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TDMS Study 93005-04 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: NCTR                                                    MALACHITE GREEN                                   DATE: 06/19/03       
EXPERIMENT: 93005 TEST: 04                                                                                     TIME: 07:21:51       
TEST TYPE:  CHRONIC                                                                                            PAGE:       1        
CONT: 224-93-00001                              ROUTE: DOSED FEED                                              NTP C#: C93005       
PATHOLOGIST: TROTTER, RONALD                                                                                   CAS: 569-64-2        
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: NCTR                                                    MALACHITE GREEN                                   DATE: 06/19/03       
EXPERIMENT: 93005 TEST: 04                                                                                     TIME: 07:21:51       
TEST TYPE:  CHRONIC                                                                                                                 
CONT: 224-93-00001                              ROUTE: DOSED FEED                                              NTP C#: C93005       
PATHOLOGIST: TROTTER, RONALD                                                                                   CAS: 569-64-2        
Mice(C57BL/6NXC3H/HEN MTN-NCTR)                                                                                                     
-----------------------------                                                                                                       
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE                                                                   
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES                                                                 
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.                                                                                      
                                                 ---------------                                                                    
                                                 Adrenal Cortex                                                                     
                                                 Adrenal Medulla                                                                    
                                                 Bone Marrow                                                                        
                                                 Islets, Pancreatic                                                                 
                                                 Liver                                                                              
                                                 Lung                                                                               
                                                 Ovary                                                                              
                                                 Pituitary Gland                                                                    
                                                 Spleen                                                                             
                                                 Thyroid Gland                                                                      
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 1       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)        -                      MALACHITE GREEN             
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Pheochromocytoma Benign                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/47 (0%)                2/46 (4%)                1/44 (2%)                1/46 (2%)       | 
|POLY-3 RATE (b)    |                  0/44.14                  2/45.38                  1/41.40                  1/43.08         | 
|POLY-3 PERCENT (g) |                  0.0%                     4.4%                     2.4%                     2.3%            | 
|TERMINAL (d)       |                  0/39 (0%)                2/43 (5%)                1/39 (3%)                1/39 (3%)       | 
|FIRST INCIDENCE    |                  ---                      727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.504                  P=0.260                  P=0.500                  P=0.500         | 
|POLY 3             |                  P=0.507                  P=0.243                  P=0.487                  P=0.495         | 
|POLY 1.5           |                  P=0.503                  P=0.239                  P=0.486                  P=0.494         | 
|POLY 6             |                  P=0.513                  P=0.249                  P=0.490                  P=0.498         | 
|LOGISTIC REGRESSION|                  (e)                      P=0.260                  P=0.500                  P=0.500         | 
|COCH-ARM / FISHERS |                  P=0.508                  P=0.242                  P=0.484                  P=0.495         | 
|ORDER RESTRICTED   |                  P=0.269                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/48 (6%)                0/48 (0%)                2/48 (4%)                3/48 (6%)       | 
|POLY-3 RATE (b)    |                  3/45.14                  0/46.93                  2/43.58                  3/45.08         | 
|POLY-3 PERCENT (g) |                  6.7%                     0.0%                     4.6%                     6.7%            | 
