National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/20992

TDMS Study 91005-07 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                             METHYLENE BLUE TRIHYDRATE                              DATE: 03/25/05       
EXPERIMENT: 91005 TEST: 07                                                                                     TIME: 10:12:59       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-05451                              ROUTE: GAVAGE                                                  NTP C#: 91005C       
PATHOLOGIST: HERSCHELL, GILES                                                                                  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: 03/25/05       
EXPERIMENT: 91005 TEST: 07                                                                                     TIME: 10:12:59       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-05451                              ROUTE: GAVAGE                                                  NTP C#: 91005C       
PATHOLOGIST: HERSCHELL, GILES                                                                                  CAS: 7220-79-3       
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                METHYLENE BLUE TRIHYDRATE                                                                         
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Medulla                        Hyperplasia                                                                                  
Esophagus                              Perforation                                                                                  
Heart                                  Cardiomyopathy                                                                               
Islets, Pancreatic                     Hyperplasia                                                                                  
Kidney                                 Infarct                                                                                      
Liver                                  Hepatodiaphragmatic Nodule                                                                   
Liver: Bile Duct                       Hyperplasia                                                                                  
Lymph Node: Mediastinal                Hyperplasia Lymphoid                                                                         
Mesentery: Fat                         Necrosis                                                                                     
Nose                                   Inflammation Chronic                                                                         
Oral Mucosa: Pharyngeal                Cyst                                                                                         
                                       Inflammation                                                                                 
Pancreas                               Atrophy                                                                                      
Pancreas: Acinus                       Hyperplasia Focal                                                                            
Pituitary Gland: Pars Distalis         Angiectasis                                                                                  
Preputial Gland                        Cyst                                                                                         
Skin                                   Inflammation Chronic                                                                         
Spleen                                 Hematopoietic Cell Proliferation                                                             
                                       Hemorrhage                                                                                   
                                       Necrosis                                                                                     
Spleen: Capsule                        Fibrosis                                                                                     
Stomach, Forestomach                   Edema                                                                                        
                                       Erosion                                                                                      
Thyroid Gland: C-Cell                  Hyperplasia                                                                                  
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Islets, Pancreatic                     Metaplasia Hepatocyte                                                                        
Liver                                  Basophilic Focus                                                                             
                                       Eosinophilic Focus                                                                           
Liver: Hepatocyte                      Vacuolization Cytoplasmic                                                                    
Lymph Node: Mediastinal                Hyperplasia Lymphoid                                                                         
Mammary Gland                          Hyperplasia                                                                                  
                                       Hyperplasia Atypical                                                                         
Mesentery: Fat                         Necrosis                                                                                     
Ovary                                  Cyst                                                                                         
Spleen                                 Fibrosis                                                                                     
Spleen: Capsule                        Fibrosis                                                                                     
Stomach, Glandular                     Erosion                                                                                      
===============================================================                                                                     
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE             
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Accessory Adrenal Cortical Nodule                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     23/50 (46%)  23/50 (46%)  28/50 (56%)  25/50 (50%) |9/50 (18%)   7/49 (14%)   8/50 (16%)   12/50 (24%)  | 
|POLY-3 RATE (b)    |     23/44.67     23/45.27     28/48.30     25/43.85    |9/45.33      7/44.04      8/44.21      12/43.60     | 
|POLY-3 PERCENT (g) |     51.5%        50.8%        58.0%        57.0%       |19.9%        15.9%        18.1%        27.5%        | 
|TERMINAL (d)       |     20/31 (65%)  17/33 (52%)  24/39 (62%)  18/31 (58%) |7/35 (20%)   5/32 (16%)   7/36 (19%)   9/35 (26%)   | 
|FIRST INCIDENCE    |     641          561          489          465         |638          702          723          223          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.307      P=0.466N     P=0.546N     P=0.416     |P=0.192      P=0.457N     P=0.486N     P=0.299      | 
|POLY 3             |     P=0.262      P=0.559N     P=0.335      P=0.376     |P=0.149      P=0.416N     P=0.523N     P=0.274      | 
|POLY 1.5           |     P=0.262      P=0.571N     P=0.278      P=0.377     |P=0.152      P=0.412N     P=0.512N     P=0.278      | 
|POLY 6             |     P=0.282      P=0.528N     P=0.423      P=0.401     |P=0.156      P=0.425N     P=0.534N     P=0.282      | 
|LOGISTIC REGRESSION|     P=0.226      P=0.535N     P=0.373      P=0.327     |P=0.155      P=0.412N     P=0.511N     P=0.331      | 
|COCH-ARM / FISHERS |     P=0.301      P=0.579N     P=0.212      P=0.421     |P=0.176      P=0.410N     P=0.500N     P=0.312      | 
|ORDER RESTRICTED   |     P=0.430      (e)          (e)          (e)         |P=0.202      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Degeneration Fatty                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   6/50 (12%)   7/50 (14%)   2/50 (4%)   |11/50 (22%)  13/49 (27%)  13/50 (26%)  8/50 (16%)   | 
|POLY-3 RATE (b)    |     7/44.39      6/44.50      7/47.25      2/41.96     |11/45.00     13/43.83     13/44.64     8/41.13      | 
|POLY-3 PERCENT (g) |     15.8%        13.5%        14.8%        4.8%        |24.5%        29.7%        29.1%        19.5%        | 
|TERMINAL (d)       |     6/31 (19%)   5/33 (15%)   4/39 (10%)   2/31 (7%)   |10/35 (29%)  13/32 (41%)  12/36 (33%)  7/35 (20%)   | 
|FIRST INCIDENCE    |     544          652          690          729 (T)     |652          729 (T)      596          725          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.074N     P=0.457N     P=0.442N     P=0.083N    |P=0.160N     P=0.305      P=0.428      P=0.305N     | 
|POLY 3             |     P=0.094N     P=0.498N     P=0.565N     P=0.092N    |P=0.270N     P=0.376      P=0.397      P=0.383N     | 
|POLY 1.5           |     P=0.091N     P=0.501N     P=0.587N     P=0.089N    |P=0.257N     P=0.383      P=0.402      P=0.369N     | 
|POLY 6             |     P=0.093N     P=0.487N     P=0.528N     P=0.091N    |P=0.257N     P=0.363      P=0.395      P=0.376N     | 
|LOGISTIC REGRESSION|     P=0.084N     P=0.490N     P=0.570N     P=0.090N    |P=0.206N     P=0.354      P=0.393      P=0.331N     | 
|COCH-ARM / FISHERS |     P=0.080N     P=0.500N     P=0.613N     P=0.080N    |P=0.193N     P=0.385      P=0.408      P=0.306N     | 
|ORDER RESTRICTED   |     P=0.095N     (e)          (e)          (e)         |P=0.303N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   5/50 (10%)   5/50 (10%)   5/50 (10%)  |5/50 (10%)   8/49 (16%)   8/50 (16%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |     6/44.06      5/44.50      5/47.41      5/42.38     |5/44.71      8/44.01      8/45.04      6/42.67      | 
|POLY-3 PERCENT (g) |     13.6%        11.2%        10.6%        11.8%       |11.2%        18.2%        17.8%        14.1%        | 
|TERMINAL (d)       |     5/31 (16%)   4/33 (12%)   3/39 (8%)    3/31 (10%)  |5/35 (14%)   6/32 (19%)   6/36 (17%)   4/35 (11%)   | 
|FIRST INCIDENCE    |     662          652          619          626         |729 (T)      702          492          284          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.463N     P=0.458N     P=0.360N     P=0.504N    |P=0.526N     P=0.225      P=0.296      P=0.490      | 
|POLY 3             |     P=0.482N     P=0.493N     P=0.449N     P=0.527N    |P=0.516      P=0.264      P=0.279      P=0.467      | 
|POLY 1.5           |     P=0.482N     P=0.497N     P=0.472N     P=0.523N    |P=0.517      P=0.265      P=0.279      P=0.469      | 
|POLY 6             |     P=0.475N     P=0.482N     P=0.415N     P=0.523N    |P=0.536      P=0.262      P=0.283      P=0.481      | 
|LOGISTIC REGRESSION|     P=0.488N     P=0.480N     P=0.454N     P=0.527N    |P=0.536      P=0.244      P=0.269      P=0.515      | 
|COCH-ARM / FISHERS |     P=0.465N     P=0.500N     P=0.500N     P=0.500N    |P=0.544N     P=0.264      P=0.277      P=0.500      | 
|ORDER RESTRICTED   |     P=0.568N     (e)          (e)          (e)         |P=0.379      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   5/50 (10%)   9/50 (18%)   8/50 (16%)  |12/50 (24%)  11/49 (22%)  13/50 (26%)  7/50 (14%)   | 
|POLY-3 RATE (b)    |     6/44.46      5/44.68      9/47.95      8/42.74     |12/45.00     11/43.83     13/44.64     7/41.13      | 
|POLY-3 PERCENT (g) |     13.5%        11.2%        18.8%        18.7%       |26.7%        25.1%        29.1%        17.0%        | 
|TERMINAL (d)       |     3/31 (10%)   3/33 (9%)    5/39 (13%)   6/31 (19%)  |11/35 (31%)  11/32 (34%)  12/36 (33%)  6/35 (17%)   | 
|FIRST INCIDENCE    |     645          652          489          530         |652          729 (T)      596          725          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.214      P=0.463N     P=0.449      P=0.381     |P=0.119N     P=0.598      P=0.524      P=0.153N     | 
|POLY 3             |     P=0.187      P=0.497N     P=0.344      P=0.355     |P=0.209N     P=0.529N     P=0.491      P=0.206N     | 
|POLY 1.5           |     P=0.192      P=0.499N     P=0.320      P=0.362     |P=0.199N     P=0.524N     P=0.495      P=0.196N     | 
|POLY 6             |     P=0.188      P=0.488N     P=0.378      P=0.355     |P=0.197N     P=0.541N     P=0.490      P=0.200N     | 
|LOGISTIC REGRESSION|     P=0.200      P=0.497N     P=0.261      P=0.361     |P=0.156N     P=0.548N     P=0.488      P=0.167N     | 
|COCH-ARM / FISHERS |     P=0.211      P=0.500N     P=0.288      P=0.387     |P=0.146N     P=0.522N     P=0.500      P=0.154N     | 
|ORDER RESTRICTED   |     P=0.330      (e)          (e)          (e)         |P=0.225N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |2/50 (4%)    1/49 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/44.19      0/44.21      0/46.96      1/41.96     |2/45.37      1/44.31      0/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     2.3%         0.0%         0.0%         2.4%        |4.4%         2.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    1/31 (3%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     620          ---          ---          729 (T)     |563          585          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.533      P=0.509N     P=0.491N     P=0.752     |P=0.117N     P=0.506N     P=0.244N     P=0.260N     | 
|POLY 3             |     P=0.529      P=0.500N     P=0.488N     P=0.749     |P=0.107N     P=0.508N     P=0.243N     P=0.260N     | 
|POLY 1.5           |     P=0.530      P=0.500N     P=0.493N     P=0.752     |P=0.106N     P=0.507N     P=0.240N     P=0.255N     | 
|POLY 6             |     P=0.528      P=0.498N     P=0.480N     P=0.749     |P=0.107N     P=0.511N     P=0.245N     P=0.259N     | 
|LOGISTIC REGRESSION|     P=0.551      P=0.496N     P=0.579N     P=0.760N    |P=0.055N     P=0.535N     P=0.243N     P=0.194N     | 
|COCH-ARM / FISHERS |     P=0.536      P=0.500N     P=0.500N     P=0.753N    |P=0.104N     P=0.508N     P=0.247N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.380      (e)          (e)          (e)         |P=0.089N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   12/50 (24%)  8/50 (16%)   2/50 (4%)   |1/50 (2%)    2/49 (4%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     7/44.47      12/44.46     8/46.97      2/42.07     |1/44.71      2/43.83      1/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     15.7%        27.0%        17.0%        4.8%        |2.2%         4.6%         2.3%         0.0%         | 
|TERMINAL (d)       |     4/31 (13%)   10/33 (30%)  7/39 (18%)   1/31 (3%)   |1/35 (3%)    2/32 (6%)    1/36 (3%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     645          673          726          703         |729 (T)      729 (T)      729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.015N*    P=0.201      P=0.543N     P=0.087N    |P=0.192N     P=0.469      P=0.756N     P=0.500N     | 
|POLY 3             |     P=0.020N*    P=0.148      P=0.546      P=0.092N    |P=0.217N     P=0.493      P=0.758      P=0.517N     | 
|POLY 1.5           |     P=0.019N*    P=0.150      P=0.526      P=0.089N    |P=0.215N     P=0.494      P=0.759      P=0.514N     | 
|POLY 6             |     P=0.019N*    P=0.150      P=0.574      P=0.092N    |P=0.215N     P=0.491      P=0.758      P=0.515N     | 
|LOGISTIC REGRESSION|     P=0.016N*    P=0.166      P=0.592      P=0.090N    |P=0.192N     P=0.469      P=0.756N     (e)          | 
|COCH-ARM / FISHERS |     P=0.017N*    P=0.154      P=0.500      P=0.080N    |P=0.200N     P=0.492      P=0.753N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.024N*    (e)          (e)          (e)         |P=0.239N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   7/50 (14%)   4/50 (8%)    9/50 (18%)  |8/50 (16%)   8/49 (16%)   9/50 (18%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |     7/44.84      7/45.97      4/48.38      9/43.64     |8/47.40      8/45.23      9/46.82      6/43.82      | 
|POLY-3 PERCENT (g) |     15.6%        15.2%        8.3%         20.6%       |16.9%        17.7%        19.2%        13.7%        | 
|TERMINAL (d)       |     3/31 (10%)   2/33 (6%)    1/39 (3%)    3/31 (10%)  |2/35 (6%)    4/32 (13%)   3/36 (8%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     563          568          489          563         |344          395          492          284          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.359      P=0.573N     P=0.194N     P=0.391     |P=0.371N     P=0.562      P=0.499      P=0.441N     | 
|POLY 3             |     P=0.354      P=0.594N     P=0.219N     P=0.369     |P=0.388N     P=0.568      P=0.489      P=0.448N     | 
