https://ntp.niehs.nih.gov/go/20679

TDMS Study 97013-07 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 06/11/04       
EXPERIMENT: 97013 TEST: 07                                                                                     TIME: 08:45:22       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: 97013G       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
------------------------------------------------------------------------------------------------------------------------------------
                                                            FINAL#1 MICE                                                            
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                       WATER DISINFECTION MODEL (BROMODICHLOROMETHANE)                   DATE: 06/11/04       
EXPERIMENT: 97013 TEST: 07                                                                                     TIME: 08:45:22       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: 97013G       
PATHOLOGIST: MISSING                                                                                           CAS: 75-27-4         
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF     WATER DISINFECTION MODEL (BROMODICHLOR                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Cortex                         Hypertrophy                                                                                  
Epididymis                             Granuloma Sperm                                                                              
Kidney: Renal Tubule                   Degeneration                                                                                 
                                       Vacuolization Cytoplasmic                                                                    
Liver: Hepatocyte                      Fatty Change                                                                                 
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Kidney                                 Casts Protein                                                                                
Liver                                  Hematopoietic Cell Proliferation                                                             
                                       Infiltration Cellular Lymphocyte                                                             
Liver: Hepatocyte                      Fatty Change                                                                                 
Thymus                                 Atrophy                                                                                      
Thyroid Gland                          Inflammation                                                                                 
===============================================================                                                                     
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODI
CHLOR                                                                                                                               
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/15 (40%)   2/15 (13%)   0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     6/15.00      2/15.00      0/15.00      0/15.00     |0/15.00      0/14.13      0/14.00      0/14.04      | 
|POLY-3 PERCENT (g) |     40.0%        13.3%        0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     6/15 (40%)   2/15 (13%)   0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/14 (0%)    0/14 (0%)    0/14 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.003N**   P=0.112N     P=0.012N*    P=0.012N*   |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001N**   P=0.105N     P=0.005N**   P=0.005N**  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001N**   P=0.105N     P=0.005N**   P=0.005N**  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001N**   P=0.105N     P=0.005N**   P=0.005N**  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.003N**   P=0.112N     (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.002N**   P=0.107N     P=0.008N**   P=0.008N**  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001N**   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/15 (13%)   6/15 (40%)   6/15 (40%)   3/15 (20%)  |14/15 (93%)  15/15 (100%) 12/15 (80%)  14/15 (93%)  | 
|POLY-3 RATE (b)    |     2/15.00      6/15.00      6/15.00      3/15.00     |14/15.00     15/15.00     12/15.00     14/15.00     | 
|POLY-3 PERCENT (g) |     13.3%        40.0%        40.0%        20.0%       |93.3%        100.0%       80.0%        93.3%        | 
