2 (100%)   3/4 (75%)    1/2 (50%)    | 
|POLY-3 RATE (b)    |     2/3.00       1/1.00       1/1.00       0/0.00      |4/4.54       2/2.00       3/4.00       1/1.58       | 
|POLY-3 PERCENT (g) |     66.7%        100.0%       100.0%       0.0%        |88.0%        100.0%       75.0%        63.2%        | 
|TERMINAL (d)       |     1/2 (50%)    0/0 (0%)     1/1 (100%)   0/0 (0%)    |3/3 (100%)   2/2 (100%)   2/3 (67%)    0/0 (0%)     | 
|FIRST INCIDENCE    |     679          631          729 (T)      ---         |646          730 (T)      725          603          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.373N     P=0.700      P=0.736N     P=0.507N    |P=0.639      P=0.484N     P=0.487N     P=0.751      | 
|POLY 3             |     (e)          P=0.691      P=0.691      (e)         |P=0.442N     P=0.885      P=0.649N     P=0.703N     | 
|POLY 1.5           |     (e)          P=0.691      P=0.691      (e)         |P=0.412N     P=0.778      P=0.680N     P=0.615N     | 
|POLY 6             |     (e)          P=0.691      P=0.691      (e)         |P=0.487N     P=0.995      P=0.593N     P=0.903N     | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.736N     (e)         |P=0.721N     P=0.484N     P=0.484N     P=0.803      | 
|COCH-ARM / FISHERS |     P=0.983      P=0.750      P=0.750      P=1.000     |P=0.365N     P=0.714      P=0.722N     P=0.524N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     34/50 (68%)  31/50 (62%)  35/50 (70%)  36/50 (72%) |22/49 (45%)  16/50 (32%)  17/50 (34%)  16/50 (32%)  | 
|POLY-3 RATE (b)    |     34/44.50     31/45.10     35/44.96     36/46.91    |22/45.58     16/47.00     17/46.09     16/44.61     | 
|POLY-3 PERCENT (g) |     76.4%        68.7%        77.9%        76.7%       |48.3%        34.0%        36.9%        35.9%        | 
|TERMINAL (d)       |     25/30 (83%)  14/21 (67%)  17/21 (81%)  24/30 (80%) |17/33 (52%)  13/39 (33%)  12/35 (34%)  14/34 (41%)  | 
|FIRST INCIDENCE    |     472          462          510          492         |610          572          665          603          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.463N     P=0.242      P=0.073      P=0.459     |P=0.301N     P=0.066N     P=0.160N     P=0.137N     | 
|POLY 3             |     P=0.386      P=0.273N     P=0.537      P=0.586     |P=0.278N     P=0.116N     P=0.184N     P=0.160N     | 
|POLY 1.5           |     P=0.339      P=0.255N     P=0.564      P=0.551     |P=0.253N     P=0.124N     P=0.188N     P=0.148N     | 
|POLY 6             |     P=0.444      P=0.322N     P=0.489      P=0.602N    |P=0.316N     P=0.107N     P=0.177N     P=0.181N     | 
|LOGISTIC REGRESSION|     P=0.356      P=0.321N     P=0.496      P=0.526     |P=0.258N     P=0.124N     P=0.169N     P=0.148N     | 
|COCH-ARM / FISHERS |     P=0.258      P=0.338N     P=0.500      P=0.414     |P=0.224N     P=0.133N     P=0.183N     P=0.133N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 12      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Thrombosis                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    4/50 (8%)    2/50 (4%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      2/39.74      4/40.31      2/42.47     |0/44.01      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         5.0%         9.9%         4.7%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    1/21 (5%)    1/30 (3%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          679          603          720         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.436      P=0.195      P=0.047 *    P=0.240     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.408      P=0.230      P=0.058      P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.402      P=0.238      P=0.061      P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.412      P=0.218      P=0.052      P=0.244     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.398      P=0.230      P=0.063      P=0.239     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.379      P=0.247      P=0.059      P=0.247     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Cecum                                                                                                           | 
|     Edema                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/49 (4%)    2/50 (4%)    3/50 (6%)    2/49 (4%)   |0/49 (0%)    0/50 (0%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/40.03      2/40.01      3/39.80      2/41.62     |0/44.01      0/45.74      1/44.62      0/44.02      | 
|POLY-3 PERCENT (g) |     5.0%         5.0%         7.5%         4.8%        |0.0%         0.0%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/29 (0%)    0/21 (0%)    0/21 (0%)    0/29 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     700          632          689          700         |---          ---          702          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.547N     P=0.618      P=0.386      P=0.687N    |P=0.800N     (e)          P=0.511      (e)          | 
|POLY 3             |     P=0.586N     P=0.695      P=0.497      P=0.680N    |P=0.787N     (e)          P=0.503      (e)          | 
|POLY 1.5           |     P=0.593N     P=0.684N     P=0.510      P=0.681N    |P=0.785N     (e)          P=0.500      (e)          | 
|POLY 6             |     P=0.577N     P=0.675      P=0.473      P=0.683N    |P=0.789N     (e)          P=0.507      (e)          | 
|LOGISTIC REGRESSION|     P=0.587N     P=0.691N     P=0.477      P=0.684N    |P=0.784N     (e)          P=0.500      (e)          | 
|COCH-ARM / FISHERS |     P=0.610N     P=0.684N     P=0.510      P=0.691N    |P=0.783N     (e)          P=0.500      (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 13      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Cecum                                                                                                           | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    2/49 (4%)   |0/49 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/39.89      0/39.45      0/39.45      2/41.44     |0/44.01      0/45.74      0/44.51      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.8%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/29 (0%)    0/21 (0%)    0/21 (0%)    2/29 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.060      (e)          (e)          P=0.238     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.043 *    (e)          (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.042 *    (e)          (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.044 *    (e)          (e)          P=0.243     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.238     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.041 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Large, Cecum: Epithelium                                                                                               | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    2/49 (4%)   |0/49 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/39.89      0/39.45      0/39.45      2/41.44     |0/44.01      0/45.74      0/44.51      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.8%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/29 (0%)    0/21 (0%)    0/21 (0%)    2/29 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.060      (e)          (e)          P=0.238     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.043 *    (e)          (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.042 *    (e)          (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.044 *    (e)          (e)          P=0.243     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.238     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.041 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 14      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   0/50 (0%)    1/49 (2%)    2/50 (4%)   |0/49 (0%)    1/50 (2%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     5/42.19      0/39.45      1/38.88      2/42.44     |0/44.01      1/45.74      0/44.51      0/44.02      | 
|POLY-3 PERCENT (g) |     11.9%        0.0%         2.6%         4.7%        |0.0%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     3/30 (10%)   0/21 (0%)    0/20 (0%)    2/30 (7%)   |0/33 (0%)    1/39 (3%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     406          ---          602          729 (T)     |---          730 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.370N     P=0.057N     P=0.155N     P=0.214N    |P=0.595N     P=0.533      (e)          (e)          | 
|POLY 3             |     P=0.387N     P=0.036N*    P=0.120N     P=0.213N    |P=0.584N     P=0.508      (e)          (e)          | 
|POLY 1.5           |     P=0.404N     P=0.032N*    P=0.110N     P=0.209N    |P=0.584N     P=0.506      (e)          (e)          | 
|POLY 6             |     P=0.363N     P=0.044N*    P=0.138N     P=0.220N    |P=0.582N     P=0.511      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.427N     P=0.035N*    P=0.112N     P=0.220N    |(e)          P=0.533      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.418N     P=0.028N*    P=0.107N     P=0.218N    |P=0.585N     P=0.505      (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |0/49 (0%)    0/50 (0%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      1/39.45      2/39.46      1/42.44     |0/44.01      0/45.74      1/44.51      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         2.5%         5.1%         2.4%        |0.0%         0.0%         2.3%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    1/21 (5%)    1/30 (3%)   |0/33 (0%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      725          729 (T)     |---          ---          730 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.545      P=0.429      P=0.167      P=0.500     |P=0.792N     (e)          P=0.512      (e)          | 
|POLY 3             |     P=0.524      P=0.493      P=0.229      P=0.507     |P=0.787N     (e)          P=0.502      (e)          | 
|POLY 1.5           |     P=0.519      P=0.500      P=0.236      P=0.507     |P=0.785N     (e)          P=0.500      (e)          | 
|POLY 6             |     P=0.526      P=0.480      P=0.215      P=0.506     |P=0.789N     (e)          P=0.506      (e)          | 
|LOGISTIC REGRESSION|     P=0.543      P=0.429      P=0.175      P=0.500     |(e)          (e)          P=0.512      (e)          | 
|COCH-ARM / FISHERS |     P=0.501      P=0.500      P=0.247      P=0.500     |P=0.783N     (e)          P=0.500      (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 15      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Hydronephrosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/49 (0%)    0/50 (0%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      2/42.83     |0/44.01      0/45.74      1/44.75      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.7%        |0.0%         0.0%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    1/30 (3%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          617         |---          ---          665          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.055      (e)          (e)          P=0.245     |P=0.792N     (e)          P=0.524      (e)          | 
|POLY 3             |     P=0.044 *    (e)          (e)          P=0.247     |P=0.787N     (e)          P=0.503      (e)          | 
|POLY 1.5           |     P=0.043 *    (e)          (e)          P=0.246     |P=0.785N     (e)          P=0.501      (e)          | 
|POLY 6             |     P=0.046 *    (e)          (e)          P=0.247     |P=0.789N     (e)          P=0.508      (e)          | 
|LOGISTIC REGRESSION|     P=0.042 *    (e)          (e)          P=0.238     |P=0.777N     (e)          P=0.511      (e)          | 
|COCH-ARM / FISHERS |     P=0.042 *    (e)          (e)          P=0.247     |P=0.783N     (e)          P=0.500      (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Infarct                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    3/50 (6%)   |0/49 (0%)    0/50 (0%)    2/49 (4%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      3/42.44     |0/44.01      0/45.74      2/45.47      3/44.70      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         7.1%        |0.0%         0.0%         4.4%         6.7%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    3/30 (10%)  |0/33 (0%)    0/39 (0%)    1/35 (3%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |---          ---          232          592          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.017 *    (e)          (e)          P=0.120     |P=0.036 *    (e)          P=0.246      P=0.126      | 
|POLY 3             |     P=0.009 **   (e)          (e)          P=0.125     |P=0.037 *    (e)          P=0.244      P=0.121      | 
|POLY 1.5           |     P=0.009 **   (e)          (e)          P=0.125     |P=0.037 *    (e)          P=0.241      P=0.122      | 
|POLY 6             |     P=0.009 **   (e)          (e)          P=0.123     |P=0.036 *    (e)          P=0.249      P=0.121      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.120     |P=0.045 *    (e)          P=0.371      P=0.133      | 
|COCH-ARM / FISHERS |     P=0.009 **   (e)          (e)          P=0.121     |P=0.039 *    (e)          P=0.247      P=0.125      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 16      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     13/50 (26%)  11/50 (22%)  13/50 (26%)  25/50 (50%) |0/49 (0%)    1/50 (2%)    1/49 (2%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     13/41.29     11/39.50     13/40.86     25/43.92    |0/44.01      1/45.74      1/44.58      3/44.02      | 
|POLY-3 PERCENT (g) |     31.5%        27.9%        31.8%        56.9%       |0.0%         2.2%         2.2%         6.8%         | 
|TERMINAL (d)       |     12/30 (40%)  10/21 (48%)  9/21 (43%)   21/30 (70%) |0/33 (0%)    1/39 (3%)    0/35 (0%)    3/34 (9%)    | 
|FIRST INCIDENCE    |     617          716          575          602         |---          730 (T)      711          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.004 **   P=0.391      P=0.248      P=0.008 **  |P=0.057      P=0.533      P=0.516      P=0.126      | 
|POLY 3             |     P<0.001 **   P=0.454N     P=0.582      P=0.012 *   |P=0.062      P=0.508      P=0.503      P=0.118      | 
|POLY 1.5           |     P<0.001 **   P=0.410N     P=0.580N     P=0.013 *   |P=0.063      P=0.506      P=0.500      P=0.120      | 
|POLY 6             |     P<0.001 **   P=0.539N     P=0.533      P=0.012 *   |P=0.060      P=0.511      P=0.506      P=0.117      | 
