National Toxicology Program

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TDMS Study 92013-05 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                4-METHYLIMIDAZOLE                                   DATE: 12/06/04       
EXPERIMENT: 92013 TEST: 05                                                                                     TIME: 08:37:02       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92013B       
PATHOLOGIST: FARNELL, DANIEL R.                                                                                CAS: 822-36-6        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                           FINAL #1 RATS                                                            
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                4-METHYLIMIDAZOLE                                   DATE: 12/06/04       
EXPERIMENT: 92013 TEST: 05                                                                                     TIME: 08:37:02       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92013B       
PATHOLOGIST: FARNELL, DANIEL R.                                                                                CAS: 822-36-6        
Rats(FISCHER 344)                                                                                                                   
-----------------------------                                                                                                       
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE                                                                   
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES                                                                 
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.                                                                                      
                                                 ---------------                                                                    
                                                 Adrenal Cortex                                                                     
                                                 Adrenal Medulla                                                                    
                                                 Brain                                                                              
                                                 Clitoral/Preputial Gland                                                           
                                                 Heart                                                                              
                                                 Islets, Pancreatic                                                                 
                                                 Kidney                                                                             
                                                 Liver                                                                              
                                                 Lung                                                                               
                                                 Nose                                                                               
                                                 Ovary                                                                              
                                                 Pancreas                                                                           
                                                 Parathyroid Gland                                                                  
                                                 Pituitary Gland                                                                    
                                                 Salivary Glands                                                                    
                                                 Spleen                                                                             
                                                 Testes                                                                             
                                                 Thyroid Gland                                                                      
                                                 Urinary Bladder                                                                    
                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                4-METHYLIMIDAZOLE                                   DATE: 12/06/04       
EXPERIMENT: 92013 TEST: 05                                                                                     TIME: 08:37:02       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92013B       
PATHOLOGIST: FARNELL, DANIEL R.                                                                                CAS: 822-36-6        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                   4-METHYLIMIDAZOLE                                                                              
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Medulla                        Pheochromocytoma Complex                                                                     
                                       Pheochromocytoma: Benign, Complex, Malignant, NOS                                            
Brain                                  Oligodendroglioma, Glioma, or Astrocytoma                                                    
Pituitary Gland: Pars Distalis or Unspecified Site                                                                                  
                                       Adenoma                                                                                      
                                       Carcinoma or Adenoma                                                                         
Skin                                   Fibroma                                                                                      
                                       Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                 
Thyroid Gland: C-Cell                  Adenoma                                                                                      
All Organs                             Benign Tumors                                                                                
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Clitoral/Preputial Gland               Adenoma                                                                                      
                                       Carcinoma or Adenoma                                                                         
Mammary Gland                          Fibroadenoma                                                                                 
                                       Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                 
Pituitary Gland: Pars Distalis or Unspecified Site                                                                                  
                                       Adenoma                                                                                      
                                       Carcinoma or Adenoma                                                                         
Uterus                                 Polyp Stromal                                                                                
                                       Sarcoma Stromal or Polyp Stromal                                                             
All Organs                             Histiocytic Sarcoma                                                                          
                                       Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                           
                                       Benign Tumors                                                                                
                                       Malignant and Benign Tumors                                                                  
===============================================================                                                                     
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 1       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)        -                    4-METHYLIMIDAZOLE      
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Pheochromocytoma Benign                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   5/50 (10%)   3/50 (6%)    3/50 (6%)   |2/48 (4%)    1/50 (2%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     8/45.33      5/43.44      3/44.41      3/44.07     |2/44.67      1/45.69      2/43.88      2/44.39      | 
|POLY-3 PERCENT (g) |     17.7%        11.5%        6.8%         6.8%        |4.5%         2.2%         4.6%         4.5%         | 
|TERMINAL (d)       |     7/31 (23%)   2/34 (6%)    3/33 (9%)    2/32 (6%)   |2/42 (5%)    1/39 (3%)    1/34 (3%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     700          700          729 (T)      607         |729 (T)      729 (T)      700          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.070N     P=0.247N     P=0.082N     P=0.096N    |P=0.453      P=0.526N     P=0.619      P=0.628      | 
|POLY 3             |     P=0.066N     P=0.303N     P=0.104N     P=0.106N    |P=0.520      P=0.492N     P=0.687      P=0.692      | 
|POLY 1.5           |     P=0.065N     P=0.298N     P=0.102N     P=0.104N    |P=0.530      P=0.486N     P=0.689N     P=0.686N     | 
|POLY 6             |     P=0.068N     P=0.298N     P=0.105N     P=0.109N    |P=0.506      P=0.500N     P=0.672      P=0.678      | 