|POLY 1.5           |     P=0.353      P=0.604N     P=0.237N     P=0.370     |P=0.381N     P=0.577      P=0.492      P=0.438N     | 
|POLY 6             |     P=0.365      P=0.576N     P=0.196N     P=0.382     |P=0.375N     P=0.554      P=0.492      P=0.443N     | 
|LOGISTIC REGRESSION|     P=0.454      P=0.614N     P=0.392N     P=0.397     |P=0.100N     P=0.581      P=0.605      P=0.169N     | 
|COCH-ARM / FISHERS |     P=0.366      P=0.613N     P=0.262N     P=0.393     |P=0.328N     P=0.590      P=0.500      P=0.387N     | 
|ORDER RESTRICTED   |     P=0.250      (e)          (e)          (e)         |P=0.467N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Compression                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   10/50 (20%)  9/50 (18%)   6/50 (12%)  |3/50 (6%)    8/49 (16%)   6/50 (12%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     7/44.90      10/47.03     9/48.07      6/43.85     |3/45.12      8/44.68      6/44.75      5/41.31      | 
|POLY-3 PERCENT (g) |     15.6%        21.3%        18.7%        13.7%       |6.7%         17.9%        13.4%        12.1%        | 
|TERMINAL (d)       |     2/31 (7%)    4/33 (12%)   4/39 (10%)   1/31 (3%)   |1/35 (3%)    4/32 (13%)   4/36 (11%)   4/35 (11%)   | 
|FIRST INCIDENCE    |     641          473          586          504         |652          628          593          677          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.326N     P=0.338      P=0.547      P=0.517N    |P=0.547N     P=0.096      P=0.255      P=0.356      | 
|POLY 3             |     P=0.329N     P=0.333      P=0.451      P=0.518N    |P=0.488      P=0.094      P=0.237      P=0.309      | 
|POLY 1.5           |     P=0.326N     P=0.318      P=0.425      P=0.517N    |P=0.502      P=0.094      P=0.240      P=0.317      | 
|POLY 6             |     P=0.326N     P=0.355      P=0.487      P=0.513N    |P=0.493      P=0.094      P=0.236      P=0.312      | 
|LOGISTIC REGRESSION|     P=0.220N     P=0.295      P=0.338      P=0.450N    |P=0.515      P=0.094      P=0.241      P=0.315      | 
|COCH-ARM / FISHERS |     P=0.303N     P=0.298      P=0.393      P=0.500N    |P=0.549N     P=0.094      P=0.243      P=0.357      | 
|ORDER RESTRICTED   |     P=0.437N     (e)          (e)          (e)         |P=0.214      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    1/49 (2%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/44.06      2/44.94      0/46.96      0/41.96     |1/45.01      1/44.12      1/44.78      0/41.11      | 
|POLY-3 PERCENT (g) |     2.3%         4.5%         0.0%         0.0%        |2.2%         2.3%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    1/33 (3%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     662          473          ---          ---         |648          648          540          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.134N     P=0.512      P=0.476N     P=0.511N    |P=0.328N     P=0.746      P=0.750      P=0.524N     | 
|POLY 3             |     P=0.131N     P=0.507      P=0.487N     P=0.510N    |P=0.320N     P=0.756      P=0.760      P=0.518N     | 
|POLY 1.5           |     P=0.133N     P=0.504      P=0.493N     P=0.508N    |P=0.317N     P=0.756      P=0.760      P=0.515N     | 
|POLY 6             |     P=0.128N     P=0.513      P=0.479N     P=0.510N    |P=0.318N     P=0.755      P=0.760      P=0.517N     | 
|LOGISTIC REGRESSION|     P=0.084N     P=0.510      P=0.542N     P=0.487N    |P=0.197N     P=0.751      P=0.745      P=0.480N     | 
|COCH-ARM / FISHERS |     P=0.134N     P=0.500      P=0.500N     P=0.500N    |P=0.300N     P=0.747      P=0.753N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.181N     (e)          (e)          (e)         |P=0.342N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |4/50 (8%)    7/48 (15%)   4/50 (8%)    6/50 (12%)   | 
|POLY-3 RATE (b)    |                                                        |4/44.71      7/44.91      4/44.74      6/41.73      | 
|POLY-3 PERCENT (g) |                                                        |9.0%         15.6%        8.9%         14.4%        | 
|TERMINAL (d)       |                                                        |4/35 (11%)   3/32 (9%)    3/36 (8%)    5/35 (14%)   | 
|FIRST INCIDENCE    |                                                        |729 (T)      395          557          527          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.492      P=0.234      P=0.631N     P=0.362      | 
|POLY 3             |                                                        |P=0.445      P=0.263      P=0.643N     P=0.326      | 
|POLY 1.5           |                                                        |P=0.454      P=0.254      P=0.643N     P=0.331      | 
|POLY 6             |                                                        |P=0.453      P=0.273      P=0.641N     P=0.336      | 
|LOGISTIC REGRESSION|                                                        |P=0.517      P=0.228      P=0.639      P=0.323      | 
|COCH-ARM / FISHERS |                                                        |P=0.503      P=0.239      P=0.643N     P=0.370      | 
|ORDER RESTRICTED   |                                                        |P=0.352      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/50 (2%)    5/48 (10%)   2/50 (4%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |                                                        |1/44.71      5/43.14      2/44.88      4/41.11      | 
|POLY-3 PERCENT (g) |                                                        |2.2%         11.6%        4.5%         9.7%         | 
|TERMINAL (d)       |                                                        |1/35 (3%)    5/32 (16%)   1/36 (3%)    4/35 (11%)   | 
|FIRST INCIDENCE    |                                                        |729 (T)      729 (T)      492          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.385      P=0.082      P=0.509      P=0.178      | 
|POLY 3             |                                                        |P=0.337      P=0.093      P=0.501      P=0.154      | 
|POLY 1.5           |                                                        |P=0.343      P=0.093      P=0.501      P=0.158      | 
|POLY 6             |                                                        |P=0.342      P=0.092      P=0.503      P=0.156      | 
|LOGISTIC REGRESSION|                                                        |P=0.336      P=0.082      P=0.496      P=0.178      | 
|COCH-ARM / FISHERS |                                                        |P=0.377      P=0.093      P=0.500      P=0.181      | 
|ORDER RESTRICTED   |                                                        |P=0.135      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Esophagus                                                                                                                        | 
|     Perforation                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/49 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      0/46.96      2/43.61     |0/44.71      0/43.83      1/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.6%        |0.0%         0.0%         2.3%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    1/36 (3%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          191         |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.042 *    (e)          (e)          P=0.233     |P=0.655      (e)          P=0.506      (e)          | 
|POLY 3             |     P=0.043 *    (e)          (e)          P=0.236     |P=0.609      (e)          P=0.498      (e)          | 
|POLY 1.5           |     P=0.042 *    (e)          (e)          P=0.236     |P=0.615      (e)          P=0.499      (e)          | 
|POLY 6             |     P=0.043 *    (e)          (e)          P=0.239     |P=0.615      (e)          P=0.497      (e)          | 
|LOGISTIC REGRESSION|     P=0.329      (e)          (e)          P=0.666     |(e)          (e)          P=0.506      (e)          | 
|COCH-ARM / FISHERS |     P=0.043 *    (e)          (e)          P=0.247     |P=0.650      (e)          P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.029 *    (e)          (e)          (e)         |P=0.379      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye                                                                                                                              | 
|     Cataract                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/49 (6%)    4/48 (8%)    3/48 (6%)   |1/50 (2%)    2/49 (4%)    5/50 (10%)   3/50 (6%)    | 
|POLY-3 RATE (b)    |     1/44.20      3/43.78      4/46.38      3/41.08     |1/44.71      2/43.83      5/44.68      3/41.11      | 
|POLY-3 PERCENT (g) |     2.3%         6.9%         8.6%         7.3%        |2.2%         4.6%         11.2%        7.3%         | 
|TERMINAL (d)       |     0/31 (0%)    2/33 (6%)    3/39 (8%)    3/31 (10%)  |1/35 (3%)    2/32 (6%)    2/36 (6%)    3/35 (9%)    | 
|FIRST INCIDENCE    |     616          723          619          729 (T)     |729 (T)      729 (T)      646          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.301      P=0.321      P=0.237      P=0.298     |P=0.219      P=0.469      P=0.113      P=0.305      | 
|POLY 3             |     P=0.270      P=0.302      P=0.194      P=0.279     |P=0.165      P=0.493      P=0.101      P=0.276      | 
|POLY 1.5           |     P=0.272      P=0.300      P=0.182      P=0.281     |P=0.171      P=0.494      P=0.101      P=0.281      | 
|POLY 6             |     P=0.275      P=0.307      P=0.211      P=0.281     |P=0.170      P=0.491      P=0.102      P=0.279      | 
|LOGISTIC REGRESSION|     P=0.278      P=0.299      P=0.104      P=0.284     |P=0.179      P=0.469      P=0.101      P=0.305      | 
|COCH-ARM / FISHERS |     P=0.287      P=0.301      P=0.168      P=0.293     |P=0.208      P=0.492      P=0.102      P=0.309      | 
|ORDER RESTRICTED   |     P=0.223      (e)          (e)          (e)         |P=0.140      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye                                                                                                                              | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/49 (0%)    1/48 (2%)    1/48 (2%)   |0/50 (0%)    2/49 (4%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/43.81      0/43.76      1/45.99      1/41.13     |0/44.71      2/44.33      0/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     2.3%         0.0%         2.2%         2.4%        |0.0%         4.5%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    1/39 (3%)    0/31 (0%)   |0/35 (0%)    1/32 (3%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      715         |---          576          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.474      P=0.488N     P=0.710N     P=0.753N    |P=0.275N     P=0.230      (e)          (e)          | 
|POLY 3             |     P=0.448      P=0.500N     P=0.750N     P=0.747     |P=0.265N     P=0.235      (e)          (e)          | 
|POLY 1.5           |     P=0.450      P=0.502N     P=0.758N     P=0.746     |P=0.264N     P=0.235      (e)          (e)          | 
|POLY 6             |     P=0.449      P=0.496N     P=0.737N     P=0.751     |P=0.264N     P=0.235      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.466      (e)          P=0.710N     P=0.759     |P=0.226N     P=0.224      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.461      P=0.505N     P=0.742      P=0.742     |P=0.262N     P=0.242      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.515      (e)          (e)          (e)         |P=0.262N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Cornea                                                                                                                      | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    0/48 (0%)    0/48 (0%)   |1/50 (2%)    0/49 (0%)    1/50 (2%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/43.76      0/45.99      0/41.08     |1/45.25      0/43.83      1/44.49      2/41.11      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.2%         0.0%         2.3%         4.9%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |563          ---          646          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.194      P=0.500N     P=0.745      P=0.482      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.185      P=0.506N     P=0.757      P=0.467      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.188      P=0.505N     P=0.758      P=0.473      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.187      P=0.509N     P=0.756      P=0.468      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.223      P=0.541N     P=0.749      P=0.504      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.205      P=0.505N     P=0.753N     P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.196      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Retina                                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/49 (4%)    4/48 (8%)    3/48 (6%)   |2/50 (4%)    2/49 (4%)    4/50 (8%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/44.20      2/43.78      4/46.38      3/41.08     |2/45.25      2/43.83      4/44.37      2/41.11      | 
|POLY-3 PERCENT (g) |     2.3%         4.6%         8.6%         7.3%        |4.4%         4.6%         9.0%         4.9%         | 
|TERMINAL (d)       |     0/31 (0%)    1/33 (3%)    3/39 (8%)    3/31 (10%)  |1/35 (3%)    2/32 (6%)    2/36 (6%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     616          723          619          729 (T)     |563          729 (T)      687          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.212      P=0.510      P=0.237      P=0.298     |P=0.529      P=0.669      P=0.350      P=0.679      | 
|POLY 3             |     P=0.188      P=0.497      P=0.194      P=0.279     |P=0.460      P=0.683      P=0.328      P=0.659      | 
|POLY 1.5           |     P=0.190      P=0.495      P=0.182      P=0.281     |P=0.471      P=0.685      P=0.332      P=0.666      | 
|POLY 6             |     P=0.191      P=0.502      P=0.211      P=0.281     |P=0.466      P=0.679      P=0.326      P=0.661      | 
|LOGISTIC REGRESSION|     P=0.196      P=0.491      P=0.104      P=0.284     |P=0.485      P=0.687      P=0.337      P=0.686      | 
|COCH-ARM / FISHERS |     P=0.203      P=0.492      P=0.168      P=0.293     |P=0.521      P=0.684      P=0.339      P=0.691N     | 
|ORDER RESTRICTED   |     P=0.205      (e)          (e)          (e)         |P=0.479      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    1/50 (2%)    4/50 (8%)   |3/50 (6%)    3/49 (6%)    3/50 (6%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     2/44.12      3/44.21      1/46.96      4/42.50     |3/45.32      3/44.53      3/44.64      4/42.19      | 
|POLY-3 PERCENT (g) |     4.5%         6.8%         2.1%         9.4%        |6.6%         6.7%         6.7%         9.5%         | 
|TERMINAL (d)       |     1/31 (3%)    3/33 (9%)    1/39 (3%)    3/31 (10%)  |1/35 (3%)    1/32 (3%)    2/36 (6%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     642          729 (T)      729 (T)      563         |640          576          596          480          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.319      P=0.523      P=0.439N     P=0.327     |P=0.389      P=0.642      P=0.648      P=0.481      | 
|POLY 3             |     P=0.319      P=0.501      P=0.478N     P=0.320     |P=0.364      P=0.654      P=0.655      P=0.461      | 
|POLY 1.5           |     P=0.319      P=0.500      P=0.488N     P=0.323     |P=0.370      P=0.654      P=0.659      P=0.466      | 
|POLY 6             |     P=0.325      P=0.505      P=0.464N     P=0.321     |P=0.372      P=0.653      P=0.653      P=0.468      | 
|LOGISTIC REGRESSION|     P=0.312      P=0.508      P=0.504N     P=0.332     |P=0.469      P=0.646      P=0.661N     P=0.537      | 
|COCH-ARM / FISHERS |     P=0.325      P=0.500      P=0.500N     P=0.339     |P=0.405      P=0.651      P=0.661N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.255      (e)          (e)          (e)         |P=0.483      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    1/50 (2%)    3/50 (6%)   |2/50 (4%)    2/49 (4%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     2/44.33      1/44.70      1/47.03      3/43.66     |2/45.30      2/44.61      1/44.88      1/42.08      | 
|POLY-3 PERCENT (g) |     4.5%         2.2%         2.1%         6.9%        |4.4%         4.5%         2.2%         2.4%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     641          582          710          504         |591          585          492          239          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.281      P=0.507N     P=0.444N     P=0.475     |P=0.351N     P=0.677      P=0.502N     P=0.527N     | 