|LOGISTIC REGRESSION|     P=0.002 **   P=0.532      P=0.481      P=0.011 *   |P=0.054      P=0.533      P=0.502      P=0.126      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.408N     P=0.590N     P=0.011 *   |P=0.066      P=0.505      P=0.500      P=0.125      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     48/50 (96%)  50/50 (100%) 50/50 (100%) 50/50 (100%)|46/49 (94%)  43/50 (86%)  45/49 (92%)  49/50 (98%)  | 
|POLY-3 RATE (b)    |     48/48.57     50/50.00     50/50.00     50/50.00    |46/48.69     43/49.04     45/47.82     49/49.53     | 
|POLY-3 PERCENT (g) |     98.8%        100.0%       100.0%       100.0%      |94.5%        87.7%        94.1%        98.9%        | 
|TERMINAL (d)       |     30/30 (100%) 21/21 (100%) 21/21 (100%) 30/30 (100%)|31/33 (94%)  35/39 (90%)  33/35 (94%)  34/34 (100%) | 
|FIRST INCIDENCE    |     216          462          368          266         |497          396          527          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.252N     P=0.037 *    P=0.040 *    P=0.482     |P=0.115      P=0.065N     P=0.325N     P=0.413      | 
|POLY 3             |     P=0.723      P=0.768      P=0.768      P=0.768     |P=0.061      P=0.195N     P=0.644N     P=0.235      | 
|POLY 1.5           |     P=0.555      P=0.587      P=0.587      P=0.587     |P=0.068      P=0.180N     P=0.622N     P=0.261      | 
|POLY 6             |     P=0.960      P=0.980      P=0.980      P=0.980     |P=0.058      P=0.224N     P=0.649N     P=0.209      | 
|LOGISTIC REGRESSION|     P=0.375      P=0.498      P=0.439      P=0.424     |P=0.068      P=0.164N     P=0.550N     P=0.281      | 
|COCH-ARM / FISHERS |     P=0.239      P=0.247      P=0.247      P=0.247     |P=0.084      P=0.167N     P=0.500N     P=0.301      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 17      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyaline Droplet                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    45/50 (90%)  43/50 (86%)  43/50 (86%) |22/49 (45%)  49/50 (98%)  49/49 (100%) 50/50 (100%) | 
|POLY-3 RATE (b)    |     3/40.97      45/48.49     43/47.80     43/48.49    |22/46.01     49/49.73     49/49.00     50/50.00     | 
|POLY-3 PERCENT (g) |     7.3%         92.8%        90.0%        88.7%       |47.8%        98.5%        100.0%       100.0%       | 
|TERMINAL (d)       |     2/30 (7%)    19/21 (91%)  21/21 (100%) 26/30 (87%) |16/33 (49%)  39/39 (100%) 35/35 (100%) 34/34 (100%) | 
|FIRST INCIDENCE    |     711          462          368          266         |497          396          232          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.002 **   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 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyperplasia Oncocytic                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/49 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      0/42.44     |0/44.01      0/45.74      0/44.51      2/44.43      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         4.5%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          610          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.038 *    (e)          (e)          P=0.238      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.041 *    (e)          (e)          P=0.239      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.041 *    (e)          (e)          P=0.240      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.040 *    (e)          (e)          P=0.239      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.045 *    (e)          (e)          P=0.252      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.043 *    (e)          (e)          P=0.253      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 18      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     35/50 (70%)  47/50 (94%)  49/50 (98%)  50/50 (100%)|45/49 (92%)  49/50 (98%)  49/49 (100%) 50/50 (100%) | 
|POLY-3 RATE (b)    |     35/46.22     47/49.26     49/50.00     50/50.00    |45/48.36     49/49.73     49/49.00     50/50.00     | 
|POLY-3 PERCENT (g) |     75.7%        95.4%        98.0%        100.0%      |93.1%        98.5%        100.0%       100.0%       | 
|TERMINAL (d)       |     21/30 (70%)  20/21 (95%)  20/21 (95%)  30/30 (100%)|31/33 (94%)  39/39 (100%) 35/35 (100%) 34/34 (100%) | 
|FIRST INCIDENCE    |     216          462          368          266         |497          396          232          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.261      P=0.002 **   P<0.001 **   P=0.019 *   |P=0.153      P=0.392N     P=0.470      P=0.283      | 
|POLY 3             |     P<0.001 **   P=0.004 **   P<0.001 **   P<0.001 **  |P=0.071      P=0.183      P=0.083      P=0.080      | 
|POLY 1.5           |     P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 **  |P=0.061      P=0.180      P=0.071      P=0.068      | 
|POLY 6             |     P<0.001 **   P=0.004 **   P<0.001 **   P<0.001 **  |P=0.089      P=0.178      P=0.102      P=0.099      | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |P=0.052      P=0.174      P=0.059      P=0.055      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |P=0.055      P=0.175      P=0.059      P=0.056      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Transitional Epithelium                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    4/50 (8%)    3/50 (6%)    2/50 (4%)   |2/49 (4%)    0/50 (0%)    1/49 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     4/40.89      4/39.69      3/39.56      2/42.78     |2/44.37      0/45.74      1/44.51      1/44.02      | 
|POLY-3 PERCENT (g) |     9.8%         10.1%        7.6%         4.7%        |4.5%         0.0%         2.3%         2.3%         | 
|TERMINAL (d)       |     4/30 (13%)   3/21 (14%)   2/21 (10%)   1/30 (3%)   |1/33 (3%)    0/39 (0%)    1/35 (3%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      665          700          634         |630          ---          730 (T)      730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.199N     P=0.456      P=0.630      P=0.333N    |P=0.630N     P=0.221N     P=0.484N     P=0.501N     | 
|POLY 3             |     P=0.222N     P=0.628      P=0.518N     P=0.316N    |P=0.618N     P=0.230N     P=0.499N     P=0.503N     | 
|POLY 1.5           |     P=0.232N     P=0.642N     P=0.501N     P=0.319N    |P=0.614N     P=0.232N     P=0.501N     P=0.499N     | 
|POLY 6             |     P=0.210N     P=0.595      P=0.550N     P=0.316N    |P=0.624N     P=0.228N     P=0.495N     P=0.508N     | 
|LOGISTIC REGRESSION|     P=0.213N     P=0.533      P=0.634N     P=0.322N    |P=0.613N     P=0.234N     P=0.500N     P=0.493N     | 
|COCH-ARM / FISHERS |     P=0.249N     P=0.643N     P=0.500N     P=0.339N    |P=0.610N     P=0.242N     P=0.500N     P=0.492N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 19      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   5/50 (10%)   0/50 (0%)    11/50 (22%) |0/49 (0%)    0/50 (0%)    2/50 (4%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     5/41.29      5/39.64      0/39.45      11/42.78    |0/44.01      0/45.74      2/45.30      4/44.43      | 
|POLY-3 PERCENT (g) |     12.1%        12.6%        0.0%         25.7%       |0.0%         0.0%         4.4%         9.0%         | 
|TERMINAL (d)       |     4/30 (13%)   4/21 (19%)   0/21 (0%)    10/30 (33%) |0/33 (0%)    0/39 (0%)    2/35 (6%)    3/34 (9%)    | 
|FIRST INCIDENCE    |     617          679          ---          634         |---          ---          730 (T)      610          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.034 *    P=0.430      P=0.063N     P=0.084     |P=0.009 **   (e)          P=0.251      P=0.066      | 
|POLY 3             |     P=0.015 *    P=0.606      P=0.034N*    P=0.092     |P=0.009 **   (e)          P=0.244      P=0.061      | 
|POLY 1.5           |     P=0.014 *    P=0.629      P=0.031N*    P=0.094     |P=0.010 *    (e)          P=0.242      P=0.062      | 
|POLY 6             |     P=0.016 *    P=0.562      P=0.040N*    P=0.087     |P=0.009 **   (e)          P=0.247      P=0.061      | 
|LOGISTIC REGRESSION|     P=0.025 *    P=0.550      P=0.039N*    P=0.091     |P=0.010 *    (e)          P=0.251      P=0.065      | 
|COCH-ARM / FISHERS |     P=0.015 *    P=0.630N     P=0.028N*    P=0.086     |P=0.011 *    (e)          P=0.253      P=0.061      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     20/50 (40%)  18/50 (36%)  18/50 (36%)  23/50 (46%) |39/49 (80%)  44/50 (88%)  41/50 (82%)  45/50 (90%)  | 
|POLY-3 RATE (b)    |     20/41.39     18/40.07     18/39.60     23/42.95    |39/46.33     44/47.60     41/47.15     45/47.78     | 
|POLY-3 PERCENT (g) |     48.3%        44.9%        45.5%        53.6%       |84.2%        92.4%        87.0%        94.2%        | 
|TERMINAL (d)       |     18/30 (60%)  15/21 (71%)  16/21 (76%)  21/30 (70%) |30/33 (91%)  38/39 (97%)  32/35 (91%)  34/34 (100%) | 
|FIRST INCIDENCE    |     617          610          700          617         |527          572          592          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.453      P=0.215      P=0.191      P=0.323     |P=0.093      P=0.488N     P=0.554N     P=0.192      | 
|POLY 3             |     P=0.268      P=0.465N     P=0.485N     P=0.393     |P=0.126      P=0.150      P=0.462      P=0.081      | 
|POLY 1.5           |     P=0.249      P=0.411N     P=0.425N     P=0.395     |P=0.137      P=0.163      P=0.447      P=0.092      | 
|POLY 6             |     P=0.293      P=0.575N     P=0.587      P=0.374     |P=0.118      P=0.144      P=0.505      P=0.072      | 
|LOGISTIC REGRESSION|     P=0.357      P=0.451      P=0.372      P=0.353     |P=0.072      P=0.216      P=0.538      P=0.064      | 
|COCH-ARM / FISHERS |     P=0.212      P=0.418N     P=0.418N     P=0.343     |P=0.167      P=0.194      P=0.480      P=0.122      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 20      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Clear Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   7/50 (14%)   9/50 (18%)   13/50 (26%) |2/49 (4%)    10/50 (20%)  4/50 (8%)    11/50 (22%)  | 
|POLY-3 RATE (b)    |     7/40.89      7/39.45      9/39.45      13/42.98    |2/44.01      10/45.74     4/45.30      11/44.63     | 
|POLY-3 PERCENT (g) |     17.1%        17.7%        22.8%        30.3%       |4.5%         21.9%        8.8%         24.7%        | 
|TERMINAL (d)       |     7/30 (23%)   7/21 (33%)   9/21 (43%)   11/30 (37%) |2/33 (6%)    10/39 (26%)  4/35 (11%)   8/34 (24%)   | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      590         |730 (T)      730 (T)      730 (T)      618          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.106      P=0.321      P=0.123      P=0.099     |P=0.027 *    P=0.029 *    P=0.363      P=0.010 *    | 
|POLY 3             |     P=0.067      P=0.587      P=0.359      P=0.121     |P=0.033 *    P=0.016 *    P=0.350      P=0.007 **   | 
|POLY 1.5           |     P=0.061      P=0.614      P=0.389      P=0.121     |P=0.034 *    P=0.015 *    P=0.347      P=0.007 **   | 
|POLY 6             |     P=0.075      P=0.534      P=0.305      P=0.119     |P=0.032 *    P=0.017 *    P=0.357      P=0.007 **   | 
|LOGISTIC REGRESSION|     P=0.088      P=0.321      P=0.123      P=0.106     |P=0.025 *    P=0.029 *    P=0.363      P=0.008 **   | 
|COCH-ARM / FISHERS |     P=0.051      P=0.613N     P=0.393      P=0.105     |P=0.038 *    P=0.015 *    P=0.349      P=0.008 **   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Degeneration Cystic                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   10/50 (20%)  11/50 (22%)  10/50 (20%) |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     7/41.06      10/40.30     11/40.92     10/42.69    |0/44.01      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     17.1%        24.8%        26.9%        23.4%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     6/30 (20%)   5/21 (24%)   6/21 (29%)   7/30 (23%)  |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     686          631          575          702         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.519      P=0.116      P=0.080      P=0.303     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.420      P=0.277      P=0.207      P=0.325     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.406      P=0.301      P=0.223      P=0.324     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.433      P=0.237      P=0.179      P=0.319     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.450      P=0.196      P=0.170      P=0.304     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.369      P=0.298      P=0.218      P=0.298     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 21      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Eosinophilic Focus                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   8/50 (16%)   6/50 (12%)   10/50 (20%) |18/49 (37%)  10/50 (20%)  18/50 (36%)  27/50 (54%)  | 
|POLY-3 RATE (b)    |     6/40.89      8/39.70      6/39.45      10/42.83    |18/46.11     10/46.17     18/45.66     27/45.13     | 
|POLY-3 PERCENT (g) |     14.7%        20.2%        15.2%        23.4%       |39.0%        21.7%        39.4%        59.8%        | 
|TERMINAL (d)       |     6/30 (20%)   6/21 (29%)   6/21 (29%)   9/30 (30%)  |12/33 (36%)  8/39 (21%)   16/35 (46%)  22/34 (65%)  | 
|FIRST INCIDENCE    |     729 (T)      679          729 (T)      617         |497          656          665          610          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.302      P=0.158      P=0.355      P=0.199     |P=0.002 **   P=0.031N*    P=0.498N     P=0.076      | 
|POLY 3             |     P=0.225      P=0.361      P=0.597      P=0.231     |P<0.001 **   P=0.053N     P=0.570      P=0.033 *    | 
|POLY 1.5           |     P=0.213      P=0.388      P=0.620      P=0.230     |P<0.001 **   P=0.053N     P=0.580      P=0.043 *    | 
|POLY 6             |     P=0.238      P=0.314      P=0.552      P=0.228     |P<0.001 **   P=0.052N     P=0.563      P=0.025 *    | 
|LOGISTIC REGRESSION|     P=0.267      P=0.209      P=0.355      P=0.210     |P=0.002 **   P=0.052N     P=0.549N     P=0.052      | 
|COCH-ARM / FISHERS |     P=0.189      P=0.387      P=0.620N     P=0.207     |P=0.003 **   P=0.052N     P=0.553N     P=0.064      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/49 (4%)    0/50 (0%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     2/42.72      0/39.45      0/39.45      0/42.44     |2/44.11      0/45.74      2/46.27      2/44.76      | 