|TERMINAL (d)       |                  3/40 (8%)                0/44 (0%)                2/40 (5%)                3/41 (7%)       | 
|FIRST INCIDENCE    |                  727 (T)                  ---                      727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.379                  P=0.105N                 P=0.500N                 P=0.652N        | 
|POLY 3             |                  P=0.370                  P=0.112N                 P=0.516N                 P=0.662         | 
|POLY 1.5           |                  P=0.372                  P=0.114N                 P=0.515N                 P=0.658         | 
|POLY 6             |                  P=0.371                  P=0.109N                 P=0.512N                 P=0.657N        | 
|LOGISTIC REGRESSION|                  P=0.379                  (e)                      P=0.500N                 P=0.652N        | 
|COCH-ARM / FISHERS |                  P=0.384                  P=0.121N                 P=0.500N                 P=0.661N        | 
|ORDER RESTRICTED   |                  P=0.345                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 2       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Adenoma                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/48 (6%)                2/48 (4%)                2/46 (4%)                2/48 (4%)       | 
|POLY-3 RATE (b)    |                  3/45.14                  2/46.93                  2/43.32                  2/45.08         | 
|POLY-3 PERCENT (g) |                  6.7%                     4.3%                     4.6%                     4.4%            | 
|TERMINAL (d)       |                  3/40 (8%)                2/44 (5%)                2/40 (5%)                2/41 (5%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.439N                 P=0.456N                 P=0.500N                 P=0.489N        | 
|POLY 3             |                  P=0.446N                 P=0.482N                 P=0.519N                 P=0.501N        | 
|POLY 1.5           |                  P=0.446N                 P=0.489N                 P=0.522N                 P=0.504N        | 
|POLY 6             |                  P=0.443N                 P=0.475N                 P=0.513N                 P=0.494N        | 
|LOGISTIC REGRESSION|                  P=0.439N                 P=0.456N                 P=0.500N                 P=0.489N        | 
|COCH-ARM / FISHERS |                  P=0.437N                 P=0.500N                 P=0.520N                 P=0.500N        | 
|ORDER RESTRICTED   |                  P=0.498N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  1/48 (2%)                2/48 (4%)                0/46 (0%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  1/45.14                  2/47.23                  0/43.32                  1/45.08         | 
|POLY-3 PERCENT (g) |                  2.2%                     4.2%                     0.0%                     2.2%            | 
|TERMINAL (d)       |                  1/40 (3%)                1/44 (2%)                0/40 (0%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  727 (T)                  644                      ---                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.491N                 P=0.527                  P=0.500N                 P=0.756N        | 
|POLY 3             |                  P=0.487N                 P=0.516                  P=0.508N                 P=0.760         | 
|POLY 1.5           |                  P=0.489N                 P=0.510                  P=0.509N                 P=0.758         | 
|POLY 6             |                  P=0.484N                 P=0.523                  P=0.506N                 P=0.758N        | 
|LOGISTIC REGRESSION|                  P=0.485N                 P=0.466                  (e)                      P=0.756N        | 
|COCH-ARM / FISHERS |                  P=0.487N                 P=0.500                  P=0.511N                 P=0.753N        | 
|ORDER RESTRICTED   |                  P=0.395N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 3       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/48 (6%)                4/48 (8%)                2/46 (4%)                3/48 (6%)       | 
|POLY-3 RATE (b)    |                  3/45.14                  4/47.23                  2/43.32                  3/45.08         | 
|POLY-3 PERCENT (g) |                  6.7%                     8.5%                     4.6%                     6.7%            | 
|TERMINAL (d)       |                  3/40 (8%)                3/44 (7%)                2/40 (5%)                3/41 (7%)       | 
|FIRST INCIDENCE    |                  727 (T)                  644                      727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.499N                 P=0.548                  P=0.500N                 P=0.652N        | 
|POLY 3             |                  P=0.501N                 P=0.525                  P=0.519N                 P=0.662         | 
|POLY 1.5           |                  P=0.503N                 P=0.515                  P=0.522N                 P=0.658         | 
|POLY 6             |                  P=0.497N                 P=0.536                  P=0.513N                 P=0.657N        | 
|LOGISTIC REGRESSION|                  P=0.501N                 P=0.503                  P=0.500N                 P=0.652N        | 
|COCH-ARM / FISHERS |                  P=0.494N                 P=0.500                  P=0.520N                 P=0.661N        | 
