https://ntp.niehs.nih.gov/go/3193

TDMS Study 92012-06 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                2-METHYLIMIDAZOLE                                   DATE: 02/24/03       
EXPERIMENT: 92012 TEST: 06                                                                                     TIME: 15:04:05       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92012B       
PATHOLOGIST: HEATH, JAMES E.                                                                                   CAS: 693-98-1        
------------------------------------------------------------------------------------------------------------------------------------
                                                     27 WEEK SSAC/FINAL#1 MICE                                                      
               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: 06                                                                                     TIME: 15:04:05       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-85420                              ROUTE: DOSED FEED                                              NTP C#: 92012B       
PATHOLOGIST: HEATH, JAMES E.                                                                                   CAS: 693-98-1        
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                   2-METHYLIMIDAZOLE                                                                              
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Cortex                         Accessory Adrenal Cortical Nodule                                                            
Bone Marrow                            Hyperplasia                                                                                  
Kidney: Renal Tubule                   Pigmentation                                                                                 
Liver                                  Infiltration Cellular Mixed Cell                                                             
Liver: Hepatocyte                      Karyomegaly                                                                                  
                                       Vacuolization Cytoplasmic                                                                    
Spleen                                 Hematopoietic Cell Proliferation                                                             
                                       Pigmentation                                                                                 
Spleen: Lymphoid Follicle              Atrophy                                                                                      
Thyroid Gland: Follicular Cell         Hypertrophy                                                                                  
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex                         Accessory Adrenal Cortical Nodule                                                            
Liver: Hepatocyte                      Vacuolization Cytoplasmic                                                                    
Spleen                                 Hematopoietic Cell Proliferation                                                             
                                       Pigmentation                                                                                 
Spleen: Lymphoid Follicle              Atrophy                                                                                      
Thyroid Gland: Follicular Cell         Hypertrophy                                                                                  
===============================================================                                                                     
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 06                                            Page 1       
                     Statistical Analysis of Non-neoplastic Lesions in        Mice(B6C3F1)  -                    2-METHYLIMIDAZOLE  
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Accessory Adrenal Cortical Nodule                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   0/10 (0%)    0/10 (0%)    1/10 (10%)  |2/10 (20%)   0/10 (0%)    0/10 (0%)    1/10 (10%)   | 
|POLY-3 RATE (b)    |     2/2.05       0/0.06       0/0.06       1/1.06      |2/2.05       0/0.06       0/0.06       1/1.06       | 
|POLY-3 PERCENT (g) |     97.6%        0.0%         0.0%         94.8%       |97.6%        0.0%         0.0%         94.8%        | 
|INT SACRIFICE 1 (c)|     2/10 (20%)   0/10 (0%)    0/10 (0%)    1/10 (10%)  |2/10 (20%)   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)     |183 (I)      ---          ---          183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.460N     P=0.234N     P=0.234N     P=0.500N    |P=0.460N     P=0.234N     P=0.234N     P=0.500N     | 
|POLY 3             |     P=0.330N     P=0.067N     P=0.067N     P=0.300N    |P=0.330N     P=0.067N     P=0.067N     P=0.300N     | 
|POLY 1.5           |     P=0.336N     P=0.076N     P=0.076N     P=0.315N    |P=0.336N     P=0.076N     P=0.076N     P=0.315N     | 