|POLY-3 PERCENT (g) |     4.7%         0.0%         0.0%         0.0%        |4.5%         0.0%         4.3%         4.5%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |1/33 (3%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     122          ---          ---          ---         |704          ---          232          592          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.238N     P=0.233N     P=0.237N     P=0.235N    |P=0.420      P=0.213N     P=0.679N     P=0.690N     | 
|POLY 3             |     P=0.222N     P=0.255N     P=0.255N     P=0.238N    |P=0.427      P=0.229N     P=0.677N     P=0.689N     | 
|POLY 1.5           |     P=0.231N     P=0.245N     P=0.245N     P=0.237N    |P=0.430      P=0.231N     P=0.681N     P=0.688N     | 
|POLY 6             |     P=0.210N     P=0.272N     P=0.271N     P=0.241N    |P=0.423      P=0.226N     P=0.672N     P=0.689N     | 
|LOGISTIC REGRESSION|     P=0.450N     P=0.762N     P=0.635N     P=0.540N    |P=0.485      P=0.227N     P=0.618N     P=0.671N     | 
|COCH-ARM / FISHERS |     P=0.239N     P=0.247N     P=0.247N     P=0.247N    |P=0.435      P=0.242N     P=0.684N     P=0.684N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 22      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    5/50 (10%)   2/50 (4%)    4/50 (8%)   |3/49 (6%)    9/50 (18%)   7/50 (14%)   7/50 (14%)   | 
|POLY-3 RATE (b)    |     3/41.84      5/40.43      2/39.56      4/43.12     |3/44.62      9/46.23      7/45.75      7/44.56      | 
|POLY-3 PERCENT (g) |     7.2%         12.4%        5.1%         9.3%        |6.7%         19.5%        15.3%        15.7%        | 
|TERMINAL (d)       |     2/30 (7%)    2/21 (10%)   1/21 (5%)    2/30 (7%)   |1/33 (3%)    7/39 (18%)   4/35 (11%)   4/34 (12%)   | 
|FIRST INCIDENCE    |     284          610          700          597         |544          605          674          657          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.568N     P=0.259      P=0.612N     P=0.507     |P=0.338      P=0.105      P=0.190      P=0.173      | 
|POLY 3             |     P=0.573      P=0.336      P=0.526N     P=0.517     |P=0.355      P=0.067      P=0.167      P=0.156      | 
|POLY 1.5           |     P=0.565      P=0.353      P=0.508N     P=0.515     |P=0.364      P=0.066      P=0.165      P=0.160      | 
|POLY 6             |     P=0.584      P=0.310      P=0.554N     P=0.517     |P=0.346      P=0.070      P=0.173      P=0.153      | 
|LOGISTIC REGRESSION|     P=0.541      P=0.343      P=0.510N     P=0.469     |P=0.366      P=0.067      P=0.167      P=0.166      | 
|COCH-ARM / FISHERS |     P=0.547      P=0.357      P=0.500N     P=0.500     |P=0.380      P=0.065      P=0.167      P=0.167      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Mixed Cell                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/50 (4%)    2/50 (4%)   |15/49 (31%)  12/50 (24%)  9/50 (18%)   11/50 (22%)  | 
|POLY-3 RATE (b)    |     0/40.89      2/39.45      2/40.63      2/42.74     |15/45.32     12/46.02     9/45.30      11/45.12     | 
|POLY-3 PERCENT (g) |     0.0%         5.1%         4.9%         4.7%        |33.1%        26.1%        19.9%        24.4%        | 
|TERMINAL (d)       |     0/30 (0%)    2/21 (10%)   0/21 (0%)    1/30 (3%)   |11/33 (33%)  11/39 (28%)  9/35 (26%)   7/34 (21%)   | 
|FIRST INCIDENCE    |     ---          729 (T)      368          645         |497          656          730 (T)      590          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.387      P=0.163      P=0.237      P=0.243     |P=0.331N     P=0.189N     P=0.091N     P=0.241N     | 
|POLY 3             |     P=0.364      P=0.229      P=0.235      P=0.247     |P=0.293N     P=0.306N     P=0.115N     P=0.246N     | 
|POLY 1.5           |     P=0.358      P=0.237      P=0.240      P=0.246     |P=0.286N     P=0.308N     P=0.115N     P=0.241N     | 
|POLY 6             |     P=0.367      P=0.214      P=0.224      P=0.246     |P=0.301N     P=0.300N     P=0.114N     P=0.251N     | 
|LOGISTIC REGRESSION|     P=0.319      P=0.163      P=0.150      P=0.242     |P=0.304N     P=0.286N     P=0.103N     P=0.236N     | 
|COCH-ARM / FISHERS |     P=0.339      P=0.247      P=0.247      P=0.247     |P=0.275N     P=0.304N     P=0.109N     P=0.228N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 23      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Mixed Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   4/50 (8%)    3/50 (6%)    9/50 (18%)  |4/49 (8%)    5/50 (10%)   6/50 (12%)   1/50 (2%)    | 
|POLY-3 RATE (b)    |     6/41.29      4/39.45      3/39.45      9/42.86     |4/44.62      5/45.74      6/45.85      1/44.17      | 
|POLY-3 PERCENT (g) |     14.5%        10.1%        7.6%         21.0%       |9.0%         10.9%        13.1%        2.3%         | 
|TERMINAL (d)       |     5/30 (17%)   4/21 (19%)   3/21 (14%)   8/30 (27%)  |2/33 (6%)    5/39 (13%)   4/35 (11%)   0/34 (0%)    | 
|FIRST INCIDENCE    |     617          729 (T)      729 (T)      607         |646          730 (T)      648          690          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.172      P=0.583N     P=0.416N     P=0.291     |P=0.114N     P=0.586      P=0.423      P=0.183N     | 
|POLY 3             |     P=0.121      P=0.397N     P=0.263N     P=0.312     |P=0.108N     P=0.516      P=0.387      P=0.181N     | 
|POLY 1.5           |     P=0.113      P=0.372N     P=0.245N     P=0.312     |P=0.104N     P=0.514      P=0.382      P=0.178N     | 
|POLY 6             |     P=0.131      P=0.445N     P=0.298N     P=0.305     |P=0.114N     P=0.519      P=0.394      P=0.186N     | 
|LOGISTIC REGRESSION|     P=0.145      P=0.476N     P=0.317N     P=0.306     |P=0.103N     P=0.522      P=0.382      P=0.169N     | 
|COCH-ARM / FISHERS |     P=0.103      P=0.370N     P=0.243N     P=0.288     |P=0.099N     P=0.513      P=0.383      P=0.175N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |4/49 (8%)    4/50 (8%)    3/50 (6%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.87      2/39.79      2/40.57      0/42.44     |4/44.01      4/46.19      3/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     4.8%         5.0%         4.9%         0.0%        |9.1%         8.7%         6.6%         0.0%         | 
|TERMINAL (d)       |     1/30 (3%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |4/33 (12%)   3/39 (8%)    3/35 (9%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     216          638          483          ---         |730 (T)      600          730 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.149N     P=0.620      P=0.670      P=0.238N    |P=0.042N*    P=0.558N     P=0.467N     P=0.059N     | 
|POLY 3             |     P=0.148N     P=0.676      P=0.683      P=0.234N    |P=0.041N*    P=0.617N     P=0.484N     P=0.060N     | 
|POLY 1.5           |     P=0.151N     P=0.689      P=0.692      P=0.233N    |P=0.040N*    P=0.624N     P=0.489N     P=0.059N     | 
|POLY 6             |     P=0.145N     P=0.654      P=0.666      P=0.236N    |P=0.043N*    P=0.604N     P=0.477N     P=0.061N     | 
|LOGISTIC REGRESSION|     P=0.200N     P=0.640      P=0.588      P=0.336N    |P=0.041N*    P=0.622N     P=0.467N     (e)          | 
|COCH-ARM / FISHERS |     P=0.156N     P=0.691N     P=0.691N     P=0.247N    |P=0.038N*    P=0.631N     P=0.489N     P=0.056N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 24      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Bile Duct                                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     33/50 (66%)  24/50 (48%)  20/50 (40%)  14/50 (28%) |1/49 (2%)    0/50 (0%)    4/50 (8%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     33/44.89     24/42.29     20/41.95     14/44.20    |1/44.11      0/45.74      4/46.60      1/44.26      | 
|POLY-3 PERCENT (g) |     73.5%        56.8%        47.7%        31.7%       |2.3%         0.0%         8.6%         2.3%         | 
|TERMINAL (d)       |     24/30 (80%)  12/21 (57%)  10/21 (48%)  7/30 (23%)  |0/33 (0%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     216          506          533          607         |704          ---          232          665          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001N**   P=0.487N     P=0.186N     P<0.001N**  |P=0.554      P=0.484N     P=0.198      P=0.754      | 
|POLY 3             |     P<0.001N**   P=0.064N     P=0.008N**   P<0.001N**  |P=0.563      P=0.493N     P=0.196      P=0.760N     | 
|POLY 1.5           |     P<0.001N**   P=0.049N*    P=0.006N**   P<0.001N**  |P=0.569      P=0.494N     P=0.191      P=0.759N     | 
|POLY 6             |     P<0.001N**   P=0.102N     P=0.013N*    P<0.001N**  |P=0.554      P=0.490N     P=0.202      P=0.760      | 
|LOGISTIC REGRESSION|     P<0.001N**   P=0.048N*    P=0.007N**   P<0.001N**  |P=0.624      P=0.495N     P=0.227      P=0.754N     | 
|COCH-ARM / FISHERS |     P<0.001N**   P=0.053N     P=0.008N**   P<0.001N**  |P=0.577      P=0.495N     P=0.187      P=0.747N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    3/50 (6%)    4/50 (8%)    2/50 (4%)   |3/49 (6%)    2/50 (4%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     3/41.22      3/39.83      4/40.42      2/42.59     |3/44.64      2/46.39      2/45.63      2/44.70      | 
|POLY-3 PERCENT (g) |     7.3%         7.5%         9.9%         4.7%        |6.7%         4.3%         4.4%         4.5%         | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    1/21 (5%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     679          679          602          700         |630          634          674          603          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.350N     P=0.541      P=0.403      P=0.500N    |P=0.517N     P=0.478N     P=0.482N     P=0.516N     | 
|POLY 3             |     P=0.371N     P=0.647      P=0.489      P=0.485N    |P=0.497N     P=0.482N     P=0.490N     P=0.499N     | 
|POLY 1.5           |     P=0.379N     P=0.662N     P=0.503      P=0.485N    |P=0.492N     P=0.487N     P=0.492N     P=0.496N     | 
|POLY 6             |     P=0.362N     P=0.618      P=0.462      P=0.490N    |P=0.505N     P=0.476N     P=0.486N     P=0.504N     | 
|LOGISTIC REGRESSION|     P=0.379N     P=0.641      P=0.498      P=0.485N    |P=0.456N     P=0.491N     P=0.481N     P=0.453N     | 
|COCH-ARM / FISHERS |     P=0.399N     P=0.661N     P=0.500      P=0.500N    |P=0.485N     P=0.490N     P=0.490N     P=0.490N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 25      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Kupffer Cell                                                                                                              | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    4/50 (8%)   |2/49 (4%)    2/50 (4%)    3/50 (6%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/40.89      1/39.86      2/39.94      4/43.24     |2/44.54      2/46.05      3/45.55      1/44.26      | 
|POLY-3 PERCENT (g) |     2.5%         2.5%         5.0%         9.3%        |4.5%         4.3%         6.6%         2.3%         | 
|TERMINAL (d)       |     1/30 (3%)    0/21 (0%)    0/21 (0%)    1/30 (3%)   |0/33 (0%)    1/39 (3%)    2/35 (6%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      610          617          607         |630          646          665          665          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.105      P=0.724      P=0.427      P=0.192     |P=0.396N     P=0.666N     P=0.526      P=0.511N     | 
|POLY 3             |     P=0.086      P=0.755      P=0.492      P=0.195     |P=0.389N     P=0.682N     P=0.510      P=0.502N     | 
|POLY 1.5           |     P=0.082      P=0.760N     P=0.501      P=0.193     |P=0.382N     P=0.684N     P=0.508      P=0.499N     | 
|POLY 6             |     P=0.093      P=0.743      P=0.474      P=0.197     |P=0.397N     P=0.678N     P=0.514      P=0.507N     | 
|LOGISTIC REGRESSION|     P=0.074      P=0.762N     P=0.496      P=0.185     |P=0.363N     P=0.691N     P=0.513      P=0.466N     | 
|COCH-ARM / FISHERS |     P=0.074      P=0.753N     P=0.500      P=0.181     |P=0.373N     P=0.684N     P=0.510      P=0.492N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |3/49 (6%)    1/50 (2%)    2/50 (4%)    5/50 (10%)   | 
|POLY-3 RATE (b)    |     0/40.89      1/40.19      2/40.27      1/42.51     |3/44.47      1/46.58      2/46.27      5/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         2.5%         5.0%         2.4%        |6.8%         2.2%         4.3%         11.4%        | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |2/33 (6%)    0/39 (0%)    1/35 (3%)    5/34 (15%)   | 
|FIRST INCIDENCE    |     ---          464          533          711         |596          396          232          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.523      P=0.513      P=0.224      P=0.506     |P=0.111      P=0.275N     P=0.484N     P=0.371      | 
|POLY 3             |     P=0.522      P=0.497      P=0.233      P=0.508     |P=0.110      P=0.289N     P=0.482N     P=0.350      | 
|POLY 1.5           |     P=0.518      P=0.502      P=0.239      P=0.507     |P=0.115      P=0.293N     P=0.486N     P=0.357      | 
|POLY 6             |     P=0.526      P=0.485      P=0.223      P=0.507     |P=0.104      P=0.284N     P=0.478N     P=0.342      | 
|LOGISTIC REGRESSION|     P=0.452      P=0.365      P=0.217      P=0.506     |P=0.145      P=0.271N     P=0.406N     P=0.354      | 
|COCH-ARM / FISHERS |     P=0.501      P=0.500      P=0.247      P=0.500     |P=0.123      P=0.301N     P=0.490N     P=0.369      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 26      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     26/50 (52%)  28/50 (56%)  27/50 (54%)  35/50 (70%) |38/49 (78%)  37/50 (74%)  34/50 (68%)  32/50 (64%)  | 
|POLY-3 RATE (b)    |     26/41.59     28/43.53     27/44.61     35/45.67    |38/47.29     37/48.27     34/47.56     32/47.03     | 
|POLY-3 PERCENT (g) |     62.5%        64.3%        60.5%        76.6%       |80.4%        76.7%        71.5%        68.1%        | 
|TERMINAL (d)       |     21/30 (70%)  14/21 (67%)  12/21 (57%)  24/30 (80%) |26/33 (79%)  32/39 (82%)  27/35 (77%)  24/34 (71%)  | 
|FIRST INCIDENCE    |     617          584          373          449         |497          396          539          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.221      P=0.059      P=0.106      P=0.069     |P=0.217N     P=0.162N     P=0.184N     P=0.164N     | 
|POLY 3             |     P=0.060      P=0.521      P=0.513N     P=0.101     |P=0.106N     P=0.422N     P=0.215N     P=0.120N     | 