|LOGISTIC REGRESSION|     P=0.074N     P=0.299N     P=0.096N     P=0.115N    |P=0.490      P=0.526N     P=0.673      P=0.628      | 
|COCH-ARM / FISHERS |     P=0.066N     P=0.277N     P=0.100N     P=0.100N    |P=0.539      P=0.485N     P=0.676N     P=0.676N     | 
|ORDER RESTRICTED   |     P=0.070N     (e)          (e)          (e)         |P=0.600      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Pheochromocytoma Complex                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/48 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/45.39      0/43.15      0/44.41      0/43.64     |0/44.67      0/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     4.4%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/31 (3%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |0/42 (0%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     685          ---          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.120N     P=0.235N     P=0.238N     P=0.253N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.109N     P=0.249N     P=0.242N     P=0.246N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.110N     P=0.246N     P=0.240N     P=0.243N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.108N     P=0.249N     P=0.244N     P=0.250N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.117N     P=0.246N     P=0.240N     P=0.244N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.115N     P=0.247N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.032N*    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 2       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Pheochromocytoma Malignant                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |1/48 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      2/43.26      0/44.41      0/43.64     |1/44.67      0/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         4.6%         0.0%         0.0%        |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    1/34 (3%)    0/33 (0%)    0/32 (0%)   |1/42 (2%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          700          ---          ---         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.419N     P=0.244      (e)          (e)         |P=0.331N     P=0.515N     P=0.542N     P=0.536N     | 
|POLY 3             |     P=0.417N     P=0.227      (e)          (e)         |P=0.298N     P=0.495N     P=0.504N     P=0.501N     | 
|POLY 1.5           |     P=0.414N     P=0.229      (e)          (e)         |P=0.301N     P=0.492N     P=0.498N     P=0.496N     | 
|POLY 6             |     P=0.419N     P=0.228      (e)          (e)         |P=0.296N     P=0.500N     P=0.513N     P=0.509N     | 
|LOGISTIC REGRESSION|     P=0.412N     P=0.228      (e)          (e)         |P=0.331N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.405N     P=0.247      (e)          (e)         |P=0.301N     P=0.490N     P=0.490N     P=0.490N     | 
|ORDER RESTRICTED   |     P=0.245N     (e)          (e)          (e)         |P=0.121N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  6/50 (12%)   3/50 (6%)    3/50 (6%)   |3/48 (6%)    1/50 (2%)    2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     10/45.50     6/43.44      3/44.41      3/44.07     |3/44.67      1/45.69      2/43.88      2/44.39      | 
|POLY-3 PERCENT (g) |     22.0%        13.8%        6.8%         6.8%        |6.7%         2.2%         4.6%         4.5%         | 
|TERMINAL (d)       |     8/31 (26%)   3/34 (9%)    3/33 (9%)    2/32 (6%)   |3/42 (7%)    1/39 (3%)    1/34 (3%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     685          700          729 (T)      607         |729 (T)      729 (T)      700          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.022N*    P=0.182N     P=0.030N*    P=0.038N*   |P=0.578N     P=0.332N     P=0.592N     P=0.583N     | 
|POLY 3             |     P=0.019N*    P=0.234N     P=0.037N*    P=0.039N*   |P=0.501N     P=0.297N     P=0.508N     P=0.503N     | 
|POLY 1.5           |     P=0.019N*    P=0.229N     P=0.037N*    P=0.038N*   |P=0.494N     P=0.291N     P=0.494N     P=0.490N     | 
|POLY 6             |     P=0.019N*    P=0.231N     P=0.038N*    P=0.040N*   |P=0.512N     P=0.305N     P=0.528N     P=0.520N     | 
|LOGISTIC REGRESSION|     P=0.022N*    P=0.230N     P=0.037N*    P=0.044N*   |P=0.542N     P=0.332N     P=0.538N     P=0.583N     | 
|COCH-ARM / FISHERS |     P=0.020N*    P=0.207N     P=0.036N*    P=0.036N*   |P=0.486N     P=0.293N     P=0.480N     P=0.480N     | 
|ORDER RESTRICTED   |     P=0.017N*    (e)          (e)          (e)         |P=0.396N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 3       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Oligodendroglioma, Glioma, or Astrocytoma                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      0/43.15      1/44.84      2/45.37     |0/46.53      1/46.50      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         4.4%        |0.0%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          605          369         |---          421          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.075      (e)          P=0.500      P=0.238     |P=0.569N     P=0.508      (e)          (e)          | 
|POLY 3             |     P=0.073      (e)          P=0.498      P=0.238     |P=0.574N     P=0.500      (e)          (e)          | 
|POLY 1.5           |     P=0.072      (e)          P=0.499      P=0.238     |P=0.569N     P=0.502      (e)          (e)          | 
|POLY 6             |     P=0.072      (e)          P=0.499      P=0.236     |P=0.581N     P=0.497      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.043 *    (e)          P=0.531      (e)         |P=0.648N     P=0.350      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.070      (e)          P=0.500      P=0.247     |P=0.567N     P=0.500      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.075      (e)          (e)          (e)         |P=0.389N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral/Preputial Gland                                                                                                         | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/50 (0%)    0/49 (0%)   |8/50 (16%)   1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/45.22      1/43.26      0/44.41      0/42.87     |8/47.04      1/46.48      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     4.4%         2.3%         0.0%         0.0%        |17.0%        2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/31 (7%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |6/43 (14%)   0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      700          ---          ---         |624          434          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.104N     P=0.485N     P=0.224N     P=0.231N    |P=0.002N**   P=0.027N*    P=0.012N*    P=0.011N*    | 
|POLY 3             |     P=0.102N     P=0.515N     P=0.241N     P=0.249N    |P<0.001N**   P=0.017N*    P=0.005N**   P=0.005N**   | 
|POLY 1.5           |     P=0.102N     P=0.512N     P=0.240N     P=0.247N    |P<0.001N**   P=0.016N*    P=0.004N**   P=0.004N**   | 
|POLY 6             |     P=0.102N     P=0.514N     P=0.242N     P=0.252N    |P<0.001N**   P=0.018N*    P=0.006N**   P=0.006N**   | 
|LOGISTIC REGRESSION|     P=0.106N     P=0.514N     (e)          (e)         |P<0.001N**   P=0.019N*    P=0.006N**   P=0.005N**   | 
|COCH-ARM / FISHERS |     P=0.102N     P=0.500N     P=0.247N     P=0.253N    |P<0.001N**   P=0.015N*    P=0.003N**   P=0.003N**   | 
|ORDER RESTRICTED   |     P=0.082N     (e)          (e)          (e)         |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 4       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral/Preputial Gland                                                                                                         | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/49 (0%)   |2/50 (4%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      0/43.15      1/45.01      0/42.87     |2/46.53      1/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.2%         0.0%        |4.3%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |2/43 (5%)    1/39 (3%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          538          ---         |729 (T)      729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.692      (e)          P=0.492      (e)         |P=0.127N     P=0.534N     P=0.291N     P=0.285N     | 
|POLY 3             |     P=0.682      (e)          P=0.499      (e)         |P=0.103N     P=0.506N     P=0.251N     P=0.248N     | 
|POLY 1.5           |     P=0.686      (e)          P=0.499      (e)         |P=0.102N     P=0.500N     P=0.244N     P=0.242N     | 
|POLY 6             |     P=0.676      (e)          P=0.499      (e)         |P=0.105N     P=0.513N     P=0.261N     P=0.256N     | 
|LOGISTIC REGRESSION|     P=0.702      (e)          P=0.543      (e)         |P=0.127N     P=0.534N     (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.692      (e)          P=0.500      (e)         |P=0.101N     P=0.500N     P=0.247N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.380      (e)          (e)          (e)         |P=0.081N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral/Preputial Gland                                                                                                         | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    1/50 (2%)    0/49 (0%)   |10/50 (20%)  2/50 (4%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/45.22      1/43.26      1/45.01      0/42.87     |10/47.04     2/46.48      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     4.4%         2.3%         2.2%         0.0%        |21.3%        4.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/31 (7%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |8/43 (19%)   1/39 (3%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      700          538          ---         |624          434          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.159N     P=0.485N     P=0.490N     P=0.231N    |P<0.001N**   P=0.025N*    P=0.004N**   P=0.004N**   | 
