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TDMS Study 05211-06 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                      EMODIN                                        DATE: 04/07/99       
EXPERIMENT: 05211 TEST: 06                                                                                     TIME: 10:51:38       
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; FINAL#1,REVISION#1                                                   
                                                                                                                                    

               REASONS FOR REMOVAL:    25022 Accidently Killed                                                                      
                                       25019 Moribund Sacrifice                                                                     
                                       25020 Natural Death                                                                          
                                       25021 Terminal Sacrifice                                                                     
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10   
LAB: Southern Research Inst                                      EMODIN                                        DATE: 04/07/99     
EXPERIMENT: 05211 TEST: 06                                                                                     TIME: 10:51:38     
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                         Hyperplasia Focal
Kidney: Renal Tubule                   Dilatation
                                       Pigmentation
Liver                                  Eosinophilic Focus
Liver: Hepatocyte                      Vacuolization Cytoplasmic Focal
Preputial Gland                        Inflammation Chronic
Seminal Vesicle                        Dilatation
Thyroid Gland: Follicular Cell         Hyperplasia
===============================================================
Female Mice
------------
Organ                                  Morphology
-----                                  ----------
Adrenal Cortex                         Cyst
Kidney                                 Nephropathy
Kidney: Renal Tubule                   Pigmentation
Liver                                  Inflammation Focal
Lymph Node, Mesenteric                 Hemorrhage
Lymph Node: Iliac                      Angiectasis
Thyroid Gland                          Degeneration Cystic Focal
Thyroid Gland: Follicular Cell         Hyperplasia
Uterus                                 Cyst
===============================================================
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                   |
|     Accessory Adrenal Cortical Nodule                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.2%         2.2%         0.0%         2.1%        |2.2%         2.2%         2.1%         0.0%         |
|TERMINAL (d)       |     1/41 (2%)    1/37 (3%)    0/40 (0%)    1/43 (2%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     728          729 (T)      ---          729 (T)     |681          727          90           ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.349N     P=0.538N     P=0.248N     P=0.486N    |P=0.312N     P=0.746N     P=0.750N     P=0.495N     |
|POLY 3             |     P=0.364N     P=0.514N     P=0.242N     P=0.499N    |P=0.310N     P=0.759N     P=0.747N     P=0.499N     |
|POLY 1.5           |     P=0.366N     P=0.509N     P=0.240N     P=0.501N    |P=0.311N     P=0.760      P=0.753N     P=0.499N     |
|POLY 6             |     P=0.362N     P=0.520N     P=0.243N     P=0.494N    |P=0.309N     P=0.756N     P=0.739N     P=0.499N     |
|LOGISTIC REGRESSION|     P=0.344N     P=0.538N     P=0.239N     P=0.481N    |P=0.275N     P=0.762N     P=0.593N     P=0.501N     |
|COCH-ARM / FISHERS |     P=0.367N     P=0.500N     P=0.247N     P=0.500N    |P=0.311N     P=0.753N     P=0.753N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     2.1%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         4.4%         |
|TERMINAL (d)       |     1/41 (2%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    2/36 (6%)    |
|FIRST INCIDENCE    |     729 (T)      ---          ---          ---         |---          ---          ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.298N     P=0.520N     P=0.505N     P=0.490N    |P=0.042 *    (e)          (e)          P=0.232      |
|POLY 3             |     P=0.302N     P=0.508N     P=0.504N     P=0.499N    |P=0.046 *    (e)          (e)          P=0.239      |
|POLY 1.5           |     P=0.303N     P=0.505N     P=0.503N     P=0.501N    |P=0.046 *    (e)          (e)          P=0.238      |
|POLY 6             |     P=0.302N     P=0.511N     P=0.505N     P=0.496N    |P=0.046 *    (e)          (e)          P=0.240      |
|LOGISTIC REGRESSION|     P=0.298N     (e)          (e)          (e)         |(e)          (e)          (e)          P=0.232      |
|COCH-ARM / FISHERS |     P=0.304N     P=0.500N     P=0.500N     P=0.500N    |P=0.046 *    (e)          (e)          P=0.247      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                   |
|     Cytoplasmic Alteration Focal                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    4/50 (8%)    1/50 (2%)    3/50 (6%)   |0/50 (0%)    1/50 (2%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         8.8%         2.1%         6.3%        |0.0%         2.2%         4.2%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    4/37 (11%)   1/40 (3%)    3/43 (7%)   |0/37 (0%)    1/39 (3%)    2/40 (5%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |---          731 (T)      731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.259      P=0.051      P=0.495      P=0.130     |P=0.627N     P=0.511      P=0.256      (e)          |
|POLY 3             |     P=0.227      P=0.055      P=0.496      P=0.120     |P=0.613N     P=0.502      P=0.247      (e)          |
|POLY 1.5           |     P=0.225      P=0.057      P=0.497      P=0.119     |P=0.614N     P=0.500      P=0.241      (e)          |
|POLY 6             |     P=0.231      P=0.053      P=0.495      P=0.122     |P=0.611N     P=0.506      P=0.256      (e)          |
|LOGISTIC REGRESSION|     (e)          P=0.051      P=0.495      P=0.130     |(e)          P=0.511      P=0.256      (e)          |
|COCH-ARM / FISHERS |     P=0.228      P=0.059      P=0.500      P=0.121     |P=0.616N     P=0.500      P=0.247      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     6.3%         0.0%         0.0%         0.0%        |2.2%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     3/41 (7%)    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)      ---          ---          ---         |731 (T)      ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.045N*    P=0.140N     P=0.126N     P=0.113N    |P=0.307N     P=0.489N     P=0.484N     P=0.505N     |
|POLY 3             |     P=0.043N*    P=0.126N     P=0.123N     P=0.118N    |P=0.305N     P=0.498N     P=0.491N     P=0.498N     |
|POLY 1.5           |     P=0.043N*    P=0.124N     P=0.121N     P=0.119N    |P=0.306N     P=0.500N     P=0.497N     P=0.499N     |
|POLY 6             |     P=0.042N*    P=0.129N     P=0.123N     P=0.116N    |P=0.306N     P=0.494N     P=0.484N     P=0.497N     |
|LOGISTIC REGRESSION|     P=0.045N*    (e)          (e)          (e)         |P=0.307N     (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.046N*    P=0.121N     P=0.121N     P=0.121N    |P=0.306N     P=0.500N     P=0.500N     P=0.500N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                   |
|     Hypertrophy Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.2%         2.2%         4.3%         2.1%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     2/41 (5%)    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)      729 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.415N     P=0.536N     P=0.686      P=0.483N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.436N     P=0.514N     P=0.686      P=0.499N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.441N     P=0.509N     P=0.689      P=0.501N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.429N     P=0.520N     P=0.685      P=0.494N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.415N     P=0.536N     P=0.686      P=0.483N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.443N     P=0.500N     P=0.691N     P=0.500N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex: Capsule                                                                                                          |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    1/50 (2%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     4.2%         2.2%         2.1%         2.1%        |2.2%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     2/41 (5%)    1/37 (3%)    1/40 (3%)    1/43 (2%)   |1/37 (3%)    0/39 (0%)    0/40 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |731 (T)      ---          ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.384N     P=0.536N     P=0.509N     P=0.483N    |P=0.589      P=0.489N     P=0.484N     P=0.756      |
|POLY 3             |     P=0.404N     P=0.514N     P=0.507N     P=0.499N    |P=0.596      P=0.498N     P=0.491N     P=0.759N     |
|POLY 1.5           |     P=0.407N     P=0.509N     P=0.505N     P=0.501N    |P=0.595      P=0.500N     P=0.497N     P=0.759N     |
|POLY 6             |     P=0.399N     P=0.520N     P=0.509N     P=0.494N    |P=0.594      P=0.494N     P=0.484N     P=0.757N     |
|LOGISTIC REGRESSION|     P=0.384N     P=0.536N     P=0.509N     P=0.483N    |P=0.589      (e)          (e)          P=0.756      |
|COCH-ARM / FISHERS |     P=0.409N     P=0.500N     P=0.500N     P=0.500N    |P=0.595      P=0.500N     P=0.500N     P=0.753N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions 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 Medulla                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    2/49 (4%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     2.1%         4.4%         0.0%         2.1%        |0.0%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     0/41 (0%)    1/37 (3%)    0/40 (0%)    1/43 (2%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     636          639          ---          729 (T)     |---          ---          ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.496N     P=0.471      P=0.517N     P=0.759     |P=0.191      (e)          (e)          P=0.495      |
|POLY 3             |     P=0.505N     P=0.480      P=0.506N     P=0.760     |P=0.200      (e)          (e)          P=0.502      |
|POLY 1.5           |     P=0.504N     P=0.485      P=0.504N     P=0.759     |P=0.200      (e)          (e)          P=0.501      |
|POLY 6             |     P=0.504N     P=0.475      P=0.507N     P=0.759N    |P=0.199      (e)          (e)          P=0.503      |
