National Toxicology Program

National Toxicology Program
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TDMS Study 92012-06 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                2-METHYLIMIDAZOLE                                   DATE: 02/25/03       
EXPERIMENT: 92012 TEST: 06                                                                                     TIME: 07:34:56       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92012B       
PATHOLOGIST: HEATH, JAMES E.                                                                                   CAS: 693-98-1        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                            FINAL#1/MICE                                                            
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    25019 Moribund Sacrifice                                                                     
                                       25020 Natural Death                                                                          
                                       25021 Terminal Sacrifice                                                                     
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                2-METHYLIMIDAZOLE                                   DATE: 02/25/03       
EXPERIMENT: 92012 TEST: 06                                                                                     TIME: 07:34:56       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92012B       
PATHOLOGIST: HEATH, JAMES E.                                                                                   CAS: 693-98-1        
Mice(B6C3F1)                                                                                                                        
-----------------------------                                                                                                       
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE                                                                   
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES                                                                 
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.                                                                                      
                                                 ---------------                                                                    
                                                 Adrenal Cortex                                                                     
                                                 Adrenal Medulla                                                                    
                                                 Bone Marrow                                                                        
                                                 Brain                                                                              
                                                 Islets, Pancreatic                                                                 
                                                 Kidney                                                                             
                                                 Liver                                                                              
                                                 Lung                                                                               
                                                 Ovary                                                                              
                                                 Pituitary Gland                                                                    
                                                 Spleen                                                                             
                                                 Testes                                                                             
                                                 Thyroid Gland                                                                      
                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                2-METHYLIMIDAZOLE                                   DATE: 02/25/03       
EXPERIMENT: 92012 TEST: 06                                                                                     TIME: 07:34:56       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92012B       
PATHOLOGIST: HEATH, JAMES E.                                                                                   CAS: 693-98-1        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                   2-METHYLIMIDAZOLE                                                                              
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Harderian Gland                        Adenoma                                                                                      
Liver                                  Hepatocellular Adenoma                                                                       
                                       Hepatocellular Carcinoma                                                                     
                                       Hepatocellular Carcinoma or Hepatocellular Adenoma                                           
                                       Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                          
Thyroid Gland: Follicular Cell         Adenoma                                                                                      
All Organs                             Benign Tumors                                                                                
                                       Malignant and Benign Tumors                                                                  