|POLY 3             |     P=0.158N     P=0.515N     P=0.502N     P=0.249N    |P<0.001N**   P=0.014N*    P<0.001N**   P<0.001N**   | 
|POLY 1.5           |     P=0.157N     P=0.512N     P=0.501N     P=0.247N    |P<0.001N**   P=0.013N*    P<0.001N**   P<0.001N**   | 
|POLY 6             |     P=0.159N     P=0.514N     P=0.501N     P=0.252N    |P<0.001N**   P=0.016N*    P=0.002N**   P<0.001N**   | 
|LOGISTIC REGRESSION|     P=0.153N     P=0.514N     P=0.480N     (e)         |P<0.001N**   P=0.016N*    P=0.002N**   P=0.002N**   | 
|COCH-ARM / FISHERS |     P=0.156N     P=0.500N     P=0.500N     P=0.253N    |P<0.001N**   P=0.014N*    P<0.001N**   P<0.001N**   | 
|ORDER RESTRICTED   |     P=0.128N     (e)          (e)          (e)         |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 5       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Schwannoma Benign                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    4/48 (8%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      0/43.15      0/44.41      0/43.64     |1/46.53      1/45.69      4/42.10      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.2%         2.2%         9.5%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |1/43 (2%)    1/39 (3%)    4/33 (12%)   0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      729 (T)      729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.522N     P=0.740      P=0.109      P=0.541N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.470N     P=0.756      P=0.150      P=0.509N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.457N     P=0.760      P=0.158      P=0.504N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.488N     P=0.752      P=0.138      P=0.517N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.522N     P=0.740      P=0.109      (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.446N     P=0.753N     P=0.168      P=0.500N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.178N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    2/49 (4%)    1/49 (2%)    1/49 (2%)   |0/49 (0%)    1/50 (2%)    0/48 (0%)    0/47 (0%)    | 
|POLY-3 RATE (b)    |     3/45.50      2/42.28      1/43.75      1/43.07     |0/45.90      1/45.69      0/42.98      0/41.55      | 
|POLY-3 PERCENT (g) |     6.6%         4.7%         2.3%         2.3%        |0.0%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/31 (7%)    2/34 (6%)    1/33 (3%)    1/32 (3%)   |0/43 (0%)    1/39 (3%)    0/34 (0%)    0/33 (0%)    | 
|FIRST INCIDENCE    |     653          729 (T)      729 (T)      729 (T)     |---          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.199N     P=0.475N     P=0.298N     P=0.309N    |P=0.607N     P=0.481      (e)          (e)          | 
|POLY 3             |     P=0.207N     P=0.533N     P=0.319N     P=0.325N    |P=0.583N     P=0.499      (e)          (e)          | 
|POLY 1.5           |     P=0.206N     P=0.528N     P=0.317N     P=0.321N    |P=0.577N     P=0.503      (e)          (e)          | 
|POLY 6             |     P=0.210N     P=0.535N     P=0.321N     P=0.331N    |P=0.591N     P=0.494      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.211N     P=0.529N     P=0.316N     P=0.322N    |(e)          P=0.481      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.204N     P=0.510N     P=0.316N     P=0.316N    |P=0.575N     P=0.505      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.240N     (e)          (e)          (e)         |P=0.397N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 6       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    2/49 (4%)    2/49 (4%)    1/49 (2%)   |0/49 (0%)    1/50 (2%)    0/48 (0%)    0/47 (0%)    | 
|POLY-3 RATE (b)    |     3/45.50      2/42.28      2/43.75      1/43.07     |0/45.90      1/45.69      0/42.98      0/41.55      | 
|POLY-3 PERCENT (g) |     6.6%         4.7%         4.6%         2.3%        |0.0%         2.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/31 (7%)    2/34 (6%)    2/33 (6%)    1/32 (3%)   |0/43 (0%)    1/39 (3%)    0/34 (0%)    0/33 (0%)    | 
|FIRST INCIDENCE    |     653          729 (T)      729 (T)      729 (T)     |---          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.232N     P=0.475N     P=0.486N     P=0.309N    |P=0.607N     P=0.481      (e)          (e)          | 
|POLY 3             |     P=0.243N     P=0.533N     P=0.518N     P=0.325N    |P=0.583N     P=0.499      (e)          (e)          | 
|POLY 1.5           |     P=0.241N     P=0.528N     P=0.515N     P=0.321N    |P=0.577N     P=0.503      (e)          (e)          | 
|POLY 6             |     P=0.248N     P=0.535N     P=0.521N     P=0.331N    |P=0.591N     P=0.494      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.248N     P=0.529N     P=0.515N     P=0.322N    |(e)          P=0.481      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.238N     P=0.510N     P=0.510N     P=0.316N    |P=0.575N     P=0.505      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.267N     (e)          (e)          (e)         |P=0.397N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Adenoma                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/48 (2%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/45.22      0/43.15      0/44.41      0/43.64     |0/46.53      0/45.69      1/43.90      2/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         2.3%         4.5%         | 
|TERMINAL (d)       |     0/31 (0%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    2/35 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          653          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.058      (e)          P=0.472      P=0.194      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.066      (e)          P=0.488      P=0.227      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.068      (e)          P=0.493      P=0.233      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.063      (e)          P=0.481      P=0.219      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.069      (e)          P=0.474      P=0.194      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.071      (e)          P=0.490      P=0.247      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.067      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 7       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      0/43.15      1/44.41      0/43.64     |0/46.53      2/46.30      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.3%         0.0%        |0.0%         4.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/34 (0%)    1/33 (3%)    0/32 (0%)   |0/43 (0%)    1/39 (3%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          536          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.697      (e)          P=0.512      (e)         |P=0.424N     P=0.229      (e)          (e)          | 
|POLY 3             |     P=0.684      (e)          P=0.496      (e)         |P=0.418N     P=0.236      (e)          (e)          | 
|POLY 1.5           |     P=0.688      (e)          P=0.498      (e)         |P=0.409N     P=0.239      (e)          (e)          | 
|POLY 6             |     P=0.678      (e)          P=0.495      (e)         |P=0.429N     P=0.233      (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.512      (e)         |P=0.410N     P=0.211      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.694      (e)          P=0.500      (e)         |P=0.405N     P=0.247      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.377      (e)          (e)          (e)         |P=0.255N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar                                                                      | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      1/43.15      1/44.41      1/43.64     |0/46.53      2/46.30      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         2.3%         2.3%         2.3%        |0.0%         4.3%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    1/34 (3%)    1/33 (3%)    1/32 (3%)   |0/43 (0%)    1/39 (3%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |---          536          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.384      P=0.518      P=0.512      P=0.506     |P=0.424N     P=0.229      (e)          (e)          | 
|POLY 3             |     P=0.373      P=0.491      P=0.496      P=0.493     |P=0.418N     P=0.236      (e)          (e)          | 
|POLY 1.5           |     P=0.377      P=0.493      P=0.498      P=0.495     |P=0.409N     P=0.239      (e)          (e)          | 
|POLY 6             |     P=0.366      P=0.491      P=0.495      P=0.490     |P=0.429N     P=0.233      (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.518      P=0.512      P=0.506     |P=0.410N     P=0.211      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.384      P=0.500      P=0.500      P=0.500     |P=0.405N     P=0.247      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.321      (e)          (e)          (e)         |P=0.255N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 8       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    1/50 (2%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      0/43.15      0/44.41      0/43.64     |2/46.67      1/45.79      2/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.3%         2.2%         4.6%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |1/43 (2%)    0/39 (0%)    2/34 (6%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |694          705          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.249N     P=0.525N     P=0.610      P=0.282N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.212N     P=0.507N     P=0.671      P=0.249N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.206N     P=0.501N     P=0.682      P=0.242N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.222N     P=0.514N     P=0.653      P=0.258N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.214N     P=0.500N     P=0.663      P=0.242N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.200N     P=0.500N     P=0.691N     P=0.247N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.165N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Fibroadenoma                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    1/50 (2%)    1/50 (2%)   |24/50 (48%)  6/50 (12%)   4/50 (8%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     3/45.22      1/43.15      1/45.01      1/43.64     |24/47.04     6/45.69      4/43.76      1/44.39      | 