|LOGISTIC REGRESSION|     P=0.486N     P=0.579      P=0.399N     P=0.748N    |(e)          (e)          (e)          P=0.495      |
|COCH-ARM / FISHERS |     P=0.502N     P=0.492      P=0.500N     P=0.753N    |P=0.198      (e)          (e)          P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Blood Vessel: Pulmonary Artery, Media                                                                                            |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/0 (0%)     0/1 (0%)     0/1 (0%)     0/0 (0%)    |0/0 (0%)     3/4 (75%)    0/2 (0%)     1/2 (50%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         95.1%        0.0%         54.0%        |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/1 (0%)     0/0 (0%)    |0/0 (0%)     3/3 (100%)   0/1 (0%)     1/1 (100%)   |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          731 (T)      ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.753N     P=1.000      (e)          P=1.000N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          P=1.000      (e)          P=1.000N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.500N     P=1.000      (e)          P=1.000      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |3/48 (6%)    1/50 (2%)    1/49 (2%)    5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     2.1%         0.0%         0.0%         2.1%        |6.8%         2.2%         2.1%         10.7%        |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    1/43 (2%)   |1/37 (3%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     680          ---          ---          729 (T)     |684          633          698          608          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.610      P=0.514N     P=0.500N     P=0.750N    |P=0.166      P=0.287N     P=0.269N     P=0.368      |
|POLY 3             |     P=0.603      P=0.509N     P=0.505N     P=0.760     |P=0.175      P=0.292N     P=0.283N     P=0.387      |
|POLY 1.5           |     P=0.600      P=0.505N     P=0.503N     P=0.759     |P=0.173      P=0.293N     P=0.292N     P=0.383      |
|POLY 6             |     P=0.607      P=0.513N     P=0.506N     P=0.758N    |P=0.176      P=0.288N     P=0.274N     P=0.392      |
|LOGISTIC REGRESSION|     P=0.598      P=0.466N     P=0.467N     P=0.760N    |P=0.169      P=0.282N     P=0.299N     P=0.383      |
|COCH-ARM / FISHERS |     P=0.597      P=0.500N     P=0.500N     P=0.753N    |P=0.171      P=0.293N     P=0.301N     P=0.381      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Atrophy Focal                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    1/49 (2%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.2%         0.0%         2.2%         6.6%         |
|TERMINAL (d)       |     0/40 (0%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |0/37 (0%)    0/39 (0%)    1/40 (3%)    2/36 (6%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |484          ---          731 (T)      709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.091      P=0.508N     P=0.756N     P=0.301      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.097      P=0.501N     P=0.759N     P=0.304      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.097      P=0.502N     P=0.757      P=0.304      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.096      P=0.499N     P=0.752N     P=0.304      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.094      P=0.264N     P=0.739N     P=0.303      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.097      P=0.500N     P=0.747      P=0.309      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                         |
|     Inflammation Focal                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/47 (0%)    0/46 (0%)    0/49 (0%)    2/50 (4%)   |0/45 (0%)    0/48 (0%)    0/45 (0%)    0/46 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         4.2%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    2/43 (5%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.055      (e)          (e)          P=0.249     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.050      (e)          (e)          P=0.249     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.050      (e)          (e)          P=0.249     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.051      (e)          (e)          P=0.250     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.249     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.052      (e)          (e)          P=0.263     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    4/50 (8%)    3/50 (6%)    3/50 (6%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         8.8%         6.4%         6.3%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    4/37 (11%)   3/40 (8%)    3/43 (7%)   |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=0.252      P=0.051      P=0.117      P=0.130     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.226      P=0.058      P=0.118      P=0.123     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.223      P=0.060      P=0.120      P=0.122     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.232      P=0.055      P=0.117      P=0.125     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          P=0.051      P=0.117      P=0.130     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.224      P=0.061      P=0.125      P=0.125     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                           |
|     Metaplasia Focal Osseous                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    2/50 (4%)    1/50 (2%)   |0/49 (0%)    2/50 (4%)    2/50 (4%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         4.3%         2.1%        |0.0%         4.4%         4.2%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    2/40 (5%)    0/43 (0%)   |0/37 (0%)    2/39 (5%)    2/40 (5%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          729 (T)      633         |---          731 (T)      731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.262      (e)          P=0.233      P=0.492     |P=0.511N     P=0.250      P=0.256      (e)          |
|POLY 3             |     P=0.261      (e)          P=0.237      P=0.506     |P=0.492N     P=0.243      P=0.251      (e)          |
|POLY 1.5           |     P=0.255      (e)          P=0.239      P=0.504     |P=0.495N     P=0.241      P=0.245      (e)          |
|POLY 6             |     P=0.271      (e)          P=0.235      P=0.509     |P=0.489N     P=0.246      P=0.258      (e)          |
|LOGISTIC REGRESSION|     P=0.253      (e)          P=0.233      P=0.564     |(e)          P=0.250      P=0.256      (e)          |
|COCH-ARM / FISHERS |     P=0.251      (e)          P=0.253      P=0.505     |P=0.501N     P=0.253      P=0.253      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     49/49 (100%) 49/50 (98%)  50/50 (100%) 49/50 (98%) |22/49 (45%)  46/50 (92%)  41/50 (82%)  48/49 (98%)  |
|POLY-3 ADJUSTED (b)|     100.0%       98.7%        100.0%       98.0%       |48.6%        92.6%        85.0%        98.4%        |
|TERMINAL (d)       |     41/41 (100%) 37/37 (100%) 40/40 (100%) 42/43 (98%) |19/37 (51%)  36/39 (92%)  34/40 (85%)  36/36 (100%) |
|FIRST INCIDENCE    |     556          446          497          281         |587          391          625          515          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.243N     P=0.209      (e)          P=0.402N    |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 3             |     P=0.338N     P=0.695N     (e)          P=0.504N    |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P=0.370N     P=0.593N     (e)          P=0.504N    |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 6             |     P=0.287N     P=0.897N     (e)          P=0.504N    |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P=0.416N     P=0.604N     (e)          (e)         |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P=0.406N     P=0.505N     (e)          P=0.505N    |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions 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: Pelvis                                                                                                                   |
|     Dilatation                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/49 (6%)    3/50 (6%)    1/50 (2%)    6/50 (12%)  |0/49 (0%)    1/50 (2%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     6.4%         6.5%         2.1%         12.6%       |0.0%         2.2%         0.0%         0.0%         |
|TERMINAL (d)       |     2/41 (5%)    1/37 (3%)    1/40 (3%)    6/43 (14%)  |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     636          639          729 (T)      729 (T)     |---          490          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.182      P=0.621      P=0.321N     P=0.262     |P=0.566N     P=0.496      (e)          (e)          |
|POLY 3             |     P=0.159      P=0.653      P=0.309N     P=0.250     |P=0.563N     P=0.508      (e)          (e)          |
|POLY 1.5           |     P=0.158      P=0.660      P=0.305N     P=0.249     |P=0.566N     P=0.506      (e)          (e)          |
|POLY 6             |     P=0.162      P=0.647      P=0.312N     P=0.254     |P=0.558N     P=0.512      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.160      P=0.616N     P=0.288N     P=0.252     |P=0.580N     P=0.723      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.159      P=0.651N     P=0.301N     P=0.254     |P=0.568N     P=0.505      (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Accumulation, Hyaline Droplet                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |1/49 (2%)    3/50 (6%)    1/50 (2%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         2.1%        |2.2%         6.4%         2.1%         4.4%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    1/43 (2%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |608          490          730          608          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.213      (e)          (e)          P=0.510     |P=0.529      P=0.322      P=0.736N     P=0.507      |
|POLY 3             |     P=0.204      (e)          (e)          P=0.504     |P=0.534      P=0.319      P=0.749N     P=0.507      |
|POLY 1.5           |     P=0.202      (e)          (e)          P=0.503     |P=0.530      P=0.315      P=0.754N     P=0.504      |
|POLY 6             |     P=0.207      (e)          (e)          P=0.507     |P=0.536      P=0.326      P=0.744N     P=0.509      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.510     |P=0.507      P=0.377      P=0.753N     P=0.449      |
|COCH-ARM / FISHERS |     P=0.201      (e)          (e)          P=0.505     |P=0.524      P=0.316      P=0.747N     P=0.500      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                             |
