National Toxicology Program

National Toxicology Program
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TDMS Study 91005-08 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                             METHYLENE BLUE TRIHYDRATE                              DATE: 04/26/05       
EXPERIMENT: 91005 TEST: 08                                                                                     TIME: 08:51:26       
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       
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                                                           FINAL #1 RATS                                                            
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                             METHYLENE BLUE TRIHYDRATE                              DATE: 04/26/05       
EXPERIMENT: 91005 TEST: 08                                                                                     TIME: 08:51:26       
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                                                                                    
-----                                 ----------                                                                                    
Bone                                   Hyperostosis                                                                                 
Islets, Pancreatic                     Hyperplasia                                                                                  
Kidney                                 Hydronephrosis                                                                               
Liver                                  Mixed Cell Focus                                                                             
Liver: Hepatocyte                      Vacuolization Cytoplasmic                                                                    
Mesentery: Fat                         Necrosis Focal                                                                               
Nose                                   Inflammation                                                                                 
Skin                                   Ulcer                                                                                        
Spleen                                 Hematopoietic Cell Proliferation                                                             
                                       Hyperplasia Lymphoid                                                                         
Thyroid Gland: Follicular Cell         Hyperplasia Focal                                                                            
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Bone Marrow                            Hyperplasia                                                                                  
Harderian Gland: Epithelium            Hyperplasia                                                                                  
Liver                                  Angiectasis Focal                                                                            
                                       Basophilic Focus                                                                             
Liver: Hepatocyte                      Necrosis Focal                                                                               
Lymph Node, Mandibular                 Hyperplasia Lymphoid                                                                         
Mesentery: Fat                         Necrosis Focal                                                                               
Nose                                   Inflammation                                                                                 
Spleen                                 Hematopoietic Cell Proliferation                                                             
                                       Hyperplasia Lymphoid                                                                         
Thyroid Gland: Follicle                Degeneration Cystic Focal                                                                    
Uterus: Endometrium                    Hyperplasia Cystic                                                                           
===============================================================                                                                     
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                   | 
|     Accessory Adrenal Cortical Nodule                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/48 (2%)    0/50 (0%)    1/50 (2%)    0/48 (0%)   |2/50 (4%)    2/50 (4%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/42.71      0/46.10      1/46.52      0/45.75     |2/44.58      2/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         0.0%         2.2%         0.0%        |4.5%         4.4%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/34 (3%)    0/38 (0%)    0/38 (0%)    0/40 (0%)   |2/33 (6%)    2/40 (5%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          690          ---         |729 (T)      729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.437N     P=0.478N     P=0.737N     P=0.468N    |P=0.052N     P=0.624N     P=0.187N     P=0.182N     | 
|POLY 3             |     P=0.460N     P=0.485N     P=0.741N     P=0.486N    |P=0.066N     P=0.684N     P=0.223N     P=0.225N     | 
|POLY 1.5           |     P=0.461N     P=0.489N     P=0.746N     P=0.492N    |P=0.067N     P=0.690N     P=0.229N     P=0.230N     | 
|POLY 6             |     P=0.459N     P=0.479N     P=0.736N     P=0.479N    |P=0.064N     P=0.674N     P=0.213N     P=0.217N     | 
|LOGISTIC REGRESSION|     P=0.462N     (e)          P=0.749N     (e)         |P=0.052N     P=0.624N     (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.467N     P=0.490N     P=0.742N     P=0.500N    |P=0.070N     P=0.691N     P=0.247N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.238N     (e)          (e)          (e)         |P=0.107N     (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 Cortex                                                                                                                   | 
|     Cytoplasmic Alteration Focal                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/48 (8%)    0/50 (0%)    5/50 (10%)   5/48 (10%)  |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     4/43.28      0/46.10      5/46.36      5/45.75     |1/44.58      0/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     9.2%         0.0%         10.8%        10.9%       |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     3/34 (9%)    0/38 (0%)    5/38 (13%)   5/40 (13%)  |1/33 (3%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     548          ---          729 (T)      729 (T)     |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.163      P=0.053N     P=0.566      P=0.594     |P=0.324N     P=0.462N     P=0.452N     P=0.447N     | 
|POLY 3             |     P=0.129      P=0.052N     P=0.543      P=0.535     |P=0.355N     P=0.495N     P=0.487N     P=0.489N     | 
|POLY 1.5           |     P=0.126      P=0.055N     P=0.534      P=0.520     |P=0.353N     P=0.498N     P=0.492N     P=0.493N     | 
|POLY 6             |     P=0.133      P=0.050N     P=0.553      P=0.552     |P=0.359N     P=0.489N     P=0.478N     P=0.481N     | 
|LOGISTIC REGRESSION|     P=0.133      P=0.057N     P=0.540      P=0.515     |P=0.324N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.117      P=0.054N     P=0.526      P=0.500     |P=0.351N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.200      (e)          (e)          (e)         |P=0.111N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions 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 Medulla                                                                                                                  | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/48 (4%)    1/50 (2%)    1/50 (2%)    1/48 (2%)   |0/50 (0%)    0/50 (0%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/42.71      1/46.10      1/46.36      1/45.75     |0/44.58      0/45.81      1/46.65      0/47.10      | 
|POLY-3 PERCENT (g) |     4.7%         2.2%         2.2%         2.2%        |0.0%         0.0%         2.1%         0.0%         | 
|TERMINAL (d)       |     2/34 (6%)    1/38 (3%)    1/38 (3%)    1/40 (3%)   |0/33 (0%)    0/40 (0%)    1/41 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.390N     P=0.461N     P=0.461N     P=0.443N    |P=0.675      (e)          P=0.543      (e)          | 
|POLY 3             |     P=0.425N     P=0.473N     P=0.471N     P=0.476N    |P=0.664      (e)          P=0.509      (e)          | 
|POLY 1.5           |     P=0.428N     P=0.481N     P=0.478N     P=0.486N    |P=0.658      (e)          P=0.503      (e)          | 
|POLY 6             |     P=0.421N     P=0.464N     P=0.464N     P=0.464N    |P=0.674      (e)          P=0.518      (e)          | 
|LOGISTIC REGRESSION|     P=0.390N     P=0.461N     P=0.461N     P=0.443N    |(e)          (e)          P=0.543      (e)          | 
|COCH-ARM / FISHERS |     P=0.436N     P=0.485N     P=0.485N     P=0.500N    |P=0.648      (e)          P=0.495      (e)          | 
|ORDER RESTRICTED   |     P=0.381N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone                                                                                                                             | 
|     Hyperostosis                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |5/50 (10%)   5/50 (10%)   4/50 (8%)    5/50 (10%)   | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      2/47.91     |5/44.94      5/46.28      4/48.17      5/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.2%        |11.1%        10.8%        8.3%         10.6%        | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    1/41 (2%)   |4/33 (12%)   4/40 (10%)   3/42 (7%)    5/43 (12%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          641         |627          589          568          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.052      (e)          (e)          P=0.275     |P=0.417N     P=0.534N     P=0.380N     P=0.472N     | 
|POLY 3             |     P=0.045 *    (e)          (e)          P=0.256     |P=0.508N     P=0.612N     P=0.457N     P=0.600N     | 
|POLY 1.5           |     P=0.044 *    (e)          (e)          P=0.248     |P=0.517N     P=0.622N     P=0.475N     P=0.612N     | 
|POLY 6             |     P=0.047 *    (e)          (e)          P=0.266     |P=0.491N     P=0.594N     P=0.429N     P=0.579N     | 
|LOGISTIC REGRESSION|     P=0.038 *    (e)          (e)          P=0.202     |P=0.527N     P=0.626N     P=0.505N     P=0.582N     | 
|COCH-ARM / FISHERS |     P=0.043 *    (e)          (e)          P=0.247     |P=0.537N     P=0.630N     P=0.500N     P=0.630N     | 
|ORDER RESTRICTED   |     P=0.036 *    (e)          (e)          (e)         |P=0.616N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    3/50 (6%)    2/50 (4%)   |10/50 (20%)  4/50 (8%)    9/49 (18%)   4/50 (8%)    | 
|POLY-3 RATE (b)    |     2/44.69      3/46.52      3/46.37      2/48.25     |10/45.69     4/45.84      9/48.02      4/47.29      | 
|POLY-3 PERCENT (g) |     4.5%         6.5%         6.5%         4.1%        |21.9%        8.7%         18.7%        8.5%         | 
|TERMINAL (d)       |     1/35 (3%)    2/38 (5%)    2/38 (5%)    1/41 (2%)   |6/33 (18%)   3/40 (8%)    5/41 (12%)   3/43 (7%)    | 
|FIRST INCIDENCE    |     544          610          727          506         |568          720          283          680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.463N     P=0.538      P=0.536      P=0.658N    |P=0.120N     P=0.045N*    P=0.338N     P=0.035N*    | 
|POLY 3             |     P=0.483N     P=0.518      P=0.517      P=0.666N    |P=0.168N     P=0.070N     P=0.452N     P=0.062N     | 
|POLY 1.5           |     P=0.495N     P=0.507      P=0.509      P=0.677N    |P=0.176N     P=0.073N     P=0.476N     P=0.066N     | 
|POLY 6             |     P=0.470N     P=0.532      P=0.526      P=0.653N    |P=0.155N     P=0.067N     P=0.418N     P=0.056N     | 
|LOGISTIC REGRESSION|     P=0.560N     P=0.506      P=0.493      P=0.493     |P=0.207N     P=0.072N     P=0.569N     P=0.072N     | 
|COCH-ARM / FISHERS |     P=0.516N     P=0.500      P=0.500      P=0.691N    |P=0.195N     P=0.074N     P=0.520N     P=0.074N     | 
|ORDER RESTRICTED   |     P=0.566N     (e)          (e)          (e)         |P=0.045N*    (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone: Vertebra                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |3/50 (6%)    2/50 (4%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      0/47.59     |3/45.43      2/47.05      1/48.01      1/47.88      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |6.6%         4.3%         2.1%         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    |     ---          ---          ---          ---         |627          521          627          445          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.195N     P=0.485N     P=0.271N     P=0.280N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.195N     P=0.484N     P=0.286N     P=0.287N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.198N     P=0.492N     P=0.294N     P=0.294N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.191N     P=0.473N     P=0.274N     P=0.277N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.285N     P=0.475N     P=0.345N     P=0.396N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.203N     P=0.500N     P=0.309N     P=0.309N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.198N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Cornea                                                                                                                      | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/45 (4%)    0/49 (0%)    0/49 (0%)    1/47 (2%)   |1/43 (2%)    1/48 (2%)    1/47 (2%)    1/47 (2%)    | 
