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TDMS Study 92012-05 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                2-METHYLIMIDAZOLE                                   DATE: 02/24/03       
EXPERIMENT: 92012 TEST: 05                                                                                     TIME: 14:13:53       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92012B       
PATHOLOGIST: FARNELL, DANIEL R.                                                                                CAS: 693-98-1        
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                                                            27 WEEK SSAC                                                            
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    25017 Scheduled Sacrifice                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                2-METHYLIMIDAZOLE                                   DATE: 02/24/03       
EXPERIMENT: 92012 TEST: 05                                                                                     TIME: 14:13:53       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92012B       
PATHOLOGIST: FARNELL, DANIEL R.                                                                                CAS: 693-98-1        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                   2-METHYLIMIDAZOLE                                                                              
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Cortex                         Accessory Adrenal Cortical Nodule                                                            
Pituitary Gland: Pars Intermedia       Cyst                                                                                         
Thyroid Gland: Follicle                Mineralization Focal                                                                         
Thyroid Gland: Follicular Cell         Hyperplasia                                                                                  
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Harderian Gland                        Inflammation Focal Granulomatous                                                             
Lymph Node: Pancreatic                 Hyperplasia Lymphoid                                                                         
Thyroid Gland: Follicle                Mineralization Focal                                                                         
Thyroid Gland: Follicular Cell         Hyperplasia                                                                                  
===============================================================                                                                     
                                                                                                                                   
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 05                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                    2-METHYLIMIDAZOLE                  
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Accessory Adrenal Cortical Nodule                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    2/10 (20%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     0/0.06       0/0.06       0/0.06       2/2.05      |0/0.06       0/0.06       0/0.06       1/1.06       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         97.6%       |0.0%         0.0%         0.0%         94.8%        | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    0/10 (0%)    0/10 (0%)    2/10 (20%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          183 (I)     |---          ---          ---          183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.040 *    (e)          (e)          P=0.234     |P=0.194      (e)          (e)          P=0.500      | 
|POLY 3             |     P=0.007 **   (e)          (e)          P=0.067     |P=0.064      (e)          (e)          P=0.160      | 
|POLY 1.5           |     P=0.008 **   (e)          (e)          P=0.076     |P=0.075      (e)          (e)          P=0.183      | 
|POLY 6             |     P=0.007 **   (e)          (e)          P=0.067     |P=0.063      (e)          (e)          P=0.159      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.038 *    (e)          (e)          P=0.237     |P=0.191      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.328      (e)          (e)          (e)         |P=0.442      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Inflammation Focal Granulomatous                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)   |0/10 (0%)    0/10 (0%)    1/10 (10%)   5/10 (50%)   | 
|POLY-3 RATE (b)    |     1/1.06       0/0.06       0/0.06       0/0.06      |0/0.06       0/0.06       1/1.06       5/5.03       | 
|POLY-3 PERCENT (g) |     94.8%        0.0%         0.0%         0.0%        |0.0%         0.0%         94.8%        99.4%        | 
|INT SACRIFICE 1 (c)|     1/10 (10%)   0/10 (0%)    0/10 (0%)    0/10 (0%)   |0/10 (0%)    0/10 (0%)    1/10 (10%)   5/10 (50%)   | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     183 (I)      ---          ---          ---         |---          ---          183 (I)      183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.474N     P=0.500N     P=0.500N     P=0.500N    |P<0.001 **   (e)          P=0.500      P=0.022 *    | 
|POLY 3             |     P=0.180N     P=0.160N     P=0.160N     P=0.160N    |P<0.001 **   (e)          P=0.160      P<0.001 **   | 
|POLY 1.5           |     P=0.197N     P=0.183N     P=0.183N     P=0.183N    |P<0.001 **   (e)          P=0.183      P=0.002 **   | 