|     Dilatation                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    3/50 (6%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         6.3%        |0.0%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    3/43 (7%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |---          ---          ---          709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.015 *    (e)          (e)          P=0.130     |P=0.192      (e)          (e)          P=0.500      |
|POLY 3             |     P=0.012 *    (e)          (e)          P=0.123     |P=0.200      (e)          (e)          P=0.504      |
|POLY 1.5           |     P=0.011 *    (e)          (e)          P=0.122     |P=0.199      (e)          (e)          P=0.503      |
|POLY 6             |     P=0.012 *    (e)          (e)          P=0.125     |P=0.200      (e)          (e)          P=0.506      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.130     |P=0.197      (e)          (e)          P=0.501      |
|COCH-ARM / FISHERS |     P=0.012 *    (e)          (e)          P=0.125     |P=0.197      (e)          (e)          P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Pigmentation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    46/50 (92%)  50/50 (100%) 50/50 (100%)|0/49 (0%)    37/50 (74%)  48/50 (96%)  49/49 (100%) |
|POLY-3 ADJUSTED (b)|     0.0%         92.7%        100.0%       100.0%      |0.0%         78.3%        98.0%        100.0%       |
|TERMINAL (d)       |     0/41 (0%)    34/37 (92%)  40/40 (100%) 43/43 (100%)|0/37 (0%)    32/39 (82%)  39/40 (98%)  36/36 (100%) |
|FIRST INCIDENCE    |     ---          446          497          281         |---          461          461          515          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    1/50 (2%)    2/50 (4%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.1%         0.0%        |0.0%         2.2%         4.2%         2.2%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    1/40 (3%)    0/43 (0%)   |0/37 (0%)    1/39 (3%)    2/40 (5%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.704      (e)          P=0.495      (e)         |P=0.354      P=0.511      P=0.256      P=0.495      |
|POLY 3             |     P=0.703      (e)          P=0.496      (e)         |P=0.370      P=0.502      P=0.247      P=0.502      |
|POLY 1.5           |     P=0.699      (e)          P=0.497      (e)         |P=0.369      P=0.500      P=0.241      P=0.501      |
|POLY 6             |     P=0.711      (e)          P=0.495      (e)         |P=0.371      P=0.506      P=0.256      P=0.503      |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.495      (e)         |(e)          P=0.511      P=0.256      P=0.495      |
|COCH-ARM / FISHERS |     P=0.697      (e)          P=0.500      (e)         |P=0.366      P=0.500      P=0.247      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.2%         0.0%         0.0%         4.2%        |0.0%         0.0%         2.1%         0.0%         |
|TERMINAL (d)       |     1/41 (2%)    0/37 (0%)    0/40 (0%)    2/43 (5%)   |0/37 (0%)    0/39 (0%)    1/40 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     639          ---          ---          729 (T)     |---          ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.520      P=0.258N     P=0.247N     P=0.682N    |P=0.693      (e)          P=0.516      (e)          |
|POLY 3             |     P=0.511      P=0.248N     P=0.244N     P=0.692     |P=0.694      (e)          P=0.509      (e)          |
|POLY 1.5           |     P=0.507      P=0.244N     P=0.241N     P=0.691     |P=0.695      (e)          P=0.503      (e)          |
|POLY 6             |     P=0.516      P=0.253N     P=0.245N     P=0.691N    |P=0.693      (e)          P=0.516      (e)          |
|LOGISTIC REGRESSION|     P=0.503      P=0.200N     P=0.203N     P=0.691N    |(e)          (e)          P=0.516      (e)          |
|COCH-ARM / FISHERS |     P=0.503      P=0.247N     P=0.247N     P=0.691N    |P=0.694      (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            |
|     Clear Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/50 (0%)    4/50 (8%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.2%         2.2%         0.0%         8.4%        |0.0%         2.2%         0.0%         0.0%         |
|TERMINAL (d)       |     2/41 (5%)    1/37 (3%)    0/40 (0%)    4/43 (9%)   |0/37 (0%)    1/39 (3%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          729 (T)     |---          731 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.190      P=0.536N     P=0.244N     P=0.359     |P=0.573N     P=0.511      (e)          (e)          |
|POLY 3             |     P=0.168      P=0.514N     P=0.242N     P=0.339     |P=0.563N     P=0.502      (e)          (e)          |
|POLY 1.5           |     P=0.166      P=0.509N     P=0.240N     P=0.336     |P=0.565N     P=0.500      (e)          (e)          |
|POLY 6             |     P=0.171      P=0.520N     P=0.243N     P=0.346     |P=0.558N     P=0.506      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.190      P=0.536N     (e)          P=0.359     |(e)          P=0.511      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.165      P=0.500N     P=0.247N     P=0.339     |P=0.567N     P=0.500      (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Congestion Focal                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    2/50 (4%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         2.1%        |2.2%         0.0%         4.2%         2.2%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    1/43 (2%)   |1/37 (3%)    0/39 (0%)    2/40 (5%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |731 (T)      ---          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.213      (e)          (e)          P=0.510     |P=0.489      P=0.489N     P=0.527      P=0.756      |
|POLY 3             |     P=0.202      (e)          (e)          P=0.501     |P=0.502      P=0.498N     P=0.515      P=0.759N     |
|POLY 1.5           |     P=0.201      (e)          (e)          P=0.499     |P=0.502      P=0.500N     P=0.506      P=0.759N     |
|POLY 6             |     P=0.205      (e)          (e)          P=0.504     |P=0.500      P=0.494N     P=0.528      P=0.757N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.510     |P=0.489      (e)          P=0.527      P=0.756      |
|COCH-ARM / FISHERS |     P=0.199      (e)          (e)          P=0.500     |P=0.500      P=0.500N     P=0.500      P=0.753N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     14.7%        0.0%         2.1%         4.2%        |0.0%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     6/41 (15%)   0/37 (0%)    1/40 (3%)    2/43 (5%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     699          ---          729 (T)      729 (T)     |---          ---          ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.066N     P=0.014N*    P=0.036N*    P=0.072N    |P=0.191      (e)          (e)          P=0.495      |
|POLY 3             |     P=0.066N     P=0.009N**   P=0.033N*    P=0.079N    |P=0.200      (e)          (e)          P=0.502      |
|POLY 1.5           |     P=0.068N     P=0.008N**   P=0.032N*    P=0.080N    |P=0.200      (e)          (e)          P=0.501      |
|POLY 6             |     P=0.063N     P=0.010N*    P=0.033N*    P=0.076N    |P=0.199      (e)          (e)          P=0.503      |
|LOGISTIC REGRESSION|     P=0.067N     P=0.012N*    P=0.034N*    P=0.073N    |(e)          (e)          (e)          P=0.495      |
|COCH-ARM / FISHERS |     P=0.075N     P=0.006N**   P=0.030N*    P=0.080N    |P=0.198      (e)          (e)          P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemorrhage Focal                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.2%         0.0%         2.1%         4.4%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |1/37 (3%)    0/39 (0%)    1/40 (3%)    2/36 (6%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |731 (T)      ---          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.234      P=0.489N     P=0.744N     P=0.490      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.250      P=0.498N     P=0.751N     P=0.503      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.249      P=0.500N     P=0.757N     P=0.502      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.248      P=0.494N     P=0.742N     P=0.505      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.234      (e)          P=0.744N     P=0.490      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.247      P=0.500N     P=0.753N     P=0.500      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            |
|     Hyperplasia Focal Lymphoid                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         4.2%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |0/37 (0%)    0/39 (0%)    2/40 (5%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.589      (e)          P=0.256      (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.596      (e)          P=0.247      (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.597      (e)          P=0.241      (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.594      (e)          P=0.256      (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          P=0.256      (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.595      (e)          P=0.247      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Inflammation Focal                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |5/50 (10%)   3/50 (6%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.1%         0.0%         0.0%         0.0%        |11.1%        6.5%         0.0%         0.0%         |
|TERMINAL (d)       |     1/41 (2%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |5/37 (14%)   2/39 (5%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          ---          ---         |731 (T)      391          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.298N     P=0.520N     P=0.505N     P=0.490N    |P=0.007N**   P=0.332N     P=0.027N*    P=0.035N*    |
|POLY 3             |     P=0.302N     P=0.508N     P=0.504N     P=0.499N    |P=0.006N**   P=0.341N     P=0.027N*    P=0.030N*    |
|POLY 1.5           |     P=0.303N     P=0.505N     P=0.503N     P=0.501N    |P=0.007N**   P=0.349N     P=0.029N*    P=0.030N*    |
|POLY 6             |     P=0.302N     P=0.511N     P=0.505N     P=0.496N    |P=0.006N**   P=0.329N     P=0.024N*    P=0.029N*    |
|LOGISTIC REGRESSION|     P=0.298N     (e)          (e)          (e)         |P=0.007N**   P=0.352N     (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.304N     P=0.500N     P=0.500N     P=0.500N    |P=0.007N**   P=0.357N     P=0.028N*    P=0.028N*    |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            |
|     Necrosis Focal                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    4/50 (8%)    2/50 (4%)    2/50 (4%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         8.5%         4.2%         4.1%        |0.0%         2.2%         0.0%         4.4%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          446          579          604         |---          681          ---          680          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.412      P=0.062      P=0.228      P=0.247     |P=0.140      P=0.510      (e)          P=0.245      |