|POLY-3 RATE (b)    |     2/40.46      0/45.12      0/45.58      1/45.73     |1/38.84      1/45.00      1/46.13      1/45.13      | 
|POLY-3 PERCENT (g) |     4.9%         0.0%         0.0%         2.2%        |2.6%         2.2%         2.2%         2.2%         | 
|TERMINAL (d)       |     2/35 (6%)    0/38 (0%)    0/38 (0%)    1/41 (2%)   |0/32 (0%)    0/40 (0%)    1/42 (2%)    1/42 (2%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          ---          729 (T)     |663          680          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.495N     P=0.220N     P=0.220N     P=0.445N    |P=0.577N     P=0.730N     P=0.711N     P=0.714N     | 
|POLY 3             |     P=0.527N     P=0.213N     P=0.211N     P=0.457N    |P=0.598N     P=0.727N     P=0.721N     P=0.726N     | 
|POLY 1.5           |     P=0.525N     P=0.217N     P=0.215N     P=0.469N    |P=0.602N     P=0.732N     P=0.728N     P=0.732N     | 
|POLY 6             |     P=0.530N     P=0.209N     P=0.207N     P=0.444N    |P=0.593N     P=0.721N     P=0.712N     P=0.719N     | 
|LOGISTIC REGRESSION|     P=0.495N     (e)          (e)          P=0.445N    |P=0.623N     P=0.739N     P=0.770N     P=0.754N     | 
|COCH-ARM / FISHERS |     P=0.526N     P=0.226N     P=0.226N     P=0.484N    |P=0.612N     P=0.725N     P=0.730N     P=0.730N     | 
|ORDER RESTRICTED   |     P=0.104N     (e)          (e)          (e)         |P=0.693N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Gallbladder                                                                                                                      | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/40 (0%)    0/44 (0%)    0/45 (0%)    0/44 (0%)   |2/42 (5%)    0/45 (0%)    1/47 (2%)    2/44 (5%)    | 
|POLY-3 RATE (b)    |     0/37.08      0/41.81      0/42.87      0/43.53     |2/38.36      0/42.33      1/46.13      2/43.04      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |5.2%         0.0%         2.2%         4.7%         | 
|TERMINAL (d)       |     0/33 (0%)    0/38 (0%)    0/37 (0%)    0/41 (0%)   |2/32 (6%)    0/39 (0%)    1/42 (2%)    2/42 (5%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.458      P=0.196N     P=0.405N     P=0.594N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.411      P=0.215N     P=0.436N     P=0.652N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.408      P=0.219N     P=0.444N     P=0.661N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.417      P=0.210N     P=0.425N     P=0.638N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.458      (e)          P=0.405N     P=0.594N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.396      P=0.230N     P=0.457N     P=0.674N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.356N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions 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: Epithelium                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |1/49 (2%)    0/50 (0%)    0/50 (0%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      1/46.36      0/47.59     |1/44.50      0/45.81      0/47.65      3/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         0.0%        |2.3%         0.0%         0.0%         6.4%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    1/38 (3%)    0/41 (0%)   |0/33 (0%)    0/40 (0%)    0/42 (0%)    3/43 (7%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |617          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.665      (e)          P=0.516      (e)         |P=0.090      P=0.509N     P=0.492N     P=0.381      | 
|POLY 3             |     P=0.673      (e)          P=0.510      (e)         |P=0.073      P=0.494N     P=0.486N     P=0.326      | 
|POLY 1.5           |     P=0.664      (e)          P=0.505      (e)         |P=0.072      P=0.496N     P=0.490N     P=0.321      | 
|POLY 6             |     P=0.682      (e)          P=0.515      (e)         |P=0.075      P=0.491N     P=0.480N     P=0.336      | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.516      (e)         |P=0.070      P=0.483N     P=0.528N     P=0.309      | 
|COCH-ARM / FISHERS |     P=0.649      (e)          P=0.500      (e)         |P=0.071      P=0.495N     P=0.495N     P=0.316      | 
|ORDER RESTRICTED   |     P=0.390      (e)          (e)          (e)         |P=0.044 *    (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: Epithelium                                                                                                      | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |1/49 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.53      0/46.10      1/46.36      0/47.59     |1/44.10      1/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     4.5%         0.0%         2.2%         0.0%        |2.3%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    0/38 (0%)    1/38 (3%)    0/41 (0%)   |1/33 (3%)    1/40 (3%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     605          ---          729 (T)      ---         |729 (T)      729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.232N     P=0.221N     P=0.469N     P=0.211N    |P=0.179N     P=0.718N     P=0.452N     P=0.447N     | 
|POLY 3             |     P=0.249N     P=0.229N     P=0.486N     P=0.223N    |P=0.203N     P=0.752N     P=0.485N     P=0.487N     | 
|POLY 1.5           |     P=0.249N     P=0.234N     P=0.493N     P=0.229N    |P=0.205N     P=0.755N     P=0.489N     P=0.490N     | 
|POLY 6             |     P=0.249N     P=0.224N     P=0.479N     P=0.216N    |P=0.201N     P=0.747N     P=0.477N     P=0.480N     | 
|LOGISTIC REGRESSION|     P=0.261N     P=0.233N     P=0.507N     P=0.286N    |P=0.179N     P=0.718N     (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.253N     P=0.247N     P=0.500N     P=0.247N    |P=0.206N     P=0.747N     P=0.495N     P=0.495N     | 
|ORDER RESTRICTED   |     P=0.066N     (e)          (e)          (e)         |P=0.239N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                               | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     17/50 (34%)  17/50 (34%)  7/49 (14%)   13/48 (27%) |0/46 (0%)    0/47 (0%)    0/49 (0%)    0/48 (0%)    | 
|POLY-3 RATE (b)    |     17/45.75     17/46.89     7/45.58      13/46.63    |0/41.35      0/43.51      0/47.17      0/45.84      | 
|POLY-3 PERCENT (g) |     37.2%        36.3%        15.4%        27.9%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     13/35 (37%)  13/38 (34%)  7/38 (18%)   11/41 (27%) |0/32 (0%)    0/40 (0%)    0/42 (0%)    0/42 (0%)    | 
|FIRST INCIDENCE    |     530          638          729 (T)      610         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.053N     P=0.470N     P=0.011N*    P=0.138N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.096N     P=0.550N     P=0.014N*    P=0.232N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.106N     P=0.577N     P=0.016N*    P=0.260N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.085N     P=0.516N     P=0.013N*    P=0.200N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.096N     P=0.557N     P=0.016N*    P=0.274N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.127N     P=0.583N     P=0.019N*    P=0.301N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.073N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Hydronephrosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/49 (4%)    0/49 (0%)    0/50 (0%)    0/48 (0%)   |0/48 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/43.27      0/45.12      0/46.36      0/46.16     |0/42.61      0/45.81      0/47.59      0/47.10      | 
|POLY-3 PERCENT (g) |     4.6%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |0/32 (0%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     723          ---          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.149N     P=0.228N     P=0.225N     P=0.212N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.165N     P=0.228N     P=0.222N     P=0.223N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.161N     P=0.234N     P=0.227N     P=0.231N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.169N     P=0.222N     P=0.217N     P=0.214N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.147N     P=0.219N     P=0.216N     P=0.207N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.161N     P=0.247N     P=0.242N     P=0.253N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.025N*    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Infarct                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    1/49 (2%)    0/50 (0%)    1/48 (2%)   |0/48 (0%)    1/50 (2%)    2/49 (4%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     0/43.24      1/45.12      0/46.36      1/46.16     |0/42.61      1/45.81      2/47.59      3/47.29      | 
|POLY-3 PERCENT (g) |     0.0%         2.2%         0.0%         2.2%        |0.0%         2.2%         4.2%         6.3%         | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    0/38 (0%)    1/41 (2%)   |0/32 (0%)    1/40 (3%)    2/42 (5%)    2/43 (5%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          729 (T)     |---          729 (T)      729 (T)      680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.493      P=0.516      (e)          P=0.532     |P=0.093      P=0.545      P=0.300      P=0.173      | 
|POLY 3             |     P=0.482      P=0.508      (e)          P=0.513     |P=0.076      P=0.514      P=0.263      P=0.138      | 
|POLY 1.5           |     P=0.473      P=0.503      (e)          P=0.506     |P=0.073      P=0.511      P=0.255      P=0.133      | 
|POLY 6             |     P=0.493      P=0.514      (e)          P=0.521     |P=0.083      P=0.520      P=0.274      P=0.148      | 
|LOGISTIC REGRESSION|     (e)          P=0.516      (e)          P=0.532     |P=0.075      P=0.545      P=0.300      P=0.134      | 
|COCH-ARM / FISHERS |     P=0.460      P=0.500      (e)          P=0.495     |P=0.067      P=0.510      P=0.253      P=0.129      | 
|ORDER RESTRICTED   |     P=0.265      (e)          (e)          (e)         |P=0.072      (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Metaplasia Focal Osseous                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/49 (6%)    0/49 (0%)    3/50 (6%)    4/48 (8%)   |2/48 (4%)    1/50 (2%)    1/49 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/43.24      0/45.12      3/47.01      4/46.16     |2/42.61      1/45.81      1/47.59      0/47.10      | 
|POLY-3 PERCENT (g) |     6.9%         0.0%         6.4%         8.7%        |4.7%         2.2%         2.1%         0.0%         | 
|TERMINAL (d)       |     3/35 (9%)    0/38 (0%)    1/38 (3%)    4/41 (10%)  |2/32 (6%)    1/40 (3%)    1/42 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          605          729 (T)     |729 (T)      729 (T)      729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.195      P=0.107N     P=0.618N     P=0.586     |P=0.129N     P=0.422N     P=0.405N     P=0.176N     | 
|POLY 3             |     P=0.162      P=0.111N     P=0.623N     P=0.536     |P=0.157N     P=0.475N     P=0.462N     P=0.215N     | 
|POLY 1.5           |     P=0.157      P=0.116N     P=0.637N     P=0.516     |P=0.159N     P=0.481N     P=0.473N     P=0.221N     | 
|POLY 6             |     P=0.170      P=0.106N     P=0.607N     P=0.559     |P=0.153N     P=0.464N     P=0.445N     P=0.207N     | 
|LOGISTIC REGRESSION|     P=0.155      (e)          P=0.654N     P=0.586     |P=0.129N     P=0.422N     P=0.405N     (e)          | 
|COCH-ARM / FISHERS |     P=0.145      P=0.121N     P=0.651N     P=0.488     |P=0.164N     P=0.485N     P=0.492N     P=0.237N     | 
|ORDER RESTRICTED   |     P=0.219      (e)          (e)          (e)         |P=0.102N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     40/49 (82%)  44/49 (90%)  44/50 (88%)  43/48 (90%) |6/48 (13%)   5/50 (10%)   9/49 (18%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     40/46.05     44/46.77     44/48.41     43/46.92    |6/43.51      5/45.81      9/47.64      5/47.29      | 
|POLY-3 PERCENT (g) |     86.9%        94.1%        90.9%        91.6%       |13.8%        10.9%        18.9%        10.6%        | 
|TERMINAL (d)       |     32/35 (91%)  37/38 (97%)  38/38 (100%) 38/41 (93%) |4/32 (13%)   5/40 (13%)   8/42 (19%)   4/43 (9%)    | 
|FIRST INCIDENCE    |     536          610          605          641         |550          729 (T)      716          680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.188N     P=0.549      P=0.556      P=0.293N    |P=0.394N     P=0.378N     P=0.474      P=0.343N     | 
