https://ntp.niehs.nih.gov/go/21000

TDMS Study 91005-08 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                             METHYLENE BLUE TRIHYDRATE                              DATE: 04/26/05       
EXPERIMENT: 91005 TEST: 08                                                                                     TIME: 09:25:37       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-05451                              ROUTE: GAVAGE                                                  NTP C#: 91005C       
PATHOLOGIST: FARNELL, DANIEL                                                                                   CAS: 7220-79-3       
------------------------------------------------------------------------------------------------------------------------------------
                                                           FINAL #1 MICE                                                            
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                             METHYLENE BLUE TRIHYDRATE                              DATE: 04/26/05       
EXPERIMENT: 91005 TEST: 08                                                                                     TIME: 09:25:37       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-05451                              ROUTE: GAVAGE                                                  NTP C#: 91005C       
PATHOLOGIST: FARNELL, DANIEL                                                                                   CAS: 7220-79-3       
Mice(B6C3F1)                                                                                                                        
-----------------------------                                                                                                       
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE                                                                   
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES                                                                 
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.                                                                                      
                                                 ---------------                                                                    
                                                 Adrenal Cortex                                                                     
                                                 Adrenal Medulla                                                                    
                                                 Bone Marrow                                                                        
                                                 Islets, Pancreatic                                                                 
                                                 Kidney                                                                             
                                                 Liver                                                                              
                                                 Lung                                                                               
                                                 Ovary                                                                              
                                                 Pancreas                                                                           
                                                 Pituitary Gland                                                                    
                                                 Spleen                                                                             
                                                 Testes                                                                             
                                                 Thyroid Gland                                                                      
                                                 Urinary Bladder                                                                    
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                             METHYLENE BLUE TRIHYDRATE                              DATE: 04/26/05       
EXPERIMENT: 91005 TEST: 08                                                                                     TIME: 09:25:37       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-05451                              ROUTE: GAVAGE                                                  NTP C#: 91005C       
PATHOLOGIST: FARNELL, DANIEL                                                                                   CAS: 7220-79-3       
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                METHYLENE BLUE TRIHYDRATE                                                                         
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Harderian Gland                        Adenoma                                                                                      
                                       Carcinoma or Adenoma                                                                         
Intestine Small: Site Unspecified      Carcinoma                                                                                    
                                       Carcinoma or Adenoma                                                                         
Liver                                  Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                          
Lung                                   Alveolar/Bronchiolar Carcinoma                                                               
All Organs                             Hemangiosarcoma                                                                              
                                       Hemangiosarcoma or Hemangioma                                                                
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Liver                                  Hepatocellular Carcinoma                                                                     
Lung                                   Alveolar/Bronchiolar Carcinoma                                                               
Pituitary Gland: Pars Distalis or Unspecified Site                                                                                  
                                       Adenoma                                                                                      
All Organs                             Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type      
                                       Benign Tumors                                                                                
                                       Malignant Tumors                                                                             
===============================================================                                                                     
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 1       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)        -                 METHYLENE BLUE TRIHYDRATE      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/48 (10%)   5/50 (10%)   2/50 (4%)    5/48 (10%)  |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     5/42.73      5/46.10      2/46.36      5/45.75     |0/44.58      0/45.81      1/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     11.7%        10.9%        4.3%         10.9%       |0.0%         0.0%         2.1%         0.0%         | 
|TERMINAL (d)       |     4/34 (12%)   5/38 (13%)   2/38 (5%)    5/40 (13%)  |0/33 (0%)    0/40 (0%)    1/42 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     723          729 (T)      729 (T)      729 (T)     |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.408N     P=0.563N     P=0.178N     P=0.529N    |P=0.676      (e)          P=0.548      (e)          | 
|POLY 3             |     P=0.469N     P=0.582N     P=0.184N     P=0.587N    |P=0.664      (e)          P=0.513      (e)          | 
|POLY 1.5           |     P=0.478N     P=0.596N     P=0.192N     P=0.605N    |P=0.659      (e)          P=0.508      (e)          | 
|POLY 6             |     P=0.457N     P=0.565N     P=0.175N     P=0.565N    |P=0.675      (e)          P=0.522      (e)          | 
|LOGISTIC REGRESSION|     P=0.421N     P=0.561N     P=0.175N     P=0.541N    |(e)          (e)          P=0.548      (e)          | 
|COCH-ARM / FISHERS |     P=0.496N     P=0.603N     P=0.201N     P=0.630N    |P=0.649      (e)          P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.407N     (e)          (e)          (e)         |P=0.393      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Pheochromocytoma Benign                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    0/50 (0%)    1/50 (2%)    2/48 (4%)   |1/50 (2%)    1/50 (2%)    2/49 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/42.71      0/46.10      1/46.36      2/45.75     |1/44.58      1/45.81      2/46.65      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         4.4%        |2.2%         2.2%         4.3%         0.0%         | 
|TERMINAL (d)       |     0/34 (0%)    0/38 (0%)    1/38 (3%)    2/40 (5%)   |1/33 (3%)    1/40 (3%)    2/41 (5%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      729 (T)     |729 (T)      729 (T)      729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.073      (e)          P=0.522      P=0.275     |P=0.319N     P=0.718N     P=0.576      P=0.447N     | 
