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TDMS Study 05211-05 Pathology Tables


NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                      EMODIN                                        DATE: 01/25/01       
EXPERIMENT: 05211 TEST: 05                                                                                     TIME: 12:58:05       
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 PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                      EMODIN                                        DATE: 01/25/01       
EXPERIMENT: 05211 TEST: 05                                                                                     TIME: 12:58:05       
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        
Rats(FISCHER 344)                                                                                                                   
-----------------------------                                                                                                       
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE                                                                   
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES                                                                 
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.                                                                                      
                                                 ---------------                                                                    
                                                 Adrenal Cortex                                                                     
                                                 Adrenal Medulla                                                                    
                                                 Brain                                                                              
                                                 Clitoral/Preputial Gland                                                           
                                                 Islets, Pancreatic                                                                 
                                                 Kidney                                                                             
                                                 Liver                                                                              
                                                 Lung                                                                               
                                                 Nose                                                                               
                                                 Ovary                                                                              
                                                 Pancreas                                                                           
                                                 Parathyroid Gland                                                                  
                                                 Pituitary Gland                                                                    
                                                 Prostate                                                                           
                                                 Salivary Glands                                                                    
                                                 Spleen                                                                             
                                                 Testes                                                                             
                                                 Thymus                                                                             
                                                 Thyroid Gland                                                                      
                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                      EMODIN                                        DATE: 01/25/01       
EXPERIMENT: 05211 TEST: 05                                                                                     TIME: 12:58:05       
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 Medulla                        Pheochromocytoma Benign                                                                      
Islets, Pancreatic                     Carcinoma or Adenoma                                                                         
Mesentery                              Sarcoma                                                                                      
Nose                                   Squamous Cell Carcinoma                                                                      
Testes                                 Adenoma                                                                                      
All Organs                             Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                           
                                       Benign Tumors                                                                                
                                       Malignant Tumors                                                                             
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Mammary Gland                          Carcinoma                                                                                    
Pituitary Gland: Pars Distalis or Unspecified Site                                                                                  
                                       Adenoma                                                                                      
Zymbal's Gland                         Carcinoma                                                                                    
All Organs                             Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                           
                                       Malignant Tumors                                                                             
===============================================================                                                                     
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 1       
                     Statistical Analysis of Primary Tumors 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 Medulla                                                                                                                  | 
|     Pheochromocytoma Benign                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   13/49 (27%)  6/50 (12%)   9/50 (18%)  |1/47 (2%)    0/50 (0%)    4/50 (8%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     7/41.06      13/40.68     6/40.39      9/43.31     |1/42.90      0/45.74      4/45.55      1/44.02      | 
|POLY-3 PERCENT (g) |     17.1%        32.0%        14.9%        20.8%       |2.3%         0.0%         8.8%         2.3%         | 
|TERMINAL (d)       |     6/30 (20%)   2/20 (10%)   2/21 (10%)   7/30 (23%)  |0/33 (0%)    0/39 (0%)    3/35 (9%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     686          511          638          539         |704          ---          665          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.407N     P=0.036 *    P=0.519      P=0.397     |P=0.556      P=0.479N     P=0.205      P=0.760N     | 
|POLY 3             |     P=0.465N     P=0.091      P=0.513N     P=0.437     |P=0.564      P=0.487N     P=0.197      P=0.755N     | 
|POLY 1.5           |     P=0.479N     P=0.100      P=0.495N     P=0.430     |P=0.573      P=0.488N     P=0.196      P=0.752N     | 
|POLY 6             |     P=0.453N     P=0.077      P=0.547N     P=0.437     |P=0.551      P=0.486N     P=0.200      P=0.759N     | 
|LOGISTIC REGRESSION|     P=0.465N     P=0.075      P=0.563N     P=0.419     |P=0.572      P=0.488N     P=0.197      P=0.759N     | 
|COCH-ARM / FISHERS |     P=0.520N     P=0.096      P=0.500N     P=0.393     |P=0.587      P=0.485N     P=0.201      P=0.737N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   13/49 (27%)  7/50 (14%)   10/50 (20%) |2/47 (4%)    0/50 (0%)    4/50 (8%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     8/41.37      13/40.68     7/40.39      10/43.31    |2/43.53      0/45.74      4/45.55      2/44.02      | 
|POLY-3 PERCENT (g) |     19.3%        32.0%        17.3%        23.1%       |4.6%         0.0%         8.8%         4.5%         | 
|TERMINAL (d)       |     6/30 (20%)   2/20 (10%)   3/21 (14%)   8/30 (27%)  |0/33 (0%)    0/39 (0%)    3/35 (9%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     646          511          638          539         |527          ---          665          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.440N     P=0.062      P=0.489      P=0.403     |P=0.444      P=0.226N     P=0.369      P=0.688N     | 
|POLY 3             |     P=0.514N     P=0.142      P=0.520N     P=0.438     |P=0.450      P=0.226N     P=0.358      P=0.690N     | 
|POLY 1.5           |     P=0.527N     P=0.156      P=0.497N     P=0.434     |P=0.461      P=0.226N     P=0.359      P=0.683N     | 
|POLY 6             |     P=0.506N     P=0.120      P=0.563N     P=0.433     |P=0.435      P=0.225N     P=0.360      P=0.690      | 
|LOGISTIC REGRESSION|     P=0.506N     P=0.127      P=0.558N     P=0.427     |P=0.484      P=0.165N     P=0.383      P=0.644N     | 