|POLY 6             |     P=0.179N     P=0.159N     P=0.159N     P=0.159N    |P<0.001 **   (e)          P=0.159      P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.474N     P=0.500N     P=0.500N     P=0.500N    |P<0.001 **   (e)          P=0.500      P=0.016 *    | 
|ORDER RESTRICTED   |     P=0.442N     (e)          (e)          (e)         |P=0.085      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 05                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    2-METHYLIMIDAZOLE                   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   0/10 (0%)    1/10 (10%)   0/10 (0%)   |1/10 (10%)   0/10 (0%)    1/10 (10%)   0/10 (0%)    | 
|POLY-3 RATE (b)    |     2/2.05       0/0.06       1/1.06       0/0.06      |1/1.06       0/0.06       1/1.06       0/0.06       | 
|POLY-3 PERCENT (g) |     97.6%        0.0%         94.8%        0.0%        |94.8%        0.0%         94.8%        0.0%         | 
|INT SACRIFICE 1 (c)|     2/10 (20%)   0/10 (0%)    1/10 (10%)   0/10 (0%)   |1/10 (10%)   0/10 (0%)    1/10 (10%)   0/10 (0%)    | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     183 (I)      ---          183 (I)      ---         |183 (I)      ---          183 (I)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.267N     P=0.234N     P=0.500N     P=0.234N    |P=0.425N     P=0.500N     P=0.766      P=0.500N     | 
|POLY 3             |     P=0.131N     P=0.067N     P=0.300N     P=0.067N    |P=0.264N     P=0.160N     P=0.530      P=0.160N     | 
|POLY 1.5           |     P=0.132N     P=0.076N     P=0.315N     P=0.076N    |P=0.269N     P=0.183N     P=0.548      P=0.183N     | 
|POLY 6             |     P=0.131N     P=0.067N     P=0.299N     P=0.067N    |P=0.263N     P=0.159N     P=0.528      P=0.159N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.265N     P=0.237N     P=0.500N     P=0.237N    |P=0.424N     P=0.500N     P=0.763N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.274N     (e)          (e)          (e)         |P=0.362N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Granulomatous                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/10 (90%)   7/10 (70%)   10/10 (100%) 10/10 (100%)|10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) | 
|POLY-3 RATE (b)    |     9/9.01       7/7.02       10/10.00     10/10.00    |10/10.00     10/10.00     10/10.00     10/10.00     | 
|POLY-3 PERCENT (g) |     99.9%        99.7%        100.0%       100.0%      |100.0%       100.0%       100.0%       100.0%       | 
|INT SACRIFICE 1 (c)|     9/10 (90%)   7/10 (70%)   10/10 (100%) 10/10 (100%)|10/10 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     183 (I)      183 (I)      183 (I)      183 (I)     |183 (I)      183 (I)      183 (I)      183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.143      P=0.293N     P=0.500      P=0.500     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.130      P=0.251N     P=0.478      P=0.478     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.130      P=0.255N     P=0.480      P=0.480     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.130      P=0.251N     P=0.478      P=0.478     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.140      P=0.291N     P=0.500      P=0.500     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.074      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 05                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    2-METHYLIMIDAZOLE                   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Mediastinal                                                                                                          | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     1/1 (100%)   0/1 (0%)     1/1 (100%)  |1/3 (33%)    1/4 (25%)    0/1 (0%)     2/3 (67%)    | 
|POLY-3 RATE (b)    |     0/0.00       1/1.00       0/0.01       1/1.00      |1/1.01       1/1.02       0/0.01       2/2.01       | 
|POLY-3 PERCENT (g) |     0.0%         100.0%       0.0%         100.0%      |98.8%        98.2%        0.0%         99.7%        | 
|INT SACRIFICE 1 (c)|     0/0 (0%)     1/1 (100%)   0/1 (0%)     1/1 (100%)  |1/3 (33.3%)  1/4 (25%)    0/1 (0%)     2/3 (66.7%)  | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          183 (I)      ---          183 (I)     |183 (I)      183 (I)      ---          183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.690      (e)          (e)          (e)         |P=0.280      P=0.712N     P=0.718N     P=0.500      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.225      P=0.501N     P=0.311N     P=0.337      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.236      P=0.517N     P=0.338N     P=0.351      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.224      P=0.500N     P=0.309N     P=0.336      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.728      (e)          (e)          (e)         |P=0.271      P=0.714N     P=0.750N     P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.276      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Pancreatic                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     0/1 (0%)     1/1 (100%)   0/1 (0%)    |0/3 (0%)     2/4 (50%)    0/1 (0%)     1/3 (33%)    | 
|POLY-3 RATE (b)    |     0/0.00       0/0.01       1/1.00       0/0.01      |0/0.02       2/2.01       0/0.01       1/1.01       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         100.0%       0.0%        |0.0%         99.4%        0.0%         98.8%        | 