|POLY 3             |     P=0.064      (e)          P=0.516      P=0.253     |P=0.359N     P=0.755N     P=0.516      P=0.489N     | 
|POLY 1.5           |     P=0.062      (e)          P=0.512      P=0.246     |P=0.365N     P=0.758N     P=0.506      P=0.493N     | 
|POLY 6             |     P=0.066      (e)          P=0.521      P=0.261     |P=0.348N     P=0.748N     P=0.531      P=0.481N     | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.522      P=0.275     |P=0.319N     P=0.718N     P=0.576      (e)          | 
|COCH-ARM / FISHERS |     P=0.058      (e)          P=0.510      P=0.247     |P=0.375N     P=0.753N     P=0.492      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.084      (e)          (e)          (e)         |P=0.271N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 2       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/44.11      2/46.35      0/46.36      0/47.59     |0/44.58      0/45.81      1/46.65      0/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         4.3%         0.0%         0.0%        |0.0%         0.0%         2.1%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |0/33 (0%)    0/40 (0%)    1/41 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      676          ---          ---         |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.122N     P=0.533      P=0.484N     P=0.468N    |P=0.675      (e)          P=0.543      (e)          | 
|POLY 3             |     P=0.126N     P=0.517      P=0.490N     P=0.485N    |P=0.664      (e)          P=0.509      (e)          | 
|POLY 1.5           |     P=0.130N     P=0.507      P=0.495N     P=0.491N    |P=0.658      (e)          P=0.503      (e)          | 
|POLY 6             |     P=0.123N     P=0.530      P=0.485N     P=0.478N    |P=0.674      (e)          P=0.518      (e)          | 
|LOGISTIC REGRESSION|     P=0.130N     P=0.507      (e)          (e)         |(e)          (e)          P=0.543      (e)          | 
|COCH-ARM / FISHERS |     P=0.134N     P=0.500      P=0.500N     P=0.500N    |P=0.648      (e)          P=0.495      (e)          | 
|ORDER RESTRICTED   |     P=0.164N     (e)          (e)          (e)         |P=0.389      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   1/50 (2%)    11/50 (22%)  5/50 (10%)  |4/50 (8%)    2/50 (4%)    7/50 (14%)   3/50 (6%)    | 
|POLY-3 RATE (b)    |     8/45.29      1/46.10      11/47.25     5/47.59     |4/45.16      2/45.99      7/48.01      3/47.10      | 
|POLY-3 PERCENT (g) |     17.7%        2.2%         23.3%        10.5%       |8.9%         4.4%         14.6%        6.4%         | 
|TERMINAL (d)       |     5/35 (14%)   1/38 (3%)    8/38 (21%)   5/41 (12%)  |2/33 (6%)    1/40 (3%)    6/42 (14%)   3/43 (7%)    | 
|FIRST INCIDENCE    |     478          729 (T)      627          729 (T)     |638          680          627          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.523      P=0.015N*    P=0.384      P=0.196N    |P=0.533N     P=0.280N     P=0.388      P=0.386N     | 
|POLY 3             |     P=0.465      P=0.014N*    P=0.341      P=0.244N    |P=0.516      P=0.329N     P=0.298      P=0.477N     | 
|POLY 1.5           |     P=0.454      P=0.016N*    P=0.323      P=0.257N    |P=0.507      P=0.335N     P=0.282      P=0.486N     | 
|POLY 6             |     P=0.478      P=0.013N*    P=0.364      P=0.230N    |P=0.532      P=0.319N     P=0.322      P=0.461N     | 
|LOGISTIC REGRESSION|     P=0.430      P=0.018N*    P=0.300      P=0.289N    |P=0.500      P=0.337N     P=0.265      P=0.491N     | 
|COCH-ARM / FISHERS |     P=0.425      P=0.015N*    P=0.306      P=0.277N    |P=0.487      P=0.339N     P=0.262      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.241N     (e)          (e)          (e)         |P=0.398      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 3       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    4/50 (8%)    1/50 (2%)   |0/50 (0%)    1/50 (2%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     3/44.13      0/46.10      4/47.22      1/47.59     |0/44.58      1/46.20      2/47.66      2/47.37      | 
|POLY-3 PERCENT (g) |     6.8%         0.0%         8.5%         2.1%        |0.0%         2.2%         4.2%         4.2%         | 
|TERMINAL (d)       |     2/35 (6%)    0/38 (0%)    2/38 (5%)    1/41 (2%)   |0/33 (0%)    0/40 (0%)    1/42 (2%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     723          ---          605          729 (T)     |---          616          726          659          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.469N     P=0.111N     P=0.546      P=0.257N    |P=0.202      P=0.496      P=0.297      P=0.285      | 
|POLY 3             |     P=0.494N     P=0.111N     P=0.537      P=0.279N    |P=0.181      P=0.507      P=0.252      P=0.251      | 
|POLY 1.5           |     P=0.500N     P=0.116N     P=0.520      P=0.290N    |P=0.175      P=0.503      P=0.246      P=0.245      | 
|POLY 6             |     P=0.487N     P=0.106N     P=0.557      P=0.267N    |P=0.193      P=0.514      P=0.263      P=0.261      | 
|LOGISTIC REGRESSION|     P=0.527N     P=0.104N     P=0.493      P=0.255N    |P=0.157      P=0.511      P=0.284      P=0.231      | 
|COCH-ARM / FISHERS |     P=0.518N     P=0.121N     P=0.500      P=0.309N    |P=0.164      P=0.500      P=0.247      P=0.247      | 
|ORDER RESTRICTED   |     P=0.211N     (e)          (e)          (e)         |P=0.167      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/50 (22%)  1/50 (2%)    15/50 (30%)  6/50 (12%)  |4/50 (8%)    3/50 (6%)    9/50 (18%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     11/45.31     1/46.10      15/48.10     6/47.59     |4/45.16      3/46.39      9/48.02      5/47.37      | 
|POLY-3 PERCENT (g) |     24.3%        2.2%         31.2%        12.6%       |8.9%         6.5%         18.7%        10.6%        | 
|TERMINAL (d)       |     7/35 (20%)   1/38 (3%)    10/38 (26%)  6/41 (15%)  |2/33 (6%)    1/40 (3%)    7/42 (17%)   4/43 (9%)    | 
|FIRST INCIDENCE    |     478          729 (T)      605          729 (T)     |638          616          627          659          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.510N     P=0.002N**   P=0.343      P=0.088N    |P=0.364      P=0.440N     P=0.221      P=0.628      | 
|POLY 3             |     P=0.521      P=0.002N**   P=0.304      P=0.117N    |P=0.279      P=0.485N     P=0.140      P=0.530      | 
|POLY 1.5           |     P=0.508      P=0.002N**   P=0.276      P=0.127N    |P=0.269      P=0.494N     P=0.130      P=0.518      | 
|POLY 6             |     P=0.537      P<0.001N**   P=0.342      P=0.106N    |P=0.297      P=0.471N     P=0.158      P=0.551      | 
|LOGISTIC REGRESSION|     P=0.471      P=0.003N**   P=0.239      P=0.130N    |P=0.254      P=0.500N     P=0.124      P=0.504      | 
|COCH-ARM / FISHERS |     P=0.471      P=0.002N**   P=0.247      P=0.143N    |P=0.250      P=0.500N     P=0.117      P=0.500      | 
|ORDER RESTRICTED   |     P=0.097N     (e)          (e)          (e)         |P=0.225      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 4       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Duodenum                                                                                                        | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      1/46.36      2/47.91     |0/44.58      0/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         4.2%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    1/38 (3%)    1/41 (2%)   |0/33 (0%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      641         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.074      (e)          P=0.516      P=0.275     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.068      (e)          P=0.510      P=0.256     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.065      (e)          P=0.505      P=0.248     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.071      (e)          P=0.515      P=0.266     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.058      (e)          P=0.516      P=0.202     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.060      (e)          P=0.500      P=0.247     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.087      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Jejunum                                                                                                         | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      2/46.36      2/47.59     |0/44.58      0/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.3%         4.2%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    2/38 (5%)    2/41 (5%)   |0/33 (0%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.087      (e)          P=0.257      P=0.274     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.079      (e)          P=0.248      P=0.255     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.076      (e)          P=0.243      P=0.247     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.083      (e)          P=0.254      P=0.263     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.257      P=0.274     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.070      (e)          P=0.247      P=0.247     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.126      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 5       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Site Unspecified                                                                                                | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    2/50 (4%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/44.11      1/46.10      2/46.36      2/47.91     |0/44.58      1/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         2.2%         4.3%         4.2%        |0.0%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    1/38 (3%)    2/38 (5%)    1/41 (2%)   |0/33 (0%)    1/40 (3%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      641         |---          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.365      P=0.743N     P=0.529      P=0.555     |P=0.419N     P=0.538      (e)          (e)          | 