|COCH-ARM / FISHERS |     P=0.559      P=0.150      P=0.500N     P=0.398     |P=0.477      P=0.232N     P=0.369      P=0.668N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 2       
                     Statistical Analysis of Primary Tumors 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                                                                                                                            | 
|     Astrocytoma Malignant                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/40.89      1/40.19      0/39.45      0/42.44     |0/44.01      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     4.9%         2.5%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/30 (7%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      464          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.162N     P=0.575N     P=0.319N     P=0.238N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.164N     P=0.506N     P=0.245N     P=0.229N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.167N     P=0.496N     P=0.238N     P=0.229N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.158N     P=0.526N     P=0.259N     P=0.230N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.176N     P=0.508N     (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.170N     P=0.500N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/40.89      2/40.60      0/39.45      0/42.44     |0/44.01      0/45.74      1/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     4.9%         4.9%         0.0%         0.0%        |0.0%         0.0%         2.2%         0.0%         | 
|TERMINAL (d)       |     2/30 (7%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      464          ---          ---         |---          ---          730 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.119N     P=0.637      P=0.319N     P=0.238N    |P=0.792N     (e)          P=0.512      (e)          | 
|POLY 3             |     P=0.119N     P=0.692      P=0.245N     P=0.229N    |P=0.787N     (e)          P=0.506      (e)          | 
|POLY 1.5           |     P=0.121N     P=0.688N     P=0.238N     P=0.229N    |P=0.785N     (e)          P=0.504      (e)          | 
|POLY 6             |     P=0.116N     P=0.675      P=0.259N     P=0.230N    |P=0.790N     (e)          P=0.509      (e)          | 
|LOGISTIC REGRESSION|     P=0.132N     P=0.684      (e)          (e)         |(e)          (e)          P=0.512      (e)          | 
|COCH-ARM / FISHERS |     P=0.124N     P=0.691N     P=0.247N     P=0.247N    |P=0.783N     (e)          P=0.505      (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 3       
                     Statistical Analysis of Primary Tumors 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/Preputial Gland                                                                                                         | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   1/50 (2%)    2/50 (4%)    3/50 (6%)   |10/49 (20%)  12/50 (24%)  8/49 (16%)   10/49 (20%)  | 
|POLY-3 RATE (b)    |     5/42.26      1/39.45      2/40.26      3/42.44     |10/45.28     12/46.07     8/44.55      10/44.11     | 
|POLY-3 PERCENT (g) |     11.8%        2.5%         5.0%         7.1%        |22.1%        26.1%        18.0%        22.7%        | 
|TERMINAL (d)       |     2/30 (7%)    1/21 (5%)    0/21 (0%)    3/30 (10%)  |8/33 (24%)   10/39 (26%)  7/34 (21%)   8/33 (24%)   | 
|FIRST INCIDENCE    |     472          729 (T)      483          729 (T)     |497          656          665          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.482N     P=0.167N     P=0.296N     P=0.355N    |P=0.548N     P=0.559      P=0.369N     P=0.593N     | 
|POLY 3             |     P=0.517N     P=0.117N     P=0.235N     P=0.353N    |P=0.517N     P=0.422      P=0.411N     P=0.574      | 
|POLY 1.5           |     P=0.530N     P=0.105N     P=0.220N     P=0.348N    |P=0.506N     P=0.420      P=0.411N     P=0.582      | 
|POLY 6             |     P=0.498N     P=0.138N     P=0.262N     P=0.365N    |P=0.531N     P=0.432      P=0.406N     P=0.566      | 
|LOGISTIC REGRESSION|     P=0.549N     P=0.104N     P=0.229N     P=0.354N    |P=0.510N     P=0.432      P=0.398N     P=0.592N     | 
|COCH-ARM / FISHERS |     P=0.544N     P=0.102N     P=0.218N     P=0.357N    |P=0.490N     P=0.426      P=0.397N     P=0.599N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral/Preputial Gland                                                                                                         | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    2/50 (4%)    1/50 (2%)    3/50 (6%)   |2/49 (4%)    3/50 (6%)    2/49 (4%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     3/41.36      2/39.60      1/39.45      3/43.22     |2/44.11      3/46.09      2/44.55      0/43.02      | 
|POLY-3 PERCENT (g) |     7.3%         5.1%         2.5%         6.9%        |4.5%         6.5%         4.5%         0.0%         | 
|TERMINAL (d)       |     2/30 (7%)    0/21 (0%)    1/21 (5%)    1/30 (3%)   |1/33 (3%)    2/39 (5%)    1/34 (3%)    0/33 (0%)    | 
|FIRST INCIDENCE    |     590          704          729 (T)      617         |704          634          665          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.564      P=0.617N     P=0.407N     P=0.649N    |P=0.131N     P=0.556      P=0.674N     P=0.246N     | 
|POLY 3             |     P=0.541      P=0.520N     P=0.322N     P=0.642N    |P=0.127N     P=0.520      P=0.690N     P=0.243N     | 
|POLY 1.5           |     P=0.528      P=0.502N     P=0.308N     P=0.644N    |P=0.124N     P=0.514      P=0.694N     P=0.241N     | 
|POLY 6             |     P=0.558      P=0.551N     P=0.347N     P=0.643N    |P=0.131N     P=0.529      P=0.685N     P=0.245N     | 
|LOGISTIC REGRESSION|     P=0.525      P=0.515N     P=0.316N     P=0.663     |P=0.121N     P=0.511      P=0.695N     P=0.244N     | 
|COCH-ARM / FISHERS |     P=0.509      P=0.500N     P=0.309N     P=0.661N    |P=0.120N     P=0.510      P=0.691N     P=0.247N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 4       
                     Statistical Analysis of Primary Tumors 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/Preputial Gland                                                                                                         | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   3/50 (6%)    3/50 (6%)    5/50 (10%)  |12/49 (24%)  15/50 (30%)  9/49 (18%)   10/49 (20%)  | 
|POLY-3 RATE (b)    |     8/42.73      3/39.60      3/40.26      5/43.22     |12/45.38     15/46.42     9/44.55      10/44.11     | 
|POLY-3 PERCENT (g) |     18.7%        7.6%         7.5%         11.6%       |26.4%        32.3%        20.2%        22.7%        | 
|TERMINAL (d)       |     4/30 (13%)   1/21 (5%)    1/21 (5%)    3/30 (10%)  |9/33 (27%)   12/39 (31%)  8/34 (24%)   8/33 (24%)   | 
|FIRST INCIDENCE    |     472          704          483          617         |497          634          665          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.379N     P=0.204N     P=0.187N     P=0.274N    |P=0.305N     P=0.494      P=0.285N     P=0.404N     | 
|POLY 3             |     P=0.411N     P=0.121N     P=0.115N     P=0.266N    |P=0.275N     P=0.349      P=0.326N     P=0.433N     | 
|POLY 1.5           |     P=0.429N     P=0.105N     P=0.102N     P=0.262N    |P=0.265N     P=0.345      P=0.326N     P=0.423N     | 
|POLY 6             |     P=0.385N     P=0.152N     P=0.141N     P=0.274N    |P=0.289N     P=0.363      P=0.323N     P=0.445N     | 
|LOGISTIC REGRESSION|     P=0.449N     P=0.100N     P=0.102N     P=0.279N    |P=0.268N     P=0.355      P=0.311N     P=0.401N     | 
|COCH-ARM / FISHERS |     P=0.452N     P=0.100N     P=0.100N     P=0.277N    |P=0.251N     P=0.349      P=0.312N     P=0.405N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    5/50 (10%)   1/49 (2%)    1/50 (2%)   |1/49 (2%)    1/50 (2%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/40.89      5/39.80      1/38.45      1/42.44     |1/44.01      1/45.74      1/44.58      0/44.02      | 
|POLY-3 PERCENT (g) |     4.9%         12.6%        2.6%         2.4%        |2.3%         2.2%         2.2%         0.0%         | 
|TERMINAL (d)       |     2/30 (7%)    4/21 (19%)   1/20 (5%)    1/30 (3%)   |1/33 (3%)    1/39 (3%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      630          729 (T)      729 (T)     |730 (T)      730 (T)      711          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.152N     P=0.110      P=0.641N     P=0.500N    |P=0.334N     P=0.724N     P=0.745N     P=0.494N     | 
|POLY 3             |     P=0.170N     P=0.203      P=0.522N     P=0.487N    |P=0.328N     P=0.752N     P=0.758N     P=0.500N     | 
|POLY 1.5           |     P=0.172N     P=0.217      P=0.509N     P=0.488N    |P=0.326N     P=0.754N     P=0.760N     P=0.499N     | 
|POLY 6             |     P=0.169N     P=0.180      P=0.545N     P=0.490N    |P=0.332N     P=0.748N     P=0.754N     P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.160N     P=0.158      P=0.641N     P=0.500N    |P=0.333N     P=0.724N     P=0.756N     (e)          | 
|COCH-ARM / FISHERS |     P=0.184N     P=0.218      P=0.508N     P=0.500N    |P=0.321N     P=0.747N     P=0.753N     P=0.495N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 5       
                     Statistical Analysis of Primary Tumors 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                                                                                                               | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    1/49 (2%)    0/50 (0%)   |0/49 (0%)    1/50 (2%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/40.89      1/39.50      1/38.86      0/42.44     |0/44.01      1/45.74      1/44.53      0/44.02      | 
