Skip to Main Navigation
Skip to Page Content
Share This:
https://ntp.niehs.nih.gov/go/2796

TDMS Study 05211-06 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                      EMODIN                                        DATE: 12/02/98       
EXPERIMENT: 05211 TEST: 06                                                                                     TIME: 10:35:44       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-85216                              ROUTE: DOSED FEED                                              NTP C#: C62408       
PATHOLOGIST: FARNELL, D.                                                                                       CAS: 518-82-1        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                          CORE STUDY MICE                                                           
                                                                                                                                    

               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: 12/02/98

EXPERIMENT: 05211 TEST: 06                                                                                     TIME: 10:35:44
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-85216                              ROUTE: DOSED FEED                                              NTP C#: C62408
PATHOLOGIST: FARNELL, D.                                                                                       CAS: 518-82-1

Mice(B6C3F1)
-----------------------------
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.
                                                 ---------------
                                                 Adrenal Cortex
                                                 Adrenal Medulla
                                                 Bone Marrow
                                                 Gallbladder
                                                 Heart
                                                 Islets, Pancreatic
                                                 Kidney
                                                 Liver
                                                 Lung
                                                 Ovary
                                                 Pancreas
                                                 Parathyroid Gland
                                                 Pituitary Gland
                                                 Spleen
                                                 Thyroid Gland
                                                 Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08   
LAB: Southern Research Inst                                      EMODIN                                        DATE: 12/02/98     
EXPERIMENT: 05211 TEST: 06                                                                                     TIME: 10:35:44     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: NO1-ES-85216                              ROUTE: DOSED FEED                                              NTP C#: C62408     
PATHOLOGIST: FARNELL, D.                                                                                       CAS: 518-82-1      



SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF                      EMODIN
===============================================================

Male Mice
------------
Organ                                 Morphology
-----                                 ----------
Adrenal Cortex                         Adenoma
Liver                                  Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
Lung                                   Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
Thyroid Gland: Follicular Cell         Carcinoma or Adenoma
All Organs                             Malignant and Benign Tumors
===============================================================
Female Mice
------------
Organ                                  Morphology
-----                                  ----------
                                       Malignant and Benign Tumors
===============================================================
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 1
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)        -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    6/50 (12%)   5/50 (10%)   2/50 (4%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     2.1%         13.1%        10.7%        4.2%        |0.0%         2.2%         0.0%         2.2%         |
|TERMINAL (d)       |     1/41 (2%)    6/37 (16%)   5/40 (13%)   2/43 (5%)   |0/37 (0%)    1/39 (3%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |---          731 (T)      ---          608          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.495N     P=0.043 *    P=0.097      P=0.517     |P=0.406      P=0.511      (e)          P=0.509      |
|POLY 3             |     P=0.538N     P=0.050      P=0.097      P=0.501     |P=0.412      P=0.502      (e)          P=0.504      |
|POLY 1.5           |     P=0.543N     P=0.052      P=0.099      P=0.499     |P=0.409      P=0.500      (e)          P=0.502      |
|POLY 6             |     P=0.526N     P=0.047 *    P=0.096      P=0.506     |P=0.416      P=0.506      (e)          P=0.506      |
|LOGISTIC REGRESSION|     P=0.495N     P=0.043 *    P=0.097      P=0.517     |P=0.403      P=0.511      (e)          P=0.516      |