|POLY 3             |     P=0.347      P=0.751N     P=0.517      P=0.529     |P=0.441N     P=0.505      (e)          (e)          | 
|POLY 1.5           |     P=0.337      P=0.757N     P=0.509      P=0.517     |P=0.445N     P=0.502      (e)          (e)          | 
|POLY 6             |     P=0.360      P=0.744N     P=0.526      P=0.543     |P=0.434N     P=0.511      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.335      P=0.743N     P=0.529      P=0.490     |(e)          P=0.538      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.318      P=0.753N     P=0.500      P=0.500     |P=0.449N     P=0.500      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.464      (e)          (e)          (e)         |P=0.376N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Site Unspecified                                                                                                | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    2/50 (4%)    4/50 (8%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.11      1/46.10      2/46.36      4/47.68     |1/44.58      0/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         2.2%         4.3%         8.4%        |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    2/38 (5%)    3/41 (7%)   |1/33 (3%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      705         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.033 *    P=0.516      P=0.257      P=0.087     |P=0.324N     P=0.462N     P=0.452N     P=0.447N     | 
|POLY 3             |     P=0.027 *    P=0.509      P=0.248      P=0.071     |P=0.355N     P=0.495N     P=0.487N     P=0.489N     | 
|POLY 1.5           |     P=0.025 *    P=0.504      P=0.243      P=0.067     |P=0.353N     P=0.498N     P=0.492N     P=0.493N     | 
|POLY 6             |     P=0.029 *    P=0.515      P=0.254      P=0.077     |P=0.359N     P=0.489N     P=0.478N     P=0.481N     | 
|LOGISTIC REGRESSION|     P=0.030 *    P=0.516      P=0.257      P=0.079     |P=0.324N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.023 *    P=0.500      P=0.247      P=0.059     |P=0.351N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.024 *    (e)          (e)          (e)         |P=0.111N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 6       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Site Unspecified                                                                                                | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    4/50 (8%)    6/50 (12%)  |1/50 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/44.11      2/46.10      4/46.36      6/48.00     |1/44.58      1/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         4.3%         8.6%         12.5%       |2.2%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    2/38 (5%)    4/38 (11%)   4/41 (10%)  |1/33 (3%)    1/40 (3%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      641         |729 (T)      729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.037 *    P=0.529      P=0.204      P=0.091     |P=0.179N     P=0.718N     P=0.452N     P=0.447N     | 
|POLY 3             |     P=0.029 *    P=0.515      P=0.194      P=0.071     |P=0.205N     P=0.755N     P=0.487N     P=0.489N     | 
|POLY 1.5           |     P=0.026 *    P=0.506      P=0.187      P=0.065     |P=0.206N     P=0.758N     P=0.492N     P=0.493N     | 
|POLY 6             |     P=0.032 *    P=0.526      P=0.202      P=0.080     |P=0.202N     P=0.748N     P=0.478N     P=0.481N     | 
|LOGISTIC REGRESSION|     P=0.030 *    P=0.529      P=0.204      P=0.066     |P=0.179N     P=0.718N     (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.023 *    P=0.500      P=0.181      P=0.056     |P=0.208N     P=0.753N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.038 *    (e)          (e)          (e)         |P=0.241N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/49 (4%)    1/48 (2%)   |1/46 (2%)    0/47 (0%)    0/49 (0%)    1/48 (2%)    | 
|POLY-3 RATE (b)    |     0/44.11      2/46.10      2/45.58      1/46.16     |1/41.35      0/43.51      0/47.17      1/45.84      | 
|POLY-3 PERCENT (g) |     0.0%         4.3%         4.4%         2.2%        |2.4%         0.0%         0.0%         2.2%         | 
|TERMINAL (d)       |     0/35 (0%)    2/38 (5%)    2/38 (5%)    1/41 (2%)   |1/32 (3%)    0/40 (0%)    0/42 (0%)    1/42 (2%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |729 (T)      ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.567      P=0.257      P=0.257      P=0.532     |P=0.578      P=0.455N     P=0.446N     P=0.700N     | 
|POLY 3             |     P=0.551      P=0.247      P=0.245      P=0.509     |P=0.552      P=0.490N     P=0.474N     P=0.737N     | 
|POLY 1.5           |     P=0.533      P=0.241      P=0.239      P=0.502     |P=0.551      P=0.493N     P=0.479N     P=0.742N     | 
|POLY 6             |     P=0.571      P=0.254      P=0.251      P=0.518     |P=0.553      P=0.484N     P=0.465N     P=0.729N     | 
|LOGISTIC REGRESSION|     (e)          P=0.257      P=0.257      P=0.532     |P=0.578      (e)          (e)          P=0.700N     | 
|COCH-ARM / FISHERS |     P=0.508      P=0.247      P=0.242      P=0.490     |P=0.545      P=0.495N     P=0.484N     P=0.742N     | 
|ORDER RESTRICTED   |     P=0.235      (e)          (e)          (e)         |P=0.367N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 7       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/49 (4%)    1/48 (2%)   |1/46 (2%)    0/47 (0%)    0/49 (0%)    2/48 (4%)    | 
|POLY-3 RATE (b)    |     0/44.11      2/46.10      2/45.58      1/46.16     |1/41.35      0/43.51      0/47.17      2/46.13      | 
|POLY-3 PERCENT (g) |     0.0%         4.3%         4.4%         2.2%        |2.4%         0.0%         0.0%         4.3%         | 
|TERMINAL (d)       |     0/35 (0%)    2/38 (5%)    2/38 (5%)    1/41 (2%)   |1/32 (3%)    0/40 (0%)    0/42 (0%)    1/42 (2%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |729 (T)      ---          ---          649          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.567      P=0.257      P=0.257      P=0.532     |P=0.243      P=0.455N     P=0.446N     P=0.576      | 
|POLY 3             |     P=0.551      P=0.247      P=0.245      P=0.509     |P=0.223      P=0.490N     P=0.474N     P=0.538      | 
|POLY 1.5           |     P=0.533      P=0.241      P=0.239      P=0.502     |P=0.221      P=0.493N     P=0.479N     P=0.529      | 
|POLY 6             |     P=0.571      P=0.254      P=0.251      P=0.518     |P=0.226      P=0.484N     P=0.465N     P=0.552      | 
|LOGISTIC REGRESSION|     (e)          P=0.257      P=0.257      P=0.532     |P=0.212      (e)          (e)          P=0.512      | 
|COCH-ARM / FISHERS |     P=0.508      P=0.247      P=0.242      P=0.490     |P=0.216      P=0.495N     P=0.484N     P=0.516      | 
|ORDER RESTRICTED   |     P=0.235      (e)          (e)          (e)         |P=0.154      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    5/50 (10%)   3/50 (6%)    1/49 (2%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.35      5/46.17      3/47.13      1/46.75     |0/44.58      0/45.81      2/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     4.5%         10.8%        6.4%         2.1%        |0.0%         0.0%         4.2%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    3/38 (8%)    0/38 (0%)    1/41 (2%)   |0/33 (0%)    0/40 (0%)    2/42 (5%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     665          717          605          729 (T)     |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.152N     P=0.258      P=0.543      P=0.447N    |P=0.579      (e)          P=0.293      (e)          | 
|POLY 3             |     P=0.162N     P=0.233      P=0.528      P=0.482N    |P=0.558      (e)          P=0.252      (e)          | 
|POLY 1.5           |     P=0.172N     P=0.223      P=0.515      P=0.492N    |P=0.550      (e)          P=0.246      (e)          | 
|POLY 6             |     P=0.151N     P=0.244      P=0.543      P=0.470N    |P=0.572      (e)          P=0.263      (e)          | 
|LOGISTIC REGRESSION|     P=0.187N     P=0.241      P=0.486      P=0.498N    |(e)          (e)          P=0.293      (e)          | 
|COCH-ARM / FISHERS |     P=0.189N     P=0.218      P=0.500      P=0.508N    |P=0.536      (e)          P=0.247      (e)          | 
|ORDER RESTRICTED   |     P=0.206N     (e)          (e)          (e)         |P=0.260      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 8       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatoblastoma                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    0/49 (0%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.11      2/46.33      2/46.52      0/46.75     |0/44.58      0/45.81      1/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     4.5%         4.3%         4.3%         0.0%        |0.0%         0.0%         2.1%         0.0%         | 