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Liver                                  Hepatocellular Adenoma                                                                       
                                       Hepatocellular Carcinoma                                                                     
                                       Hepatocellular Carcinoma or Hepatocellular Adenoma                                           
                                       Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                          
Lung                                   Alveolar/Bronchiolar Adenoma                                                                 
===============================================================                                                                     
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 1       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)        -                    2-METHYLIMIDAZOLE           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/49 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/47.43      2/48.59      0/41.44      1/44.45     |0/48.25      0/46.83      0/46.63      0/48.64      | 
|POLY-3 PERCENT (g) |     0.0%         4.1%         0.0%         2.3%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/43 (0%)    2/46 (4%)    0/36 (0%)    1/40 (3%)   |0/46 (0%)    0/43 (0%)    0/43 (0%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.509      P=0.253      (e)          P=0.486     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.513      P=0.243      (e)          P=0.487     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.513      P=0.240      (e)          P=0.487     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.513      P=0.247      (e)          P=0.487     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.253      (e)          P=0.486     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.539      P=0.247      (e)          P=0.500     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.314      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   6/50 (12%)   5/50 (10%)   3/50 (6%)   |3/50 (6%)    2/49 (4%)    6/49 (12%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |     9/47.43      6/48.59      5/41.71      3/45.07     |3/48.25      2/46.83      6/46.63      6/48.64      | 
|POLY-3 PERCENT (g) |     19.0%        12.4%        12.0%        6.7%        |6.2%         4.3%         12.9%        12.3%        | 
|TERMINAL (d)       |     9/43 (21%)   6/46 (13%)   4/36 (11%)   2/40 (5%)   |3/46 (7%)    2/43 (5%)    6/43 (14%)   6/45 (13%)   | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      654          531         |729 (T)      729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.072N     P=0.240N     P=0.304N     P=0.081N    |P=0.106      P=0.531N     P=0.210      P=0.232      | 
|POLY 3             |     P=0.060N     P=0.271N     P=0.271N     P=0.072N    |P=0.113      P=0.514N     P=0.226      P=0.247      | 
|POLY 1.5           |     P=0.060N     P=0.279N     P=0.262N     P=0.074N    |P=0.112      P=0.511N     P=0.227      P=0.246      | 
|POLY 6             |     P=0.060N     P=0.259N     P=0.278N     P=0.069N    |P=0.113      P=0.518N     P=0.223      P=0.246      | 
|LOGISTIC REGRESSION|     P=0.061N     P=0.240N     P=0.284N     P=0.073N    |P=0.106      P=0.531N     P=0.210      P=0.232      | 
|COCH-ARM / FISHERS |     P=0.046N*    P=0.288N     P=0.194N     P=0.061N    |P=0.109      P=0.510N     P=0.233      P=0.243      | 
|ORDER RESTRICTED   |     P=0.052N     (e)          (e)          (e)         |P=0.156      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 2       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    3/50 (6%)    1/50 (2%)    2/50 (4%)   |1/50 (2%)    0/49 (0%)    1/49 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/47.70      3/48.59      1/41.81      2/44.45     |1/48.25      0/46.83      1/47.00      1/48.64      | 
|POLY-3 PERCENT (g) |     2.1%         6.2%         2.4%         4.5%        |2.1%         0.0%         2.1%         2.1%         | 
|TERMINAL (d)       |     0/43 (0%)    3/46 (7%)    0/36 (0%)    2/40 (5%)   |1/46 (2%)    0/43 (0%)    0/43 (0%)    1/45 (2%)    | 
|FIRST INCIDENCE    |     657          729 (T)      623          729 (T)     |729 (T)      ---          623          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.480      P=0.329      P=0.722      P=0.473     |P=0.538      P=0.513N     P=0.750      P=0.757      | 
|POLY 3             |     P=0.485      P=0.312      P=0.730      P=0.475     |P=0.544      P=0.506N     P=0.755      P=0.759N     | 
|POLY 1.5           |     P=0.488      P=0.309      P=0.734      P=0.476     |P=0.543      P=0.505N     P=0.754      P=0.759N     | 
|POLY 6             |     P=0.483      P=0.317      P=0.727      P=0.475     |P=0.545      P=0.508N     P=0.755      P=0.759N     | 
|LOGISTIC REGRESSION|     P=0.506      P=0.305      P=0.753N     P=0.487     |P=0.536      (e)          P=0.754N     P=0.757      | 
|COCH-ARM / FISHERS |     P=0.526      P=0.309      P=0.753N     P=0.500     |P=0.540      P=0.505N     P=0.747      P=0.753N     | 
|ORDER RESTRICTED   |     P=0.435      (e)          (e)          (e)         |P=0.534      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  9/50 (18%)   6/50 (12%)   5/50 (10%)  |4/50 (8%)    2/49 (4%)    7/49 (14%)   7/50 (14%)   | 
|POLY-3 RATE (b)    |     10/47.70     9/48.59      6/42.09      5/45.07     |4/48.25      2/46.83      7/47.00      7/48.64      | 
|POLY-3 PERCENT (g) |     21.0%        18.5%        14.3%        11.1%       |8.3%         4.3%         14.9%        14.4%        | 
|TERMINAL (d)       |     9/43 (21%)   9/46 (20%)   4/36 (11%)   4/40 (10%)  |4/46 (9%)    2/43 (5%)    6/43 (14%)   7/45 (16%)   | 
|FIRST INCIDENCE    |     657          729 (T)      623          531         |729 (T)      729 (T)      623          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.128N     P=0.437N     P=0.334N     P=0.170N    |P=0.102      P=0.369N     P=0.229      P=0.249      | 