|POLY-3 PERCENT (g) |     7.3%         2.5%         2.6%         0.0%        |0.0%         2.2%         2.3%         0.0%         | 
|TERMINAL (d)       |     3/30 (10%)   0/21 (0%)    0/20 (0%)    0/30 (0%)   |0/33 (0%)    1/39 (3%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      716          609          ---         |---          730 (T)      725          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.107N     P=0.434N     P=0.416N     P=0.120N    |P=0.555N     P=0.533      P=0.511      (e)          | 
|POLY 3             |     P=0.105N     P=0.317N     P=0.323N     P=0.112N    |P=0.543N     P=0.508      P=0.502      (e)          | 
|POLY 1.5           |     P=0.110N     P=0.305N     P=0.312N     P=0.112N    |P=0.541N     P=0.506      P=0.500      (e)          | 
|POLY 6             |     P=0.099N     P=0.341N     P=0.344N     P=0.112N    |P=0.545N     P=0.511      P=0.506      (e)          | 
|LOGISTIC REGRESSION|     P=0.108N     P=0.400N     P=0.332N     (e)         |P=0.555N     P=0.533      P=0.509      (e)          | 
|COCH-ARM / FISHERS |     P=0.116N     P=0.309N     P=0.316N     P=0.121N    |P=0.538N     P=0.505      P=0.500      (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   6/50 (12%)   2/49 (4%)    1/50 (2%)   |1/49 (2%)    2/50 (4%)    2/49 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     5/40.89      6/39.86      2/38.86      1/42.44     |1/44.01      2/45.74      2/44.60      0/44.02      | 
|POLY-3 PERCENT (g) |     12.2%        15.1%        5.2%         2.4%        |2.3%         4.4%         4.5%         0.0%         | 
|TERMINAL (d)       |     5/30 (17%)   4/21 (19%)   1/20 (5%)    1/30 (3%)   |1/33 (3%)    2/39 (5%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      630          609          729 (T)     |730 (T)      730 (T)      711          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.034N*    P=0.285      P=0.372N     P=0.100N    |P=0.261N     P=0.558      P=0.523      P=0.494N     | 
|POLY 3             |     P=0.036N*    P=0.482      P=0.235N     P=0.092N    |P=0.253N     P=0.513      P=0.505      P=0.500N     | 
|POLY 1.5           |     P=0.038N*    P=0.503      P=0.223N     P=0.093N    |P=0.250N     P=0.510      P=0.501      P=0.499N     | 
|POLY 6             |     P=0.034N*    P=0.441      P=0.259N     P=0.093N    |P=0.258N     P=0.519      P=0.511      P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.036N*    P=0.375      P=0.276N     P=0.100N    |P=0.259N     P=0.558      P=0.512      (e)          | 
|COCH-ARM / FISHERS |     P=0.044N*    P=0.500      P=0.226N     P=0.102N    |P=0.245N     P=0.508      P=0.500      P=0.495N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 6       
                     Statistical Analysis of Primary Tumors 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                                                                                                                            | 
|     Hepatocellular Adenoma                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    1/50 (2%)    2/50 (4%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/40.89      1/39.45      1/39.45      2/42.44     |0/44.01      0/45.74      0/45.30      1/44.02      | 
|POLY-3 PERCENT (g) |     2.5%         2.5%         2.5%         4.7%        |0.0%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/30 (3%)    1/21 (5%)    1/21 (5%)    2/30 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |---          ---          ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.420      P=0.681      P=0.681      P=0.500     |P=0.208      (e)          (e)          P=0.506      | 
|POLY 3             |     P=0.381      P=0.753      P=0.753      P=0.513     |P=0.213      (e)          (e)          P=0.500      | 
|POLY 1.5           |     P=0.375      P=0.761      P=0.760      P=0.512     |P=0.215      (e)          (e)          P=0.501      | 
|POLY 6             |     P=0.389      P=0.738      P=0.739      P=0.510     |P=0.210      (e)          (e)          P=0.498      | 
|LOGISTIC REGRESSION|     P=0.420      P=0.681      P=0.681      P=0.500     |(e)          (e)          (e)          P=0.506      | 
|COCH-ARM / FISHERS |     P=0.361      P=0.753N     P=0.753N     P=0.500     |P=0.217      (e)          (e)          P=0.505      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    3/50 (6%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      3/39.70      3/39.91      0/42.44     |0/44.01      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         7.6%         7.5%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|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    |     ---          690          605          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.266N     P=0.080      P=0.090      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.277N     P=0.113      P=0.114      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.278N     P=0.119      P=0.119      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.279N     P=0.102      P=0.104      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.281N     P=0.101      P=0.118      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.297N     P=0.121      P=0.121      (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 7       
                     Statistical Analysis of Primary Tumors 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                                                                                                                            | 
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    4/50 (8%)    4/50 (8%)    2/50 (4%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/40.89      4/39.70      4/39.91      2/42.44     |0/44.01      0/45.74      0/45.30      1/44.02      | 
|POLY-3 PERCENT (g) |     2.5%         10.1%        10.0%        4.7%        |0.0%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/30 (3%)    2/21 (10%)   2/21 (10%)   2/30 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      690          605          729 (T)     |---          ---          ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.468N     P=0.103      P=0.112      P=0.500     |P=0.208      (e)          (e)          P=0.506      | 
|POLY 3             |     P=0.517N     P=0.168      P=0.170      P=0.513     |P=0.213      (e)          (e)          P=0.500      | 
|POLY 1.5           |     P=0.522N     P=0.179      P=0.179      P=0.512     |P=0.215      (e)          (e)          P=0.501      | 
|POLY 6             |     P=0.515N     P=0.151      P=0.154      P=0.510     |P=0.210      (e)          (e)          P=0.498      | 
|LOGISTIC REGRESSION|     P=0.500N     P=0.132      P=0.158      P=0.500     |(e)          (e)          (e)          P=0.506      | 
|COCH-ARM / FISHERS |     P=0.544N     P=0.181      P=0.181      P=0.500     |P=0.217      (e)          (e)          P=0.505      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma, Hepatocellular Adenoma,                                                                           | 
|     or Hepatoblastoma                                                                                                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    4/50 (8%)    4/50 (8%)    2/50 (4%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/40.89      4/39.70      4/39.91      2/42.44     |0/44.01      0/45.74      0/45.30      1/44.02      | 
|POLY-3 PERCENT (g) |     2.5%         10.1%        10.0%        4.7%        |0.0%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/30 (3%)    2/21 (10%)   2/21 (10%)   2/30 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      690          605          729 (T)     |---          ---          ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.468N     P=0.103      P=0.112      P=0.500     |P=0.208      (e)          (e)          P=0.506      | 
|POLY 3             |     P=0.517N     P=0.168      P=0.170      P=0.513     |P=0.213      (e)          (e)          P=0.500      | 
|POLY 1.5           |     P=0.522N     P=0.179      P=0.179      P=0.512     |P=0.215      (e)          (e)          P=0.501      | 
|POLY 6             |     P=0.515N     P=0.151      P=0.154      P=0.510     |P=0.210      (e)          (e)          P=0.498      | 
|LOGISTIC REGRESSION|     P=0.500N     P=0.132      P=0.158      P=0.500     |(e)          (e)          (e)          P=0.506      | 
|COCH-ARM / FISHERS |     P=0.544N     P=0.181      P=0.181      P=0.500     |P=0.217      (e)          (e)          P=0.505      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 8       
                     Statistical Analysis of Primary Tumors 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                                                                                                                    | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      0/42.44     |0/44.24      0/45.74      0/45.30      2/44.02      | 
|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%)    2/34 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.038 *    (e)          (e)          P=0.245      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.040 *    (e)          (e)          P=0.236      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.040 *    (e)          (e)          P=0.236      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.039 *    (e)          (e)          P=0.235      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          P=0.245      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Fibroadenoma                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    2/50 (4%)    3/50 (6%)   |23/50 (46%)  18/50 (36%)  20/50 (40%)  17/50 (34%)  | 