|INT SACRIFICE 1 (c)|     0/0 (0%)     0/1 (0%)     1/1 (100%)   0/1 (0%)    |0/3 (0%)     2/4 (50%)    0/1 (0%)     1/3 (33.3%)  | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          183 (I)      ---         |---          183 (I)      ---          183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.690N     (e)          (e)          (e)         |P=0.515      P=0.288      (e)          P=0.500      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.422      P=0.072      (e)          P=0.160      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.427      P=0.082      (e)          P=0.182      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.421      P=0.072      (e)          P=0.159      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.728N     (e)          (e)          (e)         |P=0.515      P=0.286      (e)          P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.225      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 05                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    2-METHYLIMIDAZOLE                   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Pancreatic                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     0/1 (0%)     0/1 (0%)     0/1 (0%)    |2/3 (67%)    1/4 (25%)    1/1 (100%)   0/3 (0%)     | 
|POLY-3 RATE (b)    |     0/0.00       0/0.01       0/0.01       0/0.01      |2/2.01       1/1.02       1/1.00       0/0.02       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |99.7%        98.2%        100.0%       0.0%         | 
|INT SACRIFICE 1 (c)|     0/0 (0%)     0/1 (0%)     0/1 (0%)     0/1 (0%)    |2/3 (66.7%)  1/4 (25%)    1/1 (100%)   0/3 (0%)     | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |183 (I)      183 (I)      183 (I)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.177N     P=0.380N     P=0.718      P=0.215N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.112N     P=0.214N     P=0.640      P=0.023N*    | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.113N     P=0.228N     P=0.646      P=0.028N*    | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.112N     P=0.212N     P=0.640      P=0.023N*    | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.166N     P=0.371N     P=0.750      P=0.200N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.128N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   2/10 (20%)   0/10 (0%)    1/10 (10%)  |1/10 (10%)   2/10 (20%)   0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     1/1.06       2/2.05       0/0.06       1/1.06      |1/1.06       2/2.05       0/0.06       1/1.06       | 
|POLY-3 PERCENT (g) |     94.8%        97.6%        0.0%         94.8%       |94.8%        97.6%        0.0%         94.8%        | 
|INT SACRIFICE 1 (c)|     1/10 (10%)   2/10 (20%)   0/10 (0%)    1/10 (10%)  |1/10 (10%)   2/10 (20%)   0/10 (0%)    1/10 (10%)   | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     183 (I)      183 (I)      ---          183 (I)     |183 (I)      183 (I)      ---          183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.553N     P=0.500      P=0.500N     P=0.766     |P=0.472N     P=0.500      P=0.500N     P=0.766      | 
|POLY 3             |     P=0.399N     P=0.300      P=0.160N     P=0.530     |P=0.359N     P=0.300      P=0.160N     P=0.530      | 
|POLY 1.5           |     P=0.409N     P=0.315      P=0.183N     P=0.548     |P=0.366N     P=0.315      P=0.183N     P=0.548      | 
|POLY 6             |     P=0.398N     P=0.299      P=0.159N     P=0.528     |P=0.359N     P=0.299      P=0.159N     P=0.528      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.554N     P=0.500      P=0.500N     P=0.763N    |P=0.472N     P=0.500      P=0.500N     P=0.763N     | 
|ORDER RESTRICTED   |     P=0.278N     (e)          (e)          (e)         |P=0.278N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 05                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    2-METHYLIMIDAZOLE                   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Mitotic Alteration                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    1/10 (10%)   1/10 (10%)   0/10 (0%)   |1/10 (10%)   2/10 (20%)   2/10 (20%)   2/10 (20%)   | 
|POLY-3 RATE (b)    |     0/0.06       1/1.06       1/1.06       0/0.06      |1/1.06       2/2.05       2/2.05       2/2.05       | 
|POLY-3 PERCENT (g) |     0.0%         94.8%        94.8%        0.0%        |94.8%        97.6%        97.6%        97.6%        | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    1/10 (10%)   1/10 (10%)   0/10 (0%)   |1/10 (10%)   2/10 (20%)   2/10 (20%)   2/10 (20%)   | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          183 (I)      183 (I)      ---         |183 (I)      183 (I)      183 (I)      183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.537N     P=0.500      P=0.500      (e)         |P=0.424      P=0.500      P=0.500      P=0.500      | 
|POLY 3             |     P=0.311N     P=0.160      P=0.160      (e)         |P=0.347      P=0.300      P=0.300      P=0.300      | 
|POLY 1.5           |     P=0.318N     P=0.183      P=0.183      (e)         |P=0.352      P=0.315      P=0.315      P=0.315      | 
|POLY 6             |     P=0.311N     P=0.159      P=0.159      (e)         |P=0.346      P=0.299      P=0.299      P=0.299      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.537N     P=0.500      P=0.500      (e)         |P=0.423      P=0.500      P=0.500      P=0.500      | 
|ORDER RESTRICTED   |     P=0.478      (e)          (e)          (e)         |P=0.423      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Intermedia                                                                                                 | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    2/10 (20%)  |0/10 (0%)    1/10 (10%)   1/10 (10%)   0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/0.06       0/0.06       0/0.06       2/2.05      |0/0.06       1/1.06       1/1.06       0/0.06       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         97.6%       |0.0%         94.8%        94.8%        0.0%         | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    0/10 (0%)    0/10 (0%)    2/10 (20%)  |0/10 (0%)    1/10 (10%)   1/10 (10%)   0/10 (0%)    | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          183 (I)     |---          183 (I)      183 (I)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.040 *    (e)          (e)          P=0.234     |P=0.575N     P=0.500      P=0.500      (e)          | 
