https://ntp.niehs.nih.gov/go/18911

TDMS Study 92013-06 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                4-METHYLIMIDAZOLE                                   DATE: 01/12/04       
EXPERIMENT: 92013 TEST: 06                                                                                     TIME: 14:42:07       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92013B       
PATHOLOGIST: HEATH, JAMES                                                                                      CAS: 822-36-6        
------------------------------------------------------------------------------------------------------------------------------------
                                                           FINAL #1 MICE                                                            
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                4-METHYLIMIDAZOLE                                   DATE: 01/12/04       
EXPERIMENT: 92013 TEST: 06                                                                                     TIME: 14:42:07       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92013B       
PATHOLOGIST: HEATH, JAMES                                                                                      CAS: 822-36-6        
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                                                                              
                                                 Heart                                                                              
                                                 Islets, Pancreatic                                                                 
                                                 Kidney                                                                             
                                                 Liver                                                                              
                                                 Lung                                                                               
                                                 Ovary                                                                              
                                                 Pituitary Gland                                                                    
                                                 Prostate                                                                           
                                                 Spleen                                                                             
                                                 Testes                                                                             
                                                 Thyroid Gland                                                                      
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                4-METHYLIMIDAZOLE                                   DATE: 01/12/04       
EXPERIMENT: 92013 TEST: 06                                                                                     TIME: 14:42:07       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92013B       
PATHOLOGIST: HEATH, JAMES                                                                                      CAS: 822-36-6        
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                   4-METHYLIMIDAZOLE                                                                              
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Cortex                         Adenoma                                                                                      
Lung                                   Alveolar/Bronchiolar Carcinoma                                                               
                                       Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                               
Stomach, Forestomach                   Squamous Cell Papilloma                                                                      
All Organs                             Malignant Tumors                                                                             
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Liver                                  Hepatocellular Adenoma                                                                       
                                       Hepatocellular Carcinoma or Hepatocellular Adenoma                                           
                                       Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                          
Lung                                   Alveolar/Bronchiolar Adenoma                                                                 
                                       Alveolar/Bronchiolar Carcinoma                                                               
                                       Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                               
Ovary                                  Granulosa Cell Tumor Benign                                                                  
All Organs                             Malignant Tumors                                                                             
                                       Malignant and Benign Tumors                                                                  
===============================================================                                                                     
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 1       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)        -                    4-METHYLIMIDAZOLE           
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     4/48.24      1/47.90      1/45.68      0/47.85     |0/46.61      1/47.80      0/48.01      0/46.05      | 
|POLY-3 PERCENT (g) |     8.3%         2.1%         2.2%         0.0%        |0.0%         2.1%         0.0%         0.0%         | 
|TERMINAL (d)       |     4/45 (9%)    1/44 (2%)    1/42 (2%)    0/46 (0%)   |0/43 (0%)    1/40 (3%)    0/43 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |---          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.035N*    P=0.187N     P=0.201N     P=0.061N    |P=0.574N     P=0.486      (e)          (e)          | 
|POLY 3             |     P=0.034N*    P=0.181N     P=0.196N     P=0.062N    |P=0.562N     P=0.505      (e)          (e)          | 
|POLY 1.5           |     P=0.034N*    P=0.181N     P=0.190N     P=0.061N    |P=0.563N     P=0.505      (e)          (e)          | 
|POLY 6             |     P=0.034N*    P=0.182N     P=0.203N     P=0.062N    |P=0.563N     P=0.504      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.035N*    P=0.187N     P=0.201N     (e)         |(e)          P=0.486      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.034N*    P=0.181N     P=0.181N     P=0.059N    |P=0.567N     P=0.500      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.012N*    (e)          (e)          (e)         |P=0.388N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     4/50 (8%)    9/50 (18%)   4/50 (8%)    7/50 (14%)  |6/50 (12%)   1/50 (2%)    5/50 (10%)   6/50 (12%)   | 
|POLY-3 RATE (b)    |     4/48.24      9/48.10      4/45.68      7/47.85     |6/47.07      1/47.80      5/48.04      6/46.22      | 
|POLY-3 PERCENT (g) |     8.3%         18.7%        8.8%         14.6%       |12.8%        2.1%         10.4%        13.0%        | 
|TERMINAL (d)       |     4/45 (9%)    8/44 (18%)   4/42 (10%)   7/46 (15%)  |5/43 (12%)   1/40 (3%)    4/43 (9%)    5/40 (13%)   | 
|FIRST INCIDENCE    |     729 (T)      676          729 (T)      729 (T)     |593          729 (T)      720          685          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.401      P=0.111      P=0.605      P=0.274     |P=0.310      P=0.069N     P=0.496N     P=0.574      | 
|POLY 3             |     P=0.373      P=0.115      P=0.613      P=0.257     |P=0.323      P=0.054N     P=0.486N     P=0.608      | 
|POLY 1.5           |     P=0.376      P=0.115      P=0.624      P=0.258     |P=0.329      P=0.054N     P=0.486N     P=0.617      | 