|POLY-3 RATE (b)    |     1/40.89      2/39.45      2/39.74      3/42.55     |23/46.87     18/46.52     20/46.73     17/46.07     | 
|POLY-3 PERCENT (g) |     2.5%         5.1%         5.0%         7.1%        |49.1%        38.7%        42.8%        36.9%        | 
|TERMINAL (d)       |     1/30 (3%)    2/21 (10%)   1/21 (5%)    2/30 (7%)   |14/33 (42%)  15/39 (39%)  15/35 (43%)  11/34 (32%)  | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      648          700         |596          634          592          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.336      P=0.376      P=0.401      P=0.309     |P=0.281N     P=0.109N     P=0.279N     P=0.174N     | 
|POLY 3             |     P=0.291      P=0.487      P=0.490      P=0.319     |P=0.220N     P=0.210N     P=0.343N     P=0.162N     | 
|POLY 1.5           |     P=0.285      P=0.500      P=0.500      P=0.318     |P=0.214N     P=0.208N     P=0.347N     P=0.157N     | 
|POLY 6             |     P=0.297      P=0.464      P=0.471      P=0.317     |P=0.236N     P=0.217N     P=0.346N     P=0.177N     | 
|LOGISTIC REGRESSION|     P=0.308      P=0.376      P=0.478      P=0.310     |P=0.219N     P=0.187N     P=0.333N     P=0.154N     | 
|COCH-ARM / FISHERS |     P=0.268      P=0.500      P=0.500      P=0.309     |P=0.209N     P=0.208N     P=0.343N     P=0.154N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 9       
                     Statistical Analysis of Primary Tumors 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                                                                                                                    | 
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    2/50 (4%)    3/50 (6%)   |23/50 (46%)  18/50 (36%)  20/50 (40%)  18/50 (36%)  | 
|POLY-3 RATE (b)    |     1/40.89      2/39.45      2/39.74      3/42.55     |23/46.87     18/46.52     20/46.73     18/46.07     | 
|POLY-3 PERCENT (g) |     2.5%         5.1%         5.0%         7.1%        |49.1%        38.7%        42.8%        39.1%        | 
|TERMINAL (d)       |     1/30 (3%)    2/21 (10%)   1/21 (5%)    2/30 (7%)   |14/33 (42%)  15/39 (39%)  15/35 (43%)  12/34 (35%)  | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      648          700         |596          634          592          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.336      P=0.376      P=0.401      P=0.309     |P=0.361N     P=0.109N     P=0.279N     P=0.224N     | 
|POLY 3             |     P=0.291      P=0.487      P=0.490      P=0.319     |P=0.300N     P=0.210N     P=0.343N     P=0.221N     | 
|POLY 1.5           |     P=0.285      P=0.500      P=0.500      P=0.318     |P=0.292N     P=0.208N     P=0.347N     P=0.214N     | 
|POLY 6             |     P=0.297      P=0.464      P=0.471      P=0.317     |P=0.320N     P=0.217N     P=0.346N     P=0.240N     | 
|LOGISTIC REGRESSION|     P=0.308      P=0.376      P=0.478      P=0.310     |P=0.297N     P=0.187N     P=0.333N     P=0.209N     | 
|COCH-ARM / FISHERS |     P=0.268      P=0.500      P=0.500      P=0.309     |P=0.284N     P=0.208N     P=0.343N     P=0.208N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery                                                                                                                        | 
|     Sarcoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      2/42.44     |0/44.24      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.7%        |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    |     ---          ---          ---          729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.062      (e)          (e)          P=0.238     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.044 *    (e)          (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.043 *    (e)          (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.045 *    (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=0.042 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 10      
                     Statistical Analysis of Primary Tumors 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                                                                                                                             | 
|     Squamous Cell Carcinoma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      0/39.45      0/39.45      2/43.13     |0/44.01      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.6%        |0.0%         0.0%         0.0%         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    |     ---          ---          ---          492         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.054      (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.045 *    (e)          (e)          P=0.249     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.043 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.047 *    (e)          (e)          P=0.249     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.033 *    (e)          (e)          P=0.207     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.042 *    (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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Mixed Tumor Benign                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.51      0/39.45      0/39.45      0/42.44     |0/44.01      0/45.74      0/44.51      0/44.02      | 
|POLY-3 PERCENT (g) |     4.8%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/30 (3%)    0/21 (0%)    0/21 (0%)    0/30 (0%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     528          ---          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.230N     P=0.279N     P=0.276N     P=0.235N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.226N     P=0.248N     P=0.248N     P=0.232N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.234N     P=0.239N     P=0.240N     P=0.231N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.213N     P=0.265N     P=0.264N     P=0.235N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.248N     P=0.245N     P=0.243N     P=0.251N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.239N     P=0.247N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 11      
                     Statistical Analysis of Primary Tumors 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 or Unspecified Site                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     15/49 (31%)  9/50 (18%)   10/48 (21%)  13/50 (26%) |15/49 (31%)  21/50 (42%)  25/49 (51%)  25/49 (51%)  | 
|POLY-3 RATE (b)    |     15/41.14     9/41.29      10/39.69     13/42.98    |15/46.31     21/47.49     25/45.54     25/46.10     | 
|POLY-3 PERCENT (g) |     36.5%        21.8%        25.2%        30.3%       |32.4%        44.2%        54.9%        54.2%        | 
|TERMINAL (d)       |     10/29 (35%)  4/21 (19%)   5/20 (25%)   11/30 (37%) |8/33 (24%)   16/39 (41%)  20/35 (57%)  15/33 (46%)  | 
|FIRST INCIDENCE    |     604          511          483          645         |497          600          648          590          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.439N     P=0.315N     P=0.443N     P=0.378N    |P=0.044 *    P=0.302      P=0.072      P=0.054      | 
|POLY 3             |     P=0.556      P=0.107N     P=0.193N     P=0.353N    |P=0.042 *    P=0.166      P=0.022 *    P=0.025 *    | 
|POLY 1.5           |     P=0.541      P=0.096N     P=0.177N     P=0.350N    |P=0.044 *    P=0.164      P=0.023 *    P=0.026 *    | 
|POLY 6             |     P=0.550N     P=0.134N     P=0.234N     P=0.373N    |P=0.041 *    P=0.174      P=0.021 *    P=0.025 *    | 
|LOGISTIC REGRESSION|     P=0.533N     P=0.117N     P=0.206N     P=0.337N    |P=0.047 *    P=0.162      P=0.032 *    P=0.034 *    | 
|COCH-ARM / FISHERS |     P=0.512      P=0.109N     P=0.193N     P=0.387N    |P=0.052      P=0.166      P=0.032 *    P=0.032 *    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    1/50 (2%)    3/50 (6%)   |                                                    | 
|POLY-3 RATE (b)    |     1/40.89      0/39.45      1/39.45      3/42.44     |                                                    | 
|POLY-3 PERCENT (g) |     2.5%         0.0%         2.5%         7.1%        |                                                    | 
|TERMINAL (d)       |     1/30 (3%)    0/21 (0%)    1/21 (5%)    3/30 (10%)  |                                                    | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      729 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.119      P=0.571N     P=0.681      P=0.304     |                                                    | 
|POLY 3             |     P=0.090      P=0.507N     P=0.753      P=0.318     |                                                    | 
|POLY 1.5           |     P=0.087      P=0.500N     P=0.760      P=0.318     |                                                    | 
|POLY 6             |     P=0.095      P=0.520N     P=0.739      P=0.315     |                                                    | 
|LOGISTIC REGRESSION|     P=0.119      (e)          P=0.681      P=0.304     |                                                    | 
|COCH-ARM / FISHERS |     P=0.082      P=0.500N     P=0.753N     P=0.309     |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 12      
                     Statistical Analysis of Primary Tumors 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                                                                                                                             | 