|COCH-ARM / FISHERS |     P=0.542N     P=0.056      P=0.102      P=0.500     |P=0.405      P=0.500      (e)          P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    2/50 (4%)    3/50 (6%)    4/50 (8%)   |0/50 (0%)    3/50 (6%)    3/50 (6%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     8.4%         4.4%         6.4%         8.4%        |0.0%         6.6%         6.4%         2.2%         |
|TERMINAL (d)       |     3/41 (7%)    2/37 (5%)    3/40 (8%)    4/43 (9%)   |0/37 (0%)    3/39 (8%)    3/40 (8%)    1/36 (3%)    |
|FIRST INCIDENCE    |     639          729 (T)      729 (T)      729 (T)     |---          731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.524      P=0.383N     P=0.515N     P=0.621N    |P=0.512      P=0.130      P=0.135      P=0.495      |
|POLY 3             |     P=0.492      P=0.359N     P=0.515N     P=0.641     |P=0.532      P=0.120      P=0.127      P=0.502      |
|POLY 1.5           |     P=0.486      P=0.351N     P=0.510N     P=0.639     |P=0.529      P=0.119      P=0.122      P=0.501      |
|POLY 6             |     P=0.501      P=0.369N     P=0.520N     P=0.640N    |P=0.536      P=0.124      P=0.134      P=0.503      |
|LOGISTIC REGRESSION|     P=0.501      P=0.348N     P=0.508N     P=0.643     |(e)          P=0.130      P=0.135      P=0.495      |
|COCH-ARM / FISHERS |     P=0.483      P=0.339N     P=0.500N     P=0.643N    |P=0.526      P=0.121      P=0.121      P=0.500      |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 2
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    3/50 (6%)   |1/50 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         2.1%         6.3%        |2.2%         0.0%         2.1%         4.3%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    1/40 (3%)    3/43 (7%)   |1/37 (3%)    0/39 (0%)    1/40 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          715          729 (T)      729 (T)     |731 (T)      ---          731 (T)      604          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.067      P=0.480      P=0.495      P=0.130     |P=0.242      P=0.489N     P=0.744N     P=0.499      |
|POLY 3             |     P=0.055      P=0.492      P=0.496      P=0.120     |P=0.252      P=0.498N     P=0.751N     P=0.507      |
|POLY 1.5           |     P=0.054      P=0.495      P=0.497      P=0.119     |P=0.251      P=0.500N     P=0.757N     P=0.503      |
|POLY 6             |     P=0.057      P=0.489      P=0.495      P=0.122     |P=0.252      P=0.494N     P=0.742N     P=0.511      |
|LOGISTIC REGRESSION|     P=0.062      P=0.494      P=0.495      P=0.130     |P=0.247      (e)          P=0.744N     P=0.498      |
|COCH-ARM / FISHERS |     P=0.054      P=0.500      P=0.500      P=0.121     |P=0.247      P=0.500N     P=0.753N     P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    4/50 (8%)    7/50 (14%)  |1/50 (2%)    3/50 (6%)    4/50 (8%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     8.4%         6.6%         8.6%         14.7%       |2.2%         6.6%         8.5%         6.5%         |
|TERMINAL (d)       |     3/41 (7%)    2/37 (5%)    4/40 (10%)   7/43 (16%)  |1/37 (3%)    3/39 (8%)    4/40 (10%)   2/36 (6%)    |
|FIRST INCIDENCE    |     639          715          729 (T)      729 (T)     |731 (T)      731 (T)      731 (T)      604          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.176      P=0.552N     P=0.628      P=0.287     |P=0.267      P=0.324      P=0.203      P=0.303      |
|POLY 3             |     P=0.144      P=0.525N     P=0.628      P=0.260     |P=0.293      P=0.308      P=0.192      P=0.312      |
|POLY 1.5           |     P=0.141      P=0.515N     P=0.633      P=0.258     |P=0.289      P=0.306      P=0.184      P=0.309      |
|POLY 6             |     P=0.150      P=0.536N     P=0.623      P=0.265     |P=0.299      P=0.315      P=0.204      P=0.316      |
|LOGISTIC REGRESSION|     P=0.156      P=0.514N     P=0.634      P=0.263     |P=0.286      P=0.324      P=0.203      P=0.304      |
|COCH-ARM / FISHERS |     P=0.140      P=0.500N     P=0.643N     P=0.262     |P=0.282      P=0.309      P=0.181      P=0.309      |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 3
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    4/50 (8%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         8.6%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    4/40 (10%)   0/43 (0%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.529      (e)          P=0.060      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.518      (e)          P=0.058      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.509      (e)          P=0.059      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.532      (e)          P=0.057      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.060      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.505      (e)          P=0.059      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Site Unspecified                                                                                                |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    4/50 (8%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         8.6%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    4/40 (10%)   0/43 (0%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.529      (e)          P=0.060      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.518      (e)          P=0.058      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.509      (e)          P=0.059      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.532      (e)          P=0.057      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.060      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.505      (e)          P=0.059      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 4