|POLY 3             |     P=0.433      P=0.180      P=0.375      P=0.329     |P=0.494N     P=0.464N     P=0.355      P=0.442N     | 
|POLY 1.5           |     P=0.368      P=0.148      P=0.310      P=0.267     |P=0.508N     P=0.470N     P=0.336      P=0.454N     | 
|POLY 6             |     P=0.513      P=0.233      P=0.453      P=0.417     |P=0.469N     P=0.452N     P=0.384      P=0.419N     | 
|LOGISTIC REGRESSION|     P=0.463N     P=0.357      P=0.502      P=0.613     |P=0.499N     P=0.465N     P=0.318      P=0.473N     | 
|COCH-ARM / FISHERS |     P=0.258      P=0.194      P=0.274      P=0.205     |P=0.535N     P=0.471N     P=0.303      P=0.471N     | 
|ORDER RESTRICTED   |     P=0.269      (e)          (e)          (e)         |P=0.458N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Accumulation, Hyaline Droplet                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/49 (0%)    1/50 (2%)    0/48 (0%)   |2/48 (4%)    0/50 (0%)    0/49 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/43.24      0/45.12      1/46.52      0/46.16     |2/42.71      0/45.81      0/47.59      2/47.13      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         0.0%        |4.7%         0.0%         0.0%         4.2%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |1/32 (3%)    0/40 (0%)    0/42 (0%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     ---          ---          690          ---         |704          ---          ---          722          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.666      (e)          P=0.520      (e)         |P=0.487      P=0.205N     P=0.188N     P=0.595N     | 
|POLY 3             |     P=0.676      (e)          P=0.515      (e)         |P=0.439      P=0.222N     P=0.214N     P=0.658N     | 
|POLY 1.5           |     P=0.665      (e)          P=0.510      (e)         |P=0.438      P=0.225N     P=0.221N     P=0.666N     | 
|POLY 6             |     P=0.688      (e)          P=0.520      (e)         |P=0.442      P=0.216N     P=0.204N     P=0.643N     | 
|LOGISTIC REGRESSION|     P=0.642      (e)          P=0.501      (e)         |P=0.455      P=0.217N     P=0.210N     P=0.643N     | 
|COCH-ARM / FISHERS |     P=0.647      (e)          P=0.505      (e)         |P=0.431      P=0.237N     P=0.242N     P=0.676N     | 
|ORDER RESTRICTED   |     P=0.394      (e)          (e)          (e)         |P=0.235N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/49 (8%)    2/49 (4%)    3/50 (6%)    2/48 (4%)   |1/48 (2%)    0/50 (0%)    3/49 (6%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     4/43.86      2/45.12      3/46.36      2/46.16     |1/42.61      0/45.81      3/47.59      0/47.10      | 
|POLY-3 PERCENT (g) |     9.1%         4.4%         6.5%         4.3%        |2.4%         0.0%         6.3%         0.0%         | 
|TERMINAL (d)       |     3/35 (9%)    2/38 (5%)    3/38 (8%)    2/41 (5%)   |1/32 (3%)    0/40 (0%)    3/42 (7%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     530          729 (T)      729 (T)      729 (T)     |729 (T)      ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.307N     P=0.309N     P=0.462N     P=0.280N    |P=0.509N     P=0.455N     P=0.406      P=0.441N     | 
|POLY 3             |     P=0.344N     P=0.324N     P=0.470N     P=0.314N    |P=0.551N     P=0.486N     P=0.346      P=0.480N     | 
|POLY 1.5           |     P=0.352N     P=0.333N     P=0.479N     P=0.328N    |P=0.557N     P=0.489N     P=0.333      P=0.485N     | 
|POLY 6             |     P=0.333N     P=0.314N     P=0.460N     P=0.298N    |P=0.540N     P=0.480N     P=0.364      P=0.472N     | 
|LOGISTIC REGRESSION|     P=0.351N     P=0.336N     P=0.487N     P=0.376N    |P=0.509N     (e)          P=0.406      (e)          | 
|COCH-ARM / FISHERS |     P=0.369N     P=0.339N     P=0.489N     P=0.349N    |P=0.569N     P=0.490N     P=0.316      P=0.490N     | 
|ORDER RESTRICTED   |     P=0.275N     (e)          (e)          (e)         |P=0.274N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/49 (6%)    1/49 (2%)    1/50 (2%)    1/48 (2%)   |0/48 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/43.24      1/45.26      1/46.36      1/46.16     |0/42.61      0/45.81      0/47.59      0/47.10      | 
|POLY-3 PERCENT (g) |     6.9%         2.2%         2.2%         2.2%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     3/35 (9%)    0/38 (0%)    1/38 (3%)    1/41 (2%)   |0/32 (0%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      694          729 (T)      729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.244N     P=0.274N     P=0.276N     P=0.250N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.276N     P=0.289N     P=0.281N     P=0.282N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.278N     P=0.299N     P=0.289N     P=0.295N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.273N     P=0.278N     P=0.272N     P=0.268N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.251N     P=0.280N     P=0.276N     P=0.250N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.286N     P=0.309N     P=0.301N     P=0.316N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.164N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            | 
|     Angiectasis Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      0/46.75     |2/44.58      0/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.5%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |2/33 (6%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.136N     P=0.197N     P=0.187N     P=0.182N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.160N     P=0.231N     P=0.223N     P=0.225N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.159N     P=0.235N     P=0.229N     P=0.230N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.163N     P=0.225N     P=0.213N     P=0.217N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.136N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.160N     P=0.247N     P=0.247N     P=0.247N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.025N*    (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                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    0/49 (0%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     0/44.11      1/46.10      0/46.36      0/46.75     |0/44.58      1/45.81      0/47.65      3/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         2.2%         0.0%         0.0%        |0.0%         2.2%         0.0%         6.4%         | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    0/38 (0%)    0/41 (0%)   |0/33 (0%)    1/40 (3%)    0/42 (0%)    3/43 (7%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |---          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.430N     P=0.516      (e)          (e)         |P=0.075      P=0.538      (e)          P=0.172      | 
|POLY 3             |     P=0.443N     P=0.509      (e)          (e)         |P=0.058      P=0.505      (e)          P=0.129      | 
|POLY 1.5           |     P=0.449N     P=0.504      (e)          (e)         |P=0.056      P=0.502      (e)          P=0.125      | 
|POLY 6             |     P=0.438N     P=0.515      (e)          (e)         |P=0.061      P=0.511      (e)          P=0.137      | 
|LOGISTIC REGRESSION|     (e)          P=0.516      (e)          (e)         |(e)          P=0.538      (e)          P=0.172      | 
|COCH-ARM / FISHERS |     P=0.452N     P=0.500      (e)          (e)         |P=0.054      P=0.500      (e)          P=0.121      | 
|ORDER RESTRICTED   |     P=0.379N     (e)          (e)          (e)         |P=0.024 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            | 
|     Clear Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     20/50 (40%)  19/50 (38%)  22/50 (44%)  16/49 (33%) |3/50 (6%)    3/50 (6%)    4/50 (8%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     20/44.53     19/46.20     22/46.36     16/47.16    |3/44.83      3/45.81      4/47.65      2/47.13      | 
|POLY-3 PERCENT (g) |     44.9%        41.1%        47.5%        33.9%       |6.7%         6.6%         8.4%         4.2%         | 
|TERMINAL (d)       |     19/35 (54%)  18/38 (47%)  22/38 (58%)  15/41 (37%) |2/33 (6%)    3/40 (8%)    4/42 (10%)   1/43 (2%)    | 
|FIRST INCIDENCE    |     605          704          729 (T)      610         |663          729 (T)      729 (T)      722          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.108N     P=0.361N     P=0.567      P=0.101N    |P=0.326N     P=0.579N     P=0.622      P=0.393N     | 
|POLY 3             |     P=0.199N     P=0.439N     P=0.487      P=0.192N    |P=0.398N     P=0.652N     P=0.533      P=0.477N     | 
|POLY 1.5           |     P=0.233N     P=0.478N     P=0.454      P=0.231N    |P=0.408N     P=0.659N     P=0.519      P=0.486N     | 
|POLY 6             |     P=0.161N     P=0.395N     P=0.522      P=0.151N    |P=0.382N     P=0.642N     P=0.555      P=0.461N     | 
|LOGISTIC REGRESSION|     P=0.142N     P=0.345N     P=0.571      P=0.144N    |P=0.376N     P=0.643N     P=0.552      P=0.477N     | 
|COCH-ARM / FISHERS |     P=0.299N     P=0.500N     P=0.420      P=0.291N    |P=0.425N     P=0.661N     P=0.500      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.223N     (e)          (e)          (e)         |P=0.446N     (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                                                                                                                            | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/49 (2%)   |1/50 (2%)    2/50 (4%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      1/46.89     |1/45.56      2/46.42      1/47.65      1/47.13      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         2.1%        |2.2%         4.3%         2.1%         2.1%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |0/33 (0%)    1/40 (3%)    1/42 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          694         |185          533          729 (T)      722          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.201      (e)          (e)          P=0.529     |P=0.436N     P=0.517      P=0.734N     P=0.729N     | 
|POLY 3             |     P=0.193      (e)          (e)          P=0.512     |P=0.466N     P=0.506      P=0.751N     P=0.753N     | 
|POLY 1.5           |     P=0.190      (e)          (e)          P=0.505     |P=0.472N     P=0.500      P=0.756N     P=0.757N     | 
|POLY 6             |     P=0.197      (e)          (e)          P=0.520     |P=0.455N     P=0.517      P=0.741N     P=0.744N     | 
|LOGISTIC REGRESSION|     P=0.178      (e)          (e)          P=0.482     |P=0.589N     P=0.566      P=0.705      P=0.624      | 
|COCH-ARM / FISHERS |     P=0.184      (e)          (e)          P=0.495     |P=0.477N     P=0.500      P=0.753N     P=0.753N     | 
|ORDER RESTRICTED   |     P=0.131      (e)          (e)          (e)         |P=0.575N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            | 
|     Eosinophilic Focus                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/50 (4%)    2/49 (4%)   |1/50 (2%)    1/50 (2%)    3/50 (6%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/44.11      2/46.10      2/46.36      2/46.75     |1/44.58      1/45.81      3/47.65      1/47.13      | 
|POLY-3 PERCENT (g) |     0.0%         4.3%         4.3%         4.3%        |2.2%         2.2%         6.3%         2.1%         | 
|TERMINAL (d)       |     0/35 (0%)    2/38 (5%)    2/38 (5%)    2/41 (5%)   |1/33 (3%)    1/40 (3%)    3/42 (7%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |729 (T)      729 (T)      729 (T)      722          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.326      P=0.257      P=0.257      P=0.274     |P=0.598      P=0.718N     P=0.395      P=0.698N     | 
|POLY 3             |     P=0.307      P=0.247      P=0.248      P=0.250     |P=0.547      P=0.755N     P=0.330      P=0.748N     | 
|POLY 1.5           |     P=0.294      P=0.241      P=0.243      P=0.243     |P=0.538      P=0.758N     P=0.319      P=0.753N     | 
|POLY 6             |     P=0.322      P=0.254      P=0.254      P=0.260     |P=0.564      P=0.748N     P=0.347      P=0.739N     | 
|LOGISTIC REGRESSION|     (e)          P=0.257      P=0.257      P=0.274     |P=0.582      P=0.718N     P=0.395      P=0.729N     | 
|COCH-ARM / FISHERS |     P=0.274      P=0.247      P=0.247      P=0.242     |P=0.521      P=0.753N     P=0.309      P=0.753N     | 
|ORDER RESTRICTED   |     P=0.198      (e)          (e)          (e)         |P=0.466      (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                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    0/50 (0%)    0/49 (0%)   |4/50 (8%)    1/50 (2%)    6/50 (12%)   2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/44.53      2/46.10      0/46.36      0/46.75     |4/45.25      1/45.99      6/47.70      2/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         4.3%         0.0%         0.0%        |8.8%         2.2%         12.6%        4.3%         | 
|TERMINAL (d)       |     0/35 (0%)    2/38 (5%)    0/38 (0%)    0/41 (0%)   |2/33 (6%)    0/40 (0%)    5/42 (12%)   2/43 (5%)    | 
|FIRST INCIDENCE    |     605          729 (T)      ---          ---         |604          680          716          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.121N     P=0.529      P=0.479N     P=0.479N    |P=0.445N     P=0.150N     P=0.506      P=0.253N     | 