|POLY 3             |     P=0.108N     P=0.482N     P=0.292N     P=0.157N    |P=0.107      P=0.351N     P=0.247      P=0.267      | 
|POLY 1.5           |     P=0.107N     P=0.490N     P=0.282N     P=0.159N    |P=0.106      P=0.349N     P=0.246      P=0.266      | 
|POLY 6             |     P=0.108N     P=0.470N     P=0.298N     P=0.155N    |P=0.108      P=0.356N     P=0.247      P=0.265      | 
|LOGISTIC REGRESSION|     P=0.105N     P=0.470N     P=0.280N     P=0.152N    |P=0.107      P=0.369N     P=0.245      P=0.249      | 
|COCH-ARM / FISHERS |     P=0.080N     P=0.500N     P=0.207N     P=0.131N    |P=0.103      P=0.349N     P=0.251      P=0.262      | 
|ORDER RESTRICTED   |     P=0.153N     (e)          (e)          (e)         |P=0.137      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 3       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/49 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/47.66      0/48.59      0/41.44      2/44.45     |0/48.25      0/46.83      0/46.63      0/48.64      | 
|POLY-3 PERCENT (g) |     2.1%         0.0%         0.0%         4.5%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/43 (0%)    0/46 (0%)    0/36 (0%)    2/40 (5%)   |0/46 (0%)    0/43 (0%)    0/43 (0%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     668          ---          ---          729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.225      P=0.492N     P=0.538N     P=0.475     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.230      P=0.496N     P=0.528N     P=0.476     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.232      P=0.498N     P=0.524N     P=0.477     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.227      P=0.493N     P=0.532N     P=0.475     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.233      P=0.503N     P=0.499N     P=0.485     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.246      P=0.500N     P=0.500N     P=0.500     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.116      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Adenoma                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     7/50 (14%)   14/50 (28%)  13/50 (26%)  18/50 (36%) |3/50 (6%)    4/49 (8%)    6/49 (12%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |     7/47.43      14/48.59     13/42.27     18/44.72    |3/48.27      4/46.99      6/46.63      10/48.88     | 
|POLY-3 PERCENT (g) |     14.8%        28.8%        30.8%        40.3%       |6.2%         8.5%         12.9%        20.5%        | 
|TERMINAL (d)       |     7/43 (16%)   14/46 (30%)  10/36 (28%)  17/40 (43%) |2/46 (4%)    3/43 (7%)    6/43 (14%)   9/45 (20%)   | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      611          656         |723          688          729 (T)      664          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.005 **   P=0.094      P=0.048 *    P=0.005 **  |P=0.015 *    P=0.464      P=0.212      P=0.037 *    | 
|POLY 3             |     P=0.006 **   P=0.077      P=0.058      P=0.005 **  |P=0.015 *    P=0.485      P=0.226      P=0.037 *    | 
|POLY 1.5           |     P=0.006 **   P=0.073      P=0.061      P=0.005 **  |P=0.014 *    P=0.487      P=0.227      P=0.037 *    | 
|POLY 6             |     P=0.006 **   P=0.083      P=0.056      P=0.005 **  |P=0.015 *    P=0.482      P=0.223      P=0.037 *    | 
|LOGISTIC REGRESSION|     P=0.006 **   P=0.094      P=0.056      P=0.006 **  |P=0.015 *    P=0.485      P=0.215      P=0.038 *    | 
|COCH-ARM / FISHERS |     P=0.015 *    P=0.070      P=0.105      P=0.010 *   |P=0.014 *    P=0.489      P=0.233      P=0.036 *    | 
|ORDER RESTRICTED   |     P=0.003 **   (e)          (e)          (e)         |P=0.019 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 4       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    8/50 (16%)   14/50 (28%)  6/50 (12%)  |2/50 (4%)    0/49 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     4/47.84      8/49.00      14/42.82     6/44.86     |2/48.27      0/46.83      0/46.63      0/48.64      | 
|POLY-3 PERCENT (g) |     8.4%         16.3%        32.7%        13.4%       |4.1%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     3/43 (7%)    5/46 (11%)   9/36 (25%)   4/40 (10%)  |1/46 (2%)    0/43 (0%)    0/43 (0%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     611          657          531          656         |723          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.267      P=0.219      P=0.005 **   P=0.332     |P=0.120N     P=0.257N     P=0.257N     P=0.245N     | 
|POLY 3             |     P=0.261      P=0.190      P=0.003 **   P=0.330     |P=0.114N     P=0.244N     P=0.245N     P=0.236N     | 
|POLY 1.5           |     P=0.264      P=0.184      P=0.003 **   P=0.330     |P=0.114N     P=0.243N     P=0.245N     P=0.236N     | 
|POLY 6             |     P=0.260      P=0.199      P=0.003 **   P=0.332     |P=0.113N     P=0.246N     P=0.246N     P=0.236N     | 
|LOGISTIC REGRESSION|     P=0.302      P=0.178      P=0.005 **   P=0.345     |P=0.115N     P=0.246N     P=0.246N     P=0.236N     | 
|COCH-ARM / FISHERS |     P=0.348      P=0.178      P=0.009 **   P=0.370     |P=0.115N     P=0.253N     P=0.253N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.043 *    (e)          (e)          (e)         |P=0.029N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  22/50 (44%)  22/50 (44%)  22/50 (44%) |4/50 (8%)    4/49 (8%)    6/49 (12%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |     10/47.84     22/49.00     22/43.23     22/44.86    |4/48.27      4/46.99      6/46.63      10/48.88     | 
|POLY-3 PERCENT (g) |     20.9%        44.9%        50.9%        49.0%       |8.3%         8.5%         12.9%        20.5%        | 
|TERMINAL (d)       |     9/43 (21%)   19/46 (41%)  16/36 (44%)  20/40 (50%) |3/46 (7%)    3/43 (7%)    6/43 (14%)   9/45 (20%)   | 