|     Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous                                                                      | 
|     Tumor (benign, malignant or NOS), or Trichoepithelioma                                                                      | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/40.89      2/39.45      0/39.45      2/42.91     |0/44.24      0/45.74      0/45.30      1/44.02      | 
|POLY-3 PERCENT (g) |     2.5%         5.1%         0.0%         4.7%        |0.0%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/30 (3%)    2/21 (10%)   0/21 (0%)    1/30 (3%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          590         |---          ---          ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.511      P=0.376      P=0.571N     P=0.505     |P=0.208      (e)          (e)          P=0.506      | 
|POLY 3             |     P=0.480      P=0.487      P=0.507N     P=0.517     |P=0.213      (e)          (e)          P=0.499      | 
|POLY 1.5           |     P=0.474      P=0.500      P=0.501N     P=0.514     |P=0.214      (e)          (e)          P=0.499      | 
|POLY 6             |     P=0.485      P=0.464      P=0.520N     P=0.517     |P=0.210      (e)          (e)          P=0.498      | 
|LOGISTIC REGRESSION|     P=0.483      P=0.376      (e)          P=0.506     |(e)          (e)          (e)          P=0.506      | 
|COCH-ARM / FISHERS |     P=0.460      P=0.500      P=0.500N     P=0.500     |P=0.215      (e)          (e)          P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor                                                                       | 
|     (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepitheliom                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    6/50 (12%)   3/50 (6%)    8/50 (16%)  |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     4/40.99      6/39.97      3/39.45      8/43.01     |1/44.24      0/45.74      0/45.30      1/44.02      | 
|POLY-3 PERCENT (g) |     9.8%         15.0%        7.6%         18.6%       |2.3%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     3/30 (10%)   4/21 (19%)   3/21 (14%)   6/30 (20%)  |1/33 (3%)    0/39 (0%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     704          638          729 (T)      590         |730 (T)      ---          ---          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.233      P=0.201      P=0.626      P=0.183     |P=0.532      P=0.467N     P=0.488N     P=0.755N     | 
|POLY 3             |     P=0.172      P=0.352      P=0.521N     P=0.198     |P=0.533      P=0.493N     P=0.495N     P=0.760      | 
|POLY 1.5           |     P=0.164      P=0.372      P=0.502N     P=0.196     |P=0.537      P=0.496N     P=0.498N     P=0.760      | 
|POLY 6             |     P=0.180      P=0.316      P=0.557N     P=0.196     |P=0.528      P=0.489N     P=0.492N     P=0.759      | 
|LOGISTIC REGRESSION|     P=0.193      P=0.289      P=0.639N     P=0.190     |P=0.532      (e)          (e)          P=0.755N     | 
|COCH-ARM / FISHERS |     P=0.149      P=0.370      P=0.500N     P=0.178     |P=0.541      P=0.500N     P=0.500N     P=0.753N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 13      
                     Statistical Analysis of Primary Tumors 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                                                                                                                             | 
|     Fibroma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    2/50 (4%)    5/50 (10%)  |2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/40.99      3/40.48      2/39.91      5/43.17     |2/44.26      0/45.74      1/45.38      0/44.02      | 
|POLY-3 PERCENT (g) |     2.4%         7.4%         5.0%         11.6%       |4.5%         0.0%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    3/30 (10%)  |1/33 (3%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     704          584          631          605         |725          ---          711          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.128      P=0.266      P=0.439      P=0.113     |P=0.277N     P=0.210N     P=0.477N     P=0.240N     | 
|POLY 3             |     P=0.100      P=0.300      P=0.491      P=0.113     |P=0.274N     P=0.230N     P=0.491N     P=0.238N     | 
|POLY 1.5           |     P=0.096      P=0.309      P=0.501      P=0.111     |P=0.270N     P=0.233N     P=0.496N     P=0.238N     | 
|POLY 6             |     P=0.104      P=0.283      P=0.472      P=0.113     |P=0.279N     P=0.225N     P=0.485N     P=0.239N     | 
|LOGISTIC REGRESSION|     P=0.088      P=0.301      P=0.498      P=0.109     |P=0.272N     P=0.217N     P=0.483N     P=0.241N     | 
|COCH-ARM / FISHERS |     P=0.088      P=0.309      P=0.500      P=0.102     |P=0.266N     P=0.247N     P=0.500N     P=0.247N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma,                                                                        | 
|     or Fibrous Histiocytoma                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    4/50 (8%)    2/50 (4%)    5/50 (10%)  |2/50 (4%)    1/50 (2%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/41.99      4/40.67      2/39.91      5/43.17     |2/44.26      1/45.74      2/46.35      0/44.02      | 
|POLY-3 PERCENT (g) |     4.8%         9.8%         5.0%         11.6%       |4.5%         2.2%         4.3%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    0/21 (0%)    0/21 (0%)    3/30 (10%)  |1/33 (3%)    1/39 (3%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     122          584          631          605         |725          730 (T)      232          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.267      P=0.292      P=0.644      P=0.230     |P=0.219N     P=0.449N     P=0.674N     P=0.240N     | 
|POLY 3             |     P=0.227      P=0.322      P=0.676      P=0.226     |P=0.216N     P=0.489N     P=0.677N     P=0.238N     | 
|POLY 1.5           |     P=0.222      P=0.334      P=0.687      P=0.225     |P=0.213N     P=0.494N     P=0.684N     P=0.238N     | 
|POLY 6             |     P=0.233      P=0.301      P=0.656      P=0.226     |P=0.220N     P=0.482N     P=0.670N     P=0.239N     | 
|LOGISTIC REGRESSION|     P=0.175      P=0.243      P=0.619      P=0.166     |P=0.191N     P=0.465N     P=0.664N     P=0.241N     | 
|COCH-ARM / FISHERS |     P=0.211      P=0.339      P=0.691N     P=0.218     |P=0.208N     P=0.500N     P=0.691N     P=0.247N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 14      
                     Statistical Analysis of Primary Tumors 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                                                                                                                             | 
|     Keratoacanthoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    3/50 (6%)    3/50 (6%)    3/50 (6%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/40.99      3/39.97      3/39.45      3/42.44     |1/44.24      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     7.3%         7.5%         7.6%         7.1%        |2.3%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/30 (7%)    1/21 (5%)    3/21 (14%)   3/30 (10%)  |1/33 (3%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     704          638          729 (T)      729 (T)     |730 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.522N     P=0.534      P=0.497      P=0.663     |P=0.479N     P=0.467N     P=0.488N     P=0.494N     | 
|POLY 3             |     P=0.575N     P=0.652      P=0.645      P=0.647N    |P=0.477N     P=0.493N     P=0.495N     P=0.501N     | 
|POLY 1.5           |     P=0.583N     P=0.660N     P=0.661      P=0.647N    |P=0.475N     P=0.496N     P=0.498N     P=0.501N     | 
|POLY 6             |     P=0.567N     P=0.626      P=0.615      P=0.652N    |P=0.480N     P=0.489N     P=0.492N     P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.550N     P=0.636      P=0.548      P=0.660N    |P=0.479N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.601N     P=0.661N     P=0.661N     P=0.661N    |P=0.472N     P=0.500N     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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Squamous Cell Carcinoma, Basal Cell Carcinoma, Basosquamous                                                                 | 
|     Tumor (malignant or NOS), or Carcinoma                                                                                      | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      1/39.45      0/39.45      2/42.44     |0/44.24      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         2.5%         0.0%         4.7%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    0/21 (0%)    2/30 (7%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.190      P=0.429      (e)          P=0.238     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.156      P=0.493      (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.154      P=0.500      (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.156      P=0.480      (e)          P=0.243     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.429      (e)          P=0.238     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.149      P=0.500      (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 15      