|TERMINAL (d)       |     2/15 (13%)   6/15 (40%)   6/15 (40%)   3/15 (20%)  |14/15 (93%)  14/14 (100%) 11/14 (79%)  13/14 (93%)  | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      92           10           61           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.557      P=0.112      P=0.112      P=0.500     |P=0.559      P=0.247      P=0.474N     P=0.516      | 
|POLY 3             |     P=0.558      P=0.105      P=0.105      P=0.500     |P=0.468N     P=0.500      P=0.298N     P=0.760      | 
|POLY 1.5           |     P=0.558      P=0.105      P=0.105      P=0.500     |P=0.468N     P=0.500      P=0.298N     P=0.760      | 
|POLY 6             |     P=0.558      P=0.105      P=0.105      P=0.500     |P=0.468N     P=0.500      P=0.298N     P=0.760      | 
|LOGISTIC REGRESSION|     P=0.557      P=0.112      P=0.112      P=0.500     |P=0.559      (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.558      P=0.107      P=0.107      P=0.500     |P=0.469N     P=0.500      P=0.299N     P=0.759N     | 
|ORDER RESTRICTED   |     P=0.172      (e)          (e)          (e)         |P=0.254N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis                                                                                                                       | 
|     Granuloma Sperm                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/15 (13%)   0/15 (0%)    0/15 (0%)    0/15 (0%)   |                                                    | 
|POLY-3 RATE (b)    |     2/15.00      0/15.00      0/15.00      0/15.00     |                                                    | 
|POLY-3 PERCENT (g) |     13.3%        0.0%         0.0%         0.0%        |                                                    | 
|TERMINAL (d)       |     2/15 (13%)   0/15 (0%)    0/15 (0%)    0/15 (0%)   |                                                    | 
|FIRST INCIDENCE    |     183 (T)      ---          ---          ---         |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.114N     P=0.236N     P=0.236N     P=0.236N    |                                                    | 
|POLY 3             |     P=0.107N     P=0.232N     P=0.232N     P=0.232N    |                                                    | 
|POLY 1.5           |     P=0.107N     P=0.232N     P=0.232N     P=0.232N    |                                                    | 
|POLY 6             |     P=0.107N     P=0.232N     P=0.232N     P=0.232N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.114N     (e)          (e)          (e)         |                                                    | 
|COCH-ARM / FISHERS |     P=0.112N     P=0.241N     P=0.241N     P=0.241N    |                                                    | 
|ORDER RESTRICTED   |     P=0.025N*    (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Casts Protein                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/15 (13%)   0/15 (0%)    5/15 (33%)   2/15 (13%)  |12/15 (80%)  11/15 (73%)  7/15 (47%)   7/15 (47%)   | 
|POLY-3 RATE (b)    |     2/15.00      0/15.00      5/15.00      2/15.00     |12/15.00     11/15.00     7/14.00      7/14.04      | 
|POLY-3 PERCENT (g) |     13.3%        0.0%         33.3%        13.3%       |80.0%        73.3%        50.0%        49.9%        | 
|TERMINAL (d)       |     2/15 (13%)   0/15 (0%)    5/15 (33%)   2/15 (13%)  |12/15 (80%)  10/14 (71%)  7/14 (50%)   7/14 (50%)   | 
|FIRST INCIDENCE    |     183 (T)      ---          183 (T)      183 (T)     |184 (T)      92           184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.381      P=0.236N     P=0.198      P=0.701     |P=0.045N*    P=0.617N     P=0.099N     P=0.099N     | 
|POLY 3             |     P=0.377      P=0.232N     P=0.195      P=0.698     |P=0.042N*    P=0.500N     P=0.092N     P=0.091N     | 
|POLY 1.5           |     P=0.377      P=0.232N     P=0.195      P=0.698     |P=0.039N*    P=0.500N     P=0.092N     P=0.084N     | 
|POLY 6             |     P=0.377      P=0.232N     P=0.195      P=0.698     |P=0.043N*    P=0.500N     P=0.092N     P=0.092N     | 
|LOGISTIC REGRESSION|     P=0.381      (e)          P=0.198      P=0.701     |P=0.034N*    (e)          P=0.099N     P=0.099N     | 
|COCH-ARM / FISHERS |     P=0.380      P=0.241N     P=0.195      P=0.701N    |P=0.027N*    P=0.500N     P=0.064N     P=0.064N     | 
|ORDER RESTRICTED   |     P=0.147      (e)          (e)          (e)         |P=0.066N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     8/15 (53%)   9/15 (60%)   8/15 (53%)   8/15 (53%)  |1/15 (7%)    3/15 (20%)   1/15 (7%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     8/15.00      9/15.00      8/15.00      8/15.00     |1/15.00      3/14.13      1/14.00      0/14.04      | 