|FIRST INCIDENCE    |     611          657          531          656         |723          688          729 (T)      664          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.010 *    P=0.020 *    P=0.003 **   P=0.005 **  |P=0.030 *    P=0.604      P=0.328      P=0.074      | 
|POLY 3             |     P=0.007 **   P=0.009 **   P=0.002 **   P=0.003 **  |P=0.030 *    P=0.628      P=0.348      P=0.077      | 
|POLY 1.5           |     P=0.007 **   P=0.008 **   P=0.002 **   P=0.003 **  |P=0.030 *    P=0.630      P=0.350      P=0.076      | 
|POLY 6             |     P=0.007 **   P=0.011 *    P=0.002 **   P=0.003 **  |P=0.031 *    P=0.624      P=0.345      P=0.077      | 
|LOGISTIC REGRESSION|     P=0.010 *    P=0.010 *    P=0.003 **   P=0.004 **  |P=0.030 *    P=0.628      P=0.333      P=0.077      | 
|COCH-ARM / FISHERS |     P=0.024 *    P=0.009 **   P=0.009 **   P=0.009 **  |P=0.029 *    P=0.631      P=0.357      P=0.074      | 
|ORDER RESTRICTED   |     P=0.002 **   (e)          (e)          (e)         |P=0.048 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 5       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma, Hepatocellular Adenoma,                                                                           | 
|     or Hepatoblastoma                                                                                                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  22/50 (44%)  22/50 (44%)  22/50 (44%) |4/50 (8%)    4/49 (8%)    6/49 (12%)   10/50 (20%)  | 
|POLY-3 RATE (b)    |     10/47.84     22/49.00     22/43.23     22/44.86    |4/48.27      4/46.99      6/46.63      10/48.88     | 
|POLY-3 PERCENT (g) |     20.9%        44.9%        50.9%        49.0%       |8.3%         8.5%         12.9%        20.5%        | 
|TERMINAL (d)       |     9/43 (21%)   19/46 (41%)  16/36 (44%)  20/40 (50%) |3/46 (7%)    3/43 (7%)    6/43 (14%)   9/45 (20%)   | 
|FIRST INCIDENCE    |     611          657          531          656         |723          688          729 (T)      664          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.010 *    P=0.020 *    P=0.003 **   P=0.005 **  |P=0.030 *    P=0.604      P=0.328      P=0.074      | 
|POLY 3             |     P=0.007 **   P=0.009 **   P=0.002 **   P=0.003 **  |P=0.030 *    P=0.628      P=0.348      P=0.077      | 
|POLY 1.5           |     P=0.007 **   P=0.008 **   P=0.002 **   P=0.003 **  |P=0.030 *    P=0.630      P=0.350      P=0.076      | 
|POLY 6             |     P=0.007 **   P=0.011 *    P=0.002 **   P=0.003 **  |P=0.031 *    P=0.624      P=0.345      P=0.077      | 
|LOGISTIC REGRESSION|     P=0.010 *    P=0.010 *    P=0.003 **   P=0.004 **  |P=0.030 *    P=0.628      P=0.333      P=0.077      | 
|COCH-ARM / FISHERS |     P=0.024 *    P=0.009 **   P=0.009 **   P=0.009 **  |P=0.029 *    P=0.631      P=0.357      P=0.074      | 
|ORDER RESTRICTED   |     P=0.002 **   (e)          (e)          (e)         |P=0.048 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Adenoma                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/50 (22%)  7/50 (14%)   6/50 (12%)   5/50 (10%)  |4/50 (8%)    2/49 (4%)    0/49 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     11/47.93     7/48.59      6/41.44      5/44.45     |4/48.25      2/47.22      0/46.63      1/48.64      | 
|POLY-3 PERCENT (g) |     23.0%        14.4%        14.5%        11.3%       |8.3%         4.2%         0.0%         2.1%         | 
|TERMINAL (d)       |     9/43 (21%)   7/46 (15%)   6/36 (17%)   5/40 (13%)  |4/46 (9%)    1/43 (2%)    0/43 (0%)    1/45 (2%)    | 
|FIRST INCIDENCE    |     657          729 (T)      729 (T)      729 (T)     |729 (T)      620          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.114N     P=0.180N     P=0.255N     P=0.117N    |P=0.090N     P=0.366N     P=0.072N     P=0.187N     | 
|POLY 3             |     P=0.103N     P=0.208N     P=0.229N     P=0.113N    |P=0.085N     P=0.348N     P=0.065N     P=0.177N     | 
|POLY 1.5           |     P=0.099N     P=0.212N     P=0.214N     P=0.111N    |P=0.085N     P=0.347N     P=0.065N     P=0.177N     | 
|POLY 6             |     P=0.108N     P=0.201N     P=0.245N     P=0.115N    |P=0.085N     P=0.349N     P=0.066N     P=0.177N     | 
|LOGISTIC REGRESSION|     P=0.104N     P=0.208N     P=0.224N     P=0.108N    |P=0.086N     P=0.345N     (e)          P=0.187N     | 
|COCH-ARM / FISHERS |     P=0.072N     P=0.218N     P=0.143N     P=0.086N    |P=0.086N     P=0.349N     P=0.061N     P=0.181N     | 
|ORDER RESTRICTED   |     P=0.093N     (e)          (e)          (e)         |P=0.038N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 6       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   3/50 (6%)    5/50 (10%)   5/50 (10%)  |0/50 (0%)    2/49 (4%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     6/47.43      3/48.59      5/41.71      5/44.45     |0/48.25      2/47.16      0/46.63      0/48.64      | 
|POLY-3 PERCENT (g) |     12.7%        6.2%         12.0%        11.3%       |0.0%         4.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     6/43 (14%)   3/46 (7%)    4/36 (11%)   5/40 (13%)  |0/46 (0%)    1/43 (2%)    0/43 (0%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      654          729 (T)     |---          639          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.502      P=0.210N     P=0.621N     P=0.551N    |P=0.406N     P=0.228      (e)          (e)          | 
|POLY 3             |     P=0.521      P=0.231N     P=0.589N     P=0.545N    |P=0.404N     P=0.232      (e)          (e)          | 
|POLY 1.5           |     P=0.525      P=0.236N     P=0.579N     P=0.545N    |P=0.404N     P=0.233      (e)          (e)          | 