|POLY 3             |     P=0.294      P=0.497N     P=0.479N     P=0.493     |P=0.334N     P=0.688      P=0.503N     P=0.526N     | 
|POLY 1.5           |     P=0.293      P=0.499N     P=0.488N     P=0.492     |P=0.330N     P=0.688      P=0.501N     P=0.521N     | 
|POLY 6             |     P=0.298      P=0.493N     P=0.466N     P=0.499     |P=0.333N     P=0.688      P=0.505N     P=0.524N     | 
|LOGISTIC REGRESSION|     P=0.472      P=0.493N     P=0.552N     P=0.653     |P=0.067N     P=0.672      P=0.533N     P=0.259N     | 
|COCH-ARM / FISHERS |     P=0.295      P=0.500N     P=0.500N     P=0.500     |P=0.315N     P=0.684      P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.276      (e)          (e)          (e)         |P=0.461N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     47/50 (94%)  46/50 (92%)  47/50 (94%)  45/50 (90%) |36/50 (72%)  41/49 (84%)  36/50 (72%)  32/50 (64%)  | 
|POLY-3 RATE (b)    |     47/48.34     46/49.93     47/49.22     45/47.98    |36/48.22     41/46.72     36/46.58     32/41.90     | 
|POLY-3 PERCENT (g) |     97.2%        92.1%        95.5%        93.8%       |74.7%        87.8%        77.3%        76.4%        | 
|TERMINAL (d)       |     31/31 (100%) 30/33 (91%)  38/39 (97%)  29/31 (94%) |27/35 (77%)  31/32 (97%)  29/36 (81%)  30/35 (86%)  | 
|FIRST INCIDENCE    |     563          473          489          191         |344          576          540          544          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.422N     P=0.350N     P=0.045N*    P=0.469N    |P=0.058N     P=0.093      P=0.538N     P=0.291N     | 
|POLY 3             |     P=0.478N     P=0.236N     P=0.537N     P=0.354N    |P=0.334N     P=0.074      P=0.476      P=0.523      | 
|POLY 1.5           |     P=0.421N     P=0.337N     P=0.589N     P=0.363N    |P=0.225N     P=0.090      P=0.521      P=0.552N     | 
|POLY 6             |     P=0.524N     P=0.145N     P=0.492N     P=0.320N    |P=0.415N     P=0.058      P=0.432      P=0.449      | 
|LOGISTIC REGRESSION|     P=0.502N     P=0.506N     P=0.422N     P=0.587N    |P=0.220N     P=0.124      P=0.569      P=0.514N     | 
|COCH-ARM / FISHERS |     P=0.329N     P=0.500N     P=0.661N     P=0.357N    |P=0.059N     P=0.124      P=0.588N     P=0.260N     | 
|ORDER RESTRICTED   |     P=0.332N     (e)          (e)          (e)         |P=0.372      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     13/50 (26%)  13/50 (26%)  17/50 (34%)  26/50 (52%) |13/49 (27%)  15/48 (31%)  15/48 (31%)  15/49 (31%)  | 
|POLY-3 RATE (b)    |     13/45.38     13/45.80     17/47.66     26/44.35    |13/44.97     15/44.52     15/44.11     15/42.20     | 
|POLY-3 PERCENT (g) |     28.7%        28.4%        35.7%        58.6%       |28.9%        33.7%        34.0%        35.6%        | 
|TERMINAL (d)       |     8/31 (26%)   8/33 (24%)   14/39 (36%)  19/31 (61%) |11/35 (31%)  11/32 (34%)  12/36 (33%)  11/35 (31%)  | 
|FIRST INCIDENCE    |     586          561          586          401         |638          576          593          284          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.002 **   P=0.537N     P=0.499      P=0.010 *   |P=0.445      P=0.326      P=0.430      P=0.401      | 
|POLY 3             |     P<0.001 **   P=0.581N     P=0.307      P=0.003 **  |P=0.328      P=0.397      P=0.386      P=0.332      | 
|POLY 1.5           |     P<0.001 **   P=0.586N     P=0.285      P=0.003 **  |P=0.342      P=0.393      P=0.387      P=0.343      | 
|POLY 6             |     P<0.001 **   P=0.567N     P=0.342      P=0.002 **  |P=0.343      P=0.403      P=0.392      P=0.348      | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.590N     P=0.294      P=0.004 **  |P=0.336      P=0.380      P=0.381      P=0.341      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.590N     P=0.257      P=0.007 **  |P=0.423      P=0.386      P=0.386      P=0.412      | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.405      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Metaplasia Hepatocyte                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |2/49 (4%)    0/48 (0%)    0/48 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      1/47.25      0/41.96     |2/44.36      0/43.14      0/43.32      0/40.27      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.1%         0.0%        |4.5%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |2/35 (6%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          649          ---         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.647      (e)          P=0.523      (e)         |P=0.155N     P=0.258N     P=0.232N     P=0.238N     | 
|POLY 3             |     P=0.617      (e)          P=0.515      (e)         |P=0.156N     P=0.243N     P=0.242N     P=0.259N     | 
|POLY 1.5           |     P=0.626      (e)          P=0.508      (e)         |P=0.157N     P=0.243N     P=0.242N     P=0.255N     | 
|POLY 6             |     P=0.611      (e)          P=0.525      (e)         |P=0.155N     P=0.244N     P=0.241N     P=0.257N     | 
|LOGISTIC REGRESSION|     P=0.678      (e)          P=0.446      (e)         |P=0.155N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.649      (e)          P=0.500      (e)         |P=0.160N     P=0.253N     P=0.253N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.394      (e)          (e)          (e)         |P=0.037N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Hydronephrosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/49 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/43.81      1/44.39      0/46.96      2/43.07     |0/44.71      0/43.83      0/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     0.0%         2.3%         0.0%         4.6%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          682          ---          465         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.164      P=0.511      (e)          P=0.232     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.169      P=0.503      (e)          P=0.233     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.167      P=0.501      (e)          P=0.233     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.173      P=0.507      (e)          P=0.237     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.279      P=0.500      (e)          P=0.343     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.168      P=0.500      (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.072      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Infarct                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/49 (0%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     2/44.06      0/44.21      0/46.96      0/41.96     |1/45.01      0/43.83      2/44.18      2/41.11      | 
|POLY-3 PERCENT (g) |     4.5%         0.0%         0.0%         0.0%        |2.2%         0.0%         4.5%         4.9%         | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    2/36 (6%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     662          ---          ---          ---         |648          ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.157N     P=0.230N     P=0.202N     P=0.246N    |P=0.199      P=0.514N     P=0.495      P=0.486      | 
|POLY 3             |     P=0.154N     P=0.236N     P=0.223N     P=0.248N    |P=0.170      P=0.505N     P=0.494      P=0.468      | 
|POLY 1.5           |     P=0.156N     P=0.237N     P=0.229N     P=0.246N    |P=0.175      P=0.504N     P=0.497      P=0.474      | 
|POLY 6             |     P=0.152N     P=0.234N     P=0.214N     P=0.248N    |P=0.173      P=0.507N     P=0.491      P=0.470      | 
|LOGISTIC REGRESSION|     P=0.160N     P=0.237N     P=0.243N     P=0.243N    |P=0.176      P=0.513N     P=0.498      P=0.478      | 
|COCH-ARM / FISHERS |     P=0.160N     P=0.247N     P=0.247N     P=0.247N    |P=0.197      P=0.505N     P=0.500      P=0.500      | 
|ORDER RESTRICTED   |     P=0.033N*    (e)          (e)          (e)         |P=0.241      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     35/50 (70%)  39/50 (78%)  33/50 (66%)  34/50 (68%) |14/50 (28%)  15/49 (31%)  21/50 (42%)  16/50 (32%)  | 
|POLY-3 RATE (b)    |     35/46.58     39/47.42     33/48.34     34/46.20    |14/45.97     15/44.89     21/45.27     16/41.11     | 
|POLY-3 PERCENT (g) |     75.1%        82.3%        68.3%        73.6%       |30.5%        33.4%        46.4%        38.9%        | 
|TERMINAL (d)       |     24/31 (77%)  28/33 (85%)  28/39 (72%)  22/31 (71%) |10/35 (29%)  10/32 (31%)  19/36 (53%)  16/35 (46%)  | 
|FIRST INCIDENCE    |     586          540          586          465         |591          628          521          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.284N     P=0.431      P=0.069N     P=0.522N    |P=0.340      P=0.419      P=0.118      P=0.398      | 
|POLY 3             |     P=0.245N     P=0.267      P=0.298N     P=0.527N    |P=0.162      P=0.469      P=0.085      P=0.272      | 
|POLY 1.5           |     P=0.262N     P=0.255      P=0.347N     P=0.539N    |P=0.195      P=0.473      P=0.093      P=0.306      | 
|POLY 6             |     P=0.216N     P=0.297      P=0.241N     P=0.495N    |P=0.148      P=0.461      P=0.075      P=0.258      | 
|LOGISTIC REGRESSION|     P=0.339N     P=0.233      P=0.237N     P=0.555     |P=0.205      P=0.475      P=0.094      P=0.312      | 
|COCH-ARM / FISHERS |     P=0.245N     P=0.247      P=0.415N     P=0.500N    |P=0.316      P=0.474      P=0.104      P=0.414      | 
|ORDER RESTRICTED   |     P=0.293N     (e)          (e)          (e)         |P=0.180      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   6/50 (12%)   8/50 (16%)   6/50 (12%)  |37/50 (74%)  34/49 (69%)  38/50 (76%)  40/50 (80%)  | 
|POLY-3 RATE (b)    |     5/43.81      6/44.25      8/46.96      6/41.96     |37/46.42     34/45.40     38/45.78     40/44.09     | 
|POLY-3 PERCENT (g) |     11.4%        13.6%        17.0%        14.3%       |79.7%        74.9%        83.0%        90.7%        | 
|TERMINAL (d)       |     5/31 (16%)   5/33 (15%)   8/39 (21%)   6/31 (19%)  |30/35 (86%)  28/32 (88%)  32/36 (89%)  33/35 (94%)  | 
|FIRST INCIDENCE    |     729 (T)      720          729 (T)      729 (T)     |640          576          560          480          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.427      P=0.550      P=0.437      P=0.500     |P=0.223      P=0.568N     P=0.563      P=0.298      | 
|POLY 3             |     P=0.389      P=0.507      P=0.322      P=0.470     |P=0.031 *    P=0.374N     P=0.440      P=0.101      | 
|POLY 1.5           |     P=0.395      P=0.503      P=0.301      P=0.476     |P=0.046 *    P=0.372N     P=0.474      P=0.125      | 
|POLY 6             |     P=0.391      P=0.519      P=0.354      P=0.472     |P=0.036 *    P=0.398N     P=0.398      P=0.124      | 
|LOGISTIC REGRESSION|     P=0.423      P=0.575      P=0.437      P=0.500     |P=0.008 **   P=0.374N     P=0.349      P=0.042 *    | 
|COCH-ARM / FISHERS |     P=0.425      P=0.500      P=0.277      P=0.500     |P=0.167      P=0.387N     P=0.500      P=0.318      | 
|ORDER RESTRICTED   |     P=0.452      (e)          (e)          (e)         |P=0.051      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Clear Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/50 (28%)  13/50 (26%)  16/50 (32%)  12/50 (24%) |8/50 (16%)   5/49 (10%)   9/50 (18%)   8/50 (16%)   | 
|POLY-3 RATE (b)    |     14/43.81     13/44.74     16/47.35     12/42.33    |8/45.00      5/43.83      9/45.22      8/41.11      | 
|POLY-3 PERCENT (g) |     32.0%        29.1%        33.8%        28.4%       |17.8%        11.4%        19.9%        19.5%        | 
|TERMINAL (d)       |     14/31 (45%)  12/33 (36%)  15/39 (39%)  11/31 (36%) |7/35 (20%)   5/32 (16%)   6/36 (17%)   8/35 (23%)   | 
|FIRST INCIDENCE    |     729 (T)      568          619          626         |652          729 (T)      557          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.411N     P=0.422N     P=0.466N     P=0.404N    |P=0.380      P=0.332N     P=0.513      P=0.605      | 
|POLY 3             |     P=0.471N     P=0.474N     P=0.515      P=0.448N    |P=0.285      P=0.292N     P=0.504      P=0.531      | 
|POLY 1.5           |     P=0.467N     P=0.488N     P=0.469      P=0.444N    |P=0.298      P=0.290N     P=0.503      P=0.545      | 
|POLY 6             |     P=0.458N     P=0.444N     P=0.585      P=0.433N    |P=0.294      P=0.297N     P=0.511      P=0.536      | 
|LOGISTIC REGRESSION|     P=0.450N     P=0.425N     P=0.506N     P=0.407N    |P=0.296      P=0.296N     P=0.492      P=0.574      | 
|COCH-ARM / FISHERS |     P=0.428N     P=0.500N     P=0.414      P=0.410N    |P=0.362      P=0.290N     P=0.500      P=0.607N     | 
|ORDER RESTRICTED   |     P=0.563N     (e)          (e)          (e)         |P=0.426      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Degeneration Cystic                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   3/50 (6%)    2/50 (4%)    1/50 (2%)   |1/50 (2%)    1/49 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     5/44.59      3/44.21      2/46.96      1/41.96     |1/44.71      1/43.83      0/44.18      1/41.11      | 
|POLY-3 PERCENT (g) |     11.2%        6.8%         4.3%         2.4%        |2.2%         2.3%         0.0%         2.4%         | 
|TERMINAL (d)       |     3/31 (10%)   3/33 (9%)    2/39 (5%)    1/31 (3%)   |1/35 (3%)    1/32 (3%)    0/36 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     616          729 (T)      729 (T)      729 (T)     |729 (T)      729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.067N     P=0.340N     P=0.154N     P=0.113N    |P=0.575N     P=0.742      P=0.494N     P=0.762      | 
|POLY 3             |     P=0.077N     P=0.361N     P=0.196N     P=0.115N    |P=0.589N     P=0.756      P=0.502N     P=0.742      | 
|POLY 1.5           |     P=0.076N     P=0.360N     P=0.205N     P=0.112N    |P=0.588N     P=0.756      P=0.501N     P=0.745      | 
|POLY 6             |     P=0.076N     P=0.359N     P=0.182N     P=0.117N    |P=0.589N     P=0.755      P=0.503N     P=0.744      | 
|LOGISTIC REGRESSION|     P=0.075N     P=0.354N     P=0.224N     P=0.107N    |P=0.575N     P=0.742      (e)          P=0.762      | 
|COCH-ARM / FISHERS |     P=0.072N     P=0.357N     P=0.218N     P=0.102N    |P=0.585N     P=0.747      P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P=0.068N     (e)          (e)          (e)         |P=0.552N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Eosinophilic Focus                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   1/50 (2%)    4/50 (8%)    3/50 (6%)   |3/50 (6%)    2/49 (4%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     5/43.81      1/44.21      4/47.41      3/42.58     |3/44.84      2/43.83      0/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     11.4%        2.3%         8.4%         7.1%        |6.7%         4.6%         0.0%         0.0%         | 
|TERMINAL (d)       |     5/31 (16%)   1/33 (3%)    2/39 (5%)    2/31 (7%)   |2/35 (6%)    2/32 (6%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      619          530         |698          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.545N     P=0.087N     P=0.369N     P=0.362N    |P=0.035N*    P=0.535N     P=0.118N     P=0.125N     | 
|POLY 3             |     P=0.555N     P=0.099N     P=0.451N     P=0.372N    |P=0.038N*    P=0.510N     P=0.121N     P=0.135N     | 
|POLY 1.5           |     P=0.555N     P=0.101N     P=0.473N     P=0.371N    |P=0.038N*    P=0.509N     P=0.120N     P=0.132N     | 
|POLY 6             |     P=0.550N     P=0.094N     P=0.417N     P=0.365N    |P=0.038N*    P=0.514N     P=0.122N     P=0.133N     | 
|LOGISTIC REGRESSION|     P=0.558N     P=0.087N     P=0.442N     P=0.377N    |P=0.038N*    P=0.516N     P=0.122N     P=0.132N     | 
|COCH-ARM / FISHERS |     P=0.544N     P=0.102N     P=0.500N     P=0.357N    |P=0.037N*    P=0.510N     P=0.121N     P=0.121N     | 
|ORDER RESTRICTED   |     P=0.268N     (e)          (e)          (e)         |P=0.045N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   2/50 (4%)    3/50 (6%)    4/50 (8%)   |7/50 (14%)   4/49 (8%)    7/50 (14%)   4/50 (8%)    | 
|POLY-3 RATE (b)    |     9/43.98      2/44.94      3/46.96      4/42.01     |7/45.01      4/43.83      7/44.65      4/42.08      | 
|POLY-3 PERCENT (g) |     20.5%        4.5%         6.4%         9.5%        |15.6%        9.1%         15.7%        9.5%         | 
|TERMINAL (d)       |     7/31 (23%)   1/33 (3%)    3/39 (8%)    3/31 (10%)  |6/35 (17%)   4/32 (13%)   6/36 (17%)   3/35 (9%)    | 
|FIRST INCIDENCE    |     702          473          729 (T)      717         |648          729 (T)      593          223          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.208N     P=0.022N*    P=0.025N*    P=0.117N    |P=0.333N     P=0.312N     P=0.602N     P=0.269N     | 