|ORDER RESTRICTED   |                  P=0.561N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma, Hepatocellular Adenoma,                                                                           | 
|     or Hepatoblastoma                                                                                                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/48 (6%)                4/48 (8%)                2/46 (4%)                3/48 (6%)       | 
|POLY-3 RATE (b)    |                  3/45.14                  4/47.23                  2/43.32                  3/45.08         | 
|POLY-3 PERCENT (g) |                  6.7%                     8.5%                     4.6%                     6.7%            | 
|TERMINAL (d)       |                  3/40 (8%)                3/44 (7%)                2/40 (5%)                3/41 (7%)       | 
|FIRST INCIDENCE    |                  727 (T)                  644                      727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.499N                 P=0.548                  P=0.500N                 P=0.652N        | 
|POLY 3             |                  P=0.501N                 P=0.525                  P=0.519N                 P=0.662         | 
|POLY 1.5           |                  P=0.503N                 P=0.515                  P=0.522N                 P=0.658         | 
|POLY 6             |                  P=0.497N                 P=0.536                  P=0.513N                 P=0.657N        | 
|LOGISTIC REGRESSION|                  P=0.501N                 P=0.503                  P=0.500N                 P=0.652N        | 
|COCH-ARM / FISHERS |                  P=0.494N                 P=0.500                  P=0.520N                 P=0.661N        | 
|ORDER RESTRICTED   |                  P=0.561N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 4       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Adenoma                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                4/48 (8%)                3/48 (6%)                0/48 (0%)       | 
|POLY-3 RATE (b)    |                  2/45.14                  4/46.93                  3/43.58                  0/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     8.5%                     6.9%                     0.0%            | 
|TERMINAL (d)       |                  2/40 (5%)                4/44 (9%)                3/40 (8%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.131N                 P=0.382                  P=0.500                  P=0.233N        | 
|POLY 3             |                  P=0.132N                 P=0.355                  P=0.484                  P=0.237N        | 
|POLY 1.5           |                  P=0.133N                 P=0.349                  P=0.485                  P=0.239N        | 
|POLY 6             |                  P=0.128N                 P=0.363                  P=0.488                  P=0.234N        | 
|LOGISTIC REGRESSION|                  P=0.131N                 P=0.382                  P=0.500                  (e)             | 
|COCH-ARM / FISHERS |                  P=0.129N                 P=0.339                  P=0.500                  P=0.247N        | 
|ORDER RESTRICTED   |                  P=0.112N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar                                                                      | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                5/48 (10%)               4/48 (8%)                0/48 (0%)       | 
|POLY-3 RATE (b)    |                  2/45.14                  5/46.93                  4/43.58                  0/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     10.7%                    9.2%                     0.0%            | 
|TERMINAL (d)       |                  2/40 (5%)                5/44 (11%)               4/40 (10%)               0/41 (0%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.128N                 P=0.256                  P=0.337                  P=0.233N        | 
|POLY 3             |                  P=0.128N                 P=0.232                  P=0.321                  P=0.237N        | 
|POLY 1.5           |                  P=0.130N                 P=0.227                  P=0.323                  P=0.239N        | 
|POLY 6             |                  P=0.123N                 P=0.239                  P=0.325                  P=0.234N        | 
|LOGISTIC REGRESSION|                  P=0.128N                 P=0.256                  P=0.337                  (e)             | 
|COCH-ARM / FISHERS |                  P=0.126N                 P=0.218                  P=0.339                  P=0.247N        | 
|ORDER RESTRICTED   |                  P=0.079N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 5       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                1/48 (2%)                1/48 (2%)                4/48 (8%)       | 
|POLY-3 RATE (b)    |                  2/45.14                  1/46.93                  1/43.58                  4/45.78         | 
|POLY-3 PERCENT (g) |                  4.4%                     2.1%                     2.3%                     8.7%            | 
|TERMINAL (d)       |                  2/40 (5%)                1/44 (2%)                1/40 (3%)                2/41 (5%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  626             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.159                  P=0.467N                 P=0.500N                 P=0.349         | 
|POLY 3             |                  P=0.157                  P=0.486N                 P=0.512N                 P=0.344         | 