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         4.3%         2.1%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    1/37 (3%)    2/40 (5%)    1/43 (2%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.392      P=0.480      P=0.233      P=0.510     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.377      P=0.496      P=0.237      P=0.504     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.372      P=0.499      P=0.239      P=0.503     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.385      P=0.492      P=0.235      P=0.507     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          P=0.480      P=0.233      P=0.510     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.371      P=0.505      P=0.253      P=0.505     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     6.2%         0.0%         2.1%         2.1%        |0.0%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     2/41 (5%)    0/37 (0%)    1/40 (3%)    0/43 (0%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     556          ---          729 (T)      604         |---          ---          ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.284N     P=0.139N     P=0.317N     P=0.301N    |P=0.191      (e)          (e)          P=0.495      |
|POLY 3             |     P=0.284N     P=0.128N     P=0.317N     P=0.305N    |P=0.200      (e)          (e)          P=0.502      |
|POLY 1.5           |     P=0.288N     P=0.125N     P=0.313N     P=0.307N    |P=0.200      (e)          (e)          P=0.501      |
|POLY 6             |     P=0.278N     P=0.133N     P=0.320N     P=0.300N    |P=0.199      (e)          (e)          P=0.503      |
|LOGISTIC REGRESSION|     P=0.259N     P=0.076N     P=0.257N     P=0.233N    |(e)          (e)          (e)          P=0.495      |
|COCH-ARM / FISHERS |     P=0.293N     P=0.121N     P=0.309N     P=0.309N    |P=0.198      (e)          (e)          P=0.500      |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 5
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   10/50 (20%)  12/50 (24%)  11/50 (22%) |9/50 (18%)   7/50 (14%)   12/50 (24%)  7/50 (14%)   |
|POLY-3 ADJUSTED (b)|     18.9%        21.9%        25.4%        23.1%       |19.9%        15.3%        25.4%        15.3%        |
|TERMINAL (d)       |     9/41 (22%)   10/37 (27%)  11/40 (28%)  11/43 (26%) |9/37 (24%)   5/39 (13%)   12/40 (30%)  5/36 (14%)   |
|FIRST INCIDENCE    |     729 (T)      729 (T)      497          729 (T)     |731 (T)      720          731 (T)      681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.422      P=0.399      P=0.289      P=0.447     |P=0.469N     P=0.347N     P=0.382      P=0.412N     |
|POLY 3             |     P=0.357      P=0.461      P=0.305      P=0.405     |P=0.421N     P=0.383N     P=0.351      P=0.379N     |
|POLY 1.5           |     P=0.346      P=0.476      P=0.307      P=0.399     |P=0.428N     P=0.391N     P=0.327      P=0.386N     |
|POLY 6             |     P=0.379      P=0.445      P=0.306      P=0.418     |P=0.414N     P=0.365N     P=0.387      P=0.368N     |
|LOGISTIC REGRESSION|     P=0.381      P=0.399      P=0.295      P=0.447     |P=0.431N     P=0.331N     P=0.382      P=0.379N     |
|COCH-ARM / FISHERS |     P=0.341      P=0.500      P=0.312      P=0.402     |P=0.438N     P=0.393N     P=0.312      P=0.393N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     20/50 (40%)  25/50 (50%)  22/50 (44%)  16/50 (32%) |4/50 (8%)    7/50 (14%)   9/50 (18%)   4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     41.1%        50.5%        44.0%        32.9%       |8.8%         15.4%        19.1%        8.7%         |
|TERMINAL (d)       |     15/41 (37%)  15/37 (41%)  12/40 (30%)  13/43 (30%) |3/37 (8%)    7/39 (18%)   9/40 (23%)   3/36 (8%)    |
|FIRST INCIDENCE    |     636          446          497          632         |684          731 (T)      731 (T)      646          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.124N     P=0.150      P=0.393      P=0.242N    |P=0.523N     P=0.292      P=0.150      P=0.637      |
|POLY 3             |     P=0.141N     P=0.231      P=0.465      P=0.267N    |P=0.487N     P=0.263      P=0.131      P=0.637N     |
|POLY 1.5           |     P=0.145N     P=0.223      P=0.446      P=0.272N    |P=0.493N     P=0.260      P=0.121      P=0.640N     |
|POLY 6             |     P=0.130N     P=0.243      P=0.494      P=0.254N    |P=0.481N     P=0.272      P=0.145      P=0.633N     |
|LOGISTIC REGRESSION|     P=0.156N     P=0.291      P=0.485      P=0.266N    |P=0.489N     P=0.287      P=0.161      P=0.639N     |
|COCH-ARM / FISHERS |     P=0.139N     P=0.211      P=0.420      P=0.266N    |P=0.500N     P=0.262      P=0.117      P=0.643N     |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 6
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     21/50 (42%)  25/50 (50%)  22/50 (44%)  16/50 (32%) |4/50 (8%)    7/50 (14%)   9/50 (18%)   4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     43.2%        50.5%        44.0%        32.9%       |8.8%         15.4%        19.1%        8.7%         |
|TERMINAL (d)       |     16/41 (39%)  15/37 (41%)  12/40 (30%)  13/43 (30%) |3/37 (8%)    7/39 (18%)   9/40 (23%)   3/36 (8%)    |
|FIRST INCIDENCE    |     636          446          497          632         |684          731 (T)      731 (T)      646          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.097N     P=0.192      P=0.461      P=0.186N    |P=0.523N     P=0.292      P=0.150      P=0.637      |