|POLY 1.5           |     P=0.050      P=0.511      P=0.544N     P=0.083     |P=0.099N     P=0.423N     P=0.219N     P=0.114N     | 
|POLY 6             |     P=0.078      P=0.524      P=0.494N     P=0.126     |P=0.116N     P=0.430N     P=0.206N     P=0.131N     | 
|LOGISTIC REGRESSION|     P=0.058      P=0.273      P=0.449      P=0.055     |P=0.103N     P=0.416N     P=0.200N     P=0.116N     | 
|COCH-ARM / FISHERS |     P=0.035 *    P=0.421      P=0.500      P=0.050     |P=0.086N     P=0.430N     P=0.200N     P=0.104N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |1/49 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/41.89      0/39.45      0/39.45      2/42.44     |1/44.01      1/45.90      1/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     2.4%         0.0%         0.0%         4.7%        |2.3%         2.2%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    2/30 (7%)   |1/33 (3%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     122          ---          ---          729 (T)     |730 (T)      690          730 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.222      P=0.500N     P=0.500N     P=0.500     |P=0.335N     P=0.730N     P=0.749N     P=0.494N     | 
|POLY 3             |     P=0.201      P=0.512N     P=0.512N     P=0.505     |P=0.328N     P=0.751N     P=0.754N     P=0.500N     | 
|POLY 1.5           |     P=0.196      P=0.504N     P=0.505N     P=0.505     |P=0.326N     P=0.754N     P=0.756N     P=0.499N     | 
|POLY 6             |     P=0.209      P=0.526N     P=0.525N     P=0.501     |P=0.332N     P=0.747N     P=0.751N     P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.123      (e)          (e)          P=0.382     |P=0.328N     P=0.756N     P=0.749N     (e)          | 
|COCH-ARM / FISHERS |     P=0.191      P=0.500N     P=0.500N     P=0.500     |P=0.321N     P=0.747N     P=0.747N     P=0.495N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 27      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   1/50 (2%)    2/50 (4%)    5/50 (10%)  |3/49 (6%)    4/50 (8%)    0/50 (0%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     5/41.61      1/39.45      2/39.76      5/42.55     |3/44.18      4/46.05      0/45.30      4/44.02      | 
|POLY-3 PERCENT (g) |     12.0%        2.5%         5.0%         11.8%       |6.8%         8.7%         0.0%         9.1%         | 
|TERMINAL (d)       |     3/30 (10%)   1/21 (5%)    0/21 (0%)    4/30 (13%)  |2/33 (6%)    3/39 (8%)    0/35 (0%)    4/34 (12%)   | 
|FIRST INCIDENCE    |     528          729 (T)      673          700         |685          646          ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.369      P=0.180N     P=0.333N     P=0.624N    |P=0.431      P=0.571      P=0.116N     P=0.510      | 
|POLY 3             |     P=0.318      P=0.112N     P=0.233N     P=0.617N    |P=0.448      P=0.523      P=0.114N     P=0.498      | 
|POLY 1.5           |     P=0.305      P=0.103N     P=0.219N     P=0.614N    |P=0.453      P=0.517      P=0.115N     P=0.503      | 
|POLY 6             |     P=0.337      P=0.132N     P=0.260N     P=0.627N    |P=0.440      P=0.532      P=0.112N     P=0.491      | 
|LOGISTIC REGRESSION|     P=0.326      P=0.108N     P=0.221N     P=0.610N    |P=0.437      P=0.519      P=0.114N     P=0.491      | 
|COCH-ARM / FISHERS |     P=0.290      P=0.102N     P=0.218N     P=0.630N    |P=0.461      P=0.511      P=0.117N     P=0.511      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Ectasia                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    3/50 (6%)    2/48 (4%)    1/50 (2%)   |1/49 (2%)    2/50 (4%)    6/50 (12%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |     0/39.89      3/39.64      2/38.55      1/42.44     |1/44.01      2/46.05      6/45.41      6/44.64      | 
|POLY-3 PERCENT (g) |     0.0%         7.6%         5.2%         2.4%        |2.3%         4.3%         13.2%        13.4%        | 
|TERMINAL (d)       |     0/29 (0%)    2/21 (10%)   0/20 (0%)    1/30 (3%)   |1/33 (3%)    1/39 (3%)    5/35 (14%)   3/34 (9%)    | 
|FIRST INCIDENCE    |     ---          679          624          729 (T)     |730 (T)      646          702          646          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.520N     P=0.078      P=0.230      P=0.507     |P=0.038 *    P=0.544      P=0.069      P=0.065      | 
|POLY 3             |     P=0.546N     P=0.117      P=0.229      P=0.512     |P=0.041 *    P=0.516      P=0.061      P=0.058      | 
|POLY 1.5           |     P=0.548N     P=0.123      P=0.234      P=0.512     |P=0.042 *    P=0.511      P=0.059      P=0.058      | 
|POLY 6             |     P=0.549N     P=0.106      P=0.219      P=0.511     |P=0.039 *    P=0.523      P=0.063      P=0.058      | 
|LOGISTIC REGRESSION|     P=0.548N     P=0.100      P=0.227      P=0.507     |P=0.041 *    P=0.507      P=0.066      P=0.059      | 
|COCH-ARM / FISHERS |     P=0.566N     P=0.125      P=0.242      P=0.505     |P=0.046 *    P=0.508      P=0.059      P=0.059      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 28      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    1/48 (2%)    2/50 (4%)   |2/49 (4%)    4/50 (8%)    4/50 (8%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     0/39.89      0/39.45      1/38.57      2/42.44     |2/45.15      4/45.74      4/46.52      4/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.6%         4.7%        |4.4%         8.8%         8.6%         9.1%         | 
|TERMINAL (d)       |     0/29 (0%)    0/21 (0%)    0/20 (0%)    2/30 (7%)   |0/33 (0%)    4/39 (10%)   2/35 (6%)    4/34 (12%)   | 
|FIRST INCIDENCE    |     ---          ---          483          729 (T)     |497          730 (T)      232          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.113      (e)          P=0.513      P=0.245     |P=0.372      P=0.393      P=0.359      P=0.348      | 
|POLY 3             |     P=0.096      (e)          P=0.493      P=0.251     |P=0.369      P=0.343      P=0.351      P=0.325      | 
|POLY 1.5           |     P=0.093      (e)          P=0.498      P=0.250     |P=0.380      P=0.344      P=0.349      P=0.334      | 
|POLY 6             |     P=0.099      (e)          P=0.483      P=0.249     |P=0.354      P=0.345      P=0.354      P=0.315      | 
|LOGISTIC REGRESSION|     P=0.081      (e)          P=0.406      P=0.245     |P=0.430      P=0.342      P=0.400      P=0.370      | 
|COCH-ARM / FISHERS |     P=0.088      (e)          P=0.495      P=0.253     |P=0.398      P=0.349      P=0.349      P=0.349      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/49 (2%)    0/50 (0%)    1/48 (2%)    0/50 (0%)   |1/49 (2%)    0/50 (0%)    2/50 (4%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/39.89      0/39.45      1/37.86      0/42.44     |1/44.01      0/45.74      2/46.27      1/44.90      | 
|POLY-3 PERCENT (g) |     2.5%         0.0%         2.6%         0.0%        |2.3%         0.0%         4.3%         2.2%         | 
|TERMINAL (d)       |     1/29 (3%)    0/21 (0%)    1/20 (5%)    0/30 (0%)   |1/33 (3%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |730 (T)      ---          232          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.423N     P=0.564N     P=0.677      P=0.493N    |P=0.552      P=0.467N     P=0.514      P=0.757N     | 
|POLY 3             |     P=0.441N     P=0.502N     P=0.749      P=0.488N    |P=0.558      P=0.492N     P=0.517      P=0.756N     | 
|POLY 1.5           |     P=0.449N     P=0.495N     P=0.756      P=0.488N    |P=0.561      P=0.494N     P=0.513      P=0.756N     | 
|POLY 6             |     P=0.430N     P=0.515N     P=0.736      P=0.489N    |P=0.551      P=0.489N     P=0.523      P=0.757N     | 
|LOGISTIC REGRESSION|     P=0.423N     (e)          P=0.677      (e)         |P=0.662      (e)          P=0.630      P=0.667N     | 
|COCH-ARM / FISHERS |     P=0.456N     P=0.495N     P=0.747      P=0.495N    |P=0.563      P=0.495N     P=0.508      P=0.747N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 29      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    2/50 (4%)    0/48 (0%)    2/50 (4%)   |18/49 (37%)  19/50 (38%)  21/50 (42%)  25/50 (50%)  | 
|POLY-3 RATE (b)    |     0/39.89      2/39.45      0/37.86      2/42.67     |18/45.06     19/45.74     21/46.01     25/44.54     | 
|POLY-3 PERCENT (g) |     0.0%         5.1%         0.0%         4.7%        |40.0%        41.5%        45.6%        56.1%        | 
|TERMINAL (d)       |     0/29 (0%)    2/21 (10%)   0/20 (0%)    1/30 (3%)   |12/33 (36%)  19/39 (49%)  16/35 (46%)  22/34 (65%)  | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          668         |630          730 (T)      665          646          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.335      P=0.170      (e)          P=0.243     |P=0.052      P=0.437N     P=0.435      P=0.136      | 
|POLY 3             |     P=0.299      P=0.234      (e)          P=0.252     |P=0.057      P=0.524      P=0.367      P=0.087      | 
|POLY 1.5           |     P=0.297      P=0.242      (e)          P=0.251     |P=0.068      P=0.526      P=0.362      P=0.103      | 
|POLY 6             |     P=0.298      P=0.220      (e)          P=0.252     |P=0.044 *    P=0.519      P=0.378      P=0.069      | 
|LOGISTIC REGRESSION|     P=0.316      P=0.170      (e)          P=0.250     |P=0.042 *    P=0.575N     P=0.398      P=0.088      | 
|COCH-ARM / FISHERS |     P=0.285      P=0.253      (e)          P=0.253     |P=0.088      P=0.531      P=0.371      P=0.129      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    4/50 (8%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/41.72      1/40.19      2/40.19      4/42.47     |0/44.24      0/45.74      2/46.27      1/44.48      | 
|POLY-3 PERCENT (g) |     2.4%         2.5%         5.0%         9.4%        |0.0%         0.0%         4.3%         2.3%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    3/30 (10%)  |0/33 (0%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     406          464          603          720         |---          ---          232          592          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.104      P=0.746N     P=0.498      P=0.186     |P=0.353      (e)          P=0.246      P=0.504      | 
|POLY 3             |     P=0.080      P=0.753      P=0.487      P=0.183     |P=0.352      (e)          P=0.247      P=0.501      | 
|POLY 1.5           |     P=0.078      P=0.760      P=0.498      P=0.185     |P=0.353      (e)          P=0.243      P=0.501      | 
|POLY 6             |     P=0.082      P=0.738      P=0.469      P=0.179     |P=0.349      (e)          P=0.252      P=0.502      | 
|LOGISTIC REGRESSION|     P=0.059      P=0.611      P=0.428      P=0.175     |P=0.384      (e)          P=0.318      P=0.525      | 
|COCH-ARM / FISHERS |     P=0.074      P=0.753N     P=0.500      P=0.181     |P=0.355      (e)          P=0.247      P=0.500      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 30      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    4/50 (8%)    2/50 (4%)   |1/50 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      2/40.14      4/40.60      2/42.44     |1/44.24      1/46.09      1/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         5.0%         9.9%         4.7%        |2.3%         2.2%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    2/30 (7%)   |1/33 (3%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          631          603          729 (T)     |730 (T)      634          730 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.430      P=0.228      P=0.054      P=0.238     |P=0.333N     P=0.737N     P=0.749N     P=0.494N     | 
|POLY 3             |     P=0.406      P=0.232      P=0.059      P=0.245     |P=0.330N     P=0.752N     P=0.755N     P=0.501N     | 
|POLY 1.5           |     P=0.401      P=0.239      P=0.061      P=0.245     |P=0.328N     P=0.756N     P=0.758N     P=0.501N     | 
|POLY 6             |     P=0.408      P=0.221      P=0.054      P=0.243     |P=0.333N     P=0.746N     P=0.752N     P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.378      P=0.228      P=0.062      P=0.238     |P=0.324N     P=0.756      P=0.749N     (e)          | 
|COCH-ARM / FISHERS |     P=0.379      P=0.247      P=0.059      P=0.247     |P=0.324N     P=0.753N     P=0.753N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Ectasia                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    6/50 (12%)  |0/49 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      6/43.89     |0/44.01      0/45.74      0/44.51      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         13.7%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    2/30 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          602         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P=0.023 *   |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   (e)          (e)          P=0.019 *   |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P=0.018 *   |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   (e)          (e)          P=0.020 *   |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          P=0.016 *   |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P=0.013 *   |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 31      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    2/50 (4%)   |2/49 (4%)    5/50 (10%)   2/49 (4%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     2/41.06      2/40.19      2/39.88      2/42.47     |2/44.37      5/46.19      2/45.49      4/44.73      | 
|POLY-3 PERCENT (g) |     4.9%         5.0%         5.0%         4.7%        |4.5%         10.8%        4.4%         8.9%         | 
|TERMINAL (d)       |     1/30 (3%)    1/21 (5%)    1/21 (5%)    1/30 (3%)   |1/33 (3%)    4/39 (10%)   0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     686          464          603          720         |630          600          232          602          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.563N     P=0.610      P=0.615      P=0.692     |P=0.419      P=0.273      P=0.679N     P=0.338      | 
|POLY 3             |     P=0.603N     P=0.687      P=0.684      P=0.682N    |P=0.439      P=0.233      P=0.685N     P=0.341      | 
|POLY 1.5           |     P=0.608N     P=0.691N     P=0.694N     P=0.682N    |P=0.443      P=0.229      P=0.688N     P=0.343      | 
|POLY 6             |     P=0.596N     P=0.665      P=0.664      P=0.686N    |P=0.436      P=0.239      P=0.680N     P=0.339      | 
|LOGISTIC REGRESSION|     P=0.616N     P=0.693      P=0.690      P=0.686N    |P=0.486      P=0.223      P=0.611N     P=0.359      | 