|POLY 6             |     P=0.369      P=0.115      P=0.601      P=0.256     |P=0.317      P=0.055N     P=0.488N     P=0.596      | 
|LOGISTIC REGRESSION|     P=0.374      P=0.114      P=0.605      P=0.274     |P=0.329      P=0.057N     P=0.489N     P=0.618      | 
|COCH-ARM / FISHERS |     P=0.385      P=0.117      P=0.643N     P=0.262     |P=0.338      P=0.056N     P=0.500N     P=0.620N     | 
|ORDER RESTRICTED   |     P=0.275      (e)          (e)          (e)         |P=0.284      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 2       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/48.29      1/47.90      0/45.68      1/47.85     |1/46.61      1/47.80      0/48.01      2/46.12      | 
|POLY-3 PERCENT (g) |     2.1%         2.1%         0.0%         2.1%        |2.2%         2.1%         0.0%         4.3%         | 
|TERMINAL (d)       |     0/45 (0%)    1/44 (2%)    0/42 (0%)    1/46 (2%)   |1/43 (2%)    1/40 (3%)    0/43 (0%)    1/40 (3%)    | 
|FIRST INCIDENCE    |     715          729 (T)      ---          729 (T)     |729 (T)      729 (T)      ---          711          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.611N     P=0.758      P=0.518N     P=0.758N    |P=0.353      P=0.746      P=0.500N     P=0.478      | 
|POLY 3             |     P=0.620N     P=0.759      P=0.511N     P=0.758     |P=0.364      P=0.755N     P=0.494N     P=0.496      | 
|POLY 1.5           |     P=0.618N     P=0.759      P=0.507N     P=0.759     |P=0.366      P=0.755N     P=0.495N     P=0.500      | 
|POLY 6             |     P=0.621N     P=0.758      P=0.515N     P=0.758     |P=0.362      P=0.756N     P=0.494N     P=0.492      | 
|LOGISTIC REGRESSION|     P=0.618N     P=0.761      P=0.506N     P=0.761     |P=0.356      P=0.746      (e)          P=0.491      | 
|COCH-ARM / FISHERS |     P=0.616N     P=0.753N     P=0.500N     P=0.753N    |P=0.366      P=0.753N     P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.542N     (e)          (e)          (e)         |P=0.265      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     5/50 (10%)   10/50 (20%)  4/50 (8%)    8/50 (16%)  |7/50 (14%)   2/50 (4%)    5/50 (10%)   8/50 (16%)   | 
|POLY-3 RATE (b)    |     5/48.29      10/48.10     4/45.68      8/47.85     |7/47.07      2/47.80      5/48.04      8/46.29      | 
|POLY-3 PERCENT (g) |     10.4%        20.8%        8.8%         16.7%       |14.9%        4.2%         10.4%        17.3%        | 
|TERMINAL (d)       |     4/45 (9%)    9/44 (21%)   4/42 (10%)   8/46 (17%)  |6/43 (14%)   2/40 (5%)    4/43 (9%)    6/40 (15%)   | 
|FIRST INCIDENCE    |     715          676          729 (T)      729 (T)     |593          729 (T)      720          685          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.421      P=0.127      P=0.544N     P=0.291     |P=0.221      P=0.097N     P=0.377N     P=0.448      | 
|POLY 3             |     P=0.390      P=0.128      P=0.535N     P=0.270     |P=0.233      P=0.076N     P=0.365N     P=0.486      | 
|POLY 1.5           |     P=0.394      P=0.129      P=0.522N     P=0.272     |P=0.238      P=0.075N     P=0.366N     P=0.496      | 
|POLY 6             |     P=0.385      P=0.128      P=0.548N     P=0.269     |P=0.228      P=0.078N     P=0.367N     P=0.473      | 
|LOGISTIC REGRESSION|     P=0.392      P=0.127      P=0.555N     P=0.269     |P=0.235      P=0.078N     P=0.366N     P=0.494      | 
|COCH-ARM / FISHERS |     P=0.404      P=0.131      P=0.500N     P=0.277     |P=0.246      P=0.080N     P=0.380N     P=0.500      | 
|ORDER RESTRICTED   |     P=0.292      (e)          (e)          (e)         |P=0.188      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 3       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Duodenum                                                                                                        | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/48.24      2/47.90      0/45.68      0/47.85     |0/46.61      0/47.80      2/48.01      0/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         4.2%         0.0%         0.0%        |0.0%         0.0%         4.2%         0.0%         | 
|TERMINAL (d)       |     0/45 (0%)    2/44 (5%)    0/42 (0%)    0/46 (0%)   |0/43 (0%)    0/40 (0%)    2/43 (5%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.401N     P=0.234      (e)          (e)         |P=0.585      (e)          P=0.238      (e)          | 
|POLY 3             |     P=0.410N     P=0.236      (e)          (e)         |P=0.582      (e)          P=0.244      (e)          | 
|POLY 1.5           |     P=0.408N     P=0.236      (e)          (e)         |P=0.589      (e)          P=0.243      (e)          | 
|POLY 6             |     P=0.412N     P=0.235      (e)          (e)         |P=0.574      (e)          P=0.244      (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.234      (e)          (e)         |(e)          (e)          P=0.238      (e)          | 
|COCH-ARM / FISHERS |     P=0.405N     P=0.247      (e)          (e)         |P=0.595      (e)          P=0.247      (e)          | 
|ORDER RESTRICTED   |     P=0.247N     (e)          (e)          (e)         |P=0.254      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small: Site Unspecified                                                                                                | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/48.24      3/47.90      0/45.68      0/47.85     |0/46.61      0/47.80      2/48.01      0/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         6.3%         0.0%         0.0%        |0.0%         0.0%         4.2%         0.0%         | 
|TERMINAL (d)       |     0/45 (0%)    3/44 (7%)    0/42 (0%)    0/46 (0%)   |0/43 (0%)    0/40 (0%)    2/43 (5%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.308N     P=0.117      (e)          (e)         |P=0.585      (e)          P=0.238      (e)          | 
|POLY 3             |     P=0.315N     P=0.118      (e)          (e)         |P=0.582      (e)          P=0.244      (e)          | 
|POLY 1.5           |     P=0.313N     P=0.118      (e)          (e)         |P=0.589      (e)          P=0.243      (e)          | 
|POLY 6             |     P=0.317N     P=0.117      (e)          (e)         |P=0.574      (e)          P=0.244      (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.117      (e)          (e)         |(e)          (e)          P=0.238      (e)          | 
|COCH-ARM / FISHERS |     P=0.311N     P=0.121      (e)          (e)         |P=0.595      (e)          P=0.247      (e)          | 
|ORDER RESTRICTED   |     P=0.163N     (e)          (e)          (e)         |P=0.254      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 4       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    1/49 (2%)    0/50 (0%)    1/50 (2%)   |0/49 (0%)    3/48 (6%)    0/47 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     0/47.37      1/47.79      0/45.68      1/47.85     |0/46.61      3/46.38      0/45.13      0/45.05      | 
|POLY-3 PERCENT (g) |     0.0%         2.1%         0.0%         2.1%        |0.0%         6.5%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    0/42 (0%)    1/46 (2%)   |0/43 (0%)    2/40 (5%)    0/42 (0%)    0/39 (0%)    | 
|FIRST INCIDENCE    |     ---          613          ---          729 (T)     |---          668          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.408      P=0.500      (e)          P=0.504     |P=0.326N     P=0.116      (e)          (e)          | 
|POLY 3             |     P=0.406      P=0.502      (e)          P=0.502     |P=0.314N     P=0.118      (e)          (e)          | 
|POLY 1.5           |     P=0.408      P=0.501      (e)          P=0.503     |P=0.312N     P=0.117      (e)          (e)          | 
|POLY 6             |     P=0.405      P=0.503      (e)          P=0.501     |P=0.316N     P=0.118      (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.420      P=0.543      (e)          P=0.504     |P=0.306N     P=0.113      (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.410      P=0.500      (e)          P=0.505     |P=0.312N     P=0.117      (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.254      (e)          (e)          (e)         |P=0.168N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    1/49 (2%)    0/50 (0%)    1/50 (2%)   |0/49 (0%)    4/48 (8%)    1/47 (2%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     0/47.37      1/47.79      0/45.68      1/47.85     |0/46.61      4/46.38      1/45.13      0/45.05      | 