                     Statistical Analysis of Primary Tumors 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                                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      1/39.45      0/39.45      2/42.54     |0/44.24      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         2.5%         0.0%         4.7%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    0/21 (0%)    1/30 (3%)   |0/33 (0%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          702         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.190      P=0.429      (e)          P=0.243     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.156      P=0.493      (e)          P=0.246     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.155      P=0.500      (e)          P=0.245     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.157      P=0.480      (e)          P=0.244     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.174      P=0.429      (e)          P=0.243     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.149      P=0.500      (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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Squamous Cell Papilloma, Papilloma, Squamous Cell                                                                           | 
|     Carcinoma or Keratoacanthoma                                                                                                | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    4/50 (8%)    3/50 (6%)    6/50 (12%)  |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/40.99      4/39.97      3/39.45      6/42.54     |1/44.24      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     7.3%         10.0%        7.6%         14.1%       |2.3%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/30 (7%)    2/21 (10%)   3/21 (14%)   5/30 (17%)  |1/33 (3%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     704          638          729 (T)      702         |730 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.267      P=0.353      P=0.497      P=0.245     |P=0.479N     P=0.467N     P=0.488N     P=0.494N     | 
|POLY 3             |     P=0.206      P=0.486      P=0.645      P=0.259     |P=0.477N     P=0.493N     P=0.495N     P=0.501N     | 
|POLY 1.5           |     P=0.200      P=0.503      P=0.661      P=0.259     |P=0.475N     P=0.496N     P=0.498N     P=0.501N     | 
|POLY 6             |     P=0.211      P=0.455      P=0.615      P=0.254     |P=0.480N     P=0.489N     P=0.492N     P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.234      P=0.455      P=0.548      P=0.246     |P=0.479N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.185      P=0.500      P=0.661N     P=0.243     |P=0.472N     P=0.500N     P=0.500N     P=0.500N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 16      
                     Statistical Analysis of Primary Tumors 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                                                                                                                             | 
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    4/50 (8%)    3/50 (6%)    5/50 (10%)  |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/40.99      4/39.97      3/39.45      5/42.54     |1/44.24      0/45.74      0/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     7.3%         10.0%        7.6%         11.8%       |2.3%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/30 (7%)    2/21 (10%)   3/21 (14%)   4/30 (13%)  |1/33 (3%)    0/39 (0%)    0/35 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     704          638          729 (T)      702         |730 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.405      P=0.353      P=0.497      P=0.359     |P=0.479N     P=0.467N     P=0.488N     P=0.494N     | 
|POLY 3             |     P=0.343      P=0.486      P=0.645      P=0.376     |P=0.477N     P=0.493N     P=0.495N     P=0.501N     | 
|POLY 1.5           |     P=0.336      P=0.503      P=0.661      P=0.376     |P=0.475N     P=0.496N     P=0.498N     P=0.501N     | 
|POLY 6             |     P=0.351      P=0.455      P=0.615      P=0.371     |P=0.480N     P=0.489N     P=0.492N     P=0.502N     | 
|LOGISTIC REGRESSION|     P=0.372      P=0.455      P=0.548      P=0.363     |P=0.479N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.315      P=0.500      P=0.661N     P=0.357     |P=0.472N     P=0.500N     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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     41/50 (82%)  43/50 (86%)  44/50 (88%)  48/50 (96%) |                                                    | 
|POLY-3 RATE (b)    |     41/44.33     43/45.66     44/47.50     48/48.74    |                                                    | 
|POLY-3 PERCENT (g) |     92.5%        94.2%        92.6%        98.5%       |                                                    | 
|TERMINAL (d)       |     29/30 (97%)  21/21 (100%) 20/21 (95%)  30/30 (100%)|                                                    | 
|FIRST INCIDENCE    |     528          555          510          449         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.488      P=0.020 *    P=0.022 *    P=0.165     |                                                    | 
|POLY 3             |     P=0.099      P=0.553      P=0.662      P=0.135     |                                                    | 
|POLY 1.5           |     P=0.049 *    P=0.563      P=0.542      P=0.071     |                                                    | 
|POLY 6             |     P=0.221      P=0.472      P=0.578N     P=0.249     |                                                    | 
|LOGISTIC REGRESSION|     P=0.028 *    P=0.309      P=0.320      P=0.044 *   |                                                    | 
|COCH-ARM / FISHERS |     P=0.023 *    P=0.393      P=0.288      P=0.026 *   |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 17      
                     Statistical Analysis of Primary Tumors 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                                                                                                            | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    5/50 (10%)   3/50 (6%)    3/50 (6%)   |4/49 (8%)    6/50 (12%)   4/50 (8%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     3/40.89      5/39.80      3/40.37      3/42.44     |4/44.63      6/46.09      4/45.77      3/44.02      | 
|POLY-3 PERCENT (g) |     7.3%         12.6%        7.4%         7.1%        |9.0%         13.0%        8.7%         6.8%         | 
|TERMINAL (d)       |     3/30 (10%)   4/21 (19%)   0/21 (0%)    3/30 (10%)  |3/33 (9%)    5/39 (13%)   3/35 (9%)    3/34 (9%)    | 
|FIRST INCIDENCE    |     729 (T)      632          575          729 (T)     |527          634          592          730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.377N     P=0.196      P=0.553      P=0.665     |P=0.320N     P=0.461      P=0.615N     P=0.484N     | 
|POLY 3             |     P=0.426N     P=0.340      P=0.657      P=0.646N    |P=0.315N     P=0.390      P=0.630N     P=0.508N     | 
|POLY 1.5           |     P=0.433N     P=0.358      P=0.658N     P=0.646N    |P=0.307N     P=0.385      P=0.633N     P=0.501N     | 
|POLY 6             |     P=0.420N     P=0.308      P=0.637      P=0.650N    |P=0.327N     P=0.399      P=0.622N     P=0.516N     | 
|LOGISTIC REGRESSION|     P=0.414N     P=0.268      P=0.658      P=0.665     |P=0.298N     P=0.381      P=0.628N     P=0.493N     | 
|COCH-ARM / FISHERS |     P=0.453N     P=0.357      P=0.661N     P=0.661N    |P=0.293N     P=0.383      P=0.631N     P=0.489N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: C-Cell                                                                                                            | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    1/50 (2%)    1/50 (2%)   |2/49 (4%)    2/50 (4%)    0/50 (0%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     1/40.97      1/39.45      1/39.45      1/42.83     |2/44.01      2/45.74      0/45.30      3/44.38      | 
|POLY-3 PERCENT (g) |     2.4%         2.5%         2.5%         2.3%        |4.5%         4.4%         0.0%         6.8%         | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    1/21 (5%)    0/30 (0%)   |2/33 (6%)    2/39 (5%)    0/35 (0%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     711          729 (T)      729 (T)      617         |730 (T)      730 (T)      ---          646          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.620N     P=0.687      P=0.682      P=0.751N    |P=0.342      P=0.634N     P=0.225N     P=0.508      | 
|POLY 3             |     P=0.650N     P=0.753      P=0.753      P=0.751N    |P=0.358      P=0.680N     P=0.231N     P=0.504      | 
|POLY 1.5           |     P=0.656N     P=0.761      P=0.760      P=0.752N    |P=0.360      P=0.683N     P=0.233N     P=0.505      | 
|POLY 6             |     P=0.643N     P=0.737      P=0.738      P=0.752N    |P=0.354      P=0.674N     P=0.227N     P=0.503      | 
|LOGISTIC REGRESSION|     P=0.650N     P=0.722      P=0.723      P=0.762     |P=0.348      P=0.634N     (e)          P=0.500      | 
|COCH-ARM / FISHERS |     P=0.668      P=0.753N     P=0.753N     P=0.753N    |P=0.364      P=0.684N     P=0.242N     P=0.510      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 18      
                     Statistical Analysis of Primary Tumors 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                                                                                                            | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    6/50 (12%)   4/50 (8%)    4/50 (8%)   |6/49 (12%)   8/50 (16%)   4/50 (8%)    6/50 (12%)   | 