|POLY 3             |     P=0.130N     P=0.512      P=0.492N     P=0.490N    |P=0.521N     P=0.174N     P=0.403      P=0.319N     | 
|POLY 1.5           |     P=0.132N     P=0.504      P=0.496N     P=0.496N    |P=0.527N     P=0.177N     P=0.389      P=0.326N     | 
|POLY 6             |     P=0.127N     P=0.520      P=0.488N     P=0.484N    |P=0.509N     P=0.167N     P=0.426      P=0.306N     | 
|LOGISTIC REGRESSION|     P=0.140N     P=0.500      P=0.484N     P=0.647N    |P=0.532N     P=0.179N     P=0.383      P=0.341N     | 
|COCH-ARM / FISHERS |     P=0.136N     P=0.500      P=0.500N     P=0.505N    |P=0.544N     P=0.181N     P=0.370      P=0.339N     | 
|ORDER RESTRICTED   |     P=0.166N     (e)          (e)          (e)         |P=0.306N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            | 
|     Infiltration Cellular Mixed Cell                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    2/50 (4%)    6/49 (12%)  |11/50 (22%)  12/50 (24%)  12/50 (24%)  15/50 (30%)  | 
|POLY-3 RATE (b)    |     3/44.53      1/46.10      2/46.36      6/46.75     |11/45.51     12/46.44     12/47.71     15/47.10     | 
|POLY-3 PERCENT (g) |     6.7%         2.2%         4.3%         12.8%       |24.2%        25.8%        25.2%        31.8%        | 
|TERMINAL (d)       |     2/35 (6%)    1/38 (3%)    2/38 (5%)    6/41 (15%)  |9/33 (27%)   11/40 (28%)  10/42 (24%)  15/43 (35%)  | 
|FIRST INCIDENCE    |     605          729 (T)      729 (T)      729 (T)     |550          521          716          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.086      P=0.278N     P=0.460N     P=0.323     |P=0.414      P=0.511N     P=0.448N     P=0.515      | 
|POLY 3             |     P=0.062      P=0.293N     P=0.482N     P=0.267     |P=0.237      P=0.522      P=0.552      P=0.277      | 
|POLY 1.5           |     P=0.060      P=0.301N     P=0.490N     P=0.253     |P=0.229      P=0.508      P=0.529      P=0.266      | 
|POLY 6             |     P=0.065      P=0.284N     P=0.473N     P=0.283     |P=0.257      P=0.545      P=0.589      P=0.304      | 
|LOGISTIC REGRESSION|     P=0.070      P=0.304N     P=0.493N     P=0.268     |P=0.261      P=0.512      P=0.567      P=0.313      | 
|COCH-ARM / FISHERS |     P=0.057      P=0.309N     P=0.500N     P=0.233     |P=0.209      P=0.500      P=0.500      P=0.247      | 
|ORDER RESTRICTED   |     P=0.076      (e)          (e)          (e)         |P=0.322      (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                                                                                                                            | 
|     Mixed Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    0/50 (0%)    0/49 (0%)   |2/50 (4%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     3/44.11      1/46.10      0/46.36      0/46.75     |2/44.87      1/45.81      0/47.65      1/47.10      | 
|POLY-3 PERCENT (g) |     6.8%         2.2%         0.0%         0.0%        |4.5%         2.2%         0.0%         2.1%         | 
|TERMINAL (d)       |     3/35 (9%)    1/38 (3%)    0/38 (0%)    0/41 (0%)   |1/33 (3%)    1/40 (3%)    0/42 (0%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          ---         |650          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.046N*    P=0.276N     P=0.107N     P=0.095N    |P=0.326N     P=0.450N     P=0.204N     P=0.429N     | 
|POLY 3             |     P=0.054N     P=0.290N     P=0.110N     P=0.109N    |P=0.368N     P=0.493N     P=0.224N     P=0.483N     | 
|POLY 1.5           |     P=0.054N     P=0.299N     P=0.114N     P=0.114N    |P=0.370N     P=0.498N     P=0.230N     P=0.490N     | 
|POLY 6             |     P=0.054N     P=0.279N     P=0.105N     P=0.102N    |P=0.365N     P=0.485N     P=0.216N     P=0.471N     | 
|LOGISTIC REGRESSION|     P=0.046N*    P=0.276N     (e)          (e)         |P=0.368N     P=0.498N     P=0.244N     P=0.499N     | 
|COCH-ARM / FISHERS |     P=0.056N     P=0.309N     P=0.121N     P=0.125N    |P=0.374N     P=0.500N     P=0.247N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.017N*    (e)          (e)          (e)         |P=0.209N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                            | 
|     Thrombosis                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    1/50 (2%)    1/49 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.11      2/46.26      1/46.49      1/46.84     |0/44.58      0/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         4.3%         2.2%         2.1%        |0.0%         0.0%         0.0%         0.0%         | 
|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    |     ---          694          696          705         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.609      P=0.263      P=0.516      P=0.530     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.603      P=0.248      P=0.511      P=0.512     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.590      P=0.242      P=0.506      P=0.505     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.620      P=0.256      P=0.516      P=0.520     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.574      P=0.242      P=0.499      P=0.497     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.570      P=0.247      P=0.500      P=0.495     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.281      (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    4/49 (8%)   |3/50 (6%)    3/50 (6%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.69      2/46.26      2/46.80      4/47.26     |3/44.61      3/46.02      1/47.74      0/47.10      | 
|POLY-3 PERCENT (g) |     4.5%         4.3%         4.3%         8.5%        |6.7%         6.5%         2.1%         0.0%         | 
|TERMINAL (d)       |     1/35 (3%)    0/38 (0%)    0/38 (0%)    1/41 (2%)   |2/33 (6%)    2/40 (5%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     544          694          645          641         |721          673          705          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.264      P=0.664N     P=0.663N     P=0.402     |P=0.030N*    P=0.576N     P=0.227N     P=0.081N     | 
|POLY 3             |     P=0.233      P=0.681N     P=0.677N     P=0.363     |P=0.039N*    P=0.648N     P=0.282N     P=0.109N     | 
|POLY 1.5           |     P=0.225      P=0.689N     P=0.685N     P=0.348     |P=0.041N*    P=0.656N     P=0.292N     P=0.113N     | 
|POLY 6             |     P=0.245      P=0.672N     P=0.667N     P=0.383     |P=0.037N*    P=0.634N     P=0.266N     P=0.103N     | 
|LOGISTIC REGRESSION|     P=0.180      P=0.693N     P=0.687      P=0.233     |P=0.039N*    P=0.642N     P=0.263N     P=0.090N     | 
|COCH-ARM / FISHERS |     P=0.209      P=0.691N     P=0.691N     P=0.329     |P=0.044N*    P=0.661N     P=0.309N     P=0.121N     | 
|ORDER RESTRICTED   |     P=0.307      (e)          (e)          (e)         |P=0.068N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions 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: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     29/50 (58%)  19/50 (38%)  32/50 (64%)  23/49 (47%) |12/50 (24%)  11/50 (22%)  8/50 (16%)   15/50 (30%)  | 
|POLY-3 RATE (b)    |     29/45.11     19/46.10     32/47.46     23/47.16    |12/46.70     11/46.20     8/47.65      15/47.39     | 
|POLY-3 PERCENT (g) |     64.3%        41.2%        67.4%        48.8%       |25.7%        23.8%        16.8%        31.7%        | 
|TERMINAL (d)       |     27/35 (77%)  19/38 (50%)  29/38 (76%)  22/41 (54%) |4/33 (12%)   10/40 (25%)  8/42 (19%)   13/43 (30%)  | 
|FIRST INCIDENCE    |     548          729 (T)      605          610         |604          616          729 (T)      659          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.212N     P=0.006N**   P=0.553      P=0.023N*   |P=0.465      P=0.369N     P=0.124N     P=0.569      | 
|POLY 3             |     P=0.392N     P=0.019N*    P=0.460      P=0.092N    |P=0.288      P=0.512N     P=0.210N     P=0.341      | 
|POLY 1.5           |     P=0.443N     P=0.026N*    P=0.398      P=0.126N    |P=0.284      P=0.510N     P=0.216N     P=0.338      | 
|POLY 6             |     P=0.328N     P=0.012N*    P=0.541      P=0.060N    |P=0.298      P=0.514N     P=0.202N     P=0.351      | 
|LOGISTIC REGRESSION|     P=0.320N     P=0.008N**   P=0.541      P=0.054N    |P=0.295      P=0.498N     P=0.231N     P=0.335      | 
|COCH-ARM / FISHERS |     P=0.534      P=0.036N*    P=0.341      P=0.184N    |P=0.268      P=0.500N     P=0.227N     P=0.326      | 
|ORDER RESTRICTED   |     P=0.092N     (e)          (e)          (e)         |P=0.218      (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                                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    3/50 (6%)    2/50 (4%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/44.13      0/46.10      3/46.49      2/47.59     |1/44.58      0/45.81      0/47.65      1/47.10      | 
|POLY-3 PERCENT (g) |     2.3%         0.0%         6.5%         4.2%        |2.2%         0.0%         0.0%         2.1%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    2/38 (5%)    2/41 (5%)   |1/33 (3%)    0/40 (0%)    0/42 (0%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     723          ---          696          729 (T)     |729 (T)      ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.222      P=0.489N     P=0.334      P=0.548     |P=0.579      P=0.462N     P=0.452N     P=0.702N     | 
|POLY 3             |     P=0.205      P=0.491N     P=0.324      P=0.526     |P=0.543      P=0.495N     P=0.487N     P=0.748N     | 
|POLY 1.5           |     P=0.199      P=0.497N     P=0.315      P=0.515     |P=0.541      P=0.498N     P=0.492N     P=0.753N     | 
|POLY 6             |     P=0.213      P=0.485N     P=0.334      P=0.539     |P=0.545      P=0.489N     P=0.478N     P=0.739N     | 
|LOGISTIC REGRESSION|     P=0.211      P=0.483N     P=0.331      P=0.550     |P=0.579      (e)          (e)          P=0.702N     | 
|COCH-ARM / FISHERS |     P=0.185      P=0.500N     P=0.309      P=0.500     |P=0.536      P=0.500N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P=0.203      (e)          (e)          (e)         |P=0.383N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 16      
Statistical Analysis of Non-neoplastic Lesions 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 Epithelium                                                                                                        | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    2/50 (4%)    3/50 (6%)   |2/50 (4%)    0/50 (0%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     4/44.53      3/46.10      2/46.49      3/47.59     |2/44.97      0/45.81      1/47.65      1/47.10      | 
|POLY-3 PERCENT (g) |     9.0%         6.5%         4.3%         6.3%        |4.5%         0.0%         2.1%         2.1%         | 
|TERMINAL (d)       |     3/35 (9%)    3/38 (8%)    1/38 (3%)    3/41 (7%)   |0/33 (0%)    0/40 (0%)    1/42 (2%)    1/43 (2%)    | 
|FIRST INCIDENCE    |     605          729 (T)      696          729 (T)     |650          ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.361N     P=0.455N     P=0.301N     P=0.418N    |P=0.527N     P=0.224N     P=0.437N     P=0.439N     | 
|POLY 3             |     P=0.403N     P=0.481N     P=0.317N     P=0.464N    |P=0.568N     P=0.233N     P=0.480N     P=0.484N     | 
|POLY 1.5           |     P=0.410N     P=0.493N     P=0.327N     P=0.479N    |P=0.570N     P=0.236N     P=0.488N     P=0.490N     | 
|POLY 6             |     P=0.395N     P=0.468N     P=0.307N     P=0.448N    |P=0.565N     P=0.229N     P=0.467N     P=0.473N     | 
|LOGISTIC REGRESSION|     P=0.394N     P=0.482N     P=0.331N     P=0.472N    |P=0.576N     P=0.237N     P=0.508N     P=0.507N     | 
|COCH-ARM / FISHERS |     P=0.425N     P=0.500N     P=0.339N     P=0.500N    |P=0.576N     P=0.247N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.381N     (e)          (e)          (e)         |P=0.255N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/43 (5%)    1/46 (2%)    0/48 (0%)    2/47 (4%)   |9/48 (19%)   11/49 (22%)  12/48 (25%)  16/46 (35%)  | 
|POLY-3 RATE (b)    |     2/38.60      1/43.19      0/44.77      2/45.00     |9/43.10      11/45.28     12/46.01     16/43.91     | 
|POLY-3 PERCENT (g) |     5.2%         2.3%         0.0%         4.4%        |20.9%        24.3%        26.1%        36.4%        | 
|TERMINAL (d)       |     1/31 (3%)    0/35 (0%)    0/38 (0%)    2/39 (5%)   |8/31 (26%)   10/39 (26%)  11/40 (28%)  14/39 (36%)  | 
|FIRST INCIDENCE    |     478          452          ---          729 (T)     |568          589          627          528          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.609      P=0.493N     P=0.220N     P=0.631N    |P=0.128      P=0.597N     P=0.545      P=0.211      | 
|POLY 3             |     P=0.600      P=0.461N     P=0.205N     P=0.638N    |P=0.058      P=0.449      P=0.372      P=0.084      | 
|POLY 1.5           |     P=0.599      P=0.470N     P=0.209N     P=0.648N    |P=0.052      P=0.432      P=0.345      P=0.074      | 
|POLY 6             |     P=0.603      P=0.450N     P=0.199N     P=0.625N    |P=0.071      P=0.478      P=0.417      P=0.104      | 
|LOGISTIC REGRESSION|     P=0.510      P=0.390N     P=0.195N     P=0.629     |P=0.054      P=0.452      P=0.376      P=0.078      | 