|POLY-3 PERCENT (g) |     6.6%         2.3%         2.2%         2.3%        |51.0%        13.1%        9.1%         2.3%         | 
|TERMINAL (d)       |     3/31 (10%)   1/34 (3%)    0/33 (0%)    1/32 (3%)   |22/43 (51%)  6/39 (15%)   4/34 (12%)   1/35 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      538          729 (T)     |624          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.239N     P=0.272N     P=0.293N     P=0.293N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|POLY 3             |     P=0.242N     P=0.322N     P=0.307N     P=0.318N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|POLY 1.5           |     P=0.241N     P=0.319N     P=0.307N     P=0.314N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|POLY 6             |     P=0.244N     P=0.322N     P=0.306N     P=0.323N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|LOGISTIC REGRESSION|     P=0.243N     P=0.272N     P=0.294N     P=0.293N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|COCH-ARM / FISHERS |     P=0.242N     P=0.309N     P=0.309N     P=0.309N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|ORDER RESTRICTED   |     P=0.199N     (e)          (e)          (e)         |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 9       
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    1/50 (2%)    1/50 (2%)   |25/50 (50%)  7/50 (14%)   6/50 (12%)   1/50 (2%)    | 
|POLY-3 RATE (b)    |     3/45.22      1/43.15      1/45.01      1/43.64     |25/47.04     7/45.79      6/43.76      1/44.39      | 
|POLY-3 PERCENT (g) |     6.6%         2.3%         2.2%         2.3%        |53.1%        15.3%        13.7%        2.3%         | 
|TERMINAL (d)       |     3/31 (10%)   1/34 (3%)    0/33 (0%)    1/32 (3%)   |23/43 (54%)  6/39 (15%)   6/34 (18%)   1/35 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      538          729 (T)     |624          705          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.239N     P=0.272N     P=0.293N     P=0.293N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|POLY 3             |     P=0.242N     P=0.322N     P=0.307N     P=0.318N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|POLY 1.5           |     P=0.241N     P=0.319N     P=0.307N     P=0.314N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|POLY 6             |     P=0.244N     P=0.322N     P=0.306N     P=0.323N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|LOGISTIC REGRESSION|     P=0.243N     P=0.272N     P=0.294N     P=0.293N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|COCH-ARM / FISHERS |     P=0.242N     P=0.309N     P=0.309N     P=0.309N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|ORDER RESTRICTED   |     P=0.199N     (e)          (e)          (e)         |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)                                                                       | 
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/45.22      2/43.72      0/44.41      0/43.64     |0/46.53      1/45.98      1/44.26      1/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         4.6%         0.0%         0.0%        |0.0%         2.2%         2.3%         2.3%         | 
|TERMINAL (d)       |     0/31 (0%)    1/34 (3%)    0/33 (0%)    0/32 (0%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     ---          547          ---          ---         |---          653          581          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.406N     P=0.243      (e)          (e)         |P=0.356      P=0.496      P=0.491      P=0.459      | 
|POLY 3             |     P=0.416N     P=0.230      (e)          (e)         |P=0.367      P=0.498      P=0.490      P=0.491      | 
|POLY 1.5           |     P=0.413N     P=0.231      (e)          (e)         |P=0.377      P=0.500      P=0.495      P=0.496      | 
|POLY 6             |     P=0.418N     P=0.231      (e)          (e)         |P=0.353      P=0.495      P=0.483      P=0.483      | 
|LOGISTIC REGRESSION|     P=0.399N     P=0.272      (e)          (e)         |P=0.383      P=0.488      P=0.498      P=0.459      | 
|COCH-ARM / FISHERS |     P=0.405N     P=0.247      (e)          (e)         |P=0.384      P=0.500      P=0.500      P=0.500      | 
|ORDER RESTRICTED   |     P=0.247N     (e)          (e)          (e)         |P=0.318      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 10      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/48 (0%)    0/48 (0%)    2/49 (4%)   |0/49 (0%)    0/49 (0%)    0/47 (0%)    0/47 (0%)    | 
|POLY-3 RATE (b)    |     1/45.22      0/41.86      0/43.18      2/43.07     |0/45.90      0/45.30      0/42.54      0/41.55      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         0.0%         4.6%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/31 (3%)    0/34 (0%)    0/33 (0%)    2/32 (6%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    0/33 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          ---          729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.245      P=0.482N     P=0.488N     P=0.511     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.245      P=0.515N     P=0.509N     P=0.483     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.246      P=0.515N     P=0.509N     P=0.486     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.242      P=0.513N     P=0.508N     P=0.479     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.245      (e)          (e)          P=0.511     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.244      P=0.510N     P=0.510N     P=0.492     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.122      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     16/49 (33%)  13/49 (27%)  10/48 (21%)  7/48 (15%)  |29/48 (60%)  19/50 (38%)  20/50 (40%)  9/50 (18%)   | 
|POLY-3 RATE (b)    |     16/46.40     13/43.61     10/42.84     7/43.47     |29/46.70     19/46.68     20/44.79     9/44.91      | 
|POLY-3 PERCENT (g) |     34.5%        29.8%        23.3%        16.1%       |62.1%        40.7%        44.7%        20.0%        | 
|TERMINAL (d)       |     10/31 (32%)  10/33 (30%)  10/32 (31%)  6/32 (19%)  |25/42 (60%)  15/39 (39%)  17/34 (50%)  6/35 (17%)   | 
|FIRST INCIDENCE    |     464          477          729 (T)      384         |498          636          555          642          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.018N*    P=0.309N     P=0.121N     P=0.034N*   |P<0.001N**   P=0.084N     P=0.266N     P<0.001N**   | 
|POLY 3             |     P=0.022N*    P=0.402N     P=0.176N     P=0.037N*   |P<0.001N**   P=0.029N*    P=0.068N     P<0.001N**   | 
|POLY 1.5           |     P=0.020N*    P=0.382N     P=0.160N     P=0.033N*   |P<0.001N**   P=0.024N*    P=0.052N     P<0.001N**   | 
|POLY 6             |     P=0.027N*    P=0.413N     P=0.197N     P=0.044N*   |P<0.001N**   P=0.034N*    P=0.099N     P<0.001N**   | 
|LOGISTIC REGRESSION|     P=0.020N*    P=0.331N     P=0.144N     P=0.028N*   |P<0.001N**   P=0.027N*    P=0.064N     P<0.001N**   | 
|COCH-ARM / FISHERS |     P=0.020N*    P=0.329N     P=0.139N     P=0.031N*   |P<0.001N**   P=0.022N*    P=0.034N*    P<0.001N**   | 
|ORDER RESTRICTED   |     P=0.029N*    (e)          (e)          (e)         |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 11      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     16/49 (33%)  13/49 (27%)  10/48 (21%)  7/48 (15%)  |29/48 (60%)  20/50 (40%)  20/50 (40%)  9/50 (18%)   | 
|POLY-3 RATE (b)    |     16/46.40     13/43.61     10/42.84     7/43.47     |29/46.70     20/46.68     20/44.79     9/44.91      | 
|POLY-3 PERCENT (g) |     34.5%        29.8%        23.3%        16.1%       |62.1%        42.9%        44.7%        20.0%        | 
|TERMINAL (d)       |     10/31 (32%)  10/33 (30%)  10/32 (31%)  6/32 (19%)  |25/42 (60%)  16/39 (41%)  17/34 (50%)  6/35 (17%)   | 
|FIRST INCIDENCE    |     464          477          729 (T)      384         |498          636          555          642          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.018N*    P=0.309N     P=0.121N     P=0.034N*   |P<0.001N**   P=0.118N     P=0.266N     P<0.001N**   | 
|POLY 3             |     P=0.022N*    P=0.402N     P=0.176N     P=0.037N*   |P<0.001N**   P=0.046N*    P=0.068N     P<0.001N**   | 
|POLY 1.5           |     P=0.020N*    P=0.382N     P=0.160N     P=0.033N*   |P<0.001N**   P=0.039N*    P=0.052N     P<0.001N**   | 
|POLY 6             |     P=0.027N*    P=0.413N     P=0.197N     P=0.044N*   |P<0.001N**   P=0.054N     P=0.099N     P<0.001N**   | 
|LOGISTIC REGRESSION|     P=0.020N*    P=0.331N     P=0.144N     P=0.028N*   |P<0.001N**   P=0.042N*    P=0.064N     P<0.001N**   | 
|COCH-ARM / FISHERS |     P=0.020N*    P=0.329N     P=0.139N     P=0.031N*   |P<0.001N**   P=0.034N*    P=0.034N*    P<0.001N**   | 