|POLY-3 PERCENT (g) |     0.0%         2.1%         0.0%         2.1%        |0.0%         8.6%         2.2%         0.0%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    0/42 (0%)    1/46 (2%)   |0/43 (0%)    3/40 (8%)    1/42 (2%)    0/39 (0%)    | 
|FIRST INCIDENCE    |     ---          613          ---          729 (T)     |---          668          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.408      P=0.500      (e)          P=0.504     |P=0.316N     P=0.059      P=0.495      (e)          | 
|POLY 3             |     P=0.406      P=0.502      (e)          P=0.502     |P=0.304N     P=0.060      P=0.494      (e)          | 
|POLY 1.5           |     P=0.408      P=0.501      (e)          P=0.503     |P=0.300N     P=0.059      P=0.493      (e)          | 
|POLY 6             |     P=0.405      P=0.503      (e)          P=0.501     |P=0.310N     P=0.060      P=0.494      (e)          | 
|LOGISTIC REGRESSION|     P=0.420      P=0.543      (e)          P=0.504     |P=0.300N     P=0.059      P=0.495      (e)          | 
|COCH-ARM / FISHERS |     P=0.410      P=0.500      (e)          P=0.505     |P=0.296N     P=0.056      P=0.490      (e)          | 
|ORDER RESTRICTED   |     P=0.254      (e)          (e)          (e)         |P=0.155N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 5       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      2/45.68      0/47.85     |0/46.61      0/47.80      0/48.01      0/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.4%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    2/42 (5%)    0/46 (0%)   |0/43 (0%)    0/40 (0%)    0/43 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.598      (e)          P=0.223      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.596      (e)          P=0.225      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.595      (e)          P=0.230      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.597      (e)          P=0.221      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.223      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.595      (e)          P=0.247      (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.237      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      3/45.68      0/47.85     |0/46.61      0/47.80      0/48.01      0/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         6.6%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    3/42 (7%)    0/46 (0%)   |0/43 (0%)    0/40 (0%)    0/43 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.544      (e)          P=0.109      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.540      (e)          P=0.109      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.539      (e)          P=0.113      (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.541      (e)          P=0.106      (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.109      (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.539      (e)          P=0.121      (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.153      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 6       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      2/46.46      1/47.85     |0/46.61      0/47.80      0/48.01      0/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.3%         2.1%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    1/42 (2%)    1/46 (2%)   |0/43 (0%)    0/40 (0%)    0/43 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          441          729 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.251      (e)          P=0.230      P=0.504     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.244      (e)          P=0.229      P=0.498     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.244      (e)          P=0.232      P=0.499     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.244      (e)          P=0.226      P=0.498     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.257      (e)          P=0.342      P=0.504     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.246      (e)          P=0.247      P=0.500     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.161      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Adenoma                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     17/50 (34%)  9/50 (18%)   11/50 (22%)  11/50 (22%) |4/50 (8%)    5/50 (10%)   0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     17/48.29     9/47.90      11/45.68     11/48.73    |4/46.61      5/47.80      0/48.01      1/46.05      | 
|POLY-3 PERCENT (g) |     35.2%        18.8%        24.1%        22.6%       |8.6%         10.5%        0.0%         2.2%         | 
|TERMINAL (d)       |     16/45 (36%)  9/44 (21%)   11/42 (26%)  10/46 (22%) |4/43 (9%)    5/40 (13%)   0/43 (0%)    1/40 (3%)    | 
|FIRST INCIDENCE    |     715          729 (T)      729 (T)      355         |729 (T)      729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.171N     P=0.062N     P=0.183N     P=0.123N    |P=0.055N     P=0.455      P=0.063N     P=0.202N     | 
|POLY 3             |     P=0.179N     P=0.055N     P=0.170N     P=0.125N    |P=0.048N*    P=0.516      P=0.057N     P=0.183N     | 
|POLY 1.5           |     P=0.180N     P=0.055N     P=0.155N     P=0.127N    |P=0.048N*    P=0.514      P=0.057N     P=0.179N     | 
|POLY 6             |     P=0.178N     P=0.056N     P=0.187N     P=0.124N    |P=0.049N*    P=0.513      P=0.057N     P=0.187N     | 
|LOGISTIC REGRESSION|     P=0.194N     P=0.058N     P=0.195N     P=0.132N    |P=0.055N     P=0.455      (e)          P=0.202N     | 
|COCH-ARM / FISHERS |     P=0.185N     P=0.055N     P=0.133N     P=0.133N    |P=0.050N     P=0.500      P=0.059N     P=0.181N     | 
|ORDER RESTRICTED   |     P=0.093N     (e)          (e)          (e)         |P=0.049N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 7       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/50 (20%)  13/50 (26%)  11/50 (22%)  10/50 (20%) |1/50 (2%)    2/50 (4%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     10/49.18     13/49.04     11/46.97     10/48.52    |1/46.61      2/48.07      0/48.01      1/46.05      | 
|POLY-3 PERCENT (g) |     20.3%        26.5%        23.4%        20.6%       |2.2%         4.2%         0.0%         2.2%         | 
|TERMINAL (d)       |     7/45 (16%)   9/44 (21%)   8/42 (19%)   8/46 (17%)  |1/43 (2%)    1/40 (3%)    0/43 (0%)    1/40 (3%)    | 
|FIRST INCIDENCE    |     459          586          535          628         |729 (T)      656          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.444N     P=0.312      P=0.434      P=0.582N    |P=0.513N     P=0.488      P=0.500N     P=0.746      | 
|POLY 3             |     P=0.475N     P=0.315      P=0.453      P=0.585     |P=0.499N     P=0.511      P=0.494N     P=0.758      | 
|POLY 1.5           |     P=0.469N     P=0.314      P=0.469      P=0.588     |P=0.498N     P=0.509      P=0.495N     P=0.760      | 
|POLY 6             |     P=0.478N     P=0.320      P=0.440      P=0.585     |P=0.501N     P=0.511      P=0.494N     P=0.755      | 
|LOGISTIC REGRESSION|     P=0.441N     P=0.330      P=0.557      P=0.585N    |P=0.500N     P=0.495      (e)          P=0.746      | 
|COCH-ARM / FISHERS |     P=0.454N     P=0.318      P=0.500      P=0.598N    |P=0.500N     P=0.500      P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P=0.554      (e)          (e)          (e)         |P=0.388N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     23/50 (46%)  18/50 (36%)  18/50 (36%)  20/50 (40%) |5/50 (10%)   6/50 (12%)   0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     23/49.18     18/49.04     18/46.97     20/49.40    |5/46.61      6/48.07      0/48.01      2/46.05      | 
|POLY-3 PERCENT (g) |     46.8%        36.7%        38.3%        40.5%       |10.7%        12.5%        0.0%         4.3%         | 