|POLY 1.5           |                  P=0.156                  P=0.491N                 P=0.511N                 P=0.337         | 
|POLY 6             |                  P=0.160                  P=0.481N                 P=0.509N                 P=0.355         | 
|LOGISTIC REGRESSION|                  P=0.161                  P=0.467N                 P=0.500N                 P=0.342         | 
|COCH-ARM / FISHERS |                  P=0.160                  P=0.500N                 P=0.500N                 P=0.339         | 
|ORDER RESTRICTED   |                  P=0.138                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Granulosa Cell Tumor Benign                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/48 (0%)                2/46 (4%)                0/46 (0%)                0/45 (0%)       | 
|POLY-3 RATE (b)    |                  0/45.14                  2/45.38                  0/43.32                  0/43.07         | 
|POLY-3 PERCENT (g) |                  0.0%                     4.4%                     0.0%                     0.0%            | 
|TERMINAL (d)       |                  0/40 (0%)                2/43 (5%)                0/40 (0%)                0/39 (0%)       | 
|FIRST INCIDENCE    |                  ---                      727 (T)                  ---                      ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.385N                 P=0.254                  (e)                      (e)             | 
|POLY 3             |                  P=0.377N                 P=0.238                  (e)                      (e)             | 
|POLY 1.5           |                  P=0.381N                 P=0.234                  (e)                      (e)             | 
|POLY 6             |                  P=0.371N                 P=0.243                  (e)                      (e)             | 
|LOGISTIC REGRESSION|                  (e)                      P=0.254                  (e)                      (e)             | 
|COCH-ARM / FISHERS |                  P=0.387N                 P=0.237                  (e)                      (e)             | 
|ORDER RESTRICTED   |                  P=0.257N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 6       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/48 (0%)                2/47 (4%)                2/46 (4%)                0/45 (0%)       | 
|POLY-3 RATE (b)    |                  0/45.14                  2/45.93                  2/41.58                  0/42.08         | 
|POLY-3 PERCENT (g) |                  0.0%                     4.4%                     4.8%                     0.0%            | 
|TERMINAL (d)       |                  0/40 (0%)                2/43 (5%)                2/38 (5%)                0/38 (0%)       | 
|FIRST INCIDENCE    |                  ---                      727 (T)                  727 (T)                  ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.511N                 P=0.254                  P=0.227                  (e)             | 
|POLY 3             |                  P=0.508N                 P=0.241                  P=0.219                  (e)             | 
|POLY 1.5           |                  P=0.510N                 P=0.238                  P=0.220                  (e)             | 
|POLY 6             |                  P=0.502N                 P=0.245                  P=0.221                  (e)             | 
|LOGISTIC REGRESSION|                  (e)                      P=0.254                  P=0.227                  (e)             | 
|COCH-ARM / FISHERS |                  P=0.504N                 P=0.242                  P=0.237                  (e)             | 
|ORDER RESTRICTED   |                  P=0.267                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Sarcoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  0/48 (0%)                1/48 (2%)                2/48 (4%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  0/45.14                  1/46.93                  2/43.58                  1/45.17         | 
|POLY-3 PERCENT (g) |                  0.0%                     2.1%                     4.6%                     2.2%            | 
|TERMINAL (d)       |                  0/40 (0%)                1/44 (2%)                2/40 (5%)                0/41 (0%)       | 
|FIRST INCIDENCE    |                  ---                      727 (T)                  727 (T)                  704             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.368                  P=0.519                  P=0.238                  P=0.514         | 
|POLY 3             |                  P=0.365                  P=0.508                  P=0.229                  P=0.500         | 
|POLY 1.5           |                  P=0.362                  P=0.505                  P=0.230                  P=0.498         | 
|POLY 6             |                  P=0.371                  P=0.511                  P=0.231                  P=0.503         | 
|LOGISTIC REGRESSION|                  P=0.363                  P=0.519                  P=0.238                  P=0.500         | 
|COCH-ARM / FISHERS |                  P=0.368                  P=0.500                  P=0.247                  P=0.500         | 
|ORDER RESTRICTED   |                  P=0.217                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 7       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  2/48 (4%)                1/48 (2%)                2/48 (4%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  2/45.97                  1/46.93                  2/43.58                  1/45.08         | 