|POLY 3             |     P=0.228N     P=0.022N*    P=0.045N*    P=0.131N    |P=0.395N     P=0.276N     P=0.608      P=0.300N     | 
|POLY 1.5           |     P=0.226N     P=0.024N*    P=0.051N     P=0.129N    |P=0.388N     P=0.274N     P=0.610      P=0.293N     | 
|POLY 6             |     P=0.227N     P=0.020N*    P=0.037N*    P=0.128N    |P=0.384N     P=0.280N     P=0.608      P=0.295N     | 
|LOGISTIC REGRESSION|     P=0.228N     P=0.027N*    P=0.025N*    P=0.112N    |P=0.376N     P=0.278N     P=0.604      P=0.256N     | 
|COCH-ARM / FISHERS |     P=0.216N     P=0.026N*    P=0.061N     P=0.117N    |P=0.348N     P=0.274N     P=0.613N     P=0.262N     | 
|ORDER RESTRICTED   |     P=0.024N*    (e)          (e)          (e)         |P=0.315N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |6/50 (12%)   4/49 (8%)    4/50 (8%)    5/50 (10%)   | 
|POLY-3 RATE (b)    |     0/43.81      1/44.21      0/46.96      1/42.07     |6/45.00      4/44.19      4/44.18      5/41.83      | 
|POLY-3 PERCENT (g) |     0.0%         2.3%         0.0%         2.4%        |13.3%        9.1%         9.1%         12.0%        | 
|TERMINAL (d)       |     0/31 (0%)    1/33 (3%)    0/39 (0%)    0/31 (0%)   |5/35 (14%)   3/32 (9%)    4/36 (11%)   4/35 (11%)   | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          703         |652          628          729 (T)      480          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.468      P=0.512      (e)          P=0.512     |P=0.495N     P=0.422N     P=0.358N     P=0.510N     | 
|POLY 3             |     P=0.458      P=0.502      (e)          P=0.492     |P=0.551N     P=0.381N     P=0.381N     P=0.551N     | 
|POLY 1.5           |     P=0.458      P=0.501      (e)          P=0.493     |P=0.544N     P=0.381N     P=0.376N     P=0.544N     | 
|POLY 6             |     P=0.462      P=0.505      (e)          P=0.493     |P=0.544N     P=0.382N     P=0.385N     P=0.543N     | 
|LOGISTIC REGRESSION|     P=0.457      P=0.512      (e)          P=0.493     |P=0.556N     P=0.382N     P=0.372N     P=0.542N     | 
|COCH-ARM / FISHERS |     P=0.464      P=0.500      (e)          P=0.500     |P=0.505N     P=0.383N     P=0.370N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.243      (e)          (e)          (e)         |P=0.488N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 16      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Bile Duct                                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     41/50 (82%)  35/50 (70%)  38/50 (76%)  37/50 (74%) |7/50 (14%)   5/49 (10%)   6/50 (12%)   2/50 (4%)    | 
|POLY-3 RATE (b)    |     41/47.46     35/47.66     38/47.71     37/44.29    |7/45.04      5/44.59      6/45.23      2/41.13      | 
|POLY-3 PERCENT (g) |     86.4%        73.4%        79.6%        83.5%       |15.5%        11.2%        13.3%        4.9%         | 
|TERMINAL (d)       |     28/31 (90%)  25/33 (76%)  32/39 (82%)  28/31 (90%) |6/35 (17%)   2/32 (6%)    4/36 (11%)   1/35 (3%)    | 
|FIRST INCIDENCE    |     563          473          649          530         |638          628          540          725          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.406N     P=0.110N     P=0.025N*    P=0.307N    |P=0.093N     P=0.434N     P=0.494N     P=0.087N     | 
|POLY 3             |     P=0.420      P=0.081N     P=0.261N     P=0.461N    |P=0.116N     P=0.386N     P=0.497N     P=0.102N     | 
|POLY 1.5           |     P=0.508      P=0.094N     P=0.280N     P=0.374N    |P=0.110N     P=0.389N     P=0.498N     P=0.098N     | 
|POLY 6             |     P=0.342      P=0.070N     P=0.241N     P=0.558N    |P=0.114N     P=0.383N     P=0.492N     P=0.099N     | 
|LOGISTIC REGRESSION|     P=0.536      P=0.114N     P=0.094N     P=0.424N    |P=0.098N     P=0.393N     P=0.501N     P=0.097N     | 
|COCH-ARM / FISHERS |     P=0.393N     P=0.121N     P=0.312N     P=0.235N    |P=0.086N     P=0.394N     P=0.500N     P=0.080N     | 
|ORDER RESTRICTED   |     P=0.261N     (e)          (e)          (e)         |P=0.093N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Centrilobular                                                                                                             | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |2/50 (4%)    0/49 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/43.98      0/44.21      1/47.35      2/42.37     |2/44.71      0/43.83      1/44.82      0/41.11      | 
|POLY-3 PERCENT (g) |     4.6%         0.0%         2.1%         4.7%        |4.5%         0.0%         2.2%         0.0%         | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |2/35 (6%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     685          ---          619          658         |729 (T)      ---          521          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.385      P=0.230N     P=0.441N     P=0.689     |P=0.253N     P=0.258N     P=0.491N     P=0.238N     | 
|POLY 3             |     P=0.378      P=0.236N     P=0.474N     P=0.681     |P=0.264N     P=0.241N     P=0.499N     P=0.256N     | 
|POLY 1.5           |     P=0.379      P=0.237N     P=0.486N     P=0.682     |P=0.262N     P=0.241N     P=0.499N     P=0.253N     | 
|POLY 6             |     P=0.380      P=0.233N     P=0.457N     P=0.685     |P=0.261N     P=0.242N     P=0.497N     P=0.254N     | 
|LOGISTIC REGRESSION|     P=0.408      P=0.235N     P=0.547N     P=0.689     |P=0.218N     (e)          P=0.501N     (e)          | 
|COCH-ARM / FISHERS |     P=0.387      P=0.247N     P=0.500N     P=0.691N    |P=0.251N     P=0.253N     P=0.500N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.389      (e)          (e)          (e)         |P=0.087N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 17      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   1/50 (2%)    2/50 (4%)    3/50 (6%)   |4/50 (8%)    4/49 (8%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     5/44.99      1/44.50      2/47.59      3/43.47     |4/45.81      4/44.94      0/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     11.1%        2.3%         4.2%         6.9%        |8.7%         8.9%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    0/39 (0%)    1/31 (3%)   |1/35 (3%)    1/32 (3%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     544          652          586          401         |591          395          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.497N     P=0.103N     P=0.173N     P=0.380N    |P=0.012N*    P=0.616      P=0.075N     P=0.083N     | 
|POLY 3             |     P=0.484N     P=0.103N     P=0.194N     P=0.375N    |P=0.011N*    P=0.633      P=0.065N     P=0.075N     | 
|POLY 1.5           |     P=0.486N     P=0.103N     P=0.204N     P=0.371N    |P=0.010N*    P=0.634      P=0.063N     P=0.072N     | 
|POLY 6             |     P=0.480N     P=0.102N     P=0.180N     P=0.377N    |P=0.011N*    P=0.627      P=0.067N     P=0.076N     | 
|LOGISTIC REGRESSION|     P=0.317N     P=0.100N     P=0.318N     P=0.235N    |P=0.003N**   P=0.616      P=0.062N     P=0.048N*    | 
|COCH-ARM / FISHERS |     P=0.484N     P=0.102N     P=0.218N     P=0.357N    |P=0.009N**   P=0.631      P=0.059N     P=0.059N     | 
|ORDER RESTRICTED   |     P=0.149N     (e)          (e)          (e)         |P=0.033N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    4/50 (8%)    3/50 (6%)    7/50 (14%)  |5/50 (10%)   2/49 (4%)    5/50 (10%)   8/50 (16%)   | 
|POLY-3 RATE (b)    |     3/44.88      4/46.57      3/47.52      7/44.86     |5/45.01      2/44.52      5/45.65      8/44.94      | 
|POLY-3 PERCENT (g) |     6.7%         8.6%         6.3%         15.6%       |11.1%        4.5%         11.0%        17.8%        | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    0/39 (0%)    1/31 (3%)   |4/35 (11%)   0/32 (0%)    2/36 (6%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     453          473          637          191         |648          621          560          312          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.112      P=0.500      P=0.592N     P=0.159     |P=0.067      P=0.251N     P=0.622      P=0.258      | 
|POLY 3             |     P=0.115      P=0.520      P=0.636N     P=0.156     |P=0.071      P=0.220N     P=0.622N     P=0.274      | 
|POLY 1.5           |     P=0.114      P=0.511      P=0.648N     P=0.155     |P=0.068      P=0.222N     P=0.625N     P=0.266      | 
|POLY 6             |     P=0.119      P=0.536      P=0.615N     P=0.164     |P=0.079      P=0.219N     P=0.614N     P=0.295      | 
|LOGISTIC REGRESSION|     P=0.305      P=0.605      P=0.523      P=0.310     |P=0.202      P=0.226N     P=0.627N     P=0.427      | 
|COCH-ARM / FISHERS |     P=0.117      P=0.500      P=0.661N     P=0.159     |P=0.074      P=0.226N     P=0.630N     P=0.277      | 
|ORDER RESTRICTED   |     P=0.114      (e)          (e)          (e)         |P=0.099      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 18      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Foreign Body                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    0/49 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      1/47.66      2/43.61     |0/44.71      0/43.83      0/44.18      1/41.83      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.1%         4.6%        |0.0%         0.0%         0.0%         2.4%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          489          191         |---          ---          ---          480          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.058      (e)          P=0.504      P=0.233     |P=0.176      (e)          (e)          P=0.483      | 
|POLY 3             |     P=0.060      (e)          P=0.517      P=0.236     |P=0.179      (e)          (e)          P=0.487      | 
|POLY 1.5           |     P=0.060      (e)          P=0.509      P=0.236     |P=0.180      (e)          (e)          P=0.488      | 
|POLY 6             |     P=0.060      (e)          P=0.527      P=0.239     |P=0.182      (e)          (e)          P=0.490      | 
|LOGISTIC REGRESSION|     P=0.423      (e)          P=0.307      P=0.666     |P=0.353      (e)          (e)          P=0.677      | 
|COCH-ARM / FISHERS |     P=0.060      (e)          P=0.500      P=0.247     |P=0.188      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.074      (e)          (e)          (e)         |P=0.108      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     28/50 (56%)  29/50 (58%)  36/50 (72%)  26/50 (52%) |41/50 (82%)  37/49 (76%)  39/50 (78%)  38/50 (76%)  | 
|POLY-3 RATE (b)    |     28/45.50     29/46.20     36/48.15     26/43.80    |41/48.29     37/47.25     39/46.77     38/44.10     | 
|POLY-3 PERCENT (g) |     61.5%        62.8%        74.8%        59.4%       |84.9%        78.3%        83.4%        86.2%        | 
|TERMINAL (d)       |     21/31 (68%)  22/33 (67%)  31/39 (80%)  19/31 (61%) |30/35 (86%)  27/32 (84%)  32/36 (89%)  30/35 (86%)  | 
|FIRST INCIDENCE    |     563          576          586          576         |344          395          557          480          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.430N     P=0.532N     P=0.484      P=0.438N    |P=0.358N     P=0.489N     P=0.381N     P=0.398N     | 
|POLY 3             |     P=0.536      P=0.538      P=0.115      P=0.503N    |P=0.318      P=0.276N     P=0.533N     P=0.552      | 
|POLY 1.5           |     P=0.524N     P=0.518      P=0.092      P=0.490N    |P=0.401      P=0.278N     P=0.474N     P=0.608N     | 
|POLY 6             |     P=0.524N     P=0.580      P=0.159      P=0.483N    |P=0.314      P=0.293N     P=0.607N     P=0.557      | 
|LOGISTIC REGRESSION|     P=0.534N     P=0.519      P=0.187      P=0.526N    |P=0.367      P=0.286N     P=0.437N     P=0.577      | 
|COCH-ARM / FISHERS |     P=0.435N     P=0.500      P=0.072      P=0.421N    |P=0.367N     P=0.294N     P=0.402N     P=0.312N     | 
|ORDER RESTRICTED   |     P=0.373N     (e)          (e)          (e)         |P=0.429      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 19      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     29/50 (58%)  23/50 (46%)  36/50 (72%)  30/50 (60%) |29/50 (58%)  33/49 (67%)  29/50 (58%)  33/50 (66%)  | 
|POLY-3 RATE (b)    |     29/46.82     23/46.20     36/48.47     30/45.45    |29/46.26     33/46.39     29/45.72     33/44.76     | 
|POLY-3 PERCENT (g) |     62.0%        49.8%        74.3%        66.0%       |62.7%        71.1%        63.4%        73.7%        | 
|TERMINAL (d)       |     19/31 (61%)  18/33 (55%)  31/39 (80%)  22/31 (71%) |23/35 (66%)  25/32 (78%)  26/36 (72%)  27/35 (77%)  | 
|FIRST INCIDENCE    |     544          473          586          191         |640          568          560          223          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.166      P=0.128N     P=0.544      P=0.481     |P=0.431      P=0.156      P=0.548N     P=0.258      | 
|POLY 3             |     P=0.101      P=0.160N     P=0.135      P=0.423     |P=0.254      P=0.254      P=0.558      P=0.175      | 
|POLY 1.5           |     P=0.116      P=0.158N     P=0.119      P=0.453     |P=0.285      P=0.244      P=0.573      P=0.192      | 
|POLY 6             |     P=0.091      P=0.162N     P=0.163      P=0.396     |P=0.247      P=0.262      P=0.535      P=0.178      | 
|LOGISTIC REGRESSION|     P=0.112      P=0.154N     P=0.162      P=0.449     |P=0.197      P=0.219      P=0.534      P=0.145      | 
|COCH-ARM / FISHERS |     P=0.149      P=0.158N     P=0.104      P=0.500     |P=0.389      P=0.226      P=0.580N     P=0.268      | 
|ORDER RESTRICTED   |     P=0.106      (e)          (e)          (e)         |P=0.191      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   9/50 (18%)   4/50 (8%)    6/50 (12%)  |1/50 (2%)    4/49 (8%)    3/50 (6%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     7/44.83      9/44.92      4/46.96      6/42.41     |1/44.71      4/44.60      3/44.18      2/41.31      | 
|POLY-3 PERCENT (g) |     15.6%        20.0%        8.5%         14.2%       |2.2%         9.0%         6.8%         4.8%         | 
|TERMINAL (d)       |     4/31 (13%)   6/33 (18%)   4/39 (10%)   4/31 (13%)  |1/35 (3%)    2/32 (6%)    3/36 (8%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     620          590          729 (T)      652         |729 (T)      568          729 (T)      677          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.252N     P=0.431      P=0.173N     P=0.512N    |P=0.539N     P=0.170      P=0.315      P=0.506      | 
|POLY 3             |     P=0.271N     P=0.393      P=0.235N     P=0.543N    |P=0.568      P=0.178      P=0.301      P=0.472      | 
|POLY 1.5           |     P=0.268N     P=0.392      P=0.246N     P=0.532N    |P=0.576      P=0.176      P=0.303      P=0.476      | 
|POLY 6             |     P=0.268N     P=0.400      P=0.218N     P=0.547N    |P=0.577      P=0.179      P=0.300      P=0.478      | 
|LOGISTIC REGRESSION|     P=0.268N     P=0.394      P=0.254N     P=0.524N    |P=0.573N     P=0.171      P=0.315      P=0.474      | 
|COCH-ARM / FISHERS |     P=0.252N     P=0.393      P=0.262N     P=0.500N    |P=0.544N     P=0.175      P=0.309      P=0.500      | 
|ORDER RESTRICTED   |     P=0.304N     (e)          (e)          (e)         |P=0.282      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 20      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   3/50 (6%)    4/50 (8%)    9/50 (18%)  |0/49 (0%)    1/49 (2%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     7/43.91      3/44.81      4/46.96      9/43.37     |0/44.36      1/43.83      1/44.82      0/41.11      | 
|POLY-3 PERCENT (g) |     15.9%        6.7%         8.5%         20.8%       |0.0%         2.3%         2.2%         0.0%         | 
|TERMINAL (d)       |     6/31 (19%)   2/33 (6%)    4/39 (10%)   7/31 (23%)  |0/35 (0%)    1/32 (3%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     702          540          729 (T)      465         |---          729 (T)      521          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.143      P=0.136N     P=0.146N     P=0.391     |P=0.542N     P=0.482      P=0.504      (e)          | 
|POLY 3             |     P=0.142      P=0.148N     P=0.223N     P=0.381     |P=0.553N     P=0.498      P=0.502      (e)          | 
|POLY 1.5           |     P=0.142      P=0.153N     P=0.240N     P=0.379     |P=0.549N     P=0.499      P=0.503      (e)          | 
|POLY 6             |     P=0.144      P=0.139N     P=0.199N     P=0.392     |P=0.552N     P=0.496      P=0.502      (e)          | 
|LOGISTIC REGRESSION|     P=0.140      P=0.153N     P=0.149N     P=0.367     |P=0.447N     P=0.482      P=0.424      (e)          | 
|COCH-ARM / FISHERS |     P=0.149      P=0.159N     P=0.262N     P=0.393     |P=0.531N     P=0.500      P=0.505      (e)          | 