|COCH-ARM / FISHERS |     P=0.593      P=0.474N     P=0.221N     P=0.657N    |P=0.043 *    P=0.421      P=0.311      P=0.063      | 
|ORDER RESTRICTED   |     P=0.344N     (e)          (e)          (e)         |P=0.078      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 17      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Ectasia                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/47 (0%)    0/50 (0%)    0/48 (0%)    0/48 (0%)   |0/46 (0%)    1/49 (2%)    2/49 (4%)    0/48 (0%)    | 
|POLY-3 RATE (b)    |     0/41.29      0/46.10      0/44.58      0/46.15     |0/40.91      1/44.84      2/46.66      0/45.73      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         2.2%         4.3%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/37 (0%)    0/41 (0%)   |0/30 (0%)    1/40 (3%)    2/42 (5%)    0/42 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          729 (T)      729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.526N     P=0.557      P=0.315      (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.558N     P=0.518      P=0.267      (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.567N     P=0.515      P=0.261      (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.542N     P=0.524      P=0.278      (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          P=0.557      P=0.315      (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.583N     P=0.516      P=0.263      (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.334N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/47 (0%)    0/50 (0%)    3/48 (6%)    0/48 (0%)   |1/46 (2%)    2/49 (4%)    2/49 (4%)    1/48 (2%)    | 
|POLY-3 RATE (b)    |     0/41.29      0/46.10      3/45.08      0/46.15     |1/40.91      2/45.00      2/46.66      1/45.73      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         6.7%         0.0%        |2.4%         4.4%         4.3%         2.2%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/37 (0%)    0/41 (0%)   |1/30 (3%)    1/40 (3%)    2/42 (5%)    1/42 (2%)    | 
|FIRST INCIDENCE    |     ---          ---          645          ---         |729 (T)      688          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.505      (e)          P=0.146      (e)         |P=0.439N     P=0.581      P=0.617      P=0.685N     | 
|POLY 3             |     P=0.513      (e)          P=0.135      (e)         |P=0.487N     P=0.533      P=0.546      P=0.735N     | 
|POLY 1.5           |     P=0.497      (e)          P=0.129      (e)         |P=0.497N     P=0.527      P=0.536      P=0.742N     | 
|POLY 6             |     P=0.533      (e)          P=0.142      (e)         |P=0.472N     P=0.544      P=0.561      P=0.725N     | 
|LOGISTIC REGRESSION|     P=0.449      (e)          P=0.119      (e)         |P=0.476N     P=0.535      P=0.617      P=0.685N     | 
|COCH-ARM / FISHERS |     P=0.469      (e)          P=0.125      (e)         |P=0.513N     P=0.524      P=0.524      P=0.742N     | 
|ORDER RESTRICTED   |     P=0.180      (e)          (e)          (e)         |P=0.541N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 18      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/47 (4%)    2/50 (4%)    2/48 (4%)    0/48 (0%)   |6/46 (13%)   7/49 (14%)   10/49 (20%)  8/48 (17%)   | 
|POLY-3 RATE (b)    |     2/41.29      2/46.10      2/44.58      0/46.15     |6/41.27      7/44.84      10/46.71     8/45.73      | 
|POLY-3 PERCENT (g) |     4.8%         4.3%         4.5%         0.0%        |14.5%        15.6%        21.4%        17.5%        | 
|TERMINAL (d)       |     2/35 (6%)    2/38 (5%)    2/37 (5%)    0/41 (0%)   |5/30 (17%)   7/40 (18%)   9/42 (21%)   8/42 (19%)   | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |627          729 (T)      716          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.134N     P=0.665N     P=0.675N     P=0.204N    |P=0.500      P=0.536N     P=0.443      P=0.595N     | 
|POLY 3             |     P=0.143N     P=0.654N     P=0.666N     P=0.213N    |P=0.372      P=0.564      P=0.290      P=0.467      | 
|POLY 1.5           |     P=0.149N     P=0.664N     P=0.676N     P=0.221N    |P=0.353      P=0.554      P=0.272      P=0.449      | 
|POLY 6             |     P=0.136N     P=0.642N     P=0.656N     P=0.204N    |P=0.403      P=0.581      P=0.320      P=0.498      | 
|LOGISTIC REGRESSION|     P=0.134N     P=0.665N     P=0.675N     (e)         |P=0.433      P=0.601      P=0.332      P=0.514      | 
|COCH-ARM / FISHERS |     P=0.160N     P=0.668N     P=0.684N     P=0.242N    |P=0.317      P=0.549      P=0.248      P=0.420      | 
|ORDER RESTRICTED   |     P=0.168N     (e)          (e)          (e)         |P=0.437      (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Iliac                                                                                                                | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/5 (0%)     1/3 (33%)    0/3 (0%)     0/6 (0%)    |1/7 (14%)    0/5 (0%)     2/10 (20%)   2/10 (20%)   | 
|POLY-3 RATE (b)    |     0/5.00       1/2.95       0/2.56       0/5.69      |1/6.69       0/3.99       2/9.42       2/8.17       | 
|POLY-3 PERCENT (g) |     0.0%         33.9%        0.0%         0.0%        |15.0%        0.0%         21.2%        24.5%        | 
|TERMINAL (d)       |     0/5 (0%)     0/1 (0%)     0/1 (0%)     0/4 (0%)    |0/3 (0%)     0/2 (0%)     2/8 (25%)    1/5 (20%)    | 
|FIRST INCIDENCE    |     ---          676          ---          ---         |655          ---          729 (T)      680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.428N     P=0.525      (e)          (e)         |P=0.320      P=0.481N     P=0.735      P=0.597      | 
|POLY 3             |     P=0.407N     P=0.389      (e)          (e)         |P=0.319      P=0.600N     P=0.623      P=0.574      | 
|POLY 1.5           |     P=0.400N     P=0.390      (e)          (e)         |P=0.328      P=0.585N     P=0.624      P=0.593      | 
|POLY 6             |     P=0.421N     P=0.385      (e)          (e)         |P=0.322      P=0.619N     P=0.626      P=0.561      | 
|LOGISTIC REGRESSION|     P=0.310N     (e)          (e)          (e)         |P=0.315      P=0.467N     P=0.631      P=0.619      | 
|COCH-ARM / FISHERS |     P=0.398N     P=0.375      (e)          (e)         |P=0.344      P=0.583N     P=0.640      P=0.640      | 
|ORDER RESTRICTED   |     P=0.261N     (e)          (e)          (e)         |P=0.363      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 19      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Mediastinal                                                                                                          | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/5 (0%)     0/3 (0%)     0/3 (0%)     1/6 (17%)   |2/7 (29%)    0/5 (0%)     0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/5.00       0/2.75       0/2.56       1/5.69      |2/6.41       0/3.99       0/9.42       1/7.99       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         17.6%       |31.2%        0.0%         0.0%         12.5%        | 
|TERMINAL (d)       |     0/5 (0%)     0/1 (0%)     0/1 (0%)     1/4 (25%)   |2/3 (67%)    0/2 (0%)     0/8 (0%)     1/5 (20%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          729 (T)     |729 (T)      ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.236      (e)          (e)          P=0.455     |P=0.314N     P=0.309N     P=0.055N     P=0.298N     | 
|POLY 3             |     P=0.255      (e)          (e)          P=0.526     |P=0.347N     P=0.337N     P=0.132N     P=0.417N     | 
|POLY 1.5           |     P=0.258      (e)          (e)          P=0.531     |P=0.361N     P=0.322N     P=0.136N     P=0.401N     | 
|POLY 6             |     P=0.251      (e)          (e)          P=0.516     |P=0.329N     P=0.356N     P=0.123N     P=0.426N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.455     |P=0.314N     (e)          (e)          P=0.298N     | 
|COCH-ARM / FISHERS |     P=0.245      (e)          (e)          P=0.545     |P=0.378N     P=0.318N     P=0.154N     P=0.360N     | 
|ORDER RESTRICTED   |     P=0.146      (e)          (e)          (e)         |P=0.075N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/5 (60%)    7/11 (64%)   4/5 (80%)    0/4 (0%)    |16/18 (89%)  12/14 (86%)  13/15 (87%)  4/13 (31%)   | 
|POLY-3 RATE (b)    |     3/4.79       7/9.91       4/4.87       0/3.80      |16/17.96     12/13.30     13/14.69     4/11.17      | 
|POLY-3 PERCENT (g) |     62.7%        70.7%        82.2%        0.0%        |89.1%        90.2%        88.5%        35.8%        | 
|TERMINAL (d)       |     2/3 (67%)    6/8 (75%)    3/3 (100%)   0/2 (0%)    |11/12 (92%)  10/10 (100%) 9/10 (90%)   2/7 (29%)    | 
|FIRST INCIDENCE    |     665          717          645          ---         |550          533          568          659          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.087N     P=0.644      P=0.525      P=0.142N    |P=0.007N**   P=0.325N     P=0.397N     P=0.008N**   | 
|POLY 3             |     P=0.030N*    P=0.613      P=0.516      P=0.083N    |P<0.001N**   P=0.695      P=0.692N     P<0.001N**   | 
|POLY 1.5           |     P=0.037N*    P=0.626      P=0.508      P=0.085N    |P<0.001N**   P=0.691N     P=0.663N     P<0.001N**   | 
|POLY 6             |     P=0.025N*    P=0.613      P=0.529      P=0.079N    |P<0.001N**   P=0.614      P=0.706      P=0.003N**   | 
|LOGISTIC REGRESSION|     P=0.045N*    P=0.719      P=0.500      P=0.119N    |P<0.001N**   P=0.633N     P=0.633N     P=0.002N**   | 
|COCH-ARM / FISHERS |     P=0.066N     P=0.654      P=0.500      P=0.119N    |P<0.001N**   P=0.597N     P=0.626N     P<0.001N**   | 
|ORDER RESTRICTED   |     P=0.041N*    (e)          (e)          (e)         |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 20      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    3/50 (6%)    6/50 (12%)  |0/50 (0%)    3/50 (6%)    7/50 (14%)   11/50 (22%)  | 
|POLY-3 RATE (b)    |     1/44.11      3/46.43      3/47.81      6/48.32     |0/44.58      3/45.81      7/47.71      11/47.91     | 
|POLY-3 PERCENT (g) |     2.3%         6.5%         6.3%         12.4%       |0.0%         6.6%         14.7%        23.0%        | 
|TERMINAL (d)       |     1/35 (3%)    2/38 (5%)    0/38 (0%)    3/41 (7%)   |0/33 (0%)    3/40 (8%)    5/42 (12%)   9/43 (21%)   | 
|FIRST INCIDENCE    |     729 (T)      638          261          610         |---          729 (T)      716          445          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.068      P=0.339      P=0.337      P=0.095     |P<0.001 **   P=0.157      P=0.023 *    P=0.003 **   | 
|POLY 3             |     P=0.055      P=0.324      P=0.335      P=0.072     |P<0.001 **   P=0.124      P=0.010 *    P<0.001 **   | 
|POLY 1.5           |     P=0.051      P=0.313      P=0.323      P=0.065     |P<0.001 **   P=0.121      P=0.009 **   P<0.001 **   | 
|POLY 6             |     P=0.062      P=0.337      P=0.348      P=0.082     |P<0.001 **   P=0.129      P=0.012 *    P<0.001 **   | 
|LOGISTIC REGRESSION|     P=0.025 *    P=0.310      P=0.287      P=0.051     |P<0.001 **   P=0.157      P=0.017 *    P<0.001 **   | 
|COCH-ARM / FISHERS |     P=0.043 *    P=0.309      P=0.309      P=0.056     |P<0.001 **   P=0.121      P=0.006 **   P<0.001 **   | 
|ORDER RESTRICTED   |     P=0.039 *    (e)          (e)          (e)         |P<0.001 **   (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Nasolacrimal Duct                                                                                                          | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/44.24      0/46.10      1/46.36      1/47.59     |0/44.58      1/46.42      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     6.8%         0.0%         2.2%         2.1%        |0.0%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/35 (6%)    0/38 (0%)    1/38 (3%)    1/41 (2%)   |0/33 (0%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     694          ---          729 (T)      729 (T)     |---          533          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.348N     P=0.108N     P=0.279N     P=0.253N    |P=0.454N     P=0.496      (e)          (e)          | 
|POLY 3             |     P=0.383N     P=0.111N     P=0.289N     P=0.280N    |P=0.439N     P=0.508      (e)          (e)          | 
|POLY 1.5           |     P=0.382N     P=0.116N     P=0.297N     P=0.290N    |P=0.444N     P=0.504      (e)          (e)          | 
|POLY 6             |     P=0.384N     P=0.107N     P=0.280N     P=0.268N    |P=0.431N     P=0.515      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.358N     P=0.109N     P=0.277N     P=0.266N    |P=0.519N     P=0.535      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.387N     P=0.121N     P=0.309N     P=0.309N    |P=0.449N     P=0.500      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.087N     (e)          (e)          (e)         |P=0.378N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 21      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |3/47 (6%)    2/48 (4%)    0/49 (0%)    2/48 (4%)    | 
|POLY-3 RATE (b)    |                                                        |3/42.25      2/44.02      0/46.65      2/45.10      | 