|ORDER RESTRICTED   |     P=0.029N*    (e)          (e)          (e)         |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Basal Cell Adenoma                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/45.22      0/43.15      1/44.41      2/43.64     |0/46.53      0/45.69      0/43.76      1/44.39      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         2.3%         4.6%        |0.0%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/31 (3%)    0/34 (0%)    1/33 (3%)    2/32 (6%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      729 (T)     |---          ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.246      P=0.482N     P=0.748N     P=0.511     |P=0.178      (e)          (e)          P=0.459      | 
|POLY 3             |     P=0.246      P=0.509N     P=0.757      P=0.488     |P=0.193      (e)          (e)          P=0.491      | 
|POLY 1.5           |     P=0.248      P=0.507N     P=0.758      P=0.492     |P=0.196      (e)          (e)          P=0.496      | 
|POLY 6             |     P=0.241      P=0.509N     P=0.756      P=0.482     |P=0.190      (e)          (e)          P=0.483      | 
|LOGISTIC REGRESSION|     P=0.246      (e)          P=0.748N     P=0.511     |(e)          (e)          (e)          P=0.459      | 
|COCH-ARM / FISHERS |     P=0.247      P=0.500N     P=0.753N     P=0.500     |P=0.198      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.215      (e)          (e)          (e)         |P=0.112      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 12      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Basal Cell Adenoma, Basosquamous Tumor Benign, or                                                                           | 
|     Trichoepithelioma                                                                                                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/45.22      0/43.15      1/44.41      2/43.64     |1/46.53      0/45.69      0/43.76      1/44.39      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         2.3%         4.6%        |2.2%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/31 (3%)    0/34 (0%)    1/33 (3%)    2/32 (6%)   |1/43 (2%)    0/39 (0%)    0/34 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      729 (T)     |729 (T)      ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.246      P=0.482N     P=0.748N     P=0.511     |P=0.552      P=0.519N     P=0.547N     P=0.715      | 
|POLY 3             |     P=0.246      P=0.509N     P=0.757      P=0.488     |P=0.588      P=0.504N     P=0.512N     P=0.750      | 
|POLY 1.5           |     P=0.248      P=0.507N     P=0.758      P=0.492     |P=0.591      P=0.500N     P=0.506N     P=0.756      | 
|POLY 6             |     P=0.241      P=0.509N     P=0.756      P=0.482     |P=0.584      P=0.508N     P=0.521N     P=0.742      | 
|LOGISTIC REGRESSION|     P=0.246      (e)          P=0.748N     P=0.511     |P=0.552      (e)          (e)          P=0.715      | 
|COCH-ARM / FISHERS |     P=0.247      P=0.500N     P=0.753N     P=0.500     |P=0.595      P=0.500N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P=0.215      (e)          (e)          (e)         |P=0.390      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous                                                                      | 
|     Tumor (benign, malignant or NOS), or Trichoepithelioma                                                                      | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    2/50 (4%)    2/50 (4%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/45.22      0/43.15      2/44.46      2/43.64     |1/46.53      0/45.69      0/43.76      1/44.39      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         4.5%         4.6%        |2.2%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/31 (3%)    0/34 (0%)    1/33 (3%)    2/32 (6%)   |1/43 (2%)    0/39 (0%)    0/34 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          717          729 (T)     |729 (T)      ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.243      P=0.482N     P=0.518      P=0.511     |P=0.552      P=0.519N     P=0.547N     P=0.715      | 
|POLY 3             |     P=0.241      P=0.509N     P=0.494      P=0.488     |P=0.588      P=0.504N     P=0.512N     P=0.750      | 
|POLY 1.5           |     P=0.244      P=0.507N     P=0.496      P=0.492     |P=0.591      P=0.500N     P=0.506N     P=0.756      | 
|POLY 6             |     P=0.236      P=0.509N     P=0.493      P=0.482     |P=0.584      P=0.508N     P=0.521N     P=0.742      | 
|LOGISTIC REGRESSION|     P=0.224      (e)          P=0.497      P=0.511     |P=0.552      (e)          (e)          P=0.715      | 
|COCH-ARM / FISHERS |     P=0.245      P=0.500N     P=0.500      P=0.500     |P=0.595      P=0.500N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P=0.259      (e)          (e)          (e)         |P=0.390      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 13      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor                                                                       | 
|     (M or B), Basal Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepitheliom                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    5/50 (10%)   2/50 (4%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     3/45.22      0/43.15      5/44.46      2/43.64     |2/46.53      0/45.69      0/43.76      1/44.39      | 
|POLY-3 PERCENT (g) |     6.6%         0.0%         11.3%        4.6%        |4.3%         0.0%         0.0%         2.3%         | 
|TERMINAL (d)       |     3/31 (10%)   0/34 (0%)    4/33 (12%)   2/32 (6%)   |2/43 (5%)    0/39 (0%)    0/34 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          717          729 (T)     |729 (T)      ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.546      P=0.105N     P=0.389      P=0.485N    |P=0.515N     P=0.260N     P=0.291N     P=0.572N     | 
|POLY 3             |     P=0.536      P=0.127N     P=0.347      P=0.516N    |P=0.462N     P=0.241N     P=0.251N     P=0.516N     | 
|POLY 1.5           |     P=0.541      P=0.126N     P=0.351      P=0.510N    |P=0.463N     P=0.238N     P=0.244N     P=0.507N     | 
|POLY 6             |     P=0.525      P=0.127N     P=0.344      P=0.523N    |P=0.462N     P=0.246N     P=0.261N     P=0.529N     | 
|LOGISTIC REGRESSION|     P=0.517      (e)          P=0.362      P=0.485N    |P=0.515N     (e)          (e)          P=0.572N     | 
|COCH-ARM / FISHERS |     P=0.544      P=0.121N     P=0.357      P=0.500N    |P=0.461N     P=0.247N     P=0.247N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.277      (e)          (e)          (e)         |P=0.143N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibroma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   2/50 (4%)    4/50 (8%)    3/50 (6%)   |1/50 (2%)    1/50 (2%)    5/50 (10%)   0/50 (0%)    | 
|POLY-3 RATE (b)    |     8/46.10      2/44.09      4/44.91      3/44.29     |1/46.53      1/45.81      5/44.09      0/44.39      | 
|POLY-3 PERCENT (g) |     17.4%        4.5%         8.9%         6.8%        |2.2%         2.2%         11.3%        0.0%         | 
|TERMINAL (d)       |     5/31 (16%)   1/34 (3%)    1/33 (3%)    1/32 (3%)   |1/43 (2%)    0/39 (0%)    4/34 (12%)   0/35 (0%)    | 
|FIRST INCIDENCE    |     589          275          635          628         |729 (T)      700          638          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.140N     P=0.047N*    P=0.181N     P=0.117N    |P=0.545N     P=0.744      P=0.063      P=0.541N     | 
|POLY 3             |     P=0.124N     P=0.052N     P=0.189N     P=0.111N    |P=0.502N     P=0.757      P=0.089      P=0.509N     | 
|POLY 1.5           |     P=0.123N     P=0.050N     P=0.185N     P=0.107N    |P=0.486N     P=0.760      P=0.096      P=0.504N     | 
|POLY 6             |     P=0.127N     P=0.054N     P=0.193N     P=0.116N    |P=0.522N     P=0.753      P=0.081      P=0.517N     | 
|LOGISTIC REGRESSION|     P=0.117N     P=0.029N*    P=0.177N     P=0.096N    |P=0.489N     P=0.761      P=0.090      (e)          | 
|COCH-ARM / FISHERS |     P=0.124N     P=0.046N*    P=0.178N     P=0.100N    |P=0.474N     P=0.753N     P=0.102      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.060N     (e)          (e)          (e)         |P=0.152N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 14      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma,                                                                        | 
|     or Fibrous Histiocytoma                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   2/50 (4%)    5/50 (10%)   3/50 (6%)   |1/50 (2%)    1/50 (2%)    5/50 (10%)   0/50 (0%)    | 
|POLY-3 RATE (b)    |     8/46.10      2/44.09      5/45.05      3/44.29     |1/46.53      1/45.81      5/44.09      0/44.39      | 
|POLY-3 PERCENT (g) |     17.4%        4.5%         11.1%        6.8%        |2.2%         2.2%         11.3%        0.0%         | 
|TERMINAL (d)       |     5/31 (16%)   1/34 (3%)    1/33 (3%)    1/32 (3%)   |1/43 (2%)    0/39 (0%)    4/34 (12%)   0/35 (0%)    | 
|FIRST INCIDENCE    |     589          275          635          628         |729 (T)      700          638          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.160N     P=0.047N*    P=0.277N     P=0.117N    |P=0.545N     P=0.744      P=0.063      P=0.541N     | 
|POLY 3             |     P=0.141N     P=0.052N     P=0.290N     P=0.111N    |P=0.502N     P=0.757      P=0.089      P=0.509N     | 
|POLY 1.5           |     P=0.139N     P=0.050N     P=0.285N     P=0.107N    |P=0.486N     P=0.760      P=0.096      P=0.504N     | 
|POLY 6             |     P=0.144N     P=0.054N     P=0.294N     P=0.116N    |P=0.522N     P=0.753      P=0.081      P=0.517N     | 
|LOGISTIC REGRESSION|     P=0.132N     P=0.029N*    P=0.275N     P=0.096N    |P=0.489N     P=0.761      P=0.090      (e)          | 
|COCH-ARM / FISHERS |     P=0.139N     P=0.046N*    P=0.277N     P=0.100N    |P=0.474N     P=0.753N     P=0.102      P=0.500N     | 