|ORDER RESTRICTED   |     P=0.112      (e)          (e)          (e)         |P=0.404      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Mediastinal                                                                                                          | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/21 (43%)   9/17 (53%)   10/10 (100%) 15/18 (83%) |5/15 (33%)   7/8 (88%)    8/11 (73%)   2/3 (67%)    | 
|POLY-3 RATE (b)    |     9/18.01      9/16.69      10/10.00     15/17.05    |5/13.78      7/7.70       8/10.37      2/2.06       | 
|POLY-3 PERCENT (g) |     50.0%        53.9%        100.0%       88.0%       |36.3%        90.9%        77.2%        97.1%        | 
|TERMINAL (d)       |     7/11 (64%)   5/10 (50%)   9/9 (100%)   12/13 (92%) |4/10 (40%)   4/4 (100%)   6/8 (75%)    2/2 (100%)   | 
|FIRST INCIDENCE    |     649          540          637          508         |652          395          492          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.067      P=0.557      P=0.288      P=0.119     |P=0.548      P=0.045 *    P=0.129      P=0.494      | 
|POLY 3             |     P<0.001 **   P=0.543      P=0.002 **   P=0.009 **  |P=0.042 *    P=0.010 *    P=0.044 *    P=0.206      | 
|POLY 1.5           |     P<0.001 **   P=0.475      P<0.001 **   P=0.008 **  |P=0.051      P=0.011 *    P=0.044 *    P=0.227      | 
|POLY 6             |     P<0.001 **   P=0.634      P=0.005 **   P=0.014 *   |P=0.048 *    P=0.010 *    P=0.050      P=0.209      | 
|LOGISTIC REGRESSION|     P=0.002 **   P=0.399      P=0.017 *    P=0.010 *   |P=0.103      P=0.021 *    P=0.047 *    P=0.214      | 
|COCH-ARM / FISHERS |     P=0.002 **   P=0.385      P=0.002 **   P=0.011 *   |P=0.158      P=0.019 *    P=0.055      P=0.326      | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.252      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 21      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Pancreatic                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/21 (10%)   4/17 (24%)   1/10 (10%)   1/18 (6%)   |1/15 (7%)    0/8 (0%)     1/11 (9%)    1/3 (33%)    | 
|POLY-3 RATE (b)    |     2/17.51      4/14.82      1/9.67       1/16.24     |1/13.50      0/6.25       1/9.37       1/3.00       | 
|POLY-3 PERCENT (g) |     11.4%        27.0%        10.3%        6.2%        |7.4%         0.0%         10.7%        33.3%        | 
|TERMINAL (d)       |     2/11 (18%)   4/10 (40%)   1/9 (11%)    0/13 (0%)   |1/10 (10%)   0/4 (0%)     1/8 (13%)    0/2 (0%)     | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      504         |729 (T)      ---          729 (T)      284          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.124N     P=0.272      P=0.573N     P=0.466N    |P=0.288      P=0.682N     P=0.716      P=0.596      | 
|POLY 3             |     P=0.188N     P=0.247      P=0.709N     P=0.527N    |P=0.188      P=0.649N     P=0.678      P=0.392      | 
|POLY 1.5           |     P=0.203N     P=0.241      P=0.727N     P=0.539N    |P=0.179      P=0.640N     P=0.681      P=0.381      | 
|POLY 6             |     P=0.166N     P=0.259      P=0.681N     P=0.507N    |P=0.204      P=0.656N     P=0.679      P=0.410      | 
|LOGISTIC REGRESSION|     P=0.213N     P=0.272      P=0.573N     P=0.567N    |P=0.324      (e)          P=0.716      P=0.924      | 
|COCH-ARM / FISHERS |     P=0.222N     P=0.233      P=0.704      P=0.559N    |P=0.165      P=0.652N     P=0.677      P=0.314      | 
|ORDER RESTRICTED   |     P=0.204N     (e)          (e)          (e)         |P=0.257      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     23/50 (46%)  18/50 (36%)  20/50 (40%)  20/50 (40%) |0/50 (0%)    0/49 (0%)    2/50 (4%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     23/45.74     18/48.14     20/48.62     20/44.79    |0/44.71      0/43.83      2/44.18      1/41.11      | 
|POLY-3 PERCENT (g) |     50.3%        37.4%        41.1%        44.7%       |0.0%         0.0%         4.5%         2.4%         | 
|TERMINAL (d)       |     14/31 (45%)  7/33 (21%)   12/39 (31%)  12/31 (39%) |0/35 (0%)    0/32 (0%)    2/36 (6%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     641          473          586          504         |---          ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.464N     P=0.193N     P=0.135N     P=0.377N    |P=0.218      (e)          P=0.244      P=0.500      | 
|POLY 3             |     P=0.515N     P=0.144N     P=0.245N     P=0.371N    |P=0.179      (e)          P=0.234      P=0.483      | 
|POLY 1.5           |     P=0.501N     P=0.169N     P=0.286N     P=0.372N    |P=0.184      (e)          P=0.236      P=0.486      | 
|POLY 6             |     P=0.524N     P=0.116N     P=0.197N     P=0.359N    |P=0.184      (e)          P=0.234      P=0.485      | 
|LOGISTIC REGRESSION|     P=0.442N     P=0.209N     P=0.296N     P=0.394N    |(e)          (e)          P=0.244      P=0.500      | 
|COCH-ARM / FISHERS |     P=0.449N     P=0.208N     P=0.343N     P=0.343N    |P=0.210      (e)          P=0.247      P=0.500      | 
|ORDER RESTRICTED   |     P=0.298N     (e)          (e)          (e)         |P=0.166      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 22      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |18/50 (36%)  19/49 (39%)  9/50 (18%)   7/50 (14%)   | 
|POLY-3 RATE (b)    |     1/43.81      0/44.21      1/46.96      0/41.96     |18/45.56     19/45.87     9/44.64      7/41.11      | 
|POLY-3 PERCENT (g) |     2.3%         0.0%         2.1%         0.0%        |39.5%        41.4%        20.2%        17.0%        | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    1/39 (3%)    0/31 (0%)   |15/35 (43%)  13/32 (41%)  8/36 (22%)   7/35 (20%)   | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |563          568          596          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.461N     P=0.488N     P=0.710N     P=0.500N    |P<0.001N**   P=0.396      P=0.031N*    P=0.010N*    | 
|POLY 3             |     P=0.471N     P=0.498N     P=0.745N     P=0.509N    |P=0.002N**   P=0.511      P=0.035N*    P=0.017N*    | 
|POLY 1.5           |     P=0.470N     P=0.499N     P=0.752N     P=0.507N    |P=0.002N**   P=0.494      P=0.034N*    P=0.015N*    | 
|POLY 6             |     P=0.472N     P=0.495N     P=0.734N     P=0.508N    |P=0.002N**   P=0.533      P=0.035N*    P=0.016N*    | 
|LOGISTIC REGRESSION|     P=0.461N     (e)          P=0.710N     (e)         |P=0.002N**   P=0.471      P=0.037N*    P=0.015N*    | 
|COCH-ARM / FISHERS |     P=0.464N     P=0.500N     P=0.753N     P=0.500N    |P<0.001N**   P=0.469      P=0.035N*    P=0.010N*    | 
|ORDER RESTRICTED   |     P=0.259N     (e)          (e)          (e)         |P=0.010N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia Atypical                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |3/50 (6%)    3/49 (6%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      0/46.96      0/41.96     |3/44.71      3/43.83      1/44.35      0/41.11      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |6.7%         6.9%         2.3%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |3/35 (9%)    3/32 (9%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      729 (T)      687          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.040N*    P=0.622      P=0.295N     P=0.121N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.048N*    P=0.653      P=0.308N     P=0.134N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.048N*    P=0.654      P=0.307N     P=0.132N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.047N*    P=0.652      P=0.307N     P=0.132N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.044N*    P=0.622      P=0.308N     (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.043N*    P=0.651      P=0.309N     P=0.121N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.086N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 23      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland: Duct                                                                                                              | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |31/50 (62%)  28/49 (57%)  29/50 (58%)  24/50 (48%)  | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      0/46.96      0/41.96     |31/46.75     28/46.68     29/46.26     24/41.99     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |66.3%        60.0%        62.7%        57.2%        | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |25/35 (71%)  18/32 (56%)  25/36 (69%)  21/35 (60%)  | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |563          395          492          573          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.105N     P=0.504N     P=0.383N     P=0.132N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.281N     P=0.335N     P=0.440N     P=0.248N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.231N     P=0.351N     P=0.425N     P=0.210N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.297N     P=0.317N     P=0.461N     P=0.252N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.226N     P=0.382N     P=0.449N     P=0.224N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.108N     P=0.387N     P=0.419N     P=0.114N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.296N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland: Duct                                                                                                              | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    0/49 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      0/46.96      0/41.96     |2/44.92      0/43.83      0/44.18      1/41.11      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.5%         0.0%         0.0%         2.4%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |1/35 (3%)    0/32 (0%)    0/36 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |674          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.519N     P=0.247N     P=0.234N     P=0.497N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.528N     P=0.243N     P=0.241N     P=0.531N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.528N     P=0.242N     P=0.239N     P=0.525N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.527N     P=0.244N     P=0.242N     P=0.529N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.547N     P=0.242N     P=0.238N     P=0.526N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.527N     P=0.253N     P=0.247N     P=0.500N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.150N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 24      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/16 (88%)  9/11 (82%)   8/9 (89%)    7/12 (58%)  |17/17 (100%) 14/14 (100%) 11/12 (92%)  8/8 (100%)   | 
|POLY-3 RATE (b)    |     14/15.69     9/10.53      8/8.61       7/11.21     |17/17.00     14/14.00     11/12.00     8/8.00       | 
|POLY-3 PERCENT (g) |     89.2%        85.5%        92.9%        62.5%       |100.0%       100.0%       91.7%        100.0%       | 
|TERMINAL (d)       |     9/10 (90%)   8/9 (89%)    5/5 (100%)   4/6 (67%)   |10/10 (100%) 11/11 (100%) 9/10 (90%)   7/7 (100%)   | 
|FIRST INCIDENCE    |     544          652          637          530         |344          621          557          677          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.311N     P=0.140N     P=0.398N     P=0.216N    |P=0.034N*    (e)          P=0.064N     (e)          | 
|POLY 3             |     P=0.058N     P=0.629N     P=0.674      P=0.103N    |P=0.558N     (e)          P=0.430N     (e)          | 
|POLY 1.5           |     P=0.057N     P=0.597N     P=0.686      P=0.095N    |P=0.558N     (e)          P=0.430N     (e)          | 
|POLY 6             |     P=0.069N     P=0.668N     P=0.653      P=0.124N    |P=0.558N     (e)          P=0.430N     (e)          | 
|LOGISTIC REGRESSION|     P=0.058N     P=0.490N     P=0.741N     P=0.093N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.059N     P=0.545N     P=0.757N     P=0.093N    |P=0.558N     (e)          P=0.414N     (e)          | 
|ORDER RESTRICTED   |     P=0.028N*    (e)          (e)          (e)         |P=0.371N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Foreign Body                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   4/50 (8%)    12/50 (24%)  7/50 (14%)  |4/50 (8%)    3/49 (6%)    1/50 (2%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |     7/44.37      4/44.24      12/47.40     7/42.47     |4/44.71      3/43.93      1/44.35      3/41.73      | 
|POLY-3 PERCENT (g) |     15.8%        9.0%         25.3%        16.5%       |9.0%         6.8%         2.3%         7.2%         | 
|TERMINAL (d)       |     5/31 (16%)   3/33 (9%)    10/39 (26%)  6/31 (19%)  |4/35 (11%)   2/32 (6%)    0/36 (0%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     642          723          649          576         |729 (T)      702          687          527          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.278      P=0.234N     P=0.306      P=0.601     |P=0.379N     P=0.542N     P=0.172N     P=0.509N     | 
|POLY 3             |     P=0.242      P=0.262N     P=0.192      P=0.580     |P=0.408N     P=0.510N     P=0.181N     P=0.538N     | 
|POLY 1.5           |     P=0.250      P=0.263N     P=0.174      P=0.586     |P=0.406N     P=0.509N     P=0.180N     P=0.533N     | 
|POLY 6             |     P=0.242      P=0.257N     P=0.221      P=0.581     |P=0.402N     P=0.511N     P=0.180N     P=0.528N     | 
|LOGISTIC REGRESSION|     P=0.253      P=0.246N     P=0.206      P=0.583     |P=0.419N     P=0.524N     P=0.180N     P=0.533N     | 
|COCH-ARM / FISHERS |     P=0.281      P=0.262N     P=0.154      P=0.613N    |P=0.386N     P=0.511N     P=0.181N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.220      (e)          (e)          (e)         |P=0.329N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 25      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     12/50 (24%)  3/50 (6%)    20/50 (40%)  15/50 (30%) |8/50 (16%)   7/49 (14%)   9/50 (18%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |     12/45.22     3/44.24      20/48.11     15/45.51    |8/45.30      7/44.62      9/45.74      6/41.73      | 
|POLY-3 PERCENT (g) |     26.5%        6.8%         41.6%        33.0%       |17.7%        15.7%        19.7%        14.4%        | 
|TERMINAL (d)       |     8/31 (26%)   2/33 (6%)    15/39 (39%)  7/31 (23%)  |6/35 (17%)   4/32 (13%)   4/36 (11%)   5/35 (14%)   | 
|FIRST INCIDENCE    |     563          723          586          401         |648          628          492          527          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.021 *    P=0.012N*    P=0.222      P=0.323     |P=0.391N     P=0.558N     P=0.506      P=0.405N     | 
|POLY 3             |     P=0.017 *    P=0.011N*    P=0.092      P=0.330     |P=0.457N     P=0.513N     P=0.509      P=0.451N     | 
|POLY 1.5           |     P=0.015 *    P=0.011N*    P=0.079      P=0.320     |P=0.446N     P=0.513N     P=0.506      P=0.440N     | 
|POLY 6             |     P=0.022 *    P=0.011N*    P=0.117      P=0.352     |P=0.449N     P=0.514N     P=0.518      P=0.445N     | 
|LOGISTIC REGRESSION|     P=0.019 *    P=0.012N*    P=0.077      P=0.362     |P=0.412N     P=0.516N     P=0.501      P=0.439N     | 
|COCH-ARM / FISHERS |     P=0.018 *    P=0.011N*    P=0.066      P=0.326     |P=0.382N     P=0.517N     P=0.500      P=0.387N     | 
|ORDER RESTRICTED   |     P=0.014 *    (e)          (e)          (e)         |P=0.537N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Oral Mucosa: Pharyngeal                                                                                                          | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/1 (0%)     0/0 (0%)     0/0 (0%)     2/4 (50%)   |1/2 (50%)    0/0 (0%)     0/0 (0%)     1/1 (100%)   | 
|POLY-3 RATE (b)    |     0/1.00       0/0.00       0/0.00       2/3.66      |1/1.53       0/0.00       0/0.00       1/1.00       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         54.7%       |65.2%        0.0%         0.0%         100.0%       | 
|TERMINAL (d)       |     0/1 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |1/1 (100%)   0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          576         |729 (T)      ---          ---          544          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.043 *    (e)          (e)          P=0.253     |P=0.168      P=1.000N     P=1.000N     P=0.468      | 
|POLY 3             |     (e)          (e)          (e)          P=0.559     |(e)          (e)          (e)          P=0.785      | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.568     |(e)          (e)          (e)          P=0.692      | 
|POLY 6             |     (e)          (e)          (e)          P=0.540     |(e)          (e)          (e)          P=0.956      | 
|LOGISTIC REGRESSION|     P=0.675      (e)          (e)          P=0.915     |P=0.220      (e)          (e)          P=0.546      | 