|TERMINAL (d)       |     2/35 (6%)    1/38 (3%)    1/38 (3%)    0/41 (0%)   |0/33 (0%)    0/40 (0%)    1/42 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      670          690          ---         |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.135N     P=0.660N     P=0.662N     P=0.204N    |P=0.676      (e)          P=0.548      (e)          | 
|POLY 3             |     P=0.148N     P=0.676N     P=0.675N     P=0.224N    |P=0.664      (e)          P=0.513      (e)          | 
|POLY 1.5           |     P=0.154N     P=0.686N     P=0.684N     P=0.232N    |P=0.659      (e)          P=0.508      (e)          | 
|POLY 6             |     P=0.142N     P=0.664N     P=0.664N     P=0.216N    |P=0.675      (e)          P=0.522      (e)          | 
|LOGISTIC REGRESSION|     P=0.152N     P=0.680N     P=0.669N     (e)         |(e)          (e)          P=0.548      (e)          | 
|COCH-ARM / FISHERS |     P=0.162N     P=0.691N     P=0.691N     P=0.253N    |P=0.649      (e)          P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.177N     (e)          (e)          (e)         |P=0.393      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Adenoma                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     28/50 (56%)  33/50 (66%)  26/50 (52%)  27/49 (55%) |15/50 (30%)  19/50 (38%)  22/50 (44%)  13/50 (26%)  | 
|POLY-3 RATE (b)    |     28/45.64     33/47.29     26/46.94     27/46.94    |15/45.71     19/46.42     22/48.11     13/47.10     | 
|POLY-3 PERCENT (g) |     61.4%        69.8%        55.4%        57.5%       |32.8%        40.9%        45.7%        27.6%        | 
|TERMINAL (d)       |     25/35 (71%)  28/38 (74%)  24/38 (63%)  25/41 (61%) |11/33 (33%)  17/40 (43%)  20/42 (48%)  13/43 (30%)  | 
|FIRST INCIDENCE    |     478          610          627          694         |617          616          627          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.057N     P=0.377      P=0.244N     P=0.188N    |P=0.100N     P=0.490      P=0.351      P=0.166N     | 
|POLY 3             |     P=0.183N     P=0.256      P=0.353N     P=0.434N    |P=0.243N     P=0.276      P=0.141      P=0.374N     | 
|POLY 1.5           |     P=0.210N     P=0.213      P=0.390N     P=0.483N    |P=0.257N     P=0.265      P=0.125      P=0.387N     | 
|POLY 6             |     P=0.154N     P=0.328      P=0.306N     P=0.369N    |P=0.220N     P=0.296      P=0.169      P=0.349N     | 
|LOGISTIC REGRESSION|     P=0.113N     P=0.304      P=0.273N     P=0.311N    |P=0.207N     P=0.295      P=0.156      P=0.329N     | 
|COCH-ARM / FISHERS |     P=0.267N     P=0.206      P=0.421N     P=0.545N    |P=0.292N     P=0.263      P=0.107      P=0.412N     | 
|ORDER RESTRICTED   |     P=0.283N     (e)          (e)          (e)         |P=0.167N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 9       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     13/50 (26%)  10/50 (20%)  11/50 (22%)  14/49 (29%) |5/50 (10%)   4/50 (8%)    0/50 (0%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     13/47.00     10/48.04     11/47.23     14/47.80    |5/44.87      4/45.84      0/47.65      3/47.29      | 
|POLY-3 PERCENT (g) |     27.7%        20.8%        23.3%        29.3%       |11.1%        8.7%         0.0%         6.3%         | 
|TERMINAL (d)       |     5/35 (14%)   5/38 (13%)   7/38 (18%)   10/41 (24%) |4/33 (12%)   3/40 (8%)    0/42 (0%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     536          452          638          506         |650          720          ---          680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.464      P=0.269N     P=0.336N     P=0.517N    |P=0.133N     P=0.393N     P=0.019N*    P=0.240N     | 
|POLY 3             |     P=0.332      P=0.295N     P=0.402N     P=0.520     |P=0.178N     P=0.487N     P=0.026N*    P=0.328N     | 
|POLY 1.5           |     P=0.327      P=0.312N     P=0.408N     P=0.503     |P=0.182N     P=0.495N     P=0.028N*    P=0.340N     | 
|POLY 6             |     P=0.339      P=0.279N     P=0.395N     P=0.540     |P=0.171N     P=0.472N     P=0.023N*    P=0.308N     | 
|LOGISTIC REGRESSION|     P=0.244      P=0.327N     P=0.446N     P=0.308     |P=0.172N     P=0.466N     P=0.028N*    P=0.332N     | 
|COCH-ARM / FISHERS |     P=0.307      P=0.318N     P=0.408N     P=0.475     |P=0.192N     P=0.500N     P=0.028N*    P=0.357N     | 
|ORDER RESTRICTED   |     P=0.433      (e)          (e)          (e)         |P=0.090N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma or Hepatoblastoma                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     15/50 (30%)  12/50 (24%)  13/50 (26%)  14/49 (29%) |5/50 (10%)   4/50 (8%)    1/50 (2%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     15/47.00     12/48.27     13/47.38     14/47.80    |5/44.87      4/45.84      1/47.65      3/47.29      | 
|POLY-3 PERCENT (g) |     31.9%        24.9%        27.4%        29.3%       |11.1%        8.7%         2.1%         6.3%         | 
|TERMINAL (d)       |     7/35 (20%)   6/38 (16%)   8/38 (21%)   10/41 (24%) |4/33 (12%)   3/40 (8%)    1/42 (2%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     536          452          638          506         |650          720          729 (T)      680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.416N     P=0.270N     P=0.333N     P=0.349N    |P=0.154N     P=0.393N     P=0.063N     P=0.240N     | 
|POLY 3             |     P=0.528      P=0.297N     P=0.401N     P=0.478N    |P=0.206N     P=0.487N     P=0.088N     P=0.328N     | 
|POLY 1.5           |     P=0.521      P=0.317N     P=0.410N     P=0.497N    |P=0.211N     P=0.495N     P=0.094N     P=0.340N     | 
|POLY 6             |     P=0.535      P=0.275N     P=0.391N     P=0.458N    |P=0.196N     P=0.472N     P=0.080N     P=0.308N     | 
|LOGISTIC REGRESSION|     P=0.433      P=0.337N     P=0.442N     P=0.503     |P=0.198N     P=0.466N     P=0.087N     P=0.332N     | 
|COCH-ARM / FISHERS |     P=0.498      P=0.326N     P=0.412N     P=0.526N    |P=0.222N     P=0.500N     P=0.102N     P=0.357N     | 
|ORDER RESTRICTED   |     P=0.483N     (e)          (e)          (e)         |P=0.150N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 10      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     37/50 (74%)  38/50 (76%)  33/50 (66%)  35/49 (71%) |19/50 (38%)  20/50 (40%)  22/50 (44%)  16/50 (32%)  | 
|POLY-3 RATE (b)    |     37/47.72     38/48.71     33/47.59     35/47.85    |19/46.00     20/46.45     22/48.11     16/47.29     | 
|POLY-3 PERCENT (g) |     77.5%        78.0%        69.3%        73.1%       |41.3%        43.1%        45.7%        33.8%        | 
|TERMINAL (d)       |     28/35 (80%)  30/38 (79%)  28/38 (74%)  30/41 (73%) |14/33 (42%)  17/40 (43%)  20/42 (48%)  15/43 (35%)  | 
|FIRST INCIDENCE    |     478          452          627          506         |617          616          627          680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.071N     P=0.427N     P=0.130N     P=0.118N    |P=0.090N     P=0.400N     P=0.459N     P=0.103N     | 
|POLY 3             |     P=0.264N     P=0.576      P=0.244N     P=0.395N    |P=0.236N     P=0.516      P=0.411      P=0.297N     | 
|POLY 1.5           |     P=0.274N     P=0.512      P=0.260N     P=0.430N    |P=0.249N     P=0.503      P=0.382      P=0.311N     | 
|POLY 6             |     P=0.253N     P=0.541N     P=0.220N     P=0.349N    |P=0.212N     P=0.538      P=0.456      P=0.272N     | 
|LOGISTIC REGRESSION|     P=0.218N     P=0.511      P=0.191N     P=0.373N    |P=0.202N     P=0.543      P=0.437      P=0.261N     | 
|COCH-ARM / FISHERS |     P=0.312N     P=0.500      P=0.257N     P=0.475N    |P=0.284N     P=0.500      P=0.342      P=0.338N     | 
|ORDER RESTRICTED   |     P=0.363N     (e)          (e)          (e)         |P=0.276N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma, Hepatocellular Adenoma,                                                                           | 
|     or Hepatoblastoma                                                                                                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     38/50 (76%)  39/50 (78%)  35/50 (70%)  35/49 (71%) |19/50 (38%)  20/50 (40%)  22/50 (44%)  16/50 (32%)  | 
|POLY-3 RATE (b)    |     38/47.72     39/48.94     35/47.74     35/47.85    |19/46.00     20/46.45     22/48.11     16/47.29     | 
|POLY-3 PERCENT (g) |     79.6%        79.7%        73.3%        73.1%       |41.3%        43.1%        45.7%        33.8%        | 
|TERMINAL (d)       |     29/35 (83%)  30/38 (79%)  29/38 (76%)  30/41 (73%) |14/33 (42%)  17/40 (43%)  20/42 (48%)  15/43 (35%)  | 
|FIRST INCIDENCE    |     478          452          627          506         |617          616          627          680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.049N*    P=0.420N     P=0.169N     P=0.080N    |P=0.090N     P=0.400N     P=0.459N     P=0.103N     | 
|POLY 3             |     P=0.198N     P=0.598      P=0.308N     P=0.302N    |P=0.236N     P=0.516      P=0.411      P=0.297N     | 
|POLY 1.5           |     P=0.205N     P=0.522      P=0.329N     P=0.338N    |P=0.249N     P=0.503      P=0.382      P=0.311N     | 
|POLY 6             |     P=0.190N     P=0.504N     P=0.272N     P=0.256N    |P=0.212N     P=0.538      P=0.456      P=0.272N     | 
|LOGISTIC REGRESSION|     P=0.158N     P=0.510      P=0.244N     P=0.280N    |P=0.202N     P=0.543      P=0.437      P=0.261N     | 