|POLY 3             |     P=0.106N     P=0.299      P=0.547      P=0.204N    |P=0.487N     P=0.263      P=0.131      P=0.637N     |
|POLY 1.5           |     P=0.110N     P=0.288      P=0.526      P=0.209N    |P=0.493N     P=0.260      P=0.121      P=0.640N     |
|POLY 6             |     P=0.098N     P=0.312      P=0.576      P=0.192N    |P=0.481N     P=0.272      P=0.145      P=0.633N     |
|LOGISTIC REGRESSION|     P=0.118N     P=0.363      P=0.567      P=0.204N    |P=0.489N     P=0.287      P=0.161      P=0.639N     |
|COCH-ARM / FISHERS |     P=0.105N     P=0.274      P=0.500      P=0.204N    |P=0.500N     P=0.262      P=0.117      P=0.643N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     28/50 (56%)  32/50 (64%)  31/50 (62%)  22/50 (44%) |13/50 (26%)  14/50 (28%)  21/50 (42%)  11/50 (22%)  |
|POLY-3 ADJUSTED (b)|     57.5%        64.7%        62.0%        45.3%       |28.7%        30.7%        44.5%        23.8%        |
|TERMINAL (d)       |     23/41 (56%)  22/37 (60%)  21/40 (53%)  19/43 (44%) |12/37 (32%)  12/39 (31%)  21/40 (53%)  8/36 (22%)   |
|FIRST INCIDENCE    |     636          446          497          632         |684          720          731 (T)      646          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.065N     P=0.162      P=0.320      P=0.135N    |P=0.448N     P=0.566      P=0.103      P=0.428N     |
|POLY 3             |     P=0.078N     P=0.302      P=0.403      P=0.156N    |P=0.374N     P=0.508      P=0.083      P=0.386N     |
|POLY 1.5           |     P=0.082N     P=0.289      P=0.376      P=0.163N    |P=0.388N     P=0.499      P=0.072      P=0.397N     |
|POLY 6             |     P=0.069N     P=0.320      P=0.443      P=0.142N    |P=0.358N     P=0.529      P=0.102      P=0.371N     |
|LOGISTIC REGRESSION|     P=0.082N     P=0.316      P=0.376      P=0.161N    |P=0.386N     P=0.576      P=0.142      P=0.388N     |
|COCH-ARM / FISHERS |     P=0.078N     P=0.270      P=0.342      P=0.159N    |P=0.407N     P=0.500      P=0.069      P=0.408N     |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 7
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma,                                                                           |
|     or Hepatoblastoma                                                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     29/50 (58%)  32/50 (64%)  31/50 (62%)  22/50 (44%) |13/50 (26%)  14/50 (28%)  21/50 (42%)  11/50 (22%)  |
|POLY-3 ADJUSTED (b)|     59.6%        64.7%        62.0%        45.3%       |28.7%        30.7%        44.5%        23.8%        |
|TERMINAL (d)       |     24/41 (59%)  22/37 (60%)  21/40 (53%)  19/43 (44%) |12/37 (32%)  12/39 (31%)  21/40 (53%)  8/36 (22%)   |
|FIRST INCIDENCE    |     636          446          497          632         |684          720          731 (T)      646          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.049N*    P=0.204      P=0.382      P=0.098N    |P=0.448N     P=0.566      P=0.103      P=0.428N     |
|POLY 3             |     P=0.055N     P=0.378      P=0.485      P=0.111N    |P=0.374N     P=0.508      P=0.083      P=0.386N     |
|POLY 1.5           |     P=0.059N     P=0.362      P=0.456      P=0.117N    |P=0.388N     P=0.499      P=0.072      P=0.397N     |
|POLY 6             |     P=0.048N*    P=0.399      P=0.527      P=0.100N    |P=0.358N     P=0.529      P=0.102      P=0.371N     |
|LOGISTIC REGRESSION|     P=0.059N     P=0.389      P=0.455      P=0.117N    |P=0.386N     P=0.576      P=0.142      P=0.388N     |
|COCH-ARM / FISHERS |     P=0.056N     P=0.341      P=0.419      P=0.115N    |P=0.407N     P=0.500      P=0.069      P=0.408N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   9/50 (18%)   6/50 (12%)   7/50 (14%)  |4/50 (8%)    1/50 (2%)    2/50 (4%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     18.9%        19.5%        12.7%        14.7%       |8.7%         2.2%         4.2%         2.2%         |
|TERMINAL (d)       |     8/41 (20%)   7/37 (19%)   5/40 (13%)   7/43 (16%)  |2/37 (5%)    1/39 (3%)    2/40 (5%)    0/36 (0%)    |
|FIRST INCIDENCE    |     699          636          572          729 (T)     |592          731 (T)      731 (T)      681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.239N     P=0.510      P=0.307N     P=0.353N    |P=0.167N     P=0.174N     P=0.307N     P=0.183N     |
|POLY 3             |     P=0.281N     P=0.571      P=0.296N     P=0.392N    |P=0.163N     P=0.182N     P=0.326N     P=0.180N     |
|POLY 1.5           |     P=0.288N     P=0.582      P=0.294N     P=0.396N    |P=0.164N     P=0.182N     P=0.335N     P=0.180N     |
|POLY 6             |     P=0.270N     P=0.561      P=0.296N     P=0.381N    |P=0.164N     P=0.179N     P=0.315N     P=0.181N     |
|LOGISTIC REGRESSION|     P=0.274N     P=0.551      P=0.298N     P=0.357N    |P=0.166N     P=0.172N     P=0.335N     P=0.178N     |
|COCH-ARM / FISHERS |     P=0.289N     P=0.602N     P=0.288N     P=0.393N    |P=0.165N     P=0.181N     P=0.339N     P=0.181N     |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 8
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     10/50 (20%)  9/50 (18%)   6/50 (12%)   5/50 (10%)  |2/50 (4%)    1/50 (2%)    1/50 (2%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     20.9%        19.4%        12.8%        10.5%       |4.4%         2.2%         2.1%         8.8%         |
|TERMINAL (d)       |     8/41 (20%)   7/37 (19%)   5/40 (13%)   5/43 (12%)  |1/37 (3%)    0/39 (0%)    1/40 (3%)    3/36 (8%)    |