|COCH-ARM / FISHERS |     P=0.366      (e)          (e)          P=0.600     |P=0.414      P=1.000      P=1.000      P=0.667      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 26      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Oral Mucosa: Pharyngeal                                                                                                          | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/1 (0%)     0/0 (0%)     0/0 (0%)     2/4 (50%)   |0/2 (0%)     0/0 (0%)     0/0 (0%)     0/1 (0%)     | 
|POLY-3 RATE (b)    |     0/1.00       0/0.00       0/0.00       2/3.66      |0/1.53       0/0.00       0/0.00       0/0.42       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         54.7%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/1 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/1 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          576         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.043 *    (e)          (e)          P=0.253     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          P=0.559     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.568     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          P=0.540     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.675      (e)          (e)          P=0.915     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.366      (e)          (e)          P=0.600     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |11/50 (22%)  4/49 (8%)    9/50 (18%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |                                                        |11/44.71     4/44.15      9/44.64      10/41.90     | 
|POLY-3 PERCENT (g) |                                                        |24.6%        9.1%         20.2%        23.9%        | 
|TERMINAL (d)       |                                                        |11/35 (31%)  3/32 (9%)    8/36 (22%)   8/35 (23%)   | 
|FIRST INCIDENCE    |                                                        |729 (T)      641          596          527          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.333      P=0.063N     P=0.375N     P=0.505N     | 
|POLY 3             |                                                        |P=0.255      P=0.045N*    P=0.401N     P=0.568N     | 
|POLY 1.5           |                                                        |P=0.262      P=0.046N*    P=0.401N     P=0.562N     | 
|POLY 6             |                                                        |P=0.270      P=0.043N*    P=0.396N     P=0.546N     | 
|LOGISTIC REGRESSION|                                                        |P=0.248      P=0.050N     P=0.404N     P=0.579N     | 
|COCH-ARM / FISHERS |                                                        |P=0.317      P=0.049N*    P=0.402N     P=0.500N     | 
|ORDER RESTRICTED   |                                                        |P=0.325N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 27      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     43/50 (86%)  31/50 (62%)  35/50 (70%)  32/50 (64%) |26/49 (53%)  20/48 (42%)  23/48 (48%)  23/49 (47%)  | 
|POLY-3 RATE (b)    |     43/48.10     31/48.72     35/49.06     32/44.80    |26/45.89     20/44.32     23/44.53     23/42.60     | 
|POLY-3 PERCENT (g) |     89.4%        63.6%        71.3%        71.4%       |56.7%        45.1%        51.7%        54.0%        | 
|TERMINAL (d)       |     30/31 (97%)  18/33 (55%)  28/39 (72%)  22/31 (71%) |20/35 (57%)  15/32 (47%)  19/36 (53%)  18/35 (51%)  | 
|FIRST INCIDENCE    |     544          540          586          563         |638          585          596          223          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.138N     P=0.020N*    P=0.004N**   P=0.045N*   |P=0.446N     P=0.266N     P=0.329N     P=0.376N     | 
|POLY 3             |     P=0.184N     P=0.002N**   P=0.019N*    P=0.019N*   |P=0.457      P=0.184N     P=0.393N     P=0.485N     | 
|POLY 1.5           |     P=0.146N     P=0.003N**   P=0.027N*    P=0.015N*   |P=0.482      P=0.179N     P=0.386N     P=0.453N     | 
|POLY 6             |     P=0.218N     P<0.001N**   P=0.011N*    P=0.020N*   |P=0.470      P=0.195N     P=0.397N     P=0.483N     | 
|LOGISTIC REGRESSION|     P=0.115N     P=0.006N**   P=0.026N*    P=0.020N*   |P=0.425      P=0.184N     P=0.390N     P=0.486N     | 
|COCH-ARM / FISHERS |     P=0.081N     P=0.006N**   P=0.045N*    P=0.010N*   |P=0.479N     P=0.179N     P=0.381N     P=0.343N     | 
|ORDER RESTRICTED   |     P=0.013N*    (e)          (e)          (e)         |P=0.427N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas: Acinus                                                                                                                 | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    6/50 (12%)   15/50 (30%)  12/50 (24%) |3/49 (6%)    1/48 (2%)    2/48 (4%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |     4/44.20      6/44.74      15/47.64     12/42.78    |3/44.78      1/43.14      2/43.32      1/40.47      | 
|POLY-3 PERCENT (g) |     9.1%         13.4%        31.5%        28.1%       |6.7%         2.3%         4.6%         2.5%         | 
|TERMINAL (d)       |     3/31 (10%)   5/33 (15%)   13/39 (33%)  9/31 (29%)  |1/35 (3%)    1/32 (3%)    2/36 (6%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     616          568          619          626         |648          729 (T)      729 (T)      677          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.009 **   P=0.396      P=0.020 *    P=0.029 *   |P=0.326N     P=0.333N     P=0.499N     P=0.317N     | 
|POLY 3             |     P=0.006 **   P=0.377      P=0.007 **   P=0.020 *   |P=0.358N     P=0.319N     P=0.515N     P=0.342N     | 
|POLY 1.5           |     P=0.006 **   P=0.373      P=0.005 **   P=0.021 *   |P=0.353N     P=0.316N     P=0.512N     P=0.335N     | 
|POLY 6             |     P=0.006 **   P=0.386      P=0.009 **   P=0.020 *   |P=0.353N     P=0.323N     P=0.517N     P=0.340N     | 
|LOGISTIC REGRESSION|     P=0.007 **   P=0.372      P=0.008 **   P=0.022 *   |P=0.352N     P=0.312N     P=0.510N     P=0.314N     | 
|COCH-ARM / FISHERS |     P=0.010 *    P=0.370      P=0.005 **   P=0.027 *   |P=0.328N     P=0.316N     P=0.510N     P=0.309N     | 
|ORDER RESTRICTED   |     P=0.010 *    (e)          (e)          (e)         |P=0.261N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 28      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/50 (28%)  30/50 (60%)  16/50 (32%)  15/50 (30%) |28/50 (56%)  27/49 (55%)  29/50 (58%)  21/50 (42%)  | 
|POLY-3 RATE (b)    |     14/45.17     30/48.23     16/47.92     15/44.82    |28/45.76     27/46.10     29/46.83     21/41.83     | 
|POLY-3 PERCENT (g) |     31.0%        62.2%        33.4%        33.5%       |61.2%        58.6%        61.9%        50.2%        | 
|TERMINAL (d)       |     8/31 (26%)   19/33 (58%)  12/39 (31%)  8/31 (26%)  |24/35 (69%)  19/32 (59%)  21/36 (58%)  19/35 (54%)  | 
|FIRST INCIDENCE    |     641          473          586          508         |638          568          492          573          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.105N     P=0.008 **   P=0.499N     P=0.481     |P=0.090N     P=0.496      P=0.535      P=0.115N     | 
|POLY 3             |     P=0.078N     P<0.001 **   P=0.490      P=0.490     |P=0.203N     P=0.482N     P=0.557      P=0.201N     | 
|POLY 1.5           |     P=0.082N     P<0.001 **   P=0.457      P=0.483     |P=0.176N     P=0.508N     P=0.534      P=0.184N     | 
|POLY 6             |     P=0.068N     P=0.002 **   P=0.535      P=0.512     |P=0.198N     P=0.447N     P=0.581N     P=0.189N     | 
|LOGISTIC REGRESSION|     P=0.081N     P<0.001 **   P=0.462      P=0.490     |P=0.190N     P=0.546N     P=0.463      P=0.191N     | 
|COCH-ARM / FISHERS |     P=0.082N     P<0.001 **   P=0.414      P=0.500     |P=0.091N     P=0.545N     P=0.500      P=0.115N     | 
|ORDER RESTRICTED   |     P=0.136N     (e)          (e)          (e)         |P=0.235N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   3/50 (6%)    6/50 (12%)   5/50 (10%)  |21/50 (42%)  19/49 (39%)  16/50 (32%)  23/50 (46%)  | 
|POLY-3 RATE (b)    |     6/44.01      3/44.21      6/47.11      5/42.01     |21/46.12     19/46.06     16/45.87     23/43.23     | 
|POLY-3 PERCENT (g) |     13.6%        6.8%         12.7%        11.9%       |45.5%        41.3%        34.9%        53.2%        | 
|TERMINAL (d)       |     5/31 (16%)   3/33 (9%)    5/39 (13%)   4/31 (13%)  |16/35 (46%)  13/32 (41%)  13/36 (36%)  19/35 (54%)  | 
|FIRST INCIDENCE    |     675          729 (T)      690          717         |591          395          540          480          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.494      P=0.213N     P=0.458N     P=0.500N    |P=0.383      P=0.536N     P=0.201N     P=0.396      | 
|POLY 3             |     P=0.457      P=0.239N     P=0.572N     P=0.533N    |P=0.252      P=0.418N     P=0.201N     P=0.302      | 
|POLY 1.5           |     P=0.463      P=0.241N     P=0.594N     P=0.526N    |P=0.270      P=0.427N     P=0.200N     P=0.318      | 
|POLY 6             |     P=0.458      P=0.232N     P=0.539N     P=0.532N    |P=0.260      P=0.418N     P=0.204N     P=0.316      | 
|LOGISTIC REGRESSION|     P=0.478      P=0.210N     P=0.513N     P=0.509N    |P=0.274      P=0.450N     P=0.210N     P=0.292      | 
|COCH-ARM / FISHERS |     P=0.488      P=0.243N     P=0.620N     P=0.500N    |P=0.366      P=0.452N     P=0.204N     P=0.420      | 
|ORDER RESTRICTED   |     P=0.513N     (e)          (e)          (e)         |P=0.174      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 29      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   9/50 (18%)   9/50 (18%)   13/50 (26%) |5/50 (10%)   8/49 (16%)   6/50 (12%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |     9/45.31      9/44.21      9/46.96      13/42.67    |5/45.55      8/44.33      6/44.78      6/42.22      | 
|POLY-3 PERCENT (g) |     19.9%        20.4%        19.2%        30.5%       |11.0%        18.1%        13.4%        14.2%        | 
|TERMINAL (d)       |     6/31 (19%)   9/33 (27%)   9/39 (23%)   11/31 (36%) |3/35 (9%)    7/32 (22%)   5/36 (14%)   4/35 (11%)   | 
|FIRST INCIDENCE    |     544          729 (T)      729 (T)      563         |563          576          540          544          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.159      P=0.562N     P=0.423N     P=0.225     |P=0.509N     P=0.233      P=0.504      P=0.466      | 
|POLY 3             |     P=0.140      P=0.581      P=0.571N     P=0.182     |P=0.542      P=0.257      P=0.488      P=0.447      | 
|POLY 1.5           |     P=0.145      P=0.589      P=0.585N     P=0.196     |P=0.550      P=0.261      P=0.494      P=0.454      | 
|POLY 6             |     P=0.140      P=0.578      P=0.546N     P=0.175     |P=0.551N     P=0.250      P=0.483      P=0.456      | 
|LOGISTIC REGRESSION|     P=0.140      P=0.598N     P=0.595N     P=0.207     |P=0.522N     P=0.263      P=0.502      P=0.504      | 
|COCH-ARM / FISHERS |     P=0.167      P=0.602N     P=0.602N     P=0.235     |P=0.503N     P=0.264      P=0.500      P=0.500      | 
|ORDER RESTRICTED   |     P=0.179      (e)          (e)          (e)         |P=0.451      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    0/50 (0%)    0/50 (0%)    3/50 (6%)   |                                                    | 
|POLY-3 RATE (b)    |     4/44.19      0/44.21      0/46.96      3/42.13     |                                                    | 
|POLY-3 PERCENT (g) |     9.1%         0.0%         0.0%         7.1%        |                                                    | 
|TERMINAL (d)       |     3/31 (10%)   0/33 (0%)    0/39 (0%)    2/31 (7%)   |                                                    | 
|FIRST INCIDENCE    |     620          ---          ---          687         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.523      P=0.060N     P=0.044N*    P=0.503N    |                                                    | 
|POLY 3             |     P=0.518      P=0.060N     P=0.053N     P=0.526N    |                                                    | 
|POLY 1.5           |     P=0.517      P=0.060N     P=0.056N     P=0.520N    |                                                    | 
|POLY 6             |     P=0.521      P=0.058N     P=0.048N*    P=0.526N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.508      P=0.062N     P=0.060N     P=0.522N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.519      P=0.059N     P=0.059N     P=0.500N    |                                                    | 
|ORDER RESTRICTED   |     P=0.079N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 30      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   5/50 (10%)   4/50 (8%)    4/50 (8%)   |                                                    | 
|POLY-3 RATE (b)    |     5/43.81      5/44.31      4/46.96      4/41.96     |                                                    | 
|POLY-3 PERCENT (g) |     11.4%        11.3%        8.5%         9.5%        |                                                    | 
|TERMINAL (d)       |     5/31 (16%)   3/33 (9%)    4/39 (10%)   4/31 (13%)  |                                                    | 
|FIRST INCIDENCE    |     729 (T)      712          729 (T)      729 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.379N     P=0.581N     P=0.357N     P=0.500N    |                                                    | 
|POLY 3             |     P=0.406N     P=0.624N     P=0.457N     P=0.527N    |                                                    | 
|POLY 1.5           |     P=0.405N     P=0.627N     P=0.476N     P=0.522N    |                                                    | 
|POLY 6             |     P=0.400N     P=0.613N     P=0.427N     P=0.525N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.382N     P=0.574N     P=0.357N     P=0.500N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.389N     P=0.630N     P=0.500N     P=0.500N    |                                                    | 
|ORDER RESTRICTED   |     P=0.561N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     31/50 (62%)  28/50 (56%)  27/50 (54%)  26/50 (52%) |                                                    | 
|POLY-3 RATE (b)    |     31/47.65     28/48.13     27/49.55     26/46.86    |                                                    | 
|POLY-3 PERCENT (g) |     65.1%        58.2%        54.5%        55.5%       |                                                    | 
|TERMINAL (d)       |     18/31 (58%)  17/33 (52%)  18/39 (46%)  16/31 (52%) |                                                    | 
|FIRST INCIDENCE    |     563          473          489          401         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.262N     P=0.298N     P=0.088N     P=0.288N    |                                                    | 
|POLY 3             |     P=0.225N     P=0.313N     P=0.195N     P=0.226N    |                                                    | 
|POLY 1.5           |     P=0.226N     P=0.323N     P=0.223N     P=0.226N    |                                                    | 
|POLY 6             |     P=0.225N     P=0.303N     P=0.165N     P=0.229N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.181N     P=0.344N     P=0.332N     P=0.204N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.208N     P=0.342N     P=0.272N     P=0.210N    |                                                    | 
|ORDER RESTRICTED   |     P=0.254N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 31      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    5/50 (10%)   1/50 (2%)   |0/50 (0%)    3/49 (6%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      5/47.29      1/41.96     |0/44.71      3/44.12      0/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         10.6%        2.4%        |0.0%         6.8%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    4/39 (10%)   1/31 (3%)   |0/35 (0%)    2/32 (6%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          637          729 (T)     |---          648          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.178      (e)          P=0.054      P=0.500     |P=0.170N     P=0.109      (e)          (e)          | 
|POLY 3             |     P=0.150      (e)          P=0.038 *    P=0.491     |P=0.170N     P=0.116      (e)          (e)          | 
|POLY 1.5           |     P=0.158      (e)          P=0.034 *    P=0.493     |P=0.169N     P=0.116      (e)          (e)          | 
|POLY 6             |     P=0.146      (e)          P=0.043 *    P=0.492     |P=0.169N     P=0.116      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.173      (e)          P=0.037 *    P=0.500     |P=0.174N     P=0.117      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.185      (e)          P=0.028 *    P=0.500     |P=0.167N     P=0.117      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.061      (e)          (e)          (e)         |P=0.176N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    2/50 (4%)    2/50 (4%)   |2/49 (4%)    0/48 (0%)    0/49 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     1/43.94      2/44.21      2/47.03      2/42.11     |2/44.36      0/43.14      0/43.73      0/40.27      | 