|POLY-3 PERCENT (g) |                                                        |7.1%         4.5%         0.0%         4.4%         | 
|TERMINAL (d)       |                                                        |2/32 (6%)    2/39 (5%)    0/41 (0%)    2/41 (5%)    | 
|FIRST INCIDENCE    |                                                        |673          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.301N     P=0.417N     P=0.086N     P=0.396N     | 
|POLY 3             |                                                        |P=0.349N     P=0.481N     P=0.102N     P=0.470N     | 
|POLY 1.5           |                                                        |P=0.352N     P=0.487N     P=0.106N     P=0.478N     | 
|POLY 6             |                                                        |P=0.344N     P=0.471N     P=0.096N     P=0.456N     | 
|LOGISTIC REGRESSION|                                                        |P=0.334N     P=0.472N     P=0.107N     P=0.462N     | 
|COCH-ARM / FISHERS |                                                        |P=0.359N     P=0.490N     P=0.113N     P=0.490N     | 
|ORDER RESTRICTED   |                                                        |P=0.189N     (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                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |12/47 (26%)  12/48 (25%)  16/49 (33%)  13/48 (27%)  | 
|POLY-3 RATE (b)    |                                                        |12/43.21     12/45.11     16/47.47     13/45.91     | 
|POLY-3 PERCENT (g) |                                                        |27.8%        26.6%        33.7%        28.3%        | 
|TERMINAL (d)       |                                                        |9/32 (28%)   10/39 (26%)  12/41 (29%)  11/41 (27%)  | 
|FIRST INCIDENCE    |                                                        |550          533          627          528          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.497N     P=0.419N     P=0.502      P=0.444N     | 
|POLY 3             |                                                        |P=0.449      P=0.546N     P=0.351      P=0.571      | 
|POLY 1.5           |                                                        |P=0.435      P=0.561N     P=0.326      P=0.553      | 
|POLY 6             |                                                        |P=0.478      P=0.522N     P=0.395      P=0.585N     | 
|LOGISTIC REGRESSION|                                                        |P=0.415      P=0.568N     P=0.313      P=0.537      | 
|COCH-ARM / FISHERS |                                                        |P=0.401      P=0.570N     P=0.294      P=0.525      | 
|ORDER RESTRICTED   |                                                        |P=0.542      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 22      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Thrombosis                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |3/47 (6%)    0/48 (0%)    0/49 (0%)    3/48 (6%)    | 
|POLY-3 RATE (b)    |                                                        |3/42.04      0/44.02      0/46.65      3/45.91      | 
|POLY-3 PERCENT (g) |                                                        |7.1%         0.0%         0.0%         6.5%         | 
|TERMINAL (d)       |                                                        |3/32 (9%)    0/39 (0%)    0/41 (0%)    1/41 (2%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      ---          ---          528          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.410      P=0.088N     P=0.081N     P=0.569N     | 
|POLY 3             |                                                        |P=0.371      P=0.110N     P=0.101N     P=0.621N     | 
|POLY 1.5           |                                                        |P=0.369      P=0.113N     P=0.105N     P=0.634N     | 
|POLY 6             |                                                        |P=0.374      P=0.105N     P=0.094N     P=0.600N     | 
|LOGISTIC REGRESSION|                                                        |P=0.348      (e)          (e)          P=0.658      | 
|COCH-ARM / FISHERS |                                                        |P=0.362      P=0.117N     P=0.113N     P=0.651N     | 
|ORDER RESTRICTED   |                                                        |P=0.154N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas: Duct                                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/48 (0%)    0/50 (0%)    1/49 (2%)    0/48 (0%)   |2/46 (4%)    0/46 (0%)    2/49 (4%)    2/49 (4%)    | 
|POLY-3 RATE (b)    |     0/42.16      0/46.10      1/45.58      0/46.16     |2/41.68      0/42.91      2/47.17      2/46.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         0.0%        |4.8%         0.0%         4.2%         4.3%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    1/38 (3%)    0/41 (0%)   |1/32 (3%)    0/40 (0%)    2/42 (5%)    2/42 (5%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |638          ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.665      (e)          P=0.516      (e)         |P=0.421      P=0.215N     P=0.612N     P=0.612N     | 
|POLY 3             |     P=0.676      (e)          P=0.516      (e)         |P=0.391      P=0.231N     P=0.649N     P=0.657N     | 
|POLY 1.5           |     P=0.666      (e)          P=0.510      (e)         |P=0.391      P=0.235N     P=0.658N     P=0.662N     | 
|POLY 6             |     P=0.689      (e)          P=0.522      (e)         |P=0.393      P=0.224N     P=0.634N     P=0.647N     | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.516      (e)         |P=0.390      P=0.238N     P=0.672N     P=0.669N     | 
|COCH-ARM / FISHERS |     P=0.647      (e)          P=0.505      (e)         |P=0.383      P=0.247N     P=0.667N     P=0.667N     | 
|ORDER RESTRICTED   |     P=0.395      (e)          (e)          (e)         |P=0.484      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 23      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Parathyroid Gland                                                                                                                | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/46 (0%)    3/50 (6%)    3/48 (6%)    2/46 (4%)   |1/48 (2%)    1/48 (2%)    1/46 (2%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |     0/40.69      3/46.10      3/44.79      2/44.32     |1/42.94      1/43.81      1/43.65      1/46.10      | 
|POLY-3 PERCENT (g) |     0.0%         6.5%         6.7%         4.5%        |2.3%         2.3%         2.3%         2.2%         | 
|TERMINAL (d)       |     0/32 (0%)    3/38 (8%)    2/36 (6%)    2/40 (5%)   |0/32 (0%)    1/38 (3%)    1/38 (3%)    1/42 (2%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      605          729 (T)     |638          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.437      P=0.153      P=0.144      P=0.289     |P=0.571N     P=0.741N     P=0.734N     P=0.723N     | 
|POLY 3             |     P=0.405      P=0.142      P=0.136      P=0.257     |P=0.607N     P=0.756N     P=0.757N     P=0.745N     | 
|POLY 1.5           |     P=0.386      P=0.137      P=0.132      P=0.248     |P=0.611N     P=0.759N     P=0.759      P=0.749N     | 
|POLY 6             |     P=0.430      P=0.148      P=0.142      P=0.267     |P=0.600N     P=0.751N     P=0.748N     P=0.736N     | 
|LOGISTIC REGRESSION|     P=0.378      P=0.153      P=0.125      P=0.289     |P=0.617N     P=0.763N     P=0.745      P=0.759      | 
|COCH-ARM / FISHERS |     P=0.358      P=0.137      P=0.129      P=0.247     |P=0.621N     P=0.753N     P=0.742      P=0.747N     | 
|ORDER RESTRICTED   |     P=0.154      (e)          (e)          (e)         |P=0.725N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    0/49 (0%)    0/50 (0%)   |2/46 (4%)    1/49 (2%)    0/48 (0%)    0/47 (0%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/45.10      0/45.36      0/47.59     |2/41.35      1/45.42      0/45.65      0/44.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.8%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/37 (0%)    0/37 (0%)    0/41 (0%)   |2/31 (7%)    1/40 (3%)    0/40 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.086N     P=0.411N     P=0.184N     P=0.184N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.102N     P=0.467N     P=0.216N     P=0.223N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.102N     P=0.473N     P=0.221N     P=0.227N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.102N     P=0.458N     P=0.208N     P=0.216N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.086N     P=0.411N     (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.104N     P=0.476N     P=0.237N     P=0.242N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.066N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 24      
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/49 (2%)    1/49 (2%)    3/50 (6%)   |0/46 (0%)    0/49 (0%)    1/48 (2%)    1/47 (2%)    | 
|POLY-3 RATE (b)    |     3/44.11      1/45.10      1/45.36      3/47.59     |0/41.35      0/45.42      1/45.65      1/44.10      | 
|POLY-3 PERCENT (g) |     6.8%         2.2%         2.2%         6.3%        |0.0%         0.0%         2.2%         2.3%         | 
|TERMINAL (d)       |     3/35 (9%)    1/37 (3%)    1/37 (3%)    3/41 (7%)   |0/31 (0%)    0/40 (0%)    1/40 (3%)    1/40 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |---          ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.507      P=0.285N     P=0.285N     P=0.588N    |P=0.234      (e)          P=0.551      P=0.551      | 
|POLY 3             |     P=0.467      P=0.297N     P=0.295N     P=0.627N    |P=0.215      (e)          P=0.520      P=0.513      | 
|POLY 1.5           |     P=0.462      P=0.307N     P=0.304N     P=0.641N    |P=0.213      (e)          P=0.515      P=0.510      | 
|POLY 6             |     P=0.472      P=0.287N     P=0.286N     P=0.609N    |P=0.220      (e)          P=0.527      P=0.519      | 
|LOGISTIC REGRESSION|     P=0.507      P=0.285N     P=0.285N     P=0.588N    |(e)          (e)          P=0.551      P=0.551      | 
|COCH-ARM / FISHERS |     P=0.448      P=0.316N     P=0.316N     P=0.661N    |P=0.207      (e)          P=0.511      P=0.505      | 
|ORDER RESTRICTED   |     P=0.364N     (e)          (e)          (e)         |P=0.264      (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Cytoplasmic Alteration Focal                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    0/49 (0%)    0/50 (0%)   |1/46 (2%)    4/49 (8%)    1/48 (2%)    2/47 (4%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/45.10      0/45.36      0/47.59     |1/41.35      4/45.81      1/45.65      2/44.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.4%         8.7%         2.2%         4.5%         | 
|TERMINAL (d)       |     0/35 (0%)    0/37 (0%)    0/37 (0%)    0/41 (0%)   |1/31 (3%)    3/40 (8%)    1/40 (3%)    2/40 (5%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      616          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.419N     P=0.245      P=0.704N     P=0.589      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.464N     P=0.211      P=0.738N     P=0.522      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.471N     P=0.204      P=0.744N     P=0.517      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.450N     P=0.222      P=0.729N     P=0.534      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.472N     P=0.201      P=0.704N     P=0.589      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.483N     P=0.201      P=0.742N     P=0.508      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.435      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 25      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Degeneration Cystic                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/50 (22%)  11/50 (22%)  16/50 (32%)  11/48 (23%) |                                                    | 
|POLY-3 RATE (b)    |     11/45.32     11/46.52     16/47.29     11/46.04    |                                                    | 
|POLY-3 PERCENT (g) |     24.3%        23.7%        33.8%        23.9%       |                                                    | 
|TERMINAL (d)       |     8/35 (23%)   10/38 (26%)  13/38 (34%)  9/39 (23%)  |                                                    | 
|FIRST INCIDENCE    |     559          610          605          641         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.521N     P=0.506N     P=0.270      P=0.478N    |                                                    | 
|POLY 3             |     P=0.476      P=0.569N     P=0.216      P=0.580N    |                                                    | 
|POLY 1.5           |     P=0.454      P=0.588N     P=0.200      P=0.588     |                                                    | 
|POLY 6             |     P=0.503      P=0.550N     P=0.235      P=0.553N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.452      P=0.577N     P=0.200      P=0.580     |                                                    | 
|COCH-ARM / FISHERS |     P=0.409      P=0.595N     P=0.184      P=0.553     |                                                    | 