|POLY-3 PERCENT (g) |     53.3%        60.0%        53.3%        53.3%       |6.7%         21.2%        7.1%         0.0%         | 
|TERMINAL (d)       |     8/15 (53%)   9/15 (60%)   8/15 (53%)   8/15 (53%)  |1/15 (7%)    3/14 (21%)   1/14 (7%)    0/14 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      184 (T)      184 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.517N     P=0.500      P=0.641      P=0.641     |P=0.208N     P=0.273      P=0.749      P=0.514N     | 
|POLY 3             |     P=0.517N     P=0.500      P=0.638      P=0.638     |P=0.213N     P=0.276      P=0.745      P=0.513N     | 
|POLY 1.5           |     P=0.517N     P=0.500      P=0.638      P=0.638     |P=0.210N     P=0.282      P=0.745      P=0.511N     | 
|POLY 6             |     P=0.517N     P=0.500      P=0.638      P=0.638     |P=0.214N     P=0.273      P=0.745      P=0.514N     | 
|LOGISTIC REGRESSION|     P=0.517N     P=0.500      P=0.641      P=0.641     |P=0.208N     P=0.273      P=0.749      (e)          | 
|COCH-ARM / FISHERS |     P=0.517N     P=0.500      P=0.642N     P=0.642N    |P=0.193N     P=0.299      P=0.759N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.661N     (e)          (e)          (e)         |P=0.144N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    4/15 (27%)  |0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     0/15.00      0/15.00      0/15.00      4/15.00     |0/15.00      0/14.13      0/14.00      0/14.04      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         26.7%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/15 (0%)    0/15 (0%)    0/15 (0%)    4/15 (27%)  |0/15 (0%)    0/14 (0%)    0/14 (0%)    0/14 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          183 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.003 **   (e)          (e)          P=0.057     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   (e)          (e)          P=0.045 *   |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   (e)          (e)          P=0.045 *   |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   (e)          (e)          P=0.045 *   |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.057     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.003 **   (e)          (e)          P=0.050     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     12/15 (80%)  5/15 (33%)   0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     12/15.00     5/15.00      0/15.00      0/15.00     |0/15.00      0/14.13      0/14.00      0/14.04      | 
|POLY-3 PERCENT (g) |     80.0%        33.3%        0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     12/15 (80%)  5/15 (33%)   0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/14 (0%)    0/14 (0%)    0/14 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001N**   P=0.015N*    P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001N**   P=0.008N**   P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001N**   P=0.008N**   P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001N**   P=0.008N**   P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001N**   P=0.015N*    (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001N**   P=0.013N*    P<0.001N**   P<0.001N**  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001N**   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    0/15 (0%)    2/15 (13%)   | 
|POLY-3 RATE (b)    |     0/15.00      0/15.00      0/15.00      0/15.00     |0/15.00      0/14.13      0/14.00      2/15.00      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         13.3%        | 
|TERMINAL (d)       |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/14 (0%)    0/14 (0%)    1/14 (7%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          61           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.046 *    (e)          (e)          P=0.232      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.042 *    (e)          (e)          P=0.232      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.042 *    (e)          (e)          P=0.232      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.042 *    (e)          (e)          P=0.232      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.048 *    (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.044 *    (e)          (e)          P=0.241      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.025 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    2/15 (13%)   0/15 (0%)   |5/15 (33%)   4/15 (27%)   3/15 (20%)   0/15 (0%)    | 