|ORDER RESTRICTED   |     P=0.067N     (e)          (e)          (e)         |P=0.152N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Keratoacanthoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/45.22      0/43.15      3/44.41      0/43.64     |0/46.53      0/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         6.8%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/31 (3%)    0/34 (0%)    3/33 (9%)    0/32 (0%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.498N     P=0.482N     P=0.327      P=0.494N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.507N     P=0.509N     P=0.299      P=0.507N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.503N     P=0.507N     P=0.301      P=0.505N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.514N     P=0.509N     P=0.296      P=0.510N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.498N     (e)          P=0.327      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.500N     P=0.309      P=0.500N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.266N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 15      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Squamous Cell Papilloma, Papilloma, Squamous Cell                                                                           | 
|     Carcinoma or Keratoacanthoma                                                                                                | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/45.22      0/43.15      3/44.41      0/43.64     |1/46.53      0/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     4.4%         0.0%         6.8%         0.0%        |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/31 (7%)    0/34 (0%)    3/33 (9%)    0/32 (0%)   |1/43 (2%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.291N     P=0.218N     P=0.529      P=0.231N    |P=0.334N     P=0.519N     P=0.547N     P=0.541N     | 
|POLY 3             |     P=0.298N     P=0.248N     P=0.492      P=0.245N    |P=0.303N     P=0.504N     P=0.512N     P=0.509N     | 
|POLY 1.5           |     P=0.296N     P=0.246N     P=0.495      P=0.242N    |P=0.306N     P=0.500N     P=0.506N     P=0.504N     | 
|POLY 6             |     P=0.304N     P=0.247N     P=0.489      P=0.248N    |P=0.301N     P=0.508N     P=0.521N     P=0.517N     | 
|LOGISTIC REGRESSION|     P=0.291N     (e)          P=0.529      (e)         |P=0.334N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.296N     P=0.247N     P=0.500      P=0.247N    |P=0.306N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.158N     (e)          (e)          (e)         |P=0.130N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/45.22      0/43.15      3/44.41      0/43.64     |1/46.53      0/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     2.2%         0.0%         6.8%         0.0%        |2.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/31 (3%)    0/34 (0%)    3/33 (9%)    0/32 (0%)   |1/43 (2%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.498N     P=0.482N     P=0.327      P=0.494N    |P=0.334N     P=0.519N     P=0.547N     P=0.541N     | 
|POLY 3             |     P=0.507N     P=0.509N     P=0.299      P=0.507N    |P=0.303N     P=0.504N     P=0.512N     P=0.509N     | 
|POLY 1.5           |     P=0.503N     P=0.507N     P=0.301      P=0.505N    |P=0.306N     P=0.500N     P=0.506N     P=0.504N     | 
|POLY 6             |     P=0.514N     P=0.509N     P=0.296      P=0.510N    |P=0.301N     P=0.508N     P=0.521N     P=0.517N     | 
|LOGISTIC REGRESSION|     P=0.498N     (e)          P=0.327      (e)         |P=0.334N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.500N     P=0.500N     P=0.309      P=0.500N    |P=0.306N     P=0.500N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.266N     (e)          (e)          (e)         |P=0.130N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 16      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     46/50 (92%)  44/50 (88%)  47/50 (94%)  45/50 (90%) |                                                    | 
|POLY-3 RATE (b)    |     46/48.36     44/46.88     47/49.24     45/47.41    |                                                    | 
|POLY-3 PERCENT (g) |     95.1%        93.9%        95.5%        94.9%       |                                                    | 
|TERMINAL (d)       |     30/31 (97%)  32/34 (94%)  32/33 (97%)  31/32 (97%) |                                                    | 
|FIRST INCIDENCE    |     582          516          498          607         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.498      P=0.281N     P=0.533N     P=0.524N    |                                                    | 
|POLY 3             |     P=0.571      P=0.579N     P=0.670      P=0.689N    |                                                    | 
|POLY 1.5           |     P=0.584      P=0.535N     P=0.595      P=0.625N    |                                                    | 
|POLY 6             |     P=0.563      P=0.571N     P=0.677N     P=0.735N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.560      P=0.597      P=0.405      P=0.653N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.533N     P=0.370N     P=0.500      P=0.500N    |                                                    | 
|ORDER RESTRICTED   |     P=0.664      (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: C-Cell                                                                                                            | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/47 (23%)  7/46 (15%)   3/48 (6%)    10/44 (23%) |10/47 (21%)  8/44 (18%)   6/40 (15%)   8/45 (18%)   | 
|POLY-3 RATE (b)    |     11/43.77     7/40.94      3/43.27      10/39.55    |10/44.16     8/42.14      6/38.47      8/40.99      | 
|POLY-3 PERCENT (g) |     25.1%        17.1%        6.9%         25.3%       |22.7%        19.0%        15.6%        19.5%        | 
|TERMINAL (d)       |     9/31 (29%)   7/34 (21%)   2/33 (6%)    10/32 (31%) |9/42 (21%)   8/38 (21%)   5/34 (15%)   7/34 (21%)   | 
|FIRST INCIDENCE    |     667          729 (T)      706          729 (T)     |700          729 (T)      700          642          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.489N     P=0.162N     P=0.018N*    P=0.480N    |P=0.528N     P=0.487N     P=0.356N     P=0.581N     | 
|POLY 3             |     P=0.552N     P=0.262N     P=0.019N*    P=0.593     |P=0.411N     P=0.439N     P=0.299N     P=0.465N     | 
|POLY 1.5           |     P=0.547N     P=0.254N     P=0.019N*    P=0.594N    |P=0.393N     P=0.435N     P=0.296N     P=0.442N     | 
|POLY 6             |     P=0.552      P=0.262N     P=0.020N*    P=0.588     |P=0.437N     P=0.451N     P=0.309N     P=0.498N     | 
|LOGISTIC REGRESSION|     P=0.551      P=0.224N     P=0.021N*    P=0.587N    |P=0.459N     P=0.459N     P=0.308N     P=0.495N     | 
|COCH-ARM / FISHERS |     P=0.538N     P=0.231N     P=0.018N*    P=0.569N    |P=0.384N     P=0.458N     P=0.319N     P=0.437N     | 
|ORDER RESTRICTED   |     P=0.207N     (e)          (e)          (e)         |P=0.439N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 17      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: C-Cell                                                                                                            | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/47 (0%)    0/46 (0%)    2/48 (4%)    0/44 (0%)   |1/47 (2%)    0/44 (0%)    2/40 (5%)    0/45 (0%)    | 
|POLY-3 RATE (b)    |     0/43.51      0/40.94      2/43.18      0/39.55     |1/44.04      0/42.14      2/38.35      0/40.67      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.6%         0.0%        |2.3%         0.0%         5.2%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/34 (0%)    2/33 (6%)    0/32 (0%)   |1/42 (2%)    0/38 (0%)    2/34 (6%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |729 (T)      ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.597      (e)          P=0.252      (e)         |P=0.515N     P=0.520N     P=0.426      P=0.542N     | 
|POLY 3             |     P=0.575      (e)          P=0.235      (e)         |P=0.488N     P=0.509N     P=0.452      P=0.516N     | 
|POLY 1.5           |     P=0.578      (e)          P=0.238      (e)         |P=0.480N     P=0.508N     P=0.453      P=0.510N     | 
|POLY 6             |     P=0.575      (e)          P=0.234      (e)         |P=0.499N     P=0.511N     P=0.447      P=0.523N     | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.252      (e)         |P=0.515N     (e)          P=0.426      (e)          | 
|COCH-ARM / FISHERS |     P=0.584      (e)          P=0.253      (e)         |P=0.472N     P=0.516N     P=0.439      P=0.511N     | 
|ORDER RESTRICTED   |     P=0.247      (e)          (e)          (e)         |P=0.318N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: C-Cell                                                                                                            | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/47 (23%)  7/46 (15%)   5/48 (10%)   10/44 (23%) |11/47 (23%)  8/44 (18%)   8/40 (20%)   8/45 (18%)   | 
|POLY-3 RATE (b)    |     11/43.77     7/40.94      5/43.27      10/39.55    |11/44.16     8/42.14      8/38.47      8/40.99      | 
|POLY-3 PERCENT (g) |     25.1%        17.1%        11.6%        25.3%       |24.9%        19.0%        20.8%        19.5%        | 
|TERMINAL (d)       |     9/31 (29%)   7/34 (21%)   4/33 (12%)   10/32 (31%) |10/42 (24%)  8/38 (21%)   7/34 (21%)   7/34 (21%)   | 
|FIRST INCIDENCE    |     667          729 (T)      706          729 (T)     |700          729 (T)      700          642          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.515N     P=0.162N     P=0.071N     P=0.480N    |P=0.481N     P=0.391N     P=0.496N     P=0.488N     | 
|POLY 3             |     P=0.523      P=0.262N     P=0.085N     P=0.593     |P=0.363N     P=0.344N     P=0.429N     P=0.369N     | 