|TERMINAL (d)       |     20/45 (44%)  14/44 (32%)  15/42 (36%)  17/46 (37%) |5/43 (12%)   5/40 (13%)   0/43 (0%)    2/40 (5%)    | 
|FIRST INCIDENCE    |     459          586          535          355         |729 (T)      656          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.359N     P=0.249N     P=0.309N     P=0.327N    |P=0.074N     P=0.457      P=0.033N*    P=0.246N     | 
|POLY 3             |     P=0.375N     P=0.211N     P=0.264N     P=0.336N    |P=0.065N     P=0.521      P=0.028N*    P=0.221N     | 
|POLY 1.5           |     P=0.374N     P=0.213N     P=0.245N     P=0.339N    |P=0.064N     P=0.518      P=0.029N*    P=0.217N     | 
|POLY 6             |     P=0.376N     P=0.204N     P=0.282N     P=0.332N    |P=0.066N     P=0.521      P=0.028N*    P=0.227N     | 
|LOGISTIC REGRESSION|     P=0.371N     P=0.205N     P=0.221N     P=0.330N    |P=0.069N     P=0.516      (e)          P=0.246N     | 
|COCH-ARM / FISHERS |     P=0.375N     P=0.208N     P=0.208N     P=0.343N    |P=0.066N     P=0.500      P=0.028N*    P=0.218N     | 
|ORDER RESTRICTED   |     P=0.319N     (e)          (e)          (e)         |P=0.050N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 8       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatocellular Carcinoma, Hepatocellular Adenoma,                                                                           | 
|     or Hepatoblastoma                                                                                                           | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     23/50 (46%)  18/50 (36%)  18/50 (36%)  20/50 (40%) |5/50 (10%)   6/50 (12%)   0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     23/49.18     18/49.04     18/46.97     20/49.40    |5/46.61      6/48.07      0/48.01      2/46.05      | 
|POLY-3 PERCENT (g) |     46.8%        36.7%        38.3%        40.5%       |10.7%        12.5%        0.0%         4.3%         | 
|TERMINAL (d)       |     20/45 (44%)  14/44 (32%)  15/42 (36%)  17/46 (37%) |5/43 (12%)   5/40 (13%)   0/43 (0%)    2/40 (5%)    | 
|FIRST INCIDENCE    |     459          586          535          355         |729 (T)      656          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.359N     P=0.249N     P=0.309N     P=0.327N    |P=0.074N     P=0.457      P=0.033N*    P=0.246N     | 
|POLY 3             |     P=0.375N     P=0.211N     P=0.264N     P=0.336N    |P=0.065N     P=0.521      P=0.028N*    P=0.221N     | 
|POLY 1.5           |     P=0.374N     P=0.213N     P=0.245N     P=0.339N    |P=0.064N     P=0.518      P=0.029N*    P=0.217N     | 
|POLY 6             |     P=0.376N     P=0.204N     P=0.282N     P=0.332N    |P=0.066N     P=0.521      P=0.028N*    P=0.227N     | 
|LOGISTIC REGRESSION|     P=0.371N     P=0.205N     P=0.221N     P=0.330N    |P=0.069N     P=0.516      (e)          P=0.246N     | 
|COCH-ARM / FISHERS |     P=0.375N     P=0.208N     P=0.208N     P=0.343N    |P=0.066N     P=0.500      P=0.028N*    P=0.218N     | 
|ORDER RESTRICTED   |     P=0.319N     (e)          (e)          (e)         |P=0.050N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Adenoma                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/50 (16%)   11/50 (22%)  13/50 (26%)  15/50 (30%) |0/50 (0%)    8/50 (16%)   16/50 (32%)  8/50 (16%)   | 
|POLY-3 RATE (b)    |     8/48.24      11/47.95     13/45.68     15/47.85    |0/46.61      8/48.15      16/48.18     8/46.05      | 
|POLY-3 PERCENT (g) |     16.6%        22.9%        28.5%        31.4%       |0.0%         16.6%        33.2%        17.4%        | 
|TERMINAL (d)       |     8/45 (18%)   10/44 (23%)  13/42 (31%)  15/46 (33%) |0/43 (0%)    7/40 (18%)   15/43 (35%)  8/40 (20%)   | 
|FIRST INCIDENCE    |     729 (T)      716          729 (T)      729 (T)     |---          632          684          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.070      P=0.288      P=0.120      P=0.084     |P=0.019 *    P=0.004 **   P<0.001 **   P=0.004 **   | 
|POLY 3             |     P=0.055      P=0.300      P=0.128      P=0.071     |P=0.017 *    P=0.004 **   P<0.001 **   P=0.003 **   | 
|POLY 1.5           |     P=0.056      P=0.301      P=0.140      P=0.072     |P=0.019 *    P=0.004 **   P<0.001 **   P=0.004 **   | 
|POLY 6             |     P=0.053      P=0.298      P=0.116      P=0.070     |P=0.015 *    P=0.004 **   P<0.001 **   P=0.003 **   | 
|LOGISTIC REGRESSION|     P=0.059      P=0.291      P=0.120      P=0.084     |P=0.019 *    P=0.005 **   P<0.001 **   P=0.004 **   | 
|COCH-ARM / FISHERS |     P=0.061      P=0.306      P=0.163      P=0.077     |P=0.025 *    P=0.003 **   P<0.001 **   P=0.003 **   | 
|ORDER RESTRICTED   |     P=0.067      (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 9       
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    4/50 (8%)    4/50 (8%)    8/50 (16%)  |3/50 (6%)    0/50 (0%)    2/50 (4%)    7/50 (14%)   | 
|POLY-3 RATE (b)    |     2/48.89      4/48.31      4/45.68      8/47.85     |3/46.61      0/47.80      2/48.01      7/46.21      | 
|POLY-3 PERCENT (g) |     4.1%         8.3%         8.8%         16.7%       |6.4%         0.0%         4.2%         15.2%        | 
|TERMINAL (d)       |     1/45 (2%)    3/44 (7%)    4/42 (10%)   8/46 (17%)  |3/43 (7%)    0/40 (0%)    2/43 (5%)    6/40 (15%)   | 
|FIRST INCIDENCE    |     513          613          729 (T)      729 (T)     |729 (T)      ---          729 (T)      687          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.032 *    P=0.333      P=0.311      P=0.053     |P=0.018 *    P=0.134N     P=0.500N     P=0.133      | 
|POLY 3             |     P=0.024 *    P=0.332      P=0.307      P=0.042 *   |P=0.019 *    P=0.114N     P=0.487N     P=0.154      | 
|POLY 1.5           |     P=0.025 *    P=0.334      P=0.318      P=0.043 *   |P=0.020 *    P=0.115N     P=0.489N     P=0.158      | 
|POLY 6             |     P=0.023 *    P=0.331      P=0.296      P=0.041 *   |P=0.019 *    P=0.115N     P=0.486N     P=0.149      | 
|LOGISTIC REGRESSION|     P=0.027 *    P=0.362      P=0.364      P=0.049 *   |P=0.018 *    (e)          P=0.500N     P=0.144      | 
|COCH-ARM / FISHERS |     P=0.027 *    P=0.339      P=0.339      P=0.046 *   |P=0.022 *    P=0.121N     P=0.500N     P=0.159      | 
|ORDER RESTRICTED   |     P=0.021 *    (e)          (e)          (e)         |P=0.011 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar                                                                      | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   13/50 (26%)  16/50 (32%)  22/50 (44%) |3/50 (6%)    8/50 (16%)   17/50 (34%)  14/50 (28%)  | 
|POLY-3 RATE (b)    |     9/48.89      13/48.36     16/45.68     22/47.85    |3/46.61      8/48.15      17/48.18     14/46.21     | 
|POLY-3 PERCENT (g) |     18.4%        26.9%        35.0%        46.0%       |6.4%         16.6%        35.3%        30.3%        | 
|TERMINAL (d)       |     8/45 (18%)   11/44 (25%)  16/42 (38%)  22/46 (48%) |3/43 (7%)    7/40 (18%)   16/43 (37%)  13/40 (33%)  | 
|FIRST INCIDENCE    |     513          613          729 (T)      729 (T)     |729 (T)      632          684          687          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.003 **   P=0.225      P=0.056      P=0.006 **  |P=0.002 **   P=0.084      P<0.001 **   P=0.002 **   | 
|POLY 3             |     P<0.001 **   P=0.226      P=0.053      P=0.003 **  |P=0.002 **   P=0.109      P<0.001 **   P=0.002 **   | 
|POLY 1.5           |     P=0.002 **   P=0.228      P=0.063      P=0.003 **  |P=0.002 **   P=0.108      P<0.001 **   P=0.003 **   | 
|POLY 6             |     P<0.001 **   P=0.224      P=0.045 *    P=0.002 **  |P<0.001 **   P=0.109      P<0.001 **   P=0.002 **   | 
|LOGISTIC REGRESSION|     P=0.002 **   P=0.237      P=0.061      P=0.004 **  |P=0.002 **   P=0.107      P<0.001 **   P=0.003 **   | 