|ORDER RESTRICTED   |     P=0.467      (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    2/50 (4%)    3/48 (6%)   |                                                    | 
|POLY-3 RATE (b)    |     2/44.16      1/46.10      2/46.58      3/45.64     |                                                    | 
|POLY-3 PERCENT (g) |     4.5%         2.2%         4.3%         6.6%        |                                                    | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    1/38 (3%)    2/39 (5%)   |                                                    | 
|FIRST INCIDENCE    |     723          729 (T)      673          716         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.313      P=0.478N     P=0.665N     P=0.549     |                                                    | 
|POLY 3             |     P=0.281      P=0.485N     P=0.675N     P=0.515     |                                                    | 
|POLY 1.5           |     P=0.274      P=0.494N     P=0.684N     P=0.501     |                                                    | 
|POLY 6             |     P=0.288      P=0.475N     P=0.664N     P=0.531     |                                                    | 
|LOGISTIC REGRESSION|     P=0.286      P=0.469N     P=0.680N     P=0.539     |                                                    | 
|COCH-ARM / FISHERS |     P=0.260      P=0.500N     P=0.691N     P=0.480     |                                                    | 
|ORDER RESTRICTED   |     P=0.364      (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 26      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Seminal Vesicle                                                                                                                  | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/49 (4%)    2/50 (4%)    0/50 (0%)    0/49 (0%)   |                                                    | 
|POLY-3 RATE (b)    |     2/43.13      2/46.10      0/46.36      0/46.75     |                                                    | 
|POLY-3 PERCENT (g) |     4.6%         4.3%         0.0%         0.0%        |                                                    | 
|TERMINAL (d)       |     2/35 (6%)    2/38 (5%)    0/38 (0%)    0/41 (0%)   |                                                    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          ---         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.060N     P=0.665N     P=0.220N     P=0.204N    |                                                    | 
|POLY 3             |     P=0.066N     P=0.670N     P=0.221N     P=0.220N    |                                                    | 
|POLY 1.5           |     P=0.067N     P=0.680N     P=0.227N     P=0.227N    |                                                    | 
|POLY 6             |     P=0.065N     P=0.658N     P=0.215N     P=0.211N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.060N     P=0.665N     (e)          (e)         |                                                    | 
|COCH-ARM / FISHERS |     P=0.070N     P=0.684N     P=0.242N     P=0.247N    |                                                    | 
|ORDER RESTRICTED   |     P=0.104N     (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                                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    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      0/46.36      2/47.91     |0/44.58      0/45.81      0/47.65      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.2%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    1/41 (2%)   |0/33 (0%)    0/40 (0%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          641         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.052      (e)          (e)          P=0.275     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.045 *    (e)          (e)          P=0.256     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.044 *    (e)          (e)          P=0.248     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.047 *    (e)          (e)          P=0.266     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.038 *    (e)          (e)          P=0.202     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.043 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.036 *    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 27      
Statistical Analysis of Non-neoplastic Lesions 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: Subcutaneous Tissue                                                                                                        | 
|     Edema                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/44.35      1/46.10      2/47.10      1/47.75     |0/44.58      0/45.81      0/47.65      1/47.40      | 
|POLY-3 PERCENT (g) |     2.3%         2.2%         4.3%         2.1%        |0.0%         0.0%         0.0%         2.1%         | 
|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    |     665          729 (T)      605          687         |---          ---          ---          649          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.605      P=0.741N     P=0.537      P=0.723N    |P=0.199      (e)          (e)          P=0.522      | 
|POLY 3             |     P=0.596      P=0.752N     P=0.521      P=0.744N    |P=0.194      (e)          (e)          P=0.512      | 
|POLY 1.5           |     P=0.586      P=0.757N     P=0.511      P=0.751N    |P=0.191      (e)          (e)          P=0.507      | 
|POLY 6             |     P=0.608      P=0.746N     P=0.532      P=0.736N    |P=0.199      (e)          (e)          P=0.521      | 
|LOGISTIC REGRESSION|     P=0.530      P=0.762N     P=0.497      P=0.728     |P=0.166      (e)          (e)          P=0.470      | 
|COCH-ARM / FISHERS |     P=0.569      P=0.753N     P=0.500      P=0.753N    |P=0.186      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.608      (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spinal Cord                                                                                                                      | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/4 (0%)     2/4 (50%)    0/1 (0%)     0/2 (0%)    |0/1 (0%)     0/2 (0%)     0/1 (0%)     0/1 (0%)     | 
|POLY-3 RATE (b)    |     0/3.57       2/3.78       0/0.81       0/1.85      |0/0.43       0/1.37       0/0.69       0/0.81       | 
|POLY-3 PERCENT (g) |     0.0%         53.0%        0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/3 (0%)     0/1 (0%)     0/0 (0%)     0/1 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          15           ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.247N     P=0.265      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.441N     P=0.201      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.436N     P=0.198      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.459N     P=0.204      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.627N     P=0.429      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.436N     P=0.214      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.301      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 28      
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                           | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/49 (0%)    0/48 (0%)   |0/47 (0%)    2/47 (4%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/43.24      0/46.10      0/45.58      0/46.16     |0/42.32      2/43.72      0/47.59      0/47.10      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         4.6%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |0/32 (0%)    2/40 (5%)    0/42 (0%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.227N     P=0.289      (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.238N     P=0.244      (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.244N     P=0.240      (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.230N     P=0.251      (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          P=0.289      (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.253N     P=0.247      (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.234N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/49 (29%)  16/50 (32%)  25/49 (51%)  29/48 (60%) |23/47 (49%)  21/47 (45%)  31/49 (63%)  40/50 (80%)  | 
|POLY-3 RATE (b)    |     14/45.74     16/48.28     25/47.71     29/47.72    |23/44.12     21/44.52     31/48.11     40/47.94     | 
|POLY-3 PERCENT (g) |     30.6%        33.1%        52.4%        60.8%       |52.1%        47.2%        64.4%        83.4%        | 
|TERMINAL (d)       |     7/35 (20%)   10/38 (26%)  17/38 (45%)  25/41 (61%) |15/32 (47%)  19/40 (48%)  27/42 (64%)  37/43 (86%)  | 
|FIRST INCIDENCE    |     478          452          605          506         |550          533          627          528          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.006 **   P=0.517      P=0.068      P=0.023 *   |P=0.004 **   P=0.163N     P=0.476      P=0.070      | 
|POLY 3             |     P<0.001 **   P=0.483      P=0.025 *    P=0.002 **  |P<0.001 **   P=0.400N     P=0.160      P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.456      P=0.020 *    P=0.002 **  |P<0.001 **   P=0.414N     P=0.145      P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.513      P=0.032 *    P=0.003 **  |P<0.001 **   P=0.380N     P=0.182      P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.432      P=0.017 *    P<0.001 **  |P<0.001 **   P=0.393N     P=0.180      P=0.002 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.440      P=0.019 *    P<0.001 **  |P<0.001 **   P=0.418N     P=0.113      P<0.001 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 29      
Statistical Analysis of Non-neoplastic Lesions 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                                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/49 (14%)   6/50 (12%)   2/49 (4%)    3/48 (6%)   |17/47 (36%)  15/47 (32%)  17/49 (35%)  11/50 (22%)  | 
|POLY-3 RATE (b)    |     7/43.24      6/46.10      2/45.58      3/46.16     |17/43.64     15/44.20     17/47.64     11/47.10     | 
|POLY-3 PERCENT (g) |     16.2%        13.0%        4.4%         6.5%        |39.0%        33.9%        35.7%        23.4%        | 
|TERMINAL (d)       |     7/35 (20%)   6/38 (16%)   2/38 (5%)    3/41 (7%)   |13/32 (41%)  14/40 (35%)  16/42 (38%)  11/43 (26%)  | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |617          589          716          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.045N*    P=0.435N     P=0.061N     P=0.100N    |P=0.035N*    P=0.195N     P=0.251N     P=0.027N*    | 
|POLY 3             |     P=0.063N     P=0.451N     P=0.066N     P=0.132N    |P=0.081N     P=0.395N     P=0.458N     P=0.082N     | 
|POLY 1.5           |     P=0.067N     P=0.471N     P=0.072N     P=0.146N    |P=0.082N     P=0.409N     P=0.478N     P=0.085N     | 
|POLY 6             |     P=0.057N     P=0.428N     P=0.060N     P=0.116N    |P=0.077N     P=0.374N     P=0.431N     P=0.075N     | 
|LOGISTIC REGRESSION|     P=0.045N*    P=0.435N     P=0.061N     P=0.100N    |P=0.067N     P=0.388N     P=0.426N     P=0.072N     | 
|COCH-ARM / FISHERS |     P=0.076N     P=0.484N     P=0.080N     P=0.167N    |P=0.093N     P=0.414N     P=0.525N     P=0.094N     | 
|ORDER RESTRICTED   |     P=0.067N     (e)          (e)          (e)         |P=0.086N     (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                                                                                                             | 
|     Diverticulum                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/48 (0%)   |1/50 (2%)    0/50 (0%)    1/50 (2%)    3/49 (6%)    | 
|POLY-3 RATE (b)    |     0/44.11      0/46.10      0/46.36      0/46.16     |1/44.62      0/45.81      1/47.65      3/46.84      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.2%         0.0%         2.1%         6.4%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |0/33 (0%)    0/40 (0%)    1/42 (2%)    3/43 (7%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |718          ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.104      P=0.468N     P=0.710N     P=0.401      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.079      P=0.495N     P=0.746N     P=0.323      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.077      P=0.498N     P=0.752N     P=0.313      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.082      P=0.489N     P=0.736N     P=0.339      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.093      P=0.491N     P=0.733N     P=0.366      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.072      P=0.500N     P=0.753N     P=0.301      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.091      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 30      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    0/50 (0%)    1/48 (2%)   |2/50 (4%)    0/50 (0%)    3/50 (6%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |     0/44.11      3/46.57      0/46.36      1/46.26     |2/44.91      0/45.81      3/48.27      1/47.13      | 