|POLY 3             |     P=0.007 **   (e)          (e)          P=0.067     |P=0.401N     P=0.160      P=0.160      (e)          | 
|POLY 1.5           |     P=0.008 **   (e)          (e)          P=0.076     |P=0.408N     P=0.183      P=0.183      (e)          | 
|POLY 6             |     P=0.007 **   (e)          (e)          P=0.067     |P=0.400N     P=0.159      P=0.159      (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.038 *    (e)          (e)          P=0.237     |P=0.576N     P=0.500      P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.328      (e)          (e)          (e)         |P=0.478      (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 05                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    2-METHYLIMIDAZOLE                   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Accessory Spleen                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    2/10 (20%)   0/10 (0%)    0/10 (0%)   |0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/0.06       2/2.05       0/0.06       0/0.06      |0/0.06       0/0.06       1/1.06       0/0.06       | 
|POLY-3 PERCENT (g) |     0.0%         97.6%        0.0%         0.0%        |0.0%         0.0%         94.8%        0.0%         | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    2/10 (20%)   0/10 (0%)    0/10 (0%)   |0/10 (0%)    0/10 (0%)    1/10 (10%)   0/10 (0%)    | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          183 (I)      ---          ---         |---          ---          183 (I)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.368N     P=0.234      (e)          (e)         |P=0.679      (e)          P=0.500      (e)          | 
|POLY 3             |     P=0.161N     P=0.067      (e)          (e)         |P=0.423      (e)          P=0.160      (e)          | 
|POLY 1.5           |     P=0.173N     P=0.076      (e)          (e)         |P=0.440      (e)          P=0.183      (e)          | 
|POLY 6             |     P=0.160N     P=0.067      (e)          (e)         |P=0.421      (e)          P=0.159      (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.366N     P=0.237      (e)          (e)         |P=0.681      (e)          P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.454N     (e)          (e)          (e)         |P=0.545      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicle                                                                                                          | 
|     Mineralization Focal                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   4/10 (40%)   9/10 (90%)   9/10 (90%)  |1/10 (10%)   6/10 (60%)   10/10 (100%) 10/10 (100%) | 
|POLY-3 RATE (b)    |     1/1.06       4/4.04       9/9.01       9/9.01      |1/1.06       6/6.03       10/10.00     10/10.00     | 
|POLY-3 PERCENT (g) |     94.8%        99.1%        99.9%        99.9%       |94.8%        99.6%        100.0%       100.0%       | 
|INT SACRIFICE 1 (c)|     1/10 (10%)   4/10 (40%)   9/10 (90%)   9/10 (90%)  |1/10 (10%)   6/10 (60%)   10/10 (100%) 10/10 (100%) | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     183 (I)      183 (I)      183 (I)      183 (I)     |183 (I)      183 (I)      183 (I)      183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.157      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.034 *    P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P=0.067      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.005 **   P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.072      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.006 **   P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.066      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.005 **   P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.152      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.029 *    P<0.001 **   P<0.001 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 05                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    2-METHYLIMIDAZOLE                   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         300 PPM      1000 PPM     3000 PPM    |0PPM         1000 PPM     2500 PPM     5000 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    7/10 (70%)   10/10 (100%) 10/10 (100%)|0/10 (0%)    5/10 (50%)   10/10 (100%) 10/10 (100%) | 
|POLY-3 RATE (b)    |     0/0.06       7/7.02       10/10.00     10/10.00    |0/0.06       5/5.03       10/10.00     10/10.00     | 
|POLY-3 PERCENT (g) |     0.0%         99.7%        100.0%       100.0%      |0.0%         99.4%        100.0%       100.0%       | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    7/10 (70%)   10/10 (100%) 10/10 (100%)|0/10 (0%)    5/10 (50%)   10/10 (100%) 10/10 (100%) | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          183 (I)      183 (I)      183 (I)     |---          183 (I)      183 (I)      183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.022 *    P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001N**  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001N**  |P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001N**  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.016 *    P<0.001 **   P<0.001 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (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).