|COCH-ARM / FISHERS |     P=0.002 **   P=0.235      P=0.083      P=0.004 **  |P=0.003 **   P=0.100      P<0.001 **   P=0.003 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 10      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      0/45.68      0/47.85     |1/46.61      1/47.92      0/48.01      2/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.2%         2.1%         0.0%         4.3%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    0/42 (0%)    0/46 (0%)   |1/43 (2%)    0/40 (0%)    0/43 (0%)    2/40 (5%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      697          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.349      P=0.752      P=0.500N     P=0.475      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.363      P=0.754N     P=0.494N     P=0.496      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.366      P=0.755N     P=0.495N     P=0.499      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.361      P=0.755N     P=0.494N     P=0.491      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.360      P=0.761N     (e)          P=0.475      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.366      P=0.753N     P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.264      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      0/45.68      0/47.85     |1/46.61      1/47.92      0/48.01      2/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.2%         2.1%         0.0%         4.3%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    0/42 (0%)    0/46 (0%)   |1/43 (2%)    0/40 (0%)    0/43 (0%)    2/40 (5%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      697          ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.349      P=0.752      P=0.500N     P=0.475      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.363      P=0.754N     P=0.494N     P=0.496      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.366      P=0.755N     P=0.495N     P=0.499      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.361      P=0.755N     P=0.494N     P=0.491      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.360      P=0.761N     (e)          P=0.475      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.366      P=0.753N     P=0.500N     P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.264      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 11      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cystadenoma                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |2/48 (4%)    0/49 (0%)    1/49 (2%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |                                                        |2/44.61      0/46.80      1/47.01      1/46.05      | 
|POLY-3 PERCENT (g) |                                                        |4.5%         0.0%         2.1%         2.2%         | 
|TERMINAL (d)       |                                                        |2/41 (5%)    0/39 (0%)    1/42 (2%)    1/40 (3%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.502N     P=0.249N     P=0.492N     P=0.509N     | 
|POLY 3             |                                                        |P=0.495N     P=0.227N     P=0.482N     P=0.489N     | 
|POLY 1.5           |                                                        |P=0.493N     P=0.227N     P=0.484N     P=0.486N     | 
|POLY 6             |                                                        |P=0.495N     P=0.228N     P=0.481N     P=0.494N     | 
|LOGISTIC REGRESSION|                                                        |P=0.502N     (e)          P=0.492N     P=0.509N     | 
|COCH-ARM / FISHERS |                                                        |P=0.489N     P=0.242N     P=0.492N     P=0.485N     | 
|ORDER RESTRICTED   |                                                        |P=0.257N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Granulosa Cell Tumor Benign                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |2/48 (4%)    0/49 (0%)    0/49 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |                                                        |2/44.61      0/46.80      0/47.01      0/46.05      | 
|POLY-3 PERCENT (g) |                                                        |4.5%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |                                                        |2/41 (5%)    0/39 (0%)    0/42 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |                                                        |729 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.115N     P=0.249N     P=0.233N     P=0.244N     | 
|POLY 3             |                                                        |P=0.111N     P=0.227N     P=0.226N     P=0.230N     | 
|POLY 1.5           |                                                        |P=0.112N     P=0.227N     P=0.227N     P=0.228N     | 
|POLY 6             |                                                        |P=0.110N     P=0.228N     P=0.225N     P=0.233N     | 
|LOGISTIC REGRESSION|                                                        |P=0.115N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.112N     P=0.242N     P=0.242N     P=0.237N     | 
|ORDER RESTRICTED   |                                                        |P=0.027N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 12      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Luteoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |0/48 (0%)    1/49 (2%)    2/49 (4%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |                                                        |0/44.61      1/46.89      2/47.01      2/46.21      | 
|POLY-3 PERCENT (g) |                                                        |0.0%         2.1%         4.3%         4.3%         | 
|TERMINAL (d)       |                                                        |0/41 (0%)    0/39 (0%)    2/42 (5%)    1/40 (3%)    | 
|FIRST INCIDENCE    |                                                        |---          705          729 (T)      687          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.154      P=0.491      P=0.244      P=0.230      | 
|POLY 3             |                                                        |P=0.165      P=0.510      P=0.249      P=0.245      | 
|POLY 1.5           |                                                        |P=0.168      P=0.509      P=0.248      P=0.247      | 
|POLY 6             |                                                        |P=0.162      P=0.509      P=0.249      P=0.243      | 
|LOGISTIC REGRESSION|                                                        |P=0.166      P=0.502      P=0.244      P=0.247      | 
|COCH-ARM / FISHERS |                                                        |P=0.168      P=0.505      P=0.253      P=0.258      | 
|ORDER RESTRICTED   |                                                        |P=0.162      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    1/48 (2%)    0/49 (0%)    0/50 (0%)   |5/49 (10%)   4/46 (9%)    3/49 (6%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/47.37      1/46.38      0/44.68      0/47.85     |5/45.61      4/44.25      3/47.04      2/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         2.2%         0.0%         0.0%        |11.0%        9.0%         6.4%         4.3%         | 
|TERMINAL (d)       |     0/45 (0%)    1/43 (2%)    0/41 (0%)    0/46 (0%)   |5/42 (12%)   4/38 (11%)   3/43 (7%)    2/40 (5%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |729 (T)      729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.561N     P=0.491      (e)          (e)         |P=0.154N     P=0.563N     P=0.343N     P=0.236N     | 
|POLY 3             |     P=0.567N     P=0.496      (e)          (e)         |P=0.145N     P=0.519N     P=0.340N     P=0.212N     | 
|POLY 1.5           |     P=0.565N     P=0.496      (e)          (e)         |P=0.142N     P=0.522N     P=0.343N     P=0.209N     | 
|POLY 6             |     P=0.568N     P=0.496      (e)          (e)         |P=0.149N     P=0.518N     P=0.338N     P=0.218N     | 
|LOGISTIC REGRESSION|     (e)          P=0.491      (e)          (e)         |P=0.154N     P=0.563N     P=0.343N     P=0.236N     | 
|COCH-ARM / FISHERS |     P=0.563N     P=0.495      (e)          (e)         |P=0.139N     P=0.541N     P=0.357N     P=0.210N     | 
|ORDER RESTRICTED   |     P=0.375N     (e)          (e)          (e)         |P=0.182N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 13      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma,                                                                        | 