|POLY-3 PERCENT (g) |     0.0%         6.4%         0.0%         2.2%        |4.5%         0.0%         6.2%         2.1%         | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    0/38 (0%)    0/41 (0%)   |1/33 (3%)    0/40 (0%)    1/42 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     ---          638          ---          705         |638          ---          568          649          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.441N     P=0.142      (e)          P=0.530     |P=0.597N     P=0.219N     P=0.572      P=0.449N     | 
|POLY 3             |     P=0.460N     P=0.129      (e)          P=0.509     |P=0.586      P=0.233N     P=0.533      P=0.483N     | 
|POLY 1.5           |     P=0.473N     P=0.123      (e)          P=0.502     |P=0.576      P=0.236N     P=0.519      P=0.493N     | 
|POLY 6             |     P=0.445N     P=0.136      (e)          P=0.519     |P=0.602      P=0.228N     P=0.554      P=0.468N     | 
|LOGISTIC REGRESSION|     P=0.500N     P=0.120      (e)          P=0.492     |P=0.516      P=0.237N     P=0.468      P=0.549N     | 
|COCH-ARM / FISHERS |     P=0.487N     P=0.121      (e)          P=0.490     |P=0.555      P=0.247N     P=0.500      P=0.508N     | 
|ORDER RESTRICTED   |     P=0.279      (e)          (e)          (e)         |P=0.419N     (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: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    2/50 (4%)    3/50 (6%)    2/48 (4%)   |2/50 (4%)    2/50 (4%)    2/50 (4%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |     3/44.93      2/46.43      3/46.79      2/46.40     |2/44.58      2/45.97      2/47.74      1/47.13      | 
|POLY-3 PERCENT (g) |     6.7%         4.3%         6.4%         4.3%        |4.5%         4.4%         4.2%         2.1%         | 
|TERMINAL (d)       |     0/35 (0%)    1/38 (3%)    2/38 (5%)    0/41 (0%)   |2/33 (6%)    1/40 (3%)    1/42 (2%)    0/43 (0%)    | 
|FIRST INCIDENCE    |     544          638          605          694         |729 (T)      688          705          649          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.434N     P=0.467N     P=0.622N     P=0.446N    |P=0.303N     P=0.629N     P=0.604N     P=0.426N     | 
|POLY 3             |     P=0.475N     P=0.485N     P=0.643N     P=0.485N    |P=0.348N     P=0.683N     P=0.669N     P=0.481N     | 
|POLY 1.5           |     P=0.485N     P=0.495N     P=0.652N     P=0.499N    |P=0.358N     P=0.689N     P=0.680N     P=0.491N     | 
|POLY 6             |     P=0.463N     P=0.474N     P=0.634N     P=0.468N    |P=0.334N     P=0.672N     P=0.651N     P=0.464N     | 
|LOGISTIC REGRESSION|     P=0.550N     P=0.490N     P=0.648      P=0.651N    |P=0.366N     P=0.678N     P=0.647N     P=0.509N     | 
|COCH-ARM / FISHERS |     P=0.504N     P=0.500N     P=0.661N     P=0.520N    |P=0.374N     P=0.691N     P=0.691N     P=0.508N     | 
|ORDER RESTRICTED   |     P=0.491N     (e)          (e)          (e)         |P=0.442N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 31      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Erosion                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/47 (4%)    1/47 (2%)    2/47 (4%)    1/48 (2%)   |0/45 (0%)    0/47 (0%)    0/50 (0%)    0/46 (0%)    | 
|POLY-3 RATE (b)    |     2/42.52      1/43.53      2/44.39      1/46.30     |0/40.83      0/44.30      0/47.65      0/44.39      | 
|POLY-3 PERCENT (g) |     4.7%         2.3%         4.5%         2.2%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/38 (0%)    0/41 (0%)   |0/33 (0%)    0/40 (0%)    0/42 (0%)    0/42 (0%)    | 
|FIRST INCIDENCE    |     544          670          627          610         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.444N     P=0.473N     P=0.656N     P=0.459N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.451N     P=0.492N     P=0.678N     P=0.470N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.457N     P=0.498N     P=0.686N     P=0.479N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.444N     P=0.485N     P=0.670N     P=0.460N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.559N     P=0.468N     P=0.702      P=0.737N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.471N     P=0.500N     P=0.692N     P=0.492N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.405N     (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/38 (0%)    1/47 (2%)    0/40 (0%)    0/44 (0%)   |8/43 (19%)   13/47 (28%)  11/44 (25%)  14/49 (29%)  | 
|POLY-3 RATE (b)    |     0/33.04      1/43.24      0/37.11      0/42.16     |8/38.48      13/42.97     11/42.65     14/46.29     | 
|POLY-3 PERCENT (g) |     0.0%         2.3%         0.0%         0.0%        |20.8%        30.3%        25.8%        30.2%        | 
|TERMINAL (d)       |     0/28 (0%)    1/36 (3%)    0/31 (0%)    0/37 (0%)   |8/30 (27%)   13/38 (34%)  11/39 (28%)  13/42 (31%)  | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |729 (T)      729 (T)      729 (T)      680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.426N     P=0.550      (e)          (e)         |P=0.430      P=0.344      P=0.551      P=0.363      | 
|POLY 3             |     P=0.433N     P=0.553      (e)          (e)         |P=0.315      P=0.235      P=0.395      P=0.230      | 
|POLY 1.5           |     P=0.438N     P=0.547      (e)          (e)         |P=0.296      P=0.226      P=0.369      P=0.215      | 
|POLY 6             |     P=0.426N     P=0.560      (e)          (e)         |P=0.349      P=0.250      P=0.431      P=0.258      | 
|LOGISTIC REGRESSION|     (e)          P=0.550      (e)          (e)         |P=0.388      P=0.344      P=0.551      P=0.295      | 
|COCH-ARM / FISHERS |     P=0.443N     P=0.553      (e)          (e)         |P=0.258      P=0.223      P=0.322      P=0.192      | 
|ORDER RESTRICTED   |     P=0.393N     (e)          (e)          (e)         |P=0.266      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 32      
Statistical Analysis of Non-neoplastic Lesions 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: Follicle                                                                                                          | 
|     Degeneration Cystic Focal                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   12/50 (24%)  11/49 (22%)  7/48 (15%)  |17/46 (37%)  15/50 (30%)  28/49 (57%)  23/47 (49%)  | 
|POLY-3 RATE (b)    |     6/44.78      12/46.15     11/45.71     7/46.22     |17/42.38     15/47.10     28/47.53     23/45.58     | 
|POLY-3 PERCENT (g) |     13.4%        26.0%        24.1%        15.2%       |40.1%        31.9%        58.9%        50.5%        | 
|TERMINAL (d)       |     4/35 (11%)   11/38 (29%)  10/38 (26%)  6/41 (15%)  |14/32 (44%)  12/40 (30%)  23/42 (55%)  20/41 (49%)  | 
|FIRST INCIDENCE    |     605          717          696          716         |638          521          627          649          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.301N     P=0.137      P=0.194      P=0.612     |P=0.142      P=0.196N     P=0.197      P=0.466      | 
|POLY 3             |     P=0.384N     P=0.105      P=0.151      P=0.524     |P=0.038 *    P=0.276N     P=0.055      P=0.223      | 
|POLY 1.5           |     P=0.413N     P=0.098      P=0.142      P=0.502     |P=0.034 *    P=0.293N     P=0.046 *    P=0.202      | 
|POLY 6             |     P=0.351N     P=0.113      P=0.161      P=0.551     |P=0.050      P=0.253N     P=0.075      P=0.263      | 
|LOGISTIC REGRESSION|     P=0.352N     P=0.121      P=0.164      P=0.520     |P=0.039 *    P=0.301N     P=0.059      P=0.229      | 
|COCH-ARM / FISHERS |     P=0.460N     P=0.096      P=0.133      P=0.468     |P=0.027 *    P=0.306N     P=0.039 *    P=0.169      | 
|ORDER RESTRICTED   |     P=0.252      (e)          (e)          (e)         |P=0.052      (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                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/50 (28%)  5/50 (10%)   10/49 (20%)  11/48 (23%) |5/46 (11%)   2/50 (4%)    3/49 (6%)    5/47 (11%)   | 
|POLY-3 RATE (b)    |     14/44.13     5/46.10      10/45.58     11/46.30    |5/41.57      2/45.81      3/46.66      5/44.84      | 
|POLY-3 PERCENT (g) |     31.7%        10.9%        21.9%        23.8%       |12.0%        4.4%         6.4%         11.2%        | 
|TERMINAL (d)       |     13/35 (37%)  5/38 (13%)   10/38 (26%)  10/41 (24%) |5/32 (16%)   2/40 (5%)    3/42 (7%)    5/41 (12%)   | 
|FIRST INCIDENCE    |     723          729 (T)      729 (T)      694         |729 (T)      729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.495N     P=0.011N*    P=0.167N     P=0.177N    |P=0.483      P=0.135N     P=0.217N     P=0.468N     | 
|POLY 3             |     P=0.473      P=0.013N*    P=0.209N     P=0.270N    |P=0.400      P=0.178N     P=0.295N     P=0.582N     | 
|POLY 1.5           |     P=0.452      P=0.016N*    P=0.232N     P=0.309N    |P=0.392      P=0.182N     P=0.306N     P=0.595N     | 
|POLY 6             |     P=0.502      P=0.010N*    P=0.183N     P=0.225N    |P=0.413      P=0.171N     P=0.276N     P=0.560N     | 
|LOGISTIC REGRESSION|     P=0.521N     P=0.010N*    P=0.171N     P=0.188N    |P=0.483      P=0.135N     P=0.217N     P=0.468N     | 
|COCH-ARM / FISHERS |     P=0.408      P=0.020N*    P=0.259N     P=0.365N    |P=0.372      P=0.185N     P=0.322N     P=0.616N     | 
|ORDER RESTRICTED   |     P=0.104N     (e)          (e)          (e)         |P=0.346N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 33      
Statistical Analysis of Non-neoplastic Lesions 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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Tissue NOS: Abdominal                                                                                                            | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/1 (0%)     2/2 (100%)   0/0 (0%)     0/1 (0%)    |0/3 (0%)     0/0 (0%)     0/0 (0%)     0/3 (0%)     | 
|POLY-3 RATE (b)    |     0/0.98       2/2.00       0/0.00       0/0.59      |0/2.39       0/0.00       0/0.00       0/1.47       | 
|POLY-3 PERCENT (g) |     0.0%         100.0%       0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/0 (0%)     1/1 (100%)   0/0 (0%)     0/0 (0%)    |0/1 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          717          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.439N     P=0.516      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          P=0.333      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          P=0.333      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          P=0.333      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.333      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.356N     P=0.333      (e)          (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (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        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Tooth                                                                                                                            | 
|     Dysplasia                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     43/43 (100%) 37/37 (100%) 33/33 (100%) 35/35 (100%)|2/2 (100%)   10/10 (100%) 3/3 (100%)   3/3 (100%)   | 
|POLY-3 RATE (b)    |     43/43.00     37/37.00     33/33.00     35/35.00    |2/2.00       10/10.00     3/3.00       3/3.00       | 
|POLY-3 PERCENT (g) |     100.0%       100.0%       100.0%       100.0%      |100.0%       100.0%       100.0%       100.0%       | 
|TERMINAL (d)       |     34/34 (100%) 33/33 (100%) 27/27 (100%) 29/29 (100%)|2/2 (100%)   9/9 (100%)   3/3 (100%)   2/2 (100%)   | 
|FIRST INCIDENCE    |     530          638          605          610         |729 (T)      673          729 (T)      680          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/26/05                           EXPERIMENT: 91005 TEST: 08                                            Page 34      
Statistical Analysis of Non-neoplastic Lesions 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: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |48/50 (96%)  45/50 (90%)  49/50 (98%)  48/50 (96%)  | 
|POLY-3 RATE (b)    |                                                        |48/48.45     45/48.39     49/49.06     48/48.50     | 
|POLY-3 PERCENT (g) |                                                        |99.1%        93.0%        99.9%        99.0%        | 
|TERMINAL (d)       |                                                        |33/33 (100%) 37/40 (93%)  42/42 (100%) 43/43 (100%) | 
|FIRST INCIDENCE    |                                                        |568          521          568          528          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.049N*    P=0.031N*    P=0.034N*    P=0.011N*    | 
|POLY 3             |                                                        |P=0.185      P=0.138N     P=0.918      P=0.954N     | 
|POLY 1.5           |                                                        |P=0.256      P=0.168N     P=0.737      P=0.790N     | 
|POLY 6             |                                                        |P=0.150      P=0.125N     P=1.000      P=1.000      | 
|LOGISTIC REGRESSION|                                                        |P=0.280      P=0.172N     (e)          P=0.486      | 
|COCH-ARM / FISHERS |                                                        |P=0.268      P=0.218N     P=0.500      P=0.691N     | 
|ORDER RESTRICTED   |                                                        |P=0.156      (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.