|POLY-3 RATE (b)    |     0/15.00      0/15.00      2/15.00      0/15.00     |5/15.00      4/15.00      3/14.00      0/14.04      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         13.3%        0.0%        |33.3%        26.7%        21.4%        0.0%         | 
|TERMINAL (d)       |     0/15 (0%)    0/15 (0%)    2/15 (13%)   0/15 (0%)   |5/15 (33%)   3/14 (21%)   3/14 (21%)   0/14 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          183 (T)      ---         |184 (T)      92           184 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.595      (e)          P=0.236      (e)         |P=0.020N*    P=0.542N     P=0.384N     P=0.032N*    | 
|POLY 3             |     P=0.598      (e)          P=0.232      (e)         |P=0.018N*    P=0.500N     P=0.385N     P=0.022N*    | 
|POLY 1.5           |     P=0.598      (e)          P=0.232      (e)         |P=0.017N*    P=0.500N     P=0.384N     P=0.021N*    | 
|POLY 6             |     P=0.598      (e)          P=0.232      (e)         |P=0.018N*    P=0.500N     P=0.385N     P=0.022N*    | 
|LOGISTIC REGRESSION|     (e)          (e)          P=0.236      (e)         |P=0.014N*    (e)          P=0.384N     P=0.030N*    | 
|COCH-ARM / FISHERS |     P=0.596      (e)          P=0.241      (e)         |P=0.015N*    P=0.500N     P=0.341N     P=0.021N*    | 
|ORDER RESTRICTED   |     P=0.237      (e)          (e)          (e)         |P=0.016N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     13/15 (87%)  14/15 (93%)  13/15 (87%)  15/15 (100%)|14/15 (93%)  15/15 (100%) 14/15 (93%)  14/15 (93%)  | 
|POLY-3 RATE (b)    |     13/15.00     14/15.00     13/15.00     15/15.00    |14/15.00     15/15.00     14/14.00     14/15.00     | 
|POLY-3 PERCENT (g) |     86.7%        93.3%        86.7%        100.0%      |93.3%        100.0%       100.0%       93.3%        | 
|TERMINAL (d)       |     13/15 (87%)  14/15 (93%)  13/15 (87%)  15/15 (100%)|14/15 (93%)  14/14 (100%) 14/14 (100%) 13/14 (93%)  | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      92           184 (T)      61           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.195      P=0.500      P=0.701      P=0.236     |P=0.502      P=0.247      P=0.514      P=0.516      | 
|POLY 3             |     P=0.196      P=0.500      P=0.698      P=0.232     |P=0.593N     P=0.500      P=0.514      P=0.760      | 
|POLY 1.5           |     P=0.196      P=0.500      P=0.698      P=0.232     |P=0.592N     P=0.500      P=0.519      P=0.760      | 
|POLY 6             |     P=0.196      P=0.500      P=0.698      P=0.232     |P=0.593N     P=0.500      P=0.514      P=0.760      | 
|LOGISTIC REGRESSION|     P=0.195      P=0.500      P=0.701      P=0.236     |P=0.675N     (e)          P=0.514      (e)          | 
|COCH-ARM / FISHERS |     P=0.193      P=0.500      P=0.701N     P=0.241     |P=0.540N     P=0.500      P=0.759N     P=0.759N     | 
|ORDER RESTRICTED   |     P=0.149      (e)          (e)          (e)         |P=0.403      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Fatty Change                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/15 (67%)  9/15 (60%)   4/15 (27%)   11/15 (73%) |2/15 (13%)   2/15 (13%)   3/15 (20%)   11/15 (73%)  | 
|POLY-3 RATE (b)    |     10/15.00     9/15.00      4/15.00      11/15.00    |2/15.00      2/14.13      3/14.00      11/14.04     | 
|POLY-3 PERCENT (g) |     66.7%        60.0%        26.7%        73.3%       |13.3%        14.2%        21.4%        78.4%        | 
|TERMINAL (d)       |     10/15 (67%)  9/15 (60%)   4/15 (27%)   11/15 (73%) |2/15 (13%)   2/14 (14%)   3/14 (21%)   11/14 (79%)  | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.465      P=0.500N     P=0.036N*    P=0.500     |P<0.001 **   P=0.676      P=0.467      P<0.001 **   | 
|POLY 3             |     P=0.464      P=0.500N     P=0.027N*    P=0.500     |P<0.001 **   P=0.676      P=0.467      P<0.001 **   | 
|POLY 1.5           |     P=0.464      P=0.500N     P=0.027N*    P=0.500     |P<0.001 **   P=0.682      P=0.468      P<0.001 **   | 
|POLY 6             |     P=0.464      P=0.500N     P=0.027N*    P=0.500     |P<0.001 **   P=0.673      P=0.467      P<0.001 **   | 
|LOGISTIC REGRESSION|     P=0.465      P=0.500N     P=0.036N*    P=0.500     |P<0.001 **   P=0.676      P=0.466      P<0.001 **   | 
|COCH-ARM / FISHERS |     P=0.465      P=0.500N     P=0.033N*    P=0.500     |P<0.001 **   P=0.701N     P=0.500      P<0.001 **   | 
|ORDER RESTRICTED   |     P=0.156      (e)          (e)          (e)         |P<0.001 **   (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     15/15 (100%) 15/15 (100%) 13/15 (87%)  15/15 (100%)|10/15 (67%)  9/15 (60%)   10/15 (67%)  13/15 (87%)  | 