|     or Fibrous Histiocytoma                                                                                                     | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      0/45.68      0/47.85     |2/47.26      0/47.80      0/48.01      1/46.22      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.2%         0.0%         0.0%         2.2%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    0/42 (0%)    0/46 (0%)   |0/43 (0%)    0/40 (0%)    0/43 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |555          ---          ---          685          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.470N     P=0.240N     P=0.235N     P=0.513N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.461N     P=0.235N     P=0.234N     P=0.508N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.462N     P=0.234N     P=0.234N     P=0.503N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.459N     P=0.237N     P=0.235N     P=0.514N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.493N     P=0.283N     P=0.283N     P=0.525N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.461N     P=0.247N     P=0.247N     P=0.500N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.135N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      0/45.68      0/47.85     |2/47.26      0/47.80      0/48.01      1/46.22      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.2%         0.0%         0.0%         2.2%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    0/42 (0%)    0/46 (0%)   |0/43 (0%)    0/40 (0%)    0/43 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |555          ---          ---          685          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.470N     P=0.240N     P=0.235N     P=0.513N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.461N     P=0.235N     P=0.234N     P=0.508N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.462N     P=0.234N     P=0.234N     P=0.503N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.459N     P=0.237N     P=0.235N     P=0.514N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.493N     P=0.283N     P=0.283N     P=0.525N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.461N     P=0.247N     P=0.247N     P=0.500N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.135N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 14      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      0/45.68      0/47.85     |2/46.61      0/47.80      0/48.01      1/46.29      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |4.3%         0.0%         0.0%         2.2%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    0/42 (0%)    0/46 (0%)   |2/43 (5%)    0/40 (0%)    0/43 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      ---          ---          665          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.472N     P=0.254N     P=0.238N     P=0.519N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.463N     P=0.232N     P=0.231N     P=0.502N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.463N     P=0.232N     P=0.232N     P=0.500N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.461N     P=0.233N     P=0.230N     P=0.506N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.461N     (e)          (e)          P=0.500N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.461N     P=0.247N     P=0.247N     P=0.500N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.131N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/49 (0%)    1/49 (2%)    0/50 (0%)    1/50 (2%)   |2/49 (4%)    2/49 (4%)    0/49 (0%)    0/49 (0%)    | 
|POLY-3 RATE (b)    |     0/47.24      1/47.38      0/45.68      1/47.85     |2/46.70      2/47.15      0/47.04      0/45.35      | 
|POLY-3 PERCENT (g) |     0.0%         2.1%         0.0%         2.1%        |4.3%         4.2%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/44 (0%)    1/44 (2%)    0/42 (0%)    1/46 (2%)   |1/43 (2%)    2/40 (5%)    0/43 (0%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          729 (T)     |706          729 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.415      P=0.500      (e)          P=0.509     |P=0.092N     P=0.667      P=0.240N     P=0.258N     | 
|POLY 3             |     P=0.407      P=0.501      (e)          P=0.503     |P=0.087N     P=0.690N     P=0.236N     P=0.244N     | 
|POLY 1.5           |     P=0.408      P=0.500      (e)          P=0.503     |P=0.087N     P=0.691N     P=0.236N     P=0.242N     | 
|POLY 6             |     P=0.407      P=0.501      (e)          P=0.502     |P=0.088N     P=0.691N     P=0.236N     P=0.247N     | 
|LOGISTIC REGRESSION|     (e)          P=0.500      (e)          P=0.509     |P=0.088N     P=0.691N     P=0.237N     P=0.242N     | 
|COCH-ARM / FISHERS |     P=0.410      P=0.500      (e)          P=0.505     |P=0.086N     P=0.691N     P=0.247N     P=0.247N     | 
|ORDER RESTRICTED   |     P=0.254      (e)          (e)          (e)         |P=0.122N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 15      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Carcinoma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     1/48.24      0/47.90      0/45.68      0/47.85     |0/46.61      0/47.80      2/48.01      0/46.05      | 
|POLY-3 PERCENT (g) |     2.1%         0.0%         0.0%         0.0%        |0.0%         0.0%         4.2%         0.0%         | 
|TERMINAL (d)       |     1/45 (2%)    0/44 (0%)    0/42 (0%)    0/46 (0%)   |0/43 (0%)    0/40 (0%)    2/43 (5%)    0/40 (0%)    | 
|FIRST INCIDENCE    |     729 (T)      ---          ---          ---         |---          ---          729 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.306N     P=0.504N     P=0.514N     P=0.496N    |P=0.585      (e)          P=0.238      (e)          | 
|POLY 3             |     P=0.308N     P=0.501N     P=0.511N     P=0.502N    |P=0.582      (e)          P=0.244      (e)          | 
|POLY 1.5           |     P=0.307N     P=0.501N     P=0.507N     P=0.501N    |P=0.589      (e)          P=0.243      (e)          | 
|POLY 6             |     P=0.309N     P=0.502N     P=0.515N     P=0.502N    |P=0.574      (e)          P=0.244      (e)          | 
|LOGISTIC REGRESSION|     P=0.306N     (e)          (e)          (e)         |(e)          (e)          P=0.238      (e)          | 
|COCH-ARM / FISHERS |     P=0.306N     P=0.500N     P=0.500N     P=0.500N    |P=0.595      (e)          P=0.247      (e)          | 
|ORDER RESTRICTED   |     P=0.122N     (e)          (e)          (e)         |P=0.254      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    0/50 (0%)    3/50 (6%)   |2/50 (4%)    0/50 (0%)    3/50 (6%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/48.24      2/47.90      0/45.68      3/47.85     |2/46.61      0/47.80      3/48.01      2/46.05      | 
|POLY-3 PERCENT (g) |     2.1%         4.2%         0.0%         6.3%        |4.3%         0.0%         6.3%         4.3%         | 
|TERMINAL (d)       |     1/45 (2%)    2/44 (5%)    0/42 (0%)    3/46 (7%)   |2/43 (5%)    0/40 (0%)    3/43 (7%)    2/40 (5%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          729 (T)     |729 (T)      ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.252      P=0.492      P=0.514N     P=0.313     |P=0.403      P=0.254N     P=0.500      P=0.669      | 
|POLY 3             |     P=0.237      P=0.498      P=0.511N     P=0.303     |P=0.410      P=0.232N     P=0.513      P=0.689      | 
|POLY 1.5           |     P=0.239      P=0.498      P=0.507N     P=0.303     |P=0.416      P=0.232N     P=0.511      P=0.693      | 
|POLY 6             |     P=0.236      P=0.497      P=0.515N     P=0.302     |P=0.404      P=0.233N     P=0.514      P=0.684      | 
|LOGISTIC REGRESSION|     P=0.252      P=0.492      (e)          P=0.313     |P=0.403      (e)          P=0.500      P=0.669      | 
|COCH-ARM / FISHERS |     P=0.242      P=0.500      P=0.500N     P=0.309     |P=0.422      P=0.247N     P=0.500      P=0.691N     | 