|COCH-ARM / FISHERS |     P=0.241N     P=0.500      P=0.326N     P=0.387N    |P=0.284N     P=0.500      P=0.342      P=0.338N     | 
|ORDER RESTRICTED   |     P=0.355N     (e)          (e)          (e)         |P=0.276N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 11      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Adenoma                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/50 (22%)  7/50 (14%)   8/50 (16%)   6/50 (12%)  |1/50 (2%)    2/50 (4%)    3/50 (6%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     11/44.75     7/46.10      8/46.36      6/48.16     |1/44.87      2/45.81      3/47.65      2/47.10      | 
|POLY-3 PERCENT (g) |     24.6%        15.2%        17.3%        12.5%       |2.2%         4.4%         6.3%         4.3%         | 
|TERMINAL (d)       |     9/35 (26%)   7/38 (18%)   8/38 (21%)   4/41 (10%)  |0/33 (0%)    2/40 (5%)    3/42 (7%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     605          729 (T)      729 (T)      610         |650          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.115N     P=0.164N     P=0.235N     P=0.082N    |P=0.491      P=0.550      P=0.381      P=0.571      | 
|POLY 3             |     P=0.146N     P=0.194N     P=0.273N     P=0.106N    |P=0.435      P=0.507      P=0.327      P=0.517      | 
|POLY 1.5           |     P=0.158N     P=0.209N     P=0.289N     P=0.120N    |P=0.426      P=0.502      P=0.318      P=0.510      | 
|POLY 6             |     P=0.133N     P=0.180N     P=0.260N     P=0.091N    |P=0.452      P=0.515      P=0.342      P=0.529      | 
|LOGISTIC REGRESSION|     P=0.140N     P=0.169N     P=0.241N     P=0.123N    |P=0.435      P=0.502      P=0.312      P=0.501      | 
|COCH-ARM / FISHERS |     P=0.182N     P=0.218N     P=0.306N     P=0.143N    |P=0.409      P=0.500      P=0.309      P=0.500      | 
|ORDER RESTRICTED   |     P=0.093N     (e)          (e)          (e)         |P=0.379      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    4/50 (8%)    5/50 (10%)   7/50 (14%)  |5/50 (10%)   0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/44.11      4/46.10      5/46.49      7/47.68     |5/45.18      0/45.81      0/47.65      1/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         8.7%         10.8%        14.7%       |11.1%        0.0%         0.0%         2.1%         | 
|TERMINAL (d)       |     1/35 (3%)    4/38 (11%)   4/38 (11%)   6/41 (15%)  |3/33 (9%)    0/40 (0%)    0/42 (0%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      696          705         |638          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.055      P=0.204      P=0.124      P=0.054     |P=0.088N     P=0.025N*    P=0.022N*    P=0.066N     | 
|POLY 3             |     P=0.043 *    P=0.192      P=0.114      P=0.039 *   |P=0.106N     P=0.029N*    P=0.026N*    P=0.092N     | 
|POLY 1.5           |     P=0.039 *    P=0.184      P=0.108      P=0.035 *   |P=0.106N     P=0.030N*    P=0.028N*    P=0.096N     | 
|POLY 6             |     P=0.048 *    P=0.202      P=0.121      P=0.044 *   |P=0.106N     P=0.028N*    P=0.024N*    P=0.086N     | 
|LOGISTIC REGRESSION|     P=0.049 *    P=0.204      P=0.122      P=0.049 *   |P=0.113N     P=0.033N*    P=0.034N*    P=0.102N     | 
|COCH-ARM / FISHERS |     P=0.033 *    P=0.181      P=0.102      P=0.030 *   |P=0.113N     P=0.028N*    P=0.028N*    P=0.102N     | 
|ORDER RESTRICTED   |     P=0.027 *    (e)          (e)          (e)         |P=0.002N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 12      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar                                                                      | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     12/50 (24%)  10/50 (20%)  13/50 (26%)  13/50 (26%) |6/50 (12%)   2/50 (4%)    3/50 (6%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     12/44.75     10/46.10     13/46.49     13/48.26    |6/45.47      2/45.81      3/47.65      3/47.10      | 
|POLY-3 PERCENT (g) |     26.8%        21.7%        28.0%        26.9%       |13.2%        4.4%         6.3%         6.4%         | 
|TERMINAL (d)       |     10/35 (29%)  10/38 (26%)  12/38 (32%)  10/41 (24%) |3/33 (9%)    2/40 (5%)    3/42 (7%)    3/43 (7%)    | 
|FIRST INCIDENCE    |     605          729 (T)      696          610         |638          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.481      P=0.320N     P=0.587N     P=0.502N    |P=0.239N     P=0.101N     P=0.164N     P=0.158N     | 
|POLY 3             |     P=0.406      P=0.373N     P=0.545      P=0.587     |P=0.306N     P=0.130N     P=0.220N     P=0.225N     | 
|POLY 1.5           |     P=0.379      P=0.394N     P=0.523      P=0.551     |P=0.311N     P=0.133N     P=0.229N     P=0.232N     | 
|POLY 6             |     P=0.441      P=0.352N     P=0.566      P=0.556N    |P=0.298N     P=0.126N     P=0.206N     P=0.213N     | 
|LOGISTIC REGRESSION|     P=0.426      P=0.324N     P=0.592      P=0.582     |P=0.309N     P=0.134N     P=0.242N     P=0.240N     | 
|COCH-ARM / FISHERS |     P=0.329      P=0.405N     P=0.500      P=0.500     |P=0.324N     P=0.134N     P=0.243N     P=0.243N     | 
|ORDER RESTRICTED   |     P=0.565      (e)          (e)          (e)         |P=0.134N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    1/50 (2%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      0/47.59     |2/44.83      1/45.81      0/47.65      2/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.5%         2.2%         0.0%         4.3%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |1/33 (3%)    1/40 (3%)    0/42 (0%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |663          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.597N     P=0.445N     P=0.199N     P=0.609N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.580      P=0.492N     P=0.224N     P=0.676N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.577      P=0.497N     P=0.230N     P=0.683N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.586      P=0.484N     P=0.215N     P=0.663N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.583      P=0.496N     P=0.240N     P=0.682N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.569      P=0.500N     P=0.247N     P=0.691N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.390N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 13      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery                                                                                                                        | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.11      2/46.15      0/46.36      0/47.59     |0/44.58      0/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         4.3%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    0/38 (0%)    0/41 (0%)   |0/33 (0%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          717          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.249N     P=0.258      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.248N     P=0.247      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.255N     P=0.241      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.239N     P=0.255      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.248N     P=0.256      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.264N     P=0.247      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.242N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cystadenoma                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |2/47 (4%)    3/48 (6%)    3/49 (6%)    2/48 (4%)    | 
|POLY-3 RATE (b)    |                                                        |2/42.04      3/44.02      3/46.65      2/45.10      | 
|POLY-3 PERCENT (g) |                                                        |4.8%         6.8%         6.4%         4.4%         | 
|TERMINAL (d)       |                                                        |2/32 (6%)    3/39 (8%)    3/41 (7%)    2/41 (5%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.426N     P=0.590      P=0.613      P=0.603N     | 
|POLY 3             |                                                        |P=0.484N     P=0.521      P=0.547      P=0.668N     | 
|POLY 1.5           |                                                        |P=0.492N     P=0.514      P=0.535      P=0.675N     | 
|POLY 6             |                                                        |P=0.469N     P=0.533      P=0.566      P=0.655N     | 
|LOGISTIC REGRESSION|                                                        |P=0.426N     P=0.590      P=0.613      P=0.603N     | 
|COCH-ARM / FISHERS |                                                        |P=0.508N     P=0.510      P=0.520      P=0.684N     | 
|ORDER RESTRICTED   |                                                        |P=0.587N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 14      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    0/49 (0%)    0/50 (0%)   |1/46 (2%)    7/49 (14%)   5/48 (10%)   3/47 (6%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/45.10      0/45.36      0/47.59     |1/41.35      7/45.60      5/46.17      3/44.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.4%         15.4%        10.8%        6.8%         | 