|POLY-3 PERCENT (g) |                  4.4%                     2.1%                     4.6%                     2.2%            | 
|TERMINAL (d)       |                  0/40 (0%)                1/44 (2%)                2/40 (5%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  562                      727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.459N                 P=0.484N                 P=0.682                  P=0.502N        | 
|POLY 3             |                  P=0.464N                 P=0.493N                 P=0.674                  P=0.507N        | 
|POLY 1.5           |                  P=0.463N                 P=0.495N                 P=0.678                  P=0.507N        | 
|POLY 6             |                  P=0.464N                 P=0.491N                 P=0.674                  P=0.506N        | 
|LOGISTIC REGRESSION|                  P=0.433N                 P=0.660N                 P=0.666N                 P=0.457N        | 
|COCH-ARM / FISHERS |                  P=0.451N                 P=0.500N                 P=0.692N                 P=0.500N        | 
|ORDER RESTRICTED   |                  P=0.452N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  1/48 (2%)                2/48 (4%)                1/48 (2%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  1/45.14                  2/46.93                  1/43.58                  1/45.08         | 
|POLY-3 PERCENT (g) |                  2.2%                     4.3%                     2.3%                     2.2%            | 
|TERMINAL (d)       |                  1/40 (3%)                2/44 (5%)                1/40 (3%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  727 (T)                  727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.524N                 P=0.533                  P=0.762                  P=0.756N        | 
|POLY 3             |                  P=0.525N                 P=0.514                  P=0.753                  P=0.760         | 
|POLY 1.5           |                  P=0.526N                 P=0.509                  P=0.753                  P=0.758         | 
|POLY 6             |                  P=0.521N                 P=0.519                  P=0.755                  P=0.758N        | 
|LOGISTIC REGRESSION|                  P=0.524N                 P=0.533                  P=0.762                  P=0.756N        | 
|COCH-ARM / FISHERS |                  P=0.520N                 P=0.500                  P=0.753N                 P=0.753N        | 
|ORDER RESTRICTED   |                  P=0.596N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 8       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Histiocytic Sarcoma                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  3/48 (6%)                0/48 (0%)                1/48 (2%)                1/48 (2%)       | 
|POLY-3 RATE (b)    |                  3/46.00                  0/46.93                  1/43.71                  1/45.08         | 
|POLY-3 PERCENT (g) |                  6.5%                     0.0%                     2.3%                     2.2%            | 
|TERMINAL (d)       |                  0/40 (0%)                0/44 (0%)                0/40 (0%)                1/41 (2%)       | 
|FIRST INCIDENCE    |                  562                      ---                      694                      727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.317N                 P=0.115N                 P=0.312N                 P=0.304N        | 
|POLY 3             |                  P=0.323N                 P=0.115N                 P=0.324N                 P=0.313N        | 
|POLY 1.5           |                  P=0.321N                 P=0.116N                 P=0.320N                 P=0.313N        | 
|POLY 6             |                  P=0.324N                 P=0.114N                 P=0.324N                 P=0.312N        | 
|LOGISTIC REGRESSION|                  P=0.282N                 P=0.186N                 P=0.258N                 P=0.276N        | 
|COCH-ARM / FISHERS |                  P=0.313N                 P=0.121N                 P=0.308N                 P=0.308N        | 
|ORDER RESTRICTED   |                  P=0.106N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        | 
|     NOS, or Undifferentiated Cell Type                                                                                          | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  7/48 (15%)               10/48 (21%)              6/48 (13%)               13/48 (27%)     | 
|POLY-3 RATE (b)    |                  7/45.54                  10/47.70                 6/44.83                  13/47.21        | 
|POLY-3 PERCENT (g) |                  15.4%                    21.0%                    13.4%                    27.5%           | 
|TERMINAL (d)       |                  5/40 (13%)               7/44 (16%)               3/40 (8%)                9/41 (22%)      | 
|FIRST INCIDENCE    |                  673                      596                      252                      161             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.117                  P=0.371                  P=0.504N                 P=0.126         | 
|POLY 3             |                  P=0.117                  P=0.334                  P=0.512N                 P=0.120         | 
|POLY 1.5           |                  P=0.115                  P=0.320                  P=0.512N                 P=0.114         | 
|POLY 6             |                  P=0.120                  P=0.351                  P=0.506N                 P=0.126         | 
|LOGISTIC REGRESSION|                  P=0.144                  P=0.263                  P=0.456N                 P=0.119         | 