|POLY 3             |     P=0.408      P=0.060      P=0.237      P=0.241     |P=0.143      P=0.503      (e)          P=0.241      |
|POLY 1.5           |     P=0.401      P=0.060      P=0.237      P=0.238     |P=0.141      P=0.501      (e)          P=0.239      |
|POLY 6             |     P=0.422      P=0.060      P=0.239      P=0.246     |P=0.145      P=0.507      (e)          P=0.243      |
|LOGISTIC REGRESSION|     P=0.489      P=0.156      P=0.462      P=0.278     |P=0.139      P=0.504      (e)          P=0.237      |
|COCH-ARM / FISHERS |     P=0.399      P=0.059      P=0.247      P=0.247     |P=0.140      P=0.500      (e)          P=0.247      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Hepatocyte                                                                                                                |
|     Fatty Change Diffuse                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    1/50 (2%)    1/50 (2%)   |1/50 (2%)    3/50 (6%)    2/50 (4%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     2.1%         2.2%         2.1%         2.1%        |2.2%         6.5%         4.2%         8.6%         |
|TERMINAL (d)       |     1/41 (2%)    1/37 (3%)    1/40 (3%)    1/43 (2%)   |1/37 (3%)    1/39 (3%)    1/40 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |731 (T)      552          673          604          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.609N     P=0.739      P=0.756      P=0.751N    |P=0.165      P=0.322      P=0.531      P=0.186      |
|POLY 3             |     P=0.630N     P=0.751      P=0.756      P=0.760N    |P=0.171      P=0.315      P=0.517      P=0.187      |
|POLY 1.5           |     P=0.632N     P=0.755      P=0.757      P=0.760     |P=0.167      P=0.309      P=0.507      P=0.183      |
|POLY 6             |     P=0.625N     P=0.748      P=0.755      P=0.757N    |P=0.176      P=0.326      P=0.531      P=0.192      |
|LOGISTIC REGRESSION|     P=0.609N     P=0.739      P=0.756      P=0.751N    |P=0.159      P=0.318      P=0.504      P=0.177      |
|COCH-ARM / FISHERS |     P=0.634      P=0.753N     P=0.753N     P=0.753N    |P=0.162      P=0.309      P=0.500      P=0.181      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions 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: Hepatocyte                                                                                                                |
|     Vacuolization Cytoplasmic Focal                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     13/50 (26%)  10/50 (20%)  7/50 (14%)   6/50 (12%)  |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     27.3%        21.9%        15.0%        12.6%       |0.0%         0.0%         2.1%         0.0%         |
|TERMINAL (d)       |     13/41 (32%)  10/37 (27%)  7/40 (18%)   6/43 (14%)  |0/37 (0%)    0/39 (0%)    1/40 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |---          ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.026N*    P=0.420N     P=0.112N     P=0.047N*   |P=0.693      (e)          P=0.516      (e)          |
|POLY 3             |     P=0.036N*    P=0.356N     P=0.112N     P=0.059N    |P=0.694      (e)          P=0.509      (e)          |
|POLY 1.5           |     P=0.039N*    P=0.342N     P=0.110N     P=0.062N    |P=0.695      (e)          P=0.503      (e)          |
|POLY 6             |     P=0.032N*    P=0.372N     P=0.113N     P=0.054N    |P=0.693      (e)          P=0.516      (e)          |
|LOGISTIC REGRESSION|     P=0.026N*    P=0.420N     P=0.112N     P=0.047N*   |(e)          (e)          P=0.516      (e)          |
|COCH-ARM / FISHERS |     P=0.041N*    P=0.318N     P=0.105N     P=0.062N    |P=0.694      (e)          P=0.500      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         6.5%         0.0%         4.2%        |0.0%         0.0%         4.2%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    1/37 (3%)    0/40 (0%)    2/43 (5%)   |0/37 (0%)    0/39 (0%)    2/40 (5%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          636          ---          729 (T)     |---          ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.367      P=0.109      (e)          P=0.249     |P=0.589      (e)          P=0.256      (e)          |
|POLY 3             |     P=0.343      P=0.113      (e)          P=0.238     |P=0.596      (e)          P=0.247      (e)          |
|POLY 1.5           |     P=0.342      P=0.115      (e)          P=0.237     |P=0.597      (e)          P=0.241      (e)          |
|POLY 6             |     P=0.348      P=0.112      (e)          P=0.241     |P=0.594      (e)          P=0.256      (e)          |
|LOGISTIC REGRESSION|     P=0.346      P=0.133      (e)          P=0.249     |(e)          (e)          P=0.256      (e)          |
|COCH-ARM / FISHERS |     P=0.346      P=0.121      (e)          P=0.247     |P=0.595      (e)          P=0.247      (e)          |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions 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 Epithelium                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    4/50 (8%)    0/50 (0%)   |2/50 (4%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     4.2%         2.2%         8.6%         0.0%        |4.4%         2.2%         0.0%         2.2%         |
|TERMINAL (d)       |     1/41 (2%)    0/37 (0%)    4/40 (10%)   0/43 (0%)   |2/37 (5%)    1/39 (3%)    0/40 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     639          695          729 (T)      ---         |731 (T)      731 (T)      ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.261N     P=0.525N     P=0.326      P=0.237N    |P=0.374N     P=0.482N     P=0.221N     P=0.510N     |
|POLY 3             |     P=0.270N     P=0.515N     P=0.325      P=0.238N    |P=0.364N     P=0.497N     P=0.228N     P=0.497N     |
|POLY 1.5           |     P=0.274N     P=0.510N     P=0.330      P=0.239N    |P=0.365N     P=0.500N     P=0.234N     P=0.498N     |
|POLY 6             |     P=0.262N     P=0.522N     P=0.321      P=0.236N    |P=0.362N     P=0.490N     P=0.220N     P=0.495N     |
|LOGISTIC REGRESSION|     P=0.277N     P=0.458N     P=0.333      P=0.215N    |P=0.374N     P=0.482N     (e)          P=0.510N     |
|COCH-ARM / FISHERS |     P=0.277N     P=0.500N     P=0.339      P=0.247N    |P=0.366N     P=0.500N     P=0.247N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mandibular                                                                                                           |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/49 (0%)    0/50 (0%)    0/48 (0%)   |1/48 (2%)    2/46 (4%)    1/47 (2%)    2/47 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.3%         4.8%         2.2%         4.6%         |
|TERMINAL (d)       |     0/40 (0%)    0/36 (0%)    0/40 (0%)    0/41 (0%)   |1/35 (3%)    2/36 (6%)    1/39 (3%)    2/35 (6%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |731 (T)      731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.445      P=0.510      P=0.738N     P=0.500      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.456      P=0.487      P=0.751N     P=0.503      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.450      P=0.485      P=0.759N     P=0.499      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.462      P=0.494      P=0.741N     P=0.508      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.445      P=0.510      P=0.738N     P=0.500      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.441      P=0.484      P=0.747      P=0.492      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/46 (0%)    0/50 (0%)    1/49 (2%)   |0/49 (0%)    1/48 (2%)    0/50 (0%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         2.1%        |0.0%         2.3%         0.0%         4.4%         |
|TERMINAL (d)       |     0/41 (0%)    0/34 (0%)    0/40 (0%)    0/43 (0%)   |0/37 (0%)    1/38 (3%)    0/40 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          ---          ---          723         |---          731 (T)      ---          709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.217      (e)          (e)          P=0.514     |P=0.133      P=0.505      (e)          P=0.237      |
|POLY 3             |     P=0.207      (e)          (e)          P=0.502     |P=0.145      P=0.497      (e)          P=0.243      |
|POLY 1.5           |     P=0.205      (e)          (e)          P=0.500     |P=0.143      P=0.495      (e)          P=0.241      |
|POLY 6             |     P=0.210      (e)          (e)          P=0.505     |P=0.147      P=0.500      (e)          P=0.245      |
|LOGISTIC REGRESSION|     P=0.210      (e)          (e)          P=0.503     |P=0.143      P=0.505      (e)          P=0.243      |
|COCH-ARM / FISHERS |     P=0.202      (e)          (e)          P=0.500     |P=0.141      P=0.495      (e)          P=0.247      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/49 (14%)   4/46 (9%)    3/50 (6%)    5/49 (10%)  |0/49 (0%)    0/48 (0%)    0/50 (0%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     14.9%        9.6%         6.4%         10.6%       |0.0%         0.0%         0.0%         4.4%         |
|TERMINAL (d)       |     6/41 (15%)   4/34 (12%)   2/40 (5%)    4/43 (9%)   |0/37 (0%)    0/38 (0%)    0/40 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     636          729 (T)      688          684         |---          ---          ---          680          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.302N     P=0.371N     P=0.173N     P=0.354N    |P=0.045 *    (e)          (e)          P=0.242      |
|POLY 3             |     P=0.329N     P=0.333N     P=0.160N     P=0.376N    |P=0.047 *    (e)          (e)          P=0.243      |
|POLY 1.5           |     P=0.337N     P=0.319N     P=0.157N     P=0.381N    |P=0.047 *    (e)          (e)          P=0.241      |
|POLY 6             |     P=0.317N     P=0.349N     P=0.163N     P=0.365N    |P=0.047 *    (e)          (e)          P=0.246      |
|LOGISTIC REGRESSION|     P=0.326N     P=0.337N     P=0.155N     P=0.379N    |P=0.047 *    (e)          (e)          P=0.237      |
|COCH-ARM / FISHERS |     P=0.342N     P=0.300N     P=0.151N     P=0.380N    |P=0.047 *    (e)          (e)          P=0.247      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    0/46 (0%)    1/50 (2%)    3/49 (6%)   |0/49 (0%)    0/48 (0%)    1/50 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     4.3%         0.0%         2.1%         6.4%        |0.0%         0.0%         2.1%         2.2%         |
|TERMINAL (d)       |     2/41 (5%)    0/34 (0%)    1/40 (3%)    3/43 (7%)   |0/37 (0%)    0/38 (0%)    1/40 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      729 (T)     |---          ---          731 (T)      693          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.282      P=0.280N     P=0.509N     P=0.522     |P=0.232      (e)          P=0.516      P=0.505      |