|FIRST INCIDENCE    |     680          632          688          729 (T)     |548          727          731 (T)      709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.064N     P=0.588N     P=0.224N     P=0.115N    |P=0.155      P=0.490N     P=0.482N     P=0.330      |
|POLY 3             |     P=0.078N     P=0.532N     P=0.221N     P=0.131N    |P=0.166      P=0.501N     P=0.489N     P=0.336      |
|POLY 1.5           |     P=0.080N     P=0.520N     P=0.216N     P=0.133N    |P=0.165      P=0.502N     P=0.497N     P=0.337      |
|POLY 6             |     P=0.074N     P=0.543N     P=0.224N     P=0.127N    |P=0.165      P=0.496N     P=0.479N     P=0.337      |
|LOGISTIC REGRESSION|     P=0.075N     P=0.531N     P=0.220N     P=0.123N    |P=0.165      P=0.486N     P=0.490N     P=0.335      |
|COCH-ARM / FISHERS |     P=0.080N     P=0.500N     P=0.207N     P=0.131N    |P=0.164      P=0.500N     P=0.500N     P=0.339      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar                                                                      |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     18/50 (36%)  17/50 (34%)  12/50 (24%)  10/50 (20%) |6/50 (12%)   2/50 (4%)    3/50 (6%)    5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     37.6%        36.4%        25.4%        21.0%       |12.9%        4.4%         6.4%         10.9%        |
|TERMINAL (d)       |     16/41 (39%)  13/37 (35%)  10/40 (25%)  10/43 (23%) |3/37 (8%)    1/39 (3%)    3/40 (8%)    3/36 (8%)    |
|FIRST INCIDENCE    |     680          632          572          729 (T)     |548          727          731 (T)      681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.020N*    P=0.524      P=0.159N     P=0.044N*   |P=0.557      P=0.132N     P=0.217N     P=0.506N     |
|POLY 3             |     P=0.027N*    P=0.536N     P=0.143N     P=0.057N    |P=0.569N     P=0.140N     P=0.237N     P=0.512N     |
|POLY 1.5           |     P=0.029N*    P=0.524N     P=0.142N     P=0.059N    |P=0.570N     P=0.139N     P=0.243N     P=0.507N     |
|POLY 6             |     P=0.025N*    P=0.544N     P=0.142N     P=0.053N    |P=0.567      P=0.139N     P=0.227N     P=0.517N     |
|LOGISTIC REGRESSION|     P=0.026N*    P=0.567N     P=0.152N     P=0.045N*   |P=0.568      P=0.124N     P=0.238N     P=0.505N     |
|COCH-ARM / FISHERS |     P=0.030N*    P=0.500N     P=0.138N     P=0.059N    |P=0.570      P=0.134N     P=0.243N     P=0.500N     |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 9
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |1/45 (2%)    2/44 (5%)    2/48 (4%)    1/48 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |2.4%         5.0%         4.4%         2.3%         |
|TERMINAL (d)       |                                                        |1/35 (3%)    1/34 (3%)    2/39 (5%)    1/35 (3%)    |
|FIRST INCIDENCE    |                                                        |731 (T)      681          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.547N     P=0.502      P=0.538      P=0.762      |
|POLY 3             |                                                        |P=0.518N     P=0.489      P=0.539      P=0.744N     |
|POLY 1.5           |                                                        |P=0.521N     P=0.489      P=0.529      P=0.744N     |
|POLY 6             |                                                        |P=0.518N     P=0.491      P=0.549      P=0.744N     |
|LOGISTIC REGRESSION|                                                        |P=0.518N     P=0.488      P=0.538      P=0.762      |
|COCH-ARM / FISHERS |                                                        |P=0.526N     P=0.491      P=0.524      P=0.736N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/40 (0%)    0/38 (0%)    0/42 (0%)    0/46 (0%)   |4/46 (9%)    4/45 (9%)    9/46 (20%)   8/44 (18%)   |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |9.7%         9.6%         20.7%        20.1%        |
|TERMINAL (d)       |     0/34 (0%)    0/28 (0%)    0/34 (0%)    0/41 (0%)   |4/34 (12%)   4/37 (11%)   9/39 (23%)   7/32 (22%)   |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |731 (T)      731 (T)      731 (T)      709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.060      P=0.598N     P=0.172      P=0.149      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.075      P=0.640N     P=0.133      P=0.156      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.075      P=0.638      P=0.121      P=0.156      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.074      P=0.625N     P=0.152      P=0.158      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.060      P=0.598N     P=0.172      P=0.148      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.076      P=0.631      P=0.115      P=0.156      |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 10
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.1%         0.0%         0.0%         0.0%        |4.4%         0.0%         2.1%         0.0%         |
|TERMINAL (d)       |     1/41 (2%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |1/37 (3%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          ---          ---         |587          ---          658          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.298N     P=0.520N     P=0.505N     P=0.490N    |P=0.185N     P=0.239N     P=0.473N     P=0.243N     |
|POLY 3             |     P=0.302N     P=0.508N     P=0.504N     P=0.499N    |P=0.187N     P=0.238N     P=0.486N     P=0.237N     |
|POLY 1.5           |     P=0.303N     P=0.505N     P=0.503N     P=0.501N    |P=0.187N     P=0.238N     P=0.495N     P=0.238N     |
|POLY 6             |     P=0.302N     P=0.511N     P=0.505N     P=0.496N    |P=0.188N     P=0.234N     P=0.474N     P=0.237N     |