|TERMINAL (d)       |     0/35 (0%)    0/37 (0%)    0/37 (0%)    0/41 (0%)   |1/31 (3%)    6/40 (15%)   4/40 (10%)   3/40 (8%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      680          568          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.419N     P=0.067      P=0.162      P=0.400      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.482N     P=0.041 *    P=0.129      P=0.329      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.495N     P=0.039 *    P=0.121      P=0.323      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.459N     P=0.045 *    P=0.141      P=0.340      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.498N     P=0.048 *    P=0.111      P=0.400      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.516N     P=0.036 *    P=0.112      P=0.317      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.132      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skeletal Muscle                                                                                                                  | 
|     Rhabdomyosarcoma                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      0/47.59     |0/44.58      2/45.81      2/47.70      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         4.4%         4.2%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |0/33 (0%)    2/40 (5%)    1/42 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          729 (T)      716          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.367N     P=0.282      P=0.292      (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.400N     P=0.243      P=0.253      (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.409N     P=0.240      P=0.246      (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.383N     P=0.249      P=0.264      (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.385N     P=0.282      P=0.264      (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.424N     P=0.247      P=0.247      (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.272N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 15      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma,                                                                        | 
|     or Fibrous Histiocytoma                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |3/50 (6%)    2/50 (4%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/44.53      1/46.10      0/46.36      0/47.59     |3/45.34      2/46.42      2/48.11      2/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         2.2%         0.0%         0.0%        |6.6%         4.3%         4.2%         4.3%         | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    0/38 (0%)    0/41 (0%)   |1/33 (3%)    1/40 (3%)    0/42 (0%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     605          729 (T)      ---          ---         |568          533          627          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.195N     P=0.741N     P=0.479N     P=0.479N    |P=0.394N     P=0.459N     P=0.435N     P=0.418N     | 
|POLY 3             |     P=0.206N     P=0.753N     P=0.492N     P=0.487N    |P=0.435N     P=0.489N     P=0.473N     P=0.483N     | 
|POLY 1.5           |     P=0.207N     P=0.758N     P=0.496N     P=0.492N    |P=0.439N     P=0.496N     P=0.485N     P=0.489N     | 
|POLY 6             |     P=0.205N     P=0.748N     P=0.488N     P=0.481N    |P=0.426N     P=0.479N     P=0.455N     P=0.470N     | 
|LOGISTIC REGRESSION|     P=0.220N     P=0.760N     P=0.484N     P=0.644N    |P=0.488N     P=0.490N     P=0.544N     P=0.522N     | 
|COCH-ARM / FISHERS |     P=0.208N     P=0.753N     P=0.500N     P=0.500N    |P=0.448N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.239N     (e)          (e)          (e)         |P=0.467N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibrosarcoma                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |3/50 (6%)    2/50 (4%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      0/47.59     |3/45.34      2/46.42      2/48.11      2/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |6.6%         4.3%         4.2%         4.3%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |1/33 (3%)    1/40 (3%)    0/42 (0%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |568          533          627          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.394N     P=0.459N     P=0.435N     P=0.418N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.435N     P=0.489N     P=0.473N     P=0.483N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.439N     P=0.496N     P=0.485N     P=0.489N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.426N     P=0.479N     P=0.455N     P=0.470N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.488N     P=0.490N     P=0.544N     P=0.522N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.448N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.467N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 16      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |3/50 (6%)    2/50 (4%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/44.53      0/46.10      0/46.36      0/47.59     |3/45.34      2/46.42      2/48.11      2/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         0.0%         0.0%         0.0%        |6.6%         4.3%         4.2%         4.3%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |1/33 (3%)    1/40 (3%)    0/42 (0%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     605          ---          ---          ---         |568          533          627          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.340N     P=0.483N     P=0.479N     P=0.479N    |P=0.394N     P=0.459N     P=0.435N     P=0.418N     | 
|POLY 3             |     P=0.359N     P=0.493N     P=0.492N     P=0.487N    |P=0.435N     P=0.489N     P=0.473N     P=0.483N     | 
|POLY 1.5           |     P=0.355N     P=0.498N     P=0.496N     P=0.492N    |P=0.439N     P=0.496N     P=0.485N     P=0.489N     | 
|POLY 6             |     P=0.364N     P=0.488N     P=0.488N     P=0.481N    |P=0.426N     P=0.479N     P=0.455N     P=0.470N     | 
|LOGISTIC REGRESSION|     P=0.384N     P=0.472N     P=0.484N     P=0.644N    |P=0.488N     P=0.490N     P=0.544N     P=0.522N     | 
|COCH-ARM / FISHERS |     P=0.351N     P=0.500N     P=0.500N     P=0.500N    |P=0.448N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.108N     (e)          (e)          (e)         |P=0.467N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/44.11      1/46.10      1/46.36      0/47.59     |1/44.61      1/45.81      2/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         2.2%         2.2%         0.0%        |2.2%         2.2%         4.2%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    1/38 (3%)    1/38 (3%)    0/41 (0%)   |0/33 (0%)    1/40 (3%)    2/42 (5%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |721          729 (T)      729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.275N     P=0.743N     P=0.743N     P=0.468N    |P=0.318N     P=0.720N     P=0.583      P=0.449N     | 
|POLY 3             |     P=0.291N     P=0.751N     P=0.749N     P=0.485N    |P=0.358N     P=0.755N     P=0.523      P=0.489N     | 
|POLY 1.5           |     P=0.295N     P=0.757N     P=0.755N     P=0.491N    |P=0.364N     P=0.758N     P=0.513      P=0.494N     | 
|POLY 6             |     P=0.286N     P=0.744N     P=0.744N     P=0.478N    |P=0.348N     P=0.749N     P=0.538      P=0.481N     | 
|LOGISTIC REGRESSION|     P=0.275N     P=0.743N     P=0.743N     (e)         |P=0.332N     P=0.741N     P=0.567      P=0.480N     | 
|COCH-ARM / FISHERS |     P=0.303N     P=0.753N     P=0.753N     P=0.500N    |P=0.374N     P=0.753N     P=0.500      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.314N     (e)          (e)          (e)         |P=0.274N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 17      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/49 (4%)    4/50 (8%)    1/49 (2%)    1/48 (2%)   |0/47 (0%)    0/47 (0%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/43.27      4/46.37      1/45.73      1/46.16     |0/42.32      0/43.72      1/47.59      0/47.10      | 
|POLY-3 PERCENT (g) |     4.6%         8.6%         2.2%         2.2%        |0.0%         0.0%         2.1%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    1/38 (3%)    0/38 (0%)    1/41 (2%)   |0/32 (0%)    0/40 (0%)    1/42 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     723          676          690          729 (T)     |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.144N     P=0.381      P=0.473N     P=0.452N    |P=0.679      (e)          P=0.554      (e)          | 
|POLY 3             |     P=0.156N     P=0.370      P=0.481N     P=0.477N    |P=0.667      (e)          P=0.523      (e)          | 
|POLY 1.5           |     P=0.164N     P=0.356      P=0.490N     P=0.490N    |P=0.664      (e)          P=0.518      (e)          | 
|POLY 6             |     P=0.147N     P=0.385      P=0.470N     P=0.463N    |P=0.675      (e)          P=0.531      (e)          | 
|LOGISTIC REGRESSION|     P=0.159N     P=0.371      P=0.482N     P=0.450N    |(e)          (e)          P=0.554      (e)          | 
|COCH-ARM / FISHERS |     P=0.175N     P=0.349      P=0.500N     P=0.508N    |P=0.658      (e)          P=0.510      (e)          | 
|ORDER RESTRICTED   |     P=0.239N     (e)          (e)          (e)         |P=0.401      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    2/50 (4%)    2/50 (4%)   |0/50 (0%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/44.11      1/46.10      2/46.36      2/47.59     |0/44.58      1/45.81      1/47.65      1/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         2.2%         4.3%         4.2%        |0.0%         2.2%         2.1%         2.1%         | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    2/38 (5%)    2/41 (5%)   |0/33 (0%)    1/40 (3%)    1/42 (2%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |---          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.196      P=0.516      P=0.257      P=0.274     |P=0.465      P=0.538      P=0.548      P=0.553      | 