|POLY 3             |     P=0.262      P=0.263N     P=0.501N     P=0.504     |P=0.245      (e)          P=0.512      P=0.505      |
|POLY 1.5           |     P=0.257      P=0.258N     P=0.498N     P=0.500     |P=0.242      (e)          P=0.507      P=0.503      |
|POLY 6             |     P=0.269      P=0.267N     P=0.503N     P=0.512     |P=0.245      (e)          P=0.519      P=0.507      |
|LOGISTIC REGRESSION|     P=0.282      (e)          P=0.509N     P=0.522     |P=0.239      (e)          P=0.516      P=0.494      |
|COCH-ARM / FISHERS |     P=0.252      P=0.263N     P=0.492N     P=0.500     |P=0.237      (e)          P=0.505      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    1/46 (2%)    1/50 (2%)    2/49 (4%)   |1/49 (2%)    1/48 (2%)    1/50 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.4%         2.1%         4.2%        |2.3%         2.3%         2.1%         2.2%         |
|TERMINAL (d)       |     0/41 (0%)    1/34 (3%)    1/40 (3%)    1/43 (2%)   |1/37 (3%)    0/38 (0%)    1/40 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      723         |731 (T)      707          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.180      P=0.463      P=0.495      P=0.253     |P=0.628      P=0.746N     P=0.744N     P=0.756      |
|POLY 3             |     P=0.162      P=0.478      P=0.500      P=0.239     |P=0.624N     P=0.757      P=0.747N     P=0.756N     |
|POLY 1.5           |     P=0.159      P=0.481      P=0.501      P=0.237     |P=0.626N     P=0.756      P=0.752N     P=0.757N     |
|POLY 6             |     P=0.167      P=0.474      P=0.499      P=0.243     |P=0.622N     P=0.760N     P=0.739N     P=0.754N     |
|LOGISTIC REGRESSION|     P=0.178      P=0.463      P=0.495      P=0.245     |P=0.624N     P=0.761      P=0.744N     P=0.756      |
|COCH-ARM / FISHERS |     P=0.157      P=0.484      P=0.505      P=0.247     |P=0.631N     P=0.747      P=0.747N     P=0.753N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node: Iliac                                                                                                                |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/6 (0%)     0/3 (0%)     0/4 (0%)     0/1 (0%)    |0/8 (0%)     0/7 (0%)     0/9 (0%)     2/7 (29%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         33.3%        |
|TERMINAL (d)       |     0/3 (0%)     0/2 (0%)     0/3 (0%)     0/1 (0%)    |0/3 (0%)     0/4 (0%)     0/5 (0%)     1/2 (50%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.026 *    (e)          (e)          P=0.196      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.024 *    (e)          (e)          P=0.185      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.025 *    (e)          (e)          P=0.186      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.023 *    (e)          (e)          P=0.182      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.022 *    (e)          (e)          P=0.165      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.035 *    (e)          (e)          P=0.200      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/0 (0%)     0/1 (0%)     0/1 (0%)     0/1 (0%)    |2/49 (4%)    0/50 (0%)    1/49 (2%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.4%         0.0%         2.2%         2.2%         |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/1 (0%)     0/1 (0%)    |0/36 (0%)    0/39 (0%)    1/39 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |484          ---          731 (T)      709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.506N     P=0.236N     P=0.482N     P=0.505N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.494N     P=0.234N     P=0.491N     P=0.495N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.495N     P=0.235N     P=0.498N     P=0.495N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.495N     P=0.231N     P=0.481N     P=0.495N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.498N     P=0.160N     P=0.469N     P=0.487N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.496N     P=0.242N     P=0.500N     P=0.492N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/2 (100%)   2/4 (50%)    1/6 (17%)    1/5 (20%)   |7/14 (50%)   10/16 (63%)  12/15 (80%)  6/11 (55%)   |
|POLY-3 ADJUSTED (b)|     100.0%       54.2%        20.1%        21.5%       |55.9%        68.3%        82.8%        61.8%        |
|TERMINAL (d)       |     2/2 (100%)   2/3 (67%)    1/4 (25%)    1/4 (25%)   |6/8 (75%)    8/10 (80%)   10/10 (100%) 4/5 (80%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |587          707          658          681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.100N     P=0.581N     P=0.215N     P=0.215N    |P=0.309      P=0.442      P=0.175      P=0.449      |
|POLY 3             |     P=0.061N     P=0.428N     P=0.070N     P=0.099N    |P=0.416      P=0.392      P=0.118      P=0.562      |
|POLY 1.5           |     P=0.065N     P=0.407N     P=0.058N     P=0.094N    |P=0.417      P=0.379      P=0.104      P=0.557      |
|POLY 6             |     P=0.058N     P=0.468N     P=0.096N     P=0.111N    |P=0.437      P=0.431      P=0.151      P=0.587      |
|LOGISTIC REGRESSION|     P=0.100N     P=0.581N     P=0.215N     P=0.215N    |P=0.504      P=0.560      P=0.229      P=0.624      |
|COCH-ARM / FISHERS |     P=0.085N     P=0.400N     P=0.107N     P=0.143N    |P=0.441      P=0.374      P=0.095      P=0.570      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |3/45 (7%)    0/44 (0%)    4/48 (8%)    2/48 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |7.3%         0.0%         8.7%         4.5%         |
|TERMINAL (d)       |                                                        |3/35 (9%)    0/34 (0%)    3/39 (8%)    2/35 (6%)    |
|FIRST INCIDENCE    |                                                        |731 (T)      ---          720          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.576      P=0.126N     P=0.560      P=0.500N     |
|POLY 3             |                                                        |P=0.567N     P=0.125N     P=0.561      P=0.465N     |
|POLY 1.5           |                                                        |P=0.570N     P=0.125N     P=0.546      P=0.467N     |
|POLY 6             |                                                        |P=0.568N     P=0.124N     P=0.578      P=0.466N     |
|LOGISTIC REGRESSION|                                                        |P=0.589N     (e)          P=0.590      P=0.500N     |
|COCH-ARM / FISHERS |                                                        |P=0.578N     P=0.125N     P=0.536      P=0.469N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |16/45 (36%)  11/44 (25%)  12/48 (25%)  11/48 (23%)  |
|POLY-3 ADJUSTED (b)|                                                        |38.3%        27.8%        25.8%        23.7%        |
|TERMINAL (d)       |                                                        |14/35 (40%)  10/34 (29%)  10/39 (26%)  6/35 (17%)   |
|FIRST INCIDENCE    |                                                        |608          720          625          515          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.186N     P=0.196N     P=0.158N     P=0.186N     |
|POLY 3             |                                                        |P=0.102N     P=0.220N     P=0.151N     P=0.103N     |
|POLY 1.5           |                                                        |P=0.115N     P=0.213N     P=0.172N     P=0.114N     |
|POLY 6             |                                                        |P=0.092N     P=0.225N     P=0.130N     P=0.095N     |
|LOGISTIC REGRESSION|                                                        |P=0.135N     P=0.202N     P=0.169N     P=0.140N     |
|COCH-ARM / FISHERS |                                                        |P=0.139N     P=0.197N     P=0.189N     P=0.133N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Lipomatosis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |1/48 (2%)    2/49 (4%)    2/49 (4%)    2/48 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         2.1%        |2.3%         4.5%         4.2%         4.4%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    1/43 (2%)   |0/37 (0%)    1/39 (3%)    1/40 (3%)    2/36 (6%)    |
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |699          659          625          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.213      (e)          (e)          P=0.510     |P=0.418      P=0.523      P=0.536      P=0.491      |
|POLY 3             |     P=0.204      (e)          (e)          P=0.504     |P=0.432      P=0.505      P=0.524      P=0.506      |
|POLY 1.5           |     P=0.202      (e)          (e)          P=0.503     |P=0.428      P=0.505      P=0.514      P=0.504      |
|POLY 6             |     P=0.207      (e)          (e)          P=0.507     |P=0.433      P=0.510      P=0.535      P=0.507      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.510     |P=0.416      P=0.511      P=0.511      P=0.508      |
|COCH-ARM / FISHERS |     P=0.201      (e)          (e)          P=0.505     |P=0.420      P=0.508      P=0.508      P=0.500      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas: Acinus                                                                                                                 |
|     Atrophy Focal                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |1/48 (2%)    1/49 (2%)    2/49 (4%)    1/48 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.1%         0.0%        |2.3%         2.2%         4.3%         2.2%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |1/37 (3%)    1/39 (3%)    2/40 (5%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          ---          572          ---         |731 (T)      731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.697      (e)          P=0.496      (e)         |P=0.581      P=0.750N     P=0.527      P=0.756      |
|POLY 3             |     P=0.705      (e)          P=0.502      (e)         |P=0.600      P=0.758N     P=0.522      P=0.756N     |
|POLY 1.5           |     P=0.701      (e)          P=0.502      (e)         |P=0.597      P=0.758N     P=0.513      P=0.757N     |
|POLY 6             |     P=0.712      (e)          P=0.502      (e)         |P=0.601      P=0.756N     P=0.533      P=0.755N     |
|LOGISTIC REGRESSION|     P=0.738N     (e)          P=0.748      (e)         |P=0.581      P=0.750N     P=0.527      P=0.756      |