|POLY 6             |     P=0.516      P=0.223N     P=0.596N     P=0.544N    |P=0.405N     P=0.231      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.516      P=0.210N     P=0.601N     P=0.551N    |P=0.407N     P=0.234      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.549N     P=0.243N     P=0.500N     P=0.500N    |P=0.405N     P=0.242      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.502N     (e)          (e)          (e)         |P=0.241N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar                                                                      | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     14/50 (28%)  9/50 (18%)   10/50 (20%)  9/50 (18%)  |4/50 (8%)    4/49 (8%)    0/49 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     14/47.93     9/48.59      10/41.71     9/44.45     |4/48.25      4/47.54      0/46.63      1/48.64      | 
|POLY-3 PERCENT (g) |     29.2%        18.5%        24.0%        20.3%       |8.3%         8.4%         0.0%         2.1%         | 
|TERMINAL (d)       |     12/43 (28%)  9/46 (20%)   9/36 (25%)   9/40 (23%)  |4/46 (9%)    2/43 (5%)    0/43 (0%)    1/45 (2%)    | 
|FIRST INCIDENCE    |     657          729 (T)      654          729 (T)     |729 (T)      620          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.287N     P=0.133N     P=0.420N     P=0.227N    |P=0.064N     P=0.609      P=0.072N     P=0.187N     | 
|POLY 3             |     P=0.264N     P=0.160N     P=0.376N     P=0.226N    |P=0.059N     P=0.635      P=0.065N     P=0.177N     | 
|POLY 1.5           |     P=0.256N     P=0.165N     P=0.355N     P=0.223N    |P=0.059N     P=0.634      P=0.065N     P=0.177N     | 
|POLY 6             |     P=0.275N     P=0.154N     P=0.395N     P=0.231N    |P=0.059N     P=0.635      P=0.066N     P=0.177N     | 
|LOGISTIC REGRESSION|     P=0.264N     P=0.158N     P=0.373N     P=0.216N    |P=0.060N     P=0.636      (e)          P=0.187N     | 
|COCH-ARM / FISHERS |     P=0.189N     P=0.171N     P=0.241N     P=0.171N    |P=0.060N     P=0.631      P=0.061N     P=0.181N     | 
|ORDER RESTRICTED   |     P=0.242N     (e)          (e)          (e)         |P=0.063N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 7       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/49 (0%)    0/49 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/47.43      0/48.59      0/41.44      0/44.45     |1/48.25      0/46.83      0/46.63      2/48.65      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.1%         0.0%         0.0%         4.1%         | 
|TERMINAL (d)       |     0/43 (0%)    0/46 (0%)    0/36 (0%)    0/40 (0%)   |1/46 (2%)    0/43 (0%)    0/43 (0%)    1/45 (2%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      ---          ---          727          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.249      P=0.513N     P=0.513N     P=0.495      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.249      P=0.506N     P=0.507N     P=0.503      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.249      P=0.505N     P=0.507N     P=0.502      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.250      P=0.508N     P=0.508N     P=0.502      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.251      (e)          (e)          P=0.500      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.247      P=0.505N     P=0.505N     P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.135      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma,                                                                        | 
|     or Fibrous Histiocytoma                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/49 (0%)    4/49 (8%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/47.43      1/48.59      0/41.44      0/44.45     |0/48.25      0/46.83      4/46.77      1/48.67      | 
|POLY-3 PERCENT (g) |     2.1%         2.1%         0.0%         0.0%        |0.0%         0.0%         8.6%         2.1%         | 
|TERMINAL (d)       |     1/43 (2%)    1/46 (2%)    0/36 (0%)    0/40 (0%)   |0/46 (0%)    0/43 (0%)    3/43 (7%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          ---         |---          ---          693          720          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.256N     P=0.747N     P=0.535N     P=0.514N    |P=0.250      (e)          P=0.058      P=0.500      | 
|POLY 3             |     P=0.249N     P=0.755N     P=0.527N     P=0.513N    |P=0.252      (e)          P=0.057      P=0.502      | 
|POLY 1.5           |     P=0.247N     P=0.757N     P=0.523N     P=0.513N    |P=0.250      (e)          P=0.057      P=0.501      | 
|POLY 6             |     P=0.250N     P=0.751N     P=0.530N     P=0.513N    |P=0.253      (e)          P=0.056      P=0.502      | 
|LOGISTIC REGRESSION|     P=0.256N     P=0.747N     (e)          (e)         |P=0.249      (e)          P=0.059      P=0.500      | 
|COCH-ARM / FISHERS |     P=0.236N     P=0.753N     P=0.500N     P=0.500N    |P=0.248      (e)          P=0.056      P=0.500      | 
|ORDER RESTRICTED   |     P=0.265N     (e)          (e)          (e)         |P=0.074      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 8       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibrosarcoma                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/49 (0%)    3/49 (6%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/47.43      0/48.59      0/41.44      0/44.45     |0/48.25      0/46.83      3/46.77      1/48.67      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         6.4%         2.1%         | 
|TERMINAL (d)       |     0/43 (0%)    0/46 (0%)    0/36 (0%)    0/40 (0%)   |0/46 (0%)    0/43 (0%)    2/43 (5%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          693          720          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.253      (e)          P=0.113      P=0.500      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.254      (e)          P=0.113      P=0.502      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.253      (e)          P=0.113      P=0.501      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.255      (e)          P=0.113      P=0.502      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.250      (e)          P=0.116      P=0.500      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.249      (e)          P=0.117      P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.109      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/49 (0%)    4/49 (8%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/47.43      1/48.59      0/41.44      0/44.45     |0/48.25      0/46.83      4/46.77      1/48.67      | 