|COCH-ARM / FISHERS |     P=0.622      P=0.691N     P=0.691N     P=0.691N    |P=0.450      P=0.226      P=0.691N     P=0.349      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/49 (4%)    2/50 (4%)    0/49 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      0/42.44     |2/44.01      2/45.74      0/44.51      2/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.5%         4.4%         0.0%         4.5%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |2/33 (6%)    2/39 (5%)    0/35 (0%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |730 (T)      730 (T)      ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.602      P=0.634N     P=0.225N     P=0.685N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.612      P=0.680N     P=0.235N     P=0.694N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.615      P=0.683N     P=0.237N     P=0.691N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.607      P=0.674N     P=0.231N     P=0.691      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.602      P=0.634N     (e)          P=0.685N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.621      P=0.684N     P=0.247N     P=0.684N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 32      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/49 (29%)  23/47 (49%)  10/49 (20%)  13/49 (27%) |44/49 (90%)  44/50 (88%)  42/50 (84%)  42/50 (84%)  | 
|POLY-3 RATE (b)    |     14/42.09     23/40.45     10/39.80     13/42.47    |44/47.69     44/48.57     42/47.34     42/47.58     | 
|POLY-3 PERCENT (g) |     33.3%        56.9%        25.1%        30.6%       |92.3%        90.6%        88.7%        88.3%        | 
|TERMINAL (d)       |     9/30 (30%)   9/21 (43%)   5/20 (25%)   8/30 (27%)  |30/33 (91%)  36/39 (92%)  31/35 (89%)  30/34 (88%)  | 
|FIRST INCIDENCE    |     216          584          483          645         |544          572          617          590          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.105N     P=0.010 *    P=0.549N     P=0.495N    |P=0.532N     P=0.166N     P=0.267N     P=0.387N     | 
|POLY 3             |     P=0.121N     P=0.022 *    P=0.284N     P=0.489N    |P=0.337N     P=0.529N     P=0.400N     P=0.371N     | 
|POLY 1.5           |     P=0.127N     P=0.028 *    P=0.252N     P=0.483N    |P=0.303N     P=0.527N     P=0.366N     P=0.337N     | 
|POLY 6             |     P=0.118N     P=0.017 *    P=0.347N     P=0.501N    |P=0.383N     P=0.538N     P=0.438N     P=0.417N     | 
|LOGISTIC REGRESSION|     P=0.116N     P=0.030 *    P=0.249N     P=0.466N    |P=0.339N     P=0.490N     P=0.253N     P=0.339N     | 
|COCH-ARM / FISHERS |     P=0.151N     P=0.033 *    P=0.241N     P=0.500N    |P=0.261N     P=0.514N     P=0.290N     P=0.290N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery                                                                                                                        | 
|     Accessory Spleen                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/8 (50%)    2/7 (29%)    2/13 (15%)   0/15 (0%)   |0/1 (0%)     2/6 (33%)    0/1 (0%)     2/6 (33%)    | 
|POLY-3 RATE (b)    |     4/7.89       2/6.24       2/10.24      0/12.57     |0/0.90       2/5.66       0/0.98       2/5.61       | 
|POLY-3 PERCENT (g) |     50.7%        32.1%        19.5%        0.0%        |0.0%         35.4%        0.0%         35.7%        | 
|TERMINAL (d)       |     0/3 (0%)     1/4 (25%)    0/4 (0%)     0/9 (0%)    |0/0 (0%)     2/5 (40%)    0/0 (0%)     2/5 (40%)    | 
|FIRST INCIDENCE    |     528          725          510          ---         |---          730 (T)      ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.044N*    P=0.412N     P=0.423N     P=0.067N    |P=0.677      P=1.000      (e)          P=1.000      | 
|POLY 3             |     P=0.005N**   P=0.438N     P=0.176N     P=0.003N**  |P=0.556      P=0.686      (e)          P=0.685      | 
|POLY 1.5           |     P=0.005N**   P=0.412N     P=0.144N     P=0.002N**  |P=0.554      P=0.679      (e)          P=0.679      | 
|POLY 6             |     P=0.005N**   P=0.478N     P=0.231N     P=0.004N**  |P=0.564      P=0.700      (e)          P=0.699      | 
|LOGISTIC REGRESSION|     P=0.007N**   P=0.424N     P=0.071N     P=0.006N**  |(e)          P=1.000      (e)          P=1.000      | 
|COCH-ARM / FISHERS |     P=0.008N**   P=0.378N     P=0.115N     P=0.008N**  |P=0.560      P=0.714      (e)          P=0.714      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 33      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/8 (63%)    6/7 (86%)    11/13 (85%)  12/15 (80%) |1/1 (100%)   4/6 (67%)    1/1 (100%)   5/6 (83%)    | 
|POLY-3 RATE (b)    |     5/6.88       6/6.98       11/12.24     12/14.93    |1/1.00       4/6.00       1/1.00       5/6.00       | 
|POLY-3 PERCENT (g) |     72.6%        85.9%        89.9%        80.4%       |100.0%       66.7%        100.0%       83.3%        | 
|TERMINAL (d)       |     3/3 (100%)   4/4 (100%)   4/4 (100%)   7/9 (78%)   |0/0 (0%)     3/5 (60%)    0/0 (0%)     4/5 (80%)    | 
|FIRST INCIDENCE    |     700          610          373          266         |704          634          725          618          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.428      P=0.623      P=0.063      P=0.386     |P=0.442      P=0.740N     (e)          P=0.754      | 
|POLY 3             |     P=0.599N     P=0.522      P=0.355      P=0.559     |P=0.530      P=0.673N     (e)          P=0.828N     | 
|POLY 1.5           |     P=0.587      P=0.431      P=0.303      P=0.459     |P=0.530      P=0.673N     (e)          P=0.828N     | 
|POLY 6             |     P=0.491N     P=0.671      P=0.486      P=0.702     |P=0.530      P=0.673N     (e)          P=0.828N     | 
|LOGISTIC REGRESSION|     P=0.461      P=0.396      P=0.170      P=0.338     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.464      P=0.338      P=0.262      P=0.334     |P=0.534      P=0.714N     (e)          P=0.857N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Foreign Body                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    1/50 (2%)    2/50 (4%)   |1/49 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     4/41.21      3/40.66      1/39.78      2/42.44     |1/44.60      0/45.74      1/45.30      2/44.02      | 
|POLY-3 PERCENT (g) |     9.7%         7.4%         2.5%         4.7%        |2.2%         0.0%         2.2%         4.5%         | 
|TERMINAL (d)       |     2/30 (7%)    1/21 (5%)    0/21 (0%)    2/30 (7%)   |0/33 (0%)    0/39 (0%)    1/35 (3%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     646          506          638          729 (T)     |544          ---          730 (T)      730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.268N     P=0.615N     P=0.268N     P=0.341N    |P=0.227      P=0.492N     P=0.754N     P=0.509      | 
|POLY 3             |     P=0.290N     P=0.507N     P=0.188N     P=0.323N    |P=0.229      P=0.495N     P=0.757N     P=0.495      | 
|POLY 1.5           |     P=0.296N     P=0.493N     P=0.179N     P=0.322N    |P=0.233      P=0.496N     P=0.758N     P=0.500      | 
|POLY 6             |     P=0.283N     P=0.538N     P=0.207N     P=0.329N    |P=0.223      P=0.493N     P=0.756N     P=0.490      | 
|LOGISTIC REGRESSION|     P=0.301N     P=0.500N     P=0.187N     P=0.323N    |P=0.245      P=0.417N     P=0.736N     P=0.527      | 
|COCH-ARM / FISHERS |     P=0.305N     P=0.500N     P=0.181N     P=0.339N    |P=0.238      P=0.495N     P=0.747N     P=0.508      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 34      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   8/50 (16%)   9/50 (18%)   8/50 (16%)  |6/49 (12%)   3/50 (6%)    5/50 (10%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     9/42.23      8/41.06      9/42.78      8/42.58     |6/44.72      3/46.26      5/45.91      5/44.02      | 
|POLY-3 PERCENT (g) |     21.3%        19.5%        21.0%        18.8%       |13.4%        6.5%         10.9%        11.4%        | 
|TERMINAL (d)       |     5/30 (17%)   4/21 (19%)   1/21 (5%)    6/30 (20%)  |3/33 (9%)    2/39 (5%)    3/35 (9%)    5/34 (15%)   | 
|FIRST INCIDENCE    |     406          506          533          711         |544          572          617          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.382N     P=0.498      P=0.463      P=0.494N    |P=0.518      P=0.192N     P=0.466N     P=0.489N     | 
|POLY 3             |     P=0.469N     P=0.526N     P=0.593N     P=0.492N    |P=0.525      P=0.225N     P=0.482N     P=0.511N     | 
|POLY 1.5           |     P=0.473N     P=0.498N     P=0.585N     P=0.484N    |P=0.538      P=0.229N     P=0.487N     P=0.501N     | 
|POLY 6             |     P=0.466N     P=0.577N     P=0.603      P=0.510N    |P=0.506      P=0.218N     P=0.471N     P=0.524N     | 
|LOGISTIC REGRESSION|     P=0.481N     P=0.499N     P=0.598      P=0.470N    |P=0.554      P=0.236N     P=0.484N     P=0.500N     | 
|COCH-ARM / FISHERS |     P=0.489N     P=0.500N     P=0.602N     P=0.500N    |P=0.557      P=0.233N     P=0.486N     P=0.486N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Respiratory Epithelium                                                                                                     | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   7/50 (14%)   8/50 (16%)   5/50 (10%)  |6/49 (12%)   4/50 (8%)    4/50 (8%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     6/41.27      7/40.77      8/42.80      5/42.58     |6/45.06      4/45.74      4/45.70      1/44.29      | 
|POLY-3 PERCENT (g) |     14.5%        17.2%        18.7%        11.7%       |13.3%        8.8%         8.8%         2.3%         | 
|TERMINAL (d)       |     4/30 (13%)   3/21 (14%)   0/21 (0%)    3/30 (10%)  |3/33 (9%)    4/39 (10%)   3/35 (9%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     646          506          533          711         |544          730 (T)      617          657          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.296N     P=0.309      P=0.297      P=0.494N    |P=0.064N     P=0.296N     P=0.346N     P=0.064N     | 
|POLY 3             |     P=0.338N     P=0.490      P=0.414      P=0.478N    |P=0.058N     P=0.360N     P=0.360N     P=0.058N     | 
|POLY 1.5           |     P=0.346N     P=0.510      P=0.414      P=0.477N    |P=0.056N     P=0.360N     P=0.362N     P=0.056N     | 
|POLY 6             |     P=0.331N     P=0.449      P=0.406      P=0.486N    |P=0.061N     P=0.358N     P=0.357N     P=0.061N     | 
|LOGISTIC REGRESSION|     P=0.365N     P=0.485      P=0.383      P=0.481N    |P=0.052N     P=0.358N     P=0.351N     P=0.048N*    | 
|COCH-ARM / FISHERS |     P=0.370N     P=0.500      P=0.387      P=0.500N    |P=0.053N     P=0.357N     P=0.357N     P=0.053N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 35      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Respiratory Epithelium                                                                                                     | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    5/50 (10%)   1/50 (2%)   |1/49 (2%)    1/50 (2%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     4/41.84      3/39.50      5/41.23      1/42.51     |1/44.01      1/45.74      0/45.30      2/44.02      | 
|POLY-3 PERCENT (g) |     9.6%         7.6%         12.1%        2.4%        |2.3%         2.2%         0.0%         4.5%         | 
|TERMINAL (d)       |     1/30 (3%)    2/21 (10%)   1/21 (5%)    0/30 (0%)   |1/33 (3%)    1/39 (3%)    0/35 (0%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     406          716          533          711         |730 (T)      730 (T)      ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.137N     P=0.641N     P=0.409      P=0.183N    |P=0.317      P=0.724N     P=0.488N     P=0.510      | 
|POLY 3             |     P=0.138N     P=0.532N     P=0.491      P=0.173N    |P=0.329      P=0.752N     P=0.494N     P=0.500      | 
|POLY 1.5           |     P=0.145N     P=0.508N     P=0.504      P=0.172N    |P=0.332      P=0.754N     P=0.496N     P=0.503      | 
|POLY 6             |     P=0.131N     P=0.571N     P=0.467      P=0.176N    |P=0.324      P=0.748N     P=0.491N     P=0.497      | 
|LOGISTIC REGRESSION|     P=0.161N     P=0.501N     P=0.484      P=0.185N    |P=0.317      P=0.724N     (e)          P=0.510      | 
|COCH-ARM / FISHERS |     P=0.157N     P=0.500N     P=0.500      P=0.181N    |P=0.335      P=0.747N     P=0.495N     P=0.508      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |10/49 (20%)  6/50 (12%)   6/50 (12%)   7/50 (14%)   | 
|POLY-3 RATE (b)    |                                                        |10/45.60     6/45.74      6/46.54      7/44.51      | 
|POLY-3 PERCENT (g) |                                                        |21.9%        13.1%        12.9%        15.7%        | 
|TERMINAL (d)       |                                                        |5/33 (15%)   6/39 (15%)   3/35 (9%)    5/34 (15%)   | 
|FIRST INCIDENCE    |                                                        |497          730 (T)      232          603          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.445N     P=0.146N     P=0.193N     P=0.304N     | 
|POLY 3             |                                                        |P=0.422N     P=0.202N     P=0.192N     P=0.315N     | 
|POLY 1.5           |                                                        |P=0.410N     P=0.200N     P=0.193N     P=0.302N     | 
|POLY 6             |                                                        |P=0.437N     P=0.204N     P=0.191N     P=0.332N     | 
|LOGISTIC REGRESSION|                                                        |P=0.378N     P=0.195N     P=0.174N     P=0.277N     | 
|COCH-ARM / FISHERS |                                                        |P=0.393N     P=0.194N     P=0.194N     P=0.282N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 36      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     23/50 (46%)  19/50 (38%)  16/50 (32%)  23/50 (46%) |13/49 (27%)  15/50 (30%)  18/49 (37%)  13/50 (26%)  | 
|POLY-3 RATE (b)    |     23/43.83     19/41.67     16/41.97     23/44.93    |13/44.62     15/47.10     18/45.86     13/44.68     | 
|POLY-3 PERCENT (g) |     52.5%        45.6%        38.1%        51.2%       |29.1%        31.9%        39.3%        29.1%        | 
|TERMINAL (d)       |     17/30 (57%)  10/21 (48%)  9/21 (43%)   16/30 (53%) |11/33 (33%)  11/39 (28%)  12/35 (34%)  11/34 (32%)  | 
|FIRST INCIDENCE    |     406          584          550          590         |544          572          592          597          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.486N     P=0.453      P=0.410N     P=0.551N    |P=0.507N     P=0.580N     P=0.262      P=0.562N     | 