|COCH-ARM / FISHERS |     P=0.699      (e)          P=0.505      (e)         |P=0.590      P=0.747N     P=0.508      P=0.753N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas: Duct                                                                                                                   |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |3/48 (6%)    1/49 (2%)    1/49 (2%)    2/48 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |6.8%         2.2%         2.1%         4.4%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |3/37 (8%)    0/39 (0%)    0/40 (0%)    2/36 (6%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |731 (T)      659          625          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.478N     P=0.287N     P=0.277N     P=0.513N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.467N     P=0.299N     P=0.280N     P=0.490N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.470N     P=0.300N     P=0.290N     P=0.494N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.467N     P=0.293N     P=0.268N     P=0.488N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.478N     P=0.300N     P=0.298N     P=0.513N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.476N     P=0.301N     P=0.301N     P=0.500N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Parathyroid Gland                                                                                                                |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/44 (2%)    4/47 (9%)    1/46 (2%)    0/45 (0%)   |0/44 (0%)    3/47 (6%)    0/45 (0%)    0/47 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         9.3%         2.3%         0.0%        |0.0%         6.9%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    2/35 (6%)    1/37 (3%)    0/39 (0%)   |0/31 (0%)    1/36 (3%)    0/36 (0%)    0/34 (0%)    |
|FIRST INCIDENCE    |     636          645          729 (T)      ---         |---          391          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.158N     P=0.174      P=0.757      P=0.513N    |P=0.304N     P=0.136      (e)          (e)          |
|POLY 3             |     P=0.162N     P=0.187      P=0.754N     P=0.494N    |P=0.283N     P=0.139      (e)          (e)          |
|POLY 1.5           |     P=0.164N     P=0.192      P=0.753N     P=0.496N    |P=0.291N     P=0.135      (e)          (e)          |
|POLY 6             |     P=0.158N     P=0.184      P=0.754N     P=0.491N    |P=0.273N     P=0.146      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.160N     P=0.227      P=0.735N     P=0.444N    |P=0.291N     P=0.165      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.164N     P=0.202      P=0.742N     P=0.494N    |P=0.300N     P=0.133      (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/40 (3%)    2/38 (5%)    1/42 (2%)    1/46 (2%)   |0/46 (0%)    1/45 (2%)    1/46 (2%)    0/44 (0%)    |
|POLY-3 ADJUSTED (b)|     2.6%         5.7%         2.6%         2.3%        |0.0%         2.4%         2.3%         0.0%         |
|TERMINAL (d)       |     1/34 (3%)    2/28 (7%)    1/34 (3%)    1/41 (2%)   |0/34 (0%)    1/37 (3%)    1/39 (3%)    0/32 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |---          731 (T)      731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.446N     P=0.432      P=0.762      P=0.720N    |P=0.613N     P=0.517      P=0.527      (e)          |
|POLY 3             |     P=0.475N     P=0.471      P=0.755N     P=0.728N    |P=0.599N     P=0.501      P=0.510      (e)          |
|POLY 1.5           |     P=0.477N     P=0.476      P=0.753N     P=0.730N    |P=0.601N     P=0.498      P=0.504      (e)          |
|POLY 6             |     P=0.469N     P=0.466      P=0.756N     P=0.724N    |P=0.597N     P=0.507      P=0.519      (e)          |
|LOGISTIC REGRESSION|     P=0.446N     P=0.432      P=0.762      P=0.720N    |(e)          P=0.517      P=0.527      (e)          |
|COCH-ARM / FISHERS |     P=0.477N     P=0.481      P=0.741N     P=0.717N    |P=0.603N     P=0.495      P=0.500      (e)          |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 24
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Cytoplasmic Alteration Focal                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/40 (0%)    0/38 (0%)    0/42 (0%)    0/46 (0%)   |2/46 (4%)    2/45 (4%)    3/46 (7%)    3/44 (7%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.8%         4.8%         6.9%         7.5%         |
|TERMINAL (d)       |     0/34 (0%)    0/28 (0%)    0/34 (0%)    0/41 (0%)   |2/34 (6%)    2/37 (5%)    2/39 (5%)    3/32 (9%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |731 (T)      731 (T)      730          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.336      P=0.665N     P=0.561      P=0.472      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.354      P=0.692N     P=0.523      P=0.483      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.354      P=0.691      P=0.509      P=0.481      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.353      P=0.682N     P=0.542      P=0.485      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.329      P=0.665N     P=0.577      P=0.472      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.353      P=0.683      P=0.500      P=0.479      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Hyperplasia Focal                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/40 (0%)    0/38 (0%)    0/42 (0%)    0/46 (0%)   |3/46 (7%)    1/45 (2%)    3/46 (7%)    3/44 (7%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |7.2%         2.4%         6.9%         7.5%         |
|TERMINAL (d)       |     0/34 (0%)    0/28 (0%)    0/34 (0%)    0/41 (0%)   |2/34 (6%)    1/37 (3%)    3/39 (8%)    3/32 (9%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |699          731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.422      P=0.278N     P=0.599N     P=0.637      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.435      P=0.304N     P=0.640N     P=0.644      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.437      P=0.309N     P=0.654N     P=0.643      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.431      P=0.294N     P=0.622N     P=0.645      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.434      P=0.292N     P=0.616N     P=0.648      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.438      P=0.317N     P=0.662N     P=0.640      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 25
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Degeneration Cystic                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     15/47 (32%)  21/50 (42%)  24/50 (48%)  24/50 (48%) |                                                    |
|POLY-3 ADJUSTED (b)|     32.8%        44.6%        49.8%        48.7%       |                                                    |
|TERMINAL (d)       |     10/38 (26%)  15/37 (41%)  18/40 (45%)  20/43 (47%) |                                                    |
|FIRST INCIDENCE    |     636          631          541          281         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.156      P=0.139      P=0.085      P=0.126     |                                                    |
|POLY 3             |     P=0.088      P=0.170      P=0.070      P=0.086     |                                                    |
|POLY 1.5           |     P=0.082      P=0.183      P=0.073      P=0.083     |                                                    |
|POLY 6             |     P=0.096      P=0.159      P=0.069      P=0.090     |                                                    |
|LOGISTIC REGRESSION|     P=0.074      P=0.196      P=0.083      P=0.079     |                                                    |
|COCH-ARM / FISHERS |     P=0.074      P=0.207      P=0.079      P=0.079     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/47 (17%)   6/50 (12%)   2/50 (4%)    2/50 (4%)   |                                                    |
|POLY-3 ADJUSTED (b)|     17.7%        13.1%        4.3%         4.2%        |                                                    |
|TERMINAL (d)       |     6/38 (16%)   6/37 (16%)   1/40 (3%)    2/43 (5%)   |                                                    |
|FIRST INCIDENCE    |     639          729 (T)      639          729 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.013N*    P=0.413N     P=0.048N*    P=0.036N*   |                                                    |
|POLY 3             |     P=0.013N*    P=0.377N     P=0.039N*    P=0.036N*   |                                                    |
|POLY 1.5           |     P=0.014N*    P=0.363N     P=0.038N*    P=0.037N*   |                                                    |
|POLY 6             |     P=0.013N*    P=0.396N     P=0.040N*    P=0.035N*   |                                                    |
|LOGISTIC REGRESSION|     P=0.014N*    P=0.368N     P=0.034N*    P=0.038N*   |                                                    |
|COCH-ARM / FISHERS |     P=0.015N*    P=0.339N     P=0.036N*    P=0.036N*   |                                                    |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 26
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Seminal Vesicle                                                                                                                  |
|     Dilatation                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     28/50 (56%)  25/50 (50%)  18/50 (36%)  19/50 (38%) |                                                    |
|POLY-3 ADJUSTED (b)|     57.8%        53.1%        38.5%        39.8%       |                                                    |
|TERMINAL (d)       |     24/41 (59%)  22/37 (60%)  17/40 (43%)  18/43 (42%) |                                                    |
|FIRST INCIDENCE    |     639          446          688          725         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.014N*    P=0.543N     P=0.047N*    P=0.038N*   |                                                    |
|POLY 3             |     P=0.029N*    P=0.397N     P=0.044N*    P=0.056N    |                                                    |
|POLY 1.5           |     P=0.031N*    P=0.374N     P=0.039N*    P=0.057N    |                                                    |
|POLY 6             |     P=0.026N*    P=0.434N     P=0.049N*    P=0.055N    |                                                    |
|LOGISTIC REGRESSION|     P=0.023N*    P=0.407N     P=0.042N*    P=0.043N*   |                                                    |
|COCH-ARM / FISHERS |     P=0.031N*    P=0.344N     P=0.035N*    P=0.054N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     13/50 (26%)  14/50 (28%)  14/50 (28%)  10/49 (20%) |9/48 (19%)   14/49 (29%)  17/49 (35%)  16/49 (33%)  |
|POLY-3 ADJUSTED (b)|     26.4%        29.3%        28.7%        20.8%       |20.1%        30.1%        36.0%        34.2%        |
|TERMINAL (d)       |     8/41 (20%)   7/37 (19%)   7/40 (18%)   7/43 (16%)  |5/37 (14%)   9/39 (23%)   15/40 (38%)  10/36 (28%)  |
|FIRST INCIDENCE    |     556          446          497          604         |541          490          658          525          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.222N     P=0.407      P=0.471      P=0.303N    |P=0.082      P=0.220      P=0.098      P=0.092      |