|POLY-3 PERCENT (g) |     2.1%         2.1%         0.0%         0.0%        |0.0%         0.0%         8.6%         2.1%         | 
|TERMINAL (d)       |     1/43 (2%)    1/46 (2%)    0/36 (0%)    0/40 (0%)   |0/46 (0%)    0/43 (0%)    3/43 (7%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          ---         |---          ---          693          720          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.256N     P=0.747N     P=0.535N     P=0.514N    |P=0.250      (e)          P=0.058      P=0.500      | 
|POLY 3             |     P=0.249N     P=0.755N     P=0.527N     P=0.513N    |P=0.252      (e)          P=0.057      P=0.502      | 
|POLY 1.5           |     P=0.247N     P=0.757N     P=0.523N     P=0.513N    |P=0.250      (e)          P=0.057      P=0.501      | 
|POLY 6             |     P=0.250N     P=0.751N     P=0.530N     P=0.513N    |P=0.253      (e)          P=0.056      P=0.502      | 
|LOGISTIC REGRESSION|     P=0.256N     P=0.747N     (e)          (e)         |P=0.249      (e)          P=0.059      P=0.500      | 
|COCH-ARM / FISHERS |     P=0.236N     P=0.753N     P=0.500N     P=0.500N    |P=0.248      (e)          P=0.056      P=0.500      | 
|ORDER RESTRICTED   |     P=0.265N     (e)          (e)          (e)         |P=0.074      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 9       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |2/50 (4%)    1/49 (2%)    0/49 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/47.43      1/48.59      0/41.44      1/44.45     |2/48.25      1/46.83      0/46.63      2/49.07      | 
|POLY-3 PERCENT (g) |     0.0%         2.1%         0.0%         2.3%        |4.2%         2.1%         0.0%         4.1%         | 
|TERMINAL (d)       |     0/43 (0%)    1/46 (2%)    0/36 (0%)    1/40 (3%)   |2/46 (4%)    1/43 (2%)    0/43 (0%)    1/45 (2%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          729 (T)     |729 (T)      729 (T)      ---          604          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.381      P=0.513      (e)          P=0.486     |P=0.589      P=0.524N     P=0.253N     P=0.689      | 
|POLY 3             |     P=0.385      P=0.505      (e)          P=0.487     |P=0.596      P=0.510N     P=0.245N     P=0.687N     | 
|POLY 1.5           |     P=0.385      P=0.503      (e)          P=0.487     |P=0.594      P=0.509N     P=0.245N     P=0.689N     | 
|POLY 6             |     P=0.385      P=0.508      (e)          P=0.487     |P=0.598      P=0.514N     P=0.246N     P=0.686N     | 
|LOGISTIC REGRESSION|     (e)          P=0.513      (e)          P=0.486     |P=0.589      P=0.524N     (e)          P=0.676      | 
|COCH-ARM / FISHERS |     P=0.405      P=0.500      (e)          P=0.500     |P=0.592      P=0.508N     P=0.253N     P=0.691N     | 
|ORDER RESTRICTED   |     P=0.239      (e)          (e)          (e)         |P=0.414N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    7/50 (14%)  |1/49 (2%)    0/48 (0%)    0/48 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/47.43      1/48.86      0/41.44      7/44.45     |1/47.25      0/45.83      0/45.89      1/48.64      | 
|POLY-3 PERCENT (g) |     0.0%         2.1%         0.0%         15.8%       |2.1%         0.0%         0.0%         2.1%         | 
|TERMINAL (d)       |     0/43 (0%)    0/46 (0%)    0/36 (0%)    7/40 (18%)  |1/45 (2%)    0/42 (0%)    0/43 (0%)    1/45 (2%)    | 
|FIRST INCIDENCE    |     ---          657          ---          729 (T)     |729 (T)      ---          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.508      (e)          P=0.007 **  |P=0.597      P=0.514N     P=0.509N     P=0.761      | 
|POLY 3             |     P<0.001 **   P=0.506      (e)          P=0.006 **  |P=0.602      P=0.506N     P=0.506N     P=0.754N     | 
|POLY 1.5           |     P<0.001 **   P=0.503      (e)          P=0.006 **  |P=0.601      P=0.505N     P=0.506N     P=0.754N     | 
|POLY 6             |     P<0.001 **   P=0.510      (e)          P=0.006 **  |P=0.603      P=0.508N     P=0.506N     P=0.754N     | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.496      (e)          P=0.007 **  |P=0.597      (e)          (e)          P=0.761      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.500      (e)          P=0.006 **  |P=0.599      P=0.505N     P=0.505N     P=0.747N     | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.397N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 10      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Polyp Stromal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |0/50 (0%)    0/49 (0%)    2/49 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |                                                        |0/48.25      0/46.83      2/47.00      0/48.64      | 
|POLY-3 PERCENT (g) |                                                        |0.0%         0.0%         4.3%         0.0%         | 
|TERMINAL (d)       |                                                        |0/46 (0%)    0/43 (0%)    1/43 (2%)    0/45 (0%)    | 
|FIRST INCIDENCE    |                                                        |---          ---          623          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.594      (e)          P=0.230      (e)          | 
|POLY 3             |                                                        |P=0.602      (e)          P=0.232      (e)          | 
|POLY 1.5           |                                                        |P=0.601      (e)          P=0.231      (e)          | 
|POLY 6             |                                                        |P=0.603      (e)          P=0.231      (e)          | 