|ORDER RESTRICTED   |     P=0.184      (e)          (e)          (e)         |P=0.333      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 16      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Squamous Cell Papilloma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    3/50 (6%)   |2/50 (4%)    0/50 (0%)    1/50 (2%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/48.24      2/47.90      0/45.68      3/47.85     |2/46.61      0/47.80      1/48.01      2/46.05      | 
|POLY-3 PERCENT (g) |     0.0%         4.2%         0.0%         6.3%        |4.3%         0.0%         2.1%         4.3%         | 
|TERMINAL (d)       |     0/45 (0%)    2/44 (5%)    0/42 (0%)    3/46 (7%)   |2/43 (5%)    0/40 (0%)    1/43 (2%)    2/40 (5%)    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          729 (T)     |729 (T)      ---          729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.103      P=0.234      (e)          P=0.125     |P=0.453      P=0.254N     P=0.500N     P=0.669      | 
|POLY 3             |     P=0.093      P=0.236      (e)          P=0.118     |P=0.461      P=0.232N     P=0.490N     P=0.689      | 
|POLY 1.5           |     P=0.094      P=0.236      (e)          P=0.118     |P=0.464      P=0.232N     P=0.491N     P=0.693      | 
|POLY 6             |     P=0.092      P=0.235      (e)          P=0.117     |P=0.458      P=0.233N     P=0.489N     P=0.684      | 
|LOGISTIC REGRESSION|     (e)          P=0.234      (e)          P=0.125     |P=0.453      (e)          P=0.500N     P=0.669      | 
|COCH-ARM / FISHERS |     P=0.097      P=0.247      (e)          P=0.121     |P=0.469      P=0.247N     P=0.500N     P=0.691N     | 
|ORDER RESTRICTED   |     P=0.036 *    (e)          (e)          (e)         |P=0.402      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)   |                                                    | 
|POLY-3 RATE (b)    |     0/48.24      2/47.90      0/45.68      0/47.85     |                                                    | 
|POLY-3 PERCENT (g) |     0.0%         4.2%         0.0%         0.0%        |                                                    | 
|TERMINAL (d)       |     0/45 (0%)    2/44 (5%)    0/42 (0%)    0/46 (0%)   |                                                    | 
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.401N     P=0.234      (e)          (e)         |                                                    | 
|POLY 3             |     P=0.410N     P=0.236      (e)          (e)         |                                                    | 
|POLY 1.5           |     P=0.408N     P=0.236      (e)          (e)         |                                                    | 
|POLY 6             |     P=0.412N     P=0.235      (e)          (e)         |                                                    | 
|LOGISTIC REGRESSION|     (e)          P=0.234      (e)          (e)         |                                                    | 
|COCH-ARM / FISHERS |     P=0.405N     P=0.247      (e)          (e)         |                                                    | 
|ORDER RESTRICTED   |     P=0.247N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 17      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Polyp Stromal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |0/50 (0%)    2/50 (4%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |                                                        |0/46.61      2/47.80      0/48.01      2/46.05      | 
|POLY-3 PERCENT (g) |                                                        |0.0%         4.2%         0.0%         4.3%         | 
|TERMINAL (d)       |                                                        |0/43 (0%)    2/40 (5%)    0/43 (0%)    2/40 (5%)    | 
|FIRST INCIDENCE    |                                                        |---          729 (T)      ---          729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.235      P=0.223      (e)          P=0.223      | 
|POLY 3             |                                                        |P=0.246      P=0.243      (e)          P=0.235      | 
|POLY 1.5           |                                                        |P=0.248      P=0.243      (e)          P=0.237      | 
|POLY 6             |                                                        |P=0.242      P=0.242      (e)          P=0.231      | 
|LOGISTIC REGRESSION|                                                        |(e)          P=0.223      (e)          P=0.223      | 
|COCH-ARM / FISHERS |                                                        |P=0.248      P=0.247      (e)          P=0.247      | 
|ORDER RESTRICTED   |                                                        |P=0.114      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Sarcoma Stromal or Polyp Stromal                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |0/50 (0%)    2/50 (4%)    1/50 (2%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |                                                        |0/46.61      2/47.80      1/48.01      2/46.05      | 
|POLY-3 PERCENT (g) |                                                        |0.0%         4.2%         2.1%         4.3%         | 
|TERMINAL (d)       |                                                        |0/43 (0%)    2/40 (5%)    1/43 (2%)    2/40 (5%)    | 
|FIRST INCIDENCE    |                                                        |---          729 (T)      729 (T)      729 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.232      P=0.223      P=0.500      P=0.223      | 
|POLY 3             |                                                        |P=0.242      P=0.243      P=0.506      P=0.235      | 
|POLY 1.5           |                                                        |P=0.246      P=0.243      P=0.505      P=0.237      | 
|POLY 6             |                                                        |P=0.238      P=0.242      P=0.506      P=0.231      | 
|LOGISTIC REGRESSION|                                                        |(e)          P=0.223      P=0.500      P=0.223      | 
|COCH-ARM / FISHERS |                                                        |P=0.246      P=0.247      P=0.500      P=0.247      | 
|ORDER RESTRICTED   |                                                        |P=0.153      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 18      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Hemangiosarcoma                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    3/50 (6%)    3/50 (6%)   |3/50 (6%)    4/50 (8%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     1/48.24      2/47.90      3/46.46      3/47.85     |3/46.70      4/47.83      0/48.01      2/46.29      | 
|POLY-3 PERCENT (g) |     2.1%         4.2%         6.5%         6.3%        |6.4%         8.4%         0.0%         4.3%         | 
|TERMINAL (d)       |     1/45 (2%)    2/44 (5%)    2/42 (5%)    3/46 (7%)   |2/43 (5%)    3/40 (8%)    0/43 (0%)    1/40 (3%)    | 
|FIRST INCIDENCE    |     729 (T)      729 (T)      441          729 (T)     |706          721          ---          665          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.237      P=0.492      P=0.287      P=0.313     |P=0.283N     P=0.465      P=0.123N     P=0.530N     | 
|POLY 3             |     P=0.224      P=0.498      P=0.292      P=0.303     |P=0.263N     P=0.513      P=0.114N     P=0.504N     | 
|POLY 1.5           |     P=0.226      P=0.498      P=0.297      P=0.303     |P=0.261N     P=0.512      P=0.115N     P=0.500N     | 
|POLY 6             |     P=0.224      P=0.497      P=0.287      P=0.302     |P=0.265N     P=0.510      P=0.114N     P=0.510N     | 
|LOGISTIC REGRESSION|     P=0.231      P=0.492      P=0.376      P=0.313     |P=0.266N     P=0.509      P=0.116N     P=0.501N     | 
|COCH-ARM / FISHERS |     P=0.227      P=0.500      P=0.309      P=0.309     |P=0.263N     P=0.500      P=0.121N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.255      (e)          (e)          (e)         |P=0.182N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Histiocytic Sarcoma                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    3/50 (6%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/48.24      0/47.90      0/45.68      0/47.85     |1/46.61      1/48.42      3/48.01      2/46.35      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |2.2%         2.1%         6.3%         4.3%         | 