|POLY-3 RATE (b)    |     15/15.00     15/15.00     13/15.00     15/15.00    |10/15.00     9/14.13      10/14.00     13/14.04     | 
|POLY-3 PERCENT (g) |     100.0%       100.0%       86.7%        100.0%      |66.7%        63.7%        71.4%        92.6%        | 
|TERMINAL (d)       |     15/15 (100%) 15/15 (100%) 13/15 (87%)  15/15 (100%)|10/15 (67%)  9/14 (64%)   10/14 (71%)  13/14 (93%)  | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.595N     (e)          P=0.236N     (e)         |P=0.059      P=0.599N     P=0.549      P=0.104      | 
|POLY 3             |     P=0.598N     (e)          P=0.232N     (e)         |P=0.058      P=0.585N     P=0.548      P=0.099      | 
|POLY 1.5           |     P=0.598N     (e)          P=0.232N     (e)         |P=0.062      P=0.563N     P=0.549      P=0.111      | 
|POLY 6             |     P=0.598N     (e)          P=0.232N     (e)         |P=0.058      P=0.596N     P=0.548      P=0.096      | 
|LOGISTIC REGRESSION|     P=0.595N     (e)          P=0.236N     (e)         |P=0.059      P=0.599N     P=0.549      P=0.104      | 
|COCH-ARM / FISHERS |     P=0.596N     (e)          P=0.241N     (e)         |P=0.108      P=0.500N     P=0.650N     P=0.195      | 
|ORDER RESTRICTED   |     P=0.237N     (e)          (e)          (e)         |P=0.068      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |3/15 (20%)   0/15 (0%)    2/15 (13%)   1/15 (7%)    | 
|POLY-3 RATE (b)    |     0/15.00      0/15.00      0/15.00      0/15.00     |3/15.00      0/14.13      2/14.00      1/14.04      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |20.0%        0.0%         14.3%        7.1%         | 
|TERMINAL (d)       |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |3/15 (20%)   0/14 (0%)    2/14 (14%)   1/14 (7%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |184 (T)      ---          184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.352N     P=0.128N     P=0.533N     P=0.324N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.338N     P=0.117N     P=0.533N     P=0.323N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.338N     P=0.114N     P=0.532N     P=0.319N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.337N     P=0.119N     P=0.533N     P=0.324N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.352N     (e)          P=0.534N     P=0.324N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.331N     P=0.112N     P=0.500N     P=0.299N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.200N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |2/15 (13%)   1/15 (7%)    2/15 (13%)   2/15 (13%)   | 
|POLY-3 RATE (b)    |                                                        |2/15.00      1/14.13      2/14.00      2/14.04      | 
|POLY-3 PERCENT (g) |                                                        |13.3%        7.1%         14.3%        14.3%        | 
|TERMINAL (d)       |                                                        |2/15 (13%)   1/14 (7%)    2/14 (14%)   2/14 (14%)   | 
|FIRST INCIDENCE    |                                                        |184 (T)      184 (T)      184 (T)      184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.504      P=0.525N     P=0.676      P=0.676      | 
|POLY 3             |                                                        |P=0.505      P=0.521N     P=0.673      P=0.674      | 
|POLY 1.5           |                                                        |P=0.507      P=0.516N     P=0.673      P=0.678      | 
|POLY 6             |                                                        |P=0.505      P=0.524N     P=0.673      P=0.673      | 
|LOGISTIC REGRESSION|                                                        |P=0.504      P=0.525N     P=0.676      P=0.676      | 
|COCH-ARM / FISHERS |                                                        |P=0.527      P=0.500N     P=0.701N     P=0.701N     | 
|ORDER RESTRICTED   |                                                        |P=0.586      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Parathyroid Gland                                                                                                                | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     2/2 (100%)   0/0 (0%)     | 
|POLY-3 RATE (b)    |     0/0.00       0/0.00       0/0.00       0/0.00      |0/0.00       0/0.00       2/2.00       0/0.00       | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         100.0%       0.0%         | 