|LOGISTIC REGRESSION|                                                        |P=0.593      (e)          P=0.246      (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.595      (e)          P=0.242      (e)          | 
|ORDER RESTRICTED   |                                                        |P=0.242      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Sarcoma Stromal or Polyp Stromal                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |1/50 (2%)    0/49 (0%)    2/49 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |                                                        |1/48.25      0/46.83      2/47.00      0/48.64      | 
|POLY-3 PERCENT (g) |                                                        |2.1%         0.0%         4.3%         0.0%         | 
|TERMINAL (d)       |                                                        |1/46 (2%)    0/43 (0%)    1/43 (2%)    0/45 (0%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      ---          623          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.462N     P=0.513N     P=0.482      P=0.504N     | 
|POLY 3             |                                                        |P=0.455N     P=0.506N     P=0.491      P=0.498N     | 
|POLY 1.5           |                                                        |P=0.457N     P=0.505N     P=0.490      P=0.499N     | 
|POLY 6             |                                                        |P=0.455N     P=0.508N     P=0.491      P=0.499N     | 
|LOGISTIC REGRESSION|                                                        |P=0.464N     (e)          P=0.505      (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.460N     P=0.505N     P=0.492      P=0.500N     | 
|ORDER RESTRICTED   |                                                        |P=0.317N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 11      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    1/50 (2%)    2/50 (4%)   |2/50 (4%)    2/49 (4%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/47.66      1/48.60      1/41.44      2/44.45     |2/48.86      2/47.25      0/46.63      0/48.64      | 
|POLY-3 PERCENT (g) |     4.2%         2.1%         2.4%         4.5%        |4.1%         4.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/43 (2%)    0/46 (0%)    1/36 (3%)    2/40 (5%)   |1/46 (2%)    0/43 (0%)    0/43 (0%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     668          726          729 (T)      729 (T)     |533          620          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.512      P=0.477N     P=0.563N     P=0.668     |P=0.089N     P=0.676      P=0.249N     P=0.242N     | 
|POLY 3             |     P=0.522      P=0.493N     P=0.548N     P=0.668     |P=0.087N     P=0.682      P=0.248N     P=0.238N     | 
|POLY 1.5           |     P=0.525      P=0.496N     P=0.542N     P=0.669     |P=0.087N     P=0.684      P=0.246N     P=0.238N     | 
|POLY 6             |     P=0.518      P=0.488N     P=0.555N     P=0.668     |P=0.088N     P=0.679      P=0.250N     P=0.240N     | 
|LOGISTIC REGRESSION|     P=0.526      P=0.500N     P=0.535N     P=0.677     |P=0.081N     P=0.696      P=0.193N     P=0.300N     | 
|COCH-ARM / FISHERS |     P=0.556      P=0.500N     P=0.500N     P=0.691N    |P=0.086N     P=0.684      P=0.253N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.526      (e)          (e)          (e)         |P=0.111N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangiosarcoma or Hemangioma                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    1/50 (2%)    3/50 (6%)   |2/50 (4%)    2/49 (4%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/47.66      1/48.60      1/41.44      3/44.45     |2/48.86      2/47.25      0/46.63      0/48.64      | 
|POLY-3 PERCENT (g) |     4.2%         2.1%         2.4%         6.8%        |4.1%         4.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/43 (2%)    0/46 (0%)    1/36 (3%)    3/40 (8%)   |1/46 (2%)    0/43 (0%)    0/43 (0%)    0/45 (0%)    | 
|FIRST INCIDENCE    |     668          726          729 (T)      729 (T)     |533          620          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.285      P=0.477N     P=0.563N     P=0.468     |P=0.089N     P=0.676      P=0.249N     P=0.242N     | 
|POLY 3             |     P=0.294      P=0.493N     P=0.548N     P=0.468     |P=0.087N     P=0.682      P=0.248N     P=0.238N     | 
|POLY 1.5           |     P=0.297      P=0.496N     P=0.542N     P=0.469     |P=0.087N     P=0.684      P=0.246N     P=0.238N     | 
|POLY 6             |     P=0.290      P=0.488N     P=0.555N     P=0.467     |P=0.088N     P=0.679      P=0.250N     P=0.240N     | 
|LOGISTIC REGRESSION|     P=0.295      P=0.500N     P=0.535N     P=0.474     |P=0.081N     P=0.696      P=0.193N     P=0.300N     | 
|COCH-ARM / FISHERS |     P=0.324      P=0.500N     P=0.500N     P=0.500     |P=0.086N     P=0.684      P=0.253N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.268      (e)          (e)          (e)         |P=0.111N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 12      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        | 
|     NOS, or Undifferentiated Cell Type                                                                                          | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    0/50 (0%)    1/50 (2%)   |6/50 (12%)   8/49 (16%)   6/49 (12%)   8/50 (16%)   | 
|POLY-3 RATE (b)    |     2/47.43      3/48.59      0/41.44      1/44.45     |6/48.25      8/46.99      6/46.89      8/48.64      | 
|POLY-3 PERCENT (g) |     4.2%         6.2%         0.0%         2.3%        |12.4%        17.0%        12.8%        16.5%        | 
|TERMINAL (d)       |     2/43 (5%)    3/46 (7%)    0/36 (0%)    1/40 (3%)   |6/46 (13%)   7/43 (16%)   5/43 (12%)   8/45 (18%)   | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          729 (T)     |729 (T)      688          658          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.277N     P=0.531      P=0.278N     P=0.525N    |P=0.389      P=0.338      P=0.575      P=0.369      | 