|LOGISTIC REGRESSION|     P=0.298N     (e)          (e)          (e)         |P=0.185N     P=0.221N     P=0.483N     P=0.235N     |
|COCH-ARM / FISHERS |     P=0.304N     P=0.500N     P=0.500N     P=0.500N    |P=0.188N     P=0.247N     P=0.500N     P=0.247N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         0.0%         2.1%        |4.4%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    1/37 (3%)    0/40 (0%)    1/43 (2%)   |2/37 (5%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      ---          729 (T)     |731 (T)      ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.421      P=0.480      (e)          P=0.510     |P=0.115N     P=0.227N     P=0.221N     P=0.244N     |
|POLY 3             |     P=0.403      P=0.492      (e)          P=0.501     |P=0.113N     P=0.235N     P=0.228N     P=0.235N     |
|POLY 1.5           |     P=0.402      P=0.495      (e)          P=0.499     |P=0.113N     P=0.237N     P=0.234N     P=0.236N     |
|POLY 6             |     P=0.407      P=0.489      (e)          P=0.504     |P=0.114N     P=0.231N     P=0.220N     P=0.234N     |
|LOGISTIC REGRESSION|     (e)          P=0.480      (e)          P=0.510     |P=0.115N     (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.403      P=0.500      (e)          P=0.500     |P=0.115N     P=0.247N     P=0.247N     P=0.247N     |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 11
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    5/50 (10%)   0/50 (0%)    0/50 (0%)   |2/50 (4%)    5/50 (10%)   2/50 (4%)    3/48 (6%)    |
|POLY-3 ADJUSTED (b)|     2.1%         11.0%        0.0%         0.0%        |4.4%         11.0%        4.2%         6.7%         |
|TERMINAL (d)       |     1/41 (2%)    5/37 (14%)   0/40 (0%)    0/43 (0%)   |2/37 (5%)    5/39 (13%)   2/40 (5%)    3/36 (8%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          ---         |731 (T)      731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.099N     P=0.081      P=0.505N     P=0.490N    |P=0.563      P=0.237      P=0.667N     P=0.487      |
|POLY 3             |     P=0.106N     P=0.092      P=0.504N     P=0.499N    |P=0.577      P=0.220      P=0.678N     P=0.494      |
|POLY 1.5           |     P=0.105N     P=0.096      P=0.503N     P=0.501N    |P=0.569      P=0.217      P=0.688N     P=0.489      |
|POLY 6             |     P=0.104N     P=0.089      P=0.505N     P=0.496N    |P=0.577N     P=0.227      P=0.665N     P=0.499      |
|LOGISTIC REGRESSION|     P=0.099N     P=0.081      (e)          (e)         |P=0.563      P=0.237      P=0.667N     P=0.487      |
|COCH-ARM / FISHERS |     P=0.108N     P=0.102      P=0.500N     P=0.500N    |P=0.559      P=0.218      P=0.691N     P=0.480      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    5/50 (10%)   0/50 (0%)    0/50 (0%)   |2/50 (4%)    5/50 (10%)   2/50 (4%)    3/48 (6%)    |
|POLY-3 ADJUSTED (b)|     4.2%         11.0%        0.0%         0.0%        |4.4%         11.0%        4.2%         6.7%         |
|TERMINAL (d)       |     2/41 (5%)    5/37 (14%)   0/40 (0%)    0/43 (0%)   |2/37 (5%)    5/39 (13%)   2/40 (5%)    3/36 (8%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          ---         |731 (T)      731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.049N*    P=0.176      P=0.244N     P=0.228N    |P=0.563      P=0.237      P=0.667N     P=0.487      |
|POLY 3             |     P=0.052N     P=0.200      P=0.242N     P=0.236N    |P=0.577      P=0.220      P=0.678N     P=0.494      |
|POLY 1.5           |     P=0.052N     P=0.207      P=0.240N     P=0.238N    |P=0.569      P=0.217      P=0.688N     P=0.489      |
|POLY 6             |     P=0.051N     P=0.193      P=0.243N     P=0.233N    |P=0.577N     P=0.227      P=0.665N     P=0.499      |
|LOGISTIC REGRESSION|     P=0.049N*    P=0.176      (e)          (e)         |P=0.563      P=0.237      P=0.667N     P=0.487      |
|COCH-ARM / FISHERS |     P=0.054N     P=0.218      P=0.247N     P=0.247N    |P=0.559      P=0.218      P=0.691N     P=0.480      |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 12
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/50 (4%)    2/50 (4%)    2/50 (4%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |4.4%         4.4%         4.2%         4.4%         |
|TERMINAL (d)       |                                                        |1/37 (3%)    1/39 (3%)    1/40 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |                                                        |606          633          673          681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.596      P=0.679N     P=0.662N     P=0.691      |
|POLY 3             |                                                        |P=0.593N     P=0.691N     P=0.680N     P=0.692N     |
|POLY 1.5           |                                                        |P=0.594N     P=0.693      P=0.689N     P=0.693N     |
|POLY 6             |                                                        |P=0.592N     P=0.685N     P=0.667N     P=0.691N     |
|LOGISTIC REGRESSION|                                                        |P=0.595      P=0.686N     P=0.693N     P=0.693      |
|COCH-ARM / FISHERS |                                                        |P=0.596      P=0.691N     P=0.691N     P=0.691N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.1%         0.0%         4.2%         0.0%        |0.0%         0.0%         2.1%         0.0%         |