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     2/2 (100%)   0/0 (0%)     | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          184 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/14 (7%)    4/15 (27%)   0/15 (0%)    2/15 (13%)  |0/15 (0%)    0/15 (0%)    1/15 (7%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     1/14.00      4/15.00      0/15.00      2/15.00     |0/15.00      0/14.13      1/14.00      0/14.04      | 
|POLY-3 PERCENT (g) |     7.1%         26.7%        0.0%         13.3%       |0.0%         0.0%         7.1%         0.0%         | 
|TERMINAL (d)       |     1/14 (7%)    4/15 (27%)   0/15 (0%)    2/15 (13%)  |0/15 (0%)    0/14 (0%)    1/14 (7%)    0/14 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      ---          183 (T)     |---          ---          184 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.558N     P=0.189      P=0.486N     P=0.525     |P=0.686      (e)          P=0.486      (e)          | 
|POLY 3             |     P=0.560N     P=0.185      P=0.486N     P=0.524     |P=0.675      (e)          P=0.486      (e)          | 
|POLY 1.5           |     P=0.560N     P=0.185      P=0.486N     P=0.524     |P=0.679      (e)          P=0.486      (e)          | 
|POLY 6             |     P=0.560N     P=0.185      P=0.486N     P=0.524     |P=0.675      (e)          P=0.486      (e)          | 
|LOGISTIC REGRESSION|     P=0.558N     P=0.189      (e)          P=0.525     |(e)          (e)          P=0.486      (e)          | 
|COCH-ARM / FISHERS |     P=0.559N     P=0.186      P=0.483N     P=0.527     |P=0.695      (e)          P=0.500      (e)          | 
|ORDER RESTRICTED   |     P=0.298N     (e)          (e)          (e)         |P=0.368      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    2/15 (13%)   2/15 (13%)   | 
|POLY-3 RATE (b)    |     0/15.00      0/15.00      0/15.00      0/15.00     |0/15.00      0/14.13      2/14.00      2/15.00      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         14.3%        13.3%        | 
|TERMINAL (d)       |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/14 (0%)    2/14 (14%)   1/14 (7%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          184 (T)      61           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.081      (e)          P=0.221      P=0.232      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.084      (e)          P=0.216      P=0.232      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.083      (e)          P=0.216      P=0.232      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.085      (e)          P=0.216      P=0.232      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.096      (e)          P=0.221      (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.081      (e)          P=0.241      P=0.241      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.098      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    2/15 (13%)   0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    0/15 (0%)    1/15 (7%)    | 
|POLY-3 RATE (b)    |     0/15.00      2/15.00      0/15.00      0/15.00     |0/15.00      0/14.13      0/14.00      1/14.04      | 
|POLY-3 PERCENT (g) |     0.0%         13.3%        0.0%         0.0%        |0.0%         0.0%         0.0%         7.1%         | 
|TERMINAL (d)       |     0/15 (0%)    2/15 (13%)   0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/14 (0%)    0/14 (0%)    1/14 (7%)    | 
|FIRST INCIDENCE    |     ---          183 (T)      ---          ---         |---          ---          ---          184 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.405N     P=0.236      (e)          (e)         |P=0.194      (e)          (e)          P=0.486      | 
|POLY 3             |     P=0.402N     P=0.232      (e)          (e)         |P=0.193      (e)          (e)          P=0.487      | 
|POLY 1.5           |     P=0.402N     P=0.232      (e)          (e)         |P=0.194      (e)          (e)          P=0.489      | 
|POLY 6             |     P=0.402N     P=0.232      (e)          (e)         |P=0.193      (e)          (e)          P=0.486      | 
|LOGISTIC REGRESSION|     (e)          P=0.236      (e)          (e)         |(e)          (e)          (e)          P=0.486      | 
|COCH-ARM / FISHERS |     P=0.404N     P=0.241      (e)          (e)         |P=0.197      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     P=0.237N     (e)          (e)          (e)         |P=0.108      (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/15 (20%)   2/15 (13%)   1/15 (7%)    1/15 (7%)   |                                                    | 
|POLY-3 RATE (b)    |     3/15.00      2/15.00      1/15.00      1/15.00     |                                                    | 