|POLY 3             |     P=0.185      P=0.509      P=0.248      P=0.255     |P=0.433      P=0.505      P=0.513      P=0.511      | 
|POLY 1.5           |     P=0.178      P=0.504      P=0.243      P=0.247     |P=0.425      P=0.502      P=0.508      P=0.507      | 
|POLY 6             |     P=0.195      P=0.515      P=0.254      P=0.263     |P=0.447      P=0.511      P=0.522      P=0.519      | 
|LOGISTIC REGRESSION|     (e)          P=0.516      P=0.257      P=0.274     |(e)          P=0.538      P=0.548      P=0.553      | 
|COCH-ARM / FISHERS |     P=0.164      P=0.500      P=0.247      P=0.247     |P=0.412      P=0.500      P=0.500      P=0.500      | 
|ORDER RESTRICTED   |     P=0.165      (e)          (e)          (e)         |P=0.337      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 18      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    3/49 (6%)    1/48 (2%)   |1/46 (2%)    1/50 (2%)    0/49 (0%)    1/47 (2%)    | 
|POLY-3 RATE (b)    |     3/44.11      1/46.10      3/45.58      1/46.16     |1/41.67      1/45.81      0/46.66      1/44.84      | 
|POLY-3 PERCENT (g) |     6.8%         2.2%         6.6%         2.2%        |2.4%         2.2%         0.0%         2.2%         | 
|TERMINAL (d)       |     3/35 (9%)    1/38 (3%)    3/38 (8%)    1/41 (2%)   |0/32 (0%)    1/40 (3%)    0/42 (0%)    1/41 (2%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |704          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.322N     P=0.276N     P=0.625N     P=0.250N    |P=0.544N     P=0.724N     P=0.457N     P=0.713N     | 
|POLY 3             |     P=0.366N     P=0.290N     P=0.647N     P=0.289N    |P=0.584N     P=0.739N     P=0.477N     P=0.744N     | 
|POLY 1.5           |     P=0.374N     P=0.299N     P=0.659N     P=0.302N    |P=0.586N     P=0.741N     P=0.482N     P=0.748N     | 
|POLY 6             |     P=0.355N     P=0.279N     P=0.634N     P=0.274N    |P=0.580N     P=0.736N     P=0.471N     P=0.737N     | 
|LOGISTIC REGRESSION|     P=0.322N     P=0.276N     P=0.625N     P=0.250N    |P=0.574N     P=0.740N     P=0.487N     P=0.749N     | 
|COCH-ARM / FISHERS |     P=0.392N     P=0.309N     P=0.651      P=0.324N    |P=0.591N     P=0.731N     P=0.484N     P=0.747N     | 
|ORDER RESTRICTED   |     P=0.226N     (e)          (e)          (e)         |P=0.507N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    3/49 (6%)    1/48 (2%)   |1/46 (2%)    1/50 (2%)    0/49 (0%)    2/47 (4%)    | 
|POLY-3 RATE (b)    |     3/44.11      1/46.10      3/45.58      1/46.16     |1/41.67      1/45.81      0/46.66      2/44.84      | 
|POLY-3 PERCENT (g) |     6.8%         2.2%         6.6%         2.2%        |2.4%         2.2%         0.0%         4.5%         | 
|TERMINAL (d)       |     3/35 (9%)    1/38 (3%)    3/38 (8%)    1/41 (2%)   |0/32 (0%)    1/40 (3%)    0/42 (0%)    2/41 (5%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |704          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.322N     P=0.276N     P=0.625N     P=0.250N    |P=0.424      P=0.724N     P=0.457N     P=0.577      | 
|POLY 3             |     P=0.366N     P=0.290N     P=0.647N     P=0.289N    |P=0.384      P=0.739N     P=0.477N     P=0.526      | 
|POLY 1.5           |     P=0.374N     P=0.299N     P=0.659N     P=0.302N    |P=0.379      P=0.741N     P=0.482N     P=0.519      | 
|POLY 6             |     P=0.355N     P=0.279N     P=0.634N     P=0.274N    |P=0.390      P=0.736N     P=0.471N     P=0.537      | 
|LOGISTIC REGRESSION|     P=0.322N     P=0.276N     P=0.625N     P=0.250N    |P=0.395      P=0.740N     P=0.487N     P=0.536      | 
|COCH-ARM / FISHERS |     P=0.392N     P=0.309N     P=0.651      P=0.324N    |P=0.370      P=0.731N     P=0.484N     P=0.508      | 
|ORDER RESTRICTED   |     P=0.226N     (e)          (e)          (e)         |P=0.286      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 19      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Polyp Stromal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |0/50 (0%)    2/50 (4%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |                                                        |0/44.58      2/45.97      2/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |                                                        |0.0%         4.4%         4.2%         0.0%         | 
|TERMINAL (d)       |                                                        |0/33 (0%)    1/40 (3%)    2/42 (5%)    0/43 (0%)    | 
|FIRST INCIDENCE    |                                                        |---          688          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.369N     P=0.275      P=0.293      (e)          | 
|POLY 3             |                                                        |P=0.400N     P=0.244      P=0.252      (e)          | 
|POLY 1.5           |                                                        |P=0.410N     P=0.240      P=0.246      (e)          | 
|POLY 6             |                                                        |P=0.384N     P=0.251      P=0.263      (e)          | 
|LOGISTIC REGRESSION|                                                        |P=0.406N     P=0.240      P=0.293      (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.424N     P=0.247      P=0.247      (e)          | 
|ORDER RESTRICTED   |                                                        |P=0.273N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangioma                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      1/47.59     |1/45.01      1/45.81      0/47.65      2/47.13      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         2.1%        |2.2%         2.2%         0.0%         4.2%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    1/41 (2%)   |0/33 (0%)    1/40 (3%)    0/42 (0%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |604          729 (T)      ---          722          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.203      (e)          (e)          P=0.532     |P=0.424      P=0.744N     P=0.496N     P=0.563      | 
|POLY 3             |     P=0.195      (e)          (e)          P=0.515     |P=0.386      P=0.757N     P=0.489N     P=0.516      | 
|POLY 1.5           |     P=0.192      (e)          (e)          P=0.509     |P=0.382      P=0.759N     P=0.493N     P=0.510      | 
|POLY 6             |     P=0.198      (e)          (e)          P=0.522     |P=0.394      P=0.752N     P=0.481N     P=0.528      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.532     |P=0.368      P=0.761N     P=0.539N     P=0.484      | 
|COCH-ARM / FISHERS |     P=0.186      (e)          (e)          P=0.500     |P=0.374      P=0.753N     P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.135      (e)          (e)          (e)         |P=0.285      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 20      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   7/50 (14%)   5/50 (10%)   1/50 (2%)   |3/50 (6%)    1/50 (2%)    3/50 (6%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     6/44.37      7/46.37      5/47.29      1/47.59     |3/44.66      1/45.81      3/47.65      1/47.10      | 
|POLY-3 PERCENT (g) |     13.5%        15.1%        10.6%        2.1%        |6.7%         2.2%         6.3%         2.1%         | 
|TERMINAL (d)       |     4/35 (11%)   4/38 (11%)   1/38 (3%)    1/41 (2%)   |1/33 (3%)    1/40 (3%)    3/42 (7%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     665          676          605          729 (T)     |716          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.020N*    P=0.563      P=0.441N     P=0.040N*   |P=0.297N     P=0.250N     P=0.548N     P=0.225N     | 
|POLY 3             |     P=0.020N*    P=0.534      P=0.456N     P=0.045N*   |P=0.356N     P=0.296N     P=0.632N     P=0.287N     | 
|POLY 1.5           |     P=0.022N*    P=0.513      P=0.476N     P=0.050N    |P=0.362N     P=0.302N     P=0.645N     P=0.294N     | 
|POLY 6             |     P=0.018N*    P=0.557      P=0.431N     P=0.041N*   |P=0.346N     P=0.287N     P=0.611N     P=0.273N     | 
|LOGISTIC REGRESSION|     P=0.024N*    P=0.551      P=0.498N     P=0.042N*   |P=0.318N     P=0.272N     P=0.581N     P=0.257N     | 
|COCH-ARM / FISHERS |     P=0.027N*    P=0.500      P=0.500N     P=0.056N    |P=0.374N     P=0.309N     P=0.661N     P=0.309N     | 
|ORDER RESTRICTED   |     P=0.036N*    (e)          (e)          (e)         |P=0.223N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangiosarcoma or Hemangioma                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   7/50 (14%)   5/50 (10%)   2/50 (4%)   |4/50 (8%)    2/50 (4%)    3/50 (6%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     6/44.37      7/46.37      5/47.29      2/47.59     |4/45.09      2/45.81      3/47.65      3/47.13      | 
|POLY-3 PERCENT (g) |     13.5%        15.1%        10.6%        4.2%        |8.9%         4.4%         6.3%         6.4%         | 
|TERMINAL (d)       |     4/35 (11%)   4/38 (11%)   1/38 (3%)    2/41 (5%)   |1/33 (3%)    2/40 (5%)    3/42 (7%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     665          676          605          729 (T)     |604          729 (T)      729 (T)      722          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.047N*    P=0.563      P=0.441N     P=0.096N    |P=0.444N     P=0.280N     P=0.391N     P=0.385N     | 