|POLY 1.5           |     P=0.528      P=0.254N     P=0.082N     P=0.594N    |P=0.343N     P=0.340N     P=0.424N     P=0.347N     | 
|POLY 6             |     P=0.517      P=0.262N     P=0.087N     P=0.588     |P=0.391N     P=0.355N     P=0.442N     P=0.401N     | 
|LOGISTIC REGRESSION|     P=0.519      P=0.224N     P=0.083N     P=0.587N    |P=0.412N     P=0.363N     P=0.446N     P=0.400N     | 
|COCH-ARM / FISHERS |     P=0.538      P=0.231N     P=0.078N     P=0.569N    |P=0.332N     P=0.362N     P=0.453N     P=0.342N     | 
|ORDER RESTRICTED   |     P=0.316N     (e)          (e)          (e)         |P=0.427N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 18      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/47 (0%)    1/46 (2%)    0/48 (0%)    0/44 (0%)   |2/47 (4%)    3/44 (7%)    0/40 (0%)    0/45 (0%)    | 
|POLY-3 RATE (b)    |     0/43.51      1/40.94      0/43.18      0/39.55     |2/44.04      3/42.48      0/38.35      0/40.67      | 
|POLY-3 PERCENT (g) |     0.0%         2.4%         0.0%         0.0%        |4.5%         7.1%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    1/34 (3%)    0/33 (0%)    0/32 (0%)   |2/42 (5%)    2/38 (5%)    0/34 (0%)    0/34 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |729 (T)      636          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.567N     P=0.518      (e)          (e)         |P=0.097N     P=0.464      P=0.286N     P=0.286N     | 
|POLY 3             |     P=0.583N     P=0.488      (e)          (e)         |P=0.082N     P=0.484      P=0.268N     P=0.255N     | 
|POLY 1.5           |     P=0.581N     P=0.490      (e)          (e)         |P=0.080N     P=0.484      P=0.267N     P=0.249N     | 
|POLY 6             |     P=0.584N     P=0.488      (e)          (e)         |P=0.086N     P=0.482      P=0.271N     P=0.264N     | 
|LOGISTIC REGRESSION|     (e)          P=0.518      (e)          (e)         |P=0.081N     P=0.473      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.576N     P=0.495      (e)          (e)         |P=0.081N     P=0.468      P=0.289N     P=0.258N     | 
|ORDER RESTRICTED   |     P=0.388N     (e)          (e)          (e)         |P=0.087N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Tongue                                                                                                                           | 
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/45.22      2/43.72      0/44.41      0/43.64     |0/46.53      1/45.98      1/44.26      1/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         4.6%         0.0%         0.0%        |0.0%         2.2%         2.3%         2.3%         | 
|TERMINAL (d)       |     0/31 (0%)    1/34 (3%)    0/33 (0%)    0/32 (0%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    1/35 (3%)    | 
|FIRST INCIDENCE    |     ---          547          ---          ---         |---          653          581          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.406N     P=0.243      (e)          (e)         |P=0.356      P=0.496      P=0.491      P=0.459      | 
|POLY 3             |     P=0.416N     P=0.230      (e)          (e)         |P=0.367      P=0.498      P=0.490      P=0.491      | 
|POLY 1.5           |     P=0.413N     P=0.231      (e)          (e)         |P=0.377      P=0.500      P=0.495      P=0.496      | 
|POLY 6             |     P=0.418N     P=0.231      (e)          (e)         |P=0.353      P=0.495      P=0.483      P=0.483      | 
|LOGISTIC REGRESSION|     P=0.399N     P=0.272      (e)          (e)         |P=0.383      P=0.488      P=0.498      P=0.459      | 
|COCH-ARM / FISHERS |     P=0.405N     P=0.247      (e)          (e)         |P=0.384      P=0.500      P=0.500      P=0.500      | 
|ORDER RESTRICTED   |     P=0.247N     (e)          (e)          (e)         |P=0.318      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 19      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Polyp Stromal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |16/50 (32%)  5/50 (10%)   2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |                                                        |16/47.69     5/45.89      2/43.76      2/44.39      | 
|POLY-3 PERCENT (g) |                                                        |33.6%        10.9%        4.6%         4.5%         | 
|TERMINAL (d)       |                                                        |14/43 (33%)  4/39 (10%)   2/34 (6%)    2/35 (6%)    | 
|FIRST INCIDENCE    |                                                        |302          677          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P<0.001N**   P=0.014N*    P=0.002N**   P=0.002N**   | 
|POLY 3             |                                                        |P<0.001N**   P=0.007N**   P<0.001N**   P<0.001N**   | 
|POLY 1.5           |                                                        |P<0.001N**   P=0.006N**   P<0.001N**   P<0.001N**   | 
|POLY 6             |                                                        |P<0.001N**   P=0.008N**   P<0.001N**   P<0.001N**   | 
|LOGISTIC REGRESSION|                                                        |P<0.001N**   P=0.007N**   P<0.001N**   P<0.001N**   | 
|COCH-ARM / FISHERS |                                                        |P<0.001N**   P=0.006N**   P<0.001N**   P<0.001N**   | 
|ORDER RESTRICTED   |                                                        |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Sarcoma Stromal or Polyp Stromal                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |17/50 (34%)  5/50 (10%)   2/50 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |                                                        |17/47.69     5/45.89      2/43.76      2/44.39      | 
|POLY-3 PERCENT (g) |                                                        |35.6%        10.9%        4.6%         4.5%         | 
|TERMINAL (d)       |                                                        |15/43 (35%)  4/39 (10%)   2/34 (6%)    2/35 (6%)    | 
|FIRST INCIDENCE    |                                                        |302          677          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P<0.001N**   P=0.009N**   P<0.001N**   P<0.001N**   | 
|POLY 3             |                                                        |P<0.001N**   P=0.004N**   P<0.001N**   P<0.001N**   | 
|POLY 1.5           |                                                        |P<0.001N**   P=0.003N**   P<0.001N**   P<0.001N**   | 
|POLY 6             |                                                        |P<0.001N**   P=0.004N**   P<0.001N**   P<0.001N**   | 
|LOGISTIC REGRESSION|                                                        |P<0.001N**   P=0.004N**   P<0.001N**   P<0.001N**   | 
|COCH-ARM / FISHERS |                                                        |P<0.001N**   P=0.004N**   P<0.001N**   P<0.001N**   | 
|ORDER RESTRICTED   |                                                        |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 20      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Zymbal's Gland                                                                                                                   | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    1/50 (2%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     3/46.20      1/43.15      2/45.02      0/43.64     |0/46.53      2/45.69      1/43.88      0/44.39      | 
|POLY-3 PERCENT (g) |     6.5%         2.3%         4.4%         0.0%        |0.0%         4.4%         2.3%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    1/34 (3%)    1/33 (3%)    0/32 (0%)   |0/43 (0%)    2/39 (5%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     547          729 (T)      531          ---         |---          729 (T)      700          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.114N     P=0.319N     P=0.515N     P=0.146N    |P=0.510N     P=0.217      P=0.465      (e)          | 
|POLY 3             |     P=0.107N     P=0.330N     P=0.512N     P=0.129N    |P=0.480N     P=0.233      P=0.488      (e)          | 
|POLY 1.5           |     P=0.105N     P=0.323N     P=0.507N     P=0.125N    |P=0.468N     P=0.237      P=0.494      (e)          | 
|POLY 6             |     P=0.110N     P=0.335N     P=0.518N     P=0.135N    |P=0.495N     P=0.229      P=0.480      (e)          | 
|LOGISTIC REGRESSION|     P=0.097N     P=0.258N     P=0.443N     P=0.080N    |P=0.480N     P=0.217      P=0.498      (e)          | 
|COCH-ARM / FISHERS |     P=0.104N     P=0.309N     P=0.500N     P=0.121N    |P=0.461N     P=0.247      P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.064N     (e)          (e)          (e)         |P=0.319      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Histiocytic Sarcoma                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      0/43.15      1/44.48      1/44.02     |2/47.21      0/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         2.3%         2.3%        |4.2%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    0/34 (0%)    0/33 (0%)    0/32 (0%)   |1/43 (2%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          712          622         |498          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.235      (e)          P=0.506      P=0.504     |P=0.127N     P=0.253N     P=0.265N     P=0.262N     | 
|POLY 3             |     P=0.233      (e)          P=0.497      P=0.495     |P=0.112N     P=0.245N     P=0.255N     P=0.251N     | 
|POLY 1.5           |     P=0.235      (e)          P=0.498      P=0.496     |P=0.113N     P=0.240N     P=0.246N     P=0.244N     | 
|POLY 6             |     P=0.230      (e)          P=0.496      P=0.493     |P=0.111N     P=0.250N     P=0.266N     P=0.261N     | 
|LOGISTIC REGRESSION|     P=0.237      (e)          P=0.496      P=0.552     |P=0.118N     P=0.261N     P=0.234N     P=0.249N     | 