|POLY 3             |     P=0.266N     P=0.511      P=0.269N     P=0.523N    |P=0.403      P=0.367      P=0.600      P=0.393      | 
|POLY 1.5           |     P=0.264N     P=0.506      P=0.264N     P=0.523N    |P=0.402      P=0.369      P=0.599      P=0.392      | 
|POLY 6             |     P=0.268N     P=0.519      P=0.272N     P=0.522N    |P=0.403      P=0.362      P=0.599      P=0.392      | 
|LOGISTIC REGRESSION|     P=0.277N     P=0.531      (e)          P=0.525N    |P=0.404      P=0.356      P=0.598      P=0.369      | 
|COCH-ARM / FISHERS |     P=0.242N     P=0.500      P=0.247N     P=0.500N    |P=0.396      P=0.371      P=0.606      P=0.387      | 
|ORDER RESTRICTED   |     P=0.217N     (e)          (e)          (e)         |P=0.456      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     23/50 (46%)  25/50 (50%)  24/50 (48%)  30/50 (60%) |13/50 (26%)  12/49 (24%)  14/49 (29%)  20/50 (40%)  | 
|POLY-3 RATE (b)    |     23/48.07     25/48.86     24/42.55     30/45.48    |13/48.27     12/47.41     14/47.00     20/49.31     | 
|POLY-3 PERCENT (g) |     47.9%        51.2%        56.4%        66.0%       |26.9%        25.3%        29.8%        40.6%        | 
|TERMINAL (d)       |     20/43 (47%)  24/46 (52%)  20/36 (56%)  27/40 (68%) |12/46 (26%)  9/43 (21%)   13/43 (30%)  18/45 (40%)  | 
|FIRST INCIDENCE    |     657          657          611          531         |723          620          623          604          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.030 *    P=0.546      P=0.213      P=0.063     |P=0.054      P=0.572N     P=0.421      P=0.095      | 
|POLY 3             |     P=0.037 *    P=0.451      P=0.273      P=0.057     |P=0.058      P=0.521N     P=0.468      P=0.113      | 
|POLY 1.5           |     P=0.038 *    P=0.438      P=0.295      P=0.057     |P=0.055      P=0.521N     P=0.465      P=0.109      | 
|POLY 6             |     P=0.035 *    P=0.471      P=0.259      P=0.058     |P=0.060      P=0.521N     P=0.467      P=0.117      | 
|LOGISTIC REGRESSION|     P=0.035 *    P=0.454      P=0.260      P=0.057     |P=0.054      P=0.532N     P=0.457      P=0.105      | 
|COCH-ARM / FISHERS |     P=0.098      P=0.421      P=0.500      P=0.115     |P=0.051      P=0.523N     P=0.475      P=0.101      | 
|ORDER RESTRICTED   |     P=0.053      (e)          (e)          (e)         |P=0.090      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/25/03                           EXPERIMENT: 92012 TEST: 06                                            Page 13      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    2-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     20/50 (40%)  16/50 (32%)  21/50 (42%)  14/50 (28%) |12/50 (24%)  12/49 (24%)  15/49 (31%)  14/50 (28%)  | 
|POLY-3 RATE (b)    |     20/48.77     16/49.00     21/43.75     14/45.00    |12/49.71     12/47.74     15/47.45     14/49.36     | 
|POLY-3 PERCENT (g) |     41.0%        32.7%        48.0%        31.1%       |24.1%        25.1%        31.6%        28.4%        | 
|TERMINAL (d)       |     15/43 (35%)  13/46 (28%)  14/36 (39%)  11/40 (28%) |9/46 (20%)   8/43 (19%)   11/43 (26%)  10/45 (22%)  | 
|FIRST INCIDENCE    |     611          657          512          656         |402          620          623          604          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.330N     P=0.213N     P=0.263      P=0.227N    |P=0.334      P=0.523      P=0.276      P=0.400      | 
|POLY 3             |     P=0.291N     P=0.260N     P=0.322      P=0.218N    |P=0.325      P=0.548      P=0.277      P=0.402      | 
|POLY 1.5           |     P=0.280N     P=0.263N     P=0.334      P=0.211N    |P=0.326      P=0.554      P=0.281      P=0.405      | 
|POLY 6             |     P=0.306N     P=0.255N     P=0.314      P=0.227N    |P=0.326      P=0.543      P=0.276      P=0.402      | 
|LOGISTIC REGRESSION|     P=0.247N     P=0.260N     P=0.364      P=0.189N    |P=0.317      P=0.585      P=0.322      P=0.375      | 
|COCH-ARM / FISHERS |     P=0.178N     P=0.266N     P=0.500      P=0.146N    |P=0.328      P=0.570      P=0.304      P=0.410      | 
|ORDER RESTRICTED   |     P=0.256N     (e)          (e)          (e)         |P=0.407      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     32/50 (64%)  34/50 (68%)  34/50 (68%)  38/50 (76%) |23/50 (46%)  20/49 (41%)  23/49 (47%)  29/50 (58%)  | 
|POLY-3 RATE (b)    |     32/48.77     34/49.00     34/44.17     38/45.61    |23/49.71     20/47.74     23/47.45     29/49.36     | 
|POLY-3 PERCENT (g) |     65.6%        69.4%        77.0%        83.3%       |46.3%        41.9%        48.5%        58.8%        | 
|TERMINAL (d)       |     27/43 (63%)  31/46 (67%)  26/36 (72%)  34/40 (85%) |20/46 (44%)  16/43 (37%)  19/43 (44%)  25/45 (56%)  | 
|FIRST INCIDENCE    |     611          657          512          531         |402          620          623          604          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.031 *    P=0.562N     P=0.112      P=0.069     |P=0.096      P=0.454N     P=0.466      P=0.158      | 
|POLY 3             |     P=0.023 *    P=0.428      P=0.164      P=0.040 *   |P=0.078      P=0.409N     P=0.494      P=0.148      | 
|POLY 1.5           |     P=0.025 *    P=0.423      P=0.172      P=0.042 *   |P=0.079      P=0.399N     P=0.501      P=0.152      | 
|POLY 6             |     P=0.020 *    P=0.438      P=0.165      P=0.036 *   |P=0.079      P=0.416N     P=0.492      P=0.147      | 
|LOGISTIC REGRESSION|     P=0.027 *    P=0.441      P=0.162      P=0.049 *   |P=0.083      P=0.369N     P=0.543      P=0.150      | 
|COCH-ARM / FISHERS |     P=0.117      P=0.417      P=0.417      P=0.138     |P=0.082      P=0.376N     P=0.543      P=0.158      | 
|ORDER RESTRICTED   |     P=0.034 *    (e)          (e)          (e)         |P=0.107      (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.