|POLY-3 PERCENT (g) |     2.3%         4.5%         4.3%         4.8%        |4.5%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    2/33 (6%)    1/39 (3%)    1/31 (3%)   |2/35 (6%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     694          729 (T)      712          692         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.442      P=0.521      P=0.576      P=0.497     |P=0.155N     P=0.258N     P=0.232N     P=0.238N     | 
|POLY 3             |     P=0.424      P=0.502      P=0.524      P=0.485     |P=0.156N     P=0.243N     P=0.240N     P=0.259N     | 
|POLY 1.5           |     P=0.427      P=0.501      P=0.513      P=0.488     |P=0.157N     P=0.243N     P=0.239N     P=0.255N     | 
|POLY 6             |     P=0.427      P=0.507      P=0.539      P=0.487     |P=0.155N     P=0.244N     P=0.240N     P=0.257N     | 
|LOGISTIC REGRESSION|     P=0.429      P=0.512      P=0.524      P=0.487     |P=0.155N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.442      P=0.500      P=0.500      P=0.500     |P=0.159N     P=0.253N     P=0.247N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.446      (e)          (e)          (e)         |P=0.037N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 32      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/50 (22%)  12/50 (24%)  17/50 (34%)  20/50 (40%) |3/49 (6%)    5/48 (10%)   7/49 (14%)   8/49 (16%)   | 
|POLY-3 RATE (b)    |     11/45.05     12/46.56     17/48.19     20/45.44    |3/45.11      5/44.22      7/46.31      8/40.86      | 
|POLY-3 PERCENT (g) |     24.4%        25.8%        35.3%        44.0%       |6.7%         11.3%        15.1%        19.6%        | 
|TERMINAL (d)       |     6/31 (19%)   5/33 (15%)   13/39 (33%)  9/31 (29%)  |1/35 (3%)    2/32 (6%)    2/36 (6%)    7/35 (20%)   | 
|FIRST INCIDENCE    |     563          540          586          504         |563          395          492          544          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.023 *    P=0.552      P=0.321      P=0.060     |P=0.078      P=0.341      P=0.171      P=0.098      | 
|POLY 3             |     P=0.014 *    P=0.536      P=0.179      P=0.037 *   |P=0.052      P=0.345      P=0.168      P=0.069      | 
|POLY 1.5           |     P=0.013 *    P=0.519      P=0.157      P=0.035 *   |P=0.056      P=0.347      P=0.164      P=0.075      | 
|POLY 6             |     P=0.017 *    P=0.567      P=0.214      P=0.046 *   |P=0.053      P=0.341      P=0.174      P=0.070      | 
|LOGISTIC REGRESSION|     P=0.018 *    P=0.498      P=0.138      P=0.040 *   |P=0.130      P=0.340      P=0.177      P=0.085      | 
|COCH-ARM / FISHERS |     P=0.016 *    P=0.500      P=0.133      P=0.041 *   |P=0.078      P=0.346      P=0.159      P=0.100      | 
|ORDER RESTRICTED   |     P=0.031 *    (e)          (e)          (e)         |P=0.057      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/49 (0%)    0/48 (0%)    0/49 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      0/46.96      2/42.11     |0/44.36      0/43.14      0/43.73      0/40.27      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         4.8%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    1/31 (3%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          692         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.040 *    (e)          (e)          P=0.240     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.041 *    (e)          (e)          P=0.228     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.041 *    (e)          (e)          P=0.230     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.042 *    (e)          (e)          P=0.230     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.039 *    (e)          (e)          P=0.229     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.043 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.026 *    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 33      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/49 (2%)    0/48 (0%)    0/49 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     2/44.36      0/44.21      0/46.96      0/41.96     |1/44.83      0/43.14      0/43.73      0/40.27      | 
|POLY-3 PERCENT (g) |     4.5%         0.0%         0.0%         0.0%        |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     620          ---          ---          ---         |591          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.158N     P=0.242N     P=0.213N     P=0.248N    |P=0.373N     P=0.509N     P=0.513N     P=0.537N     | 
|POLY 3             |     P=0.153N     P=0.238N     P=0.225N     P=0.250N    |P=0.340N     P=0.508N     P=0.505N     P=0.521N     | 
|POLY 1.5           |     P=0.156N     P=0.238N     P=0.230N     P=0.246N    |P=0.342N     P=0.506N     P=0.503N     P=0.517N     | 
|POLY 6             |     P=0.151N     P=0.236N     P=0.217N     P=0.251N    |P=0.339N     P=0.510N     P=0.506N     P=0.521N     | 
|LOGISTIC REGRESSION|     P=0.137N     P=0.235N     P=0.289N     P=0.212N    |P=0.254N     P=0.521N     P=0.530N     P=0.429N     | 
|COCH-ARM / FISHERS |     P=0.160N     P=0.247N     P=0.247N     P=0.247N    |P=0.350N     P=0.505N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.034N*    (e)          (e)          (e)         |P=0.140N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen: Capsule                                                                                                                  | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    7/50 (14%)   12/50 (24%)  30/50 (60%) |8/49 (16%)   17/48 (35%)  12/49 (24%)  20/49 (41%)  | 
|POLY-3 RATE (b)    |     1/44.13      7/44.21      12/47.51     30/45.11    |8/44.73      17/44.46     12/45.18     20/41.90     | 
|POLY-3 PERCENT (g) |     2.3%         15.8%        25.3%        66.5%       |17.9%        38.2%        26.6%        47.7%        | 
|TERMINAL (d)       |     0/31 (0%)    7/33 (21%)   10/39 (26%)  22/31 (71%) |6/35 (17%)   12/32 (38%)  9/36 (25%)   17/35 (49%)  | 
|FIRST INCIDENCE    |     641          729 (T)      586          504         |648          621          492          544          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.038 *    P=0.005 **   P<0.001 **  |P=0.040 *    P=0.024 *    P=0.242      P=0.007 **   | 
|POLY 3             |     P<0.001 **   P=0.030 *    P<0.001 **   P<0.001 **  |P=0.016 *    P=0.026 *    P=0.231      P=0.002 **   | 
|POLY 1.5           |     P<0.001 **   P=0.030 *    P<0.001 **   P<0.001 **  |P=0.018 *    P=0.026 *    P=0.230      P=0.002 **   | 
|POLY 6             |     P<0.001 **   P=0.030 *    P=0.002 **   P<0.001 **  |P=0.018 *    P=0.026 *    P=0.236      P=0.002 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.035 *    P=0.002 **   P<0.001 **  |P=0.017 *    P=0.026 *    P=0.224      P=0.003 **   | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.030 *    P<0.001 **   P<0.001 **  |P=0.034 *    P=0.027 *    P=0.226      P=0.007 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 34      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Edema                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   0/50 (0%)    1/50 (2%)    2/50 (4%)   |2/50 (4%)    3/49 (6%)    1/49 (2%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     6/45.33      0/44.21      1/47.44      2/43.47     |2/45.25      3/44.45      1/44.18      0/40.27      | 
|POLY-3 PERCENT (g) |     13.2%        0.0%         2.1%         4.6%        |4.4%         6.8%         2.3%         0.0%         | 
|TERMINAL (d)       |     2/31 (7%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |1/35 (3%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     544          ---          586          401         |563          641          596          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.243N     P=0.020N*    P=0.046N*    P=0.159N    |P=0.089N     P=0.492      P=0.512N     P=0.257N     | 
|POLY 3             |     P=0.219N     P=0.016N*    P=0.049N*    P=0.146N    |P=0.090N     P=0.492      P=0.508N     P=0.264N     | 
|POLY 1.5           |     P=0.224N     P=0.016N*    P=0.052N     P=0.143N    |P=0.088N     P=0.492      P=0.508N     P=0.260N     | 
|POLY 6             |     P=0.213N     P=0.017N*    P=0.044N*    P=0.148N    |P=0.089N     P=0.492      P=0.507N     P=0.262N     | 
|LOGISTIC REGRESSION|     P=0.094N     P=0.016N*    P=0.104N     P=0.055N    |P=0.052N     P=0.480      P=0.531N     P=0.212N     | 
|COCH-ARM / FISHERS |     P=0.231N     P=0.013N*    P=0.056N     P=0.134N    |P=0.079N     P=0.490      P=0.508N     P=0.253N     | 
|ORDER RESTRICTED   |     P=0.011N*    (e)          (e)          (e)         |P=0.126N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Erosion                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/49 (0%)    0/49 (0%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |     3/44.05      0/44.21      0/46.96      1/41.96     |0/44.71      0/43.83      0/43.73      1/40.27      | 
|POLY-3 PERCENT (g) |     6.8%         0.0%         0.0%         2.4%        |0.0%         0.0%         0.0%         2.5%         | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    0/39 (0%)    1/31 (3%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     694          ---          ---          729 (T)     |---          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.322N     P=0.111N     P=0.088N     P=0.308N    |P=0.192      (e)          (e)          P=0.500      | 
|POLY 3             |     P=0.319N     P=0.118N     P=0.108N     P=0.323N    |P=0.174      (e)          (e)          P=0.479      | 
|POLY 1.5           |     P=0.322N     P=0.119N     P=0.113N     P=0.319N    |P=0.176      (e)          (e)          P=0.482      | 
|POLY 6             |     P=0.316N     P=0.116N     P=0.101N     P=0.323N    |P=0.176      (e)          (e)          P=0.482      | 
|LOGISTIC REGRESSION|     P=0.332N     P=0.118N     P=0.110N     P=0.318N    |(e)          (e)          (e)          P=0.500      | 
|COCH-ARM / FISHERS |     P=0.327N     P=0.121N     P=0.121N     P=0.309N    |P=0.185      (e)          (e)          P=0.495      | 
|ORDER RESTRICTED   |     P=0.042N*    (e)          (e)          (e)         |P=0.104      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 35      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/49 (0%)    0/49 (0%)    2/49 (4%)    | 
|POLY-3 RATE (b)    |     0/43.81      0/44.21      0/46.96      0/41.96     |1/45.25      0/43.83      0/43.73      2/40.27      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.2%         0.0%         0.0%         5.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |563          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.204      P=0.500N     P=0.513N     P=0.482      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.195      P=0.506N     P=0.507N     P=0.459      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.196      P=0.505N     P=0.506N     P=0.466      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.197      P=0.509N     P=0.507N     P=0.462      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.215      P=0.541N     P=0.566N     P=0.496      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.206      P=0.505N     P=0.505N     P=0.492      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.106      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    2/50 (4%)    2/50 (4%)   |4/50 (8%)    3/49 (6%)    1/49 (2%)    1/49 (2%)    | 
|POLY-3 RATE (b)    |     4/44.97      1/44.39      2/47.50      2/43.37     |4/45.69      3/44.45      1/44.18      1/40.29      | 
|POLY-3 PERCENT (g) |     8.9%         2.3%         4.2%         4.6%        |8.8%         6.8%         2.3%         2.5%         | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |2/35 (6%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     586          682          619          465         |516          641          596          725          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.424N     P=0.187N     P=0.283N     P=0.365N    |P=0.102N     P=0.520N     P=0.192N     P=0.201N     | 
|POLY 3             |     P=0.416N     P=0.182N     P=0.312N     P=0.354N    |P=0.105N     P=0.515N     P=0.189N     P=0.219N     | 
|POLY 1.5           |     P=0.418N     P=0.181N     P=0.324N     P=0.351N    |P=0.103N     P=0.513N     P=0.187N     P=0.212N     | 
|POLY 6             |     P=0.412N     P=0.181N     P=0.296N     P=0.354N    |P=0.105N     P=0.517N     P=0.189N     P=0.218N     | 
|LOGISTIC REGRESSION|     P=0.246N     P=0.174N     P=0.468N     P=0.187N    |P=0.065N     P=0.523N     P=0.192N     P=0.172N     | 
|COCH-ARM / FISHERS |     P=0.414N     P=0.181N     P=0.339N     P=0.339N    |P=0.092N     P=0.511N     P=0.187N     P=0.187N     | 
|ORDER RESTRICTED   |     P=0.211N     (e)          (e)          (e)         |P=0.145N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 36      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    0/50 (0%)    3/50 (6%)    3/50 (6%)   |2/50 (4%)    2/49 (4%)    2/49 (4%)    3/49 (6%)    | 
|POLY-3 RATE (b)    |     4/44.64      0/44.21      3/47.59      3/43.47     |2/45.90      2/44.28      2/45.02      3/41.24      | 
|POLY-3 PERCENT (g) |     9.0%         0.0%         6.3%         6.9%        |4.4%         4.5%         4.4%         7.3%         | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    1/39 (3%)    1/31 (3%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     544          ---          586          401         |516          641          492          239          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.410      P=0.061N     P=0.414N     P=0.513N    |P=0.355      P=0.688      P=0.688      P=0.472      | 
|POLY 3             |     P=0.413      P=0.061N     P=0.465N     P=0.514N    |P=0.341      P=0.681      P=0.687      P=0.451      | 
|POLY 1.5           |     P=0.412      P=0.061N     P=0.481N     P=0.512N    |P=0.348      P=0.683      P=0.687      P=0.460      | 
|POLY 6             |     P=0.416      P=0.060N     P=0.442N     P=0.513N    |P=0.344      P=0.678      P=0.688      P=0.452      | 
|LOGISTIC REGRESSION|     P=0.566      P=0.062N     P=0.603N     P=0.373N    |P=0.461N     P=0.666      P=0.712      P=0.689N     | 
|COCH-ARM / FISHERS |     P=0.418      P=0.059N     P=0.500N     P=0.500N    |P=0.375      P=0.684      P=0.684      P=0.490      | 
|ORDER RESTRICTED   |     P=0.284N     (e)          (e)          (e)         |P=0.429      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Edema                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |2/50 (4%)    1/49 (2%)    1/48 (2%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     1/44.06      0/44.21      0/46.96      2/42.70     |2/45.25      1/43.99      1/43.78      0/40.27      | 
|POLY-3 PERCENT (g) |     2.3%         0.0%         0.0%         4.7%        |4.4%         2.3%         2.3%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    1/31 (3%)   |1/35 (3%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     662          ---          ---          465         |563          687          596          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.201      P=0.495N     P=0.476N     P=0.492     |P=0.183N     P=0.507N     P=0.512N     P=0.257N     | 
|POLY 3             |     P=0.207      P=0.499N     P=0.487N     P=0.489     |P=0.186N     P=0.510N     P=0.512N     P=0.264N     | 
|POLY 1.5           |     P=0.206      P=0.500N     P=0.493N     P=0.491     |P=0.184N     P=0.508N     P=0.513N     P=0.260N     | 
|POLY 6             |     P=0.208      P=0.497N     P=0.479N     P=0.491     |P=0.183N     P=0.513N     P=0.508N     P=0.262N     | 
|LOGISTIC REGRESSION|     P=0.290      P=0.499N     P=0.542N     P=0.579     |P=0.122N     P=0.517N     P=0.554N     P=0.212N     | 
|COCH-ARM / FISHERS |     P=0.208      P=0.500N     P=0.500N     P=0.500     |P=0.172N     P=0.508N     P=0.515N     P=0.253N     | 
|ORDER RESTRICTED   |     P=0.122      (e)          (e)          (e)         |P=0.140N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 37      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Erosion                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    2/50 (4%)    1/50 (2%)    1/50 (2%)   |2/50 (4%)    2/49 (4%)    0/48 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     4/44.81      2/44.53      1/47.35      1/42.25     |2/45.51      2/45.15      0/43.32      0/40.27      | 