|POLY 3             |     P=0.264N     P=0.461      P=0.487      P=0.343N    |P=0.099      P=0.195      P=0.069      P=0.098      |
|POLY 1.5           |     P=0.271N     P=0.476      P=0.492      P=0.346N    |P=0.096      P=0.188      P=0.062      P=0.095      |
|POLY 6             |     P=0.250N     P=0.445      P=0.485      P=0.334N    |P=0.101      P=0.208      P=0.078      P=0.100      |
|LOGISTIC REGRESSION|     P=0.284N     P=0.555N     P=0.582N     P=0.328N    |P=0.090      P=0.192      P=0.068      P=0.089      |
|COCH-ARM / FISHERS |     P=0.267N     P=0.500      P=0.500      P=0.337N    |P=0.090      P=0.185      P=0.061      P=0.091      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 27
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    4/50 (8%)    3/50 (6%)    2/49 (4%)   |9/48 (19%)   10/49 (20%)  10/49 (20%)  12/49 (24%)  |
|POLY-3 ADJUSTED (b)|     0.0%         8.8%         6.4%         4.2%        |20.4%        22.4%        21.3%        26.5%        |
|TERMINAL (d)       |     0/41 (0%)    4/37 (11%)   3/40 (8%)    2/43 (5%)   |8/37 (22%)   9/39 (23%)   10/40 (25%)  12/36 (33%)  |
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |681          707          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.420      P=0.051      P=0.117      P=0.249     |P=0.229      P=0.553      P=0.577      P=0.284      |
|POLY 3             |     P=0.380      P=0.055      P=0.115      P=0.235     |P=0.293      P=0.513      P=0.560      P=0.336      |
|POLY 1.5           |     P=0.374      P=0.057      P=0.117      P=0.233     |P=0.290      P=0.512      P=0.537      P=0.335      |
|POLY 6             |     P=0.393      P=0.053      P=0.114      P=0.239     |P=0.289      P=0.522      P=0.587      P=0.331      |
|LOGISTIC REGRESSION|     (e)          P=0.051      P=0.117      P=0.249     |P=0.265      P=0.537      P=0.586N     P=0.316      |
|COCH-ARM / FISHERS |     P=0.374      P=0.059      P=0.121      P=0.242     |P=0.281      P=0.520      P=0.520      P=0.331      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach: Epithelium                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    3/50 (6%)   |1/50 (2%)    0/49 (0%)    2/48 (4%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         2.1%         6.2%        |2.2%         0.0%         4.3%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    0/40 (0%)    2/43 (5%)   |0/37 (0%)    0/39 (0%)    1/40 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          631          688          281         |587          ---          658          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.062      P=0.492      P=0.505      P=0.129     |P=0.457N     P=0.509N     P=0.527      P=0.500N     |
|POLY 3             |     P=0.057      P=0.493      P=0.496      P=0.123     |P=0.462N     P=0.505N     P=0.505      P=0.502N     |
|POLY 1.5           |     P=0.056      P=0.496      P=0.498      P=0.121     |P=0.463N     P=0.505N     P=0.494      P=0.503N     |
|POLY 6             |     P=0.059      P=0.491      P=0.496      P=0.126     |P=0.463N     P=0.502N     P=0.518      P=0.501N     |
|LOGISTIC REGRESSION|     P=0.071      P=0.608      P=0.523      P=0.183     |P=0.472N     P=0.433N     P=0.497      P=0.498N     |
|COCH-ARM / FISHERS |     P=0.054      P=0.500      P=0.500      P=0.121     |P=0.466N     P=0.505N     P=0.485      P=0.505N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 28
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular: Glands                                                                                                       |
|     Degeneration Cystic Focal                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    5/50 (10%)   1/50 (2%)   |1/50 (2%)    3/49 (6%)    1/48 (2%)    1/48 (2%)    |
|POLY-3 ADJUSTED (b)|     2.1%         6.5%         10.7%        2.1%        |2.2%         6.7%         2.2%         2.2%         |
|TERMINAL (d)       |     1/41 (2%)    2/37 (5%)    3/40 (8%)    1/43 (2%)   |0/37 (0%)    3/39 (8%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      639          688          729 (T)     |721          731 (T)      658          709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.511N     P=0.274      P=0.105      P=0.751N    |P=0.449N     P=0.325      P=0.734N     P=0.757      |
|POLY 3             |     P=0.538N     P=0.294      P=0.098      P=0.760N    |P=0.441N     P=0.300      P=0.755N     P=0.760      |
|POLY 1.5           |     P=0.544N     P=0.298      P=0.099      P=0.760     |P=0.449N     P=0.298      P=0.758      P=0.757      |
|POLY 6             |     P=0.526N     P=0.289      P=0.099      P=0.757N    |P=0.433N     P=0.307      P=0.745N     P=0.758N     |
|LOGISTIC REGRESSION|     P=0.544N     P=0.307      P=0.100      P=0.751N    |P=0.451N     P=0.318      P=0.753      P=0.761      |
|COCH-ARM / FISHERS |     P=0.544N     P=0.309      P=0.102      P=0.753N    |P=0.459N     P=0.301      P=0.742      P=0.742      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thymus                                                                                                                           |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/42 (5%)    4/45 (9%)    3/46 (7%)    0/39 (0%)   |0/49 (0%)    0/49 (0%)    0/46 (0%)    1/48 (2%)    |
|POLY-3 ADJUSTED (b)|     5.0%         9.8%         6.9%         0.0%        |0.0%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     2/36 (6%)    3/34 (9%)    2/38 (5%)    0/34 (0%)   |0/37 (0%)    0/39 (0%)    0/38 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      699          688          ---         |---          ---          ---          681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.141N     P=0.309      P=0.520      P=0.251N    |P=0.200      (e)          (e)          P=0.510      |
|POLY 3             |     P=0.151N     P=0.344      P=0.532      P=0.254N    |P=0.199      (e)          (e)          P=0.501      |
|POLY 1.5           |     P=0.154N     P=0.354      P=0.535      P=0.255N    |P=0.198      (e)          (e)          P=0.499      |
|POLY 6             |     P=0.146N     P=0.333      P=0.531      P=0.251N    |P=0.200      (e)          (e)          P=0.503      |
|LOGISTIC REGRESSION|     P=0.149N     P=0.323      P=0.532      (e)         |P=0.194      (e)          (e)          P=0.490      |
|COCH-ARM / FISHERS |     P=0.152N     P=0.372      P=0.544      P=0.266N    |P=0.196      (e)          (e)          P=0.495      |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 29
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thymus                                                                                                                           |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/42 (0%)    0/45 (0%)    0/46 (0%)    0/39 (0%)   |2/49 (4%)    1/49 (2%)    0/46 (0%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.5%         2.2%         0.0%         0.0%         |
|TERMINAL (d)       |     0/36 (0%)    0/34 (0%)    0/38 (0%)    0/34 (0%)   |2/37 (5%)    1/39 (3%)    0/38 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |731 (T)      731 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.103N     P=0.482N     P=0.232N     P=0.244N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.103N     P=0.493N     P=0.239N     P=0.237N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.104N     P=0.497N     P=0.246N     P=0.239N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.103N     P=0.485N     P=0.231N     P=0.235N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.103N     P=0.482N     (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.105N     P=0.500N     P=0.263N     P=0.253N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland                                                                                                                    |
|     Degeneration Cystic Focal                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    6/50 (12%)   8/50 (16%)   4/50 (8%)   |14/50 (28%)  1/50 (2%)    5/50 (10%)   9/48 (19%)   |
|POLY-3 ADJUSTED (b)|     6.3%         13.1%        17.1%        8.4%        |30.5%        2.2%         10.5%        19.6%        |
|TERMINAL (d)       |     2/41 (5%)    6/37 (16%)   6/40 (15%)   3/43 (7%)   |10/37 (27%)  1/39 (3%)    3/40 (8%)    4/36 (11%)   |
|FIRST INCIDENCE    |     680          729 (T)      688          723         |645          731 (T)      658          604          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.540      P=0.197      P=0.101      P=0.527     |P=0.370N     P<0.001N**   P=0.016N*    P=0.194N     |
|POLY 3             |     P=0.492      P=0.221      P=0.092      P=0.500     |P=0.355N     P<0.001N**   P=0.014N*    P=0.168N     |
|POLY 1.5           |     P=0.484      P=0.229      P=0.095      P=0.498     |P=0.367N     P<0.001N**   P=0.017N*    P=0.181N     |
|POLY 6             |     P=0.507      P=0.211      P=0.090      P=0.506     |P=0.345N     P<0.001N**   P=0.012N*    P=0.153N     |
|LOGISTIC REGRESSION|     P=0.517      P=0.210      P=0.093      P=0.503     |P=0.381N     P<0.001N**   P=0.016N*    P=0.197N     |
|COCH-ARM / FISHERS |     P=0.484      P=0.243      P=0.100      P=0.500     |P=0.388N     P<0.001N**   P=0.020N*    P=0.200N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 30
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                    |
|     Inflammation Chronic Focal                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    1/50 (2%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.1%         0.0%        |4.4%         0.0%         2.1%         0.0%         |
|TERMINAL (d)       |     0/41 (0%)    0/37 (0%)    1/40 (3%)    0/43 (0%)   |2/37 (5%)    0/39 (0%)    1/40 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |731 (T)      ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.704      (e)          P=0.495      (e)         |P=0.190N     P=0.227N     P=0.473N     P=0.244N     |
|POLY 3             |     P=0.703      (e)          P=0.496      (e)         |P=0.191N     P=0.235N     P=0.485N     P=0.240N     |
|POLY 1.5           |     P=0.699      (e)          P=0.497      (e)         |P=0.192N     P=0.237N     P=0.494N     P=0.243N     |
|POLY 6             |     P=0.711      (e)          P=0.495      (e)         |P=0.192N     P=0.231N     P=0.472N     P=0.237N     |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.495      (e)         |P=0.190N     (e)          P=0.473N     (e)          |
|COCH-ARM / FISHERS |     P=0.697      (e)          P=0.500      (e)         |P=0.194N     P=0.247N     P=0.500N     P=0.258N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicle                                                                                                          |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     4.2%         2.2%         0.0%         2.1%        |0.0%         0.0%         2.1%         0.0%         |