|POLY-3 RATE (b)    |     4/40.97      6/39.80      4/40.37      4/42.83     |6/44.63      8/46.09      4/45.77      6/44.38      | 
|POLY-3 PERCENT (g) |     9.8%         15.1%        9.9%         9.3%        |13.4%        17.4%        8.7%         13.5%        | 
|TERMINAL (d)       |     3/30 (10%)   5/21 (24%)   1/21 (5%)    3/30 (10%)  |5/33 (15%)   7/39 (18%)   3/35 (9%)    4/34 (12%)   | 
|FIRST INCIDENCE    |     711          632          575          617         |527          634          592          646          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.371N     P=0.190      P=0.497      P=0.637N    |P=0.507N     P=0.504      P=0.339N     P=0.602N     | 
|POLY 3             |     P=0.420N     P=0.350      P=0.636      P=0.619N    |P=0.489N     P=0.411      P=0.354N     P=0.617      | 
|POLY 1.5           |     P=0.431N     P=0.371      P=0.639N     P=0.622N    |P=0.480N     P=0.406      P=0.359N     P=0.618N     | 
|POLY 6             |     P=0.408N     P=0.311      P=0.611      P=0.621N    |P=0.499N     P=0.423      P=0.345N     P=0.612      | 
|LOGISTIC REGRESSION|     P=0.415N     P=0.266      P=0.628      P=0.628N    |P=0.481N     P=0.409      P=0.356N     P=0.616N     | 
|COCH-ARM / FISHERS |     P=0.458N     P=0.370      P=0.643N     P=0.643N    |P=0.467N     P=0.403      P=0.357N     P=0.606N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |0/49 (0%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/40.89      2/39.46      2/39.46      0/42.44     |0/44.01      1/45.74      1/45.30      0/44.02      | 
|POLY-3 PERCENT (g) |     0.0%         5.1%         5.1%         0.0%        |0.0%         2.2%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/30 (0%)    1/21 (5%)    1/21 (5%)    0/30 (0%)   |0/33 (0%)    1/39 (3%)    1/35 (3%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          725          725          ---         |---          730 (T)      730 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.354N     P=0.167      P=0.167      (e)         |P=0.551N     P=0.533      P=0.512      (e)          | 
|POLY 3             |     P=0.370N     P=0.229      P=0.229      (e)         |P=0.543N     P=0.508      P=0.506      (e)          | 
|POLY 1.5           |     P=0.372N     P=0.237      P=0.236      (e)         |P=0.541N     P=0.506      P=0.504      (e)          | 
|POLY 6             |     P=0.373N     P=0.214      P=0.215      (e)         |P=0.546N     P=0.511      P=0.509      (e)          | 
|LOGISTIC REGRESSION|     P=0.353N     P=0.175      P=0.175      (e)         |(e)          P=0.533      P=0.512      (e)          | 
|COCH-ARM / FISHERS |     P=0.386N     P=0.247      P=0.247      (e)         |P=0.538N     P=0.505      P=0.505      (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 19      
                     Statistical Analysis of Primary Tumors 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: Follicular Cell                                                                                                   | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    2/50 (4%)    0/50 (0%)   |0/49 (0%)    2/50 (4%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/40.89      3/39.46      2/39.46      0/42.44     |0/44.01      2/45.74      1/45.30      1/44.02      | 
|POLY-3 PERCENT (g) |     2.5%         7.6%         5.1%         0.0%        |0.0%         4.4%         2.2%         2.3%         | 
|TERMINAL (d)       |     1/30 (3%)    2/21 (10%)   1/21 (5%)    0/30 (0%)   |0/33 (0%)    2/39 (5%)    1/35 (3%)    1/34 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      725          725          ---         |---          730 (T)      730 (T)      730 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.167N     P=0.190      P=0.379      P=0.500N    |P=0.602      P=0.276      P=0.512      P=0.506      | 
|POLY 3             |     P=0.174N     P=0.292      P=0.488      P=0.493N    |P=0.609      P=0.246      P=0.506      P=0.500      | 
|POLY 1.5           |     P=0.176N     P=0.305      P=0.499      P=0.493N    |P=0.612      P=0.244      P=0.504      P=0.501      | 
|POLY 6             |     P=0.173N     P=0.268      P=0.466      P=0.494N    |P=0.605      P=0.249      P=0.509      P=0.498      | 
|LOGISTIC REGRESSION|     P=0.163N     P=0.198      P=0.395      (e)         |(e)          P=0.276      P=0.512      P=0.506      | 
|COCH-ARM / FISHERS |     P=0.187N     P=0.309      P=0.500      P=0.500N    |P=0.617      P=0.253      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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Polyp Stromal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |10/50 (20%)  8/50 (16%)   7/50 (14%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |                                                        |10/45.55     8/45.74      7/46.22      10/44.48     | 
|POLY-3 PERCENT (g) |                                                        |22.0%        17.5%        15.2%        22.5%        | 
|TERMINAL (d)       |                                                        |5/33 (15%)   8/39 (21%)   4/35 (11%)   9/34 (27%)   | 
|FIRST INCIDENCE    |                                                        |630          730 (T)      527          592          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.411      P=0.291N     P=0.268N     P=0.583N     | 
|POLY 3             |                                                        |P=0.425      P=0.393N     P=0.285N     P=0.576      | 
|POLY 1.5           |                                                        |P=0.438      P=0.394N     P=0.292N     P=0.587      | 
|POLY 6             |                                                        |P=0.405      P=0.395N     P=0.279N     P=0.555      | 
|LOGISTIC REGRESSION|                                                        |P=0.439      P=0.374N     P=0.299N     P=0.595      | 
|COCH-ARM / FISHERS |                                                        |P=0.452      P=0.398N     P=0.298N     P=0.598N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 20      
                     Statistical Analysis of Primary Tumors 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                                                                                                                           | 
|     Sarcoma Stromal or Polyp Stromal                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |11/50 (22%)  8/50 (16%)   7/50 (14%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |                                                        |11/45.57     8/45.74      7/46.22      10/44.48     | 
|POLY-3 PERCENT (g) |                                                        |24.1%        17.5%        15.2%        22.5%        | 
|TERMINAL (d)       |                                                        |5/33 (15%)   8/39 (21%)   4/35 (11%)   9/34 (27%)   | 
|FIRST INCIDENCE    |                                                        |630          730 (T)      527          592          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.477      P=0.214N     P=0.197N     P=0.489N     | 
|POLY 3             |                                                        |P=0.494      P=0.300N     P=0.205N     P=0.525N     | 
|POLY 1.5           |                                                        |P=0.506      P=0.302N     P=0.212N     P=0.513N     | 
|POLY 6             |                                                        |P=0.474      P=0.302N     P=0.201N     P=0.549N     | 
|LOGISTIC REGRESSION|                                                        |P=0.507      P=0.281N     P=0.218N     P=0.504N     | 
|COCH-ARM / FISHERS |                                                        |P=0.521      P=0.306N     P=0.218N     P=0.500N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Zymbal's Gland                                                                                                                   | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     0/40.89      1/40.19      0/39.45      1/42.44     |0/44.24      0/45.74      0/45.30      3/45.82      | 
|POLY-3 PERCENT (g) |     0.0%         2.5%         0.0%         2.4%        |0.0%         0.0%         0.0%         6.6%         | 
|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    |     ---          462          ---          729 (T)     |---          ---          ---          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.479      P=0.517      (e)          P=0.500     |P=0.010 *    (e)          (e)          P=0.128      | 
|POLY 3             |     P=0.469      P=0.497      (e)          P=0.507     |P=0.008 **   (e)          (e)          P=0.125      | 
|POLY 1.5           |     P=0.469      P=0.502      (e)          P=0.507     |P=0.008 **   (e)          (e)          P=0.123      | 
|POLY 6             |     P=0.468      P=0.485      (e)          P=0.506     |P=0.008 **   (e)          (e)          P=0.127      | 
|LOGISTIC REGRESSION|     P=0.424      P=0.363      (e)          P=0.500     |P=0.007 **   (e)          (e)          P=0.093      | 
|COCH-ARM / FISHERS |     P=0.459      P=0.500      (e)          P=0.500     |P=0.009 **   (e)          (e)          P=0.121      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 21      
                     Statistical Analysis of Primary Tumors 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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or                                                                           | 
|     Undifferentiated                                                                                                            | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     28/50 (56%)  31/50 (62%)  29/50 (58%)  18/50 (36%) |14/50 (28%)  17/50 (34%)  16/50 (32%)  3/50 (6%)    | 