|POLY 6             |     P=0.329N     P=0.067N     P=0.067N     P=0.299N    |P=0.329N     P=0.067N     P=0.067N     P=0.299N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.460N     P=0.237N     P=0.237N     P=0.500N    |P=0.460N     P=0.237N     P=0.237N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.041N*    (e)          (e)          (e)         |P=0.041N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   0/10 (0%)    2/10 (20%)   5/10 (50%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     1/1.06       0/0.06       2/2.05       5/5.03      |0/0.06       0/0.06       0/0.06       0/0.06       | 
|POLY-3 PERCENT (g) |     94.8%        0.0%         97.6%        99.4%       |0.0%         0.0%         0.0%         0.0%         | 
|INT SACRIFICE 1 (c)|     1/10 (10%)   0/10 (0%)    2/10 (20%)   5/10 (50%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    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=0.009 **   P=0.500N     P=0.500      P=0.077     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.003 **   P=0.160N     P=0.300      P=0.023 *   |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.003 **   P=0.183N     P=0.315      P=0.025 *   |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.003 **   P=0.159N     P=0.299      P=0.023 *   |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.008 **   P=0.500N     P=0.500      P=0.070     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.002 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 06                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                    2-METHYLIMIDAZOLE   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/10 (10%)   0/10 (0%)    1/10 (10%)   2/10 (20%)  |1/10 (10%)   1/10 (10%)   0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     1/1.06       0/0.06       1/1.06       2/2.05      |1/1.06       1/1.06       0/0.06       0/0.06       | 
|POLY-3 PERCENT (g) |     94.8%        0.0%         94.8%        97.6%       |94.8%        94.8%        0.0%         0.0%         | 
|INT SACRIFICE 1 (c)|     1/10 (10%)   0/10 (0%)    1/10 (10%)   2/10 (20%)  |1/10 (10%)   1/10 (10%)   0/10 (0%)    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)      183 (I)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.241      P=0.500N     P=0.766      P=0.500     |P=0.234N     P=0.766      P=0.500N     P=0.500N     | 
|POLY 3             |     P=0.161      P=0.160N     P=0.530      P=0.300     |P=0.121N     P=0.530      P=0.160N     P=0.160N     | 
|POLY 1.5           |     P=0.168      P=0.183N     P=0.548      P=0.315     |P=0.124N     P=0.548      P=0.183N     P=0.183N     | 
|POLY 6             |     P=0.161      P=0.159N     P=0.528      P=0.299     |P=0.121N     P=0.528      P=0.159N     P=0.159N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.238      P=0.500N     P=0.763N     P=0.500     |P=0.231N     P=0.763N     P=0.500N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.140      (e)          (e)          (e)         |P=0.362N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    1/10 (10%)   10/10 (100%)|0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/0.06       0/0.06       1/1.06       10/10.00    |0/0.06       0/0.06       0/0.06       0/0.06       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         94.8%        100.0%      |0.0%         0.0%         0.0%         0.0%         | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    0/10 (0%)    1/10 (10%)   10/10 (100%)|0/10 (0%)    0/10 (0%)    0/10 (0%)    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<0.001 **   (e)          P=0.500      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   (e)          P=0.160      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   (e)          P=0.183      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   (e)          P=0.159      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          P=0.500      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 06                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                    2-METHYLIMIDAZOLE   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Mixed Cell                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/10 (20%)   3/10 (30%)   6/10 (60%)   2/10 (20%)  |6/10 (60%)   7/10 (70%)   3/10 (30%)   5/10 (50%)   | 
|POLY-3 RATE (b)    |     2/2.05       3/3.04       6/6.03       2/2.05      |6/6.03       7/7.02       3/3.04       5/5.03       | 
|POLY-3 PERCENT (g) |     97.6%        98.6%        99.6%        97.6%       |99.6%        99.7%        98.6%        99.4%        | 
|INT SACRIFICE 1 (c)|     2/10 (20%)   3/10 (30%)   6/10 (60%)   2/10 (20%)  |6/10 (60%)   7/10 (70%)   3/10 (30%)   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)      183 (I)     |183 (I)      183 (I)      183 (I)      183 (I)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.567      P=0.500      P=0.091      P=0.707     |P=0.281N     P=0.500      P=0.190N     P=0.500N     | 
|POLY 3             |     P=0.493      P=0.353      P=0.037 *    P=0.543     |P=0.249N     P=0.437      P=0.119N     P=0.423N     | 
|POLY 1.5           |     P=0.498      P=0.364      P=0.040 *    P=0.555     |P=0.251N     P=0.442      P=0.124N     P=0.428N     | 
|POLY 6             |     P=0.493      P=0.352      P=0.037 *    P=0.542     |P=0.249N     P=0.436      P=0.119N     P=0.422N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.278N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.568      P=0.500      P=0.085      P=0.709N    |P=0.278N     P=0.500      P=0.185N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.341      (e)          (e)          (e)         |P=0.172N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Karyomegaly                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    5/10 (50%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)    | 