|TERMINAL (d)       |     0/45 (0%)    0/44 (0%)    0/42 (0%)    0/46 (0%)   |1/43 (2%)    0/40 (0%)    3/43 (7%)    1/40 (3%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |729 (T)      525          729 (T)      647          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.311      P=0.755      P=0.305      P=0.483      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.316      P=0.752N     P=0.316      P=0.498      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.321      P=0.753N     P=0.315      P=0.501      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.311      P=0.752N     P=0.317      P=0.495      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.319      P=0.714      P=0.305      P=0.500      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.324      P=0.753N     P=0.309      P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.333      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 19      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        | 
|     NOS, or Undifferentiated Cell Type                                                                                          | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    3/50 (6%)    4/50 (8%)    2/50 (4%)   |7/50 (14%)   10/50 (20%)  12/50 (24%)  13/50 (26%)  | 
|POLY-3 RATE (b)    |     3/48.24      3/47.95      4/46.05      2/47.85     |7/46.61      10/48.51     12/49.23     13/48.13     | 
|POLY-3 PERCENT (g) |     6.2%         6.3%         8.7%         4.2%        |15.0%        20.6%        24.4%        27.0%        | 
|TERMINAL (d)       |     3/45 (7%)    2/44 (5%)    3/42 (7%)    2/46 (4%)   |7/43 (16%)   6/40 (15%)   7/43 (16%)   9/40 (23%)   | 
|FIRST INCIDENCE    |     729 (T)      716          623          729 (T)     |729 (T)      629          541          409          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.412N     P=0.653      P=0.463      P=0.490N    |P=0.081      P=0.264      P=0.170      P=0.088      | 
|POLY 3             |     P=0.426N     P=0.659      P=0.475      P=0.504N    |P=0.100      P=0.329      P=0.187      P=0.119      | 
|POLY 1.5           |     P=0.425N     P=0.660      P=0.484      P=0.503N    |P=0.099      P=0.322      P=0.177      P=0.117      | 
|POLY 6             |     P=0.428N     P=0.659      P=0.467      P=0.504N    |P=0.100      P=0.334      P=0.198      P=0.119      | 
|LOGISTIC REGRESSION|     P=0.425N     P=0.658      P=0.488      P=0.490N    |P=0.089      P=0.312      P=0.154      P=0.103      | 
|COCH-ARM / FISHERS |     P=0.420N     P=0.661N     P=0.500      P=0.500N    |P=0.089      P=0.298      P=0.154      P=0.105      | 
|ORDER RESTRICTED   |     P=0.448N     (e)          (e)          (e)         |P=0.124      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     26/50 (52%)  29/50 (58%)  23/50 (46%)  27/50 (54%) |18/50 (36%)  23/50 (46%)  23/50 (46%)  21/50 (42%)  | 
|POLY-3 RATE (b)    |     26/48.29     29/48.56     23/45.68     27/48.73    |18/47.07     23/48.47     23/48.22     21/46.68     | 
|POLY-3 PERCENT (g) |     53.8%        59.7%        50.4%        55.4%       |38.2%        47.5%        47.7%        45.0%        | 
|TERMINAL (d)       |     25/45 (56%)  26/44 (59%)  23/42 (55%)  26/46 (57%) |17/43 (40%)  20/40 (50%)  21/43 (49%)  18/40 (45%)  | 
|FIRST INCIDENCE    |     715          613          729 (T)      355         |593          632          684          647          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.462N     P=0.306      P=0.475N     P=0.545     |P=0.299      P=0.144      P=0.212      P=0.251      | 
|POLY 3             |     P=0.508N     P=0.352      P=0.448N     P=0.519     |P=0.347      P=0.241      P=0.234      P=0.325      | 
|POLY 1.5           |     P=0.505N     P=0.345      P=0.408N     P=0.514     |P=0.366      P=0.237      P=0.232      P=0.339      | 
|POLY 6             |     P=0.519N     P=0.364      P=0.491N     P=0.519     |P=0.330      P=0.240      P=0.232      P=0.311      | 
|LOGISTIC REGRESSION|     P=0.538      P=0.325      P=0.509N     P=0.487     |P=0.332      P=0.237      P=0.244      P=0.314      | 
|COCH-ARM / FISHERS |     P=0.509N     P=0.344      P=0.345N     P=0.500     |P=0.377      P=0.208      P=0.208      P=0.341      | 
|ORDER RESTRICTED   |     P=0.550N     (e)          (e)          (e)         |P=0.326      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  01/12/04                           EXPERIMENT: 92013 TEST: 06                                            Page 20      
                     Statistical Analysis of Primary Tumors in Mice(B6C3F1)       -                    4-METHYLIMIDAZOLE            
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     15/50 (30%)  25/50 (50%)  21/50 (42%)  22/50 (44%) |20/50 (40%)  20/50 (40%)  23/50 (46%)  29/50 (58%)  | 
|POLY-3 RATE (b)    |     15/49.83     25/49.10     21/48.76     22/48.52    |20/47.95     20/49.64     23/49.83     29/50.00     | 
|POLY-3 PERCENT (g) |     30.1%        50.9%        43.1%        45.4%       |41.7%        40.3%        46.2%        58.0%        | 
|TERMINAL (d)       |     11/45 (24%)  20/44 (46%)  15/42 (36%)  20/46 (44%) |16/43 (37%)  12/40 (30%)  17/43 (40%)  19/40 (48%)  | 
|FIRST INCIDENCE    |     459          586          441          628         |539          525          539          409          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.242      P=0.042 *    P=0.124      P=0.135     |P=0.033 *    P=0.499      P=0.367      P=0.055      | 
|POLY 3             |     P=0.163      P=0.027 *    P=0.130      P=0.087     |P=0.038 *    P=0.525N     P=0.406      P=0.078      | 
|POLY 1.5           |     P=0.173      P=0.028 *    P=0.135      P=0.093     |P=0.035 *    P=0.536N     P=0.392      P=0.072      | 
|POLY 6             |     P=0.157      P=0.027 *    P=0.126      P=0.085     |P=0.042 *    P=0.516N     P=0.419      P=0.086      | 
|LOGISTIC REGRESSION|     P=0.207      P=0.034 *    P=0.233      P=0.111     |P=0.030 *    P=0.565      P=0.330      P=0.054      | 
|COCH-ARM / FISHERS |     P=0.198      P=0.033 *    P=0.149      P=0.107     |P=0.028 *    P=0.581N     P=0.343      P=0.055      | 
|ORDER RESTRICTED   |     P=0.074      (e)          (e)          (e)         |P=0.068      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 PPM        312 PPM      625 PPM      1250 PPM    |0 PPM        312 PPM      625 PPM      1250 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     34/50 (68%)  38/50 (76%)  36/50 (72%)  39/50 (78%) |29/50 (58%)  36/50 (72%)  37/50 (74%)  40/50 (80%)  | 
|POLY-3 RATE (b)    |     34/49.83     38/49.10     36/48.76     39/49.40    |29/48.41     36/49.99     37/50.00     40/50.00     | 
|POLY-3 PERCENT (g) |     68.2%        77.4%        73.8%        79.0%       |59.9%        72.0%        74.0%        80.0%        | 
|TERMINAL (d)       |     30/45 (67%)  33/44 (75%)  30/42 (71%)  36/46 (78%) |24/43 (56%)  27/40 (68%)  30/43 (70%)  30/40 (75%)  | 
|FIRST INCIDENCE    |     459          586          441          355         |539          525          539          409          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.285      P=0.239      P=0.268      P=0.256     |P=0.024 *    P=0.091      P=0.115      P=0.019 *    | 
|POLY 3             |     P=0.179      P=0.213      P=0.348      P=0.162     |P=0.025 *    P=0.146      P=0.101      P=0.023 *    | 
|POLY 1.5           |     P=0.188      P=0.220      P=0.367      P=0.170     |P=0.023 *    P=0.137      P=0.094      P=0.021 *    | 
|POLY 6             |     P=0.172      P=0.215      P=0.337      P=0.157     |P=0.027 *    P=0.153      P=0.107      P=0.025 *    | 
|LOGISTIC REGRESSION|     P=0.197      P=0.249      P=0.430      P=0.187     |P=0.016 *    P=0.109      P=0.074      P=0.015 *    | 
|COCH-ARM / FISHERS |     P=0.201      P=0.252      P=0.414      P=0.184     |P=0.015 *    P=0.104      P=0.069      P=0.015 *    | 
|ORDER RESTRICTED   |     P=0.169      (e)          (e)          (e)         |P=0.018 *    (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).