|POLY-3 PERCENT (g) |     20.0%        13.3%        6.7%         6.7%        |                                                    | 
|TERMINAL (d)       |     3/15 (20%)   2/15 (13%)   1/15 (7%)    1/15 (7%)   |                                                    | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |                                                    | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.190N     P=0.500N     P=0.299N     P=0.299N    |                                                    | 
|POLY 3             |     P=0.193N     P=0.500N     P=0.298N     P=0.298N    |                                                    | 
|POLY 1.5           |     P=0.193N     P=0.500N     P=0.298N     P=0.298N    |                                                    | 
|POLY 6             |     P=0.193N     P=0.500N     P=0.298N     P=0.298N    |                                                    | 
|LOGISTIC REGRESSION|     P=0.190N     P=0.500N     P=0.299N     P=0.299N    |                                                    | 
|COCH-ARM / FISHERS |     P=0.188N     P=0.500N     P=0.299N     P=0.299N    |                                                    | 
|ORDER RESTRICTED   |     P=0.207N     (e)          (e)          (e)         |                                                    | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/15 (0%)    0/15 (0%)    2/15 (13%)   | 
|POLY-3 RATE (b)    |     0/15.00      0/15.00      0/15.00      0/15.00     |0/15.00      0/14.13      0/14.00      2/15.00      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         13.3%        | 
|TERMINAL (d)       |     0/15 (0%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |0/15 (0%)    0/14 (0%)    0/14 (0%)    1/14 (7%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          61           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.046 *    (e)          (e)          P=0.232      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.042 *    (e)          (e)          P=0.232      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.042 *    (e)          (e)          P=0.232      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.042 *    (e)          (e)          P=0.232      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.048 *    (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.044 *    (e)          (e)          P=0.241      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.025 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     11/15 (73%)  9/15 (60%)   9/15 (60%)   11/15 (73%) |6/15 (40%)   5/15 (33%)   9/15 (60%)   7/15 (47%)   | 
|POLY-3 RATE (b)    |     11/15.00     9/15.00      9/15.00      11/15.00    |6/15.00      5/14.13      9/14.00      7/15.00      | 
|POLY-3 PERCENT (g) |     73.3%        60.0%        60.0%        73.3%       |40.0%        35.4%        64.3%        46.7%        | 
|TERMINAL (d)       |     11/15 (73%)  9/15 (60%)   9/15 (60%)   11/15 (73%) |6/15 (40%)   5/14 (36%)   9/14 (64%)   6/14 (43%)   | 
|FIRST INCIDENCE    |     183 (T)      183 (T)      183 (T)      183 (T)     |184 (T)      184 (T)      184 (T)      61           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.500      P=0.352N     P=0.352N     P=0.658     |P=0.271      P=0.557N     P=0.179      P=0.443      | 
|POLY 3             |     P=0.500      P=0.353N     P=0.353N     P=0.655     |P=0.333      P=0.549N     P=0.176      P=0.500      | 
|POLY 1.5           |     P=0.500      P=0.353N     P=0.353N     P=0.655     |P=0.327      P=0.536N     P=0.177      P=0.500      | 
|POLY 6             |     P=0.500      P=0.353N     P=0.353N     P=0.655     |P=0.336      P=0.555N     P=0.176      P=0.500      | 
|LOGISTIC REGRESSION|     P=0.500      P=0.352N     P=0.352N     P=0.658     |P=0.298      P=0.557N     P=0.179      (e)          | 
|COCH-ARM / FISHERS |     P=0.500      P=0.350N     P=0.350N     P=0.659N    |P=0.315      P=0.500N     P=0.233      P=0.500      | 
|ORDER RESTRICTED   |     P=0.484      (e)          (e)          (e)         |P=0.268      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |3/15 (20%)   1/15 (7%)    1/15 (7%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |     1/15.00      0/15.00      0/15.00      0/15.00     |3/15.00      1/15.00      1/14.00      0/14.04      | 
|POLY-3 PERCENT (g) |     6.7%         0.0%         0.0%         0.0%        |20.0%        6.7%         7.1%         0.0%         | 
|TERMINAL (d)       |     1/15 (7%)    0/15 (0%)    0/15 (0%)    0/15 (0%)   |3/15 (20%)   0/14 (0%)    1/14 (7%)    0/14 (0%)    | 
