National Toxicology Program

National Toxicology Program
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).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.