|POLY-3 RATE (b)    |     28/45.54     31/47.64     29/45.54     18/46.53    |14/46.56     17/47.71     16/47.73     3/44.70      | 
|POLY-3 PERCENT (g) |     61.5%        65.1%        63.7%        38.7%       |30.1%        35.6%        33.5%        6.7%         | 
|TERMINAL (d)       |     16/30 (53%)  7/21 (33%)   11/21 (52%)  6/30 (20%)  |7/33 (21%)   12/39 (31%)  9/35 (26%)   1/34 (3%)    | 
|FIRST INCIDENCE    |     284          491          373          266         |448          575          527          603          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.012N*    P=0.129      P=0.174      P=0.063N    |P=0.002N**   P=0.487      P=0.477      P=0.006N**   | 
|POLY 3             |     P=0.003N**   P=0.442      P=0.500      P=0.021N*   |P<0.001N**   P=0.361      P=0.445      P=0.003N**   | 
|POLY 1.5           |     P=0.003N**   P=0.425      P=0.528      P=0.021N*   |P<0.001N**   P=0.347      P=0.426      P=0.003N**   | 
|POLY 6             |     P=0.003N**   P=0.460      P=0.455      P=0.021N*   |P<0.001N**   P=0.385      P=0.471      P=0.004N**   | 
|LOGISTIC REGRESSION|     P=0.007N**   P=0.341      P=0.505      P=0.037N*   |P<0.001N**   P=0.304      P=0.401      P=0.004N**   | 
|COCH-ARM / FISHERS |     P=0.006N**   P=0.342      P=0.500      P=0.035N*   |P<0.001N**   P=0.333      P=0.414      P=0.003N**   | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Mesothelioma: Benign, Malignant, NOS                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    3/50 (6%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     2/41.52      1/39.78      3/40.35      1/42.83     |0/44.24      0/45.74      0/45.30      1/44.17      | 
|POLY-3 PERCENT (g) |     4.8%         2.5%         7.4%         2.3%        |0.0%         0.0%         0.0%         2.3%         | 
|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    |     604          636          603          617         |---          ---          ---          690          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.436N     P=0.531N     P=0.466      P=0.489N    |P=0.203      (e)          (e)          P=0.495      | 
|POLY 3             |     P=0.440N     P=0.515N     P=0.487      P=0.489N    |P=0.213      (e)          (e)          P=0.500      | 
|POLY 1.5           |     P=0.450N     P=0.501N     P=0.500      P=0.489N    |P=0.214      (e)          (e)          P=0.500      | 
|POLY 6             |     P=0.429N     P=0.539N     P=0.462      P=0.493N    |P=0.211      (e)          (e)          P=0.499      | 
|LOGISTIC REGRESSION|     P=0.489N     P=0.508N     P=0.495      P=0.524N    |P=0.216      (e)          (e)          P=0.500      | 
|COCH-ARM / FISHERS |     P=0.466N     P=0.500N     P=0.500      P=0.500N    |P=0.215      (e)          (e)          P=0.500      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 22      
                     Statistical Analysis of Primary Tumors 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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Mesothelioma: Malignant                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    3/50 (6%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     2/41.52      1/39.78      3/40.35      1/42.83     |0/44.24      0/45.74      0/45.30      1/44.17      | 
|POLY-3 PERCENT (g) |     4.8%         2.5%         7.4%         2.3%        |0.0%         0.0%         0.0%         2.3%         | 
|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    |     604          636          603          617         |---          ---          ---          690          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.436N     P=0.531N     P=0.466      P=0.489N    |P=0.203      (e)          (e)          P=0.495      | 
|POLY 3             |     P=0.440N     P=0.515N     P=0.487      P=0.489N    |P=0.213      (e)          (e)          P=0.500      | 
|POLY 1.5           |     P=0.450N     P=0.501N     P=0.500      P=0.489N    |P=0.214      (e)          (e)          P=0.500      | 
|POLY 6             |     P=0.429N     P=0.539N     P=0.462      P=0.493N    |P=0.211      (e)          (e)          P=0.499      | 
|LOGISTIC REGRESSION|     P=0.489N     P=0.508N     P=0.495      P=0.524N    |P=0.216      (e)          (e)          P=0.500      | 
|COCH-ARM / FISHERS |     P=0.466N     P=0.500N     P=0.500      P=0.500N    |P=0.215      (e)          (e)          P=0.500      | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     45/50 (90%)  46/50 (92%)  47/50 (94%)  49/50 (98%) |41/50 (82%)  39/50 (78%)  41/50 (82%)  37/50 (74%)  | 
|POLY-3 RATE (b)    |     45/45.79     46/47.15     47/48.25     49/49.05    |41/49.13     39/47.70     41/48.10     37/47.72     | 
|POLY-3 PERCENT (g) |     98.3%        97.6%        97.4%        99.9%       |83.5%        81.8%        85.2%        77.5%        | 
|TERMINAL (d)       |     30/30 (100%) 21/21 (100%) 21/21 (100%) 30/30 (100%)|26/33 (79%)  32/39 (82%)  31/35 (89%)  26/34 (77%)  | 
|FIRST INCIDENCE    |     472          511          483          449         |497          600          527          529          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.391N     P=0.036 *    P=0.031 *    P=0.344     |P=0.405N     P=0.134N     P=0.411N     P=0.280N     | 
|POLY 3             |     P=0.292      P=0.792N     P=0.698N     P=0.656     |P=0.260N     P=0.520N     P=0.515      P=0.313N     | 
|POLY 1.5           |     P=0.148      P=0.648N     P=0.752N     P=0.313     |P=0.240N     P=0.470N     P=0.538      P=0.278N     | 
|POLY 6             |     P=0.589      P=0.998N     P=0.636N     P=0.991     |P=0.296N     P=0.578N     P=0.487      P=0.367N     | 
|LOGISTIC REGRESSION|     P=0.099      P=0.634N     P=0.629      P=0.281     |P=0.242N     P=0.355N     P=0.597N     P=0.237N     | 
|COCH-ARM / FISHERS |     P=0.078      P=0.500      P=0.357      P=0.102     |P=0.220N     P=0.402N     P=0.602N     P=0.235N     | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  01/25/01                           EXPERIMENT: 05211 TEST: 05                                            Page 23      
                     Statistical Analysis of Primary Tumors 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          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     36/50 (72%)  38/50 (76%)  36/50 (72%)  28/50 (56%) |22/50 (44%)  24/50 (48%)  22/50 (44%)  15/50 (30%)  | 
|POLY-3 RATE (b)    |     36/48.14     38/49.51     36/47.55     28/48.03    |22/47.70     24/49.57     22/48.96     15/47.76     | 
|POLY-3 PERCENT (g) |     74.8%        76.8%        75.7%        58.3%       |46.1%        48.4%        44.9%        31.4%        | 
|TERMINAL (d)       |     20/30 (67%)  10/21 (48%)  13/21 (62%)  12/30 (40%) |12/33 (36%)  15/39 (39%)  12/35 (34%)  5/34 (15%)   | 
|FIRST INCIDENCE    |     122          462          368          266         |448          396          232          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.034N*    P=0.134      P=0.182      P=0.134N    |P=0.096N     P=0.522N     P=0.496N     P=0.142N     | 
|POLY 3             |     P=0.018N*    P=0.504      P=0.553      P=0.063N    |P=0.047N*    P=0.491      P=0.535N     P=0.101N     | 
|POLY 1.5           |     P=0.017N*    P=0.480      P=0.583      P=0.062N    |P=0.045N*    P=0.461      P=0.553N     P=0.103N     | 
|POLY 6             |     P=0.020N*    P=0.530      P=0.513      P=0.066N    |P=0.050N     P=0.529      P=0.513N     P=0.098N     | 
|LOGISTIC REGRESSION|     P=0.027N*    P=0.443      P=0.588N     P=0.086N    |P=0.025N*    P=0.336      P=0.528      P=0.094N     | 
|COCH-ARM / FISHERS |     P=0.019N*    P=0.410      P=0.588N     P=0.072N    |P=0.043N*    P=0.421      P=0.580N     P=0.107N     | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0            280          830          2500        |0            280          830          2500         | 
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     49/50 (98%)  50/50 (100%) 50/50 (100%) 50/50 (100%)|45/50 (90%)  47/50 (94%)  48/50 (96%)  43/50 (86%)  | 
|POLY-3 RATE (b)    |     49/49.03     50/50.00     50/50.00     50/50.00    |45/50.00     47/50.00     48/50.00     43/50.00     | 
|POLY-3 PERCENT (g) |     100.0%       100.0%       100.0%       100.0%      |90.0%        94.0%        96.0%        86.0%        | 
|TERMINAL (d)       |     30/30 (100%) 21/21 (100%) 21/21 (100%) 30/30 (100%)|28/33 (85%)  36/39 (92%)  33/35 (94%)  27/34 (79%)  | 
|FIRST INCIDENCE    |     122          462          368          266         |448          396          232          360          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.224N     P=0.052      P=0.056      P=0.548     |P=0.450N     P=0.308N     P=0.533      P=0.404N     | 
|POLY 3             |     P=1.000      P=1.000      P=1.000      P=1.000     |P=0.159N     P=0.357      P=0.217      P=0.380N     | 
|POLY 1.5           |     P=1.000      P=1.000      P=1.000      P=1.000     |P=0.159N     P=0.357      P=0.217      P=0.380N     | 
|POLY 6             |     P=1.000      P=1.000      P=1.000      P=1.000     |P=0.159N     P=0.357      P=0.217      P=0.380N     | 
|LOGISTIC REGRESSION|     P=0.754      P=0.987      P=0.949      P=0.860     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.472      P=0.500      P=0.500      P=0.500     |P=0.159N     P=0.357      P=0.218      P=0.380N     | 
|=================================================================================================================================| 
(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).