|TERMINAL (d)       |     1/41 (2%)    0/37 (0%)    1/40 (3%)    0/43 (0%)   |0/37 (0%)    0/39 (0%)    1/40 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          497          ---         |---          ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.445N     P=0.520N     P=0.494      P=0.490N    |P=0.693      (e)          P=0.516      (e)          |
|POLY 3             |     P=0.449N     P=0.508N     P=0.498      P=0.499N    |P=0.694      (e)          P=0.509      (e)          |
|POLY 1.5           |     P=0.454N     P=0.505N     P=0.498      P=0.501N    |P=0.695      (e)          P=0.503      (e)          |
|POLY 6             |     P=0.442N     P=0.511N     P=0.498      P=0.496N    |P=0.693      (e)          P=0.516      (e)          |
|LOGISTIC REGRESSION|     P=0.405N     (e)          P=0.625      (e)         |(e)          (e)          P=0.516      (e)          |
|COCH-ARM / FISHERS |     P=0.458N     P=0.500N     P=0.500      P=0.500N    |P=0.694      (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 13
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    2/50 (4%)    2/50 (4%)   |1/50 (2%)    1/50 (2%)    2/50 (4%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     6.2%         2.2%         4.3%         4.2%        |2.2%         2.2%         4.2%         8.7%         |
|TERMINAL (d)       |     2/41 (5%)    1/37 (3%)    2/40 (5%)    0/43 (0%)   |1/37 (3%)    1/39 (3%)    0/40 (0%)    3/36 (8%)    |
|FIRST INCIDENCE    |     556          729 (T)      729 (T)      604         |731 (T)      731 (T)      625          646          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.471N     P=0.340N     P=0.513N     P=0.487N    |P=0.071      P=0.750N     P=0.535      P=0.180      |
|POLY 3             |     P=0.488N     P=0.324N     P=0.515N     P=0.499N    |P=0.074      P=0.759N     P=0.520      P=0.183      |
|POLY 1.5           |     P=0.494N     P=0.317N     P=0.509N     P=0.502N    |P=0.073      P=0.760N     P=0.508      P=0.181      |
|POLY 6             |     P=0.479N     P=0.332N     P=0.519N     P=0.493N    |P=0.075      P=0.754N     P=0.535      P=0.187      |
|LOGISTIC REGRESSION|     P=0.487N     P=0.255N     P=0.465N     P=0.440N    |P=0.071      P=0.750N     P=0.506      P=0.182      |
|COCH-ARM / FISHERS |     P=0.498N     P=0.309N     P=0.500N     P=0.500N    |P=0.072      P=0.753N     P=0.500      P=0.181      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    4/50 (8%)    2/50 (4%)   |1/50 (2%)    1/50 (2%)    3/50 (6%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     8.3%         2.2%         8.5%         4.2%        |2.2%         2.2%         6.3%         8.7%         |
|TERMINAL (d)       |     3/41 (7%)    1/37 (3%)    3/40 (8%)    0/43 (0%)   |1/37 (3%)    1/39 (3%)    1/40 (3%)    3/36 (8%)    |
|FIRST INCIDENCE    |     556          729 (T)      497          604         |731 (T)      731 (T)      625          646          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.367N     P=0.211N     P=0.629      P=0.326N    |P=0.073      P=0.750N     P=0.342      P=0.180      |
|POLY 3             |     P=0.379N     P=0.195N     P=0.633      P=0.337N    |P=0.078      P=0.759N     P=0.326      P=0.183      |
|POLY 1.5           |     P=0.387N     P=0.189N     P=0.636      P=0.340N    |P=0.077      P=0.760N     P=0.314      P=0.181      |
|POLY 6             |     P=0.366N     P=0.202N     P=0.631      P=0.330N    |P=0.079      P=0.754N     P=0.343      P=0.187      |
|LOGISTIC REGRESSION|     P=0.365N     P=0.152N     P=0.557N     P=0.291N    |P=0.075      P=0.750N     P=0.305      P=0.182      |
|COCH-ARM / FISHERS |     P=0.393N     P=0.181N     P=0.643N     P=0.339N    |P=0.075      P=0.753N     P=0.309      P=0.181      |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 14
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    2/50 (4%)    5/50 (10%)   3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         0.0%         0.0%        |2.2%         4.3%         10.4%        6.4%         |
|TERMINAL (d)       |     0/41 (0%)    1/37 (3%)    0/40 (0%)    0/43 (0%)   |0/37 (0%)    0/39 (0%)    2/40 (5%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |608          490          461          445          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.560N     P=0.480      (e)          (e)         |P=0.218      P=0.505      P=0.129      P=0.314      |
|POLY 3             |     P=0.578N     P=0.492      (e)          (e)         |P=0.224      P=0.508      P=0.114      P=0.313      |
|POLY 1.5           |     P=0.576N     P=0.495      (e)          (e)         |P=0.221      P=0.503      P=0.107      P=0.310      |
|POLY 6             |     P=0.579N     P=0.489      (e)          (e)         |P=0.225      P=0.516      P=0.123      P=0.316      |
|LOGISTIC REGRESSION|     (e)          P=0.480      (e)          (e)         |P=0.205      P=0.627      P=0.108      P=0.307      |
|COCH-ARM / FISHERS |     P=0.573N     P=0.500      (e)          (e)         |P=0.216      P=0.500      P=0.102      P=0.309      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   3/50 (6%)    3/50 (6%)    1/50 (2%)   |9/50 (18%)   10/50 (20%)  8/50 (16%)   10/50 (20%)  |
|POLY-3 ADJUSTED (b)|     10.5%        6.6%         6.4%         2.1%        |19.4%        21.7%        16.9%        21.6%        |
|TERMINAL (d)       |     5/41 (12%)   3/37 (8%)    2/40 (5%)    1/43 (2%)   |5/37 (14%)   7/39 (18%)   6/40 (15%)   8/36 (22%)   |
|FIRST INCIDENCE    |     729 (T)      729 (T)      727          729 (T)     |606          659          698          608          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.069N     P=0.413N     P=0.371N     P=0.093N    |P=0.470      P=0.545      P=0.425N     P=0.496      |