|POLY 3             |     P=0.458      P=0.333N     P=0.125N     P=0.537N    |P=0.484N     P=0.478      P=0.213      P=0.591N     | 
|POLY 1.5           |     P=0.426      P=0.279N     P=0.105N     P=0.535N    |P=0.463N     P=0.457      P=0.197      P=0.583N     | 
|POLY 6             |     P=0.503      P=0.425N     P=0.165N     P=0.542N    |P=0.510N     P=0.513      P=0.244      P=0.590      | 
|LOGISTIC REGRESSION|     P=0.454      P=0.291N     P=0.112N     P=0.523N    |P=0.464N     P=0.448      P=0.198      P=0.585      | 
|COCH-ARM / FISHERS |     P=0.374      P=0.272N     P=0.109N     P=0.579N    |P=0.433N     P=0.437      P=0.193      P=0.567N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/49 (2%)    0/50 (0%)    1/48 (2%)    1/50 (2%)   |9/49 (18%)   10/50 (20%)  6/49 (12%)   5/49 (10%)   | 
|POLY-3 RATE (b)    |     1/39.89      0/39.45      1/38.39      1/42.44     |9/44.68      10/45.74     6/44.59      5/43.29      | 
|POLY-3 PERCENT (g) |     2.5%         0.0%         2.6%         2.4%        |20.1%        21.9%        13.5%        11.6%        | 
|TERMINAL (d)       |     1/29 (3%)    0/21 (0%)    0/20 (0%)    1/30 (3%)   |7/33 (21%)   10/39 (26%)  5/35 (14%)   4/33 (12%)   | 
|FIRST INCIDENCE    |     729 (T)      ---          624          729 (T)     |630          730 (T)      711          657          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.585      P=0.564N     P=0.720      P=0.755N    |P=0.140N     P=0.559N     P=0.249N     P=0.199N     | 
|POLY 3             |     P=0.576      P=0.502N     P=0.753      P=0.747N    |P=0.127N     P=0.523      P=0.287N     P=0.209N     | 
|POLY 1.5           |     P=0.567      P=0.495N     P=0.758      P=0.748N    |P=0.122N     P=0.520      P=0.291N     P=0.203N     | 
|POLY 6             |     P=0.588      P=0.515N     P=0.742      P=0.749N    |P=0.134N     P=0.528      P=0.281N     P=0.217N     | 
|LOGISTIC REGRESSION|     P=0.568      (e)          P=0.758      P=0.755N    |P=0.135N     P=0.555      P=0.272N     P=0.206N     | 
|COCH-ARM / FISHERS |     P=0.554      P=0.495N     P=0.747      P=0.747N    |P=0.115N     P=0.520      P=0.288N     P=0.194N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 37      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/49 (14%)   9/50 (18%)   5/48 (10%)   3/50 (6%)   |22/49 (45%)  11/50 (22%)  13/49 (27%)  16/49 (33%)  | 
|POLY-3 RATE (b)    |     7/40.81      9/41.23      5/39.12      3/42.55     |22/45.25     11/46.05     13/46.82     16/44.46     | 
|POLY-3 PERCENT (g) |     17.2%        21.8%        12.8%        7.1%        |48.6%        23.9%        27.8%        36.0%        | 
|TERMINAL (d)       |     4/29 (14%)   3/21 (14%)   1/20 (5%)    2/30 (7%)   |16/33 (49%)  10/39 (26%)  9/35 (26%)   12/33 (36%)  | 
|FIRST INCIDENCE    |     406          561          605          700         |610          646          232          590          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.054N     P=0.238      P=0.552N     P=0.154N    |P=0.515N     P=0.006N**   P=0.041N*    P=0.170N     | 
|POLY 3             |     P=0.054N     P=0.399      P=0.408N     P=0.138N    |P=0.457N     P=0.010N*    P=0.029N*    P=0.156N     | 
|POLY 1.5           |     P=0.057N     P=0.418      P=0.391N     P=0.138N    |P=0.448N     P=0.011N*    P=0.035N*    P=0.154N     | 
|POLY 6             |     P=0.052N     P=0.366      P=0.436N     P=0.141N    |P=0.469N     P=0.009N**   P=0.025N*    P=0.160N     | 
|LOGISTIC REGRESSION|     P=0.059N     P=0.410      P=0.393N     P=0.138N    |P=0.442N     P=0.010N*    P=0.045N*    P=0.168N     | 
|COCH-ARM / FISHERS |     P=0.065N     P=0.410      P=0.394N     P=0.151N    |P=0.434N     P=0.013N*    P=0.046N*    P=0.150N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/49 (12%)   3/50 (6%)    5/48 (10%)   1/50 (2%)   |13/49 (27%)  10/50 (20%)  3/49 (6%)    5/49 (10%)   | 
|POLY-3 RATE (b)    |     6/40.55      3/40.00      5/38.76      1/42.44     |13/45.15     10/45.74     3/44.52      5/43.02      | 
|POLY-3 PERCENT (g) |     14.8%        7.5%         12.9%        2.4%        |28.8%        21.9%        6.7%         11.6%        | 
|TERMINAL (d)       |     3/29 (10%)   2/21 (10%)   3/20 (15%)   1/30 (3%)   |10/33 (30%)  10/39 (26%)  3/35 (9%)    5/33 (15%)   | 
|FIRST INCIDENCE    |     590          557          602          729 (T)     |527          730 (T)      730 (T)      730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.057N     P=0.380N     P=0.573      P=0.057N    |P=0.038N*    P=0.187N     P=0.005N**   P=0.035N*    | 
|POLY 3             |     P=0.059N     P=0.246N     P=0.532N     P=0.048N*   |P=0.033N*    P=0.302N     P=0.006N**   P=0.039N*    | 
|POLY 1.5           |     P=0.064N     P=0.230N     P=0.512N     P=0.048N*   |P=0.031N*    P=0.302N     P=0.006N**   P=0.036N*    | 
|POLY 6             |     P=0.054N     P=0.280N     P=0.571N     P=0.050N    |P=0.036N*    P=0.299N     P=0.005N**   P=0.043N*    | 
|LOGISTIC REGRESSION|     P=0.064N     P=0.240N     P=0.530N     P=0.049N*   |P=0.036N*    P=0.276N     P=0.007N**   P=0.037N*    | 
|COCH-ARM / FISHERS |     P=0.072N     P=0.233N     P=0.515N     P=0.053N    |P=0.031N*    P=0.298N     P=0.006N**   P=0.033N*    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 38      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     17/50 (34%)  20/50 (40%)  13/50 (26%)  20/50 (40%) |                                                    | 
|POLY-3 RATE (b)    |     17/43.04     20/42.86     13/42.91     20/44.92    |                                                    | 
|POLY-3 PERCENT (g) |     39.5%        46.7%        30.3%        44.5%       |                                                    | 
|TERMINAL (d)       |     12/30 (40%)  10/21 (48%)  5/21 (24%)   12/30 (40%) |                                                    | 
|FIRST INCIDENCE    |     122          464          368          539         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.537N     P=0.101      P=0.548N     P=0.370     |                                                    | 
|POLY 3             |     P=0.423      P=0.322      P=0.249N     P=0.396     |                                                    | 
|POLY 1.5           |     P=0.396      P=0.346      P=0.237N     P=0.380     |                                                    | 
|POLY 6             |     P=0.459      P=0.278      P=0.289N     P=0.408     |                                                    | 
|LOGISTIC REGRESSION|     P=0.377      P=0.340      P=0.258N     P=0.368     |                                                    | 
|COCH-ARM / FISHERS |     P=0.358      P=0.339      P=0.257N     P=0.339     |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   5/50 (10%)   4/50 (8%)    6/50 (12%)  |                                                    | 
|POLY-3 RATE (b)    |     5/41.30      5/40.59      4/39.55      6/42.51     |                                                    | 
|POLY-3 PERCENT (g) |     12.1%        12.3%        10.1%        14.1%       |                                                    | 
|TERMINAL (d)       |     3/30 (10%)   3/21 (14%)   3/21 (14%)   5/30 (17%)  |                                                    | 
|FIRST INCIDENCE    |     617          511          704          711         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.522      P=0.467      P=0.588      P=0.503     |                                                    | 
|POLY 3             |     P=0.448      P=0.621      P=0.527N     P=0.520     |                                                    | 
|POLY 1.5           |     P=0.440      P=0.624N     P=0.504N     P=0.522     |                                                    | 
|POLY 6             |     P=0.456      P=0.585      P=0.569N     P=0.511     |                                                    | 
|LOGISTIC REGRESSION|     P=0.468      P=0.627      P=0.580N     P=0.518     |                                                    | 
|COCH-ARM / FISHERS |     P=0.420      P=0.630N     P=0.500N     P=0.500     |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 39      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     26/50 (52%)  24/50 (48%)  28/50 (56%)  29/50 (58%) |                                                    | 
|POLY-3 RATE (b)    |     26/45.50     24/44.58     28/46.88     29/48.61    |                                                    | 
|POLY-3 PERCENT (g) |     57.1%        53.8%        59.7%        59.7%       |                                                    | 
|TERMINAL (d)       |     15/30 (50%)  9/21 (43%)   8/21 (38%)   15/30 (50%) |                                                    | 
|FIRST INCIDENCE    |     122          491          368          266         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.483      P=0.336      P=0.169      P=0.406     |                                                    | 
|POLY 3             |     P=0.386      P=0.458N     P=0.483      P=0.485     |                                                    | 
|POLY 1.5           |     P=0.328      P=0.422N     P=0.479      P=0.446     |                                                    | 
|POLY 6             |     P=0.451      P=0.521N     P=0.469      P=0.514     |                                                    | 
|LOGISTIC REGRESSION|     P=0.195      P=0.420N     P=0.417      P=0.313     |                                                    | 
|COCH-ARM / FISHERS |     P=0.230      P=0.421N     P=0.421      P=0.344     |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate: Epithelium                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     12/50 (24%)  3/50 (6%)    10/50 (20%)  9/50 (18%)  |                                                    | 
|POLY-3 RATE (b)    |     12/41.52     3/39.60      10/41.10     9/43.28     |                                                    | 
|POLY-3 PERCENT (g) |     28.9%        7.6%         24.3%        20.8%       |                                                    | 
|TERMINAL (d)       |     10/30 (33%)  2/21 (10%)   4/21 (19%)   6/30 (20%)  |                                                    | 
|FIRST INCIDENCE    |     604          690          617          605         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.500N     P=0.051N     P=0.509      P=0.304N    |                                                    | 
|POLY 3             |     P=0.566N     P=0.012N*    P=0.412N     P=0.269N    |                                                    | 
|POLY 1.5           |     P=0.536      P=0.010N*    P=0.392N     P=0.275N    |                                                    | 
|POLY 6             |     P=0.521N     P=0.017N*    P=0.451N     P=0.270N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.556      P=0.021N*    P=0.456N     P=0.278N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.491      P=0.011N*    P=0.405N     P=0.312N    |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 40      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |1/49 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      0/41.51     |1/44.01      0/45.74      1/45.32      2/44.32      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.3%         0.0%         2.2%         4.5%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |1/33 (3%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |730 (T)      ---          725          646          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.222      P=0.467N     P=0.748N     P=0.507      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.232      P=0.492N     P=0.754N     P=0.502      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.235      P=0.494N     P=0.756N     P=0.504      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.228      P=0.489N     P=0.751N     P=0.501      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.233      (e)          P=0.750N     P=0.504      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.238      P=0.495N     P=0.747N     P=0.508      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Cyst Epithelial Inclusion                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    3/49 (6%)    2/49 (4%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      3/39.03      2/41.47     |0/44.01      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         7.7%         4.8%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    1/29 (3%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          689          720         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.202      (e)          P=0.082      P=0.236     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.169      (e)          P=0.110      P=0.240     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.164      (e)          P=0.115      P=0.240     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.174      (e)          P=0.101      P=0.238     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.177      (e)          P=0.102      P=0.233     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.154      (e)          P=0.117      P=0.242     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 41      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Hyperkeratosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    1/49 (2%)    0/49 (0%)   |1/49 (2%)    1/50 (2%)    1/50 (2%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     2/41.09      3/39.53      1/39.06      0/41.44     |1/44.01      1/45.74      1/45.30      3/44.02      | 
|POLY-3 PERCENT (g) |     4.9%         7.6%         2.6%         0.0%        |2.3%         2.2%         2.2%         6.8%         | 
|TERMINAL (d)       |     1/30 (3%)    1/21 (5%)    0/21 (0%)    0/29 (0%)   |1/33 (3%)    1/39 (3%)    1/35 (3%)    3/34 (9%)    | 
|FIRST INCIDENCE    |     679          714          644          ---         |730 (T)      730 (T)      730 (T)      730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.103N     P=0.368      P=0.575N     P=0.247N    |P=0.143      P=0.724N     P=0.749N     P=0.315      | 
|POLY 3             |     P=0.103N     P=0.482      P=0.518N     P=0.235N    |P=0.153      P=0.752N     P=0.754N     P=0.305      | 
|POLY 1.5           |     P=0.104N     P=0.499      P=0.507N     P=0.235N    |P=0.156      P=0.754N     P=0.756N     P=0.308      | 
|POLY 6             |     P=0.102N     P=0.451      P=0.537N     P=0.238N    |P=0.149      P=0.748N     P=0.751N     P=0.302      | 
|LOGISTIC REGRESSION|     P=0.103N     P=0.432      P=0.511N     P=0.235N    |P=0.143      P=0.724N     P=0.749N     P=0.315      | 