|COCH-ARM / FISHERS |     P=0.236      (e)          P=0.500      P=0.500     |P=0.115N     P=0.247N     P=0.247N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.246      (e)          (e)          (e)         |P=0.035N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 21      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or                                                                           | 
|     Undifferentiated                                                                                                            | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     15/50 (30%)  18/50 (36%)  22/50 (44%)  20/50 (40%) |9/50 (18%)   7/50 (14%)   16/50 (32%)  20/50 (40%)  | 
|POLY-3 RATE (b)    |     15/47.00     18/45.55     22/47.58     20/47.38    |9/47.04      7/47.43      16/46.44     20/47.92     | 
|POLY-3 PERCENT (g) |     31.9%        39.5%        46.2%        42.2%       |19.1%        14.8%        34.5%        41.7%        | 
|TERMINAL (d)       |     5/31 (16%)   9/34 (27%)   12/33 (36%)  7/32 (22%)  |7/43 (16%)   4/39 (10%)   7/34 (21%)   11/35 (31%)  | 
|FIRST INCIDENCE    |     582          567          493          584         |624          434          578          368          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.181      P=0.375      P=0.160      P=0.211     |P<0.001 **   P=0.458N     P=0.041 *    P=0.007 **   | 
|POLY 3             |     P=0.184      P=0.292      P=0.110      P=0.205     |P<0.001 **   P=0.386N     P=0.073      P=0.013 *    | 
|POLY 1.5           |     P=0.175      P=0.297      P=0.108      P=0.198     |P<0.001 **   P=0.379N     P=0.078      P=0.014 *    | 
|POLY 6             |     P=0.200      P=0.303      P=0.113      P=0.221     |P<0.001 **   P=0.398N     P=0.068      P=0.012 *    | 
|LOGISTIC REGRESSION|     P=0.172      P=0.325      P=0.115      P=0.226     |P=0.002 **   P=0.402N     P=0.081      P=0.014 *    | 
|COCH-ARM / FISHERS |     P=0.168      P=0.335      P=0.107      P=0.201     |P=0.002 **   P=0.393N     P=0.083      P=0.013 *    | 
|ORDER RESTRICTED   |     P=0.169      (e)          (e)          (e)         |P=0.003 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Mesothelioma: Benign, Malignant, NOS                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    3/50 (6%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      2/43.68      3/44.87      1/43.94     |0/46.53      0/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         4.6%         6.7%         2.3%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    1/34 (3%)    2/33 (6%)    0/32 (0%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          567          594          650         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.449      P=0.243      P=0.130      P=0.491     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.428      P=0.229      P=0.117      P=0.494     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.434      P=0.231      P=0.118      P=0.496     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.421      P=0.231      P=0.117      P=0.492     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.450      P=0.264      P=0.124      P=0.529     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.444      P=0.247      P=0.121      P=0.500     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.183      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 22      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Mesothelioma: Malignant                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    3/50 (6%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/45.22      2/43.68      3/44.87      1/43.94     |0/46.53      0/45.69      0/43.76      0/44.39      | 
|POLY-3 PERCENT (g) |     0.0%         4.6%         6.7%         2.3%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/31 (0%)    1/34 (3%)    2/33 (6%)    0/32 (0%)   |0/43 (0%)    0/39 (0%)    0/34 (0%)    0/35 (0%)    | 
|FIRST INCIDENCE    |     ---          567          594          650         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.449      P=0.243      P=0.130      P=0.491     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.428      P=0.229      P=0.117      P=0.494     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.434      P=0.231      P=0.118      P=0.496     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.421      P=0.231      P=0.117      P=0.492     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.450      P=0.264      P=0.124      P=0.529     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.444      P=0.247      P=0.121      P=0.500     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.183      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     50/50 (100%) 49/50 (98%)  48/50 (96%)  47/50 (94%) |48/50 (96%)  32/50 (64%)  29/50 (58%)  20/50 (40%)  | 
|POLY-3 RATE (b)    |     50/50.00     49/49.05     48/49.24     47/48.27    |48/49.00     32/47.78     29/45.80     20/45.23     | 
|POLY-3 PERCENT (g) |     100.0%       99.9%        97.5%        97.4%       |98.0%        67.0%        63.3%        44.2%        | 
|TERMINAL (d)       |     31/31 (100%) 34/34 (100%) 33/33 (100%) 32/32 (100%)|42/43 (98%)  25/39 (64%)  22/34 (65%)  16/35 (46%)  | 
|FIRST INCIDENCE    |     464          275          498          384         |302          434          555          642          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.369N     P=0.354N     P=0.331N     P=0.390N    |P<0.001N**   P=0.011N*    P=0.022N*    P<0.001N**   | 
|POLY 3             |     P=0.123N     P=1.000N     P=0.399N     P=0.362N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|POLY 1.5           |     P=0.071N     P=0.999N     P=0.317N     P=0.213N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|POLY 6             |     P=0.289N     P=1.000N     P=0.512N     P=0.750N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|LOGISTIC REGRESSION|     P=0.046N*    (e)          P=0.267N     P=0.215N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|COCH-ARM / FISHERS |     P=0.062N     P=0.500N     P=0.247N     P=0.121N    |P<0.001N**   P<0.001N**   P<0.001N**   P<0.001N**   | 
|ORDER RESTRICTED   |     P=0.116N     (e)          (e)          (e)         |P<0.001N**   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/06/04                           EXPERIMENT: 92013 TEST: 05                                            Page 23      
                     Statistical Analysis of Primary Tumors in Rats(FISCHER 344)       -                    4-METHYLIMIDAZOLE       
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     22/50 (44%)  21/50 (42%)  30/50 (60%)  24/50 (48%) |19/50 (38%)  15/50 (30%)  25/50 (50%)  21/50 (42%)  | 
|POLY-3 RATE (b)    |     22/48.23     21/46.12     30/49.89     24/49.35    |19/47.72     15/49.00     25/46.69     21/47.92     | 
|POLY-3 PERCENT (g) |     45.6%        45.5%        60.1%        48.6%       |39.8%        30.6%        53.5%        43.8%        | 
|TERMINAL (d)       |     7/31 (23%)   11/34 (32%)  14/33 (42%)  8/32 (25%)  |16/43 (37%)  8/39 (21%)   14/34 (41%)  12/35 (34%)  | 
|FIRST INCIDENCE    |     547          547          493          369         |498          421          578          368          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.281      P=0.482N     P=0.159      P=0.384     |P=0.102      P=0.371N     P=0.051      P=0.220      | 
|POLY 3             |     P=0.354      P=0.579N     P=0.106      P=0.462     |P=0.201      P=0.232N     P=0.128      P=0.425      | 
|POLY 1.5           |     P=0.328      P=0.562N     P=0.095      P=0.446     |P=0.214      P=0.231N     P=0.141      P=0.438      | 
|POLY 6             |     P=0.376      P=0.582      P=0.121      P=0.478     |P=0.187      P=0.240N     P=0.117      P=0.405      | 
|LOGISTIC REGRESSION|     P=0.302      P=0.492N     P=0.090      P=0.533     |P=0.226      P=0.269N     P=0.142      P=0.422      | 
|COCH-ARM / FISHERS |     P=0.275      P=0.500N     P=0.080      P=0.421     |P=0.217      P=0.263N     P=0.157      P=0.419      | 
|ORDER RESTRICTED   |     P=0.300      (e)          (e)          (e)         |P=0.138      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        625 PPM      1250 PPM     2500 PPM    |0 PPM        1250 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     50/50 (100%) 49/50 (98%)  50/50 (100%) 50/50 (100%)|48/50 (96%)  39/50 (78%)  42/50 (84%)  36/50 (72%)  | 
|POLY-3 RATE (b)    |     50/50.00     49/49.05     50/50.00     50/50.00    |48/49.00     39/50.00     42/47.58     36/48.81     | 
|POLY-3 PERCENT (g) |     100.0%       99.9%        100.0%       100.0%      |98.0%        78.0%        88.3%        73.8%        | 
|TERMINAL (d)       |     31/31 (100%) 34/34 (100%) 33/33 (100%) 32/32 (100%)|42/43 (98%)  28/39 (72%)  29/34 (85%)  23/35 (66%)  | 
|FIRST INCIDENCE    |     464          275          493          369         |302          421          555          368          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.457      P=0.354N     (e)          (e)         |P=0.343N     P=0.201N     P=0.320      P=0.252N     | 
|POLY 3             |     P=1.000      P=1.000N     (e)          (e)         |P=0.004N**   P=0.002N**   P=0.062N     P<0.001N**   | 
|POLY 1.5           |     P=0.992      P=0.999N     (e)          (e)         |P=0.003N**   P=0.002N**   P=0.045N*    P<0.001N**   | 
|POLY 6             |     P=1.000      P=1.000N     (e)          (e)         |P=0.005N**   P=0.002N**   P=0.080N     P<0.001N**   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.005N**   P=0.007N**   P=0.039N*    P<0.001N**   | 
|COCH-ARM / FISHERS |     P=0.567      P=0.500N     (e)          (e)         |P=0.005N**   P=0.007N**   P=0.046N*    P<0.001N**   | 
|ORDER RESTRICTED   |     P=0.379      (e)          (e)          (e)         |P<0.001N**   (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.