|POLY 3             |     P=0.050N     P=0.534      P=0.456N     P=0.111N    |P=0.524N     P=0.330N     P=0.470N     P=0.476N     | 
|POLY 1.5           |     P=0.055N     P=0.513      P=0.476N     P=0.120N    |P=0.530N     P=0.335N     P=0.483N     P=0.485N     | 
|POLY 6             |     P=0.046N*    P=0.557      P=0.431N     P=0.102N    |P=0.512N     P=0.321N     P=0.450N     P=0.459N     | 
|LOGISTIC REGRESSION|     P=0.057N     P=0.551      P=0.498N     P=0.101N    |P=0.521N     P=0.333N     P=0.489N     P=0.490N     | 
|COCH-ARM / FISHERS |     P=0.063N     P=0.500      P=0.500N     P=0.134N    |P=0.545N     P=0.339N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.091N     (e)          (e)          (e)         |P=0.426N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 21      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Histiocytic Sarcoma                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      3/46.96      0/47.59     |2/44.72      0/45.81      0/47.65      1/47.13      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         6.4%         0.0%        |4.5%         0.0%         0.0%         2.1%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |0/33 (0%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          645          ---         |704          ---          ---          722          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.501      (e)          P=0.144      (e)         |P=0.480N     P=0.212N     P=0.195N     P=0.421N     | 
|POLY 3             |     P=0.507      (e)          P=0.130      (e)         |P=0.528N     P=0.232N     P=0.223N     P=0.482N     | 
|POLY 1.5           |     P=0.494      (e)          P=0.125      (e)         |P=0.527N     P=0.235N     P=0.229N     P=0.489N     | 
|POLY 6             |     P=0.521      (e)          P=0.137      (e)         |P=0.530N     P=0.226N     P=0.215N     P=0.469N     | 
|LOGISTIC REGRESSION|     P=0.447      (e)          P=0.115      (e)         |P=0.519N     P=0.233N     P=0.228N     P=0.482N     | 
|COCH-ARM / FISHERS |     P=0.471      (e)          P=0.121      (e)         |P=0.529N     P=0.247N     P=0.247N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.174      (e)          (e)          (e)         |P=0.119N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        | 
|     NOS, or Undifferentiated Cell Type                                                                                          | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    5/50 (10%)  |6/50 (12%)   4/50 (8%)    9/50 (18%)   12/50 (24%)  | 
|POLY-3 RATE (b)    |     2/44.11      2/46.15      2/46.36      5/47.75     |6/45.54      4/46.21      9/48.48      12/48.93     | 
|POLY-3 PERCENT (g) |     4.5%         4.3%         4.3%         10.5%       |13.2%        8.7%         18.6%        24.5%        | 
|TERMINAL (d)       |     2/35 (6%)    1/38 (3%)    2/38 (5%)    4/41 (10%)  |4/33 (12%)   2/40 (5%)    7/42 (17%)   8/43 (19%)   | 
|FIRST INCIDENCE    |     729 (T)      717          729 (T)      687         |568          673          568          445          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.150      P=0.664N     P=0.665N     P=0.288     |P=0.048 *    P=0.292N     P=0.436      P=0.211      | 
|POLY 3             |     P=0.126      P=0.678N     P=0.676N     P=0.250     |P=0.025 *    P=0.360N     P=0.334      P=0.126      | 
|POLY 1.5           |     P=0.121      P=0.687N     P=0.684N     P=0.236     |P=0.022 *    P=0.368N     P=0.314      P=0.114      | 
|POLY 6             |     P=0.133      P=0.666N     P=0.666N     P=0.267     |P=0.030 *    P=0.346N     P=0.367      P=0.147      | 
|LOGISTIC REGRESSION|     P=0.139      P=0.663N     P=0.665N     P=0.268     |P=0.013 *    P=0.370N     P=0.268      P=0.070      | 
|COCH-ARM / FISHERS |     P=0.111      P=0.691N     P=0.691N     P=0.218     |P=0.017 *    P=0.370N     P=0.288      P=0.096      | 
|ORDER RESTRICTED   |     P=0.171      (e)          (e)          (e)         |P=0.052      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 22      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     37/50 (74%)  38/50 (76%)  39/50 (78%)  35/50 (70%) |25/50 (50%)  29/50 (58%)  32/50 (64%)  22/50 (44%)  | 
|POLY-3 RATE (b)    |     37/46.55     38/47.29     39/47.60     35/48.67    |25/46.86     29/46.76     32/48.63     22/47.13     | 
|POLY-3 PERCENT (g) |     79.5%        80.4%        81.9%        71.9%       |53.4%        62.0%        65.8%        46.7%        | 
|TERMINAL (d)       |     30/35 (86%)  33/38 (87%)  33/38 (87%)  30/41 (73%) |17/33 (52%)  25/40 (63%)  29/42 (69%)  21/43 (49%)  | 
|FIRST INCIDENCE    |     478          610          627          610         |604          616          568          722          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.070N     P=0.406N     P=0.487N     P=0.096N    |P=0.041N*    P=0.543N     P=0.509      P=0.077N     | 
|POLY 3             |     P=0.180N     P=0.563      P=0.483      P=0.260N    |P=0.197N     P=0.259      P=0.149      P=0.329N     | 
|POLY 1.5           |     P=0.229N     P=0.501      P=0.434      P=0.324N    |P=0.200N     P=0.257      P=0.133      P=0.330N     | 
|POLY 6             |     P=0.128N     P=0.583N     P=0.550      P=0.190N    |P=0.189N     P=0.267      P=0.175      P=0.322N     | 
|LOGISTIC REGRESSION|     P=0.123N     P=0.509N     P=0.560N     P=0.196N    |P=0.149N     P=0.302      P=0.152      P=0.259N     | 
|COCH-ARM / FISHERS |     P=0.333N     P=0.500      P=0.408      P=0.412N    |P=0.230N     P=0.274      P=0.113      P=0.344N     | 
|ORDER RESTRICTED   |     P=0.224N     (e)          (e)          (e)         |P=0.133N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     26/50 (52%)  23/50 (46%)  25/50 (50%)  26/50 (52%) |26/50 (52%)  15/50 (30%)  18/50 (36%)  24/50 (48%)  | 
|POLY-3 RATE (b)    |     26/48.10     23/48.86     25/48.67     26/48.85    |26/47.15     15/47.72     18/49.01     24/49.38     | 
|POLY-3 PERCENT (g) |     54.1%        47.1%        51.4%        53.2%       |55.2%        31.4%        36.7%        48.6%        | 
|TERMINAL (d)       |     15/35 (43%)  13/38 (34%)  16/38 (42%)  20/41 (49%) |15/33 (46%)  9/40 (23%)   12/42 (29%)  18/43 (42%)  | 
|FIRST INCIDENCE    |     536          452          605          506         |568          533          568          445          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.414N     P=0.258N     P=0.362N     P=0.326N    |P=0.432N     P=0.012N*    P=0.025N*    P=0.141N     | 
|POLY 3             |     P=0.440      P=0.315N     P=0.476N     P=0.548N    |P=0.422      P=0.015N*    P=0.052N     P=0.330N     | 
|POLY 1.5           |     P=0.443      P=0.340N     P=0.493N     P=0.558N    |P=0.403      P=0.017N*    P=0.061N     P=0.359N     | 
|POLY 6             |     P=0.431      P=0.289N     P=0.453N     P=0.544N    |P=0.448      P=0.012N*    P=0.041N*    P=0.294N     | 
|LOGISTIC REGRESSION|     P=0.390      P=0.355N     P=0.532N     P=0.507     |P=0.338      P=0.021N*    P=0.075N     P=0.431N     | 
|COCH-ARM / FISHERS |     P=0.422      P=0.345N     P=0.500N     P=0.579N    |P=0.351      P=0.021N*    P=0.079N     P=0.421N     | 
|ORDER RESTRICTED   |     P=0.573N     (e)          (e)          (e)         |P=0.079N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 23      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                 METHYLENE BLUE TRIHYDRATE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      2.5          12.5         25          |0 MG/KG      2.5          12.5         25           | 
|                   |                  MG/KG        MG/KG        MG/KG       |             MG/KG        MG/KG        MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     46/50 (92%)  47/50 (94%)  46/50 (92%)  47/50 (94%) |39/50 (78%)  36/50 (72%)  40/50 (80%)  37/50 (74%)  | 
|POLY-3 RATE (b)    |     46/48.96     47/49.00     46/49.05     47/49.59    |39/48.08     36/47.88     40/49.01     37/49.38     | 
|POLY-3 PERCENT (g) |     94.0%        95.9%        93.8%        94.8%       |81.1%        75.2%        81.6%        74.9%        | 
|TERMINAL (d)       |     33/35 (94%)  36/38 (95%)  35/38 (92%)  39/41 (95%) |25/33 (76%)  29/40 (73%)  34/42 (81%)  31/43 (72%)  | 
|FIRST INCIDENCE    |     478          452          605          506         |568          533          568          445          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.153N     P=0.368N     P=0.297N     P=0.164N    |P=0.095N     P=0.091N     P=0.129N     P=0.052N     | 
|POLY 3             |     P=0.565N     P=0.508      P=0.655N     P=0.608     |P=0.381N     P=0.323N     P=0.578      P=0.310N     | 
|POLY 1.5           |     P=0.577N     P=0.436      P=0.638      P=0.563     |P=0.405N     P=0.329N     P=0.553      P=0.331N     | 
|POLY 6             |     P=0.553N     P=0.599      P=0.589N     P=0.658     |P=0.354N     P=0.320N     P=0.597N     P=0.290N     | 
|LOGISTIC REGRESSION|     P=0.490N     P=0.452      P=0.603N     P=0.647     |P=0.427N     P=0.302N     P=0.598      P=0.359N     | 
|COCH-ARM / FISHERS |     P=0.486      P=0.500      P=0.643N     P=0.500     |P=0.508N     P=0.322N     P=0.500      P=0.408N     | 
|ORDER RESTRICTED   |     P=0.652      (e)          (e)          (e)         |P=0.363N     (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).