|POLY-3 PERCENT (g) |     8.9%         4.5%         2.1%         2.4%        |4.4%         4.4%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     544          652          619          652         |591          395          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.130N     P=0.319N     P=0.149N     P=0.195N    |P=0.085N     P=0.680      P=0.260N     P=0.279N     | 
|POLY 3             |     P=0.129N     P=0.340N     P=0.162N     P=0.197N    |P=0.077N     P=0.691      P=0.248N     P=0.265N     | 
|POLY 1.5           |     P=0.129N     P=0.340N     P=0.170N     P=0.192N    |P=0.076N     P=0.690      P=0.247N     P=0.260N     | 
|POLY 6             |     P=0.127N     P=0.336N     P=0.152N     P=0.198N    |P=0.076N     P=0.689      P=0.249N     P=0.265N     | 
|LOGISTIC REGRESSION|     P=0.094N     P=0.335N     P=0.261N     P=0.149N    |P=0.011N*    P=0.667      P=0.275N     P=0.182N     | 
|COCH-ARM / FISHERS |     P=0.126N     P=0.339N     P=0.181N     P=0.181N    |P=0.072N     P=0.684      P=0.258N     P=0.253N     | 
|ORDER RESTRICTED   |     P=0.104N     (e)          (e)          (e)         |P=0.138N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |2/50 (4%)    1/49 (2%)    1/48 (2%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     2/44.54      1/44.21      2/47.59      1/41.96     |2/45.36      1/43.99      1/43.78      0/40.27      | 
|POLY-3 PERCENT (g) |     4.5%         2.3%         4.2%         2.4%        |4.4%         2.3%         2.3%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    1/33 (3%)    0/39 (0%)    1/31 (3%)   |1/35 (3%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     586          729 (T)      586          729 (T)     |516          687          596          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.487N     P=0.500N     P=0.653N     P=0.519N    |P=0.180N     P=0.510N     P=0.505N     P=0.254N     | 
|POLY 3             |     P=0.493N     P=0.503N     P=0.670N     P=0.521N    |P=0.186N     P=0.511N     P=0.512N     P=0.264N     | 
|POLY 1.5           |     P=0.491N     P=0.502N     P=0.680N     P=0.515N    |P=0.184N     P=0.509N     P=0.513N     P=0.260N     | 
|POLY 6             |     P=0.492N     P=0.501N     P=0.654N     P=0.524N    |P=0.183N     P=0.513N     P=0.509N     P=0.263N     | 
|LOGISTIC REGRESSION|     P=0.432N     P=0.498N     P=0.570      P=0.474N    |P=0.109N     P=0.523N     P=0.567N     P=0.190N     | 
|COCH-ARM / FISHERS |     P=0.479N     P=0.500N     P=0.691N     P=0.500N    |P=0.172N     P=0.508N     P=0.515N     P=0.253N     | 
|ORDER RESTRICTED   |     P=0.469N     (e)          (e)          (e)         |P=0.140N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 38      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Bilateral, Germinal Epithelium                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |                                                    | 
|POLY-3 RATE (b)    |     1/43.94      0/44.21      2/47.44      0/41.96     |                                                    | 
|POLY-3 PERCENT (g) |     2.3%         0.0%         4.2%         0.0%        |                                                    | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    1/39 (3%)    0/31 (0%)   |                                                    | 
|FIRST INCIDENCE    |     694          ---          586          ---         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.536N     P=0.489N     P=0.552      P=0.506N    |                                                    | 
|POLY 3             |     P=0.547N     P=0.499N     P=0.527      P=0.509N    |                                                    | 
|POLY 1.5           |     P=0.543N     P=0.500N     P=0.515      P=0.507N    |                                                    | 
|POLY 6             |     P=0.550N     P=0.496N     P=0.544      P=0.509N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.504N     P=0.500N     P=0.439      P=0.505N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.529N     P=0.500N     P=0.500      P=0.500N    |                                                    | 
|ORDER RESTRICTED   |     P=0.334N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    2/50 (4%)    1/50 (2%)   |                                                    | 
|POLY-3 RATE (b)    |     2/43.94      0/44.21      2/47.44      1/41.96     |                                                    | 
|POLY-3 PERCENT (g) |     4.6%         0.0%         4.2%         2.4%        |                                                    | 
|TERMINAL (d)       |     1/31 (3%)    0/33 (0%)    1/39 (3%)    1/31 (3%)   |                                                    | 
|FIRST INCIDENCE    |     694          ---          586          729 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.612      P=0.227N     P=0.630N     P=0.503N    |                                                    | 
|POLY 3             |     P=0.590      P=0.236N     P=0.666N     P=0.516N    |                                                    | 
|POLY 1.5           |     P=0.595      P=0.237N     P=0.678N     P=0.513N    |                                                    | 
|POLY 6             |     P=0.586      P=0.233N     P=0.648N     P=0.516N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.613      P=0.233N     P=0.662      P=0.511N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.613      P=0.247N     P=0.691N     P=0.500N    |                                                    | 
|ORDER RESTRICTED   |     P=0.417N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 39      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Ultimobranchial Cyst                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |2/50 (4%)    0/49 (0%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/43.91      1/44.21      0/46.96      2/42.07     |2/44.71      0/43.83      1/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     6.8%         2.3%         0.0%         4.8%        |4.5%         0.0%         2.3%         0.0%         | 
|TERMINAL (d)       |     2/31 (7%)    1/33 (3%)    0/39 (0%)    1/31 (3%)   |2/35 (6%)    0/32 (0%)    1/36 (3%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     702          729 (T)      ---          703         |729 (T)      ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.473N     P=0.280N     P=0.085N     P=0.492N    |P=0.243N     P=0.258N     P=0.490N     P=0.238N     | 
|POLY 3             |     P=0.473N     P=0.303N     P=0.107N     P=0.520N    |P=0.265N     P=0.241N     P=0.504N     P=0.256N     | 
|POLY 1.5           |     P=0.477N     P=0.305N     P=0.112N     P=0.516N    |P=0.263N     P=0.241N     P=0.502N     P=0.253N     | 
|POLY 6             |     P=0.468N     P=0.297N     P=0.100N     P=0.518N    |P=0.262N     P=0.242N     P=0.505N     P=0.254N     | 
|LOGISTIC REGRESSION|     P=0.487N     P=0.283N     P=0.095N     P=0.513N    |P=0.243N     (e)          P=0.490N     (e)          | 
|COCH-ARM / FISHERS |     P=0.479N     P=0.309N     P=0.121N     P=0.500N    |P=0.251N     P=0.253N     P=0.500N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.192N     (e)          (e)          (e)         |P=0.087N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: C-Cell                                                                                                            | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   2/50 (4%)    9/50 (18%)   4/50 (8%)   |10/50 (20%)  11/49 (22%)  7/50 (14%)   5/50 (10%)   | 
|POLY-3 RATE (b)    |     8/43.91      2/44.21      9/46.96      4/42.76     |10/45.83     11/44.91     7/44.18      5/41.83      | 
|POLY-3 PERCENT (g) |     18.2%        4.5%         19.2%        9.4%        |21.8%        24.5%        15.8%        12.0%        | 
|TERMINAL (d)       |     7/31 (23%)   2/33 (6%)    9/39 (23%)   2/31 (7%)   |6/35 (17%)   7/32 (22%)   7/36 (19%)   4/35 (11%)   | 
|FIRST INCIDENCE    |     702          729 (T)      729 (T)      576         |591          576          729 (T)      480          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.437N     P=0.036N*    P=0.506N     P=0.183N    |P=0.052N     P=0.431      P=0.293N     P=0.153N     | 
|POLY 3             |     P=0.466N     P=0.043N*    P=0.561      P=0.188N    |P=0.074N     P=0.479      P=0.325N     P=0.173N     | 
|POLY 1.5           |     P=0.465N     P=0.044N*    P=0.533      P=0.189N    |P=0.069N     P=0.481      P=0.312N     P=0.164N     | 
|POLY 6             |     P=0.458N     P=0.040N*    P=0.601      P=0.179N    |P=0.074N     P=0.473      P=0.340N     P=0.173N     | 
|LOGISTIC REGRESSION|     P=0.464N     P=0.032N*    P=0.507N     P=0.196N    |P=0.065N     P=0.480      P=0.305N     P=0.149N     | 
|COCH-ARM / FISHERS |     P=0.444N     P=0.046N*    P=0.500      P=0.178N    |P=0.050N     P=0.479      P=0.298N     P=0.131N     | 
|ORDER RESTRICTED   |     P=0.170N     (e)          (e)          (e)         |P=0.140N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 40      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicle                                                                                                          | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    4/50 (8%)    1/50 (2%)   |2/50 (4%)    1/49 (2%)    2/50 (4%)    4/50 (8%)    | 
|POLY-3 RATE (b)    |     1/43.81      2/44.21      4/47.35      1/41.96     |2/44.92      1/43.83      2/44.18      4/41.11      | 
|POLY-3 PERCENT (g) |     2.3%         4.5%         8.5%         2.4%        |4.5%         2.3%         4.5%         9.7%         | 
|TERMINAL (d)       |     1/31 (3%)    2/33 (6%)    3/39 (8%)    1/31 (3%)   |1/35 (3%)    1/32 (3%)    2/36 (6%)    4/35 (11%)   | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      619          729 (T)     |674          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.591N     P=0.522      P=0.246      P=0.762     |P=0.152      P=0.518N     P=0.684N     P=0.340      | 
|POLY 3             |     P=0.557      P=0.503      P=0.203      P=0.751     |P=0.121      P=0.509N     P=0.688      P=0.297      | 
|POLY 1.5           |     P=0.565      P=0.501      P=0.192      P=0.753     |P=0.125      P=0.507N     P=0.691      P=0.304      | 
|POLY 6             |     P=0.557      P=0.509      P=0.221      P=0.752     |P=0.123      P=0.512N     P=0.686      P=0.299      | 
|LOGISTIC REGRESSION|     P=0.580      P=0.522      P=0.186      P=0.762     |P=0.129      P=0.507N     P=0.691      P=0.306      | 
|COCH-ARM / FISHERS |     P=0.591      P=0.500      P=0.181      P=0.753N    |P=0.142      P=0.508N     P=0.691N     P=0.339      | 
|ORDER RESTRICTED   |     P=0.371      (e)          (e)          (e)         |P=0.146      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Urinary Bladder                                                                                                                  | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    1/49 (2%)   |0/50 (0%)    0/49 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/43.81      2/44.42      0/46.96      1/41.94     |0/44.71      0/43.83      0/44.18      0/41.11      | 
|POLY-3 PERCENT (g) |     0.0%         4.5%         0.0%         2.4%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/33 (0%)    0/39 (0%)    0/31 (0%)   |0/35 (0%)    0/32 (0%)    0/36 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          682          ---          465         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.644      P=0.259      (e)          P=0.496     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.639      P=0.240      (e)          P=0.491     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.637      P=0.238      (e)          P=0.491     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.632N     P=0.245      (e)          P=0.494     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.555N     P=0.239      (e)          P=0.702     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.640      P=0.247      (e)          P=0.495     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.317      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 41      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/50 (2%)    3/49 (6%)    2/50 (4%)    3/50 (6%)    | 
|POLY-3 RATE (b)    |                                                        |1/44.71      3/43.83      2/44.21      3/41.11      | 
|POLY-3 PERCENT (g) |                                                        |2.2%         6.9%         4.5%         7.3%         | 
|TERMINAL (d)       |                                                        |1/35 (3%)    3/32 (9%)    1/36 (3%)    3/35 (9%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      729 (T)      723          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.371      P=0.273      P=0.513      P=0.305      | 
|POLY 3             |                                                        |P=0.315      P=0.298      P=0.496      P=0.276      | 
|POLY 1.5           |                                                        |P=0.321      P=0.299      P=0.498      P=0.281      | 
|POLY 6             |                                                        |P=0.319      P=0.296      P=0.496      P=0.279      | 
|LOGISTIC REGRESSION|                                                        |P=0.368      P=0.273      P=0.508      P=0.305      | 
|COCH-ARM / FISHERS |                                                        |P=0.353      P=0.301      P=0.500      P=0.309      | 
|ORDER RESTRICTED   |                                                        |P=0.236      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hydrometra                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/50 (2%)    4/49 (8%)    2/50 (4%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |                                                        |1/45.00      4/43.83      2/44.29      1/42.05      | 
|POLY-3 PERCENT (g) |                                                        |2.2%         9.1%         4.5%         2.4%         | 
|TERMINAL (d)       |                                                        |0/35 (0%)    4/32 (13%)   1/36 (3%)    0/35 (0%)    | 
|FIRST INCIDENCE    |                                                        |652          729 (T)      702          284          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.301N     P=0.158      P=0.501      P=0.748      | 
|POLY 3             |                                                        |P=0.330N     P=0.170      P=0.494      P=0.745      | 
|POLY 1.5           |                                                        |P=0.325N     P=0.172      P=0.497      P=0.748      | 
|POLY 6             |                                                        |P=0.327N     P=0.167      P=0.493      P=0.748      | 
|LOGISTIC REGRESSION|                                                        |P=0.249N     P=0.172      P=0.500      P=0.574N     | 
|COCH-ARM / FISHERS |                                                        |P=0.303N     P=0.175      P=0.500      P=0.753N     | 
|ORDER RESTRICTED   |                                                        |P=0.373N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  03/25/05                           EXPERIMENT: 91005 TEST: 07                                            Page 42      
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHYLENE BLUE TRIHYDRATE              
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG    |0 MG/KG      5 MG/KG      25 MG/KG     50 MG/KG     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |4/50 (8%)    1/49 (2%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |                                                        |4/45.01      1/43.93      0/44.18      2/41.11      | 
|POLY-3 PERCENT (g) |                                                        |8.9%         2.3%         0.0%         4.9%         | 
|TERMINAL (d)       |                                                        |3/35 (9%)    0/32 (0%)    0/36 (0%)    2/35 (6%)    | 
|FIRST INCIDENCE    |                                                        |648          702          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.323N     P=0.204N     P=0.065N     P=0.347N     | 
|POLY 3             |                                                        |P=0.336N     P=0.186N     P=0.062N     P=0.380N     | 
|POLY 1.5           |                                                        |P=0.335N     P=0.185N     P=0.062N     P=0.372N     | 
|POLY 6             |                                                        |P=0.335N     P=0.188N     P=0.063N     P=0.377N     | 
|LOGISTIC REGRESSION|                                                        |P=0.353N     P=0.185N     P=0.064N     P=0.371N     | 
|COCH-ARM / FISHERS |                                                        |P=0.326N     P=0.187N     P=0.059N     P=0.339N     | 
|ORDER RESTRICTED   |                                                        |P=0.093N     (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.