|POLY-3 RATE (b)    |     0/0.06       0/0.06       0/0.06       5/5.03      |0/0.06       0/0.06       0/0.06       0/0.06       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         99.4%       |0.0%         0.0%         0.0%         0.0%         | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    0/10 (0%)    0/10 (0%)    5/10 (50%)  |0/10 (0%)    0/10 (0%)    0/10 (0%)    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)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P=0.022 *   |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   (e)          (e)          P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P=0.002 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   (e)          (e)          P<0.001 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P=0.016 *   |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.091      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 06                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                    2-METHYLIMIDAZOLE   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    0/10 (0%)    4/10 (40%)  |0/10 (0%)    1/10 (10%)   2/10 (20%)   4/10 (40%)   | 
|POLY-3 RATE (b)    |     0/0.06       0/0.06       0/0.06       4/4.04      |0/0.06       1/1.06       2/2.05       4/4.04       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         99.1%       |0.0%         94.8%        97.6%        99.1%        | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    0/10 (0%)    0/10 (0%)    4/10 (40%)  |0/10 (0%)    1/10 (10%)   2/10 (20%)   4/10 (40%)   | 
|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=0.002 **   (e)          (e)          P=0.051     |P=0.016 *    P=0.500      P=0.234      P=0.051      | 
|POLY 3             |     P<0.001 **   (e)          (e)          P=0.007 **  |P=0.007 **   P=0.160      P=0.067      P=0.007 **   | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P=0.008 **  |P=0.007 **   P=0.183      P=0.076      P=0.008 **   | 
|POLY 6             |     P<0.001 **   (e)          (e)          P=0.007 **  |P=0.007 **   P=0.159      P=0.067      P=0.007 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.002 **   (e)          (e)          P=0.043 *   |P=0.015 *    P=0.500      P=0.237      P=0.043 *    | 
|ORDER RESTRICTED   |     P=0.154      (e)          (e)          (e)         |P=0.095      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/9 (0%)     0/9 (0%)     0/10 (0%)   |2/10 (20%)   1/10 (10%)   0/10 (0%)    2/10 (20%)   | 
|POLY-3 RATE (b)    |     0/0.06       0/0.06       0/0.06       0/0.06      |2/2.05       1/1.06       0/0.06       2/2.05       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |97.6%        94.8%        0.0%         97.6%        | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    0/9 (0%)     0/9 (0%)     0/10 (0%)   |2/10 (20%)   1/10 (10%)   0/10 (0%)    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)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.595      P=0.500N     P=0.234N     P=0.707      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.496      P=0.300N     P=0.067N     P=0.543      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.504      P=0.315N     P=0.076N     P=0.555      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.495      P=0.299N     P=0.067N     P=0.542      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.596      P=0.500N     P=0.237N     P=0.709N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.328      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 06                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                    2-METHYLIMIDAZOLE   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    5/10 (50%)   10/10 (100%) 10/10 (100%)|2/10 (20%)   5/10 (50%)   6/10 (60%)   10/10 (100%) | 
|POLY-3 RATE (b)    |     0/0.06       5/5.03       10/10.00     10/10.00    |2/2.05       5/5.03       6/6.03       10/10.00     | 
|POLY-3 PERCENT (g) |     0.0%         99.4%        100.0%       100.0%      |97.6%        99.4%        99.6%        100.0%       | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    5/10 (50%)   10/10 (100%) 10/10 (100%)|2/10 (20%)   5/10 (50%)   6/10 (60%)   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)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.022 *    P<0.001 **   P<0.001 **  |P<0.001 **   P=0.180      P=0.091      P<0.001 **   | 
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.099      P=0.037 *    P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.104      P=0.040 *    P<0.001 **   | 
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P=0.098      P=0.037 *    P<0.001 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.016 *    P<0.001 **   P<0.001 **  |P<0.001 **   P=0.175      P=0.085      P<0.001 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    1/10 (10%)   10/10 (100%) 10/10 (100%)|1/10 (10%)   3/10 (30%)   7/10 (70%)   10/10 (100%) | 
|POLY-3 RATE (b)    |     0/0.06       1/1.06       10/10.00     10/10.00    |1/1.06       3/3.04       7/7.02       10/10.00     | 