|COCH-ARM / FISHERS |                  P=0.110                  P=0.297                  P=0.500N                 P=0.104         | 
|ORDER RESTRICTED   |                  P=0.105                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 9       
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  12/48 (25%)              11/48 (23%)              11/48 (23%)              8/48 (17%)      | 
|POLY-3 RATE (b)    |                  12/45.97                 11/46.93                 11/43.58                 8/45.08         | 
|POLY-3 PERCENT (g) |                  26.1%                    23.4%                    25.2%                    17.8%           | 
|TERMINAL (d)       |                  10/40 (25%)              11/44 (25%)              11/40 (28%)              8/41 (20%)      | 
|FIRST INCIDENCE    |                  562                      727 (T)                  727 (T)                  727 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.196N                 P=0.405N                 P=0.505N                 P=0.213N        | 
|POLY 3             |                  P=0.215N                 P=0.477N                 P=0.559N                 P=0.240N        | 
|POLY 1.5           |                  P=0.212N                 P=0.485N                 P=0.546N                 P=0.240N        | 
|POLY 6             |                  P=0.213N                 P=0.471N                 P=0.562N                 P=0.236N        | 
|LOGISTIC REGRESSION|                  P=0.200N                 P=0.486N                 P=0.535N                 P=0.229N        | 
|COCH-ARM / FISHERS |                  P=0.189N                 P=0.500N                 P=0.500N                 P=0.226N        | 
|ORDER RESTRICTED   |                  P=0.274N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  18/48 (38%)              15/48 (31%)              12/48 (25%)              20/48 (42%)     | 
|POLY-3 RATE (b)    |                  18/47.56                 15/48.00                 12/44.96                 20/48.00        | 
|POLY-3 PERCENT (g) |                  37.9%                    31.3%                    26.7%                    41.7%           | 
|TERMINAL (d)       |                  11/40 (28%)              11/44 (25%)              8/40 (20%)               13/41 (32%)     | 
|FIRST INCIDENCE    |                  378                      596                      252                      161             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.330                  P=0.264N                 P=0.166N                 P=0.453         | 
|POLY 3             |                  P=0.322                  P=0.323N                 P=0.178N                 P=0.432         | 
|POLY 1.5           |                  P=0.322                  P=0.328N                 P=0.166N                 P=0.426         | 
|POLY 6             |                  P=0.324                  P=0.316N                 P=0.186N                 P=0.440         | 
|LOGISTIC REGRESSION|                  P=0.384                  P=0.521N                 P=0.105N                 P=0.343         | 
|COCH-ARM / FISHERS |                  P=0.327                  P=0.334N                 P=0.135N                 P=0.417         | 
|ORDER RESTRICTED   |                  P=0.253                  (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  06/19/03                           EXPERIMENT: 93005 TEST: 04                                            Page 10      
Statistical Analysis of Primary Tumors in Mice(C57BL/6NXC3H/HEN MTN-NCTR)       -                      MALACHITE GREEN              
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |                  0 PPM                    100 PPM                  225 PPM                  450 PPM         | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                  #                        #                        #                        #               | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                  25/48 (52%)              23/48 (48%)              20/48 (42%)              25/48 (52%)     | 
|POLY-3 RATE (b)    |                  25/47.56                 23/48.00                 20/44.96                 25/48.00        | 
|POLY-3 PERCENT (g) |                  52.6%                    47.9%                    44.5%                    52.1%           | 
|TERMINAL (d)       |                  18/40 (45%)              19/44 (43%)              16/40 (40%)              18/41 (44%)     | 
|FIRST INCIDENCE    |                  378                      596                      252                      161             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                  P=0.504                  P=0.297N                 P=0.241N                 P=0.535N        | 
|POLY 3             |                  P=0.524                  P=0.402N                 P=0.285N                 P=0.562N        | 
|POLY 1.5           |                  P=0.523                  P=0.410N                 P=0.263N                 P=0.570N        | 
|POLY 6             |                  P=0.529                  P=0.392N                 P=0.299N                 P=0.552N        | 
|LOGISTIC REGRESSION|                  P=0.514N                 P=0.550N                 P=0.199N                 P=0.540         | 
|COCH-ARM / FISHERS |                  P=0.528                  P=0.419N                 P=0.207N                 P=0.581N        | 
|ORDER RESTRICTED   |                  P=0.528N                 (e)                      (e)                      (e)             | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).