|POLY 3             |     P=0.076N     P=0.379N     P=0.368N     P=0.101N    |P=0.489      P=0.493      P=0.483N     P=0.496      |
|POLY 1.5           |     P=0.078N     P=0.371N     P=0.364N     P=0.103N    |P=0.489      P=0.492      P=0.497N     P=0.498      |
|POLY 6             |     P=0.072N     P=0.388N     P=0.370N     P=0.097N    |P=0.484      P=0.501      P=0.465N     P=0.492      |
|LOGISTIC REGRESSION|     P=0.065N     P=0.413N     P=0.359N     P=0.093N    |P=0.493      P=0.500      P=0.496N     P=0.500      |
|COCH-ARM / FISHERS |     P=0.079N     P=0.357N     P=0.357N     P=0.102N    |P=0.488      P=0.500      P=0.500N     P=0.500      |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 15
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     24/50 (48%)  27/50 (54%)  24/50 (48%)  22/50 (44%) |21/50 (42%)  23/50 (46%)  25/50 (50%)  19/50 (38%)  |
|POLY-3 ADJUSTED (b)|     49.7%        58.5%        50.3%        46.1%       |44.7%        49.8%        52.8%        40.9%        |
|TERMINAL (d)       |     21/41 (51%)  24/37 (65%)  21/40 (53%)  22/43 (51%) |17/37 (46%)  19/39 (49%)  24/40 (60%)  15/36 (42%)  |
|FIRST INCIDENCE    |     636          636          497          729 (T)     |587          633          673          608          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.178N     P=0.182      P=0.530      P=0.342N    |P=0.400N     P=0.504      P=0.401      P=0.449N     |
|POLY 3             |     P=0.289N     P=0.254      P=0.559      P=0.442N    |P=0.354N     P=0.387      P=0.282      P=0.434N     |
|POLY 1.5           |     P=0.297N     P=0.289      P=0.567      P=0.441N    |P=0.352N     P=0.394      P=0.266      P=0.429N     |
|POLY 6             |     P=0.273N     P=0.217      P=0.551      P=0.438N    |P=0.358N     P=0.396      P=0.306      P=0.439N     |
|LOGISTIC REGRESSION|     P=0.247N     P=0.234      P=0.550      P=0.383N    |P=0.324N     P=0.429      P=0.325      P=0.409N     |
|COCH-ARM / FISHERS |     P=0.293N     P=0.345      P=0.579N     P=0.421N    |P=0.350N     P=0.420      P=0.274      P=0.419N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     31/50 (62%)  33/50 (66%)  32/50 (64%)  26/50 (52%) |22/50 (44%)  22/50 (44%)  25/50 (50%)  25/50 (50%)  |
|POLY-3 ADJUSTED (b)|     62.4%        66.6%        64.0%        52.0%       |44.4%        46.1%        51.1%        51.7%        |
|TERMINAL (d)       |     23/41 (56%)  22/37 (60%)  22/40 (55%)  20/43 (47%) |10/37 (27%)  15/39 (39%)  17/40 (43%)  15/36 (42%)  |
|FIRST INCIDENCE    |     556          446          497          281         |484          490          461          445          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.112N     P=0.263      P=0.448      P=0.198N    |P=0.276      P=0.510N     P=0.491      P=0.365      |
|POLY 3             |     P=0.119N     P=0.410      P=0.517      P=0.200N    |P=0.244      P=0.515      P=0.324      P=0.303      |
|POLY 1.5           |     P=0.124N     P=0.414      P=0.509      P=0.204N    |P=0.253      P=0.536      P=0.320      P=0.320      |
|POLY 6             |     P=0.111N     P=0.403      P=0.528      P=0.192N    |P=0.231      P=0.500      P=0.331      P=0.285      |
|LOGISTIC REGRESSION|     P=0.184N     P=0.509      P=0.527      P=0.252N    |P=0.257      P=0.576      P=0.298      P=0.308      |
|COCH-ARM / FISHERS |     P=0.130N     P=0.418      P=0.500      P=0.210N    |P=0.267      P=0.580N     P=0.344      P=0.344      |
|=================================================================================================================================|
       Date:  12/02/98                           EXPERIMENT: 05211 TEST: 06                                            Page 16
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                       EMODIN
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     43/50 (86%)  46/50 (92%)  43/50 (86%)  37/50 (74%) |34/50 (68%)  33/50 (66%)  43/50 (86%)  37/50 (74%)  |
|POLY-3 ADJUSTED (b)|     86.0%        92.7%        86.0%        74.0%       |68.0%        69.1%        87.8%        76.2%        |
|TERMINAL (d)       |     34/41 (83%)  34/37 (92%)  33/40 (83%)  31/43 (72%) |21/37 (57%)  26/39 (67%)  35/40 (88%)  26/36 (72%)  |
|FIRST INCIDENCE    |     556          446          497          281         |484          490          461          445          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.036N*    P=0.129      P=0.492      P=0.115N    |P=0.192      P=0.409N     P=0.204      P=0.352      |
|POLY 3             |     P=0.023N*    P=0.225      P=0.612      P=0.106N    |P=0.123      P=0.539      P=0.015 *    P=0.248      |
|POLY 1.5           |     P=0.024N*    P=0.242      P=0.612      P=0.106N    |P=0.139      P=0.584      P=0.015 *    P=0.279      |
|POLY 6             |     P=0.022N*    P=0.203      P=0.612      P=0.106N    |P=0.106      P=0.499      P=0.014 *    P=0.217      |
|LOGISTIC REGRESSION|     P=0.035N*    P=0.291      (e)          P=0.129N    |P=0.174      P=0.500N     P=0.029 *    P=0.317      |
|COCH-ARM / FISHERS |     P=0.026N*    P=0.262      P=0.613N     P=0.105N    |P=0.171      P=0.500N     P=0.028 *    P=0.330      |
|=================================================================================================================================|

(a)  Number of tumor-bearing animals /  number of animals examined at site.
(b)  Poly-3 adjusted lifetime tumor incidence.
(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.
(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).