|POLY-3 PERCENT (g) |     0.0%         94.8%        100.0%       100.0%      |94.8%        98.6%        99.7%        100.0%       | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    1/10 (10%)   10/10 (100%) 10/10 (100%)|1/10 (10%)   3/10 (30%)   7/10 (70%)   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)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.500      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.293      P=0.013 *    P<0.001 **   | 
|POLY 3             |     P<0.001 **   P=0.160      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.152      P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.183      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.163      P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P=0.159      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.152      P<0.001 **   P<0.001 **   | 
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.500      P<0.001 **   P<0.001 **  |P<0.001 **   P=0.291      P=0.010 *    P<0.001 **   | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  02/24/03                           EXPERIMENT: 92012 TEST: 06                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                    2-METHYLIMIDAZOLE   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen: Lymphoid Follicle                                                                                                        | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    0/10 (0%)    5/10 (50%)   10/10 (100%)|0/10 (0%)    0/10 (0%)    0/10 (0%)    4/10 (40%)   | 
|POLY-3 RATE (b)    |     0/0.06       0/0.06       5/5.03       10/10.00    |0/0.06       0/0.06       0/0.06       4/4.04       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         99.4%        100.0%      |0.0%         0.0%         0.0%         99.1%        | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    0/10 (0%)    5/10 (50%)   10/10 (100%)|0/10 (0%)    0/10 (0%)    0/10 (0%)    4/10 (40%)   | 
|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<0.001 **   (e)          P=0.022 *    P<0.001 **  |P=0.002 **   (e)          (e)          P=0.051      | 
|POLY 3             |     P<0.001 **   (e)          P<0.001 **   P<0.001 **  |P<0.001 **   (e)          (e)          P=0.007 **   | 
|POLY 1.5           |     P<0.001 **   (e)          P=0.002 **   P<0.001 **  |P<0.001 **   (e)          (e)          P=0.008 **   | 
|POLY 6             |     P<0.001 **   (e)          P<0.001 **   P<0.001 **  |P<0.001 **   (e)          (e)          P=0.007 **   | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   (e)          P=0.016 *    P<0.001 **  |P=0.002 **   (e)          (e)          P=0.043 *    | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.154      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/10 (0%)    5/10 (50%)   9/10 (90%)   10/10 (100%)|0/8 (0%)     8/10 (80%)   10/10 (100%) 10/10 (100%) | 
|POLY-3 RATE (b)    |     0/0.06       5/5.03       9/9.01       10/10.00    |0/0.05       8/8.01       10/10.00     10/10.00     | 
|POLY-3 PERCENT (g) |     0.0%         99.4%        99.9%        100.0%      |0.0%         99.9%        100.0%       100.0%       | 
|INT SACRIFICE 1 (c)|     0/10 (0%)    5/10 (50%)   9/10 (90%)   10/10 (100%)|0/8 (0%)     8/10 (80%)   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=0.022 *    P<0.001 **   P<0.001 **  |P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **   | 
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|POLY 1.5           |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   | 
|POLY 6             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |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=0.016 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   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: 06                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                    2-METHYLIMIDAZOLE   
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0PPM         625 PPM      1250 PPM     2500 PPM    |0PPM         625 PPM      1250 PPM     2500 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |3/10 (30%)   1/10 (10%)   4/10 (40%)   1/10 (10%)   | 
|POLY-3 RATE (b)    |                                                        |3/3.04       1/1.06       4/4.04       1/1.06       | 
|POLY-3 PERCENT (g) |                                                        |98.6%        94.8%        99.1%        94.8%        | 
|INT SACRIFICE 1 (c)|                                                        |3/10 (30%)   1/10 (10%)   4/10 (40%)   1/10 (10%)   | 
|TERMINAL (d)       |                                                        |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=0.329N     P=0.293N     P=0.500      P=0.293N     | 
|POLY 3             |                                                        |P=0.256N     P=0.152N     P=0.384      P=0.152N     | 
|POLY 1.5           |                                                        |P=0.259N     P=0.163N     P=0.393      P=0.163N     | 
|POLY 6             |                                                        |P=0.256N     P=0.152N     P=0.383      P=0.152N     | 
|LOGISTIC REGRESSION|                                                        |P=0.327N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.327N     P=0.291N     P=0.500      P=0.291N     | 
|ORDER RESTRICTED   |                                                        |P=0.221N     (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).