|COCH-ARM / FISHERS |     P=0.110N     P=0.500      P=0.508N     P=0.253N    |P=0.159      P=0.747N     P=0.747N     P=0.316      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    0/49 (0%)    1/49 (2%)   |1/49 (2%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.09      2/39.62      0/38.75      1/42.20     |1/44.01      0/45.74      1/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     4.9%         5.1%         0.0%         2.4%        |2.3%         0.0%         2.2%         0.0%         | 
|TERMINAL (d)       |     1/30 (3%)    0/21 (0%)    0/21 (0%)    0/29 (0%)   |1/33 (3%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     679          690          ---          449         |730 (T)      ---          730 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.363N     P=0.590      P=0.304N     P=0.500N    |P=0.468N     P=0.467N     P=0.749N     P=0.494N     | 
|POLY 3             |     P=0.378N     P=0.682      P=0.250N     P=0.491N    |P=0.464N     P=0.492N     P=0.754N     P=0.500N     | 
|POLY 1.5           |     P=0.384N     P=0.694      P=0.242N     P=0.492N    |P=0.461N     P=0.494N     P=0.756N     P=0.499N     | 
|POLY 6             |     P=0.372N     P=0.658      P=0.264N     P=0.493N    |P=0.469N     P=0.489N     P=0.751N     P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.400N     P=0.666      P=0.255N     P=0.540N    |P=0.468N     (e)          P=0.749N     (e)          | 
|COCH-ARM / FISHERS |     P=0.393N     P=0.691N     P=0.253N     P=0.508N    |P=0.457N     P=0.495N     P=0.747N     P=0.495N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 42      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/49 (0%)    0/49 (0%)   |2/49 (4%)    1/50 (2%)    4/50 (8%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     0/40.89      2/40.01      0/38.75      0/41.44     |2/44.01      1/45.74      4/45.30      3/44.64      | 
|POLY-3 PERCENT (g) |     0.0%         5.0%         0.0%         0.0%        |4.5%         2.2%         8.8%         6.7%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/29 (0%)   |2/33 (6%)    1/39 (3%)    4/35 (11%)   2/34 (6%)    | 
|FIRST INCIDENCE    |     ---          610          ---          ---         |730 (T)      730 (T)      730 (T)      529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.367N     P=0.217      (e)          (e)         |P=0.320      P=0.442N     P=0.363      P=0.515      | 
|POLY 3             |     P=0.382N     P=0.232      (e)          (e)         |P=0.336      P=0.487N     P=0.350      P=0.506      | 
|POLY 1.5           |     P=0.379N     P=0.239      (e)          (e)         |P=0.340      P=0.490N     P=0.347      P=0.507      | 
|POLY 6             |     P=0.391N     P=0.220      (e)          (e)         |P=0.329      P=0.481N     P=0.357      P=0.506      | 
|LOGISTIC REGRESSION|     P=0.391N     P=0.235      (e)          (e)         |P=0.333      P=0.442N     P=0.363      P=0.514      | 
|COCH-ARM / FISHERS |     P=0.386N     P=0.247      (e)          (e)         |P=0.345      P=0.492N     P=0.349      P=0.510      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin: Epidermis                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    0/49 (0%)    0/49 (0%)   |4/49 (8%)    2/50 (4%)    5/50 (10%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     1/40.89      3/39.62      0/38.75      0/41.44     |4/44.01      2/45.74      5/45.30      5/44.64      | 
|POLY-3 PERCENT (g) |     2.5%         7.6%         0.0%         0.0%        |9.1%         4.4%         11.0%        11.2%        | 
|TERMINAL (d)       |     1/30 (3%)    1/21 (5%)    0/21 (0%)    0/29 (0%)   |4/33 (12%)   2/39 (5%)    5/35 (14%)   4/34 (12%)   | 
|FIRST INCIDENCE    |     729 (T)      690          ---          ---         |730 (T)      730 (T)      730 (T)      529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.149N     P=0.202      P=0.571N     P=0.507N    |P=0.276      P=0.262N     P=0.537      P=0.520      | 
|POLY 3             |     P=0.154N     P=0.293      P=0.511N     P=0.497N    |P=0.298      P=0.319N     P=0.518      P=0.509      | 
|POLY 1.5           |     P=0.153N     P=0.306      P=0.504N     P=0.497N    |P=0.303      P=0.324N     P=0.513      P=0.510      | 
|POLY 6             |     P=0.157N     P=0.271      P=0.522N     P=0.499N    |P=0.290      P=0.311N     P=0.527      P=0.508      | 
|LOGISTIC REGRESSION|     P=0.150N     P=0.242      (e)          (e)         |P=0.283      P=0.262N     P=0.537      P=0.503      | 
|COCH-ARM / FISHERS |     P=0.160N     P=0.309      P=0.505N     P=0.505N    |P=0.308      P=0.329N     P=0.513      P=0.513      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 43      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   9/50 (18%)   3/50 (6%)    3/50 (6%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     8/40.89      9/40.67      3/39.98      3/43.03     |0/44.24      0/45.74      0/45.30      2/44.45      | 
|POLY-3 PERCENT (g) |     19.6%        22.1%        7.5%         7.0%        |0.0%         0.0%         0.0%         4.5%         | 
|TERMINAL (d)       |     8/30 (27%)   5/21 (24%)   1/21 (5%)    2/30 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      610          603          539         |---          ---          ---          603          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.032N*    P=0.253      P=0.226N     P=0.095N    |P=0.039 *    (e)          (e)          P=0.241      | 
|POLY 3             |     P=0.032N*    P=0.495      P=0.102N     P=0.081N    |P=0.040 *    (e)          (e)          P=0.238      | 
|POLY 1.5           |     P=0.036N*    P=0.514      P=0.095N     P=0.084N    |P=0.041 *    (e)          (e)          P=0.238      | 
|POLY 6             |     P=0.029N*    P=0.458      P=0.117N     P=0.079N    |P=0.040 *    (e)          (e)          P=0.238      | 
|LOGISTIC REGRESSION|     P=0.036N*    P=0.408      P=0.143N     P=0.089N    |P=0.043 *    (e)          (e)          P=0.240      | 
|COCH-ARM / FISHERS |     P=0.045N*    P=0.500      P=0.100N     P=0.100N    |P=0.042 *    (e)          (e)          P=0.247      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    5/50 (10%)   4/50 (8%)    8/50 (16%)  |27/50 (54%)  24/50 (48%)  31/50 (62%)  40/50 (80%)  | 
|POLY-3 RATE (b)    |     3/43.19      5/40.68      4/40.74      8/43.30     |27/47.19     24/47.08     31/47.89     40/48.43     | 
|POLY-3 PERCENT (g) |     7.0%         12.3%        9.8%         18.5%       |57.2%        51.0%        64.7%        82.6%        | 
|TERMINAL (d)       |     0/30 (0%)    2/21 (10%)   0/21 (0%)    5/30 (17%)  |18/33 (55%)  21/39 (54%)  23/35 (66%)  29/34 (85%)  | 
|FIRST INCIDENCE    |     122          464          603          617         |497          396          232          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.128      P=0.299      P=0.484      P=0.116     |P<0.001 **   P=0.157N     P=0.406      P=0.026 *    | 
|POLY 3             |     P=0.082      P=0.323      P=0.468      P=0.097     |P<0.001 **   P=0.342N     P=0.291      P=0.004 **   | 
|POLY 1.5           |     P=0.080      P=0.343      P=0.486      P=0.100     |P<0.001 **   P=0.340N     P=0.285      P=0.004 **   | 
|POLY 6             |     P=0.084      P=0.290      P=0.441      P=0.094     |P<0.001 **   P=0.354N     P=0.296      P=0.004 **   | 
|LOGISTIC REGRESSION|     P=0.054      P=0.221      P=0.364      P=0.064     |P<0.001 **   P=0.327N     P=0.274      P=0.005 **   | 
|COCH-ARM / FISHERS |     P=0.078      P=0.357      P=0.500      P=0.100     |P<0.001 **   P=0.345N     P=0.272      P=0.005 **   | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 44      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/41.06      1/39.60      2/40.41      1/42.51     |1/44.41      1/46.19      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     2.4%         2.5%         5.0%         2.4%        |2.3%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     686          690          373          711         |686          600          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.597N     P=0.705      P=0.451      P=0.757N    |P=0.313N     P=0.747N     P=0.495N     P=0.505N     | 
|POLY 3             |     P=0.620N     P=0.753      P=0.494      P=0.753N    |P=0.309N     P=0.752N     P=0.496N     P=0.502N     | 
|POLY 1.5           |     P=0.626N     P=0.761      P=0.504      P=0.753N    |P=0.308N     P=0.756N     P=0.498N     P=0.501N     | 
|POLY 6             |     P=0.614N     P=0.738      P=0.475      P=0.756N    |P=0.311N     P=0.747N     P=0.493N     P=0.503N     | 
|LOGISTIC REGRESSION|     P=0.644      P=0.759      P=0.462      P=0.756N    |P=0.297N     P=0.749      P=0.500N     P=0.499N     | 
|COCH-ARM / FISHERS |     P=0.639N     P=0.753N     P=0.500      P=0.753N    |P=0.306N     P=0.753N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    4/50 (8%)    4/50 (8%)   |30/50 (60%)  30/50 (60%)  35/50 (70%)  43/50 (86%)  | 
|POLY-3 RATE (b)    |     1/40.89      2/40.19      4/40.66      4/43.17     |30/46.81     30/46.75     35/46.35     43/47.35     | 
|POLY-3 PERCENT (g) |     2.5%         5.0%         9.8%         9.3%        |64.1%        64.2%        75.5%        90.8%        | 
|TERMINAL (d)       |     1/30 (3%)    1/21 (5%)    1/21 (5%)    2/30 (7%)   |23/33 (70%)  26/39 (67%)  29/35 (83%)  33/34 (97%)  | 
|FIRST INCIDENCE    |     729 (T)      462          483          607         |497          572          648          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.212      P=0.427      P=0.135      P=0.189     |P<0.001 **   P=0.254N     P=0.341      P=0.014 *    | 
|POLY 3             |     P=0.184      P=0.494      P=0.176      P=0.195     |P<0.001 **   P=0.584      P=0.155      P<0.001 **   | 
|POLY 1.5           |     P=0.176      P=0.504      P=0.182      P=0.192     |P<0.001 **   P=0.580      P=0.165      P<0.001 **   | 
|POLY 6             |     P=0.195      P=0.474      P=0.162      P=0.196     |P<0.001 **   P=0.586N     P=0.150      P<0.001 **   | 
|LOGISTIC REGRESSION|     P=0.147      P=0.492      P=0.178      P=0.186     |P<0.001 **   P=0.510N     P=0.243      P=0.002 **   | 
|COCH-ARM / FISHERS |     P=0.159      P=0.500      P=0.181      P=0.181     |P<0.001 **   P=0.581N     P=0.201      P=0.003 **   | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 45      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Edema                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    2/49 (4%)    5/48 (10%)  |1/49 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     4/42.59      3/40.07      2/39.67      5/41.61     |1/44.37      1/46.05      1/46.27      0/44.02      | 
|POLY-3 PERCENT (g) |     9.4%         7.5%         5.0%         12.0%       |2.3%         2.2%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/20 (0%)    1/29 (3%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     284          638          368          597         |630          646          232          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.386      P=0.572N     P=0.366N     P=0.516     |P=0.331N     P=0.755N     P=0.758N     P=0.514N     | 
|POLY 3             |     P=0.331      P=0.533N     P=0.370N     P=0.485     |P=0.330N     P=0.752N     P=0.751N     P=0.502N     | 
|POLY 1.5           |     P=0.322      P=0.510N     P=0.352N     P=0.487     |P=0.327N     P=0.754N     P=0.753N     P=0.499N     | 
|POLY 6             |     P=0.344      P=0.571N     P=0.403N     P=0.480     |P=0.335N     P=0.749N     P=0.749N     P=0.505N     | 
|LOGISTIC REGRESSION|     P=0.254      P=0.540N     P=0.432N     P=0.424     |P=0.236N     P=0.753N     P=0.591N     P=0.460N     | 
|COCH-ARM / FISHERS |     P=0.307      P=0.500N     P=0.349N     P=0.474     |P=0.321N     P=0.747N     P=0.747N     P=0.495N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   2/50 (4%)    4/49 (8%)    4/48 (8%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     6/43.28      2/39.97      4/39.48      4/41.49     |0/44.01      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     13.9%        5.0%         10.1%        9.6%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/20 (0%)    0/29 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     284          638          603          597         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.473N     P=0.190N     P=0.439N     P=0.362N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.525N     P=0.158N     P=0.428N     P=0.396N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.539N     P=0.142N     P=0.400N     P=0.390N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.506N     P=0.188N     P=0.472N     P=0.406N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.583      P=0.159N     P=0.409N     P=0.455N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.557N     P=0.134N     P=0.383N     P=0.397N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 46      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   4/50 (8%)    7/49 (14%)   5/48 (10%)  |1/49 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     5/42.17      4/40.84      7/40.77      5/41.00     |1/44.70      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     11.9%        9.8%         17.2%        12.2%       |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/30 (3%)    1/21 (5%)    0/20 (0%)    2/29 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     528          464          550          634         |497          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.549N     P=0.594N     P=0.312      P=0.623N    |P=0.472N     P=0.500N     P=0.500N     P=0.500N     | 
|POLY 3             |     P=0.526      P=0.520N     P=0.354      P=0.613     |P=0.470N     P=0.495N     P=0.497N     P=0.503N     | 
|POLY 1.5           |     P=0.520      P=0.499N     P=0.370      P=0.618     |P=0.470N     P=0.496N     P=0.498N     P=0.500N     | 
|POLY 6             |     P=0.533      P=0.560N     P=0.327      P=0.602     |P=0.471N     P=0.493N     P=0.496N     P=0.506N     | 
|LOGISTIC REGRESSION|     P=0.483      P=0.517N     P=0.357      P=0.613     |P=0.431N     P=0.353N     P=0.346N     P=0.316N     | 
|COCH-ARM / FISHERS |     P=0.502      P=0.500N     P=0.365      P=0.603     |P=0.470N     P=0.495N     P=0.495N     P=0.495N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Edema                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    0/49 (0%)    0/48 (0%)   |0/49 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/41.01      3/39.79      0/38.45      0/40.55     |0/44.01      0/45.74      1/46.27      0/44.02      | 