|TERMINAL (d)       |     2/41 (5%)    1/37 (3%)    0/40 (0%)    1/43 (2%)   |0/37 (0%)    0/39 (0%)    1/40 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          729 (T)     |---          ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.347N     P=0.536N     P=0.244N     P=0.483N    |P=0.693      (e)          P=0.516      (e)          |
|POLY 3             |     P=0.364N     P=0.514N     P=0.242N     P=0.499N    |P=0.698      (e)          P=0.509      (e)          |
|POLY 1.5           |     P=0.366N     P=0.509N     P=0.240N     P=0.501N    |P=0.695      (e)          P=0.503      (e)          |
|POLY 6             |     P=0.362N     P=0.520N     P=0.243N     P=0.494N    |P=0.699      (e)          P=0.516      (e)          |
|LOGISTIC REGRESSION|     P=0.347N     P=0.536N     (e)          P=0.483N    |(e)          (e)          P=0.516      (e)          |
|COCH-ARM / FISHERS |     P=0.367N     P=0.500N     P=0.247N     P=0.500N    |P=0.690      (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 31
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/50 (22%)  6/50 (12%)   16/50 (32%)  18/50 (36%) |9/50 (18%)   11/50 (22%)  20/50 (40%)  8/48 (17%)   |
|POLY-3 ADJUSTED (b)|     22.8%        13.1%        34.4%        37.4%       |19.9%        24.0%        42.4%        18.0%        |
|TERMINAL (d)       |     8/41 (20%)   5/37 (14%)   16/40 (40%)  17/43 (40%) |9/37 (24%)   10/39 (26%)  19/40 (48%)  8/36 (22%)   |
|FIRST INCIDENCE    |     636          639          729 (T)      632         |731 (T)      659          720          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.030 *    P=0.207N     P=0.165      P=0.122     |P=0.542N     P=0.453      P=0.021 *    P=0.526N     |
|POLY 3             |     P=0.015 *    P=0.167N     P=0.154      P=0.089     |P=0.512N     P=0.415      P=0.016 *    P=0.512N     |
|POLY 1.5           |     P=0.014 *    P=0.157N     P=0.166      P=0.088     |P=0.526N     P=0.405      P=0.013 *    P=0.522N     |
|POLY 6             |     P=0.017 *    P=0.178N     P=0.143      P=0.093     |P=0.501N     P=0.439      P=0.021 *    P=0.501N     |
|LOGISTIC REGRESSION|     P=0.020 *    P=0.155N     P=0.162      P=0.093     |P=0.510N     P=0.451      P=0.030 *    P=0.526N     |
|COCH-ARM / FISHERS |     P=0.016 *    P=0.143N     P=0.184      P=0.093     |P=0.541      P=0.402      P=0.013 *    P=0.537N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Tooth                                                                                                                            |
|     Developmental Malformation                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     12/12 (100%) 16/17 (94%)  18/18 (100%) 10/10 (100%)|0/0 (0%)     0/0 (0%)     1/2 (50%)    0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     100.0%       94.1%        100.0%       100.0%      |0.0%         0.0%         50.0%        0.0%         |
|TERMINAL (d)       |     11/11 (100%) 15/16 (94%)  16/16 (100%) 10/10 (100%)|0/0 (0%)     0/0 (0%)     1/2 (50%)    0/0 (0%)     |
|FIRST INCIDENCE    |     680          699          688          729 (T)     |---          ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.439N     P=0.562N     (e)          (e)         |P=1.000N     (e)          P=1.000N     (e)          |
|POLY 3             |     P=0.616      P=0.569N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.616      P=0.569N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.616      P=0.569N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          P=1.000N     (e)          |
|COCH-ARM / FISHERS |     P=0.618      P=0.586N     (e)          (e)         |P=1.000N     (e)          P=1.000      (e)          |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 32
                     Statistical Analysis of Non-neoplastic Lesions 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          |
|=================================================================================================================================|
|                                                                                                                                 |
|Tooth                                                                                                                            |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/12 (0%)    0/17 (0%)    2/18 (11%)   0/10 (0%)   |0/0 (0%)     0/0 (0%)     0/2 (0%)     0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         11.2%        0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/11 (0%)    0/16 (0%)    2/16 (13%)   0/10 (0%)   |0/0 (0%)     0/0 (0%)     0/2 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.573      (e)          P=0.322      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.570      (e)          P=0.330      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.566      (e)          P=0.329      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.576      (e)          P=0.331      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.322      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.562      (e)          P=0.352      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder: Transitional Epithelium                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/49 (0%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     2.1%         0.0%         4.3%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/41 (2%)    0/37 (0%)    0/40 (0%)    0/43 (0%)   |0/37 (0%)    0/39 (0%)    0/40 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          688          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.441N     P=0.520N     P=0.502      P=0.490N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.445N     P=0.504N     P=0.502      P=0.496N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.450N     P=0.501N     P=0.503      P=0.497N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.438N     P=0.508N     P=0.502      P=0.493N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.452N     (e)          P=0.522      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.453N     P=0.495N     P=0.508      P=0.495N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 33
                     Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                           |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/50 (0%)    0/50 (0%)    0/49 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         0.0%         0.0%         4.4%         |
|TERMINAL (d)       |                                                        |0/37 (0%)    0/39 (0%)    0/40 (0%)    2/36 (6%)    |
|FIRST INCIDENCE    |                                                        |---          ---          ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.042 *    (e)          (e)          P=0.232      |
|POLY 3             |                                                        |P=0.046 *    (e)          (e)          P=0.239      |
|POLY 1.5           |                                                        |P=0.046 *    (e)          (e)          P=0.238      |
|POLY 6             |                                                        |P=0.046 *    (e)          (e)          P=0.240      |
|LOGISTIC REGRESSION|                                                        |(e)          (e)          (e)          P=0.232      |
|COCH-ARM / FISHERS |                                                        |P=0.047 *    (e)          (e)          P=0.247      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0            160          312          625         |0            312          625          1250         |
|                   |     PPM          PPM          PPM          PPM         |PPM          PPM          PPM          PPM          |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hydrometra                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |17/50 (34%)  16/50 (32%)  13/49 (27%)  13/50 (26%)  |
|POLY-3 ADJUSTED (b)|                                                        |36.4%        34.7%        27.5%        28.1%        |
|TERMINAL (d)       |                                                        |12/37 (32%)  15/39 (39%)  10/40 (25%)  11/36 (31%)  |
|FIRST INCIDENCE    |                                                        |592          527          673          515          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.224N     P=0.439N     P=0.192N     P=0.285N     |
|POLY 3             |                                                        |P=0.193N     P=0.516N     P=0.240N     P=0.262N     |
|POLY 1.5           |                                                        |P=0.194N     P=0.513N     P=0.263N     P=0.259N     |
|POLY 6             |                                                        |P=0.199N     P=0.513N     P=0.216N     P=0.273N     |
|LOGISTIC REGRESSION|                                                        |P=0.187N     P=0.496N     P=0.258N     P=0.251N     |
|COCH-ARM / FISHERS |                                                        |P=0.196N     P=0.500N     P=0.278N     P=0.257N     |
|=================================================================================================================================|
       Date:  04/07/99                           EXPERIMENT: 05211 TEST: 06                                            Page 34
                     Statistical Analysis of Non-neoplastic Lesions 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: Endometrium                                                                                                              |
|     Hyperplasia Cystic                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |47/50 (94%)  45/50 (90%)  48/49 (98%)  45/50 (90%)  |
|POLY-3 ADJUSTED (b)|                                                        |96.8%        94.8%        98.2%        94.1%        |
|TERMINAL (d)       |                                                        |37/37 (100%) 39/39 (100%) 40/40 (100%) 36/36 (100%) |
|FIRST INCIDENCE    |                                                        |484          391          90           525          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.543      P=0.213N     P=0.339N     P=0.487N     |
|POLY 3             |                                                        |P=0.388N     P=0.510N     P=0.593      P=0.436N     |
|POLY 1.5           |                                                        |P=0.393N     P=0.440N     P=0.443      P=0.403N     |
|POLY 6             |                                                        |P=0.371N     P=0.598N     P=0.840      P=0.479N     |
|LOGISTIC REGRESSION|                                                        |P=0.335N     P=0.472N     P=0.268      P=0.300N     |
|COCH-ARM / FISHERS |                                                        |P=0.388N     P=0.357N     P=0.316      P=0.357N     |
|=================================================================================================================================|

(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).