|FIRST INCIDENCE    |     183 (T)      ---          ---          ---         |184 (T)      92           184 (T)      ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.306N     P=0.500N     P=0.500N     P=0.500N    |P=0.079N     P=0.322N     P=0.324N     P=0.128N     | 
|POLY 3             |     P=0.306N     P=0.500N     P=0.500N     P=0.500N    |P=0.073N     P=0.298N     P=0.324N     P=0.119N     | 
|POLY 1.5           |     P=0.306N     P=0.500N     P=0.500N     P=0.500N    |P=0.072N     P=0.298N     P=0.324N     P=0.116N     | 
|POLY 6             |     P=0.306N     P=0.500N     P=0.500N     P=0.500N    |P=0.073N     P=0.298N     P=0.324N     P=0.119N     | 
|LOGISTIC REGRESSION|     P=0.306N     (e)          (e)          (e)         |P=0.052N     (e)          P=0.324N     P=0.124N     | 
|COCH-ARM / FISHERS |     P=0.305N     P=0.500N     P=0.500N     P=0.500N    |P=0.067N     P=0.299N     P=0.299N     P=0.112N     | 
|ORDER RESTRICTED   |     P=0.121N     (e)          (e)          (e)         |P=0.038N*    (e)          (e)          (e)          | 
|=================================================================================================================================| 
       Date:  06/11/04                           EXPERIMENT: 97013 TEST: 07                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -      WATER DISINFECTION MODEL (BROMODIC
HLOR                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |2/15 (13%)   2/15 (13%)   0/15 (0%)    0/15 (0%)    | 
|POLY-3 RATE (b)    |                                                        |2/15.00      2/14.13      0/14.00      0/14.04      | 
|POLY-3 PERCENT (g) |                                                        |13.3%        14.2%        0.0%         0.0%         | 
|TERMINAL (d)       |                                                        |2/15 (13%)   2/14 (14%)   0/14 (0%)    0/14 (0%)    | 
|FIRST INCIDENCE    |                                                        |184 (T)      184 (T)      ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.090N     P=0.676      P=0.251N     P=0.251N     | 
|POLY 3             |                                                        |P=0.086N     P=0.676      P=0.248N     P=0.247N     | 
|POLY 1.5           |                                                        |P=0.085N     P=0.682      P=0.247N     P=0.244N     | 
|POLY 6             |                                                        |P=0.086N     P=0.673      P=0.248N     P=0.248N     | 
|LOGISTIC REGRESSION|                                                        |P=0.090N     P=0.676      (e)          (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.081N     P=0.701N     P=0.241N     P=0.241N     | 
|ORDER RESTRICTED   |                                                        |P=0.108N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     0 MG/KG      25 MG/KG     50 MG/KG     100         |0 MG/KG      25 MG/KG     50 MG/KG     100          | 
|                   |                                            MG/KG       |                                       MG/KG        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |9/15 (60%)   9/15 (60%)   12/15 (80%)  10/15 (67%)  | 
|POLY-3 RATE (b)    |                                                        |9/15.00      9/14.13      12/14.00     10/15.00     | 
|POLY-3 PERCENT (g) |                                                        |60.0%        63.7%        85.7%        66.7%        | 
|TERMINAL (d)       |                                                        |9/15 (60%)   9/14 (64%)   12/14 (86%)  9/14 (64%)   | 
|FIRST INCIDENCE    |                                                        |184 (T)      184 (T)      184 (T)      61           | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.279      P=0.557      P=0.133      P=0.413      | 
|POLY 3             |                                                        |P=0.377      P=0.567      P=0.127      P=0.500      | 
|POLY 1.5           |                                                        |P=0.369      P=0.588      P=0.128      P=0.500      | 
|POLY 6             |                                                        |P=0.381      P=0.557      P=0.127      P=0.500      | 
|LOGISTIC REGRESSION|                                                        |P=0.307      P=0.557      P=0.133      (e)          | 
|COCH-ARM / FISHERS |                                                        |P=0.356      P=0.645N     P=0.213      P=0.500      | 
|ORDER RESTRICTED   |                                                        |P=0.274      (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).