|POLY-3 PERCENT (g) |     2.4%         7.5%         0.0%         0.0%        |0.0%         0.0%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    0/20 (0%)    0/29 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     700          679          ---          ---         |---          ---          232          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.151N     P=0.222      P=0.546N     P=0.500N    |P=0.784N     (e)          P=0.500      (e)          | 
|POLY 3             |     P=0.157N     P=0.294      P=0.513N     P=0.502N    |P=0.787N     (e)          P=0.510      (e)          | 
|POLY 1.5           |     P=0.157N     P=0.306      P=0.505N     P=0.502N    |P=0.785N     (e)          P=0.507      (e)          | 
|POLY 6             |     P=0.160N     P=0.272      P=0.527N     P=0.505N    |P=0.790N     (e)          P=0.513      (e)          | 
|LOGISTIC REGRESSION|     P=0.156N     P=0.284      P=0.517N     P=0.503N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.163N     P=0.309      P=0.505N     P=0.510N    |P=0.783N     (e)          P=0.505      (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 47      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Erosion                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    3/49 (6%)    1/48 (2%)   |0/49 (0%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/41.72      2/39.86      3/39.11      1/40.97     |0/44.01      1/46.12      1/45.32      1/44.29      | 
|POLY-3 PERCENT (g) |     2.4%         5.0%         7.7%         2.4%        |0.0%         2.2%         2.2%         2.3%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/20 (0%)    0/29 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     406          630          603          607         |---          624          725          657          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.476N     P=0.478      P=0.274      P=0.747N    |P=0.469      P=0.504      P=0.511      P=0.505      | 
|POLY 3             |     P=0.510N     P=0.484      P=0.282      P=0.757     |P=0.480      P=0.509      P=0.506      P=0.501      | 
|POLY 1.5           |     P=0.514N     P=0.497      P=0.294      P=0.757     |P=0.482      P=0.507      P=0.504      P=0.502      | 
|POLY 6             |     P=0.505N     P=0.463      P=0.262      P=0.756     |P=0.477      P=0.514      P=0.509      P=0.501      | 
|LOGISTIC REGRESSION|     P=0.563N     P=0.445      P=0.270      P=0.680     |P=0.500      P=0.521      P=0.511      P=0.522      | 
|COCH-ARM / FISHERS |     P=0.528N     P=0.500      P=0.301      P=0.742     |P=0.487      P=0.505      P=0.505      P=0.505      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    1/49 (2%)    1/48 (2%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.03      3/39.86      1/38.75      1/40.66     |0/44.01      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     4.9%         7.5%         2.6%         2.5%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/20 (0%)    0/29 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     700          636          645          702         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.274N     P=0.385      P=0.579N     P=0.500N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.302N     P=0.487      P=0.520N     P=0.503N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.306N     P=0.502      P=0.508N     P=0.503N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.299N     P=0.460      P=0.541N     P=0.507N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.301N     P=0.474      P=0.517N     P=0.505N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.316N     P=0.500      P=0.508N     P=0.515N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 48      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   12/50 (24%)  3/50 (6%)    8/50 (16%)  |                                                    | 
|POLY-3 RATE (b)    |     7/43.00      12/43.46     3/39.90      8/43.03     |                                                    | 
|POLY-3 PERCENT (g) |     16.3%        27.6%        7.5%         18.6%       |                                                    | 
|TERMINAL (d)       |     2/30 (7%)    3/21 (14%)   1/21 (5%)    7/30 (23%)  |                                                    | 
|FIRST INCIDENCE    |     406          462          603          539         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.384N     P=0.109      P=0.252N     P=0.514     |                                                    | 
|POLY 3             |     P=0.463N     P=0.154      P=0.187N     P=0.501     |                                                    | 
|POLY 1.5           |     P=0.458N     P=0.165      P=0.167N     P=0.512     |                                                    | 
|POLY 6             |     P=0.477N     P=0.132      P=0.224N     P=0.478     |                                                    | 
|LOGISTIC REGRESSION|     P=0.493N     P=0.130      P=0.161N     P=0.501     |                                                    | 
|COCH-ARM / FISHERS |     P=0.468N     P=0.154      P=0.159N     P=0.500     |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Interstitial Cell                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    8/50 (16%)   3/50 (6%)    5/50 (10%)  |                                                    | 
|POLY-3 RATE (b)    |     4/42.02      8/42.52      3/40.29      5/43.37     |                                                    | 
|POLY-3 PERCENT (g) |     9.5%         18.8%        7.5%         11.5%       |                                                    | 
|TERMINAL (d)       |     2/30 (7%)    2/21 (10%)   0/21 (0%)    2/30 (7%)   |                                                    | 
|FIRST INCIDENCE    |     472          464          603          602         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.435N     P=0.139      P=0.569N     P=0.521     |                                                    | 
|POLY 3             |     P=0.477N     P=0.180      P=0.523N     P=0.520     |                                                    | 
|POLY 1.5           |     P=0.482N     P=0.189      P=0.504N     P=0.520     |                                                    | 
|POLY 6             |     P=0.473N     P=0.161      P=0.555N     P=0.517     |                                                    | 
|LOGISTIC REGRESSION|     P=0.547N     P=0.146      P=0.507N     P=0.488     |                                                    | 
|COCH-ARM / FISHERS |     P=0.501N     P=0.178      P=0.500N     P=0.500     |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 49      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: C-Cell                                                                                                            | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   2/50 (4%)    7/50 (14%)   4/50 (8%)   |21/49 (43%)  9/50 (18%)   11/50 (22%)  12/50 (24%)  | 
|POLY-3 RATE (b)    |     7/42.02      2/39.69      7/40.17      4/42.54     |21/44.65     9/46.26      11/45.40     12/45.09     | 
|POLY-3 PERCENT (g) |     16.7%        5.0%         17.4%        9.4%        |47.0%        19.5%        24.2%        26.6%        | 
|TERMINAL (d)       |     5/30 (17%)   1/21 (5%)    5/21 (24%)   3/30 (10%)  |17/33 (52%)  8/39 (21%)   9/35 (26%)   9/34 (27%)   | 
|FIRST INCIDENCE    |     472          665          609          702         |610          572          711          590          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.334N     P=0.157N     P=0.411      P=0.258N    |P=0.229N     P=0.002N**   P=0.018N*    P=0.042N*    | 
|POLY 3             |     P=0.379N     P=0.091N     P=0.580      P=0.252N    |P=0.184N     P=0.004N**   P=0.018N*    P=0.033N*    | 
|POLY 1.5           |     P=0.395N     P=0.081N     P=0.607      P=0.248N    |P=0.180N     P=0.004N**   P=0.020N*    P=0.035N*    | 
|POLY 6             |     P=0.358N     P=0.111N     P=0.532      P=0.261N    |P=0.190N     P=0.003N**   P=0.015N*    P=0.032N*    | 
|LOGISTIC REGRESSION|     P=0.381N     P=0.082N     P=0.601      P=0.244N    |P=0.209N     P=0.004N**   P=0.014N*    P=0.042N*    | 
|COCH-ARM / FISHERS |     P=0.419N     P=0.080N     P=0.613N     P=0.262N    |P=0.178N     P=0.006N**   P=0.022N*    P=0.037N*    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicle                                                                                                          | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    1/50 (2%)    1/50 (2%)   |1/49 (2%)    1/50 (2%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/40.89      3/39.45      1/39.45      1/42.44     |1/44.01      1/45.74      2/45.30      2/44.02      | 
|POLY-3 PERCENT (g) |     2.5%         7.6%         2.5%         2.4%        |2.3%         2.2%         4.4%         4.5%         | 
|TERMINAL (d)       |     1/30 (3%)    3/21 (14%)   1/21 (5%)    1/30 (3%)   |1/33 (3%)    1/39 (3%)    2/35 (6%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |730 (T)      730 (T)      730 (T)      730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.376N     P=0.186      P=0.681      P=0.762     |P=0.366      P=0.724N     P=0.521      P=0.510      | 
|POLY 3             |     P=0.415N     P=0.292      P=0.753      P=0.753N    |P=0.376      P=0.752N     P=0.510      P=0.500      | 
|POLY 1.5           |     P=0.418N     P=0.305      P=0.760      P=0.753N    |P=0.382      P=0.754N     P=0.507      P=0.503      | 
|POLY 6             |     P=0.416N     P=0.268      P=0.739      P=0.755N    |P=0.369      P=0.748N     P=0.515      P=0.497      | 
|LOGISTIC REGRESSION|     P=0.376N     P=0.186      P=0.681      P=0.762     |P=0.366      P=0.724N     P=0.521      P=0.510      | 
|COCH-ARM / FISHERS |     P=0.430N     P=0.309      P=0.753N     P=0.753N    |P=0.388      P=0.747N     P=0.508      P=0.508      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 50      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hydrometra                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |5/49 (10%)   3/50 (6%)    5/50 (10%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |                                                        |5/44.18      3/46.05      5/45.32      6/44.29      | 
|POLY-3 PERCENT (g) |                                                        |11.3%        6.5%         11.0%        13.6%        | 
|TERMINAL (d)       |                                                        |4/33 (12%)   2/39 (5%)    4/35 (11%)   4/34 (12%)   | 
|FIRST INCIDENCE    |                                                        |685          646          725          674          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.280      P=0.286N     P=0.596N     P=0.510      | 
|POLY 3             |                                                        |P=0.297      P=0.334N     P=0.614N     P=0.502      | 
|POLY 1.5           |                                                        |P=0.305      P=0.340N     P=0.618N     P=0.506      | 
|POLY 6             |                                                        |P=0.285      P=0.324N     P=0.608N     P=0.497      | 
|LOGISTIC REGRESSION|                                                        |P=0.285      P=0.334N     P=0.597N     P=0.492      | 
|COCH-ARM / FISHERS |                                                        |P=0.316      P=0.346N     P=0.617N     P=0.514      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/49 (2%)    5/50 (10%)   4/50 (8%)    7/50 (14%)   | 
|POLY-3 RATE (b)    |                                                        |1/44.37      5/45.74      4/45.32      7/44.94      | 
|POLY-3 PERCENT (g) |                                                        |2.3%         10.9%        8.8%         15.6%        | 
|TERMINAL (d)       |                                                        |0/33 (0%)    5/39 (13%)   3/35 (9%)    5/34 (15%)   | 
|FIRST INCIDENCE    |                                                        |630          730 (T)      725          590          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.049 *    P=0.139      P=0.199      P=0.038 *    | 
|POLY 3             |                                                        |P=0.055      P=0.108      P=0.185      P=0.031 *    | 
|POLY 1.5           |                                                        |P=0.057      P=0.107      P=0.184      P=0.032 *    | 
|POLY 6             |                                                        |P=0.054      P=0.110      P=0.187      P=0.030 *    | 
|LOGISTIC REGRESSION|                                                        |P=0.055      P=0.112      P=0.186      P=0.037 *    | 
|COCH-ARM / FISHERS |                                                        |P=0.059      P=0.107      P=0.187      P=0.032 *    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 51      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                       EMODIN      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/49 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |                                                        |1/44.37      0/45.74      1/45.30      2/44.02      | 
|POLY-3 PERCENT (g) |                                                        |2.3%         0.0%         2.2%         4.5%         | 
|TERMINAL (d)       |                                                        |0/33 (0%)    0/39 (0%)    1/35 (3%)    2/34 (6%)    | 
|FIRST INCIDENCE    |                                                        |630          ---          730 (T)      730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.221      P=0.500N     P=0.751N     P=0.499      | 
|POLY 3             |                                                        |P=0.229      P=0.494N     P=0.756N     P=0.497      | 
|POLY 1.5           |                                                        |P=0.234      P=0.495N     P=0.757N     P=0.501      | 
|POLY 6             |                                                        |P=0.223      P=0.492N     P=0.754N     P=0.492      | 
|LOGISTIC REGRESSION|                                                        |P=0.235      P=0.482N     P=0.754N     P=0.507      | 
|COCH-ARM / FISHERS |                                                        |P=0.238      P=0.495N     P=0.747N     P=0.508      | 
|=================================================================================================================================| 
(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).